Index
A
AA. See Alzheimer’s Association
AADC. See L-aromatic amino acid decarboxylase
AAV. See adeno-associated virus
ABC. See Adult Behavior Checklist
abstinence, craving and, 728–730
spontaneous, 728
abuse classifications, of SUD, 772–774
acceptance, as coping mechanism, 1149
acetylcholine (ACh)
AD and
inhibitory mechanisms, 844
in treatment therapies, 844–845
end-plate potentials, 12
for LBD, 882
for MCI, 845
memantine and, 845
neurotransmitters and, 12
sleep cycles and, 1130
acoustic emission signals, 153
acoustic parameter dependence, 153–154
action potential
brain function and, 64
activation likelihood estimation (ALE) methods, 257–258
activator protein-1 (AP-1)
composition changes over time, 83–84
genomic transcription control by, 82–84
Jun proteins, 83
response elements in, 83
activity-based anorexia, 1183
AD. See Alzheimer’s disease
ADAM10 genes, 808
ADAPT. See Alzheimer’s disease anti-inflammatory prevention trial
addiction. See also drug addiction; reward, addiction and; substance use disorder; transcriptional mechanisms, of addiction
adolescence and
brain development during, 707
risk factors for, 709
for individual traits, 711
neuroimaging for, 721
BDNF and, 688
brain development and, 707–709
during adolescence, 707
dopaminergic changes, 707
PFC, 708
regional differences in, 707–708
cellular physiology of, 689–690
cognitive control loss, 689–690
NAc in, 689
optogenetics in, 690
receptor availability in, 690
structural plasticity changes, 689
synaptic plasticity in, 689
clinical indications for, 683
compulsivity and
neurocircuitry of, 685
transition to, 736
spontaneous, 728
DAs and
activation in, 686
brain development and, 707, 707–708
hyperdopaminergia, 685
mediated signaling by, 685–686
neurocircuitry of, 683
definition of, 675
diagnosis of, 703
in DSM-V, 697
family studies for, 697
for inheritance of, 699
genetic basis of. See also inheritance, genetic
alcohol-induced flushing and, 699–700
with alcohol metabolizing genes, 700
alleles in, 696
in candidate gene studies, 700
clinical categories of, 697
correlation in, 698
endophenotypes for, 699
environmental interaction in, 698–699
evolutionary context for, 696
exposure factors for, 697
gene identification, 700–701, 704
5HTTLPR polymorphism, 701
inheritance range in, 696
intermediate phenotypes in, 699–700
mapping technologies for, 696
with monoamine transmitters, 700–701
as multistage, 704
neuroimaging for, 700
in receptors, 699
resilience in, 696
serotonins and, 701
signaling pathways for, 696
genetic mapping technologies for, 696
glutamate homeostasis hypothesis and, 687–688
BDNF and, 688
GPCR and, 688
Homer proteins in, 688
mediated relapse by, 687
metabotropic receptors, 688
regulation in, 687
hedonic hypothesis for, 706
individual traits for, 709–711
low self-control, 709
positive affect and, 710
prenatal exposure and, 710–711
stimulant medication and, 711
causation in, 697
cross-transmission of, 698
epistatic model for, 698
through family studies, 697
shared, 698
unshared, 698
morbidity rates for, 683
NAc and
cellular physiology of, 689
negative reinforcement and, 738
neurocircuitry of, 683–685, 706
compulsivity in, 685
CRF and, 685
DA functions and, 683
habenula, 685
HPA axis and, 685
insula in, 685
PFC in, 684
septum in, 685
neuroimaging for, 700, 738–740. See also craving, addiction and
in animal models, 721, 723–725
applications in studies of, 716
blood flow and, 727
brain development and, 707–708
environmental factors, 720
genetic basis of, 700
for glucose metabolism, 716, 722, 727–728
for heroine, 726
for methamphetamine, 726
for opioids, 727
pharmacokinetic profiles and, 722
for research, 740
risk identification through, 740
of serotonins, 727
severity measures, 738
with SPECT, 716
opponent-process models of, 737
prevalence rates for, 706
public health costs of, 683
receptor-mediated signaling in, 685–688
in cellular physiology, 690
metabotropic receptors, 688
for regulated relapse, 686–688
research on, 683
risk factors for, 709
during adolescence, 709
susceptibility in
behavioral phenotypes in, 680
impulsivity and, 681
novelty-seeking traits in, 680–681
reward sensitivity in, 681
sex factors in, 680
social factors in, 680
vulnerability towards, 716–721
addictive behaviors. See also alcohol use disorders; drug abuse
DNA methylation and, 95
epigenetic mechanisms and, 95–96
histone methylation and, 95
transgenic rat models for, 111
viral-mediated gene transfer and, 118
adenine, 76
in TATA box, 80
adeno-associated virus (AAV), viral-mediated gene transfer, 117
ADH1B gene. See alcohol dehydrogenase 1B gene
ADHD. See attention deficit hyperactivity disorder
ADNI. See Alzheimer’s Disease Neuroimaging Initiative
adolescence
addiction and
brain development during, 707
risk factors for, 709
fear development during, 598–603
of contextual fear and extinction, 600–601
of cue fear extinction, 599–600
hippocampal involvement, 600–601
psychopathology and, 598
schizophrenia during, 328
adoption studies, for ADHD, 1037
ADRDA. See Alzheimer’s Disease and Related Disorders Association
adrenal glucocorticoids, depression and, 430–431
Adult Behavior Checklist (ABC), 1061
animal models of, 1119
dopamines in, 1121
oxytocin in, 1121
partner preference in, 1120–1121
selective aggression in, 1121–1123
separation distress in, 1123
chemical substrates for, 1120–1123
neurobiology of, 1124
affective disorders. See also specific disorders
bipolar, 380
psychoses compared to, 224
African Americans, AD in, 801–802
after-hyperpolarization (AHP), 70
neurons and, 29
age. See also childhood; early childhood, fear development during
bipolar disorder and, 384
MDD and, 384
aggression
alcohol use and, 1109
amygdala activity and, 1106–1107
in reactive aggression, 1109–1110
ASD and, treatment therapies for, 1029–1030
ASPD and, 1094
instrumental aggression and, 1095, 1104
benzodiazepines and, 1109
in BPD
impulsive dimensions in, 1091–1092
reactive aggression in, 1104
COMT and, 1109
definition of, 1103
5HTTLPR polymorphism and, 1109
as adaptive, 1104
ASPD and, 1104
CD and, 1104
cortical circuits in, 1109
flexibility of, 1104
reactive compared to, 1103–1104
stimulus-reinforcement learning and, 1104–1105
MAOA and, 1109
neurobiology of
molecular mechanisms in, 1108–1109
OFC in, 1106
for reactive aggression, 1106, 1107–1108
PSAP and, 1107
amygdala activity and, 1109–1110
in BPD, 1104
components of, 1103
instrumental compared to, 1103–1104
neurobiology of, 1106, 1107–1108
risks for, 1103
serotonin and, 1108–1109, 1110
TAP and, 1107
taxonomies of, 1103. See also reactive aggression
Aghajanian, George K., 71
aging
neurodegenerative diseases and, 150
agomelatine, 516
agoraphobia, 532
AGTR genes. See angiotensin receptor genes
AHDS. See Allan-Herndon-Dudley syndrome
AHP. See after-hyperpolarization
AIS. See axon initial segment
alcohol dehydrogenase 1B (ADH1B) gene, 700
alcohol-induced flushing, 699–700
alcohol use
aggression and, 1109
in animal models, 677
alcohol use disorders (AUDs)
intrinsic plasticity of brain and, 71
ketamine response and, 443
MRS studies for
cognitive performance and, 751–752
treatment therapies for, 752–753
tobacco use and, 753
aldehyde dehydrogenase 2 (ALDH2) gene, 700
ALE methods. See activation likelihood estimation methods
alexia without agraphia, 796
Allan-Herndon-Dudley syndrome (AHDS), 1017
clinical indications for, 1017
gene expression for, 1017
prevalence rates for, 1017
Allen Brain Atlas, 190
alpha-thalassemia intellectual disability (ATRX) syndrome, 102, 1017–1018
clinical features of, 1017
discovery of, 1017
epigenetics for, 102
gene mutations in, 1018
genetic expression in, 1017–1018
ALS. See amyotrophic lateral sclerosis
altruism, resilience and, 1150–1151
Alzheimer’s Association (AA), 792
Alzheimer’s disease (AD). See also disease modification, for AD
amino acid transmitters in, 805
limitations of, 828
animal models of
acetylcholine system in, 810–811
amyloid injection models, 811–812
brain lesions in, 811
cholinergic hypothesis for, 810–811
tacrine in, 811
APP transgenic mouse models for, 812–819
BACE1 genes, 815
behavioral changes in, 815–818
BRI fusion proteins, 814
crossing with alternative lines, 815
gene targeting in, 815
Morris water maze for, 815–816
mutations in, 814
object recognition in, 816
ownership of, 815
pathology sequencing in, 818
physiological changes in, 818
radial arm water maze for, 817–818
Tau depositing mice, 818
biomarkers for, 798–799, 793–794, 834–840
abnormalities in, 792
amyloid imaging for, 798
APP proteins, 836
assay performance and, 841–842
in clinical trials, 857–858, 861–862, 862–864
cognitive decline and, 842
diagnosis through, 798, 840, 842
in diagnostic criteria, 798, 840
in disease modification, 856–857
future applications for, 840–842
neuroimaging for, 821–825, 828–830
for pathophysiology, 836
standardization of techniques for, 798, 841
in treatment therapies, 840
BOLD signaling in, 825
brain functions, 799
executive, 799
as chronic disease, 834
clinical indications for, 834
clinical trials for
for asymptomatic patients, 858
biomarkers for, 857–858, 861–862, 862–864
cognitive outcomes for, 860
computerized outcomes in, 861
considered populations in, 857–859
for dementia, onset of, 859
functional outcomes for, 860
globalization as influence on, 863
global outcomes for, 860
MCI onset and, 859
NINCDS-ADRDA criteria for, 857
patient-reported outcomes in, 861
for patients at biological risk, 857
for patients at genetic risk, 857
recruitment challenges in, 862
representative samples in, 863
retention challenges in, 863
secondary outcomes in, 861
slope change in, 860
continuum of, 792
DIAN and, 792
CSF and
amyloid mechanisms, 835
APP, 836
asymptomatic AD, 836
with dementia, 835
NFTs in, 835
Tau protein, 835
advanced, 797
alexia without agraphia, 796
aphasia and, 796
Capgras syndrome and, 798
cardiovascular risk factors and, 849–851
clinical course of, 796
clinical trials for, 859
CSF in, 835
depression and, 798
Gerstmann’s syndrome, 796
history taking for, 794
lab evaluation of, 796
mental status tests for, 795
neuroimaging for, 796
neurological examinations for, 796
neuropsychiatric features, 797–798
neuropsychological evaluations for, 795–796
phenotypes for, 797
prevalence rates for, 854
radiological evaluation of, 796
diagnostic criteria for, 792–796, 834
development of, 792
early, 834
postmortem identification in, 834
in primary care settings, 834
in secondary care settings, 834
discovery of, 791
early-onset familial, genetics of, 805–807
fMRI for, 825
default networks in, 825
gene targeting approaches for,
in transgenic mouse
models, 815
genetics of
amino acid sequences in, 805
chromosomal markers in, 805–806
development of, 805
early-onset familial AD, 805–807
through family studies, 805
inheritance in, 805
mutations in, 806
onset of, 805
through post-mortem examinations, 805
risk factors, 805
through twin studies, 805
in Hispanic Americans, 801–802
homocysteine levels and, 847
intrinsic plasticity and, 71
late life depression and, 478
LBD compared to, 874
LOAD, 792
ADAM10 genes, 808
GWAS for, 807
risk factors for, 806
ACh for, 845
clinical trials for, 859
etiology of, 823
for hippocampal volume, 822–823
National Alzheimer’s Project Act, 844
neuroimaging for
benefits of, 821
with biomarkers, 821–825, 828–830
with dementia, 796
function of, 821
neurodegeneration estimation with, 821–825
purpose of, 821
neuropsychological features, 799–802
ascertainment bias, 800
for attention, 799
brain regions and, 799
cognitive testing of, 800
in diverse populations, 801–802
EM and, 799
executive functioning, 799
biomarker abnormalities in, 792
brain hypometabolism in, 792
causes in, 792
diagnostic criteria in, 792
plaques in, 791
treatment therapies in, 792
phenomenology of, 854
phenotypes for, 133
prevalence rates for, 791, 834
prodromal period of, 133
stem cell modeling for, 132–133
symptoms of, 791
synaptic plasticity and, 67
transgenic mouse models for, 110, 812–818
BRI fusion proteins, 814
development of, 813
features of, 813
gene targeting in, 815
introduction of, 812
mutations in, 814
overexpression in, 814
treatment therapies for
ADAPT, 846
with anti-hypertensive drugs, 850
with anti-inflammatory drugs, 846
biomarkers in, 840
B vitamins in, 847
cardiovascular risk factors and, 849–851
with cholesterol lowering agents, 850
with COX enzymes, 846
with curcumin, 848
with diabetes medications, 850–851
FDA approvals for, 844
future research on, 851
with gingko, 848
with gonadal hormones, 849
homocysteine levels and, 847
with memantine, 845
with NSAIDs, 846
with omega-3 fatty acids, 847–848
pathophysiology and, 792
with Resveratrol, 848
cognitive impact of, 907
VCI and, 900
Alzheimer’s Disease and Related Disorders Association
(ADRDA), 792
Alzheimer’s disease anti-inflammatory prevention trial (ADAPT), 846
Alzheimer’s Disease Neuroimaging Initiative (ADNI), 828–830
amantadine, 882
American Psychiatric Association (APA), 1067
amino acid transmitters, 19–21. See also γ-aminobutyric acid; glutamate
in AD, 805
anatomy of, 20
glutamic acid decarboxylase
and, 19
inactivation of, 20
monoamine transmitters compared to, 19
regulation of, 20
VGLuTs, 20
γ-aminobutyric acid (GABA)
anxiety and
clinical proof of concept for, 577–578
conflict resolution and, 575–576
cortical microcircuits, 575–576
domain-specific systems, 568–569
GABA deficits, 567
novel drug development, 576–577
pharmacology of subtypes with, 569
presynaptic modulation, 574–575
states of, 567
synaptic receptor activation, 567–568
depression and, drug development for, 578
Down syndrome and, 1063
active coping, 575
in cortical microcircuits, 576
extinction mechanisms, 575
inhibition mechanisms, 575
passive coping, 575
α-GABA receptors
anxiolysis mediation, 571, 572–573
dependence liability mediation by, 569–571
hippocampal-dependent memory regulation, 573
synaptic plasticity and, 573
memory and, drug development for, 577–578
in network oscillations, 302–303
neurodevelopmental disorders and, 990–991
panic disorder and, 567
receptors, 302
anatomy of, 20
anxiolytics and, 36
benzodiazepines and, 36, 61, 571
GAD and, 19
inactivation of, 20
monoamine transmitters compared to, 19
neuroimaging of, in psychiatric disorders, 264, 265
regulation of, 20
subtypes, , 301
VGLuTs, 20
reward and, 734
alterations specific to, 307–309
in alternate brain regions, 307
calretinin cells in, 307
CCK cell alterations, 306, 309
GAD1 genes, 308
network oscillations and, 309
neurotransmission of, 304
NMDA hypofunction in, 308
reduced excitation consequences in, 309
SST neurons and, 307
synthesis alterations, 304
TrkB genes, 308
uptake alterations, 304
in vivo measurements, 307
WM and, 309
sleep cycles and, 1131
AMPA receptors, neurodevelopmental disorders and, 991
amphetamine, psychosis and, 349
amygdala activity
lateral circuits in, 574
BPD and, 1092
depression and, 428
emotions and, 474
in neurocircuitry-based models, 465–466
emotional regulation and, 607–609
during infancy, development of, 596
lateral circuits in, 574
GAD and, 614
in neurocircuitry of addiction, 684–685
panic disorder and, 615
reactive aggression and, 1109–1110
reward and, 734
amyloid imaging
limitations of, 828
costs of, 208
florbetapir, 208
PIB, 208
amyloid injection models, 811–812
amyloid precursor protein (APP)
as biomarker, 836
transgenic mouse models
BACE1 genes, 815
behavioral changes in, 815–818
BRI fusion proteins, 814
crossing with alternative lines, 815
gene targeting in, 815
Morris water maze for, 815–816
mutations in, 814
object recognition in, 816
ownership of, 815
pathology sequencing in, 818
physiological changes in, 818
radial arm water maze for, 817–818
Tau depositing mice, 818
amyotrophic lateral sclerosis (ALS), 150
riluzole therapy for, 445
AN. See anorexia nervosa
anandamide, 50
androgens, mood regulation and
in males, 493
antidepressants for, 493
testosterone levels and, 493
Angelman syndrome (AS), 99–101, 252, 1024
cause of, 100
angiotensin receptor (AGTR) genes, 477
anhedonia
anticipatory, 393
DAs and, 733
decisional, 393
animal models. See also associative conditioning animal models; knockout rat models; mouse models; rat models
of AD
acetylcholine system in, 810–811
amyloid injection models, 811–812
brain lesions in, 811
cholinergic hypothesis for, 810–811
tacrine in, 811
of addiction, 679–680. See also susceptibility, in addiction
for individual traits, 711
neuroimaging for, 721, 723–725
chemical, 976
environmental, 976
neurotransmitters in, 1035
in adult bonding, 1119
of adult bonding, 1119
dopamines in, 1121
oxytocin in, 1121
partner preference in, 1120–1121
selective aggression in, 1121–1123
separation distress in, 1123
alcohol use in, 677
for antidepressants, 37
for anxiety disorders, 543–546, 552–560
abnormal responses, 553
benzodiazepines in, 546
gene identification in, 543–545
gene-targeting approaches for, 545–546
normal responses, 553
selective breeding of, 544–545
state anxiety, 553
trait anxiety, 553
translational neurogenetics, 546
translational studies for, 543
appetitive tasks in, 415
NSF in, 415
arrays for, 969
environmental, 972
for FXS, 971
15q11-13 duplication/deletion syndrome and, 971
for RTT, 971
validity-based, 972
VPA intake in, 972
for memory, 358
memory and, 358
stress response and, 358
brain development in, 10
of childhood psychiatric disorders, 937
behavioral tests in, 968
criteria for, 967
prenatal stress in, 958
purpose of, 967
glial loss, 430
neurogenesis and, 430
chromosomal trisomy and, 973
dosage-sensitive gene expression in, 973
with mice, 973
transgenic, 110
of drug addiction, 679
electrophysiology for, recording of, 32–33
epigenetics in, of childhood psychiatric disorders, 957–958
of fear, 553–560. See also associative conditioning animal models; conditioned fear
antipredator, 554
for fear learning, 593
instrumental avoidance conditioning, 558–560
functions, 123
Fmr1KO, 974
point mutation, 974
therapeutic implications for, 974–975
transgenic, 974
gene targeting approaches in, for anxiety disorders, 545–546
grooming behaviors in, 417
of ID, 972–973. See also Down syndrome; Fragile X syndrome
environmental, 975
metabolism errors, 975
PKU in, 975
appetitive tasks in, 415
behavioral validity of, 414
CMS, 418
developmental stressors in, 419–420
early life stressors in, 419–420
learned helplessness in, 418–419
olfactory bulbectomy, 418
pathological validity of, 414
repeated social defeat stress in, 420–421
microbubbles in, 149
of mood disorders, 296
for CMS, 411
computer-generated programs, 411
construct validity of, 411–412
for drug screening, 411
neuroimaging abnormalities in, 462
pathological validity of, 413
predictive validity of, 413
purpose of, 411
symptom modeling, 413
mutant analysis for, 109
signal transduction pathways, 109
transcriptional hierarchies, 109
of normal anxiety, 553–560. See also associative conditioning animal models
antipredator models, 554
instrumental avoidance conditioning, 558–560
antipredator, 554
instrumental avoidance conditioning, 558–560
for circuit abnormalities, 652–653
future applications of, 653
for genetic abnormalities, 652
of pathological anxiety, 560–564
developmental manipulations in, 561
genetic manipulations in, 561–562
incubation in, 563
individual differences in, 562
psychological manipulations in, 561
reconsolidation in, 563
stress-enhanced fear learning in, 561
treatment processes in, 562–564
developmental manipulations in, 561
genetic manipulations in, 561–562
incubation in, 563
individual differences in, 562
psychological manipulations in, 561
reconsolidation in, 563
stress-enhanced fear learning in, 561
treatment processes in, 562–564
of PD, 810
MPTP model, 810
for psychiatric disorders, 133–134
endogenous neurogenesis models, 133–134
neural precursors, 133
stem cells and, 133
with in vivo transplantation, 133
of psychosis, 349–350, 358–359
fear conditioning models, 664
repeated chronic stress models, 664–665
single prolonged stress models, 665
purpose of, 810
for disease mechanisms, 810
for treatment therapies, 810
with depressed mice, 422
FSL rat model, 421
in signal transduction pathways, 39, 109
through mutant analysis, 109
social avoidance behaviors in, 416–417
stress in, 418
of SUD, 763–764. See also susceptibility, in addiction; withdrawal model
AUD in, 677
conditioned place preference paradigms in, 677–678
CPP models, 763
for drug addiction, 679
epidemiology of, 784
ICSS in, 678
incubation of craving model, 764
maladaptive patterns in, 675
operant paradigms in, 677
schedule requirements in, 677
self-administration methods, 677
structural plasticity in, 675
of tic disorders, 1050
gene expression in, 1050
transcription control in, 109
treatment therapies and, 810
for resilience, 1163
autoimmune models, 977
dopamine transporter genes in, 977
gene expression in, 1050
monkey focal striatal disinhibition in, 977
psychostimulant model, 977
anorexia nervosa (AN)
activity-based, 1183
genetic vulnerability for, 1172–1174
through candidate gene studies, 1174
through GWAS, 1174
neurobiology of, 1171
predictors of, 1171
harm avoidance, 1182
perfectionism and, 1182
anterior neural ridge (ANR), 983–985
antibodies
in disease modification, for AD, 867–868
anticipatory anhedonia, 393
antidepressants
animal models for, 37
electrophysiology of, 518
genetic, 518
neuroimaging for, 518
biperiden, 446
CAD and, 503
catecholamines and, 61
development of, 509
diabetes mellitus and, 503–504
epigenetic influence on development of, 96–97
future developments for, 523–524
HIV/AIDS and, 504
inflammatory cytokines and, 432
alcohol dependence and, 443
molecular mechanisms in, 442
with ketamine-like targets, 434–435
for males, 493
endogenous, 512
reversible, 512
side effects of, 511
SAM-e, 522
plasma membrane transport inhibition and, 61
molecular mechanisms of, 448
remission rates for, 516
side effects of, 516
somatic, 466
dosage regimen for, 512
drug interactions with, 512–514
half-life of, 512
for medical illness, depression and, 502
side effects of, 512
TCAs compared to, 509
dosages, 509
SSRIs compared to, 509
toxicity of, 511
atypical antipsychotics for, 517
augmentation therapy for, 517–518
combination therapy for, 517
hormonal strategies for, 517–518
lithium in, 517
usage demographics for, 513
Antidepressant Treatment History Form (ATHF), 390
anti-hypertensive drugs, AD treatment and, 850
anti-inflammatory drugs, AD treatment and, 846
antioxidants
in AD treatment therapies, 846–847
antipredator models, 554
antipsychotic drugs
depolarization block and, 37
drug development for, 256, 350
extrapyramidal symptoms of, 37
glutamatergic, 352
muscarine agonists, 352
neuroleptics, 61
olanzapine, 351
quetiapine, 351
risperidone, 351
for schizophrenia, 329
second generation, 351
for tic disorders, 1058
for TRD, 517
for TS, 1058
antisocial personality disorder (ASPD), 1093–1097
aggression and, 1094
candidate gene studies for, 1097
childhood antecedents for, 1094
clinical indications for, 1093–1094
cognitive function and, 1096
comorbidities with, 1094
development of, 1094
in DSM-IV, 1094
epidemiology of, 1094
genetic vulnerability of, 1096
instrumental aggression and, 1104
linkage analysis for, 1096–1097
neurobiology of, 1095
prefrontal abnormalities for, 1095
prevalence rates for, 1094
psychopathy compared to, 1094
reactive aggression and, 1094–1095
anxiety. See also fear; pathological anxiety; pathological fear
lateral circuits in, 574
animal models of, 553–560. See also associative conditioning animal models
antipredator, 554
instrumental avoidance conditioning, 558–560
BI theory of, 564
definition of, 550
FBS and, 550
fear compared to, 550
GABA receptors
clinical proof of concept for, 577–578
conflict resolution and, 575–576
cortical microcircuits, 575–576
deficits in, 567
domain-specific systems, 568–569
novel drug development, 576–577
pharmacology of subtypes with, 569
presynaptic modulation, 574–575
states of, 567
synaptic receptor activation, 567–568
inhibition of, 560
conditioned, 560
latent, 560
negative feedback, 560
normal compared to pathological, 552
separation disorder and, 531–532
in DSM-V, 1069
pediatric, 539
stress responses to, 552
anxiety disorders. See also fear; pathological anxiety; pathological fear; specific disorders
animal models for, 543–546, 552–560
abnormal responses, 553
benzodiazepines in, 546
gene identification in, 543–545
gene-targeting approaches for, 545–546
normal responses, 553
selective breeding of, 544–545
translational neurogenetics, 546
translational studies for, 543
conceptual framework for, 549–551
conditioned fear as model, 606–607
for emotional regulation, 606–607
defensive responding in, 549–550
exaggerated, 552
FBS and, 550
hyper-responsive, 552
inappropriate, 552
pathological anxiety and, 552
pathological fear and, 552
prolonged, 552
topography of, 550
diagnosis of
development history of, 529
emotional regulation and, 587–589
family studies
genetic epidemiology in, 537–539
for pediatric anxiety disorders, 539
genetic epidemiology of, 537–540
developmental changes in, 539–540
in gene association studies, 540–541
susceptibilities in, 540
transporter genes, 541
language framework for, 549–551
optogenetic technology for, 142
pediatric
age of onset for, 539
family studies, 539
separation anxiety disorder, 539
SOC, 539
twin studies, 539
prevalence rates for, 527
dysregulation types in, 1083–1084
fear circuit dimensions for, 1083
heterogeneity of expression for, 1083
in twin studies, 1083
threat processing and, 549–550
treatment therapies for. See also cognitive bias modification therapy; D-cycloserine therapy
access to, 622
with benzodiazepines, 622, 636–637
CBT, 621
cognitive approaches to, 626–630, 636–638
cost effectiveness of, 631–632
exposure therapies, 622
with glucocorticoids, 623, 633–634
with MAOIs, 636
RCTs for, 621
with SNRIs, 636
with TCAs, 636
with yohimbine hydrochloride, 623–624, 633–634
anxiolytics
GABA and, 36
AP-1. See activator protein-1
APA. See American Psychiatric Association
aphasia, 796
diagnostic criteria for, 889
logopenic variants for, 892
nfvPPA, 891
semantic variants for, 891–892
apoptosis
signal transduction pathways and, 55
APP. See amyloid precursor protein
appetitive tasks, 415
NSF in, 415
Aricept, 845
L-aromatic amino acid decarboxylase (AADC), 13–14
arterial spin labeling MRI (ASL MRI), 199–200
AS. See Angelman syndrome
ascertainment bias, 800
ASD. See autism spectrum disorder
asenapine, 351
ASL MRI. See arterial spin labeling MRI
ASPD. See antisocial personality disorder
association analysis
for genetic epidemiology, 161–162, 163
limitations of, 161
associative conditioning animal models, 554–558
behavioral aspects of, 554
molecular mechanisms of, 556
procedure variations for, 556–558
synaptic plasticity, 556
ATHF. See Antidepressant Treatment History Form
atorvastatin, 850
ATRX syndrome. See alpha-thalassemia intellectual disability syndrome
attachment. See social attachment
attention
AD and, 799
treatment therapies for, 1030–1031
attention bias modification (CBM-A) therapy, 627–628
empirical evidence for, 628
attention deficit hyperactivity disorder (ADHD), 322, 950
chemical, 976
environmental, 976
neurotransmitters in, 1035
biological adversity and, 1039–1040
clinical features of, 1034
CNVs in, 939, 950, 950–951, 1039
Cognitive-Energetic model, 1041
Conner’s Rating Scale for, 937
definition of, 934
dopamine transfer deficit model for, 1041
Dynamic Developmental Theory for, 1041
environmental risk factors for, 1039–1041
etiology of, 937
as extreme variant trait, 937
family dysfunction and, 1040–1041
family studies for, 1035–1036, 1036–1047
Feingold hypothesis for, 1039–1040
functional connectivity in, 1006
adoption studies for, 1037
CNVs in, 1039
through GWAS, 1038
linkage studies for, 1038
molecular studies for, 1037–1038
heritability of, 936
iron levels and, 1040
with DTI, 1044
with MRS, 1043
with PET, 1043
with SPECT, 1043
neuropsychological studies for, 1041–1042
neurotransmitters and, 1034–1035
animal models of, 1035
catecholaminergic systems, 1035
pathogenesis model of, 1044–1045
etiologic heterogeneity in, 1044–1045
implications for, 1045
multifactorial causation in, 1045
pregnancy complications and, 1040
prevalence of, 934, 936, 1034, 1036
protective factors for, 1039–1041
psychosocial adversity and, 1040–1041
subtypes of, 934
SUD and, 680
tobacco use and, 1040
trajectory into adulthood, 935
triple pathway model for, 1041
zinc levels and, 1040
atypical depression, 522
AUDs. See alcohol use disorders
autism spectrum disorder (ASD), 128, 948–949
cause of, 100
arrays for, 969
environmental, 972
for FXS, 971
15q11-13 duplication/deletion syndrome and, 971
for RTT, 971
validity-based, 972
VPA intake in, 972
classification of, 1022
clinical features of, 948, 1022
clinical trials for, 1062
diagnosis of, 1022
through twin studies, 1022
exome sequencing for, 949
as extreme variant trait, 937
functional connectivity in, 1005–1006
animal models of, 971
epigenetics for, 101
phenotypes for, 130
stem cell modeling for, 130
treatment therapies for, 1031–1032
gender ratio for, 936
gene expression in, 187, 949, 967, 1027–1028
common variations for, 1027
model systems in, 1028
rare variations for, 1027–1028
single-gene syndromes, 940
systems genetics and, 1028
health care costs for, 934
infant-parental attachment and, 1115–1116
maternal stress and, 956
mGluR5 receptors in, 1061–1062
of brain enlargement, 1024–1025
with DTI, 1026
cognitive deficits in, 1023
hyperactivity in, 1023
impulsivity in, 1023
inattention in, 1023
joint attention behaviors in, 1022–1023
onset patterns in, 1023
repetitive behaviors in, 1023
social communication deficits in, 1022
PKU and, 1024
PMS and, 1024
treatment therapies for, 1031–1032
polygenic sources of, 1074
prevalence rates for, 934, 935–936
reproductive disadvantage with, 939
RTT
animal models of, 971
characterizations of, 129
clinical features of, 98
gene expression conditional controls, 116
IGF-1 and, 1062
MeCP2 protein and, 98–99, 129, 971
22q13 deletion syndrome, 1062
stem cell modeling for, 129
treatment therapies for, 1031–1032
X chromosome in, 129
sensory symptoms of, 1023
synaptic disease and, 322
trajectory into adulthood, 934–935
treatment therapies for, 1028–1031
for aggressive behaviors, 1029–1030
for anxiety behaviors, 1031
for attention deficit, 1030–1031
behavioral interventions, 1028–1029
future applications of, 1031
with PBS, 1029
with pharmacotherapy, 1029–1031
with RDI, 1029
for repetitive behaviors, 1031
treatment therapies for, 1031–1032
twin studies for, 936
diagnosis through, 1022
types of, 936
WBS, 252
autonomic dysfunction, with LBD, 877
treatment therapies for, 883
autophosphorylation
homeostatic plasticity of brain and, 74
of protein tyrosine kinase
receptors, 44
axons, intrinsic plasticity and, 69
axon initial segment (AIS), 68–69
axon pathways
in brain development, 8
defasciculation in, 8
fasciculation in, 8
growth cones, 8
B
BACE1 genes, in APP mouse models, 815
bacterial artificial chromosomes (BACs), 110
Bailarger, Jules, 368
Balint’s syndrome, 796
Bardet-Biedl syndrome (BBS), 1014–1015
comorbidities with, 1015
diagnosis of, 1014
discovery of, 1014
genetic expression of, 1014
prevalence of, 1014
treatment of, 1015
Bartus, Ray, 811
base pairing, in nucleic acids, 76
BBB. See blood-brain barrier
BBS. See Bardet-Biedl syndrome
BDNF. See brain-derived
neurotrophic factor
BED. See binge eating disorder
behavioral emotional regulation, 584–587
behavioral variant of frontal lobe dementia (bvFTD), 888–890
psychiatric features of, 889–890
testing of, 890
behavior inhibition (BI) theory, 564
benzodiazepines
aggression and, 1109
in animal models, for anxiety disorders, 546
for anxiety disorders, 622, 636–637
diazepam, 567
for PTSD, 641
for SOC, 644
Berger, Hans, 1127
Bernard, Claude, 71
Bertram, Lars, 806
beta-catenin pathway, 294
binge eating disorder (BED), 1183
food addiction and, 1183
biomarkers
for AD, 793–794, 798–799, 834–840,
abnormalities in, 792
amyloid imaging for, 798
APP proteins, 836
assay performance and, 841–842
in clinical trials, 857–858, 861–862
cognitive decline and, 842
diagnosis through, 798, 840, 842
in diagnostic criteria, 798, 840
in disease modification, 856–857
future applications for, 840–842
neuroimaging for, 821–825, 828–830
for pathophysiology, 836
standardization of techniques for, 798, 841
in treatment therapies, 840
electrophysiology of, 518
genetic, 518
neuroimaging for, 518
APP as, 836
depression pathogenesis and, 438
in DSM-V, categorization of, 1070
neuroimaging for
for antidepressants, 518
biophysiology, of disease
biomedical sciences and technology, 183–184
bottoms-up modeling approaches, 196
correlations compared to, 187
for metabolic diseases, 195
in molecular settings, 186–187
structural learning and, 187
complexity of, 183, 185–186, 195
descriptive models for, 186
DNA influences, 183
future developments in, 196
GWAS for, 186
nucleotide changes, 183
predictive gene networks in, 189–195
alternative omics data in, 192
Bayesian networks in, 191, 192, 193–194
genetic data integration in, 191–192
inflammatomes in, 195
MCMC, 191
small molecule-protein interactions in, 192
TFBS data in, 192
predictive models for, 186
SNPs, 183
biperiden, 446
bipolar affective disorders, 380
bipolar depression, 523
bipolar disorder
memory and, 358
stress response and, 358
during childhood, 951
diagnostic systems for, 380
in DSM-IV, 229
environmental factors, 233–234
family studies for, 233
genetic overlap with schizophrenia, 233
incidence rates for, 232
non-inherited factors, 233–234
twin studies for, 233
genetic study methods for, 234–235
with candidate genes, 235
future applications for, 245
with GWAS, 234
overlap with schizophrenia, 242
phenotypes for, 242
large-scale sequencing studies for, 242–245
in late life, 384
MDD and
by bipolar type, 398
differentiation between, 399
family studies for, 399
beta-catenin pathway, 294
CACNA1C gene, 293
circadian-rhythm-related genes, 294
DGK models, 294
future developments for, 295–296
in Madison strain, 294
neurocan gene, 294
ODZ4 gene, 294
neurobiology of
circadian abnormalities in, 357
clinical predictors in, 356
cognitive predictors in, 356
genetics of, 355
GSK3 pathway, 360
mitochondrial dysfunction in, 360–361
neurogenesis and, 360
neuroplasticity and, 360
prodrome, 356
risk factors for, 355
polygenic sources of, 1074
rapid cycling in, 384
RDoC for, 225
recurrence risks for, 234
BI theory. See behavior inhibition theory
Blessed, Gary, 791
blood–brain barrier (BBB)
acoustic parameter dependence and, 153–154
assessment methods for, 151–153
with acoustic emission signals, 153
in disease modification, for AD, 868
drug delivery systems through, 151
FUS and, 151
functions of, 148
assessment methods with, 151–152
in drug delivery systems, 151
HIFU, 148
impermeability of, 148
inducing methods for, 151–153, 150–152
in large animals, 155
in animal models, 149
assessment methods with, 151–152
in blood supply, 149
in contrast ultrasounds, 149–150
in drug delivery systems, 151
FDA approval of, 149
Optison, 148
molecular delivery through, 154
neurodegenerative diseases and, 150–151
neurotherapeutics and, 148, 155–157
physiology of, 148
properties, 155
GKM and, 155
reversibility of, 154
safety of, 154
blood oxygenation level dependent (BOLD) signals, 200
in AD, 825
body image perception, 1182
borderline personality disorder (BPD), 1090–1093
affective dysregulation and, 1091–1092
genetics of, 1092
aggression and
impulsive dimensions in, genetics of, 1092
reactive, 1104
amygdala function and, 1092
clinical evidence for, 1090
depression and, 1091
diagnostic criteria for, 1090
FFM and, 1090
fMRI for, 1092
gender and, 1091
genetics of, 1092
illness burden with, 1090–1091
impulsive aggression dimensions in, 1091–1092
genetics of, 1092
neuroimaging for, 1091–1092, 1093
of emotion regulation, 1093
of interpersonal processes, 1093
neuropeptide model of, 1092–1093
opioids and, 1093
oxytocin for, in treatment therapies for, 1092–1093
prevalence rates for, 1090
reactive aggression and, 1104
remission rates for, 1090
self-cutting behaviors and, 1093
serotonergic system and, 1092
trauma and, 1091
treatment therapy utilization for, 1090–1091
Trier Social Stress Test for, 1093
Bourdieu, Pierre, 367
Bowen, David, 810
BPD. See borderline personality disorder
brain. See also amygdala activity; cerebral metabolic rate of oxygen; neuroimaging methodologies; prefrontal cortex
AD and, 799
executive functioning, 799
during adolescence, fear development and, 598–599
cortical-subcortical network dysfunction, 263–264
cognitive dysmetria hypothesis, 264
depression neurobiology, 459
development. See also central nervous system; homeostatic plasticity, of brain; intrinsic plasticity, of brain; postnatal brain development; prenatal brain development; synapses; synaptic plasticity
in animals, 10
axon pathways in, 8
cell migration in, 7
in childhood, 980
critical periods of, 10
differentiation of cells in, 7
emotional behavior mediation, 128
endogenous stem cells and, 128
epigenomes in, 10
excitation/inhibition balance in, 10
glial cells, 7
long-term depression in, 10
LTP in, 10
NAc, 67
in neonates, 10
neurodevelopmental disorders and, 1004–1005
neurons, 7
Notch signaling in, 7
sleep functions for, 1139–1140
synapse development, 8
VTA, 67
disease phenotypes, 322–324. See also synaptic disease
epigenetics
chromatin architecture, 174–175
coding sequence mutations, 177
developmental plasticity of, 175–176
DNA structural variants, 178–179
drug development for, 178, 177–178
eraser proteins, 177
euchromatin, 173
foundations of, 172
heterochromatin, 173
histones, 174
monogenetic etiologies, 176–177
nucleosomes, 173
for PTSD, 176
reader proteins, 177
writer proteins, 177
functions. See also homeostatic plasticity, of brain; intrinsic plasticity, of brain; synapses; synaptic plasticity
action potentials and, 64
AD and, 799
EPSP and, 64
information transmission, 64
IPSPs and, 64
neuronal network for, 64
neurotransmitters and, 64
saving, 70
GABA and, schizophrenia and, 307
habenula, in neurocircuitry of addiction, 685
hippocampus
depression and, 428
emotional regulation and, 610
fear development and, 597, 600–601
α-GABA receptors, 573
hypometabolism, in AD, 792
hypothalamus
circadian clock influenced by, 1131
emotional regulation and, 609
encephalitis lethargica and, 1131
sleep cycles and, 1131
insula
emotional regulation and, 609
in neurocircuitry of addiction, 685
PTSD and, 617
social anxiety disorder and, 612
lateral habenula, 735
lesions
in animal models, of AD, 811
in late life depression, 470–471
BOLD, 200
Cho peak, 743
GluR genes, 742
for metabolite abnormalities, 757
MI, 743
NAA, 742
PCr, 744
in personality disorders, 1089
in reward, 735
periaqueductal gray region, emotional regulation and, 609
postnatal development, 987–990
chromatins in, 987
critical periods of, 987
environmental influences on, 987–988
LRRTMs in, 989
multiprotein complexes in, 988
neural plasticity and, 988
stress and, 987
synaptogenic proteins and, 988–989
cellular migration in, 985
cortical migration and, 985–987
dysraphias and, 981
mechanistic models for, 985
neural tube regionalization in, 982–983
neuroepithelium support, 983–984
SHH and, 983
transcriptional support in, 984–985
psychiatric disorders and, neuroimaging of, 257–258, 258
in schizophrenia neurodevelopmental model, 328
functions of, 1139
social
evolution of, 1113
social attachment and, neurobiology of, 1124–1125
stimulation methodologies. See also deep brain stimulation; transcranial direct current stimulation; transcranial magnetic stimulation
future applications for, 218–219
structure compared to function in, 212
targeting in, 213
targeted treatment therapies in, 1076
brain-derived neurotrophic factor (BDNF), 25
addiction and, 688
in depression treatment responses, 432–433
late life depression and, 477
network-wide homeostatic plasticity and, 74
neurotherapeutics and, 155–157
resilience and, 1157
brain lesions
in animal models, of AD, 811
in late life depression, 470–471
BRI fusion proteins, 814
Brown-Sequard, Charles, 483
bulimia nervosa
development of, 1172
genetic vulnerability for, 1174–1175
neurobiology of, 1171
for appetite, 1181
for body image perception, 1182
for emotional processing, 1181–1182
prevalence rates for, 1172
bupropion, 515
Burton, Robert, 470
bvFTD. See behavioral variant of frontal lobe dementia
B vitamins, in AD treatment, 847
C
CA2+. See calcium
CACNA1C gene, 293
CAD. See coronary artery disease
Cade, John, 390
calcium (CA2+)
calmodulin, 47
depolarization of neurons and, 47–49
IP3 receptors, 47
in neurons, 28
ryanodine receptors and, 47
in signal transduction pathways, 47–49, 53–54
target proteins for, 53
TS and, 130
calmodulin, 47
promoter genes, 116
calretinin cells, 307
cAMP. See cyclic adenosine 3’-5’-monophosphate
cancer
depression and, 501
antidepressant therapy, 504–505
cytokines and, 501
prevalence rates for, 501
sickness syndrome and, 501
targeted treatment therapies for, 1076
candidate gene studies
for AN, 1174
for addiction, 700
for ASPD, 1097
for PTSD, 541
for tic disorders, 1050
for TS, 1050
canine adenovirus (CAV), 117
cannabinoids. See endocannabinoids
Capgras syndrome, 798
Caraka Samhita, 368
carbamazepine, 514
cardiac disease. See coronary artery disease
cardio-facio-cutaneous syndrome (CFCS), 1011–1012
clinical indications for, 1011
Costello syndrome and, 1011
Noonan syndrome and, 1011
pregnancy and, 1011
prevalence rates for, 1011
Carter, Sue, 1120
catecholamines, 13–18. See also dopamines
in ADHD, 1035
antidepressants and, 61
DATs, 17
enzymatic inactivation of, 16
GABA receptors, anxiety and, 574–575
MAOs and, 16
NETs, 17
phenylalanine, 14
storage of, 15
TH and, 14
trace amines, 15
VMAT and, 15
catechol-O-methyltransferase (COMT), 666
aggression and, 1109
caudolateral prefrontal cortex (CLPFC), 457
causality, in biophysiology of disease, 186–189
correlations compared to, 187
in molecular settings, 186–187
structural learning and, 187
CAV. See canine adenovirus
CBM-A. See attention bias modification therapy
CBM-I therapy. See interpretive bias modification therapy
CBM therapy. See cognitive bias modification therapy
CBS. See corticobasal syndrome
CBT. See cognitive behavioral therapy
CCK. See cholecystokinin
CD. See conduct disorder, instrumental aggression and
CDR. See Clinical Dementia Rating
cells. See also apoptosis; glial cells; stem cells
in CNS, migration of, 7
fate of, in brain development, 7, 7–8
migration of, in brain development, 7
proliferation of, in brain development, 5–7
cell-autonomous plasticity, 72–73
central nervous system (CNS). See also induction, in CNS; neurochemical systems, in CNS
cell migration in, 7
organizers in, 3
in visual system, 9
cerebral metabolic rate of oxygen (CMRO2), 205–207
deformation-based morphometry for, 208
measure of, 206
MRI and, 206
cerebral perfusion, MRI assessment, 199–200
DSC, 199
SS contrast, 199
cerebrospinal fluid (CSF)
AD and
amyloid mechanisms, 835
APP, 836
asymptomatic, 836
with dementia, 835
NFTs in, 835
Tau protein, 835
childhood psychiatric disorders and, 957
FTD and, 893
CFCS. See cardio-facio-cutaneous syndrome
CGH. See comparative genomic hybridization
channel rhodopsins (ChRs), 138
childhood, psychiatric disorders during. See also attention deficit hyperactivity disorder; autism spectrum disorder; intellectual disability; pediatric anxiety disorders; postnatal brain development; prenatal brain development; specific disorders
animal models of, 937
behavioral tests in, 968
criteria for, 967
prenatal stress in, 958
purpose of, 967
bipolar disorder, 951
genetic expression of, 944–945
common DNA variants in, 938–939
SNVs in, 950
developmental disorders during
pervasive, 933
prevalence rates of, 933
research history on, 933
in DSM-V, 1069
epidemiology of, 956
epigenetics of
11β-HSD2 in, 963
for affective disorders, 956–957
for ASD, 956
corticosterones in, 963
CRF concentration in, 957
CSF concentration in, 957
DNMTs and, 963
epidemiology of, 956
fetal antecedents in, 955, 955–957
germ cell programming in, 959
high fat diets in, 960
history of, 955
immune activation in, 959
mechanisms of, 955
miRNA in, 963
obesity models for, 960
placental contributions in, 962–963
PPI and, 959
prenatal infection in, 959
prenatal stress and, 958
transgenerational, 965
genetic expression of, 938–941
DNA in, 944
exome sequencing for, 947–948, 949, 950
genetic susceptibility, 951
with GWAS, 938–939, 940–941, 944
of ID, 933
with MPS, 945
SNPs and, 945
genetics of, 938
GWAS for, 938–939, 940–941, 944
IED, 951
maternal influences on, 955–956
MDD during, from trauma, 399
normal trait variations in, 936–938
phenotypic relationships between, 938
prevalence rates of, 933, 935–936
RDoC and, 1078
reproductive disadvantage and, 938–939
research history on, 933
schizophrenia during, 328
SNPs and, 945
in ASD, 949
in COS, 950
in genetic expression, 944–945
trajectories in adulthood, 934–935
childhood onset schizophrenia (COS), 949–950
exome sequencing for, 950
SNVs in, 950
childhood overanxious disorder (OAD), 540
cholecystokinin (CCK), 1176–1177
cholesterol lowering agents, AD treatment and, 850
cholinergic hypothesis, for AD, 810–811
clinical trials with, 446–450, 447
neuroimaging and, 449
mecamylamine, 450
varenicline, 450
physiology of, 446
WM and, 449
Cho peak, MRs for, 743
chromatins, 91
epigenetic mechanisms of addiction, 691
neuroepigenetics
euchromatin, 173
heterochromatin, 173
in postnatal brain development, 987
CNVs and, 247
IBD, 161
in RTT, 129
X, 129
YACs, 110
chronic diseases
AD as, 834
SUD as, 777
chronic mild stress (CMS), 411
epigenetic response to, 96
MDD and, 96
in animal models, 418
chronic unit recording, 32
ChRs. See channel rhodopsins
ciliary neurotrophic factor (CNTF), 84
circadian clock, sleep cycles and, 1131
hypothalamic influences on, 1131
circadian-rhythm-related genes, 294
CJD. See Creutzfeldt-Jakob disease
classical conditioning models, of drug addiction, 737
classical neurotransmitters, 13. See also catecholamines
definitional criteria for, 13
peptide compared to, 21
synthesis of, 13
Clinical Dementia Rating (CDR), 794–795
clinical trials, for AD
for asymptomatic patients, 858
biomarkers for, 857–858, 861–864
cognitive outcomes for, 860
computerized outcomes in, 861
considered populations in, 857–859
for dementia, onset of, 859
functional outcomes for, 860
globalization as influence on, 863
global outcomes for, 860
MCI onset and, 859
NINCDS-ADRDA criteria for, 857
patient-reported outcomes in, 861
for patients at biological risk, 857
for patients at genetic risk, 857
recruitment challenges in, 862
representative samples in, 863
retention challenges in, 863
secondary outcomes in, 861
slope change in, 860
CLPFC. See caudolateral prefrontal cortex
CMRO2. See cerebral metabolic rate of oxygen
CMS. See chronic mild stress
CNS. See central nervous system
CNTF. See ciliary neurotrophic factor
CNTRICS. See Cognitive Neuroscience for Translational Research in Cognition in Schizophrenia
CNVs. See copy number variants
cocaine use. See also drug abuse
epigenetics and, 95
ΔFosB transcription factor, 115
withdrawal model for, 679
Cognex. See tacrine
cognitive behavioral therapy (CBT), 521
for anxiety disorders, 621
ICT and, 631
limitations of, 658
for PTSD, 669
cognitive bias modification (CBM) therapy, 627–630
empirical evidence for, 628
CBM-I, 628
cost effectiveness of, 632
empirical evidence for, 628–629
clinical potential of, 630
empirical evidence for, 628–629
future research directions for, 630
mechanisms of action for, 629–630, 633
cognitive dysmetria hypothesis, 264
cognitive emotional regulation, 584–587
Cognitive-Energetic model, 1041
Cognitive Neuroscience for Translational Research in Cognition in Schizophrenia (CNTRICS), 1078
cognitive therapy (CT), for OCD, 658
Cohen syndrome (CS), 1015–1016
clinical indications for, 1015–1016
phenotypes for, 1015
combinatorial optogenetics, 144
comparative genomic hybridization (CGH), 944–945
compulsivity, addiction and
neurocircuitry of, 685
transition to, 736
COMT. See catechol-O-methyltransferase
conditional knockout mouse models, 116–117
NT-3 factors, 116
RTT, 116
as anxiety disorder model, 606–607
Little Albert case study, 607
PFC and, 595
resilience and, 1160
conditioned place preference paradigms, 677–678
in SUD animal models, 763
conduct disorder (CD), instrumental aggression and, 1104
connectomes, 995, 997–998, 1000
connectomics, 1073
Conner’s Rating Scale, 937
consciousness, during sleep, 1137
in NREM sleep, 1137
context processing, in schizophrenia, 269–270
coping mechanisms
GABA, fear and, 575
pathological anxiety and, 562–564
pathological fear and, 562–564
resilience and, 1148, 1149–1150
acceptance, 1149
facing fears, 1149
humor as, 1149
physical exercise as, 1149–1150
social support and, 1150
coprolalia, 1048
copy number variants (CNVs)
bipolar disorder and, 235–237, 253
in childhood psychiatric disorders, 939–940, 951
chromosomal deletions in, 247
for MDD, 404
schizophrenia and, 235–237, 248
duplications, 250–251, 251, 252–253
coronary artery disease (CAD), depression and, 498–499
antidepressant therapy, 503
autonomic nervous system and, 499
comorbidity mechanisms with, 498–499
endothelial dysfunction and, 499
HPA axis and, 498
inflammation and, 498
statins for, 498
sympathoadrenal hyperactivity and, 498
cortical-subcortical network dysfunction, 263–264
cognitive dysmetria hypothesis, 264
corticobasal syndrome (CBS), 892
corticosterones, 963
cortico-striatal models, for schizophrenia, 264
cortico-striato-thalamo-cortical (CSTC) circuits, 648–649
corticotropin-releasing factor (CRF), 450–451
childhood psychiatric disorders and, 957
in neurocircuitry of addiction, 685
corticotropin-releasing hormones (CRH)
CRHR1, 666
cortisol, resilience and, 1151–1154
COS. See childhood onset schizophrenia
Costello syndrome, 1011
COX enzymes. See cyclooxygenase enzymes
craving
spontaneous, 728
SUD and, 774
CREB protein. See cyclic adenosine monophosphate response element binding proteins
Creutzfeldt, Hans, 915
Creutzfeldt-Jakob disease (CJD), 835
diagnostic testing for, 921
discovery of, 915
fCJD, 923
diagnostic criteria for, 918
EEG for, 919
neuropsychiatric features of, 919
prevalence rates for, 920
CRF. See corticotropin-releasing factor
CRH. See corticotropin-releasing hormones
cross mutual information, 1003
CS. See Cohen syndrome
CSF. See cerebrospinal fluid
CSTC circuits. See cortico-striato-thalamo-cortical circuits
CT. See cognitive therapy
curcumin, 848
cyclic adenosine 3′-5′- monophosphate (cAMP), 50
cyclic adenosine monophosphate response element binding (CREB) proteins
characterization methods for, 82
protein family for, 82
regulation mechanisms for, 82
signaling pathways for, 2, 50, 82
as transcription factor, 81–82
TS and, 129
viral-mediated gene transfer applications, 118–119
cyclic nucleotides, 46
cyclooxygenase (COX) enzymes, 846
cyclosporine, 514
cyclothymia, 368
diagnostic systems for, 380
symptoms of, 380
cytokines
childhood psychiatric disorders and, 963
CNTF, 84
antidepressant therapy and, 432
cancer and, 501
long-term consequences of, 431–432
mechanisms of, 431
gene expression regulated by, 84
IL-6, 84
LIF, 84
cytosine, 76
D
DAs. See dopamines
DATs. See dopamine transporters
Davies, Peter, 810
DBH. See dopamine-β-hydroxylase
DBS. See deep brain stimulation
DCM. See dynamic causal modeling
D-cycloserine (DCS) therapy, 624–626
clinical potential for, 626
cost effectiveness of, 632
empirical evidence for, 624–625
future research directions for, 625–626
mechanisms of action for, 633
for OCD, 625
for panic disorder, 625
decisional anhedonia, 393
deep brain stimulation (DBS), 217–218, 520
description of, 217
effect imaging in, 218
interleaved scanning in, 218
for neurocircuitry-based models of depression, 466
for OCD, 659
placement targeting in, 218
for tic disorders, 1058
for Tourette’s syndrome, 1058
defasciculation, 8
default mode network (DMN), 272–273
exaggerated, 552
FBS and, 550
hyper-responsive, 552
inappropriate, 552
pathological anxiety and, 552
pathological fear and, 552
prolonged, 552
topography of, 550
deformation-based morphometry, 208
dehydroepiandrosterone (DHEA), 1154–1155
dementia. See also Alzheimer’s disease; Lewy body dementias; Parkinson’s disease
advanced, 797
alexia without agraphia, 796
aphasia and, 796
Capgras syndrome and, 798
cardiovascular risk factors and, 849–851
clinical course of, 796
clinical trials for, 859
CSF in, 835
depression and, 798
Gerstmann’s syndrome, 796
history taking for, 794
lab evaluation of, 796
mental status tests for, 795
neuroimaging for, 796
neurological examinations for, 796
neuropsychiatric features, 797–798
neuropsychological evaluations for, 795–796
neuropsychological testing for, 795–796
phenotypes for, 797
prevalence rates for, 854
radiological evaluation of, 796
dementia praecox, diagnosis of, 223
clinical features of, 874
delusions with, 876
depression with, 876
diagnostic criteria for, 873–874
hallucinations with, 876
memory deficits with, 876
neuroleptic sensitivity in, 878
PDD compared to, 874
psychiatric symptoms with, 876
visuospatial deficits in, 875
FTD
causes of, 887
CBS and, 892
clinical syndromes with, 887, 888
CSF and, 893
diagnostic criteria for, 889
discovery of, 887
EEG for, 893
FTD-MND, 890
FTLD, 887
by gender, 888
mortality rates for, 888
MRI for, 892
PSP and, 892
treatment therapies for, 895–897
as public health crisis, 790
dementias with Lewy bodies (DLB), 872–874
clinical features of, 874
delusions with, 876
depression with, 876
diagnostic criteria for, 873–874
hallucinations with, 876
memory deficits with, 876
neuroleptic sensitivity in, 878
PDD compared to, 874
psychiatric symptoms with, 876
visuospatial deficits in, 875
dendrites, 68
DENT study, for MDD, 400
deoxyribonucleic acid (DNA), 76–77. See also gene expression; methylation, of DNA; transcription control, for genomes
BACs, 110
base pairing in, 76
biophysiology influenced by, 183
in childhood psychiatric disorders, 944
chromatins and, 91
DNMTs, 88
in epigenetics of childhood psychiatric disorders, 963
information flow in, to proteins, 77–78
NAHR and, 944
neuroepigenetics, 173–174, 178–179
nucleosomes in, 79
nucleotide bases in, 76
satellite, 78
structure of, 76
transcription into RNA, 77
in transgenic mouse models, 109–110
YACs, 110
depolarization block, 37
deprenyl, 16
depression. See also antidepressants; glutamate system; major depressive disorder; medical illness, depression and
adrenal glucocorticoids and, 430–431
AD with dementia and, 798
antidepressant therapy for, 37
glial loss, 430
neurogenesis and, 430
atypical, 522
bipolar, 523
BPD and, 1091
antidepressant therapy, 503
autonomic nervous system and, 499
comorbidity mechanisms with, 498–499
endothelial dysfunction and, 499
HPA axis and, 498
inflammation and, 498
statins for, 498
sympathoadrenal hyperactivity and, 498
cancer and, 501
antidepressant therapy, 504–505
cytokines and, 501
prevalence rates for, 501
sickness syndrome and, 501
cholinergic system and
neuroimaging and, 449
physiology of, 446
WM and, 449
antidepressant therapy and, 432
cancer and, 501
long-term consequences of, 431–432
mechanisms of, 431
diabetes mellitus and, 499–500
antidepressant therapy, 503–504
cellular glucose transporters and, 500
comorbidity mechanisms, 499–500
HPA axis and, 500
neuroimaging for, 500
psychosocial burden as factor in, 499–500
with DLB, 876
DLB with, 876
experimental medicine therapy for, 451
GABA receptors, drug development and, 578
genetic definition of, 396
history of, 439
physiology of, 439
riluzole therapy, 445
VGLuTs in, 439
gonadal steroids and
menstrual cycle effects, 486
HIV/AIDS and, 380–381, 500–501
antidepressant therapy, 504
comorbidity mechanisms, 500–501
HPA axis and, 501
prevalence rates for, 500
inflammatory cytokines and, 431–432
antidepressant therapy and, 432
long-term consequences of, 431–432
mechanisms of, 431
in late life
AD and, 478
AGTR genes, 477
basal ganglia circuits and, 475
BDNF and, 477
degenerative diseases and, 478
genetics of, 477
historical recognition of, 470
5HTTLPR polymorphism, 477
lesions and, location of, 470–471, 472–473
metabolomic studies for, 477–478
MRI for, 470
PD and, 478
subcortical ischemic disease and, 476
LTD, 10
LTP compared to, 65
NMDA receptors, 66
melancholic, 522
neurobiology of
brainstem projections and, 459
CLPFC in, 457
connection regions in, 458
cortico-striatal-thalamic circuits, 459–460
history of, 455
hypothalamus projections and, 459
intralaminar thalamic nuclei in, 460
medial prefrontal network in, 456–457
mediodorsal nucleus, 459
orbital prefrontal network in, 456
prefrontal projections in, 460
neurocircuitry-based models of, 465–466
amygdala-mediation of, 465–466
DBS for, 466
in default mode system, 466
neuroimaging of, 428
of amygdala, 428
for diabetes mellitus, 500
functional compared to structural, 462–463
of hippocampus, 428
of NAc, 428
for PFC subregions, 428
neuroplasticity disruption in, 427–428
neuroticism and, 396
neurotransmission alterations in, 425–427
heterogeneity in, 426
neurotrophic factors, in treatment responses, 432–433
FGF2 and, 433
VEGF and, 433
opioid therapy for, 451
pathogenesis of
biological mechanisms of, 438
biomarker development in, 438
with PDD, 876
onset triggers for, 492
risk predictors for, 491
postmortem studies of, 428–429
gonadal steroids and, 491
hormone studies for, 490
prevalence rates for, 490
psychotic, 522
stress-mediated pathways in, 430–431
structural abnormalities in, 428–430
treatment refractory, 466
viral-mediated gene transfer for, 118–119
descriptive psychiatry, 1073–1075
diagnostic reliability and, 1073
diagnostic validity and, 1074
pharmacological advancements as influence on, 1073
despair
escape avoidance and, 416
dextran, multi-size, 151
DGK mouse models. See diacylglycerol kinase mouse models
DGS. See DiGeorge syndrome
DHEA. See dehydroepiandrosterone
diabetes mellitus
AD treatment therapies and, 850–851
antidepressant therapy, 503–504
cellular glucose transporters and, 500
comorbidity mechanisms, 499–500
HPA axis and, 500
neuroimaging for, 500
psychosocial burden as factor in, 499–500
diacylglycerol kinase (DGK) mouse models, 294
diagnoses. See diagnostic systems; psychoses, diagnosis of
Diagnosis of Statistical Manual of Mental Disorders (DSM). See also diagnostic systems
from 369, 1840–1940
goals of, 1074
incorporation of psychiatric disorders into, 369
influence of, 1072
intellectual roots of, 1073
pharmacological revolution and, 370
purpose of, 1072
recategorization within, 370
as regulatory approval standard, 1077
during World War II, 369
Diagnosis of Statistical Manual of Mental Disorders, Fifth Edition (DSM-V), 393–394, 229–230. See also diagnostic systems
addiction in, 697
for separation, 1069
APA and, 1067
childhood psychiatric disorders in, 1069
classification criteria for, 1068
neurobiological, 1068
research strategies for, 1068
conceptual framework of, 1067–1068
developmental perspective in, 1069
diagnostic categorization in, 1068–1069
for biomarkers, 1070
integration of disorders and, 1069
validity in, 1068
intellectual roots of, 1073
neurobiological data in, 1069–1070
organization of, 1070
pathophysiological data in, 1069–1070
psychiatric disorders in, construct of, 1068
psychosis in, construct of, 1067–1068
public health implications for, 1070
RDoC and, 1068
research agenda for, 1067
structure of, 1070
Diagnosis of Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), 226. See also diagnostic systems
ASPD in, 1094
bipolar disorder in, 229
development of, 370
intellectual roots of, 1073
mood disorder diagnostic systems and, 371
psychotic disorders in, 226
schizoaffective disorder, 226–228
schizophrenia, 226
Diagnosis of Statistical Manual of Mental Disorders, Third Edition (DSM-III)
clinical phenomenology in, 1075
connectomics in, 1073
intellectual roots of, 1073
life science developments through, 1072–1073
molecular biology as influence on, 1073
as prototype, 1072
Diagnostic Interview for Genetic Studies (DIGS), 230
diagnostic systems
behavioral constructs, 393
mood disorders
accuracy of, 389
atypical features of, 383
for bipolar disorders, 380
catatonic features of, 383
core criteria selection, 391
for cyclothymia, 380
differential diagnosis, 384–388, 385–387
in DSM-IV, 371
for dysthymic disorder, 380
etiologic approach to, 388
exclusive approaches in, 388
for full interepisode recovery, 384
for hypomanic episode, 379
inclusive approaches in, 388
increased threshold approach to, 388
in late life, 384
for manic episodes, 371
for MDD, 371, 379–380, 382–384
melancholic features, 383
neurobiological mechanisms in, 392
postpartum onset, 383
psychotic features of, 382
with rapid cycling, 384
reliability of, 389
remission of, 382
seasonal patterning in, 384
severity of, 382
subsyndromal mixed states and, 391
symptom substitution approach to, 388
tests in, 390
thresholds for, 391
trauma history in, 391
treatment resistance and, 390
spectrum concepts, 392
DIAN. See Dominantly Inherited Alzheimer Network
principles of, 202
diffusion tensor imaging (DTI), 203
for ADHD, 1044
for ASD, 1026
development of, 202
future alternatives to, 203–204
purpose of, 1073
diffusion-weighted imaging (DWI), 202
diffusion-weighted magnetic resonance imaging (DW-MRI), for neurodevelopmental disorders, 996
DiGeorge syndrome (DGS), 973–974, 982
DIGS. See Diagnostic Interview for Genetic Studies
dimers
in genome transcription control, 80
DISC1 genes. See disrupted in schizophrenia 1 gene
diseases, neuropsychiatric. See also biophysiology, of disease; synaptic disease
gene expression conditional controls, 116–117
knockout, 112
large-clone transgenic, 110
transgenic, 110
optogenetic technology for, 141–144
for anxiety disorders, 142
combinatorial, 144
excitation-inhibition imbalance in, 142, 144
fiberoptic neural interface, 142
IUE, 142
for memory deficits, 142
projection targeting in, 142
disease modification, for AD
clinical trials for
for asymptomatic patients, 858
biomarkers for, 857–858, 861–864
cognitive outcomes for, 860
computerized outcomes in, 861
considered populations in, 857–859
for dementia, onset of, 859
functional outcomes for, 860
globalization as influence on, 863
global outcomes for, 860
MCI onset and, 859
NINCDS-ADRDA criteria for, 857
patient-reported outcomes in, 861
for patients at biological risk, 857
for patients at genetic risk, 857
recruitment challenges in, 862
representative samples in, 863
retention challenges in, 863
secondary outcomes in, 861
slope change in, 860
delay of disability in, 856
FDA and, 855
neuroimaging for, 855
placebos in, 857
in clinical trials, 859, 864–865
symptomatic compounds compared to, 855
terminology of, 855
treatment therapies for, 865–869, 865
administration modes for, 865–866
antibody development in, 867–868
with Aβ proteins, 867, 866–867
BBB involvement in, 868
cellular targets in, 866
development of, 855
neuroprotection in, 869
with NSAIDs, 869
research applications for, 869
in vaccination studies, 867
disrupted in schizophrenia 1 (DISC1) gene, 134, 335
Kalirin and, 335
in mouse models, 291–292, 292–293
mutant human, 293
in neuronal pathways, 334
over-expression of, 292
Wnt pathways, 332
DLB. See dementias with Lewy bodies
DMN. See default mode network
DNA. See deoxyribonucleic acid
DNA methyltransferases (DNMTs), 88
in epigenetics of childhood psychiatric disorders, 963
DNMTs. See DNA methyltransferases
Dominantly Inherited Alzheimer Network (DIAN), 792
L-DOPA. See L-aromatic amino acid decarboxylase
dopamines (DAs)
addiction and
activation in, 686
brain development and, 707–708
hyperdopaminergia, 685
mediated signaling by, 685–686
neurocircuitry of, 683
in adult bonding animal models, 1121
anhedonia hypothesis, 733
DATs, 17
eating disorders and, 1179–1180
knockout mouse models and, 112, 114
PD and, 131
psychotic disorders and, discovery of, 256
in schizophrenia, 347
in STPD, 1098
VMATs and, 112
dopamine hypotheses
hyperfunction hypothesis, 347
of schizophrenia, 347
dopamine transfer deficit model, 1041
dopamine transporters (DATs), 17
in TS animal models, 977
dopamine-β-hydroxylase (DBH), 14, 15
dorsolateral prefrontal cortex (DLPFC), schizophrenia and, 278–279
Down syndrome, 939
chromosomal trisomy and, 973
dosage-sensitive gene expression in, 973
with mice, 973
transgenic, 110
GABA antagonists and, 1063
doxorubicin, 151
Drachman, David, 810
drug abuse. See also substance use disorder
ΔFosB transcription factor and, 115
intrinsic plasticity of brain and, 71
molecular adaptations to, 723–728
NAc and, 71
drug addiction. See also substance
use disorder
animal models of, 679
classical conditioning models of, 737
negative reinforcement and, 736–737
classical conditioning models of, 737
methamphetamines and, 737
opponent-process models of, 737
self-medication models of, 737
tobacco use and, 737
relapse and, 737
self-medication models, 737
drug delivery systems
BBB and, , 151
FUS and, 151
through lipidization, 150
microbubbles in, 151
for neurodegenerative diseases, 151
neurosurgically-based, 151
drug development, neuroepigenetics, 177–178
HDACs and, 178
drug-elicited craving, 729–730
DSC MRI. See dynamic susceptibility contrast MRI
DSM. See Diagnosis of Statistical Manual of Mental Disorders
DSM-III. See Diagnosis of Statistical Manual of Mental Disorders, Third Edition
DSM-IV. See Diagnosis of Statistical Manual of Mental Disorders, Fourth Edition
DSM-V. See Diagnosis of Statistical Manual of Mental Disorders, Fifth Edition
DTI. See diffusion tensor imaging
DWI. See diffusion-weighted imaging
DW-MRI. See diffusion-weighted magnetic resonance imaging
dynamic causal modeling (DCM), 1000–1001
Dynamic Developmental Theory, 1041
dynamic susceptibility contrast MRI (DSC MRI), 199
dysbindin genes, 290
dysraphias, 981
dysthymia, 368
diagnostic systems for, 380
E
EAATs. See excitatory amino acid transporters
early childhood, fear development
during, 597–598
early-onset familial AD, genetics of, 805–807
eating disorders. See also anorexia nervosa; bulimia nervosa
BED, 1183
food addiction and, 1183
gender influences on, 1182
hormonal dysregulation and, 1175–1178
for appetite-regulation, 1176–1178
of eCB system, 1178
for endorphins, 1178
ghrelin and, 1177
HPA axis and, 1178
for leptin, 1177
melanocortin, 1178
for NPY, 1177
obestatin and, 1177
for PYY, 1177
of TRH, 1178
for weight-regulation, 1176–1178
neurotransmitter dysregulation and, 1178–1180
prenatal risks for, 1175
starvation and, psychopathology of, 1182
eCBs. See endocannabinoids
ecstasy. See 3, 4–methylenedioxy-N-methylamphetamine
ECT. See electroconvulsive therapy
EEG. See electroencephalograms
effort computation, schizophrenia and, 276
eicosanoids, 50
Eldepryl. See selegiline
elderly. See late life
electric-inhibitory channels, 146
electroconvulsive therapy (ECT), 519–520
for OCD, 659
electroencephalograms (EEG)
for FTD, 893
for functional connectivity, in neurodevelopmental disorders, 1002–1003
limitations of, 1004
for sCJD, 919
for sleep stages, 1127
electromyelogram (EMG), 1127
electrooculogram (EOG), 1127
electrophysiology
alternative recording options, 34
chronic unit recording, 32
definition of, 32
methods of, 27
microiontophoresis, 32
of psychomimetics, 36
of psychotropic drug action, 35–38
for schizophrenia, 343
whole-cell patch recording, 33
EM. See episodic memory
EMA. See European Medicines Agency
embryonic stem (ES) cells, 124
hESCs, 124
modification of, in knockout mouse models, 111
EMG. See electromyelogram
emotions. See also specific emotions
amygdala role in, 474
for emotional regulation, 607–609
anxiety disorders and, 549–550
bulimia nervosa and, 1181–1182
mediation of, 128
emotional regulation and, 610–611
positive, in resilience, 1147–1148
limbic structure imaging, 464–465
negative emotional bias, 465
regulation of, 580. See also anxiety; anxiety disorders; fear
anxiety disorders and, 587–589,
developmental influences on, 590
function of, 580
genetic influences on, 590
hippocampal influence on, 610
hormonal influences on, 589, 589–590
hypothalamus and, 609
insula and, 609
periaqueductal gray region and, 609
personality factors for, 589
reactivity and, 607
research history of, 580
stress factors in, 589
as top-down process, 580
encephalitis lethargica, 1131
Encyclopedia of DNA Elements (ENCODE) project, 164
endocannabinoids (eCBs)
anandamide, 50
eating disorders and, 1178
inactivation of, 23
psychoactive effects of, 24
release of, 23
resilience and, 1158
signal transduction pathways and, 50
therapeutic potential of, 24
endogenous stem cells, 128
brain development and, 128
endorphins, eating disorders and, 1178
endothelial NOS (eNOS), 23
enhancer elements, 80
eNOS. See endothelial NOS
ENU model. See N-nitroso-N-ethylurea model
EOG. See electrooculogram
epidemiology
developmental changes in, 539–540
susceptibilities in, 540
of ASPD, 1094
environmental factors, 233–234
family studies for, 233
genetic overlap with schizophrenia, 233
incidence rates for, 232
non-inherited factors, 233–234
twin studies for, 233
of childhood psychiatric disorders, 956
of LBD, 874
mapping technologies for, 161–162
through association analysis, 161–162, 163
through family studies, 161
for genotypes, 160
through linkage analysis, 161
for phenotypes, 160
through segregation analysis, 161
with GWAS, 397
heritability in, 397
relative risks in, 397
in twin studies, 398
of PTSD, 662
of resilience, 1144
environmental factors, 233–234
genetic overlap with bipolar disorder, 233
incidence rates for, 232
non-inherited factors, 233–234
of SUD
abuse classifications in, 772–774
among adolescents, 777, 781, 784–785
among adults, 776–777, 778–781
through animal models, 784
as chronic disorder, 777
comorbidities for, across substances, 777
craving and, 774
in DSM-IV, 772
measurement criteria for, 772–776
NAc and, 783
with NCSs, 774
by race, 779, 781
VTA and, 783
withdrawal symptoms, 772
epigenetics. See also methylation, of DNA
chromatin, 691
HDACs, 691
histone methyltransferase, 691
addictive behaviors and, 95–96
of affective disorders, 956–957
antidepressant development and, 96–97
for anxiety disorders, in animal models, 546–547
for ATRX, 102
brain
chromatin architecture, 174–175
coding sequence mutations, 177
developmental plasticity of, 175–176
DNA structural variants, 178–179
eraser proteins, 177
euchromatin, 173
foundations of, 172
heterochromatin, 173
histones, 174
monogenetic etiologies, 176–177
nucleosomes, 173
for PTSD, 176
reader proteins, 177
writer proteins, 177
of childhood psychiatric disorders
11β-HSD2 in, 963
for affective disorders, 956–957
for ASD, 956
corticosterones in, 963
CRF concentration in, 957
CSF concentration in, 957
DNMTs and, 963
epidemiology of, 956
germ cell programming in, 959
high fat diets in, 960
history of, 955
immune activation in, 959
mechanisms of, 955
miRNA in, 963
obesity models for, 960
placental contributions in, 962–963
PPI and, 959
prenatal infection in, 959
prenatal stress and, 958
transgenerational, 965
chromatins
heterochromatin, 173
cocaine use and, 95
definition of, 88
for FXS, 101
histone protein modifications in, 91–92
for Kabuki syndrome, 101
methyl-CpG-binding proteins and, 88–91
mutations in, linked psychiatric syndromes for, 98
nicotine abuse and, 95
in postnatal brain development, 987–988
epigenomes, 10
episodic memory (EM)
AD and, 799
cognitive deficits and, 274–275
cognitive neuroscience models, 273
hippocampal activity, 273, 274
PFC and, 273
epistasis
in genetic inheritance model, 698
in synaptic disease, 322
eplivanserin, 767
EPSP. See excitatory postsynaptic potential
eraser proteins, 177
ERP therapy. See exposure and response prevention therapy
escape avoidance, 416
ES cells. See embryonic stem cells
escitalopram, 1031
ESM. See European Staging Model
Esquirol, Jean Étienne Dominique, 368
Essential Prescriptions of the Golden Chest, 368
ethnicity. See also African Americans; Hispanic Americans
SUD and, 779, 781
euchromatin, 173
eukaryotic chromosomes, 78, 79
European Medicines Agency (EMA), 855
European Staging Model (ESM), 390
excitation-inhibition imbalance, 142, 144
excitatory amino acid transporters (EAATs), 439
excitatory postsynaptic potential (EPSP), 28–29
brain function and, 64
executive functioning
AD and, 799
exome sequencing
for ASD, 949
for COS, 950
whole, 169
experimental medicine therapy, for depression, 451
exposure and response prevention (ERP) therapy
for PTSD, 670
extinction training, in relapse model, 679
extracellular signals
gene expression regulated by, 81
extrapyramidal symptoms, of antipsychotic drugs, 37
eyes. See visual system
F
Falret, Jean Pierre, 368
familial Creutzfeldt-Jakob disease (fCJD), 923
familial dysautonomia (FD)
splicing defects, 130
stem cell modeling for, 130
family dysfunction, ADHD and, 1040–1041
family studies
for AD, 805
for addiction, 697
for inheritance of, 699
for anxiety disorders, 537–539
pediatric, 539
for bipolar disorder, 233
MDD and, 399
for GAD, 538
for genetic epidemiology, 161
for MDD, 399
for OCD, 538
for panic disorder, 537
phobias, 538
for schizophrenia, 161, 232–233
MDD and, 399
for tic disorders, 1049
for TS, 1049
fasciculation, 8
fast-spiking (FS) receptors, 301
fatal familial insomnia (FFI), 927
neuropathology of, 927
FBS. See functional behavior systems
fCJD. See familial Creutzfeldt-Jakob disease
FD. See familial dysautonomia
FDA. See Food and Drug Administration
FDG PET. See fluorodeoxyglucose PET
fear. See also pathological fear
during adolescence, development of, 598–603
of contextual fear and extinction, 600–601
of cue fear extinction, 599–600
hippocampal involvement, 600–601
amygdala and, 573–574, 607–609
during infancy, development of, 596
lateral circuits in, 574
animal models of, 553–560.
See also associative conditioning animal
models
antipredator, 554
for conditioned fear, 593, 594–595
for fear learning, 593
instrumental avoidance conditioning, 558–560
anxiety compared to, 550
as anxiety disorder model, 606–607
during early childhood, development of, 597–598
hippocampus and, 597
ecological significance of, 595
FBS and, 550
active coping, 575
in cortical microcircuits, 576
extinction mechanisms, 575
inhibition mechanisms, 575
passive coping, 575
during infancy, development of, 595–596
amygdala role in, 596
ecological perspective on, 596
infant odor-shock and, 597–598, 598
maternal odor learning and, 597–598
inhibition of, 560
conditioned, 560
GABA receptors and, 575
latent, 560
negative feedback, 560
normal compared to pathological, 552
conditioned fear and, 595
extinction of memory, 1160–1162
fear conditioning, 1160
reconsolidation of memory, 1160–1162
stress responses to, 552
fear conditioning, in APP mouse models, 816–817
Feigner Criteria, 224
for psychiatric disorders, 1074
Feingold hypothesis, 1039–1040
fenobam, 766
FFI. See fatal familial insomnia
FFM. See Five Factor Model, for personality
FGF2. See fibroblast growth factor 2
FGS. See Opitz-Kaveggia syndrome
fiberoptic neural interfaces, 142
fibroblasts, stem cell direct programming, 124
fibroblast growth factor 2 (FGF2), 433
first rank symptoms (FRS), 223
Five Factor Model (FFM), for personality, 1089
Flinder’s sensitive line (FSL) rat models, 421
fluorodeoxyglucose (FDG) PET, 825–827
limitations of, 827
metabolism assessment with, 826
fluoxetine, 512
Fmr1KO mouse models, 974
fMRI. See functional magnetic resonance imaging
focused ultrasound (FUS), BBB and, 148–149
assessment methods with, 151–152
in drug delivery systems, 151
HIFU, 148
food addiction, 1183
Food and Drug Administration (FDA), 149
AD treatment approvals, 844
disease modification under, for AD, 855
Fos proteins, 83
as IEG, 83
regulation of, 84
signal pathway activation for, 84
ΔFosB transcription factor, 115
genomic strategies, 119
Fragile X syndrome (FXS), 940, 1024
animal models of, 971, 974–975
Fmr1KO, 974
point mutation, 974
therapeutic implications for, 974–975
transgenic, 974
clinical trials for, 1062
epigenetics for, 101
mGluR5 receptors in, 1061–1062
phenotypes for, 130
stem cell modeling for, 130
treatment therapies for, 1031–1032
frontal lobe dementia (FTD)
psychiatric features of, 889–890
testing of, 890
causes of, 887
CBS and, 892
clinical syndromes with, 887, 888
CSF and, 893
diagnostic criteria for, 889
discovery of, 887
EEG for, 893
FTD-MND, 890
FTLD, 887
by gender, 888
mortality rates for, 888
MRI for, 892
diagnostic criteria for, 889
logopenic variants for, 892
nfvPPA, 891
semantic variants for, 891–892
PSP and, 892
treatment therapies for, 895–897
frontotemporal dementia with motor neuron disease (FTD-MND), 890
frontotemporal lobar degeneration (FTLD), 887
FRS. See first rank symptoms
FSL rat models. See Flinder’s sensitive line rat models
FS receptors. See fast-spiking receptors
FTD. See frontal lobe dementia
FTD-MND. See frontotemporal dementia with motor neuron disease
FTLD. See frontotemporal lobar degeneration
functional behavior systems
(FBS), 550
functional connectivity, neurodevelopmental disorders and, 990–991
in ADHD, 1006
brain movies as system for, 995
connectomes and, 995, 997–998, 1000
cross mutual information in, 1003
limitations of, 1004
generalized synchronization in, 1003–1004
global features of, 998
Granger causality mapping in, 1001
ICA for, 1000
motivation for, 995
MSC for, 1003
in OCD, 1007
PDC and, 1003
PLV and, 1003
in schizophrenia, 1005
signaling in, 996
in TS, 1007
functional magnetic resonance imaging (fMRI)
for AD, 825
default networks in, 825
for BPD, 1092
brain function assessment, 200–202
for neurodevelopmental disorders, 999
purpose of, 1073
for schizophrenia, 342
for tic disorders, 1054
for TS, 1054
FUS. See focused ultrasound
FXS. See Fragile X syndrome
G
GABA. See γ-aminobutyric acid
α-GABA receptors
anxiolysis mediation, 571, 572–573
dependence liability mediation by, 569–571
hippocampal-dependent memory regulation, 573
synaptic plasticity and, 573
GAD. See generalized anxiety
disorder; glutamic acid decarboxylase
GAD1 genes, 308
galanin, resilience and, 1156
gas neurotransmitters, 23
Gaupp, Robert, 470
GDNF. See glial derived neurotrophic factor
gender
ASD and, 936
BPD by, 1091
eating disorders by, 1182
FTD and, 888
genes, 78–79. See also epidemiology; transcription control, for genomes; viral-mediated gene transfer
in association analysis, 161–162
candidate, MDD and, 400
emotional regulation and, 590
GluR, 119
IEGs, 83
in mouse models
functional studies, 109
reverse genetic strategy, 109
transgenic, 110
Reeler, 112
schizophrenia and, 187
genetic variations for, 329–330
viral-mediated gene transfer and, 120
gene-environment interaction, 160
gene expression, 79. See also transcription control, for genomes; viral-mediated gene transfer
through candidate gene
studies, 1174
through GWAS, 1174
in AD
amino acid sequences in, 805
chromosomal markers in, 805–806
development of, 805
through family studies, 805
inheritance in, 805
mutations in, 806
onset of, 805
through post-mortem examinations, 805
risk factors, 805
through twin studies, 805
in addiction. See also inheritance, genetic
alcohol-induced flushing and, 699–700
with alcohol metabolizing genes, 700
alleles in, 696
in candidate gene studies, 700
clinical categories of, 697
endophenotypes for, 699
environmental interaction in, 698–699
evolutionary context for, 696
exposure factors for, 697
gene identification, 700–701, 704
genetic correlation in, 698
5HTTLPR polymorphism, 701
inheritance range in, 696
intermediate phenotypes in, 699–700
mapping technologies for, 696
with monoamine transmitters, 700–701
as multistage, 704
neuroimaging for, 700
in receptors, 699
resilience in, 696
serotonins and, 701
signaling pathways for, 696
adoption studies for, 1037
CNVs in, 1039
through GWAS, 1038
linkage studies for, 1038
molecular studies for, 1037–1038
for AHDS, 1017
in gene association studies, 540–541
transporter genes, 541
in ASD, 187, 949, 967, 1027–1028
common variations for, 1027
model systems in, 1028
rare variations for, 1027–1028
single-gene syndromes, 940
systems genetics and, 1028
in ASPD, 1096
in autism, 187
in BBS, 1014
in BPD, 1092
in childhood psychiatric disorders, 938–941. See also copy number variants
DNA in, 944
genetic susceptibility, 951
with GWAS, 938–939, 940–941, 944
of ID, 933
with MPS, 945
SNPs and, 945
conditional knockout models, 116–117
site-specific recombination systems, 115–116
transcriptional transactivator systems, 114–115
cytokine regulation of, 84
DNA methylation and, 89
emotional regulation and, 590
extracellular signal regulation of, 81
through histone proteins, 92
for ID, 933
single-gene syndromes, 940
MAP and, 57
in MDD genetic studies, 400
neurodevelopmental disorders and, 980
nonreceptor protein tyrosine kinase regulation of, 84
CHR and, 1145
CRF and, 1145
GR and, 1145
HPA axis in, 1145
PACAP receptor, 1146
variations in, 1145
in schizophrenia, 187
in signal transduction pathways, 40, 57–59
transcription phases, 79
Wnt signaling cascades and, 85
generalized anxiety disorder (GAD), 533–534
clinical indications for, 642
family studies for, 538
amygdala activity, 614
prevalence rates for, 642
treatment therapies for, 642–643
first-line approaches, 642
second-line approaches, 642–643
twin studies for, 538
general kinetic model (GKM), 155
geneset-enrichment analysis, 164–165
gene targeting approaches
for AD, in transgenic mouse models, 815
for anxiety disorders, in animal models, 545–546
genetics. See genes; gene expression
genetic association models
for psychosis, 349
for social attachment, 1112–1113
animal models for, 1112
genetic code, 77
genetic inheritance. See inheritance, genetic
genetic mapping technologies. See also copy number variants; genome-wide association studies
for allele identification, 160
biological pathways in, 160
for childhood psychiatric disorders, 944–945
disease alleles, frequency spectrum of, 168
multiple variants for, 168
for schizophrenia, 168
structural variants for, 168, 168–169
through association analysis, 161–162, 163
through family studies, 161
for genotypes, 160
through linkage analysis, 161
for phenotypes, 160
through segregation analysis, 161
exome sequencing
for ASD, 949
for COS, 950
whole, 169
for genetic architecture, 160
goals of, 160
with ENCODE project, 164
haplotypes in, 163
with 1000 Genomes Project, 164
phasing in, 163
recombination events in, 163
for inheritance modes, 160
with integrative analysis, 170
MPS, 945
for neuropsychiatric diseases, 168–169
with singletons, 169
whole-exome sequencing, 169
pleiotropy and, 160
purpose of, 1073
risk prediction in, 160
sample size requirements, 165–164
for SNVs
in ASD, 949
in childhood psychiatric disorders, 944–945
in COS, 950
genetic prion diseases (gPrDs), 921–922. See also Creutzfeldt-Jakob disease
diagnostic testing for, 924
FFI, 924
neuropathology of, 927
neuropathology of, 926
Genetics of Recurrent Early-onset Depression (GenRED) study, 398–399, 400
genetic studies. See family studies; twin studies
genomes. See also transcription control, for genomes
in biophysiology of disease, 190–191
genetic mapping technologies for, 162–164
with ENCODE project, 164
with GWAS, 163
haplotypes in, 163
with 1000 Genomes Project, 164
phasing in, 163
recombination events in, 163
for schizophrenia
low-resolution approaches to, 247
mutation rates in, 253
selection coefficients in, 253, 254
VCFS, 247
genome-wide association studies (GWAS), 163, 164, 237–242
for AN, 1174
for ADHD, 1038
for anxiety disorders, 541–543
for biophysiology of diseases, 186
for bipolar disorder, 234, 240–242, 239, 241
overlap with schizophrenia, 242
phenotypes for, 242
for childhood psychiatric disorders, 938–939, 940–941, 944
geneset-enrichment analysis, 164–165
Hardy-Weinberg equilibrium in, 167
for LOAD, 807
for MDD, 397, 400, 402–405, 403
cross-disorder findings of, 404
meta-analysis in, 165
for polygenic diseases, 165
population stratification in, 165
for schizophrenia, 234, 237–240, 238–239, 239
linkage disequilibrium variances, 237–238
mouse models of, 289
overlap with bipolar disorder, 242
risks in, 238
for tic disorders, 1050
for TS, 1050
type II errors in, 165
GenRED study. See Genetics of Recurrent Early-onset Depression study
germ cell programming, 959
Gerstmann’s syndrome, 796
Gerstmann-Sträussler-Scheinker (GSS) mutations, 923–924
neuropathology of, 926
GFP. See green fluorescent protein
ghrelin, 1177
gingko, in AD treatment, 848
GKM. See general kinetic model
Glenner, George, 812
glial cells
in brain development, 7
GDNF, 45
microglia, 7
postnatal processes, 10
glial derived neurotrophic factor (GDNF), 45
GLMT system. See glutamate system
glucocorticoid receptor (GR), 47
in anxiety disorder treatment therapies, 623
mechanisms of action in, 633
resilience and, 1145
glucose metabolism, addiction and, 716
GluR genes, 119
MRS for, 742
glutamatergic drugs, 352
glutamate (GLMT) system, 439–445
addiction and
BDNF and, 688
GPCR and, 688
homeostasis hypothesis of, 687–688
Homer proteins in, 688
mediated relapse by, 687
metabotropic receptors, 688
regulation in, 687
anatomy of, 20
clinical trials with, 439–445, 440–447
history of, 439
physiology of, 439
riluzole therapy, 445
VGLuTs in, 439
glutamatergic drugs, 352
glutamic acid decarboxylase and, 19
inactivation of, 20
memantine and, 845
monoamine transmitters compared to, 19
OCD and, 647
psychosis and, 348
regulation of, 20
in reward, 734
SUD and, in pharmacotherapy, 765–766
VGLuTs, 20
depression and, 439
wakefulness and, 1130
glutamic acid decarboxylase, 19
neurodevelopmental disorders and, 991
glycogen synthase kinase 3 (GSK3) pathway, 360
goal-directed action, schizophrenia and, 278–279
goal representations, schizophrenia and, 275–280
effort computation and, 276
outcome achievements and, 276
Golde, Todd, 814
gonadal hormones, for AD treatment, 849
gonadal steroids
activation of, 485
biological effects of, 483–485
cell regulation by, 485
depression and
menstrual cycle effects, 486
environmental interactions, 485
genomic effects of, 485
hormone receptors in, 485
midlife depression and, 492–493
mood disorders and, history of, 483
NRAMs and, 485
PPD and, 491
production of, 483
theelin and, 483
GPCR. See G-protein coupled receptor
gPrDs. See genetic prion diseases
G proteins, 48
functions of, 48
heterotrimeric, 48
hydrolysis in, 61
neurons and, 32
in signal transduction pathways, 41, 43, 46, 59–61
G-protein coupled receptor (GPCR), 141
addiction and, 688
GR. See glucocorticoid receptor
Granger causality, 1001
Gray, Jeffrey, 564
green fluorescent protein (GFP), 110
transgene tagging with, 119
grooming behaviors, 417
growth cones, 8
GSK3 pathway. See glycogen synthase kinase 3 pathway
GSS mutations. See Gerstmann-Sträussler-Scheinker mutations
GTP-binding proteins, 48
guanine, 76
Gusella, James, 805
GWAS. See genome-wide association studies
H
habenula, in neurocircuitry of addiction, 685
Haines, Jonathan, 805
hallucinations
with DLB, 876
hypnagogic, 1137
with PDD, 876
hallucinogens. See psychomimetics
halorhodopsins, 138
light-activated, 141
haplo-insufficiency, 112
imputation leverages in, 163
LD in, 163
Hardy, John, 815
Hardy-Weinberg equilibrium, 167
Hare Psychopathy Checklist, 1094
Harkany, Tibor, 811
Harlow, Harry F., 70
harm avoidance, AN and, 1182
HD. See Huntington’s disease
HDACs. See histone deacetylases
Heavenly Emporium of Benevolent Knowledge, 1075
Hebbian LTP, 65
hedonic hypothesis, for addiction, 706
Herceptin, 151
heroine, neuroimaging for, 726
herpes simplex virus (HSV-1), viral-mediated gene transfer, 117
hESCs. See human embryonic stem cells
heterochromatin, 173
heterotrimeric G proteins, 48
HIFU. See high-intensity focused ultrasound
Higgins, Gerry, 813
high fat diets, in childhood psychiatric disorders, 960
high-intensity focused ultrasound (HIFU), 148
hippocampus
depression and, 428
dysfunction
α-GABA receptors and, 573
emotional regulation and, 610
fear development and
during early childhood, 597
Hippocrates, 368
Hispanic Americans, AD in, 801–802
histamines, in sleep cycles, 1130
histones
neuroepigenetics, 174
proteins
acetylation of, 92
deacetylation of, 92
gene expression through, 92
nicotine abuse and, 95
histone deacetylases (HDACs), 92
epigenetic addiction mechanisms, 691
neuroepigenetic drug development, 178
histone methyltransferase, addiction mechanisms and, 691
HIV. See human immunodeficiency virus
HIV/AIDS. See human immunodeficiency virus/acquired immune deficiency syndrome
homeostasis, 71
GLMT system, in hypothesis of, 687–688
sleep functions and, 1139
homeostatic plasticity, of brain, 71–74
autophosphorylation and, 74
as concept, development of, 71–72
molecular substrates and, 74
network-wide, 74
Homer proteins, 688
homocysteine levels, 847
homocysteine levels, AD and, 847
hormones. See also gonadal steroids; steroid hormones
childhood psychiatric disorders and, 963
eating disorders and, dysregulation of, 1175–1178
for appetite-regulation, 1176–1178
of eCB system, 1178
for endorphins, 1178
ghrelin and, 1177
HPA axis and, 1178
for leptin, 1177
melanocortin, 1178
for NPY, 1177
obestatin and, 1177
for PYY, 1177
of TRH, 1178
for weight-regulation, 1176–1178
emotional regulation and, 589
gonadal, for AD treatment, 849
melatonin, 1132
OCD and, 648
perimenopausal depression and
in therapy treatments, 492
PMDD and, 487
PPD and, 490
sex, emotional regulation and, 589–590
horseradish peroxidase, 151
HPA axis. See hypothalamic-pituitary-adrenal axis
HPO. See human phenotype ontology
11β-HSD2. See 11β-hydroxysteroid dehydrogenase-2
Hsiao, Karen. See Ashe, Karen
HSV-1. See herpes simplex virus
5-HT receptors. See 5-hydroxytryptophan receptors
HTR2B receptors, 703
5HTTLPR polymorphism, 477, 666
addiction and, 701
aggression and, 1109
human embryonic stem cells (hESCs), 124
human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), depression and, 380–381, 500–501
antidepressant therapy, 504
comorbidity mechanisms, 500–501
HPA axis and, 501
MRS studies, psychostimulant use and, 746
prevalence rates for, 500
human phenotype ontology (HPO), 322–323
humor, as coping mechanism, 1149
Huntington’s disease (HD)
mouse models for, 287
mutation phenotypes in, 322
rat models for, 111
stem cell modeling for, 131–132
Huperzine A, 845
Husserl, Edmund, 223
Hutton, Mike, 814
11β-hydroxysteroid dehydrogenase-2 (11β-HSD2), 963
5-hydroxytryptamine. See serotonin
5-hydroxytryptophan (5-HT) receptors, 18
eating disorders and, 1179, 1180
MDD and, 425
psychomimetics and, 36
in SUD pharmacotherapy, 766–767
Hyman, Steven, 1077
hyperactivity, treatment therapies for, 1030–1031
hyperdopaminergia, 685
hypnagogic hallucinations, 1137
hypomanic episode, diagnostic system for, 379
hypothalamic-pituitary-adrenal (HPA) axis, 430–431
CAD and, 498
diabetes mellitus and, 500
eating disorders and, 1178
HIV/AIDS and, 501
in neurocircuitry of addiction, 685
resilience and
development of, 1146
genetics of, 1145
hypothalamus
circadian clock influenced by, 1131
emotional regulation and, 609
encephalitis lethargica and, 1131
sleep cycles and, 1131
I
IBD chromosomes. See identical-by-descent chromosomes
ICA. See independent component analysis
ICD. See International Classification of Disease
ICD-10. See International Classification of Disease, 10th Revision
ICSS. See intracranial self-stimulation
ICT. See Internet and computer-based psychotherapy
ID. See intellectual disability
identical-by-descent (IBD) chromosomes, 161
IED. See intermittent explosive disorder
IEGs. See immediate early genes
IGF-1. See insulin-like growth factor-1
IL-6. See interleukin-6
iloperidone, 351
imaging. See neuroimaging methodologies
imipramine, 508, 509, 640, 643
immediate early genes (IEGs), 83
activation of, 84
immune system
childhood psychiatric disorders and, 959
depression and, 497
immunotherapies, for AD, 867–868
regulation mechanisms for, 94–95
impulsivity, 681
ASD and, 1023
treatment therapies for, 1030–1031
individual traits for, 709–710
incentive salience, 733
incubation of craving models, 764
independent component analysis (ICA), 1000
induced pluripotent stem cells (iPSCs), 8, 124
karyotyping of, 124
markers, 124
in patient-specific studies, 125–126
properties of, 124
schizophrenia and, 132
stability of, 124
teratoma assays, 124
inducible transgenic strategy, 114–115
FGFs in, 3
lateral, 3
medial, 3
neural, , 3
regionalization process in, 4
infancy, development of fear, 595–596
amygdala role in, 596
ecological perspective on, 596
infant odor-shock and, 597–598
maternal odor learning and, 597–598
retention of, 598
infant-parental attachment, 1113–1116
development of, 1113
motivation circuits in, 1115
chemical substrates in, 1115
neuroanatomy and, 1115
oxytocin in, 1115
social approaches to, 1115
infarction patterns, VCI and, 901
inflammation
CAD and, 498
inflammatomes, 195
inheritance, genetic, of addiction, 697–698
causation in, 697
cross-transmission of, 698
epistatic model for, 698
in family studies, 697, 699
shared, 698
unshared, 698
inhibitory postsynaptic potential (IPSP), 31
brain function and, 64
iNOS. See macrophage-inducible NOS
inositol-trisphosphate (IP3) receptors, 47, 52
Institute of Medicine (IOM), 1076
instrumental aggression, 1104–1106
as adaptive, 1104
ASPD and, 1104
CD and, 1104
cortical circuits in, 1109
flexibility of, 1104
reactive compared to, 1103–1104
stimulus-reinforcement learning and, 1104–1105
instrumental avoidance conditioning, 558–560
inhibitory avoidance, 558
insula
emotional regulation and, 609
in neurocircuitry of addiction, 685
PTSD and, 617
social anxiety disorder and, 612
insulin-like growth factor-1 (IGF-1), 1062
intellectual disability (ID), 945–948
AHDS and, 1017
clinical indications for, 1017
gene expression for, 1017
prevalence rates for, 1017
environmental, 975
metabolism errors, 975
PKU in, 975
ATRX syndrome and, 102, 1017–1018
clinical features of, 1017
discovery of, 1017
epigenetics for, 102
gene mutations in, 1018
genetic expression in, 1017–1018
autosomal recessive, 1014–1017
comorbidities with, 1015
diagnosis of, 1014
discovery of, 1014
genetic expression of, 1014
prevalence of, 1014
treatment of, 1015
clinical indications for, 1011
Costello syndrome and, 1011
Noonan syndrome and, 1011
pregnancy and, 1011
prevalence rates for, 1011
clinical indications for, 1015–1016
phenotypes for, 1015
definition of, 933
deletion syndromes in, 946
Down syndrome, 939
spine pathology with, 990
transgenic models, 110
duplication syndromes in, 946
etiological classification of, 1011
as extreme variant trait, 937
clinical features of, 1018
diagnosis of, 1018
gene mutations in, 1018
prevalence of, 1019
FXS, 940
animal models of, 971, 974–975
clinical trials for, 1062
epigenetics for, 101
mGluR5 receptors in, 1061–1062
phenotypes for, 130
stem cell modeling for, 130
treatment therapies for, 1031–1032
single-gene syndromes, 940
IQ and, 946
comorbidities with, 1013
diagnostic criteria for, 1012–1013
gene mutations with, 1013
prevalence rates for, 1012
reproductive disadvantage with, 939
clinical indications for, 1016
comorbidities with, 1016
diagnosis of, 1016
prevalence rates for, 1016
treatment therapies for, 1016–1017
causes of, 1014
clinical indications for, 1013–1014
NSD1 gene and, 1014
trajectory into adulthood, 934
intellectual quotient (IQ), 946
interleaved scanning
DBS, 218
tDCS, 215
TMS, 216
interleukin-6 (IL-6), 84
intermittent explosive disorder (IED), 951
International Classification of Disease (ICD)
WHO adoption of, 370
International Classification of Disease, 10th Revision (ICD-10)
bipolar disorder in, 227–228, 229
development of, 370
mood disorder diagnostic systems and, 371, 372–385
schizoaffective disorder in, 227–229
schizophrenia in, 226, 227–228
Internet and computer-based psychotherapy (ICT), 631
CBT and, 631
cost effectiveness of, 632
mechanisms of action for, 633
interpersonal therapy (IPT), 521
interpretive bias modification (CBM-I) therapy, 628
cost effectiveness of, 632
empirical evidence for, 628–629
intracranial self-stimulation (ICSS), 678
intrauterine growth restriction (IUGR) phenotypes, 959–960
intrinsic plasticity, of brain, 67–71. See also ion channels
AD and, 71
AHP and, 70
AUD and, 71
axons and, 69
at axo-somatic level, 68
dendrites and, 68
drug abuse and, 71
molecular substrates and, 69–70
morphine exposure and, 71
in neurological disorders, 71
postnatal brain development and, 988
in saving, 70
SUD and, 675
after TBI, 71
voltage-gated ion channels and, 67–68
in utero electroporation (IUE), 142
in vivo transplantation, 133
IOM. See Institute of Medicine
ion channels. See also voltage-gated ion channels
ligand-gated, 31
molecular substrates and, 69–70
neurons and, 27
in signal transduction pathways, 40–41
in synaptic disease, 313
ionotropic receptors, 32
ion pumps, 27
Iowa Gambling task, 278
IP3 receptors. See inositol-trisphosphate receptors
iproniazid, 508
iPSCs. See induced pluripotent stem cells
IPSP. See inhibitory postsynaptic potential
IPT. See interpersonal therapy
IQ. See intellectual quotient
iron levels, ADHD and, 1040
ischemia, VCI and, 900–901, 909
SBI, 903
WMH and, 903
treatment therapies for, 910–911
isocarboxazid, 511
IUE. See in utero electroporation
IUGR phenotypes. See intrauterine growth restriction phenotypes
ivacaftor, 1076
J
Jackson, John Hughlings, 223
Jakob, Alfons, 915
Janet, Pierre, 369
Janus tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) receptors, 46
Jaspers, Karl, 224
Joubert syndrome, 982
Jun proteins, 83
as IEG, 83
K
Kabuki syndrome (KS), 101, 1012–1013
comorbidities with, 1013
diagnostic criteria for, 1012–1013
gene mutations with, 1013
prevalence rates for, 1012
Kahlbaum, Karl, 368
Kalirin, 335
Kalydeco. See ivacaftor
Katzman, Robert, 791
ketamine, 36
molecular mechanisms in, 442
clinical trials with, 442
in glutamergic system, 439–444
for MDD, 425
side effects of, 442
knockout mouse models, 111–113
NT-3 factors, 116
RTT, 116
disease models, 112
dopaminergic system and, 112, 114
ES cell line modifications, 111
haplo-insufficiency, 112
lethality issues, 113
Reeler gene, 112
of schizophrenia, 292
TH, 113
transgenic compared to, 111
knockout rat models, 112
mood disorder diagnosis under, 368
neuroimaging methodologies influenced by, 256
phenomenology of, 1073
KS. See Kabuki syndrome
Kuhn, Franz, 1075
Kuru, neuropathology of, 927
L
Landau Kleffner syndrome (LKS), 1023–1024
language deficits
with LBD, 876
with PDD, 876
large-clone transgenic mouse models
for disease states, 110
Down Syndrome, 110
GFP, 110
large-scale sequencing studies, 242–245
late life, onset of disease in.
See also late onset Alzheimer’s disease
bipolar disorder, 384
depression
AD and, 478
AGTR genes, 477
basal ganglia circuits and, 475
BDNF and, 477
degenerative diseases and, 478
genetics of, 477
historical recognition of, 470
5HTTLPR polymorphism, 477
lesions and, location of, 470–473
metabolomic studies for, 477–478
MRI for, 470
PD and, 478
subcortical ischemic disease and, 476
MDD, 384
mood disorders, diagnostic systems for, 384
subcortical ischemic disease, 475–476
depression and, 476
latent growth mixture modeling (LGMM), 1144
late onset Alzheimer’s disease
(LOAD), 792
ADAM10 genes, 808
functions of, 807
GWAS for, 807
risk factors for, 806
lateral geniculate nucleus (LGN), 9
lateral habenula, reward and, 735
lateral induction, in CNS, 3
LBD. See Lewy body dementias
LC-NE system. See locus coeruleus-norepinephrine system, resilience and
LD. See linkage disequilibrium
learned helplessness paradigm
construct validity of, 419
pathological validity of, 419
predictive validity of, 419
learning
AHP in, 70
intrinsic plasticity in, 70–71
permissive role in, 70
psychosis and, 349
stimulus-reinforcement, 1104–1105
leptin, 1177
leucine-rich repeat transmembrane neuronal proteins (LRRTMs), 989
leukemia inhibitory factor (LIF), 84
levodopa, 882
Lewis, Jada, 818
Lewy Body Dementia Association, 881–882
Lewy body dementias (LBD)
AD compared to, 874
attention deficits in, 874–875
autonomic dysfunction with, 877
treatment therapies for, 883
behavioral features of, 876
caregiver issues with, 881–882
cognitive fluctuations with, 872, 877
construction deficits with, 875
clinical features of, 874
delusions with, 876
depression with, 876
diagnostic criteria for, 873–874
hallucinations with, 876
memory deficits with, 876
neuroleptic sensitivity in, 878
PDD compared to, 874
psychiatric symptoms with, 876
visuospatial deficits in, 875
epidemiology of, 874
executive function deficits with, 874–875
language deficits with, 876
neuropsychiatric features of, 876
neuropsychological features of, 874–876
PDD, 872
cognitive impairments in, 872
depression with, 876
diagnostic criteria for, 873
DLB compared to, 874
executive function deficits in, 874–875
hallucinations with, 876
language deficits with, 876
memory deficits with, 876
neuropathology of, 878
personality changes with, 876–877
prevalence rates of, 874
RBD, 872
sleep disorders with, 878
treatment therapies for, 882–883
with ACh, 882
for autonomic dysfunction, 883
for behavioral symptoms, 882–883
for cognitive symptoms, 882
with memantine, 882
for motor symptoms, 882
visuospatial deficits with, 875
LFMS. See low field magnetic
stimulation
LGMM. See latent growth mixture modeling
LGN. See lateral geniculate nucleus
LIF. See leukemia inhibitory factor
ligand-gated ion channels, 31
light-activated halorhodopsins, 141
light-sensors, in optogenetic technology, 145–146
linkage analysis
for ADHD, 1038
for genetic epidemiology, 161
for IBD chromosomes, 161
linkage disequilibrium (LD), 162–163
in HapMAP project, 163
structure of, 163
linkage disequilibrium analysis. See association analysis
lipidization, 150
lithium
signal transduction pathways and, 40, 61
for TRD, 517
Little Albert case study, 607
LKS. See Landau Kleffner syndrome
LOAD. See late onset
Alzheimer’s disease
locus coeruleus-norepinephrine (LC-NE) system, resilience and, 1155
long-term depression (LTD), 10
LTP compared to, 65
NMDA receptors, 66
long-term potentiation (LTP)
in brain development, 10
cellular mechanisms for, 65–67
discovery of, 64
features of, 65
Hebbian, 65
LTD compared to, 65
phases of, 65
STP and, 65
lorcaserin, 767
low field magnetic stimulation
(LFMS), 520
low protein diets, childhood psychiatric disorders and, 959–960
low self-control, 709
LRRTMs. See leucine-rich repeat transmembrane neuronal proteins
LTD. See long-term depression
LTP. See long-term potentiation
Ludiomil. See maprotiline
lurasidone, 351
M
macrophage-inducible NOS (iNOS), 23
MADD. See mixed anxiety/depression disorder
magnetic resonance imaging (MRI). See also functional magnetic resonance imaging
etiology of, 823
for hippocampal volume, 822–823
brain function assessment, 200–202
BOLD, 200
for cerebral perfusion assessment, 199–200
DSC, 199
SS contrast, 199
CMRO2 and, 206
DWI, 202
principles of, 202
DW-MRI, 996
for FTD, 892
for late life depression, 470
purpose of, 1073
magnetic resonance spectroscopy (MRS), 204–205
for ADHD, 1043
for AUDs
for cognitive performance, 751–752
treatment therapies for, 752–753
abnormalities in, 757
Cho peak, 743
GluR genes, 742
MI, 743
NAA, 742
PCr, 744
development of, 204
of inhalants, 747
neurotransmitters and, 205
PRESS, 204
for psychiatric disorders, 264, 266
HIV and, 746
spatial localization in, 204
spectral quantification in, 205
STEAM, 204
for SUD
function of, 742
future applications for, 756–758
summary of findings for, 756
magnetic seizure therapy (MST), 520
Magnevist, 151
magnitude squared coherence (MSC), 1003
MAGUK associated signaling complexes (MASC), 312–321
proteins in, 314
major depressive disorder (MDD). See also glutamate system
adverse life events and, 399
animal models of, 37, 413, 417–422
appetitive tasks in, 415
behavioral validity of, 414
CMS, 418
developmental stressors in, 419–420
early life stressors in, 419–420
learned helplessness in, 418–419
olfactory bulbectomy, 418
pathological validity of, 414
repeated social defeat stress in, 420–421
behavioral domains of, 415–417
appetitive tasks, 415
ethologically-relevant, 416–417
differentiation between, 399
family studies for, 399
by type, 398
cell reprogramming technologies for, 408
childhood trauma and, 399
chronic stress and, 96
definition of, 396
DENT study for, 400
diagnostic systems for, 371, 379–380
emotional processing in, 463–465
limbic structure imaging, 464–465
negative emotional bias, 465
endophenotypes of, 396
experimental medicine therapy for, 451
familial risk factors for, 397–398
Feigner Criteria for, 391, 396
GABA and, 425
genetic epidemiology of, 396–397
heritability in, 397
relative risks in, 397
in twin studies, 398
genetic studies for
with candidate genes, 400, 405–407
CNVs for, 404
with gene expression, 400
through GWAS, 400, 402–405, 403
with linkage analysis, 399–403
5-HT receptors, 425
ketamine treatment for, 425
in late life, 384
NE and, 425
neuroimaging of, 425
family studies for, 399
treatment therapies for. See also antidepressants
monoamine hypothesis for, 508–509
viral-mediated gene transfer and, 118–119
major histocompatibility complex (MHC), 238–240
males
ASD in, 936
BPD in, 1091
eating disorders among, 1182
FTD and, 888
mood disorders in, androgens and, 493
mammalian target of rapamycin (mTOR), 61, 60
mania
Feigner Criteria for, 225
melancholia and, 368
mouse models of, 288
manic episodes
diagnostic systems for, 371
as medically-induced, 381
MAOA. See monoamine oxidase A
MAOIs. See monoamine oxidase inhibitors
MAP. See mitogen-activated protein
maprotiline, 509
MAPT gene. See microtubule-associated protein tau gene
marijuana, 23. See also endocannabinoids
psychoactive effects of, 24
Marplan. See isocarboxazid
MASC. See MAGUK associated signaling complexes
Massachusetts General Hospital Staging Model (MGH-s), 390
massive parallel sequencing (MPS), 945
maternal neglect, 1118
maternal odor learning, 597–598
Maudsley Staging Model (MSM), 390
MCI. See mild cognitive impairment
MCMC. See Monte Carlo Markov Chain
MDD. See major depressive disorder
MDMA. See 3, 4-methylenedioxy-N-methylamphetamine
mecamylamine, 450
RTT and, 971
media induction, in CNS, 3
medial prefrontal cortex (mPFC), in reward, 735
medical foods
efficacy of, 849
Souvenaid, 849
medical illness, depression and
antidepressant therapy, 503
autonomic nervous system and, 499
comorbidity mechanisms with, 498–499
endothelial dysfunction and, 499
HPA axis and, 498
statins for, 498
sympathoadrenal hyperactivity and, 498
cancer, 501
antidepressant therapy, 504–505
cytokines and, 501
prevalence rates for, 501
sickness syndrome and, 501
comorbidity mechanisms, 496–502
antidepressant therapy, 503–504
cellular glucose transporters and, 500
comorbidity mechanisms, 499–500
HPA axis and, 500
neuroimaging for, 500
psychosocial burden as factor in, 499–500
antidepressant therapy, 504
comorbidity mechanisms, 500–501
HPA axis and, 501
prevalence rates for, 500
immune system dysregulation and, 497
prevalence rates for, 496
screening tools for, 502
treatment therapies, 502–503. See also antidepressants
neuromodulatory, 503
with psychostimulants, 503
with SSRIs, 502
medically-induced mood disorders
diagnostic systems for, 380–381
general symptoms with, 381
manic symptoms with, 381
melancholia. See also depression
mania and, 368
in mood disorder diagnostic systems, 383
melancholic depression, 522
melanocortin, 1178
melatonin, 1132
ACh and, 845
for AD, 845
affinity levels for, 845
approval process for, 845
GLMT system and, 845
for LBD, 882
memory. See also episodic memory; working memory
bipolar disorder and, 358
consolidation of, resilience and, 1160–1162
deficits in, optogenetic technology for, 142
DLB and, 876
extinction of, resilience and, 1160–1162
fear development and, during adolescence, 601–603
GABA receptors, drug development and, 577–578
intrinsic plasticity in, 70–71
PDD and, 876
psychosis and, 349
PTSD and, 617
sleep functions and, 1138–1139
Mendel, Emanuel, 368
Menninger, William, 369
menstrual cycle, gonadal steroids and, 486
mental illness. See also psychotropic drugs
NMDA upregulation and, 35
psychomimetics and, 36
messenger ribonucleic acid (mRNA)
coding information in, 77
information flow in, 77
TH and, 14
metabolic diseases, biophysiological causality in, 195
for late life depression, 477–478
metabotropic receptors, 32
addiction and, 688
methamphetamines
negative reinforcement and, 737
neuroimaging for, 726
active, 90
addictive behaviors and, 95
binding protein families in, 89–90
DNMT mediation of, 88
epigenetic mechanisms of addiction and, 691–692
gene expression and, 89
mechanisms of, 91
schizophrenia and, 97
methyl-CpG-binding proteins
location of, 88
3, 4-methylenedioxy-N-methylamphetamine (MDMA) (ecstasy), 747, 748
N-methyl-D-aspartate (NMDA) receptors
glutamate and, 31–32, 439, 444
LTD and, 66
mental illness and, 35
psychomimetics and, 36
schizophrenia and, 308
site-specific recombination systems, 116
synaptic plasticity and, 65–66
methylphenidate, 711, 1029–1030
Meyer, Adolph, 369
MGH-s. See Massachusetts General Hospital Staging Model
ABC and, 1061
in RCTs, 1061
MHC. See major histocompatibility complex
MI, as glial marker, 743
in animal models, 149
assessment methods with, 151–152
in blood supply, 149
in contrast ultrasounds, 149–150, 149
in drug delivery systems, 151
FDA approval of, 149
Optison, 148
microglia, in brain development, 7
microiontophoresis, 32
microRNA (miRNA), 77
in epigenetics of childhood psychiatric disorders, 963
microsleep episodes, 1127
microtubule-associated protein Tau (MAPT) gene, 894
midazolam, 514
mild cognitive impairment (MCI), 792–793, 834, 859
ACh for, 845
Mini Mental State Examination (MMSE), 795
minocycline, 657
miRNA. See microRNA
mirtazapine, 515
mitochondria, in bipolar disorder, 360–361
mitogen-activated protein (MAP), 57
Ras/MAP-kinase pathway, 49
mixed anxiety/depression disorder (MADD), 531
mixed episodes, diagnostic system for, 371–379
MMSE. See Mini Mental State Examination
MOAs. See monoamine oxidases
MOCA. See Montreal Cognitive Assessment
molecular biology. See also deoxyribonucleic acid; gene expression; ribonucleic acid; transcription control, for genomes
contemporary research in, 76
DSM-III influenced by, 1073
nucleosomes, 79
monoamine oxidases (MAOs), 16
monoamine oxidase A (MAOA), 1109
monoamine oxidase inhibitors (MAOIs), 503, 510–513. See also specific drugs
for anxiety disorders, 636
endogenous, 512
reversible, 512
side effects of, 511
monoamine transmitters
amino acid transmitters compared to, 19
monoclonal antibodies, for SUDs, 768
monogenic diseases, stem cell modeling for, 128
Monte Carlo Markov Chain (MCMC), 191
Montreal Cognitive Assessment (MOCA), 795
mood disorders. See also depression; major depressive disorder; reproductive endocrine-related mood disorders
androgens and
in men, 493
animal models of, 296
for CMS, 411
computer-generated programs, 411
construct validity of, 411–412
for drug screening, 411
pathological validity of, 413
predictive validity of, 413
purpose of, 411
symptom modeling, 413
diagnosis of
Bleuler and, 368
challenges as result of, 367
development of, 367
false positives in, 367
during Middle Ages, 368
modern concepts of, 367
optimal research for, 367
purpose of, 367
diagnostic systems
accuracy of, 389
atypical features of, 383
for bipolar disorders, 380
catatonic features of, 383
core criteria selection, 391
for cyclothymia, 380
differential diagnosis, 384–388
in DSM-IV, 371
for dysthymic disorder, 380
etiologic approach to, 388
exclusive approaches in, 388
for full interepisode recovery, 384
for hypomanic episode, 379
inclusive approaches in, 388
increased threshold approach to, 388
in late life, 384
for manic episodes, 371
for MDD, 371, 379–380, 382–384
melancholic features, 383
neurobiological mechanisms in, 392
postpartum onset, 383
psychotic features of, 382
with rapid cycling, 384
remission of, 382
seasonal patterning in, 384
severity of, 382
subsyndromal mixed states and, 391
symptom substitution approach to, 388
tests in, 390
thresholds for, 391
trauma history in, 391
treatment resistance and, 390
in DSM. See also Diagnosis of Statistical Manual of Mental Disorders, Fifth Edition; Diagnosis of Statistical Manual of Mental Disorders, Fourth Edition
from 369, 1840–1940
incorporation of psychiatric disorders into, 369
pharmacological revolution and, 370
recategorization within, 370
during World War II, 369
gonadal steroids and, history of, 483
in ICD. See also International Classification of Disease, 10th Revision
WHO adoption of, 370
medically-induced
diagnostic systems for, 380–381
general symptoms with, 381
manic symptoms with, 381
neuroimaging abnormalities in, 460–463
in animal models, 462
brain structural abnormalities, 461–462
neuropathological correlations in, 462–463
of oligodendrocytes, 462
observations of, 460
dysregulation types in, 1083–1084
fear circuit dimensions for, 1083
heterogeneity of expression for, 1083
in twin studies, 1083
related conditions with, 391–392
substance-induced
diagnostic systems for, 380–381
general symptoms of, 381
mood states, 471. See also emotions
moral compass, resilience and, 1150
religion and spirituality as part of, 1150
morphine, intrinsic plasticity of brain and, 71
mother-infant attachment, 1116–1118
chemical substrates of, 1116–1118
development of, 1116
maternal neglect and, 1118
mouse models
beta-catenin pathway, 294
CACNA1C gene, 293
circadian-rhythm-related genes, 294
DGK models, 294
future developments for, 295–296
in Madison strain, 294
neurocan gene, 294
ODZ4 gene, 294
of Down syndrome, 973
Fmr1KO, 974
gene function studies in, 109
reverse genetic strategy, 109
for HD, 287
knockout, 111–113. See also conditional knockout mouse models
disease models, 112
dopaminergic system and, 112, 114
ES cell line modifications, 111
haplo-insufficiency, 112
lethality issues, 113
Reeler gene, 112
TH, 113
transgenic compared to, 111
of mania, 288
of schizophrenia
dysbindin genes, 290
etiologic models, 287
future developments for, 295–296
genetic, 288
through GWAS, 289
knockout models, 292
with linkage study genes, 290–292
non-genetic models, 288
pathogenic models, 288
pathophysiological models, 287
PCP-induced hyperactivity in, 288
pharmacological models, 288
phenotypic models, 287
risk allele models, 292
symptom-oriented models, 288
transgenic, 109–111. See also amyloid precursor protein
disease models, 110
family lines, 110
gene expression, 110
knockout models compared to, 111
large-clone, , 110
YACs, 110
mPFC. See medial prefrontal cortex
MPS. See massive parallel sequencing
MPTP animal model, of PD, 810
MRI. See magnetic resonance imaging
mRNA. See messenger ribonucleic acid
MRS. See magnetic resonance spectroscopy
MSC. See magnitude squared coherence
MSM. See Maudsley Staging Model
MST. See magnetic seizure therapy
mTOR. See mammalian target of rapamycin
Mullan, Michael, 815
multiple sclerosis, 150
muscarine agonists, 352
mutant analysis, 109
myelin, schizophrenia and, 328–329
N
NAA, MRS for, 742
NAc. See nucleus accumbens
N-acetylcysteine, 657
NAHR. See non-allelic homologous recombination
Nardil. See phenelzine
National Alzheimer’s Project Act, 844
National Comorbidity Studies
(NCSs), 774
National Institute of Health (NIH), 1067
National Institute of Mental Health (NIMH), 535, 1076–1077
drug development under, 1086
strategic aims of, 1077
National Institute on Aging (NIA), 792
National Institute on Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Dementias Association (NINCDS-ADRDA), 792, 857
ncRNA. See non-coding RNA
NCSs. See National Comorbidity Studies
NE. See norepinephrine
negative reinforcement
addiction and, 738
classical conditioning models of, 737
methamphetamines and, 737
opponent-process models of, 737
self-medication models of, 737
tobacco use and, 737
neglect. See maternal neglect
neonates, brain development in, 10
schizophrenia and, 327
nerve growth factor (NGF), 25
in signal transduction pathways, 43
synapses and, 8
NETs. See norepinephrine transporters
network-wide homeostatic plasticity, 74
BDNF release and, 74
neurological disorders and, 74
neural induction, in CNS, 3
neuromeres, 3
prosomeres, 3
neuregulin-1 (NRG1) genes, 290–291
neurobiology. See also neurodevelopmental disorders
of AN, 1171
compulsivity in, 685
CRF and, 685
DA functions and, 683
habenula in, 685
HPA axis and, 685
insula in, 685
PFC in, 684
septum in, 685
of aggression
molecular mechanisms in, 1108–1109
OFC in, 1106
of ASPD, 1095
of bipolar disorder
circadian abnormalities in, 357
clinical predictors in, 356
cognitive predictors in, 356
genetics of, 355
GSK3 pathway, 360
mitochondrial dysfunction in, 360–361
neurogenesis and, 360
neuroplasticity and, 360
prodrome, 356
risk factors for, 355
of bulimia nervosa, 1171
for appetite, 1181
for body image perception, 1182
for emotional processing, 1181–1182
of depression
brainstem projections and, 459
CLPFC in, 457
connection regions in, 458
cortico-striatal-thalamic circuits, 459–460
history of, 455
hypothalamus projections and, 459
intralaminar thalamic nuclei in, 460
medial prefrontal network in, 456–457
mediodorsal nucleus, 459
orbital prefrontal network in, 456
prefrontal projections in, 460
amygdala activity, 614
of late life depression, 471–472
challenges of, 651
cognitive activation studies of, 649
neuroanatomy in, 649
neuroimaging of, 649
phenotype heterogeneity and, 651
amygdala and, 615
PFC activity and, 616
of pathological anxiety, 606
of pathological fear, 606
of personality disorders
of ASPD, 1095
avoidant disorders, 1089
development of, 1089
function of, 1089
OFC and, 1089
risk factors in, 1089
of STPD, 1089
amygdala activity, 616–618, 667–668
memory deficits and, 617
of reactive aggression, 1106, 1107–1108
of REM sleep, 1136
of resilience, 1151–1158, 1159
BDNF, 1157
eCBs, 1158
galanin and, 1156
LC-NE system, 1155
serotonin, 1156
amygdala, 734
lateral habenula, 735
mPFC, 735
OFC, 735
of schizophrenia, 338
electrophysiology for, 343
neurobehavioral performance, 338–339
olfactory identification in, 339
social cognition in, 339
for blood flow, 1136
for metabolism, 1136
REM, 1136
spontaneous activity, 1134
stimuli response, 1136
for wakefulness, 1134
social anxiety disorder, 611–613
insula dysfunction, 612
of social attachment, 1112–1113
for adult bonding, 1124
in animal models, 1112
future brain applications in, 1124–1125
for infant-parental attachment, 1113–1116
for mother-infant attachment, 1116–1118
parent-offspring bonding, 1113–1119, 1124
social brain hypothesis for, 1112
of SUD, 732
of wakefulness, 1134
neurocan gene, 294
neurochemical systems, in CNS. See also neurotransmitters
classic view of, 12
neurocircuitry-based models of depression, 465–466
amygdala-mediation of, 465–466
DBS for, 466
in default mode system, 466
neurodegenerative diseases. See also Alzheimer’s disease; Parkinson’s disease
aging and, 150
BBB disruption and, 150–151, 150–152
drug delivery in, 151
neurodevelopmental disorders. See also autism spectrum disorder
AMPA receptors and, 991
applications in, 1004
classification for, 980
diagnostic categories for, 981
excitatory imbalances in, 990–991
functional connectivity and, 990–991
in ADHD, 1006
brain movies as system for, 995
cross mutual information in, 1003
generalized synchronization in, 1003–1004
global features of, 998
Granger causality mapping for, 1001
ICA for, 1000
motivation for, 995
MSC for, 1003
in OCD, 1007
PDC and, 1003
PLV in, 1003
in schizophrenia, 1005
signaling in, 996
in TS, 1007
genetic risks and, 980
glutamic acid decarboxylase and, 991
inhibitory imbalances in, 990–991
neuroimaging for
functional connectivity and, 995, 996
structural connectivity and, 996
normal brain development and, 1004–1005
postnatal brain development and, 987–990
chromatins in, 987
critical periods of, 987
environmental influences on, 987–988
LRRTMs in, 989
multiprotein complexes in, 988
neural plasticity and, 988
stress and, 987
synaptogenic proteins and, 988–989
prenatal brain development and, 980–985
cellular migration in, 985
cortical migration and, 985–987
dysraphias and, 981
mechanistic models for, 985
neural tube regionalization in, 982–983
neuroepithelium support, 983–984
SHH and, 983
transcriptional support in, 984–985
structural connectivity and, 996–999
DW-MRI, 996
fMRI-based, 999
tract-based, 996
voxel-based, 998
chromatin architecture, 174–175
coding sequence mutations, 177
developmental plasticity in, 175–176
DNA
eraser proteins, 177
euchromatin, 173
foundations of, 172
heterochromatin, 173
histones, 174
monogenetic etiologies, 176–177
nucleosomes, 173
for PTSD, 176
reader proteins, 177
writer proteins, 177
neurofibrillary tangles (NFTs), 791–792
in CSF, 835
neurogenesis. See brain; neuroepigenetics; neurons
neuroimaging methodologies. See also amyloid imaging; functional magnetic resonance imaging; magnetic resonance imaging
for AD
benefits of, 821
with biomarkers, 821–825, 828–830
with dementia, 796
disease modification for, 855
function of, 821
neurodegeneration estimation with, 821–825
purpose of, 821
for addiction, 700. See also craving, addiction and
in animal models, 721, 723–725
applications in studies of, 716
blood flow and, 727
brain development and, 707–708
environmental factors, 720
genetic basis of, 700
for glucose metabolism, 716, 722, 727–728
for heroine, 726
for methamphetamine, 726
for nicotine, 723
for opioids, 727
pharmacokinetic profiles and, 722
for research, 740
risk identification through, 740
of serotonins, 727
severity measures, 738
with SPECT, 716
with DTI, 1044
with MRS, 1043
with PET, 1043
with SPECT, 1043
for antidepressant biomarkers, 518
of brain enlargement, 1024–1025
with DTI, 1026
for biomarkers
for antidepressants, 518
of emotion regulation, 1093
of interpersonal processes, 1093
brain stimulation. See also deep brain stimulation; transcranial direct current stimulation; transcranial magnetic stimulation
future applications for, 218–219
structure compared to function in, 212
targeting in, 213
cholinergic system and, 449
deformation-based morphometry for, 208
measure of, 206
MRI and, 206
for depression, 428
for amygdala, 428
diabetes mellitus, 500
functional compared to structural, 462–463
for hippocampus, 428
for NAc, 428
for PFC subregions, 428
for functional connectivity, in neurodevelopmental disorders, 995, 996
for MDD, 425
methamphetamine use, 726
in animal models, 462
brain structural abnormalities, 461–462
neuropathological correlations in, 462–463
of oligodendrocytes, 462
development of, 204
neurotransmitters and, 205
PRESS, 204
for psychiatric disorders, 264, 265–266
spatial localization in, 204
spectral quantification in, 205
STEAM, 204
for nicotine, 723, 726, 725–726
for OCD, 649
for psychiatric disorders
for brain function, 258
development of, 256
function of, 256
of GABA receptors, 264
for genetic mechanisms, 266
in high-risk studies, 260
for illness effects, 259
Kraepelin’s influence on, 256
in longitudinal studies, 259–260
for neurochemical systems, 264–266
with PET, 258
of PFC, 258
ROIs and, 257
statistical considerations for, 260
themes in, 256
for treatment therapies, 259
VBMs and, 257
with fMRI, 342
for tic disorders, 1054
with fMRI, 1054
with PET, 1054
for TS, 1054
with fMRI, 1054
with PET, 1054
neuroleptics, 61
drug development for, 256
neurological disorders. See also biophysiology, of disease; specific disorders
intrinsic plasticity in, 71
network-wide homeostatic plasticity and, 74
for FD, 130
for FXS, 130
for monogenic diseases, 128
for polygenic diseases, 132
for RTT, 129
for schizophrenia, 132
synaptic plasticity in, 67
neurons. See also brain; catecholamines; electrophysiology; neurotransmitters
AHP and, 29
in brain development, 7
calcium in, 28
chemical messengers in, 13
depolarization of calcium in, 47–49
extracellular fluid in, 27
G proteins and, 32
ion channels, 27
ionotropic receptors and, 32
ion pumps and, 27
IPSP and, 31
metabotropic receptors and, 32
neurotransmitters and, 13, 30–32
potassium in, 27
receptors and, 27
refractory periods for, 30
stem cell direct programming and, 124–128
Oct4 genes, 127
thresholds in, 28
types, 7
neuronal NOS (nNOS), 23
neuronal pathways, for schizophrenia, 330–334
DISC1 genes, 334
early developmental, 330
neuropeptide model, of BPD, 1092–1093
neuropeptide Y (NPY)
eating disorders and, 1177
neuroplasticity, in depression, 427–428
neuroprotection, 869
neurosteroids, PMDD and, 487
neurotensin (NT)
inactivation of, 22
release of, 22
neurotherapeutics. See also psychopharmacologic agents
neuroticism
depression and, 396
neurotransmitters. See also amino acid transmitters; γ-aminobutyric acid; catecholamines; classical neurotransmitters; dopamines; glutamate system; peptide transmitters; serotonin
ACh and, 12
animal models of, 1035
catecholaminergic systems, 1035
brain function and, 64
cholinergic system, 445–450. See also antidepressants
clinical trials with, 446–450, 447
physiology of, 446
definition of, 12
depletion rates for, 13
depression and, alterations in, 425–427
heterogeneity in, 426
eating disorders and, dysregulation and, 1178–1180
gas, 23
gated ion channels in, 40–41, 42
GLMT system, 439–445. See also depression
anatomy of, 20
drug development, 352
glutamic acid decarboxylase and, 19
history of, 439
inactivation of, 20
monoamine transmitters compared to, 19
NMDA receptors and, 31–32, 439–444
physiology of, 439
psychosis and, 348
regulation of, 20
in reward, 734
riluzole, 445
information coding by, 13
monoamines, 19
MRS and, 205
NO, 23
peptide, 13
release sites for, 13
dopamine hypothesis of reward, 733–734
GABA, 734
glutamates, 734
incentive salience and, 733
reward prediction error and, 733
serotonin, 734
schizophrenia and, 329
serotonin
anatomy of, 19
antidepressants and, 36–37, 61
inactivation of, 19
OCD and, 647
PMDD and, 487
psychosis and, 352
reward and, 734
synthesis of, 18
tryptophan and, 18
substance identification for, 12
synaptic specialization and, 13
synthesis of, 12
temporal aspects of, 13
tic disorders and, 1053
TS and, 1053
neurotransmitter-gated ion channels, 40–41, 42
neurotrophic factors
BDNF, 25
CNTF, 84
conditional knockout mouse models, 116
in depression treatment responses, 432–433
FGF2 and, 433
VEGF and, 433
functions of, 25
GDNF, 45
NGF, 25
NT-3, 116
pathways for, 25
regulation of, 25
regulatory functions of, 25
synthesis of, 25
types of, 24
next-generation sequencing (NGS), 163–164
with singletons, 169
whole-exome sequencing, 169
NFTs. See neurofibrillary tangles
NF-κB. See nuclear factor κB
NGF. See nerve growth factor
NGS. See next-generation
sequencing
NIA. See National Institute on Aging
abuse of, 95
neuroimaging for, 723, 725–726
nicotinic cholinergic agents, 449–450
mecamylamine, 450
varenicline, 450
NIH. See National Institute of
Health
NIMH. See National Institute of Mental Health
NINCDS-ADRDA. See National Institute on Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Dementias Association
nitric oxide (NO)
eNOS, 23
iNOS, 23
as neurotransmitter, 23
nNOS, 23
in signal transduction pathways, 51–52, 54
N-nitroso-N-ethylurea (ENU)
model, 292
NMDA. See N-methyl-D-aspartate receptors
nNOS. See neuronal NOS
NO. See nitric oxide
non-allelic homologous recombination (NAHR), 944
non-coding RNA (ncRNA), 77, 95–96
non-fast-spiking (non-FS) receptors, 301
non-rapid eye movement (NREM) sleep, 1127–1128
awakenings during, 1137
blood flow and, 1136
metabolism and, 1136
microsleep episodes, 1127
stimuli responsiveness in, 1136
non-steroidal anti-inflammatory drugs (NSAIDs), in AD treatment, 846
in disease modification, 869
Noonan syndrome, 1011
norepinephrine (NE)
MDD and, 425
sleep cycles and, 1130
norepinephrine reuptake inhibitors (NRIs), 516–519
norepinephrine transporters (NETs), 17
nortriptyline, 511
Notch signaling, in brain development, 7
novelty-seeking traits, 680–681
novelty suppressed feeding
(NSF), 415
NPY. See neuropeptide Y
NRAMs. See nuclear receptor alternate site modifiers
NREM sleep. See non-rapid eye movement sleep
NRG1 genes. See neuregulin-1 genes
NRIs. See norepinephrine reuptake inhibitors
NSAIDs. See non-steroidal anti-inflammatory drugs
NSD1 gene. See nuclear-receptor-binding SET-domain-containing protein 1 gene
NSF. See novelty suppressed feeding
NT. See neurotensin
NT-3. See neurotrophin 3
nuclear factor κB (NF-κB), 81
nuclear receptor alternate site modifiers (NRAMs), 485
nuclear-receptor-binding SET-domain- containing protein 1 (NSD1) gene, 1014
nucleic acids. See deoxyribonucleic acid; ribonucleic acid
nucleosomes, 79
neuroepigenetics, 173
nucleotides
in biophysiology, change frequency of, 183
cyclic, 46
nucleus accumbens (NAc), 67
addiction and
cellular physiology of, 689
AUD and, 71
depression and, 428
drug abuse and, 71
in neurocircuitry of addiction, 683–684
SUD and, 783
O
OAD. See childhood overanxious disorder
obestatin, 1177
obsessive-compulsive disorder (OCD), 530
for circuit abnormalities, 652–653
future applications of, 653
for genetic abnormalities, 652
clinical features of, 646
DCS therapy for, 625
environmental factors for, 647–648
glutamate and, 647
hormonal agents in, 648
psychological trauma in, 648
serotonin and, 647
family studies for, 538
functional connectivity in, 1007
neurobiology of, 648–650, 1089
challenges of, 651
cognitive activation studies of, 649
neuroanatomy in, 649
neuroimaging of, 649
phenotype heterogeneity and, 651
pathophysiology of, working model for, 650–651
prevalence rates for, 538, 646
treatment therapies for, 653–659
with CT, 658
with DBS, 659
with ECT, 659
novel medications in, 657
with SSRIs, 653–655, 656, 656–657
with surgery, 659
with TMS, 659
twin studies for, 538
OCD. See obsessive-compulsive disorder
Oct4 genes, 127
ocular dominance columns, 9
ODZ4 gene, 294
OFC. See orbital prefrontal cortex
olfactory bulbectomy, 418
oligodendrocytes
neuroimaging of, with mood disorders, 462
Omniscan, 151
1000 Genomes Project, 164
opioids. See also heroine, neuroimaging for; morphine, intrinsic plasticity of brain and
BPD and, 1093
for depression, 451
neuroimaging for, 727
self-cutting and, 1093
Opitz-Kaveggia syndrome (FGS), 1018–1019
clinical features of, 1018
diagnosis of, 1018
gene mutations in, 1018
prevalence of, 1019
opponent-process models, of addiction, 737
optimization of, 139
rhodopsins and, 138
Optison, 148
optogenetic technology, for disease research
action spectrum engineering for, 145
for addiction, 690
biochemical-signaling expansion in, 146
electric-inhibitory channels in, 146
experimental potential of, 141
functions of, 138
halorhodopsins, 138
light-activated, 141
mammalian biology issues and, 144
neuropsychiatric disease models, 141–144
for anxiety disorders, 142
combinatorial optogenetics, 144
excitation-inhibition imbalance in, 142, 144
fiberoptic neural interface, 142
IUE, 142
for memory deficits, 142
projection targeting in, 142
neuroscience applications, 141–144
non-genetically tractable cell types in, 145
optimization of, 139
rhodopsins and, 138
reverse engineering in, 145
tool mutations in, 146
versatile strategizing with, 144
wiring extraction patterns and, 145
orbital prefrontal cortex (OFC), 474–475
aggression and, 1106
in personality disorders, 1089
in reward, 735
orexin, 22
organotherapy, 483
orofaciodigital syndrome, 982
overconsolidation theory, of PTSD, 561
Owen, Michael, 1084
oxytocin
in adult bonding animal models, 1121
infant-parental attachment and, 1115
mother-infant attachment and, 1116–1118
P
PACAP. See pituitary adenylate cyclase-activating polypeptide
paliperidone, 351
PANDAS. See Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections
panic disorder, 532
DCS therapy for, 625
family studies for, 537
GABA and, 567
amygdala and, 615
PFC activity and, 616
symptoms of, 637
treatment therapy for
with DCS, 625
first-line approaches to, 637–640
second-line approaches to, 640–641
twin studies for, 537
paradoxical sleep, 1128. See also rapid-eye movement sleep
parent-offspring bonding
father-infant attachment, 1118–1119
chemical substrates in, 1119
display behaviors in, 1118–1119
neuroanatomy of, 1119
infant-parental attachment, 1113–1116
development of, 1113
motivation circuits in, 1115
neurobiology of, 1115
social approaches to, 1115
mother-infant attachment, 1116–1118
chemical substrates of, 1116–1118
development of, 1116
maternal neglect and, 1118
neurobiology of, 1113–1119, 1124
for infant-parental attachment, 1115, 1113–1116
for mother-infant attachment, 1116–1118
Parkinson, James, 872
Parkinson’s disease (PD)
animal models of, 810
MPTP model, 810
autonomic dysfunction with, 877
deprenyl and, 16
dopamines and, 131
gene editing in, 131
late life depression and, 478
neuropathology of, 878
PDD
cognitive impairments in, 872
depression with, 876
development of, 872
diagnostic criteria for, 873
DLB compared to, 874
executive function deficits in, 874–875
hallucinations with, 876
language deficits with, 876
memory deficits with, 876
neuropathology of, 878
phenotypes in, 131
prevalence rates for, 872
stem cell modeling for, 130–131
viral-mediated gene transfer and, 117–118
ZFN and, 131
Parkinson’s disease dementia (PDD)
cognitive impairments in, 872
depression with, 876
development of, 872
diagnostic criteria for, 873
DLB compared to, 874
executive function deficits in, 874–875
hallucinations with, 876
language deficits with, 876
memory deficits with, 876
neuropathology of, 878
Parnate. See tranylcypromine
partial directed coherence (PDC), 1003
parvalbumin (PV) neurons, 304–309
pathological anxiety, 552
developmental manipulations in, 561
genetic manipulations in, 561–562
incubation in, 563
individual differences in, 562
psychological manipulations in, 561
reconsolidation in, 563
stress-enhanced fear learning in, 561
treatment processes in, 562–564
defensive responding and, 552
neurobiology of, 606
stress responses to, 552
pathological fear, 552
developmental manipulations in, 561
genetic manipulations in, 561–562
incubation in, 563
individual differences in, 562
psychological manipulations in, 561
reconsolidation in, 563
stress-enhanced fear learning in, 561
treatment processes in, 562–564
defensive responding and, 552
neurobiology of, 606
stress responses to, 552
pathways. See axon pathways; signal transduction pathways
Pavlovian threat conditioning (PTC), 554–558
behavioral aspects of, 554
molecular mechanisms of, 556
procedure variations for, 556–558
synaptic plasticity, 556
PBS. See positive behavioral support
PcG proteins. See Polycomb-Group proteins
PCP. See phenylcyclidine
PCr. See phosphocreatine
PD. See Parkinson’s disease
PDC. See partial directed coherence
PDD. See Parkinson’s disease dementia
pediatric anxiety disorders
age of onset for, 539
family studies for, 539
design of, 539
OAD, 540
separation anxiety disorder, 539
SOC, 539
twin studies for, 539
Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS), 1056–1057
Pepeu, Giancarlo, 811
peptide transmitters
classical compared to, 21
hypocretin, 22
inactivation of, 22
orexin, 22
release of, 22
types of, 1014
peptide YY (PYY), 1177
perfectionism, AN and, 1182
perimenopausal depression, 491–492
hormones
in therapy treatments, 492
onset triggers for, 492
risk predictors for, 491
personality
BPD
diagnostic criteria for, 1090
FFM and, 1090
emotional regulation and, 589
personality disorders. See also obsessive-compulsive disorder
candidate gene studies for, 1097
childhood antecedents for, 1094
clinical indications for, 1093–1094
cognitive function and, 1096
comorbidities with, 1094
development of, 1094
in DSM-IV, 1094
epidemiology of, 1094
genetic vulnerability of, 1096
linkage analysis for, 1096–1097
neurobiology of, 1095
prefrontal abnormalities for, 1095
prevalence rates for, 1094
psychopathy compared to, 1094
avoidant, 1089
neurobiology of, 1089
affective dysregulation and, 1091–1092
amygdala function and, 1092
clinical evidence for, 1090
depression and, 1091
fMRI for, 1092
gender and, 1091
genetics of, 1092
illness burden with, 1090–1091
impulsive aggression dimensions in, 1091–1092
neuroimaging for, 1091–1092, 1093
neuropeptide model of, 1092–1093
opioids and, 1093
oxytocin for, in treatment therapies for, 1092–1093
prevalence rates for, 1090
remission rates for, 1090
self-cutting behaviors and, 1093
serotonergic system and, 1092
trauma and, 1091
treatment therapy utilization for, 1090–1091
Trier Social Stress Test for, 1093
comorbidity rates and, 1090
externalizing, 1090
internalizing, 1090
neurobiology of
of ASPD, 1095
avoidant disorders, 1089
development of, 1089
function of, 1089
OFC and, 1089
risk factors in, 1089
of STPD, 1089
OCD, 1089
cognitive impairments and deficits and, 1098
diagnostic criteria for, 1097
dopaminergic activity and, 1098
genetic vulnerability and, 1098–1099
information processing and, 1098
neurobiology of, 1089
prevalence rates for, 1097
psychoticism dimension of, 1098
WM and, 1098
PET. See positron emission tomography
PFC. See prefrontal cortex
PGRN gene. See progranulin gene
phase locking value (PLV), 1003
Phelan-McDermid syndrome (PMS), 1024
treatment therapies for, 1031–1032
phenylalanine, 14
phenylcyclidine (PCP), 36
psychosis and, 349
schizophrenia and, in mouse
models, 288
phenylethanolamine-N-methyltransferase (PNMT), 14, 15
phenylketonuria (PKU)
animal models of, 975
ASD and, 1024
phobias
family studies for, 538
twin studies for, 538
phosphocreatine (PCr), 744
phospholipid metabolites, 46–47, 51
phosphoprotein phosphatases, 54–55, 57
classification of, 56
physical exercise, as coping mechanism, 1149–1150
PIB. See Pittsburgh Compound-B
Pick’s disease, 893
pimozide, 514
PIT. See Predatory Imminence Theory
Pitman, Roger, 561
Pittsburgh Compound-B (PIB), 208
pituitary adenylate cyclase-activating polypeptide (PACAP), 666
resilience and, 1146
PKU. See phenylketonuria
placebos, in AD treatment
in clinical trials, 859, 864–865
in disease modification, 857
plaques, in AD, 791
plasticity. See homeostatic plasticity, of brain; intrinsic plasticity, of brain; synaptic plasticity
pleiotropy, genetic mapping technologies and, 160
PLV. See phase locking value
PMDD. See premenstrual dysphoric disorder
PMS. See Phelan-McDermid syndrome
PNMT. See phenylethanolamine-N-methyltransferase
point resolved spectroscopy (PRESS), 204
Point Subtraction Aggression Paradigm (PSAP), 1107
Polycomb-Group (PcG) proteins, 92–93
polygenic diseases
GWAS for, 165
stem cell modeling for, 132
positive affect, addiction and, 710
positive behavioral support (PBS), 1029
positive cognitive reappraisal, 1148–1149
positron emission tomography (PET)
for addiction, 716, 720–721, 722
for ADHD, 1043
amyloid imaging with, 208, 827–828
costs of, 208
florbetapir, 208
PIB, 208
limitations of, 827
metabolism assessment with, 826
for psychiatric disorders, 258
purpose of, 1073
for tic disorders, 1054
for TS, 1054
postnatal brain development, 987–990
chromatins in, 987
critical periods of, 987
environmental influences on, 987–988
LRRTMs in, 989
multiprotein complexes in, 988
neural plasticity and, 988
stress and, 987
synaptogenic proteins and, 988–989
postpartum depression (PPD), 490–491
gonadal steroids and, 491
hormone studies for, 490
onset of, 383
prevalence rates for, 490
post-stroke dementia (PSD), 901–903
post-synaptic density, 312
post-traumatic stress disorder (PTSD), 530–531
animal models of, 562, 664–665
fear conditioning models, 664
repeated chronic stress models, 664–665
single prolonged stress models, 665
candidate gene studies in, 541
clinical indications for, 641, 662
diagnostic criteria for, 531
differential pathways to, 665–666
through developmental trauma, 665
genetic vulnerability, 665–666
epidemiology of, 662
morbidity of, 662
neurobiology of, 616–618, 666–669
amygdala activity, 616–618, 667–668
memory deficits and, 617
neuroepigenetics for, 176
overconsolidation theory of, 561
prevalence rates for, 641
resilience and, 1144
risk factors for, 538
translational studies of, 662–664
treatment therapies for, 641–642, 669–670
with benzodiazepines, 641
with CBT, 669
first-line approaches to, 641
neurobiological targets in, 670
pharmacological approaches, 670
psychotherapeutic approaches, 669
second-line approaches to, 641–642
potassium, in neurons, 27
PPA. See primary progressive aphasia
PPD. See postpartum depression
PPI. See pre-pulse inhibition
Prader-Willi syndrome (PWS), 99–101, 252
pravastatin, 850
precision medicine, RDoC criteria for, 1086
predatory aggression, 1103, 1104
Predatory Imminence Theory (PIT), 550
preferred activity pattern in, 550
predictive gene networks, 189–195
alternative omics data in, 192
Bayesian networks in, 191, 192, 193–194
genetic data integration in, 191–192
inflammatomes in, 195
MCMC, 191
small molecule-protein interactions in, 192
TFBS data in, 192
preferred activity pattern, 550
prefrontal cortex (PFC)
addiction and, 708
depression and, 428
CLPFC in, 457
conditioned, 595
mPFC, in reward, 735
in neurocircuitry of addiction, 684
in reward, 735
panic disorder and, 616
PTSD and, 617
reversal learning and, 583–584
schizophrenia and, 258
alterations as influence on, 263
EM and, 273
in proactive control mechanisms, 270
WM and, 272
pregnancy. See also postpartum depression
ADHD and, 1040
CFCS and, 1011
premenstrual dysphoric disorder (PMDD), 487–490
hormone studies for, 487
neurosteroids and, 487
serotonin and, 487
susceptibility to, 489
symptoms of, 487
treatment studies for, 489–490
triggers for, 489
prenatal brain development, 980–985
cellular migration in, 985
cortical migration and, 985–987
dysraphias and, 981
mechanistic models for, 985
neural tube regionalization in, 982–983
neuroepithelium support, 983–984
SHH and, 983
transcriptional support in, 984–985
pre-pulse inhibition (PPI), 959
PRESS. See point resolved spectroscopy
Price, Don, 813
primary progressive aphasia (PPA), 891–892
diagnostic criteria for, 889
logopenic variants for, 892
nfvPPA, 891
semantic variants for, 891–892
prion diseases. See also Creutzfeldt-Jakob disease
clinical features of, 918
detection of, 927
diagnostic testing for, 924
history of, 915
Kuru, neuropathology of, 927
modes of acquisition for, 916–917
neuropathology of, 925
protein-only hypothesis for, 915–916
replication in, 927
strains of, 928
transmission of, 927
treatment therapies for, 928
proactive control, in schizophrenia, 270
in PFC, 270
prodromal AD, 133
prodrome, of bipolar disorder, 356
progranulin (PGRN) gene, 894
progressive supranuclear palsy (PSP), 892
promoter elements, 80
calmodulin, 116
proteasomes, 57
proteins. See also neurotransmitters; neurotrophic factors; receptors; specific proteins
in synapses, 311
protein-only hypothesis, for prion diseases, 915–916
protein phosphorylation, in signal transduction pathways, 52–55, 55
protein types, 56
reversibility of, 61
protein tyrosine kinase receptors, 44
autophosphorylation of, 44
gene expression regulated by, 84
proteolysis, signal transduction pathways and, 55–57, 58
proteomes, in synapses, 311
Prusiner, Stanley, 915
PSAP. See Point Subtraction Aggression Paradigm
PSD. See post-stroke dementia;
post-synaptic density
PSP. See progressive supranuclear palsy
psychiatric disorders. See also specific disorders
endogenous neurogenesis as, 133–134
neural precursors and, 133
stem cells and, 133
with in vivo transplantation, 133
in DSM-V, 1068
Feigner Criteria for, 1074
genetic mapping technologies for, 168–169
neuroimaging of
for brain function, 258
development of, 256
function of, 256
of GABA receptors, 264
for genetic mechanisms, 266
in high-risk studies, 260
for illness effects, 259
Kraepelin’s influence on, 256
in longitudinal studies, 259–260
for neurochemical systems, 264–266
with PET, 258
of PFC, 258
ROIs and, 257
statistical considerations for, 260
themes in, 256
for treatment therapies, 259
VBMs and, 257
RDoC for, 1074
SUD comorbidities with, 779–782
synaptogenic proteins and, 988–989
targeted treatment therapies for, 1076
psychomimetics
5-HT receptors and, 36
ketamine, 36
mental illness and, 36
NMDA and, 36
PCP, 36
psychopathology, adolescence and, 598
psychopathy
ASPD compared to, 1094
cognitive function and, 1096
Hare Checklist, 1094
psychopharmacologic agents. See also antidepressants; antipsychotic drugs; anxiolytics; psychomimetics
signal transduction pathways and, 61
psychoses, diagnosis of. See also specific disorders
for dementia praecox, 223
dichotomous distinctions between, 223
in DSM-III, 1072
in DSM-IV, 226
bipolar disorder in, 229
schizoaffective disorder, 226–228
schizophrenia, 226
Feigner Criteria for, 224
for mania, 225
for schizophrenia, 225
in ICD-10
bipolar disorder, 227–228, 229
schizoaffective disorder, 227–229
nosology for, 224
primary compared to affective disorders, 224
rating scales for, 230
for bipolar disorder, 225
future applications for, 230–231
for schizoaffective disorder, 226, 225
for schizophrenia, 225, 225–227
universal language for, 224
psychosis. See also antipsychotic drugs; schizophrenia
amphetamines and, 349
animal models of, 349–350, 358–359
clinical manifestations of, 346
as clinical phenotype, 346–347
cognitive dysfunction in, 352–353
disorientation and, 346
dopamine hyperfunction hypothesis, 347
genetic association models, 349
glutamate transmission and, 348
learning and, 349
memory plasticity dysfunction in, 349
molecular mechanisms of, 347–350
models of, 348
PCP and, 349
serotonin and, 352
symptoms of, 346
treatment therapies for, 350–352
psychostimulants, 503
psychotic depression, 522
psychotic disorders. See also schizophrenia; specific disorders
antipsychotic drug development and, 256
dopamines and, discovery of, 256
neuroleptic drug development and, 256
psychotropic drugs. See also antidepressants; antipsychotic drugs; anxiolytics; psychomimetics; specific drugs
PTC. See Pavlovian threat conditioning
PTSD. See post-traumatic stress disorder
purines, 76
purpose in life, 1149
PV neurons. See parvalbumin neurons
PWS. See Prader-Willi syndrome
PYY. See peptide YY
q
15q11-13 duplication/deletion syndrome, 971
22q13 deletion syndrome, 1062
quantitative trait loci (QTL), 543–544
quetiapine, 351
r
race. See also African Americans
SUD and, 779, 781
radial arm water maze, 817–818
Raf proteins, 49
Ramon y Cajal, Santiago, 12, 64
randomized controlled trials (RCTs), 1061
rapid cycling, in bipolar disorder, 384
rapid-eye movement (REM) sleep, 1128
blood flow and, 1136
metabolism and, 1136
neurobiology of, 1136
phasic features of, 1128
sleep generator, 1131
stimuli responsiveness in, 1136–1137
tonic features of, 1128
rapid-eye movement sleep behavior disorder (RBD), 872, 878
Ras/MAP-kinase pathway, 49
Raf proteins, 49
rat models
for Huntington’s disease, 111
knockout, 112
olfactory bulbectomy in, 418
selective breeding
FSL, 421
transgenic, 111
for addictive behaviors, 111
ES cell modification in, 111
RBD. See rapid-eye movement sleep behavior disorder
RCTs. See randomized controlled trials
RDI. See Relationship Development Intervention
RDoC. See Research Diagnostic Criteria
reactive aggression, 1103, 1106–1108
amygdala activity and, 1109–1110
in BPD, 1104
components of, 1103
instrumental compared to, 1103–1104
neurobiology of, 1106, 1107–1108
reactive control, in schizophrenia, 270
reader proteins, 177
receptors. See also γ-aminobutyric acid; brain-derived neurotrophic factor; serotonin; specific receptors
in addiction, mediated signaling by, 685–688, 699
metabotropic receptors, 688
for regulated relapse, 686–688
AGTR genes, 477
extracellular signals and, 40–46
GDNF, 45
GR, 47
HTR2B, 703
ionotropic, 32
JAK-STAT, 46
metabotropic, 32
addiction and, 688
in neurons, 27
neurotransmitter-gated ion channels in, 40–41
NGF, 43
PACAP, 666
resilience and, 1146
at plasma membrane level, 40–45
protein tyrosine kinase, 44
ryanodine receptors, 47
in signal transduction pathways, 39, 40–46
for steroid hormones, 47
TGFβ, 45
Reeler gene, 112
refractory periods, for neurons, 30
region-of-interest (ROI), 257
reinforcement models, of SUD, 675–678
drug administration in, 675
learning requirements in, 676
relapse model
for addiction
receptor-mediated signaling in, 686–688
drug addiction and, 737
extinction training in, 679
susceptibility in, 679
Relationship Development Intervention (RDI), 1029
religion, resilience from, 1150
Remeron. See mirtazapine
REM sleep. See rapid-eye movement sleep
repeated social defeat stress, 420–421
reproductive endocrine-related mood disorders
perimenopausal depression, 491–492
onset triggers for, 492
risk predictors for, 491
hormone studies for, 487
neurosteroids and, 487
serotonin and, 487
susceptibility to, 489
symptoms of, 487
treatment studies for, 489–490
triggers for, 489
gonadal steroids and, 491
hormone studies for, 490
prevalence rates for, 490
repurposed compounds, for SUD, 761
Research Diagnostic Criteria (RDoC), 224–226
for anxiety disorders, 1082–1084
dysregulation types in, 1083–1084
fear circuit dimensions for, 1083
heterogeneity of expression
for, 1083
in twin studies, 1083
for bipolar disorder, 225
childhood nosology and, 1078
CNTRICS and, 1078
conceptual structure of, 1080–1082
in conceptual structure, 1080–1081
grain size for, 1081
status of, 1081
in diagnostic systems, 393–394
domains for, 1077
DSM-V and, 1068
environmental influences in, 1078
functional gene groups for, 1086
future applications for, 230–231
goals of, 1079
integrative features of, 1080
dysregulation types in, 1083–1084
fear circuit dimensions for, 1083
heterogeneity of expression for, 1083
in twin studies, 1083
origins of, 1077
for psychiatric disorders, 1074
psychopathological approach to, 1079
for psychotic spectrum disorders, 1084–1086
research variables for, 1079
for schizoaffective disorder, 226, 225
for schizophrenia, 1085–1086, 225, 225–227
symptoms in
clinical relevance of, 1082
in conceptual structure, 1081–1082
measurement criteria for, 1082
specificity of, 1081
translational perspective of, 1079
for treatment therapies, 1086
policy development for, 1086
with precision medicine, 1086
updates of, 1080
resilience
active coping styles, 1148, 1149–1150
acceptance, 1149
facing fears, 1149
humor as, 1149
physical exercise as, 1149–1150
social support and, 1150
animal models of, 1163
definition of, 1144
HPA axis and, 1146
stress and, 1146
epidemiology of, 1144
epigenetics of, 1147
stress reactivity and, 1147
extinction of memory, 1160–1162
fear conditioning, 1160
reconsolidation of memory, 1160–1162
CRF and, 1145
CRH and, 1145
GR and, 1145
HPA axis in, 1145
PACAP receptor, 1146
variations in, 1145
moral compass and, 1150
religion and spirituality as part of, 1150
neurobiology of, 1151–1158, 1159
BDNF, 1157
eCBs, 1158
galanin and, 1156
LC-NE system, 1155
serotonin, 1156
neurocircuitry for, 1162
prevalence of, 1144
LGMM for, 1144
prevention implications for, 1162–1163
psychobiological features of, 1147–1151
positive cognitive reappraisal, 1148–1149
purpose in life, 1149
PTSD and, 1144
research history on, 1144
reward pathways and, 1158–1160
stress and, 1152
development of, 1146
in epigenetics, 1147
treatment therapies for, 1162–1163
in animal models, 1163
response elements, in AP-1 proteins, 83
resting potential, in neurons, 27–28
Resveratrol, 848
Rett syndrome (RTT)
animal models of, 971
characterizations of, 129
clinical features of, 98
clinical trials for, 1062
gene expression conditional controls, 116
IGF-1 and, 1062
MeCP2 protein and, 98–99, 129, 971
22q13 deletion syndrome, 1062
stem cell modeling for, 129
treatment therapies for, 1031–1032
X chromosome in, 129
reversal learning, PFC and, 583–584
reverse engineering, for optogenetic technology, 145
reverse genetic strategy, 109
reversible MAOIs, 512
reward, addiction and, 735–736
dysregulation of, 738
compulsion phase, transitions to, 736
definition of, 732
individual differences in, 736
initiation phase, 736
amygdala, 734
lateral habenula, 735
mPFC, 735
OFC, 735
neurotransmitter systems in, 733–734
dopamine hypothesis of reward, 733–734
GABA, 734
glutamates, 734
incentive salience and, 733
reward prediction error and, 733
serotonin, 734
drug administration in, 675
learning requirements in, 676
survival component and, 683
reward prediction
errors, 733
reward sensitivity, 681
rhodopsins
ChRs, 138
opsin genes and, 138
optogenetic technology, 138
ribonucleic acid (RNA), 76–77. See also gene expression; transcription control, for genomes
base pairing in, 76
DNA transcription into, 77
information flow in, to proteins, 77–78
nucleosomes in, 79
transcription phases, 79
risperidone, 351, 641–642, 895, 1029–1030, 1031, 1058
The Rites of Zhou, 368
RNA. See ribonucleic acid
RNA interference (RNAi), 93–94
ROI. See region-of-interest
Roth, Martin, 791
RTT. See Rett syndrome
Rubinstein-Taybi syndrome (RSTS), 101
ryanodine receptors, 47
s
Sacks, Elyn, 346
SAD. See seasonal affective disorder
S-adenosylmethionine (SAM-e), 522
SADS. See Schedule for Affective Disorders and Schizophrenia
SAM-e. See S-adenosylmethionine
satellite DNA, 78
saving, 70
SBI. See silent brain ischemia
scanning. See interleaved scanning
Schedule for Affective Disorders and Schizophrenia (SADS), 230
schizoaffective disorder
schizophrenia
academic development of, as psychosis, 223
affect and, 223
affective deficits and, 280–281
ambivalence and, 223
antipsychotic drugs for, 329
associations and, 223
autism and, 223
Bleuler and, 223
cognitive deficits and, 280–281
context processing in, 269–270
exome sequencing for, 950
SNVs in, 950
cost-benefit analysis and, 275–276
neuronal pathways for, 334
Wnt pathways and, 332
DNA methylation and, 97
dopamine hypothesis, 347
in DSM-IV, 226
effort computations in, 278
cognitive deficits and, 274–275
cognitive neuroscience models, 273
hippocampal activity, 273, 274
PFC and, 273
environmental factors, 233–234
genetic overlap with bipolar disorder, 233
non-inherited factors, 233–234
epigenetics and, 97–98, 955–956
factor analysis of, 223
family studies for, 161
Feigner Criteria for, 225
four A’s of, 223
functional connectivity in, 1005
alterations specific to, 307–309
in alternate brain regions, 307
calretinin cells in, 307
CCK cell alterations, 306, 309
GAD1 genes, 308
network oscillations and, 309
neurotransmission of, 304
NMDA hypofunction in, 308
reduced excitation consequences in, 309
SST neurons and, 307
synthesis alterations, 304
TrkB genes, 308
uptake alterations, 304
in vivo measurements, 307
WM and, 309
gene expression in, 187
genetic mapping technologies for, 168
genetic study methods for, 234–235
with candidate genes, 235
future applications for, 245
genomic syndromes in
low-resolution approaches to, 247
mutation rates in, 253
selection coefficients in, 253, 254
VCFS, 247
goal-directed action and, 278–279
goal representations in, 275–280
effort computation and, 276
outcome achievements and, 276
groups, 223
as genetic study method, 234
linkage disequilibrium variances, 237–238
overlap with bipolar disorder, 242
risks in, 238
hedonics and liking and, 275, 276–277
hippocampal dysfunction, 263
histone protein modifications and, 97–98
iPSCs and, 132
Jackson and, 223
large-scale sequencing studies for, 242–245
family studies for, 399
microRNA and, 98
miRNA
expression and, 98
pathways, 335
motivational deficits in, 275–280
mouse models of
dysbindin genes, 290
etiologic models, 287
future developments for, 295–296
genetic, 288
through GWAS, 289
knockout, 292
with linkage study genes, 290–292
non-genetic, 288
pathogenic, 288
pathophysiological, 287
PCP-induced hyperactivity in, 288
pharmacological, 288
phenotypic, 287
risk allele, 292
symptom-oriented, 288
neural mechanisms for
cortical-subcortical network dysfunction, 263–264
in cortico-striatal models, 264
hippocampal dysfunction, 263
PFC alterations in, 263
neurobiology of
electrophysiology for, 343
neurobehavioral performance, 338–339
olfactory identification in, 339
prodromal concept, 338
social cognition in, 339
neurodevelopmental model of, 327–329
brain volume in, 328
channel pathways in, 335
environmental effects in, 327–328
immigrant status and, 327
minority status as influence in, 327
neonatal influences in, 327
neurotransmitters in, 329
stress factors in, 327
neuroimaging for, 258–259. See also neurobiology, of schizophrenia
with fMRI, 342
neuronal pathways for, 330–334
DISC1 genes, 334
early developmental, 330
neuropathology of, 328
onset of
during adolescence, 328
during childhood, 328
PFC and, 258
alterations as influence on, 263
EM and, 273
in proactive control mechanisms, 270
WM and, 272
polygenic sources of, 1074
proactive control in, 270
reactive control in, 270
recurrence risks for, 234
reward prediction/wanting and, 275, 277–280
risk factors, 132
stem cell modeling for, 132
SUD and, 780
symptoms
core, 269
FRS, 223
negative, 223
positive, 223
second rank, 223
synaptic disease and, 322
synaptic pathways, 334
synaptic transmission, 335
SZ, 132
altered default mode processing during, 272–273
behavioral findings on, 271
cognitive neuroscience models, 270–271
deficit expression, 271
encoding phases of, 271
maintenance phase of, 271
PFC recruitment in, 272
temporal aspects of, 271
DISC1 genes, 332
for neuronal development, 332
psychiatric disease genes, 332–333
worldwide incidence rates for, 327
schizotypal personality disorder (STPD), 1089, 1097–1099
cognitive impairments and deficits and, 1098
diagnostic criteria for, 1097
dopaminergic activity and, 1098
genetic vulnerability and, 1098–1099
information processing and, 1098
prevalence rates for, 1097
psychoticism dimension of, 1098
WM and, 1098
Schneider, Kurt, 223
SCID. See Structured Clinical Interview for DSM Disorders
sCJD. See sporadic Creutzfeldt-Jakob disease
molecular mechanisms of, 448
SDM methods. See signed differential mapping methods
seasonal affective disorder (SAD), 523
segregation analysis, 161
for Mendelian disease, 161
selective breeding, in animal models, 421–422
with depressed mice, 422
FSL rat model, 421
selective serotonin norepinephrine reuptake inhibitors (SNRIs), 515–516
for anxiety disorders, 636
remission rates for, 516
side effects of, 516
selective serotonin reuptake inhibitors (SSRIs), 36–37, 512–515. See also antidepressants; specific drugs
for anxiety disorders, 621–622
dosage regimen for, 512
drug interactions with, 512–514
half-lives of, 512
for medical illness, depression and, 502
augmentation strategies, 656–657
limitations of, 656
side effects of, 512
TCAs compared to, 509
selegiline, 511
self-cutting behaviors, 1093
self-medication models, of drug addiction, 737
semaphorins, 8
separation anxiety disorder, 531–532
in DSM-V, 1069
pediatric, 539
separation distress, 1123
serotonin
addiction and, 701
neuroimaging for, 727
aggression and, 1108–1109, 1110
anatomy of, 19
antidepressants and, 36–37, 61
BPD and, 1092
inactivation of, 19
OCD and, 647
PMDD and, 487
psychosis and, 352
resilience and, 1156
reward and, 734
sleep cycles and, 1130
synthesis of, 18
tryptophan and, 18
sex hormones, emotional regulation and, 589–590. See also androgens, mood regulation and; testosterone, mood disorders in males and
SFOs. See step-function opsins
SH2. See Src-homology domain 2
SH3. See Src-homology domain 3
Shaker gene, 70
SHH gene. See Sonic Hedgehog gene
short-term potentiation (STP), 65
SHRP. See stress hyporesponsive period
sickness syndrome, 501
signal transduction pathways
in addiction, 696
cellular physiology, 690
metabotropic receptors, 688
for regulated relapse, 686–688
amplification in, 39
in animal models, 39
through mutant analysis, 109
apoptosis and, 55
cAMP in, 50
cyclic nucleotides in, 46
diffusible molecules in, 49–52
eCBs and, 50
eicosanoids and, 50
elucidation of, 40
enzymes in, as receptors, 41–45
extracellular signals and, 40–46
Fos protein activation by, 84
in functional connectivity, 996
GDNF, 45
G proteins in, 41, 43, 46, 59–61
JAK-STAT receptors, 46
multiple signal integration in, 39–40
networks of, 40
neurotransmitter-gated ion channels in, 40–41, 42
NGF in, 43
parameters of, 39
phospholipid metabolites in, 46–47, 51
phosphoprotein phosphatases in, 54–55, 56, 57
at plasma membrane level, 40–45
pleiotropy of, 39
proteasomes in, 57
protein phosphorylation in, 52–55, 61, 55, 56
protein types in, 41
psychopharmacologic agents and, 61
Ras/MAP-kinase, 49
reversible reactions in, 59
specificity in, 39
TGFβ in, 45
ubiquitin in, 57
signed differential mapping (SDM) methods, 257–258
sildenafil, 514
silent brain ischemia (SBI), 903
WMH and, 903
simple phobia. See specific phobia
simvastatin, 850
single nucleotide polymorphisms (SNPs), 183
during childhood psychiatric disorders, 945
single number variants (SNVs)
in childhood psychiatric disorders, 944–945
in COS, 950
single photon emission computed tomography (SPECT)
for addiction, 716, 720–721, 722
for ADHD, 1043
site-specific recombination systems, 115–116
NMDA, 116
sleep
clinical research on, 1127
consciousness during, 1137
in NREM sleep, 1137
ACh and, 1130
circadian clock and, 1131
GABA and, 1131
histamines in, 1130
humoral factors for, 1131–1132
hypocretin and, 1131
hypothalamic influences on, 1131
lengths of, 1129
NE and, 1130
regulation of, 1129
serotonin and, 1130
definition of, 1127
effects of, 1133
of REM sleep, 1133
disorders, with LBD, 878
for brain development, 1139–1140
brain restitution and, 1139
synaptic homeostasis, 1139
during life span, 1128
melatonin and, 1132
for blood flow, 1136
for metabolism, 1136
REM sleep, 1136
spontaneous activity, 1134
stimuli response, 1136
for wakefulness, 1134
awakenings during, 1137
blood flow and, 1136
metabolism and, 1136
microsleep episodes, 1127
stimuli responsiveness in, 1136
SWS, 1128
onset of, 1137
wakefulness and, 1129
REM, 1128
blood flow and, 1136
deprivation of, 1133
metabolism and, 1136
neurobiology of, 1136
phasic features of, 1128
sleep generator, 1131
stimuli responsiveness in, 1136–1137
tonic features of, 1128
discovery of, 1127
EEG for, 1127
EMG for, 1127
EOG for, 1127
wakefulness and, 1127
GLMT system and, 1130
histamines and, 1130
maintenance of, 1129
neurobiology of, 1134
regulation of, 1129
Slit proteins, 8
SLOS. See Smith-Lemli-Opitz-syndrome
slow wave sleep (SWS), 1128
Smith-Lemli-Opitz-syndrome (SLOS), 1016–1017
clinical indications for, 1016
comorbidities with, 1016
diagnosis of, 1016
prevalence rates for, 1016
treatment therapies for, 1016–1017
smoking. See tobacco use
SNARE complexes. See soluble N-ethylmaleimide-sensitive factor attachment receptor complexes
SNPs. See single nucleotide polymorphisms
SNRIs. See selective serotonin norepinephrine reuptake inhibitors
SNVs. See single number variants
SOC. See social phobia
social anxiety disorder, 533
insula dysfunction, 612
social phobia and, 533
social attachment. See also adult bonding
adult bonding and, neurobiology of, 1124
animal models of
neurobiology in, 1112
behavioral components of, 1112
definition of, 1112
father-infant attachment, 1118–1119
chemical substrates in, 1119
display behaviors in, 1118–1119
neuroanatomy of, 1119
infant-parental attachment, 1113–1116
development of, 1113
motivation circuits in, 1115
neurobiology of, 1115
social approaches to, 1115
mother-infant attachment, 1116–1118
chemical substrates of, 1116–1118
development of, 1116
maternal neglect and, 1118
for adult bonding, 1124
in animal models, 1112
future brain applications in, 1124–1125
for infant-parental attachment, 1115, 1113–1116
for mother-infant attachment, 1116–1118
parent-offspring bonding, 1113–1119, 1124
social brain hypothesis for, 1112
social brain and
evolution of, 1113
social systems as influence on, 1112
social avoidance behaviors, 416–417
social brain
evolution of, 1113
clinical indications for, 643
pediatric, 539
treatment therapies for, 643–644
with benzodiazepines, 644
first-line approaches, 643–644
second-line approaches, 644
social systems, social attachment influenced by, 1112
soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) complexes, 439
somatic antidepressants, 466
somatic treatment therapies, for MDD, 519–520, 519
DBS, 520
MST, 520
TMS, 520
LFMS, 520
VNS, 520
Sonic Hedgehog (SHH) gene, 983
Sotos syndrome (SoS), 1013–1014
causes of, 1014
clinical indications for, 1013–1014
NSD1 gene and, 1014
Souvenaid, 849
specific phobia (SP), 532–533, 538
SPECT. See single photon emission computed tomography
spirituality, resilience from, 1150
spontaneous craving, 728
sporadic Creutzfeldt-Jakob disease (sCJD), 918–921
diagnostic criteria for, 918
EEG for, 919
neuropsychiatric features of, 919
prevalence rates for, 920
sporadic schizophrenia (SZ), 132
Src-homology domain 2 (SH2), 45
Src-homology domain 3 (SH3), 45
SSFOs. See stabilized step-function opsins
SS MRI. See steady-state contrast MRI
SSRIs. See selective serotonin reuptake inhibitors
SST neurons, 307
St. George-Hyslop, Peter, 805
stabilized step-function opsins (SSFOs), 139–140
starvation, psychopathology of, 1182
steady-state contrast MRI (SS MRI), 199
STEAM. See stimulated echo acquisition mode
stem cells
in animal models, for psychiatric disorders, 133
cellular reprogramming with, 123–124
differentiation of, 123
direct programming of, 124–128
fibroblasts and, 124
endogenous, 128
brain development and, 128
ES, 124
hESCs, 124
modification of, in knockout mouse models, 111
karyotyping of, 124
markers, 124
in patient-specific studies, 125–126
properties of, 124
schizophrenia and, 132
stability of, 124
teratoma assays, 124
neurological disorder modeling with, 128–133
for FD, 130
for FXS, 130
for monogenic diseases, 128
for polygenic diseases, 132
for RTT, 129
for schizophrenia, 132
properties of, 123
self-renewal of, 123
step-function opsins (SFOs), 139–140
steroid hormones, 47. See also gonadal steroids
GR protein, 47
nucleus translocation for, 86
transcription control by, 85–86
stimulant medication, addiction and, 711
stimulated echo acquisition mode (STEAM), 204
stimulus-reinforcement learning, 1104–1105
STP. See short-term potentiation
STPD. See schizotypal personality disorder
stress
adrenal glucocorticoids and, 430–431
in animal models
CMS, 418
developmental stressors, 419–420
repeated social defeat stress, 420–421
anxiety and, 552
in bipolar disorder, 358
childhood psychiatric disorders and, 958–959
CMS, 411
in animal models, 418
epigenetic response to, 96
MDD and, 96
emotional regulation and, 589
epigenetic response to, 96
fear and, 552
postnatal brain development and, 987
resilience from, 1146, 1147, 1152
stress-enhanced fear learning, 561
stress hyporesponsive period (SHRP), 596–597
Stroop test, 799
structural connectivity, in neurodevelopmental disorders, 996–999
DW-MRI, 996
fMRI-based, 999
tract-based, 996
voxel-based, 998
Structured Clinical Interview for DSM Disorders (SCID), 230
subcortical ischemic disease, 475–476
late life depression and, 476
subcortical vascular dementia (SVD), 903–904
substance-induced mood disorders
diagnostic systems for, 380–381
epidemiology of
development of, 772
with NCSs, 774
general symptoms of, 381
withdrawal model for
affective states, 679
for cocaine, 679
substance use disorder (SUD). See also alcohol use disorders
ADHD and, 680
animal models of, 763–764. See also susceptibility, in addiction; withdrawal model
alcohol use in, 677
conditioned place preference paradigms in, 677–678
CPP models, 763
for drug addiction, 679
epidemiology of, 784
ICSS in, 678
incubation of craving models, 764
maladaptive patterns in, 675
operant paradigms in, 677
schedule requirements in, 677
self-administration methods, 677
structural plasticity in, 675
for psychiatric disorders, 779–782
definition of, 675
epidemiology of
abuse classifications in, 772–774
among adolescents, 777, 784–785, 781
among adults, 776–777, 778–781
as chronic disorder, 777
comorbidities in, across substances, 777
craving and, 774
in DSM-IV, 772, 773–775, 775–778
by ethnicity, 779, 781
measurement criteria for, 772–776
NAc and, 783
by race, 779, 781
VTA and, 783
withdrawal symptoms, 772
etiology of, 763
health care costs for, 732
individual traits for, 709–711
low self-control, 709
positive affect and, 710
prenatal exposure and, 710–711
stimulant medication and, 711
intrinsic plasticity of brain and, 675
MRS studies for
function of, 742
future applications for, 756–758
summary of findings for, 756
neurobiology of, 732
pharmacotherapy for
abstinence as influence on, 763
biological approaches to, 767–768
clinical trials for, 761–762, 768
development of, 761
economic considerations of, 761
with engineered enzymes, 768
with monoclonal antibodies, 768
with MPEP/MTEP compounds, 765–766
regulatory hurdles for, 762–763
with repurposed compounds, 761
prevalence rates for, 732
psychiatric disorders and, 779–782
schizophrenia and, 780
craving in, 679
phenotypes, 678
subunits, in proteins, 78
SUD. See substance use disorder
surgical treatments, for OCD, 659
susceptibility, in addiction
behavioral phenotypes in, 680
impulsivity and, 681
novelty-seeking traits in, 680–681
reward sensitivity in, 681
sex factors in, 680
social factors in, 680
relapse model for, 679
SVD. See subcortical vascular dementia
Swan Rating Scale, 937
SWS. See slow wave sleep
sympathoadrenal hyperactivity, 498
synapses. See also synaptic disease; synaptic plasticity
in brain development, 8
functions of, 311
homeostatic plasticity and, 73–74
neurotransmitters and, 13
NGF and, 8
prenatal brain development and, 985–987
proteins in, 311
proteomes in, 311
PSD, 312
sleep functions and, 1139
specialization of, 13
synapse-specific homeostatic
plasticity, 73–74
synaptic disease
ASD and, 322
epistasis and, 322
historical perspective on, 311
pharmacological studies, 311
technological advances, 311
ion channels in, 313
proteins in, 314
neurotransmitters in, 313, 321
proteins and, 321
in MASC, 314
synaptic complexes, 322
schizophrenia and, 322
synaptic plasticity, 64–67. See also
long-term potentiation
AD and, 67
addiction and, cellular physiology of, 689
cellular mechanisms for, 65–67
as concept, development history of, 64–65
experience-dependent, 67
α-GABA receptors, 573
in NAc, 67
in neurological disorders, 67
PTC, 556
STP, 65
in VTA, 67
synaptogenic proteins, 988–989
SZ. See sporadic schizophrenia
t
TAP. See Taylor Aggression Paradigm
targeted treatment therapies, 1076
within brain, 1076
for cancers, 1076
diagnostic tests in, 1076
for psychiatric disorders, 1076
TATA box, 80
Tau depositing mouse models, 818
Tau proteins, 835
in disease modification, for AD, 868–869
in MAPT, 894
Taylor Aggression Paradigm (TAP), 1107
TBI. See traumatic brain injury
TCAs. See tricyclic antidepressants
tDCS. See transcranial direct current stimulation
teratoma assays, 124
testosterone, mood disorders in males and, 493
tetracycline transactivator (tTA), 114–115
TFBS. See transcription factor binding site
TGFβ. See transforming growth factor beta
TH. See tyrosine hydroxylase
Thase Rush Staging Model (TRSM), 390
theelin, 483
3D light delivery, in optogenetic technology, 144–145
thymine, 76
in TATA box, 80
thyrotropin-releasing hormone (TRH), 1178
tic disorders, 933. See also Tourette’s syndrome
animal models of, 1056
gene expression in, 1050
characteristics of, 1048
classification of, 1048
clinical indications of, 1048
coprolalia, 1048
through animal models, 1050
through basal ganglia connections, 1051–1053
through candidate gene studies, 1050
cytogenetic findings, 1050
through family studies, 1049
through GWAS, 1050
neurotransmitters in, 1053
immune dysfunction in, 1056–1057
integrative models of, 1057
action selection in, 1057
neuroimaging for, 1054
with fMRI, 1054
with PET, 1054
onset of, 1049
phenomenology of, 1048
treatment therapies for, 1058
with antipsychotics, 1058
with DBS, 1058
Timothy syndrome
calcium channels in, 130
CREB pathways in, 129
stem cell modeling for, 129–130
TMS. See transcranial magnetic stimulation
tobacco use. See also nicotine
ADHD and, 1040
AUDs and, 753
negative reinforcement and, 737
neuroimaging for addiction, 722
Tomlinson, Bernard, 791
topiramate, 657
Tourette, Georges Gilles de la, 934
Tourette’s syndrome (TS), 322, 950–951
animal models of, 976–977, 1056
autoimmune models, 977
dopamine transporter genes in, 977
gene expression in, 1050
monkey focal striatal disinhibition in, 977
psychostimulant model, 977
clinical indications of, 934, 1048
definition of, 934
functional connectivity in, 1007
through animal models, 1050
through basal ganglia connections, 1051–1053
through candidate gene studies, 1050
cytogenetic findings, 1050
through family studies, 1049
through GWAS, 1050
neurotransmitters in, 1053
heritability for, 936
immune dysfunction in, 1056–1057
integrative models of, 1057
action selection in, 1057
natural history for, 1048–1049
neuroimaging for, 1054
with fMRI, 1054
with PET, 1054
onset of, 1049
phenomenology of, 1048
prevalence rates for, 936
research on, 1048
trajectory into adulthood, 935
treatment therapies for, 1058
with antipsychotics, 1058
with DBS, 1058
Trail Making test, 799
transcranial direct current stimulation (tDCS), 213
computer models for, 215
effect imaging, 215
interleaved scanning, 215
placement targeting, 215
transcranial magnetic stimulation (TMS), 215–216, 520
computer models, 215
effect imaging, 216
interleaved scanning, 216
LFMS, 520
for OCD, 659
transcriptional mechanisms, of addiction, 690–692
chromatin, 691
HDACs, 691
histone methyltransferase, 691
transcriptional transactivator systems, 114–115
inducible transgenics, 114–115
transcription control, for genomes, 79–86
animal models
conditional knockout mice, 116
through mutant analysis, 109
cis-regulatory elements in, 80
dimers in, 80
enhancer elements in, 80
ΔFosB factor, 115
genomic strategies, 119
NF-κB in, 81
in optogenetic technology, 145–146
in prenatal brain development, 984–985
promoter elements in, 80
regulatory sequences in, 80
TATA box in, 80
TH in, 80
transcription factor binding site (TFBS), 192
transforming growth factor beta (TGFβ), 45
transgene tagging, 119
with GFP, 119
transgenic mouse models, 109–111
BRI fusion proteins, 814
development of, 813
features of, 813
gene targeting in, 815
introduction of, 812
mutations in, 814
overexpression in, 814
APP
BACE1 genes, 815
behavioral changes in, 815–818
BRI fusion proteins, 814
crossing with alternative lines, 815
gene targeting in, 815
Morris water maze for, 815–816
mutations in, 814
object recognition in, 816
ownership of, 815
pathology sequencing in, 818
physiological changes in, 818
radial arm water maze for, 817–818
Tau depositing mice, 818
disease models, 110
family lines, 110
of FXS, 974
gene expression, 110
knockout models compared to, 111
large-clone
for disease states, 110
Down Syndrome, 110
GFP, 110
YACs, 110
transgenic rat models, 111
for addictive behaviors, 111
ES cell modification in, 111
transporter genes, anxiety disorders and, 541
tranylcypromine, 511
trauma, BPD and, 1091
traumatic brain injury (TBI), 71
TRD. See treatment-resistant depression
treatment refractory depression, 466
treatment-resistant depression (TRD), 516–518
atypical antipsychotics for, 517
augmentation therapy for, 517–518
combination therapy for, 517
hormonal strategies for, 517–518
lithium for, 517
treatment therapies. See also antidepressants
for AD. See also disease modification, for AD
ADAPT, 846
administration modes for, 865–866
with anti-hypertensive drugs, 850
with anti-inflammatory drugs, 846
biomarkers for, 840
biomarkers in, 840
B vitamins in, 847
cardiovascular risk factors and, 849–851
with cholesterol lowering agents, 850
with COX enzymes, 846
with curcumin, 848
with diabetes medications, 850–851
FDA approvals for, 844
future research on, 851
with gingko, 848
with gonadal hormones, 849
homocysteine levels and, 847
with memantine, 845
with NSAIDs, 846
with omega-3 fatty acids, 847–848
pathophysiology and, 792
placebos in, 857, 859, 864–865
with Resveratrol, 848
for addiction, neuroimaging for, 738–740
animal models and, 810
for resilience, 1163
for anxiety disorders. See also cognitive bias modification therapy; D-cycloserine therapy
access to, 622
with benzodiazepines, 622, 636–637
CBT, 621
cognitive approaches to, 626–630, 636–638
cost effectiveness of, 631–632
exposure therapies, 622
with glucocorticoids, 623, 633–634
with MAOIs, 636
RCTs for, 621
with SNRIs, 636
with TCAs, 636
with yohimbine hydrochloride, 623–624, 633–634
for aggressive behaviors, 1029–1030
for anxiety behaviors, 1031
for attention deficit, 1030–1031
behavioral interventions, 1028–1029
future applications of, 1031
with PBS, 1029
with pharmacotherapy, 1029–1031
with RDI, 1029
for repetitive behaviors, 1031
for BBS, 1015
neuromodulatory, 503
neurotrophic factors and, 432–433
with psychostimulants, 503
with SSRIs, 502
in disease modification, for AD, 865–869
administration modes for, 865–866
antibody development in, 867–868
BBB involvement in, 868
cellular targets in, 866
development of, 855
neuroprotection in, 869
with NSAIDs, 869
research applications for, 869
in vaccination studies, 867
first-line approaches, 642
second-line approaches, 642–643
with ACh, 882
for autonomic dysfunction, 883
for behavioral symptoms, 882–883
for cognitive symptoms, 882
with memantine, 882
for motor symptoms, 882
neuroimaging methodologies for, 259
for OCD
with CT, 658
with DBS, 659
with ECT, 659
novel medications in, 657
pharmacological approaches, 653–657
psychotherapeutical approaches, 657–658
with surgery, 659
with TMS, 659
for panic disorder
with DCS, 625
first-line approaches to, 637–640
second-line approaches to, 640–641
for perimenopausal depression, 492
for prion diseases, 928
CBT, 521
IPT, 521
with benzodiazepines, 641
with CBT, 669
first-line approaches to, 641
neurobiological targets in, 670
pharmacological approaches, 670
second-line approaches to, 641–642
RDoC for, 1086
policy development for, 1086
with precision medicine, 1086
in animal models, 1163
with benzodiazepines, 644
first-line approaches, 643–644
second-line approaches, 644
DBS, 520
MST, 520
TMS, 520
VNS, 520
for SUD
abstinence as influence on, 763
biological approaches to, 767–768
clinical trials for, 761–762, 768
development of, 761
economic considerations of, 761
with engineered enzymes, 768
with monoclonal antibodies, 768
with MPEP/MTEP compounds, 765–766
regulatory hurdles for, 762–763
with repurposed compounds, 761
targeted, 1076
within brain, 1076
for cancers, 1076
diagnostic tests in, 1076
for psychiatric disorders, 1076
for tic disorders, 1058
with antipsychotics, 1058
with DBS, 1058
for TS, 1058
with antipsychotics, 1058
with DBS, 1058
prevention trials in, 911
TRH. See thyrotropin-releasing hormone
tricyclic antidepressants (TCAs), 502–503, 509–511. See also specific drugs
for anxiety disorders, 636
dosages, 509
SSRIs compared to, 509
toxicity of, 511
Trier Social Stress Test, 1093
triple pathway model, 1041
trithorax-Group (trx-G) proteins, 92–93
TrkB genes, 308
TRSM. See Thase Rush Staging Model
trx-G proteins. See trithorax-Group proteins
Trypan Blue, 151
tryptophan
forms, 18
5-HTP, 18
serotonin and, 18
TS. See Tourette’s syndrome
TSC. See tuberous sclerosis; Tuberous Sclerosis Complex
tTA. See tetracycline transactivator
tuberous sclerosis complex (TSC), 940, 1024
treatment therapies for, 1031–1032
twin studies
for AD, 805
for anxiety disorders, 537–539
pediatric, 539
RDoC for, 1083
for ASD, in childhood, 936
diagnosis through, 1022
for bipolar disorder, 233
for childhood psychiatric disorders, 937, 938
for depression, in late life, 472–473
for GAD, 538
for MDD, 398
for mood disorders, 1083
for OCD, 538
for panic disorder, 537
phobias, 538
RDoC and, 1083
RDoC for, 1083
VATSPSUD, 537
VET Registry, 537
in signal transduction pathways, 52, 55
tyrosine hydroxylase (TH), 14
in genome transcription control, 80
knockout mouse models, 113
mRNAs, 14
u
ubiquitin, 57
Uniform Data Set (UDS), 794–795
Urbach-Weithe disease, 552
v
vaccines
in disease modification, for AD, 867
vagus nerve stimulation (VNS), 520
valproic acid (VPA), 972
varenicline, 450
variant Creutzfeldt-Jakob disease (vCJD), 924–925
vascular brain injury (VBI), 900, 905–906
cognitive impact of, 907
vascular cognitive impairment (VCI), 900
AD and, 900
diagnostic criteria for, 904–905
infarction patterns and, 901
treatment therapies for, 910–911
neuropathological evaluation of, 905
prevalent types for, 900
SBI and, 903
WMH and, 903
treatment therapy for, 907–913
prevention trials in, 911
vascular depression, in late life, 476–477
vascular endothelial growth factor (VEGF), 433
VATSPSUD. See Virginia Adult Twin Study of Psychiatric and Substance Abuse Disorders
VBI. See vascular brain injury
VBM. See voxel-based morphometry
VCFS. See Velo-Cardio-Facial syndrome
VCI. See vascular cognitive impairment
vCJD. See variant Creutzfeldt-Jakob disease
VEGF. See vascular endothelial growth factor
Velo-Cardio-Facial syndrome (VCFS), 247
vemurafenib, 1076
venlafaxine, 515–516, 641, 642, 1031
ventral tegmental area (VTA), 67, 685–686
SUD and, 783
ventromedial PFC (vmPFC), 585–587
vesicular glutamate transporters (VGLuTs), 20, 439
vesicular monoamine transporter (VMAT) protein, 15
DAs, 112
VET Registry. See Vietnam Era Twin Registry
VGLuTs. See vesicular glutamate transporters
Vietnam Era Twin (VET) Registry, 537
vilazodone, 512
VILIP-1. See visinin-like protein 1
viral-mediated gene transfer, 117–120
AAV, 117
for addictive behaviors, 118
future, 120
for Parkinson’s disease, 117–118
by vector type, 117
CAV, 117
expression duration in, 119
gene activation/deactivation in, 120
HSV-1, 117
limitations of, 120
neuronal specificity with, 119
transgene tagging in, 119
with GFP, 119
vector types, 117
amplicon, 117
application functions, 117
genomic, 117
Virginia Adult Twin Study of Psychiatric and Substance Abuse Disorders (VATSPSUD), 537
visinin-like protein 1 (VILIP-1), 836–837
visual cortex, 9
visual system
CNS wiring for, 9
LGN in, 9
ocular dominance columns, 9
visual cortex, 9
visuospatial deficits, with LBD, 875
VMAT protein. See vesicular monoamine transporter protein
vmPFC. See ventromedial PFC
VNS. See vagus nerve stimulation
voltage-gated ion channels
dendrites and, 68
intrinsic plasticity and, 67–68
voxel-based morphometry (VBM), 207–208
for psychiatric disorders, 257
VPA. See valproic acid
VTA. See ventral tegmental area
w
Waardenburg syndrome, 982
Waddington, Conrad, 88
Wadsworth, Sam, 813
Wagner, Steve, 806
wakefulness, 1127
GLMT system and, 1130
histamines and, 1130
maintenance of, 1129
neurobiology of, 1134
regulation of, 1129
Watkins, Paul, 805
WBS. See Williams-Beuren
syndrome
Wellbutrin. See bupropion
white matter hyperintensities (WMH), 903
WHO. See World Health
Organization
whole-cell patch recording, 33
whole-exome sequencing, 169. See also exome sequencing
Williams-Beuren syndrome (WBS), 252
wingless (Wnt) proteins, 85
pathways, in schizophrenia development, 330–334
DISC1 genes, 332
for neuronal development, 332
psychiatric disease genes, 332–333
wiring extraction patterns, 145
Wistar-Kyto (WKY) rat model, 421–422
withdrawal model, for SUD, 678–679
affective states, 679
for cocaine, 679
craving, 679
phenotypes, 678
WKY rat model. See Wistar-Kyto rat model
WM. See working memory
WMH. See white matter hyperintensities
Wnt proteins. See wingless proteins
women. See also reproductive
endocrine-related mood
disorders
androgens and, mood regulation and, 493–494
ASD in, 936
BPD in, 1091
eating disorders among, 1182
FTD and, 888
perimenopausal depression in, 491–492
onset triggers for, 492
risk predictors for, 491
hormone studies for, 487
neurosteroids and, 487
serotonin and, 487
susceptibility to, 489
symptoms of, 487
treatment studies for, 489–490
triggers for, 489
gonadal steroids and, 491
hormone studies for, 490
onset of, 383
prevalence rates for, 490
Wordsworth, William, 931
working memory (WM)
cholinergic system and, 449
altered default mode processing during, 272–273
behavioral findings on, 271
cognitive neuroscience models, 270–271
deficit expression, 271
encoding phases of, 271
GABA and, 309
maintenance phase of, 271
PFC recruitment in, 272
temporal aspects of, 271
STPD and, 1098
World Health Organization (WHO), 370, 1067
writer proteins, 177
x
X chromosome, in Rett syndrome, 129
X linked lissencephaly, 975
y
yeast artificial chromosomes (YACs), 110
yohimbine hydrochloride, 623–624
mechanism of action for, 633
z
zaleplon, 514
Zelboraf. See vemurafenib
zinc-finger-nuclease (ZFN), 131
zinc levels, ADHD and, 1040
ziprasidone, 351
zolpidem, 514