“The problem with the gene pool is there aren't any lifeguards.”
—Anonymous
We already know that genes have dramatic effects on virtually every aspect of the human body—height, weight, skin color, and even the ability to process oxygen. But sometimes we forget how important genes are in shaping personality. As behavioral geneticist Robert Plomin has pointed out, the answer to the question “how much does heredity affect behavior” is “a lot.”1 Indeed, as Plomin notes, genetic influence is so ubiquitous that we should not be asking what is heritable with regard to behavior. Instead, we should be asking what is not heritable. “So far,” he notes, “the only domain that shows little or no genetic influence involves beliefs such as religiosity and political values; another possibility is creativity independent of IQ.”a.2
Recent research has even undermined the long-held belief that troubled, argumentative marriages cause problematic behavior in the children brought up in those households. A recent study of adult twins and their offspring revealed that it is not the family discord that causes problematic behavior but rather the genes that troubled parents pass along. In fact, the parents’ own genes apparently determine how often they argue with each other.3
Ultimately, then, since genes are so crucially important to understanding personality—including its Machiavellian manifestations—it's a good idea to take a quick review of some fundamentals. A human body is composed of about a trillion tiny, membrane-enclosed cells—bone cells, nerve cells, white blood cells, and so on. Each cell is alive and carries out its own suite of “life functions” by following the instructions encoded in its genes. The genes are portions of chromosomes, sequestered in the cell's spherical nucleus. Most human cells (there are a few exceptions) contain forty-six chromosomes—twenty-three inherited from the mother, and another twenty-three from the father. Each chromosome is a long, slender DNA molecule. If all the DNA in one cell's chromosomes were stretched out, they would total about six feet in length. That means that the average chromosome is a couple of inches long—which makes a DNA strand a giant, as molecules go. But because DNA is extraordinarily slender—thousands of times thinner than a hair—all forty-six human chromosomes are easily wadded up like a molecular-sized ball of string inside the cell's nucleus.
Fig. 3.1. The 46 human chromosomes
DNA molecules are not only long and skinny but also very simple in structure. The famous DNA “double helix” consists of two parallel (but twisted) chains of molecular building blocks called nucleotides. There are only four kinds of nucleotides, and what makes the four different from one another are parts of the nucleotides called bases—adenine, guanine, thymine, and cytosine. The four DNA bases are almost always abbreviated A, G, T, and C. The DNA “code” consists of sequences of nucleotides with various bases. ATTCGACCTCC tells a cell to do one thing, TGACCTGCAG says something else. You can think of a cell's chromosomes as a set of cookbooks, with each chromosome being a volume, and each gene a recipe. There are hundreds of gene “recipes” strung along each chromosome, and roughly 70 percent of all those genes participate in the development and operation of our brain.
Fig. 3.2.
Along the chromosome, each gene—each recipe, if you will—is a sequence of DNA letters that tells a cell how to make a particular protein. The proteins, in turn, make up much of the structure of a cell and, hence, the body, and carry out cellular functions. Thus, the genome consists of genes—sequences of DNA bases along the chromosomes—each of which codes for the assembly of a particular protein. Depending on the information in the genes, the proteins build an ant, a pine tree, or a human—with brown eyes or blue.
We humans are estimated to have about twenty-two thousand genes sprinkled among our chromosomes—that's only about 5 percent of the total DNA.4 The other 95 percent, sometimes called “junk DNA,” has long been thought of as sitting around twiddling its molecular thumbs doing nothing in particular. However, researchers are discovering that some junk DNA is intricately involved in the regulation of which genes are turned on or off in which tissues. This in turn ultimately determines an organism's phenotype—how an organism appears. Thus, although genes are still of paramount importance, there is a whole additional layer of complexity involving control of those genes—a sort of “index”—that we are just barely beginning to understand. What makes us special among primates may not so much be the genetic recipes themselves but when and where the regulatory sequences turn the genes on and off.
Even more interesting are recent findings based on how often genes repeat themselves—“copy number variants.”5 Perhaps 10 percent of genes, it seems, are in regions that can easily find themselves doubled, tripled, quadrupled, deleted, or scrambled. These different numbers and types of genetic copies can make dramatic differences in the genetic makeup between different population groups, as well as between more closely related individuals—perhaps even between siblings. The number of copies of different genes has already been linked with a variety of medical conditions, including Alzheimer's, kidney disease, and HIV. The expectation is that these copy number variants may become very significant in personality disorder research as well.
Differing versions of a gene that can fill a slot on a chromosome are called alleles. Alleles are simply variants of genes—kind of like a recipe variant where egg whites are substituted for egg yolks when baking a cake. But alleles can also be thought of as competitive versions of a gene. A different, “new and improved” version of an allele, for example, might help build a better molecule for ferrying oxygen around or might help grow sturdier bones.
But how do different alleles for a gene arise? Primarily through mutation. One of the bases—A, C, T, or G—might be miscopied when reproduction is taking place. Alternatively, sometimes genes stutter when they are copied, repeating certain parts of themselves, or, like dropping a stitch, losing a section. Either way, a slightly different allele is created that is passed down to future generations. Incidentally, about 25 percent of all human genes have alternate versions available. The lowest average number of alternate versions is found in the populations of New Guinea and Australia, while the dazzlingly highest number of alternate versions is found in the Middle East, western Asia, and southern, central, and eastern Europe.6
Yet even one simple change of a nucleotide at a single location can lead to problems—as if a cook used a teaspoon of salt instead of yeast in a recipe for bread. Such a change in a gene (making a new allele, or “flavor” of that gene) causes a change in the protein it builds. This often means that the protein doesn't function normally. Just such single mutations are responsible, not only for cystic fibrosis but for dozens of other devastating conditions such as hemophilia and sickle-cell anemia. Diseases such as Alzheimer's or schizophrenia, on the other hand, often involve more complicated confluences of unlucky alleles. The illustration below shows a few of the common and unusual illnesses that have so far been found to be associated with genes just on chromosome 17.
Our genotype is the actual information contained on the long strands of DNA molecules in the nucleus of our cells—we can determine our genotype only by using molecular methods. Our phenotype, on the other hand, relates to our appearance, which is determined by the output of the genotype and sometimes by environment as well.
Now we're ready to return to the subject of evolution. As we have seen, traits are controlled by a mix of genes—various alleles that affect characteristics such as skin color, disease resistance, memory, and even novelty seeking. If an allele helps produce a trait that confers an advantage, individuals who bear that allele will leave more offspring. That trait and that allele will occur in a greater proportion of individuals in the next generation, and the next generation as a whole will be better adapted to the environment. Sometimes, especially in small populations, chance events can also alter the mix of alleles in the next generation, a phenomenon called genetic drift. These incremental shifts in the frequency of alleles in the population—changes in the population's “gene pool”—constitute evolution. Specifically, they constitute a small-scale process termed microevolution. Larger-scale evolutionary change, such as the origin of new species or the founding of orders and classes, is called macroevolution.
Fig. 3.3.
MACHIAVELLIAN GENES
A complex array of varying genes underlies the many different outward manifestations—phenotypes—of many different personality disorders. A person with an unlucky shake of the genetic dice can actually end up with full-blown versions of those disorders right out of the chute—these unfortunates often show their dysfunctional characteristics in early childhood, despite a loving and stress-free environment.
However, a person with a lighter dose of the genetics for a personality disorder is not necessarily predestined to descend into a full-blown, clinical version. There are two routes such a person can follow. With a relatively stress-free environment, the person may simply grow into someone who is “normal” but who can sometimes be difficult to deal with emotionally. The other route involves succumbing to all-out traits of a personality disorder.
How might this happen?
The key, it appears, is often stress. When a person experiences bodily stress, for example, physical exercise, it can turn certain genes on or off—perhaps through the regulatory function of the junk DNA. In the case of exercise, this stress can turn on genes that cause muscle growth—you see the result in the form of bulging biceps. But a body can experience stress in other ways—for example, by being beaten by a parent, working for a bullying boss, or drinking too much alcohol. All of these activities, amazingly, can switch different sections of one's genetic code from quiescence to an all-too-active state—or vice versa.7 The resultant proteins, which have different properties from the nonstressed versions, can, in turn, affect our personalities. Depending on the stress and our genetic predisposition, we can be pushed toward depression, eating disorders, drug abuse, or cancer.8 If a person already has a mild form of a personality disorder, he or she can be pushed into a full-blown version.
Intermediate Phenotype
Intermediate phenotype is a concept used by researchers who are wrestling with the relationship between genes and phenotype. To understand “intermediate phenotype,” it's helpful to remember that there is often an intermediate case between a full-blown manifestation of a disease and a less harmful variant. In personality disorders, intermediate phenotypes, sometimes called endophenotypes, are used to describe people with subclinical symptoms of diseases like schizophrenia or borderline personality disorder. The stipulation for an intermediate phenotype is that it be found in mildly ill but not “certifiable” siblings and other relatives, and that it even be found in some psychiatrically well relatives. This establishes that the phenotypes are related to risk for an illness and are not the illness itself.
So far, the concept of intermediate phenotypes has been most powerfully developed and used by Dr. Michael Egan and his colleagues at the National Institute of Mental Health for their research on schizophrenia. Schizophrenia, like borderline personality disorder, is a complex disease that results from many causes, including a multitude of genes and environmental factors such as drug abuse, head injury, infections, and even a person's conscious thinking processes—all of which can influence each other.
Egan's work clarified the relationship between a particular allele related to cognitive function that had previously been weakly and inconsistently associated with schizophrenia. When Egan's group applied the concepts of intermediate phenotype by studying brain function and comparing genotypes in a wide variety of people—including patients with schizophrenia, their healthy siblings, and controls—the suspect allele suddenly popped out as a strong predictor of abnormal prefrontal brain function. This happened in every person sampled, whether or not the person had schizophrenia. Egan's study was one of the first times that a correlation of an intermediate phenotype with a gene was shown to clarify how a gene related to a complex clinical diagnosis.9
“What's so surprising,” marvels Daniel Weinberger, Egan's colleague at the National Institute of Mental Health, “is that it works.”10 It appears that the next step beyond imaging genetics may relate to the synergistic use of genotyping, neuroimaging, and intermediate phenotypes. It will be exciting to see what future studies reveal when these techniques are applied to antisocial personality disorder, other related syndromes, and their subclinical “intermediate phenotypes.”
Faced with the overwhelming variety of phenotypes that can arise from this mixture of genes and environment, it's hard to know where to even begin looking at a person's genome to determine which alleles might be key in motivating behavioral traits. But a fascinating new discipline, imaging genetics, has recently arisen that provides precisely the necessary tool. Imaging genetics uses medical imaging techniques to figure out a person's phenotype—the word phenotype meaning, in this case, the size and shape of organs such as the amygdala and cingulate cortex—and then evaluating the same person's genes to see how they compare. The value of using medical imaging for the comparison with genetics, instead of old-fashioned questionnaires and interviews, is that genes act much more directly on neural components like the amygdala than they do on a person's ultimate behavior—and they don't lie. You might think of the old research as being the equivalent of trying to figure out how a racing car works by comparing its blueprints (genome) with its performance statistics (behavior)—a dry and thankless exercise at best. Today's imaging genetics allow you to open the car's hood and look around with sophisticated measurement tools on hand. This, in turn, allows you to make comparisons between blueprints and performance even while the engine is running, so you can figure out what's really going on.
But, you might ask, are we seeing the cause of certain thinking patterns? Or the effect? Clearly for some organic brain diseases, such as schizophrenia, we are seeing the effect. But for other conditions, it's often not clear. After all, use of antidepressants can alleviate depression by changing brain chemistry—these changes can be clearly seen with imaging techniques.11 But the same changes in neural chemistry can be seen after a patient has used cognitive therapy techniques to change her thinking patterns!12
If you ever want to know whether your tax dollars are being used for a good purpose, go take a look at the extraordinary work that the National Institute of Mental Health and other National Institutes of Health are doing in digging out the genetic bases of psychiatric illnesses. Dr. Weinberger, quoted above, also happens to be the director of the National Institute of Mental Health's Genes, Cognition, and Psychosis program. He is one of the leading researchers in this area, as indicated by the number of key papers related to the genetics of personality disorders that bear his name. When I spoke with him about this book, he reiterated his feelings that genes are about risk—not fate—and that no single gene by itself can predict personality.13
Most especially, we know that there is no single gene known to create a psychopath, or to cause someone to suffer from antisocial personality disorder, or to generate more sinisterly successful variants of either one of these disorders. But there are a number of genes and gene complexes that have been found to affect brain function—most importantly, for our purposes, regarding traits such as impulsivity, mood, and anxiety. Through the use of such sophisticated new techniques and concepts as imaging genetics and intermediate phenotypes, researchers are discovering how alleles of particular genes can help underpin the dysfunctional behavior that can lead to a problematic personality or full-blown clinical pathology. In a sense, you might call these evil genes.b. Let's focus on a few of them.
Serotonin Receptors and Behavior
A variety of different studies have converged on serotonin as being a key communication molecule—“neurotransmitter”—behind the generation and control of emotions. Neurotransmitters are like little flares that carry information across the gaps—synapses—between sending and receiving neurons (see the picture on the next page). It turns out that the serotonin flares can interact with about fifteen different types of receiving cell landing sites, called “receptors.” Once serotonin lands on a particular type of receptor, it sets in motion a whole Rube Goldberg–style chain of events. If serotonin hits one receptor, for example, it's metabolically akin to flipping a switch to start a ball bearing rolling down a ramp to bash against your toaster handle and start your morning toast. On the other hand, if it hits another kind of receptor, it's a sort of physiological equivalent of pushing a button that launches the ball bearing out a bedroom window, allowing it to bounce against a plate on a tree and back in the kitchen window below, thus tapping a coffeepot's ON switch and starting your morning cup of cellular java.
Why are there so many different kinds of serotonin receptors? Researchers speculate that serotonin has apparently been used as a communication molecule dating back even to very primitive organisms. This common molecule is found, after all, in pretty much anything with a backbone, as well as in spineless creatures such as flatworms, nematodes, and leeches. For all of these creatures, serotonin assists with sensing, motion-related, as well as cardiovascular functions. Basically, serotonin is a handy molecule for many different purposes.14 Different receptors on different receiving cells each respond to the little serotonin molecules by kicking their own pathways into gear. Serotonin receptors are each created according to templates set out by specific sets of genes, with each gene often having two, three, or even more different versions—that is, alleles. Obviously, all these different possibilities can make for a dizzying variety of potential genes related to serotonin receptors alone.
Fig. 3.4. The molecules of serotonin shown in this illustration are given off by the cell that is sending the message. The serotonin binds to “docks” (receptors) in the receiving cell and instructs that cell to either fire or stop firing, among other processes. The amount of serotonin in the gap known as the synapse, as well as the types of receptors (there are at least fifteen types), influences the cell's response. Two different types of sending cell molecules can reduce serotonin levels in synapses. Autoreceptors direct the cells to slow down serotonin production, while reuptake transporters absorb the neurotransmitter back into the sending cell to prepare for the next firing.
Different serotonin-related alleles have been found to be strongly associated with various aspects of personality and temperament, as well as mood disorders. But because these alleles interact and overlap, it's difficult to state definitively that any given allele is responsible for a given personality disorder. Sometimes an allele might help produce a disorder—but if that same allele is found with a constellation of other mitigating alleles, it might not produce the disorder at all. Indeed, the idea that groups of genes underlie personality types is an important one and has been given the name “QTL (Quantitative Trait Loci) Model” for behavioral traits.15
Our knowledge of how the different serotonin receptors relate to emotions is currently rather limited. We do know that one of those receptors, with the cryptic name 5-HT1B, plays a selective role in controlling offensive aggression.16 Other serotonin receptors have also been implicated in problematic behaviors. Certain alleles of the 5-HT2A receptor, for example, have been found to be associated with self-mutilation, anorexia, and a history of suicide attempts.17 The HT3A receptor, on the other hand, appears to have a critical influence on the amygdala (the “fight-or-flight” decision-making area of the brain), especially when a person is reacting to another's facial expressions. The HT3A receptor also affects how fast certain areas of the brain process information. Some versions of alleles related to this receptor appear to cause the extremes of neural activity seen in bipolar disorder.18 Overall, research about serotonin receptors and their associated alleles is just at the “tip of the iceberg” stage—enough to hint that there may be something going on related to precisely the sorts of emotions and behavior that are seen in various subclinical and clinical personality disorders.
On the other hand, if we switch our attention to serotonin transporters, as opposed to receptors, we will find that research is far more advanced.
The Long and the Short of It—Serotonin Transporters
Reflecting on the illustration a few pages back showing synapses and serotonin, we are reminded that serotonin receptors are equivalent to docking points that help trigger reactions in the next neuron. Once the reaction is triggered—the switch is flipped—the serotonin is then free to go back and float around in the space between the neurons. But if serotonin is already filling the space, how can a “sending” cell release new serotonin to trigger a new reaction? Somehow, the serotonin already in that space has to be pulled back into the original trigger neuron so that it can be used to trigger the next signal. One of the key molecules that helps do this is a special transporter molecule called SERT (for “serotonin transporter”). You can think of SERT as a cleverly designed protein conveyer belt that helps scoop excess serotonin out of the cleft between neurons and carry it back into the trigger neuron. Two different alleles have been found that help produce SERT—a short allele with fourteen tandem repeats, and a longer version with sixteen tandem repeats. (“Tandem repeats” is short for “repeated tandem base pairs,” such as GCGCGCGCGCGC. Sometimes the tandem repeats confuse the cell's DNA copying apparatus, so it's easier for these alleles to be miscopied and made shorter or longer.) The difference between the short and long SERT alleles doesn't lie in the information that codes for the transporter molecule itself but rather in the part of the gene that controls how often the transporter molecule gets produced. The short version of the allele doesn't allow for production of as many transporter molecules. You might think of it as a copy machine that puts out only half the copies you request. The resulting lack of transporter molecules allows serotonin to linger longer and appears to predispose people toward anxiety, impulsivity, suicidal thoughts, affective instability, bulimia, and binge drinking.19 People with two shorts (one from the mother and another from the father) have fewest transporters and seem to feel these effects most strongly.
The ultimate effect of the short SERT allele is that the part of the brain that is supposed to dampen down your fear responses doesn't seem to be able to do its job very well. Remember that serotonin provides a connection between two neurons. If something happens to that connection, problems are bound to occur—neurons aren't able to communicate clearly. It's like trying to speak (send out serotonin) in a room filled with people who are already talking loudly (serotonin is already in the space between the neurons). It's hard for important messages to get through. The short allele may produce depression simply because natural anxiety and fearfulness aren't restrained.
Fig. 3.5. This figure shows two vital, emotion-related organs—the amygdala and the cingulate cortex—that are affected by reduced serotonin transport.
Researchers are beginning to home in on how all this happens. Using functional magnetic resonance imaging, researchers have found that in normal and depressed people with one or two “shorts,” not only were the cingulate cortex and amygdala reduced in size, but the circuits that connected the two organs also appeared to be weakened.20 (The cingulate cortex is that part of the brain that helps us to focus our attention and “tune in” to thoughts, while the amygdala, again, is the “fight-or-flight” coordinator of the body's emotions.) You can see the weakened “speech” between the amygdala and the cingulate in the illustrations on the next page. The picture on the left shows a normal control loop for fear—the kind of loop that would be seen in a person with long/long SERT genes. The amygdala sends a signal to the lower part of the cingulate, and then on to the upper, and finally, a “calm down” signal is sent back to the amygdala. In real life, this process might relate to something like the fear you feel—due to the amygdala's response—as your plane suddenly begins jouncing up and down. This fear would be communicated by the amygdala to the cingulate cortex, which would turn back around and control the amygdala's response by communicating something like: “Calm down, it's okay—it's just turbulence as we're flying over the Rockies.”
The illustration on the right, however, shows the circuit response in people with at least one short SERT allele. Although the amygdala is activated, it can't send a strong signal out to the cingulate cortex because of all the other chatter going on. (Remember those serotonin transporters? There are fewer of them, so they don't transport very well—like stagehands who haven't bothered to clear the stage for the next act in the play.) Consequently, the controlling “whoa—take it easy” signal from the cingulate cortex back down to the amygdala is also weaker. The resulting thought pattern might go like this: “Calm down—it's just turbulence. I mean, I think it's just turbulence. But…the people on Flight 587 thought it was just turbulence, too. My God, that plane shook itself apart midair. Every one of the 260 people on board was killed! I'm going to die!!!” As you might imagine, this kind of negative thinking can lead to all sorts of problems—depression not the least of them.
Fig. 3.6. Those with the long/long genotype, as shown on the left, have a full feedback control system that damps down the aroused amygdala. This allows a person to relax after first being startled. Notice how much thinner some of the signaling arrows are in the image on the right. Those with one or two short carriers aren't able to take advantage of feedback—their amygdalae continue to be revved up even after the person has consciously realized there is nothing to feel threatened about.
Pleiotropy—The Naughty-Nice Aspects of “Evil Genes”
Given the many different negative aspects of the short version of the SERT allele on a personality, why hasn't the allele for the short version of the transporter molecule just died out? Surprisingly, it may be because the long version of the allele can also create problems—not necessarily with emotions, as the short allele does, but in other areas of the body. For example, primary pulmonary hypertension—a serious disorder that causes the heart to essentially overpump—appears to become a problem if a person has received long versions of the allele from both the mother and the father. This double mother-father dose allows for excessive serotonin that spurs the growth of pulmonary artery smooth muscle cells, which eventually blocks the blood's pipeline to the lungs.21
Remember, it is a single gene, the gene that produces the serotonin transporter molecule, that has all these varied effects on the body's neural, cardiac, and even the immune systems. The concept that one gene can affect many different areas of the body is so crucial that it even has a name: pleiotropy, from the Greek pleio, meaning “many,” and tropo, meaning “turning toward.”
An example of pleiotropy can be found in the APOE4 allele (short for apolipoprotein E 4). This allele, which is situated on chromosome 19, may have predisposed my father to Alzheimer's disease after his slip from the peaked roof of the covered bridge. Inflammation from his resulting concussion could have caused the allele's activation.22 (If my father had had a double set of APOE4 alleles, one from each of his parents, he would have been even more likely to have wound up with Alzheimer's, although a number of other genes undoubtedly also play a role.) If all of this wasn't bad enough, the APOE4 allele has another nasty effect. It seems to be associated with high cholesterol—from which my father also suffered.
But it seems that there are several good aspects to the APOE4 allele. One is that, if this allele is switched on by nutritional stress, it may help children survive severe malnutrition early in life.23 (The trade-off, of course, comes at the other end of the life span.) Another nice aspect of APOE4 is that, although you may lose your memory when you get old, you may actually have a sharper memory when you're young.24
The flip side of pleiotropy is polygeny. Polygeny simply means that a single trait can be influenced by many genes. For example, even though Alzheimer's is associated with the APOE4 allele, other genes may ameliorate the errant allele's effect. This may be why many APOE4 carriers never succumb to Alzheimer's. Polygeny appears to underlie personality disorders that are related to some types of sinister behavior—behavior much like my sister Carolyn's.
Brain-Derived Neurotrophic Factor
Another gene related to mood and anxiety is the gene that produces BDNF—Brain-Derived Neurotrophic Factor. This factor helps support the survival of existing neurons and encourages the growth of new neurons and synapses. There are two common alleles for this gene, dubbed val (short for valine—an amino acid in the protein coded by the gene), and met (short for methionine—a different amino acid that is substituted for valine at the same spot in the protein). It turns out that people who have two versions of valine have exceptionally good memories—the double val alleles seem to have a stronger effect on memory than any other factor ever studied.25 Unfortunately, these people are also more neurotic—that is, they have more negative emotionality in regard to anxiety, low mood, and hostility.26 This instance of multiple effects of a single gene is another example of pleiotropy.
Daniel Weinberger believes the met allele may have evolved because a double dose (one from the father and another from the mother) of the met BDNF allele just can't “hear” serotonin very well—which could be a real advantage in ignoring the higher anxiety signal that results from short serotonin transporter genes. A double val dose, on the other hand, appears as if it may magnify the effect of the short serotonin transporter. Psychiatrist Jim Phelps relays an analogy from Weinberger:
Imagine that [val/val] BDNF alleles, with their memory-improving capacity, make your brain function like a 200 mile-per-hour race car. If you've got a hot rig like that, you'd better be a good driver who's capable of handling a fast, but temperamental car. In this analogy, that's the long/long allele pair for the SERT gene: the driver won't get over-anxious and allow the car to get out of control. That's important, because if you smash your car into the wall very often, your car won't run very well. In real life, if you take too many stress-hits, you end up depressed.
By comparison, if you inherit the short/short pair for SERT, and thus are less able to handle anxiety-producing situations such as conflict, trauma, and loss—you are a more cautious and potentially distractible, frightenable driver. In this case, you might be better off with a slower but more crash-resistant car, one that you can smash up against the wall quite a few times without changing how it performs very much. In this analogy, that's the met/met allele pair for the BDNF gene.
By this analogy, perhaps the “slower” met allele was selected for (evolution-speak) in humans to help people with “two shorts” get through life better. If two shorts make you more cautious, and two met's make you less likely to worry about things, for some people that could make a durable, reliable combination that in dangerous times might be better than the high-performance but “higher-maintenance” val/val and long/long combination. Of course at this point that's almost entirely a guess, but it gives us a beginning of a model which might help us understand these genetic variations in humans.27
Certain alleles for BDNF receptors have been found to be strongly associated with bulimia and anorexia, which are in turn associated with such personality traits as anticipatory worry and pessimism.28 Some BDNF alleles are also associated with depression, bipolar disorder, and neuroticism.
Warrior or Worrier? The COMT Gene
Trade-offs—there are always trade-offs. And nowhere is that more clear than with the COMT gene (short for the ungainly catechol-O-methyltransferase), which is a key gene underlying our general intelligence. This gene works by serving as the blueprint for an enzyme that breaks down dopamine and other neurotransmitters. It turns out that the more slowly you metabolize dopamine, the smarter you are, so if you have versions of the COMT gene that don't metabolize dopamine well, chances are you have a higher IQ (other genes and the environment also play a role here, of course). Like the BDNF gene, COMT also has val and met versions, with the met being a slow metabolizer, and the val fast.29 People with val/val versions of the COMT gene can be a bit less intelligent—they may also have a slightly increased risk for schizophrenia. Val/vals are also at increased risk for antisocial behavior and hyperactivity. None of these detrimental, fast-metabolizing val effects are particularly surprising—after all, amphetamines and cocaine, which increase the transmission of dopamine, cause the psychotic, aggressive behavior that is so familiar to emergency room physicians. Compared to val/vals, met/mets can be smarter, and have a markedly better memory.30 People with mixed val/met versions of the alleles seem to be halfway in between.
Given the advantages of met, it would seem that val would have died out. Instead, it is common in many human populations, with increases of met being balanced by decreases in val, and vice versa, in a sort of yin-yang relationship.31 Why? Val versus met has been aptly described as “warrior” versus “worrier.”32 It seems that although vals may not be as smart on average and they have the mixed blessing of increased aggressivity, they can handle stress better than mets. Additionally, val cognition, although perhaps not as quick or deep, is more flexible—vals can more easily adapt when the rules of the game suddenly change.33 Conversely, the met allele is instead associated with more anxiety or, in research-speak: “lower emotional resilience against negative mood states.”34 It is more frequently seen in individuals with obsessive compulsive disorder, which is characterized by distressing intrusive thoughts and the compulsive performance of rituals. Met is also associated with feeling pain more strongly and reacting more negatively to prolonged pain—people with met alleles simply don't get the same natural soothing opiates that vals get.35 Although met COMT enhances intelligence and memory, it can also add to the effects of a short SERT allele, making a person even more anxious and neurotic.36 You might think of this as the Woody Allen of genes—producing brilliance coupled with deep neuroticism.
Monoamine Oxidase A
Monoamine oxidase A—MAO-A for short—is a term for an enzyme that helps break down neurotransmitters like serotonin and dopamine so they don't continuously build up inside neurons. As with the SERT gene, it seems that low-functioning versions of the MAO-A gene have been linked to problematic personality traits. These traits involve both impulsive and aggressive behavior, as well as depression, substance abuse, criminal behavior, attention deficit disorder, and social phobias.37 One recent study has linked the low-functioning versions of the MAO-A gene to those with the dramatic, emotional, and erratic personalities known as “Cluster B” disorders (which include antisocial and narcissistic personality disorders).38 Differences in neural behavior in those with different versions of the gene have been spotted even in those with mild intermediate phenotypes—that is, in normal or relatively normal people who would fly under the radar of clinical significance for diagnosis of a personality disorder.39
One study analyzed one hundred normal volunteer men and women to see whether they carried the high- or low-efficiency versions of the MAO-A gene.40 These volunteers were then imaged. The upshot was that those with the low-efficiency MAO-A alleles had smaller limbic organs, such as the amygdala and cingulate gyrus. The amygdala reacted strongly when these subjects were given a very mild scare, but the increased amygdala reaction was accompanied by an unexpected decreased reaction in the orbitofrontal and cingulate cortices (generally the amygdala would activate these two cortices, which would in turn send signals back to the amygdala to calm it down). These are the types of neurological reactions that are associated with impulsive violence. These reactions display the same sort of tamped down neural control circuitry between the amygdala and the cingulate cortex that we saw earlier in the individuals with short serotonin transporter alleles. It's just that in this case, not only is there a damped connection between the cingulate cortex and the amygdala, there's also a damped connection between the orbitofrontal cortex and the amygdala. Weakening this latter circuit means someone might have trouble with stimulus-reinforcement learning. A typical example of this type of behavior might be the knuckleheaded kid who continues to saunter in late for classes even though he knows he'll get detention.
The low-efficiency MAO-A allele appears to be particularly associated with impulsive violence, as opposed to violence as a purposeful means toward an end. The effects of MAO-A genes were, in fact, first discovered in a Dutch family in which certain males had inherited an unusual mutation that did not allow their MAO-A to metabolize serotonin or other neurotransmitters. Generations of family members had shown bizarre aggressive behavior, such as an attempt to run an employer over with a car; stabbing a warden in the chest with a pitchfork; or entering sisters’ rooms at night, armed with a knife, and forcing them to undress.41
The MAO-A system is interesting, too, because it was the first neurotransmitter system to reveal how the same environment might have a different effect on people with different genetics. In 2002, Avshalom Caspi and his colleagues gave evidence that indicated why some children who are maltreated grow up to develop antisocial behavior, whereas others do not.42 The key to the differences, it turned out in this study, lay in the children's genotype. Children who grew up in positive environments generally had no developmental difficulties, whatever their genotype. But those children who grew up being maltreated showed significant differences depending on whether they had high- or low-efficiency MAO-A alleles. Maltreated kids with efficient MAO-A activity weathered the storms of their youth relatively well. However, those with inefficient MAO-A activity developed significant antisocial problems—85 percent of those with a low-activity MAO-A genotype who were severely maltreated developed some form of antisocial behavior. That result was twice as high as the high-activity group under severely maltreated conditions. It was thought that deficient MAO-A activity disposes the kids toward neural hyperreactivity to threat.
How, precisely, might the genes operate differently under different environmental conditions? As mentioned earlier, stress might cause an increase in certain chemicals that in turn cause the DNA copiers to jump their tracks and begin copying from different parts of the DNA strand. This makes slightly different proteins, which in turn cause the properties of the synapses to subtly shift.43 This type of effect, where a particular allele is problem-free unless the environment (or another gene) kicks it off track, might happen with many different personality-related genes.44
Other Moody Genes
A number of other genes also affect mood, although our understanding of how is limited at present. Tryptophan hydroxylase (TPH), for example, is an enzyme that helps in synthesizing serotonin. Various types of TPH and their associated genes appear to be associated with a number of different psychiatric and behavioral disorders—including those, as we shall see, which relate to Machiavellian behavior.45 Another gene—this one with the cryptic handle of D4DR—has been linked to novelty seeking. D4DR has a variable number of repeats in its nucleotide building blocks that can affect how quickly dopamine is metabolized by the body. The higher the number of repeats, the more novelty-seeking behavior a person seems to exhibit—and the more extroverted a person often is. Shorter forms may be associated with crankier personalities.46
And another recent discovery, the DARPP-32 gene, has been found to be associated with both optimized thinking circuitry and, sadly, increased risk of schizophrenia. Daniel Weinberger explains: “Our results raise the question of whether a gene variant favored by evolution, that would normally confer advantage, may translate into a disadvantage if the prefrontal cortex is impaired…. Normally, enhanced cortex connectivity with the striatum would provide increased flexibility, working memory capacity and executive control. But if other genes and environmental events conspire to render the cortex incapable of handling such information, it could backfire—resulting in the neural equivalent of a superhighway to a dead-end.”47 It turns out that DARPP-32 is associated with depression and substance abuse as well as with schizophrenia.
Still more genes relate to the hormones vasopressin and oxytocin and help produce the feelings of love we may feel for others.c.48 Perhaps, when set on “high,” these genes help produce the kind of person who continually, gullibly forgives all manner of purposeful emotional and physical abuse.
In the end, all of the genes mentioned above, and many others as yet unknown, could prove important in any number of personality traits. It will be interesting to watch developments as the field of behavioral genetics unfolds.
EMERGENIC PHENOMENA
A particularly significant concept that we must not ignore here is something called emergenesis. This term refers to genetic traits that, surprisingly, don't commonly run in families. Examples of this might include leadership, many different types of genius, and psychopathological syndromes like psychopathy and borderline personality disorder.49 The way this occurs isn't all that difficult to understand. Let's say, for example, that a brilliant executive, known for his extraordinary leadership skills and visionary sense of business, along with his petite wife, who had won a gold medal in the Olympics as a teenage gymnast, has a large family of ten children. What might we expect?
The children would each receive half their genes from their mother, and half from their father, although there's no telling beforehand what scrambled mixture they might receive. Let's say that part of the father's business acumen and leadership skills relate to an outstanding memory provided by a val/val BDNF set of alleles, coupled with a calming long/long serotonin transporter (SERT) allele set. (Of course, there are many other genes that play a role here, but we're simplifying this just to make the point.) The executive's fortunate confluence of BDNF and SERT alleles are part of why he thinks fast and can remain unflustered no matter what might arise. The gymnast wife, on the other hand, may have a short/short serotonin transporter molecule, making her routinely more anxious, but her met/met BDNF alleles mean she's still fairly easygoing, although they also ensure her memory is nowhere near as sharp as that of her husband.
With this setup, none of the ten children would have any real chance at all of having precisely the same four genes as either of their parents. Just the slight difference in these genes might be enough to take the edge off of each child's ability to replicate either of the parents’ successes (or, if the scenario were changed—their failures). And that's for those four genes alone. Multiply this by the as yet unknown number of total genes that have substantive effects on any particular personality trait—two hundred? Two thousand? And remember, there's also that, as yet barely understood, control information hidden in the junk DNA. You couldn't possibly have a chance at replicating precisely the same personality-related genome that the parent has into a child—although you could definitely inherit a confluence of genes that would allow you to show some key factors, including impulsivity, anxiety, intelligence, or extraversion. Put differently, if your father were a Leonardo da Vinci–caliber genius, chances are you'd be pretty smart but no genius yourself.
Inheritance of personality is particularly touchy because other, seemingly nonpersonality-related genes also factor into the equation. Even if a child is given nearly the identical personality underpinnings as the parent, her entire life might be different, for example, if she also happened to inherit a difficult-to-battle tendency toward obesity. Or perhaps she might have inherited genes that gave her a particular delight in music or skill at dancing, or predisposed her toward preternatural enjoyment of the buzz of alcohol, or gave her a low ability to maintain focus even on things that interest her.50 And of course environment can play a role too. Even within the same family, she might have been treated very differently than her older sister was. Or maybe her mother played with a cat and was infected with toxoplasma gondii before she even knew she was pregnant, setting up the conditions for her daughter to become schizophrenic.51 Or perhaps she was kidnapped and brutally raped as a nine-year-old and dumped bloody and bruised by the side of the road.
All of these reasons, both genetic and environmental, are why virtually all parents with more than one child are amazed at how their children could be so very different. (“Night and day” is the common refrain.) Only identical twins could be expected to have nearly precisely the same genotype—and even that genotype, of course, will be quite different from that of the parents.
WHY WE CAN'T SIMPLY ELIMINATE “EVIL” GENES
Some studies have shown that if one of your first-degree relatives has the emotionally unstable condition known as borderline personality disorder, you've got an 11 percent possibility of having the disorder yourself—a substantial increase over the 1 to 2 percent chance for the disorder in the general population, but far from absolute certainty.d.52 The concept of emergenesis explains this spotty evidence for heritability. Having full-blown borderline personality disorder probably requires inheriting just the right confluence of genes related to very different traits involving cognitive dysfunction, mood disorder, and impulsivity, and often needs a final spark from a stressful environment to set things afire. Indeed, studies have shown that the borderline traits of affective instability and impulsivity run in families.54 But since each of the unlucky borderline traits involving impulsivity, mood disturbances, and cognitive dysfunction is, for the most part, separately heritable, it's unlikely that you'd inherit every one of them, even if one of your parents were to be borderline. We have reason to believe that the spotty heritability situation is similar with antisocial personality disorder (which can actually arise from many different causes, some of which are solely environmental), and even psychopathy.
An Emergenic Prodigy Speaks of Jewish “Smarts”
Norbert Wiener was a child prodigy who received his doctorate from Harvard at age eighteen; he would go on to discover important mathematical properties related to communications, robotics, computer control, and automation. Wiener's father claimed that it was his training methods alone that had made his son so brilliant—otherwise Norbert would have been a perfectly ordinary child. Given the fact that the three other children in the family were not especially gifted, Norbert, with his emergenic genius, found his father's statements extraordinarily galling.53 In tandem with his intellectual brilliance, Norbert was hypersensitive to criticism and subject to fits of depression.
Due to fear of anti-Semitism, Wiener's Jewish heritage was kept a secret from him as a child—afterward he became interested in Jewish culture and heritage. (Actually, Wiener was fascinated by virtually everything.) Anticipating research findings that would come a half century later, Wiener wrote:
Let me insert here a word or two about the Jewish family structure which is not irrelevant to the Jewish tradition of learning. At all times, the young learned man, and especially the rabbi, whether or not he had an ounce of practical judgment [shades of the COMT intellect-emotion trade-off] and was able to make a good career for himself in life, was always a match for the daughter of the rich merchant. Biologically this led to a situation in sharp contrast to that of the Christians of earlier times. The Western Christian learned man was absorbed in the church, and whether he had children or not, he was certainly not supposed to have them, and actually tended to be less fertile than the community around him. On the other hand, the Jewish scholar was very often in a position to have a large family. Thus the biological habits of the Christians tended to breed out of the race whatever hereditary qualities make for learning, whereas the biological habits of the Jew tended to breed these qualities in. To what extent this genetic difference supplemented the cultural trend for learning among the Jews is difficult to say. But there is no reason to believe that the genetic factor was negligible.55
Wiener had no way of coming up with a more concrete, testable model for his speculations. But in 2005, scientist Gregory Cochran, working independently of any institution, along with Jason Hardy and Henry Harpending of the University of Utah, finally proposed just such a model. Cochran and his colleagues suggested that a group of European Jews known as the Ashkenazi commonly carried several genetic mutations that explained their naturally high intelligence. (Ashkenazim score about twelve to fifteen points above the average of one hundred on IQ tests—the highest of any group of humans.) A single dose of the novel alleles can increase the growth and number of connections between nerve cells. As with many seemingly beneficial genes, there are trade-offs. Those with a double dose of the allelles can wind up with neurological disorders such as Tay-Sachs disease, as well as with cancer.56 Of course, the above findings are highly controversial.
But just what is the difference between, say, the mind of a psychopath and that of a normal person? We are at the cusp of cutting-edge technology that allows us to see. And seeing the differences between psychopathic and normal neurological processes is a crucial step in allowing us to begin to understand the underpinnings of some types of Machiavellian behavior. As we shall discover, understanding the “why” of Machiavellian behavior will also help us to understand why there are Machiavellians at all—and why some of them are so successful.
a.Since Plomin's comments, a twin study has shown that a tendency toward being religious does indeed appear to be moderately heritable. Such a tendency, it seems, is strongly influenced by the environment during adolescence. However, by adulthood, religiousness seems to slip away somewhat unless you've got genes that predispose you toward religion.
b.Okay, if you really wanted to be picky here, you could say “problematic alleles,” or even “quantitative trait loci that have been affiliated with specific personality disorders,” with the caveat that environment can often play an important accompanying role in those with a genome that has set them at risk. But it doesn't have quite the same ring, does it? In any case, it's important to remember that depending on the constellation of other genes in a body, supposedly evil genes might have a neutral, or even positive effect. Or such genes could have mixed positive and negative effects, such as increased intelligence coupled with increased neuroticism.
c.Indeed, since the first edition of Evil Genes, a study by researchers at the Hebrew University in Jerusalem has demonstrated a tentative link between ruthless behavior and variations in a gene that produces vasopressin receptors. For this study, roughly two hundred students had their DNA sampled and were then asked to play a game that (unbeknownst to the students) was called the Dictator Game. Students with shorter versions of the vasopressin receptor gene (AVPR1a) were more likely to behave selfishly.
d.Twin studies show that if one identical twin has full-blown borderline personality disorder, there is a 35% chance the other has it, while fraternal twins have only an 8% chance of sharing the disorder. Subclinical borderline personality disorder, on the other hand, showed a concordance of 38% for identical and 11% for fraternal twins.