BIO-BABBLE?
On a sunny Saturday morning on August 12, 2003, six people entered a church in Pasadena, California, set up a suite of computers, and began sending e-mails around the country announcing that their hunger strike had begun. Their protest was about human rights abuses perpetrated by an institution the hunger strikers claimed had tortured them in their youth, by incarcerating them against their will, poisoning them, firing electrical currents into their brains, branding them insane, and affirming the improbability of their ever being fully sane again. To these protestors this institution is known as a system of legalized mental and emotional abuse. To most of the rest of us it is known as medical psychiatry.
In late 2011, I spoke to one of the striker’s leaders, 56-year-old David Oaks. My aim was to discover why this group had taken such drastic steps to be heard. Oaks chose to answer my question by telling me his story.69 As an undergraduate entering Harvard University in the mid-1970s, he had great difficulty adapting to his new environment. He had been raised in a working-class family on Chicago’s South Side, and so found the world of privilege at Harvard so fundamentally alien to all he had known that he had struggled to find his place. He soon started experimenting with marijuana, which only deepened his feelings of estrangement and alienation. And as these difficult feelings spiraled, it was not long until he entered what he called an “altered state.”
Once a couple of people noticed this change in him, it wasn’t long before he was sent to the college infirmary. There they classified his experiences according to the DSM’s definition of schizophrenia. He was therefore prescribed heavy doses of Thorazine, a powerful antipsychotic drug. But the drug did not help him; in fact, it seemed only to deepen his confusion.
By the following semester, Oaks was admitted to the famous McLean Hospital, where it was decided that what he needed was heavy sedation. But Oaks did not want to be heavily medicated, so the authorities did what they are entitled to do if a psychiatric patient does not comply with treatment—they locked him in solitary confinement and subjected him to forced drugging. The medication with which they injected him was so powerful that he could barely eat, think, or move—let alone continue to uphold his spirited protest.
During one particularly agonizing night locked up in solitary confinement, David became so overwhelmed with shame and disgust at the way he’d been handled that he made a lifelong pledge: “I remember looking out through one of those impenetrable metal window screens,” David Oaks recalled emotionally, “and there and then I pounded on the screen with my fist, vowing to do something for human rights once I got out.”
Thirty-five years have now passed since that harrowing episode, but Oaks has more than honored that vow. After his discharge from hospital (which he secured by threatening legal action unless they released him), he graduated from Harvard University in 1977 with honors. Since then he has dedicated his life to protecting the rights of psychiatric patients, or as he would call them “psychiatric survivors.”
He first worked with the Mental Patients Liberation Front, organizing rallies during the early 1980s against the American Psychiatric Association’s sanctioning of electroshock therapy. He also wrote for the influential Madness Network News, becoming one of America’s foremost advocates for psychiatric patients’ rights. In the 1990s he helped found Support Coalition, now called MindFreedom, of which he is now executive director. Over the years, this organization has gone from strength to strength, recently being accredited by the United Nations as a nongovernmental organization with consulting status.
David Oaks’s history of patient advocacy and activism is the backdrop against which we find him protesting with five other hunger strikers in that church in Pasadena. Each of the other strikers could also tell their own tales of woe—some were force-fed drugs they didn’t want, others were given ECT against their will, and most had suffered from the stigma and crippling side effects of their psychiatric treatment. So together they all sat in that church, refusing solid food until their demands were met.
So what were their demands? What did the hunger strikers exactly want? David Oaks was forthright about this: “We wanted something very simple—we wanted the American Psychiatric Association and two other major organizations to answer some basic questions. We wanted them to provide evidence for what we had been led to believe as patients: that the major mental illnesses are actually biologically-based brain diseases; that psychiatric diagnosis is objective; that there are chemical imbalances that can be corrected by psychiatric drugs; and that psychiatric drugs actually cure us rather than temporarily alter us like recreational drugs do.”
After sending these requests from their overheating computers, the hunger strikers sat back and waited … and waited … and … well … waited some more. Two of the organizations (National Alliance for the Mentally Ill (NAMI) and the Office of the Surgeon General of the United States) completely ignored the hunger strikers’ requests, acting as though the whole event was just not taking place. “Their total silence could’ve made the situation very sticky,” recalled Oaks, “if the American Psychiatric Association had not finally clicked that they actually needed to respond.”
And respond they did. It came in the form of a brief 247-word PR statement declaring that the APA was committed to promoting “the highest quality care for individuals with mental illness,” and further adding that in recent years, “there has been substantial progress in understanding the neuroscientific basis of many mental illnesses.” The APA therefore did not provide the evidence that Oaks and his fellow protesters had specifically asked for. Instead, the APA told the strikers if they wanted to learn about the biology of mental distress, then there were three good psychiatric textbooks that they should consult for the evidence they sought.
This somewhat dismissive response would soon backfire for the APA, because what they did not know was that the protestors had organized a scientific panel to assess the APA’s response. This panel was comprised of fifteen senior academics and clinicians from the United States and Europe, including Professor Mary Boyle (University of East London), Professor David Cohen (University of Texas), Dr. Patricia E. Deegan (Boston University), Professor Tom Greening (UCLA), and Dr. Peter Breggin (founder of the ICSPP). “These guys worked incredibly hard,” said Oaks energetically, “and yes, they went away and scoured those textbooks for any relevant studies and citations, etc.”
So what did the scientific panel find? Did the textbooks provide the evidence the protesters asked for? “In short,” said Oaks, “they did not.” Instead, the scientific panel found the books littered with confessions of failure, such as: “The precise causes (etiology) of mental disorders are not known;” and “Few lesions or physiologic abnormalities define the mental disorders, and for the most part their causes remain unknown;” and “Although reliable criteria have been constructed for many psychiatric disorders, validation of the diagnostic categories as specific entities has not been established;” and “In the areas of pathophysiology and etiology, psychiatry has more uncharted territory than the rest of medicine.”70
Given that these statements hardly supported the APA’s earlier claim that modern psychiatry had made “substantial progress in understanding the neuroscientific basis of many mental illnesses,” the scientific panel sent these and other statements back to the APA, stating that they had neither found, nor once again been given, the evidence they wanted. When the APA responded, now for the second time, it was clear they had become irritated: “It is unfortunate that in the face of … [psychiatry’s] remarkable scientific and clinical progress,” they wrote, “[that] a small number of individuals and groups persist in questioning the reality and clinical legitimacy of disorders that affect the mind, brain, and behavior.” The APA then reaffirmed that there is “research” and “compelling evidence” showing that some disorders have a strong genetic component, and that schizophrenia reveals reproducible abnormalities of brain structure.
But after asking the APA, now for a third time, to provide its “compelling evidence,” not a single specific reference or piece of scientific research was provided to back up their claims. As Oaks told me with a twinkle in his eye, “They could not give us what we wanted because what we wanted does not exist. We knew that, they knew that, but I think they realized coming clean publicly would be a PR disaster.”
Toward the end of our interview, I asked what Oaks felt the hunger strike had achieved. “It did not change psychiatry, that’s for sure. Biopsychiatry is now more powerful than ever in its entire history. But we did consider it a success to the extent we got our message out there. Many media outlets covered the story, like the Washington Post, the LA Times, and the BBC. And people saw firsthand how the APA operates—concealing information, distorting the facts, and unwilling to be held to account. We even won a real concession: the APA’s final statement conceded that psychiatry cannot yet readily point to any ‘discernible pathological lesions or genetic abnormalities’ in mental disorders.71 Now, that is something you won’t hear them admit every day.”
Oaks is not opposed to all psychiatric treatment. He recognizes that in some cases drugs may help the most severely distressed in society. What he objects to is the treatment and sectioning of patients against their will, psychiatry’s dubious financial dependency on the pharmaceutical industry, psychiatry’s medicalization of our most basic everyday problems, and finally the psychiatric myth that our emotional troubles are rooted in biochemical imbalances or genetic dispositions.
As this current chapter is primarily interested in the biology of mental distress, it is now time to focus more closely on that final statement about genes and biochemical imbalances. Are they indeed at the root of our mental ill-health, as much of the public have been led to suppose?
2
In the early 1960s, a young medical researcher from the wrong side of Brooklyn stumbled upon an idea that would launch a paradigm shift in psychiatry. The researcher was called Joseph Schildkraut, and the idea he advanced was rather simple: fluctuations in our moods may be due to chemical imbalances in our brains. To be sure, Schildkraut was not the first person to entertain this compelling idea. It had been floating around the psychiatric community in one form or another since the mid-1950s when the first antidepressants started to be used. But for some reason when Schildkraut published his hypothesis in the American Journal of Psychiatry in 1965, his views took the community by storm.72
In fact, his paper, which has since become one of the most cited papers in psychiatric history and which was ungainly entitled “The Catecholamine Hypothesis of Affective Disorders,” is now regarded as the first and clearest articulation of what is now widely called the chemical imbalance theory of mental illness.
What prompted Schildkraut to write this paper was a confluence of many things. One spur of particular note was that, while working as a researcher at the National Institute of Mental Health, Schildkraut had become fascinated with the observation that certain depressed people who did not respond well to talk therapy often seemed to improve when given certain drugs. But he, like others at that time, was uncomfortable with the “drug-centered” view I discussed in the last chapter: the idea that psychiatric drugs were merely soothing tonics that have mood-altering effects like recreational drugs do. Schildkraut was rather convinced they must have a more curative effect.
It was this conviction that led him to try and explain the biology of this “curative effect” in his 1965 article. His method was to review data from many different pharmacological studies, mainly conducted on animals, which seemed to suggest depression was due to a brain deficiency in a chemical called norepinephrine. His theory was that the two types of antidepressant in most widespread use at the time (the tricyclics and the monoamineoxidase inhibitors [MAOIs]) worked by increasing the amount of norepinephrine available in the central nervous system—the implication being that depression was an outcome of some kind of norepinephrine deficiency.
Now the first thing to say about Schildkraut’s theory was that he himself called it at the time “at best a reductionist simplification” that could neither be rejected nor confirmed “on the basis of data currently available.” In other words, Schildkraut explicitly acknowledged that the chemical imbalance theory was just that—a theory for which the science of the day offered no clear support. This meant that his now famous article actually proved nothing at all. All it did was postulate an idea. An idea that, it would soon turn out, would come to captivate an entire new generation. As the medical historian David Healy puts it:
Despite the fact that such a hypothesis could have been proposed earlier and despite the many flaws inherent in it, this particular statement in 1965 came to dominate the field, set research agendas, and direct drug company efforts for the following two decades. It crystallized a split in psychiatry between biological and psychodynamic branches, each group having its own journals, its own meetings, and de facto very little to do with each other.73
Let’s now fast-forward three years to 1967. At this time, Schildkraut’s theory was taken in an unexpected direction by a British psychiatrist called Alec Coppen. What Coppen argued, in a paper published in the British Journal of Psychiatry entitled “The Biochemistry of Affective Disorders,” was that norepinephrine is not the only chemical implicated in mood irregularities. Others were crucial too, especially a neurotransmitter chemical called serotonin. But again, after reviewing all the relevant studies available at that time, Coppen, like Schildkraut before him, was still cautious with his conclusions, adding the following caveat at the end of his article:
We must face the very real possibility that we are far from the primary disturbance in depression. The changes [in serotonin] may all be secondary to other abnormalities which have not been taken into account at all … In spite of all the numerous investigations and very exciting leads that are now opening up, we are perhaps only in a slightly better position than Sanctorius of Padua … [when he said some three hundred years ago]: “Where the bond of union is between the mind and the animal fluids, God Almighty alone knows …”74
Coppen’s theory that the “animal fluid” of serotonin may be crucial in shaping our mental lives cleared the path for the second generation of antidepressants: the SSRIs (selective serotonin reuptake inhibitors). These newer medications included, as we have already seen, drugs like fluoxetine (Prozac), Paroxetine (Paxil, Seroxat), Sertraline (Zoloft), fluvoxamine (Luvox), Citalopram (Celexa), etc. All of these were thought to alter mood irregularities by inhibiting the reuptake of serotonin by neurons in the brain. All of these, in other words, assumed that Coppen’s theory of the chemical imbalance (this time of serotonin) was correct.
But was his theory correct? That is the crucial question. A question we cannot hope to answer without first getting a handle upon some of the very basics of neuroscience. I promise I’ll be very brief.
The brain is famously made up of about one billion nerve cells called neurons. Each of these neurons resembles a piece of string with little branches coming off it called dendrites. The neurons do not actually touch each other, but they do communicate with each other by way of discharging chemicals into the tiny gaps sitting between them. These gaps are called synapses, and the chemicals that flood them are called neurotransmitters. They are called neurotransmitters because they “transmit” complex electrical messages from one neuron to another, ensuring that these neurons are in a constant and highly complex conversation.
To simplify things greatly: when neuron A has received enough transmitters from surrounding neurons, it “fires” its own transmitters to other neurons around it. When thousands of neurons are triggering each other in this way, this is called a cascade. And cascades are thought to be what facilitate our thoughts, perceptions, and emotions.
Neurotransmitters are therefore widely acknowledged to be crucial to how our brains operate. This is why people who speculate about chemical imbalances say that if there’s a deficiency in these chemicals, this will impair our brain’s functioning. And this is where antidepressants like SSRIs come in: they aim to increase the amount of neurotransmitters sitting in the synapses. And they do this by cutting off what we might call “backflow.”
For example, imagine waves rolling onto a beach. The waves roll in and then out. That’s pretty much how neurotransmitters work: they roll into the synapse, deposit their message in the neighboring neuron, and then roll back out again. What SSRIs try to do is inhibit that rolling-back action, which essentially means that more of the chemical stays in the synapse for more of the time, resulting in higher levels. Different antidepressants target different types of neurotransmitters, but broadly speaking there are thought to be three neurotransmitters that matter most: serotonin and norepinephrine, which are considered most relevant to depression, and dopamine, which is considered crucial for major mental illnesses like schizophrenia.
So that, in short, is the basic neuroscience behind the chemical imbalance theory. Mental illness is caused by irregularities in neurotransmitter levels, which can be altered by psychiatric drugs. The theory is seductively simple and has remained so for now nearly fifty years. But what matters most to us is whether during that entire time the theory has ever been proven correct.
3
Dr. Alec Coppen, the architect of the serotonin theory of depression and thus the intellectual grandfather of one of the most prescribed pills in history—the SSRI antidepressant—was more than happy to help me answer this question when I called him at his home in London in April 2012.
As soon as Coppen started to speak, I felt immediately transported into another era—he had one of those near-extinct 1940s BBC newscaster accents, which betrayed his public school education of the 1930s and the fact that he is now ninety years of age. Coppen is still as active as ever, especially when it came to championing the virtues of the drug Lithium on the telephone (an enthusiasm I could not empathize with, given Lithium’s nasty negative effects and troubled history: in the late 1800s it stopped being used to treat gout because in high doses it was fatal, while in the 1940s it was finally banned from the soft drink 7UP because of its toxic qualities). Nonetheless, I waited while Coppen talked enthusiastically about the drug, until the moment arrived when I could jump in.
“So Dr. Coppen,” I interrupted once Coppen had paused for thought, “do you think Lithium works because it acts upon certain chemical imbalances like serotonin?”
“Eh, yes, I think there’s some serotonin effect,” responded Coppen, noticing I’d changed the subject.
“And since you think Lithium works on these chemicals,” I continued, “do you think this might provide evidence for the chemical imbalance theory? I mean, if drugs increase neurotransmitter levels, and drugs also treat depression, perhaps depression is therefore caused by a deficiency in these neurotransmitters. Do you believe this is so?”
“Well, yes, indeed.”
“So tell me, Dr. Coppen,” I said, now getting to the point, “what would you therefore say to those people who argue that the chemical imbalance theory is still unsubstantiated?”
Coppen went silent for a moment before responding in a way that surprised me. “I think there is a lot of evidence for the theory, actually. I don’t think people are working on it today because it’s generally accepted.”
I was surprised to hear this, because in all my interviews with psychiatrists of different persuasions (from the most humanistic to the most biologically reductionist) this was the first time someone had said they believed there was a lot of evidence for the theory, or in other words that the theory was largely supported. This is not to say that there aren’t people out there who actually believe this. It’s just to say that it’s rare to find anyone who will declare this position openly and without caveats. And there is a plain reason why—the theory isn’t supported. And there are three separate reasons, I heard again and again, that explain as to why.
Number one: The main evidence for the theory is arrived at deductively—because antidepressant drugs like SSRIs increase our serotonin levels, and because antidepressants alleviate depression, depression is therefore probably caused by some kind of serotonin deficiency. Now, although the syllogism is deceptively neat (and therefore remarkably beguiling), critics say it is nevertheless logically flawed. In the first place, it’s clear that antidepressants don’t alleviate depression for the chemical reasons most people believe. As the last three chapters have shown, we can account for a positive effect of an antidepressant largely in terms of its placebo effects, not in terms of its rebalancing chemical imbalances. It is therefore wrong to say the chemical imbalance theory is supported because antidepressants work, since antidepressants probably work for non-chemical reasons.
Number two: Even if antidepressants did work for chemical reasons, critics point out this would still not substantiate the chemical imbalance theory. If my headache feels better when I take some aspirin, I do not conclude that my headache was therefore caused by a deficiency of aspirin in my brain. Arguing deductively in this way is simply poor reasoning. After all, my headache could have been caused by one of many factors—noisy neighbors, a late night, too much wine, and so on. All the aspirin has done is interfere with my capacity to experience my headache, rather than topped up the chemicals whose deficit was its supposed cause.
Now finally to argument number three, the argument referred to time and again as the strongest against the chemical imbalance theory, which goes like this: Despite thousands of studies conducted by researchers who have tried to show that a serotonin or norepinephrine deficiency is responsible for depression, not one has yet been able to provide direct evidence that this is so. For instance, studies of the neurotransmitter norepinephrine say very contradictory things; there are as many concluding that people with depression have high levels of norepinephrine as there are concluding that depressed people have low levels.75 Furthermore, the largest recent meta-analysis of serotonin studies, conducted at the University of Amsterdam, has shown that low serotonin does not act as a depressant because when it was lowered in healthy individuals it produced no decrease in mood at all. As the authors summarized: “Although previously the monoamine systems were considered to be responsible for the development of MDD [major depressive disorder], the available evidence to date does not support a direct causal relationship with MDD.”76
These facts are consistent with earlier studies showing that special drinks that deplete serotonin and norepinephrine levels do not actually produce depressive symptoms (e.g., when depressed people take them, their mood does not worsen; when non-depressed people take them, they remain chirpy; the only slight fluctuation is found in some people who, having recovered from depression, suffered some minor “transient depressive symptoms” but certainly not full-blown depression).77
Research like the above not only challenges the idea that serotonin and norepinephrine are causative agents in mental illness, but is consistent with what research on the third major neurotransmitter, dopamine, also tells us. As the psychiatrist Daniel Carlat summarized:
For years, the going explanation for schizophrenia was the “dopamine hypothesis”; because anti-psychotics block the action of the neurotransmitter dopamine, it seemed reasonable to presume that psychosis must be caused by too much dopamine. You can’t measure dopamine directly in the brain, but you can measure the main byproduct in the spinal fluid. More than a dozen studies have compared levels of dopamine metabolites in schizophrenics … In most studies, there were no differences, and in a few, the levels were lower in schizophrenics, exactly the opposite of what would be predicted by the dopamine hypothesis. Other studies, looking at post-mortem brains or PET scans of living patients, have been inconclusive, partly because most of the patients have already been taking antipsychotics. This means that any alterations found in dopamine receptors are as likely to be an artifact of the medication as they are to reflect the underlying cause of schizophrenia … It is crucial that we realize how much we know and how much we do not know. In virtually all of the psychiatric disorders—including depression, schizophrenia, bipolar disorder, and anxiety disorders—the shadow of our ignorance overwhelms the few dim lights of our knowledge.78
Carlat’s last point is in agreement with a recent and definitive review of all basic antidepressant research published in the New England Journal of Medicine. This revealed that “numerous studies of norepinephrine and serotonin metabolities in plasma, urine, and cerebrospinal fluid, as well as postmortem studies of the brains of patients with depression, have yet to identify the purported deficiency reliably.”79 In other words, and to quote the leading journal The Pharmacological Basis of Therapeutics, the data for the neurotransmitter hypothesis of mood disorder “are inconclusive and have not been consistently useful either diagnostically or therapeutically.”
In recent years such disproving research has begun to erode the profession’s faith in the chemical imbalance theory. This has led increasing numbers of prominent figures in the mental health profession to declare their defection publically. To pique your interest in this sea change, here are a few quotations I’ve managed to gather:
“Many neuroscientists no longer consider a chemical imbalance theory of depression and anxiety to be valid.” (Dr. David D. Burns, Professor of Psychiatry, Stanford University)
“Chemical imbalance is sort of last-century thinking. It’s much more complicated than that.” (Dr. Joseph Coyle, Professor of Neuroscience, Harvard Medical School)
“After decades of trying to prove [the chemical-imbalance theory] researchers have still come up empty-handed.” (Marcia Angell, former editor, The New England Journal of Medicine)
“Despite pseudoscientific terms like ‘chemical imbalance,’ nobody really knows what causes mental illness. There’s no blood test or brain scan for major depression.” (Dr. Darshak Sanghavi, clinical fellow, Harvard Medical School)
“We do not know the etiology of really any of the mental disorders at the present time.” (previous Director of Research, American Psychiatric Association)
“Research has yet to identify specific biological causes of any of these [mental] disorders.” (US Congressional Report entitled “The Biology of Mental Disorders, New Developments in Neuroscience”)
“The results of decades of neurotransmitter-depletion studies point to one inescapable conclusion: low levels or serotonin, norepinephrine, or dopamine do not cause depression.” (Professor Irving Kirsch, Harvard Medical School)
“We still don’t know the relationship between biology and the mental disorders.” (Carol Bernstein, previous president of the American Psychiatric Association)
“Patients have been diagnosed with chemical imbalances, despite that no test exists to support such a claim, and that there is no real conception of what a correct chemical balance would look like.” (Dr. David Kaiser, Psychiatric Times)
“As a scientific venture, the theory that low serotonin causes depression appears to be on the verge of collapse. This is as it should be; the nature of science is ultimately to be self-correcting. Ideas must yield before evidence.” (Dr. Jonathan Rottenberg, Psychology Today)
“A simplistic biological reductionism has increasingly ruled the psychiatric roost … [we have] learned to attribute mental illness to faulty brain biochemistry, defects of dopamine, or a shortage of serotonin. It is bio-babble as deeply misleading and unscientific as the psycho-babble it replaced.” (Andrew Skull, Professor of History of Psychiatry, Princeton University, Lancet)
There is no point piling up more quotations. By now you get the picture: the public defections continue because after nearly fifty years of investigation into the chemical imbalance theory, there is not one piece of convincing evidence that the theory is actually correct.
So if the chemical imbalance theory is now on its knees, where can psychiatry go from here? In what biological substrate can it now locate the causes of mental disorder? Perhaps the fascinating discoveries of genetics can lead the way out of the current impasse? Let’s have a look at the evidence.
4
Up until about ten years ago, if you were studying any of the social sciences at university you’d have likely encountered a question like the following in an examination: What primarily determines whom you become—your nature or how you are nurtured? In other words, are you a product of your inherited biology or the environment in which you were raised?
Ten years ago, if a student had taken a forceful side in this debate, it is possible he might have still received top marks. This is because a decade ago the academic community was still at war over this issue, making an either/or answer intellectually possible. Today, however, the situation has changed. Given the huge advances in genetics over the last ten years, the scientific community has had to fundamentally revise its position. It now broadly accepts that it is virtually impossible to understand how our biology works outside the context of our environment. This has seen the either/or debate retreat to the wings, and bio/social complexity assume center stage.
To put the new genetics in the simplest terms (which, I have to say, isn’t easy), virtually no neurological disorders or psychological problems have been demonstrated to result from the mutation of a single gene. Rather, they are now known to involve molecular disturbances that implicate multiple genes and the signals that control their expression.80 In other words, the popular idea that so-and-so gene causes so-and-so mental trait has been surpassed by the notion that it is interactions between our genes and their environment that actually shape us. This is because we now know there to be thousands of molecules attached to our DNA that can literally turn our genes on and off. These molecules, or “epigenetic markers” as they are more technically known, actually alter and develop as an individual adapts to his or her environment.
Dr. Nessa Carey, a former Senior Lecturer in Molecular Biology at Imperial College, London, summarizes this new genetics for me rather well: “We have our set of genes, but those genes can be switched on or switched off, and they can be switched on to higher or lower volume levels depending on the environmental stimuli. And epigenetics is a bit like the volume control on an MP3 player. Your MP3 player contains the tracks that you have loaded onto it, the ones you choose to play and how loudly you choose to play them, that’s controlled by epigenetics.”
The equation this new idea obliges us to embrace therefore runs something like this: because our environment affects these molecules, and because these molecules can turn our genes on or off, the environment can no longer be seen as irrelevant to how our genes determine our functioning and development.
Studies of rats have illustrated this point well. Baby rats born to mothers that displayed little affection (that licked their pups rarely) were given to foster mothers that were very affectionate (that licked them a lot). After dissection, it was clear that the affectionately raised rats had brain characteristics different from those receiving little affection: affectionately raised rats possessed more receptors in the neurons of their hippocampus—receptors that are considered crucial stepping-stones in slowing down the production of stress hormones. It turns out that a stretch of DNA serving as a switch for a gene related to these neural receptors had been suppressed in the less–affectionately raised rats. This meant that the rats receiving less affection (fewer licks) were far more stressed as adults than those that had received more. The conclusion is that adult personality differences related to stress weren’t determined by genes inherited from their biological mothers, but were an outcome of how they were raised as pups.81
The same groups of researchers performed a related study of human beings. This involved analyzing the brains of thirty-six people postmortem. Twelve of these people had died of natural causes, while the rest (twenty-four) had committed suicide. And of the twenty-four suicide victims, twelve of these had been abused as children, whereas the other twelve had not. When the brains of these three groups were compared, the group that had suffered childhood abuse again stuck out. People in this group shared the same pattern of fewer receptors linked to stress hormones, as those found in the non-affectionately raised mice. Their brains, via epigenetic changes, had reacted to the environmental abuse—leading them to grow in a direction different from brains receiving environmental care.82
Studies like these show that genes can be “switched on or off” by molecules that are themselves altered by environmental factors.83 We know, for example, that there are two genes strongly associated with hereditary breast cancer (BRCA1 and BRCA2). But we also know these genes are responsible for only about 10 percent of all breast cancers (and that only about a further 10 percent to 20 percent of breast cancers are related to any kind of gene or variant). This means that most women who develop breast cancer may not be hereditarily disposed to do so.84 But even if they are hereditarily disposed, it also means they won’t necessarily develop the condition. As the American Society for Clinical Oncology (ASCO) asserts, a woman with a 75 percent chance of developing breast cancer may remain perfectly healthy, while a woman with a 25 percent chance of developing breast cancer may eventually develop the disease.85 Again, the presence of the relevant gene alone is not enough to account for the disease’s onset. The environment influencing epigenetic factors play a crucial role.
The complexity of the new genetics makes those who have accepted the old genetic reductionism seem flatly out of date. I remember giving a talk some years ago at a seminar at Oxford University’s John Radcliff Hospital. At one point I said that many mental health professionals regrettably used simplistic genetic reductionism to avoid the complexity of thinking through the various social, economic, and environmental factors influencing who we are, what we do, and who we become.
At the end of my talk a senior psychiatrist approached me, looking none too happy. “James, you’ve got it wrong,” he said curtly and authoritatively. “I have patients who are absolutely convinced their troubles are genetic, and who believe any intervention ignoring this is a complete waste of time. And most of these patients are right, especially if there is a history of depression in their family.”
I remember replying that a history of family depression proves nothing definitively—perhaps the family atmosphere or culture passed on over generations was the corrosive factor. I also said that reductionist beliefs often breed a destructive attitude in many patients, leading them to think, as one of my patients put it, “As my mother and grandmother had depression, I figure I’m biologically doomed to follow them.” This kind of fatalism, I responded, is not only scientifically unjustified but is potentially psychologically damaging—it makes people believe that no matter what they do, they are biologically doomed to suffer.
After making my points, this particular psychiatrist merely sighed and shook his head. “Well, James, for me most cases of depression have clear genetic markers, and even if science can’t show this yet, it will do so in the future.”
Statements like these are unhelpful and betray a now-discredited way of thinking that dominated genetics over fifteen years ago. Back then there was great anticipation of finding singular gene mutations to account for most emotionally or cognitively related problems. This was inspired by a few interesting discoveries related to what are now known as the organic brain diseases. Perhaps the best-known example is Huntington’s disease. This is caused by a gene carried on Chromosome 4 that destroys brain cells on the frontal lobes, leading to impairments in cognitive functioning. But these clear-cut cases in the realm of mental health are very much the exception.
Most genetic influences on disease are greatly more complicated than those early pioneers of the genome project could have dreamed. For instance, in the realm of psychiatry there is no known gene or clear genetic variants for around 97 percent of all the mental disorders now contained in the current DSM and ICD. And even where genes may be implicated, in disorders like bipolar disorder and schizophrenia, research now reveals such mind-boggling complexity that nothing definitive can be said. A researcher who scanned the genetic sequences of twenty thousand normal people and then compared them with the sequences of ten thousand patients diagnosed with schizophrenia, for example, found that more than ten thousand different gene variants could have a role in the onset of schizophrenia. Furthermore, this study did not take the findings of epigenetics into account (the environmentally susceptible molecules that interfere with these genetic variants).86
Of course, there have been periods of great excitement. In 2003, for example, a study was published in the journal Science in which the researchers asked why stressful experiences lead to depression in some people but not in others. After analyzing 847 patients over time, the researchers found that those who had one or two copies of a gene variant that interfered with serotonin transport were three times as likely to develop depression if subjected to certain stressful life events, like losing a job or getting divorced. This study was thought to provide evidence of a gene-by-environment interaction, in which an individual’s response to environmental stresses is moderated by his or her genetic makeup.87
This finding generated a great deal of excitement until another study, published a few years later, failed to replicate these findings. The researchers in this next study assessed over fourteen thousand people via a meta-analysis of fourteen studies. But the conclusion that was reached dampened the previous excitement: “This meta-analysis yielded no evidence that the serotonin transporter genotype alone or in interaction with stressful life events is associated with an elevated risk of depression in men alone, women alone, or in both sexes combined.”88
Nobody wants the efforts of geneticists to be frustrated. We all desire scientists to succeed and lead us out of the dark. But given the developments in fields like epigenetics (not to mention the disappointments brought about by non-replicable findings), all we can do today is embrace a position thoroughly littered with caveats. It goes something like this: where genetics play a role in our mental lives, they do so via a given, yet-defined, constellation of genes that may predispose a person to an unknown degree of vulnerability to developing a given form of mental distress if other social or psychological conditions trigger it, and if environmentally influenced epigenetic factors permit it. Such tentativeness is now slowly trickling through to the mental health establishment, as can be seen from the World Health Organization’s (WHO) recent official statement on the causes of depression:
Depression is a complex disorder which can manifest itself under a variety of circumstances and due to a multiplicity of factors … biological (genetic and biochemical), sociological (stressors), and psychological (development and life experiences) factors interact to produce a picture of depression. Research during the last fifty years indicates that there is no single factor which can explain the cause for depression.89
The WHO does not say genes or biochemical imbalances cause depression. All it says is all anyone can say: of course our biology is implicated in mental distress, just as it is implicated in any emotional, physical, or mental state that is experienced as either positive or negative. But precisely how it’s implicated, and precisely to what degree, we do not as yet really know. As long as we are alive, the things we feel, see, and think can affect our brains. But today exceedingly little is known about what the effects may be, so it is possible that little or nothing of our emotional suffering actually originates in the brain.
5
“The problem, you see,” said David Oaks as he once again recalled his hunger strike, “is that there is no proof for the things we were told: that our problems were due to brain-based diseases. And this is why the APA ducked our requests. It couldn’t scientifically justify what we were led to believe as patients.”
“Do you think that patients today are receiving the same message you heard long ago?”
“I don’t think, I know,” said Oaks decisively, “and this is misleading a lot of people into believing that only bio-psychiatry can offer a way out.”
If we therefore accept that the biological myth of mental disorders is overplayed and oversold in psychiatry, the question follows as to why this may be. I believe if we have any hope of reaching an answer, it is necessary that we move away from psychiatry momentarily in order to investigate one of the most powerful industries in contemporary society: the pharmaceutical industry. What precise role has that industry played in promoting the biological theory of mental distress and for what end? Furthermore, who has that promotion really benefited—patients, psychiatry, or the industry itself?
To those thorny questions I now turn.