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From darkness to darkness: the search for the biological basis of mental illness

Psychiatry always thinks it’s on the verge of understanding and curing mental illness, but its real history is a story of torturers and frauds, a new book shows. Danyl Mclauchlan reviews Mind Fixers by Anne Harrington.

If you visit your GP and tell them you have the symptoms of a mental illness – maybe your mind is constantly racing, or you can’t sleep, or perhaps you want to sleep all the time; maybe you keep thinking about hurting yourself, or you always feel sad, or angry or exhausted, or don’t ever seem to feel anything; maybe you have delusive thoughts, or hear voices, or your mood cycles from delusional highs to crippling lows – it’ll seem like a normal appointment. Most GPs hear similar complaints on a routine basis. They’ll listen, make a diagnosis and probably prescribe a medication. It’s just like presenting with the symptoms of diabetes, or asthma, or high blood pressure, or any other physical illness.

What’s very different, but not obvious to the patient is that most GPs have a pretty good understanding of the biology behind high blood pressure, diabetes, etc. They also have a rough grasp of the mechanism of action behind the medications they prescribe to treat them (although some physicians are bigger pharmacology nerds than others). And if your disease is complicated or resistant to treatment they can refer you to a specialist, who’ll have a very sophisticated understanding of the pathology of the disorder and how your treatment works (although they may lack the social skills to explain any of it to you). Even if you have an incurable cancer they still know what’s wrong with you; they just can’t treat it.

None of this is the case if you present to your doctor, or a psychologist or psychiatrist, with symptoms for depression or anxiety or bipolar disorder. None of these experts have the slightest understanding of the biology of how these disorders work, or what causes them, because nobody does. Nor is there any consensus on why the various classes of medication – SSRIs, monoamine oxidase inhibitors, lithium, anticonvulsants – treats them; or, as is often the case, why they treat some people but not others, or why they treat some people for a while and then stop working, or why some people discontinue the drugs effortlessly while others suffer terrifying discontinuation symptoms. Nobody knows.

Most disease symptoms point to an underlying disorder that you can verify via clinical diagnostics: you can do a blood test, or a urine sample or an x-ray and look for broken bones or other biomarkers. With mood disorders, symptoms are all we have. It isn’t clear if anxiety and bipolarity and depression are symptoms of many different disorders, or one single disorder, or spectrums or combinations of disorders, or even if they’re disorders at all.

(Some people worry that if they reveal such symptoms then their doctor will have them committed to a psychiatric institution but this is definitely not something you need to worry about: our streets and prisons are filled with homeless people suffering from acute mental illness. There’s no way the public mental health system has the funding to hospitalise you.)

A Rorshach test, created by German psychiatrist Hermann Rorschach, 1921 (public domain)

Most popular science histories are progressive, optimistic: voyages from ignorance into light. They start in the bad old days, when we didn’t understand natural selection or general relativity or the germ theory of disease and gradually lead to the happy and enlightened present, checking in with various eccentric geniuses and Nobel Prize winners along the way.

Anne Harrington’s Mind Fixers, a history of modern psychiatry, focusing on the search for the biological basis of mental illness, is very much not in this tradition. It’s a journey from darkness to darkness, punctuated by many false dawns. Psychiatry always thinks it’s on the verge of understanding and curing mental illness: there’s always a new paradigm, new categories of diagnosis, new miracle treatments and public health policies which, on further investigation turn out to be dubious if not downright fraudulent, but which always earn psychiatrists (and, increasingly their allies and generous benefactors, the multinational pharmaceutical companies) a lot of money and intellectual prestige before the debunking years or decades later.

Harrington is a chaired professor of history of science at Harvard University. Her book is more of a history than a science book: the science is mostly pseudoscience and the history is relentlessly grim. She begins in the mid 19th century, as Europe and the US experienced a vast and inexplicable surge in mental illness. (Every new generation for at least the last 170 years sees itself as the subject of a mental health crisis, and every generation of social scientists fabricates dubious but fashionable theories to explain it all.)

In the 1850s the default explanation for mental illness was moral failure, caused by promiscuity, gambling, drinking, atheism and so on, but as the asylums filled then overflowed, psychiatrists and neurologists wondered if there was a physical basis for their patients’ conditions and began dissecting the brains of their deceased inmates, looking for answers.

There is a modern, consensus-based history that the psychiatric industry tells itself about their own profession. It’s a progressive optimistic story, ie the polar opposite of Mindfixers, in which this late 19th century turn to biology was the moment psychiatry became a real science. The biologists examining and dissecting brains were on the right track, this folk history goes, until a palace coup by Sigmund Freud and his admirers derailed the practice of psychiatry for much of the 20th century, hijacking it with nonsense about penis envy and oedipal complexes and dream interpretations. The 1980s saw the decline of the Freudians and the return of scientific psychiatry, in which mental illness was finally understood as a ‘chemical imbalance’, a mere problem of malfunctioning neurotransmitters, which could be cured by the newly discovered antidepressants and antipsychotic drugs that are still widely prescribed today.

Harrington’s mission is to complicate this overly neat history. The first problem with the folk story, she explains, is that most of the theories and treatments of the pre-Freudian ‘scientific’ psychiatrists looked less like science or medicine, and more like indiscriminate torture. This was the psychiatry of ice baths, insulin comas and malaria therapy (I’d never heard of this: asylums deliberately infected mentally ill patients with malaria in the hope that the fever would cure them. Then they’d cure the malaria, mostly. About 15% of patients died, and some patients were kept perpetually infected so that the hospital had a reservoir of the microorganisms to draw from.)

This was also the psychiatry of lobotomies, in which thousands of ‘surgical procedures’ were performed with picks, penetrating the brain via the eye socket and causing enough damage to the patient’s prefrontal cortex to ‘cure’ them. It was the psychiatry of indiscriminate electro-shock treatment delivered indiscriminately and without anaesthetic or consent (ECT is still used sometimes – with anaesthetic and consent – as an effective treatment for drug resistant depression).

And it was also the psychiatry of selective eugenics. Many forms of mental illness seem to be hereditary, and the logical conclusion early 20th century psychiatrists drew from this was that the cure for mental illness was compulsory sterilisation. “Three generations of imbeciles are enough,” the US Supreme Court decided when ruling in favour of the compulsory sterilisation of an eighteen year old girl who became pregnant after being raped, and whose mother was already committed to the Virginia State Colony for Epileptics and Feebleminded (“feeblemindedness” was a catch-all phrase, encompassing everyone from shoplifters to developmentally disabled children to promiscuous women).

Over 60,000 people were forcibly sterilised in the United States over the course of the 20th century. It was seen as an enlightened, progressive policy, supported by most reasonable, intelligent, educated people. Was it not ending poverty and mental illness? The National Socialist government in Germany agreed and imitated the programme, beginning with forced sterilisation of the mentally ill before scaling up to their euthanasia, eventually expanding the operation to the mass murder of anyone suspected of diluting the purity of the nation’s racial health.

The turn away from biological science to Freudian psychiatry wasn’t that baffling, is Harrington’s point here, and the mid-century discrediting of biological psychiatry was well earned. But that’s not to say that the rise of the Freudians was a good thing. It was mostly horrible, but horrible in a different direction.

Austrian psychoanalyst Sigmund Freud leaves Victoria Station after his arrival in London, 6 June 1938. (Image: AFP/Getty Images)

Freud himself was not overly concerned with motherhood. He understood that women had children out of a sense of inferiority to compensate for their lack of a penis: that much was obvious to him. But the Freudian School’s famous obsession with mothers was primarily a post-war phenomenon. During the war psychiatrists played a key role in military recruitment, rejecting almost two million young men for ‘neuropsychiatric’ reasons, but after the war they found over a million soldiers who saw active duty suffered from severe psychological problems – what we’d now refer to as post-traumatic stress disorder.

This was probably the fault of their mothers, the psychiatrists concluded. Overprotective women who coddled their children were bad. Neglectful and unloving mothers were worse. But the worst mothers of all were the dreaded ‘schizophrenogenic mothers’: mothers who were midway between being neglectful and overprotective. These women were responsible for the acute outbreaks of schizophrenia and homosexuality (a “sociopathic personality disorder” according to the first Diagnostic and Statistical Manual of Mental Disorders, or DSM, published in 1952, reclassified as a form of sexual deviance analogous to pedophilia in the 1968 DSM before being removed in 1973) sweeping the US during the 1940s and 50s. Leading psychiatrists sternly warned mothers that they were a grave danger to national security: they were undermining America’s ability to defend itself against Communism.

Schizophrenia was a very vague yet all-encompassing diagnosis. Difficult children had ‘childhood schizophrenia’, especially those who avoided eye-contact, or had trouble parsing the emotional cues of those around them. Wives who didn’t want to have sex with their husbands or who didn’t want to get married at all might be schizophrenic, but immoral and immodest young women might also be schizophrenic. Being unpatriotic was a potential symptom. Depression and anxiety weren’t classified as separate disorders under the reign of the Freudians. Instead they were symptoms of schizophrenia, symptoms indicating that the person’s ‘psychic energy’ had been damaged, almost certainly by their mother.

The cure was generally lifelong institutionalisation accompanied by stern lectures to the families whose poor parenting had driven their children insane. Sometimes patients were treated with Freudian psychoanalysis: dream interpretations, Rorschach blots, free association, repressed memories and so on. Of course none of this ever cured anyone. Mostly those who’d been committed lived and worked at their asylums until they died. Or until the asylums closed down.

A Rorshach test, created by German psychiatrist Hermann Rorschach, 1921 (public domain)

In January of 1973 the psychologist David Rosenhan published an article in Science, one of the world’s most influential academic journals, titled ‘On Being Sane in Insane Places’. He’d conducted an experiment in which eight people (including himself) presented to twelve different psychiatric hospitals across the US, complaining of audible hallucinations: the words they claimed to hear were specifically chosen because they didn’t correspond to anything in the published literature linking them to psychotic symptoms. They were all diagnosed with either schizophrenia or ‘manic depressive psychosis’ and committed. Upon admission they started behaving normally and taking notes about the environment, in such an overt manner that their fellow patients accused them of being professors or journalists checking up on the hospital. At no point did any medical staff suspect they were not mentally ill. Eventually they were all discharged with a diagnosis of ‘schizophrenia in remission.’

Rosenham’s article ended with a story about a well regarded teaching and research hospital that had heard of his study and challenged him to send pseudo-patients to them, confident that they could detect such imposters. Over a period of several weeks they identified 41 individuals whom they diagnosed as sane but pretending to be mad. Rosenham had not actually recruited anyone for this study: these were genuine patients, 41 false negatives. Another critic of psychiatry, Thomas Szasz, made the point that none of this looked remotely like medicine. What psychiatrists seemed to do was identify people who behaved in unusual, socially unorthodox ways and declare that they were ‘sick’, and therefore in need of confinement and treatment, which they applied whether the patient wanted to be treated or not. Psychiatrists seemed to be violating the basic civil rights of their patients on an astonishingly vast scale.

It was all in the name of science, but none of it seemed very scientific. Studies into the accuracy of clinical diagnosis in Freudian psychiatry showed that different doctors examining the same patient only matched their diagnosis 30% of the time. The profession was further discredited by a series of journalistic exposes revealing the horrific conditions of many mental institutions and the systemic abuse of patients imprisoned in them.

At the same time, new drugs developed by the pharmaceutical companies in the 1950s and 60s were proving far more effective at treating people suffering from schizophrenia, bipolar disorder and depression: which were looking more like different disorders, all with a very strong hereditary basis and nothing to do with toxic mothers or psychic energy. The new drugs targetted neurotransmitters – tiny chemical messengers between brain cells – and they functioned by regulating the amount of a given neurotransmitter in the brain, which pointed at a biological explanation for the nature of mental illness: these disorders were obviously caused by an imbalance of these chemical messengers, which the medications then treated.

The new drugs drove new categories of diagnosis. Depression, previously seen as a symptom of other forms of mental illness, was quickly redescribed as a separate illness in its own right and also, suddenly, a very widespread one ‘as common as the common cold’. It could be treated by a class of drugs known as SSRIs: selective serotonin re-uptake inhibitors, a name which tells a neat little story about chemical imbalance and the mechanism of the medication that fixes it.

The mass confinement of mental health patients had been a public health disaster. It was also very expensive. Given that the new antipsychotic drugs and mood stabilisers were so effective and safe – or so the companies manufacturing them assured everyone – public health officials convinced themselves that closing the hospitals and releasing the mentally ill back into the community was best for everyone. It was a solution that worked well for those who responded well to the new medications, and/or had families to return to, and/or who could manage their illness themselves. Many of those who fell through these very large cracks wound up in the prison system, which quickly became the new de facto mental health system.

The 21st century has not been kind to the scientific credibility of biological psychiatry. The ‘chemical imbalance’ of mental illness theory was debunked in the 1990s. If depression is an imbalance of serotonin, why do SSRIs treat some people with depression but not others? How does bipolar disorder make sense under the chemical imbalance paradigm? There’s no consensus around what new paradigm might replace it, outside a general agreement that most mental illness is probably due to a fiendishly complex combination of genes, biochemistry and environment interacting in mutually reinforcing feedback loops.

The antidepressants that were the mainstay of the old theory clearly treat some patients very effectively: they literally save lives. But when studied at scale their effect size – the ability to distinguish them from placebos administered in randomised double-blind trials – are close to clinically insignificant. Some of the meta-studies (not cited by Harrington but easy to find once you search the clinical literature) suggest SSRIs are good at treating some people with moderate to severe depression, but that they’re massively over-prescribed by medical professionals and that this dilutes their apparent efficacy when examined in clinical trials.

In 2006 the New York Times published an exposé of the drug company Eli Lilly, and their marketing strategy for a drug they’d developed called Zyprexa. This was originally developed as a schizophrenia medication, but you couldn’t get rich by treating schizophrenics – there just aren’t enough of them – and the company’s patent on Prozac was due to expire. So it conspired to market the new drug to psychiatrists and primary care physicians as a cure for depression, dementia, insomnia, moodiness, irritability and insomnia, while at the same time concealing the data from their clinical trials linking the drug to obesity, high blood sugar and diabetes.

This came after a wave of related scandals in which pharmaceutical companies were caught hiring marketing companies to fabricate patient advocacy groups to raise awareness of mental health conditions that didn’t exist until the company invented drugs to treat them, then lobbied psychiatrists to begin diagnosing the manufactured condition. (Every lazy/gullible journalist in New Zealand who’s run the drug companies’ attack lines against Pharmac should be forced to read the last hundred pages of this book to see what happens if you don’t have a centralised drug buyer for your health system and the pharma companies get to lobby doctors and health bureaucrats directly.)

But by the 2010s Big Pharma, still reeling from these exposes and massive class action suits, is an industry in retreat from large scale mental health research. There are still no biomarkers, no objective diagnostics for mental illness. Cancer is where the real money is. Now mental health patients and physicians play a game, Harrington argues. The patient presents to their doctor with acute mental or emotional distress; doctors look for a diagnosis among the existing categories that might make sense, then prescribe a drug because that’s what’s available. Sometimes the drugs work, and given the potency of the placebo effect in mental health treatments, even it doesn’t ‘work’ it often cures people anyway.

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Two of the final quotes in the book come from high ranking members of the psychiatric priesthood, summing up the current state of the science. This first is Thomas Insel, a former director of the US National Institute of Mental Health for 13 years, who wrote:

“I spent 13 years at NIMH really pushing on the neuroscience and genetics of mental disorders, and when I look back on that I realize that while I succeeded at getting lots of really cool papers published by cool scientists at fairly large costs – I think $20 billion – I don’t think we moved the needle in reducing suicide, reducing hospitalizations or improving recovery for the tens of millions of people who have mental illness.”

And in 2016 the psychiatrist Shekhar Saxena, director of the World Health Organisation’s mental health unit, remarked that if he was diagnosed with schizophrenia he’d prefer to live in Addis Ababa in Ethiopia, or Colombo in Sri Lanka, where he could live as a productive if eccentric member of the community, as opposed to New York or London, where he’d be stigmatised and relegated to the margins of society.

Mind Fixers: Psychiatry’s Troubled Search for the Biology of Mental Illness, by Anne Harrington (Norton, $43)


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