These days, we are increasingly aware that mental health problems can be as debilitating as physical ones. Unfortunately, much of what we thought we knew about what causes mental illness has recently turned out to be wrong.
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In a way, this shouldn’t be surprising, says Allen Frances at Duke University in North Carolina, lead author of a major US psychiatry textbook, the Diagnostic and Statistical Manual of Mental Disorders IV. “The brain is the most complicated thing in the known universe, and it reveals its secrets very slowly,” he says.
A couple of decades ago, we seemed on the verge of unlocking the secrets of several mental health conditions. The cause was thought to be irregular levels of various brain chemicals, which could be remedied with drugs. Depression, for example, was thought to stem from a lack of the brain signalling chemical serotonin, partly because the most common kind of antidepressants raise levels of this compound. Genetic studies also found that people with depression were more likely to have a gene variant that lowers serotonin. Schizophrenia was thought to be caused by excess activity of circuitry involving a different brain chemical, called dopamine.
But this neat picture turned out to be a mirage. The latest evidence suggests that low serotonin isn’t a cause of depression, and many early genetic studies that implicated single brain chemicals as a cause of specific conditions were carried out using scientific methods now considered to have been flawed.
Mental health conditions do have a strong heritable component. For instance, someone whose identical twin has schizophrenia has about an 80 per cent chance of developing the condition themselves. But the genetics are complex. The most recent genetic studies show that more than 100 gene variants influence our risk of depression, for example, each with only a tiny impact.
Genes and mental illness
Every other mental health condition investigated so far is similarly influenced by multiple genes. And many of the same genes are involved in predisposing people to what are usually thought of as very different conditions, including depression, anxiety, bipolar disorder and obsessive compulsive disorder. “We’ve given up on a small number of genes explaining any mental illness,” says Frances.
The genetic revelations have lent support to a recent idea that, rather than being a set of discrete entities, all mental health conditions may have their roots in a common underlying cause, sometimes called the “p factor”. The idea is that these gene variants together make the brain more vulnerable to mental illnesses. Perhaps which condition someone develops depends on different external triggers or even chance events.
What that vulnerability may consist of isn’t clear. In April, a large brain-scanning study suggested it could be down to insufficient “pruning”, the process of getting rid of unhelpful connections between brain cells, which begins in early childhood but intensifies in adolescence. “It’s a single underlying neurobiological factor,” says Barbara Sahakian at the University of Cambridge.
This is unlikely to be the final word, though, especially as brain-scanning studies have a long history of producing divergent results that even experts can’t agree on. Perhaps the most important thing to understand about mental illness, then, is how much we have yet to understand.
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