New research bolsters the idea that the risk for psychiatric and developmental disorders isn’t specific to particular conditions — and that could mean new opportunities to treat mental illnesses that focus more on their common genetic roots.
Mental illnesses like depression and schizophrenia clearly run in families, but neuroscientists have always assumed that the biological drivers behind these disorders were distinct. However, expanding on results reported earlier this year from psychiatry’s largest ever experiment, researchers now report that known genetic variations account for 17% to 29% of the risk for schizophrenia, depression, bipolar disorder, autism and attention-deficit/hyperactivity disorder (ADHD). And risk for one condition is often strongly linked with risk for others.
Published in Nature Genetics, the study was funded by the National Institute on Mental Health (NIMH) and involved collaboration between nearly 400 scientists in 20 countries working with genetic data from some 59,000 people.
Studying gene-based differences among the patients and in people who did not have mental illnesses, the scientists detailed with unprecedented precision how groups of the same genetic mutations could be linked to different mental illnesses. Bipolar disorder and schizophrenia were most highly correlated — a finding that jibes with both earlier research and the fact that the conditions can sometimes be mistaken for each other in the clinic. The latest data suggests that seemingly disparate symptoms — patients with bipolar experience extreme mood swings, while people with schizophrenia often suffer from delusions and paranoia — may not necessarily derive from different genes, but rather from different timing of exposures to risk factors, such as toxins or infectious disease during pregnancy, or early life trauma.
“It has long been hypothesized that psychiatric disorder diagnoses are superimposed onto an underlying spectrum,” says lead author Naomi Wray, associate professor of statistical and psychiatric genetics at the University of Queensland in Australia, referring to the idea that the same genes can produce different symptoms in different circumstances. “Our results provide direct empirical support for this.”
“We thought these were completely distinct diseases,” says Bruce Cuthbert, director of the division of adult translational research and treatment development at NIMH, explaining that the idea of a distinction between bipolar and schizophrenia has been a core part of psychiatry for over a century. But now, he says, “We’re gradually seeing that these are, in fact, highly related conditions and only appear different from the surface symptoms.”
Some of the connections were less obvious. While bipolar and schizophrenia were the most strongly linked, and bipolar and depression were moderately linked (not surprisingly), the association between depression and schizophrenia was almost as strong as that between bipolar and unipolar depression. Prior studies had suggested the possibility that these conditions tended to occur in families, but since living with a severely mentally ill relative can be stressful and contribute to depression, it seemed more likely that such environmental reasons explained the connection rather than any inherited mutations.
The new results offer support for a new approach to diagnosis that NIMH’s director Dr. Thomas Insel announced in May. Noting that the current system hasn’t been particularly fruitful in generating new treatments, Insel said the agency would be moving away from funding research projects based on Diagnostic and Statistical Manual of Mental Disorders (DSM) categories, which classify disorders simply by noting clusters of symptoms. This often results in people carrying multiple diagnoses, since, for example, obsessive focus can be a symptom of both autism and obsessive-compulsive disorder and a lack of pleasureful emotions can be a symptom of depression, bipolar disorder or schizophrenia.
Instead, the new Research Domain Criteria systems will look for the genetic roots of individual symptoms. That should reduce multiple diagnoses and improve genetic research by narrowing it down to specific problems with particular brain systems. And that could open up new ways of thinking about and treating mental disorders that may seem disparate in the clinic but actually share biological roots. If Grandma’s schizophrenia and Uncle John’s depression are caused by the same combination of genes affecting the brain’s motivational systems, it may be possible to target this system early to prevent John Jr. from ever becoming ill.
When the latest version of the manual, DSM-5, was issued in May, Insel told TIME, “We know that the DSM approach is not the way to understand these disorders. It may be a way to bill for them, but it’s not a way to develop science or even identify who should get what treatment.” The latest genetic findings suggest he may be right, and if mental disorders share more in common than previously thought, that could mean that more people might benefit from more targeted use of existing treatments as well, which is good news for those affected by some of the most devastating disorders in medicine.