Supposedly distinct psychiatric conditions may have same root causes

An analysis of gene variants in more than a million people diagnosed with neurodiversity and mental disorders—by far the largest study of its kind to date—found that 14 conditions typically thought of as separate actually fall into five major genetic groups.

This discovery is encouraging for those Diagnosed with several mental illnessesspeaks Andrew Grotzinger from the University of Colorado Boulder, a member of the research team that conducted the analysis. According to him, people feel that this means something is wrong with them, but there can only be one underlying reason.

“For the millions of people who are diagnosed with multiple mental illnesses, that means they don't have a lot of different things,” Grotzinger says. “I think it’s very important for the patient to hear that.”

When biologists began looking for genetic variants associated with a higher likelihood of developing a range of mental illnesses, they expected to find different variants for each. Instead, it became clear that there are many coincidences. Some researchers have even suggested that all such conditions have a single underlying causecalled the p-factor.

The latest research suggests that reality lies somewhere in between these two extremes. This doesn't provide much support for the p-factor idea: While some gene variants are associated with all 14 conditions, they are involved in underlying processes that cause many different problems beyond mental illness when they go wrong, Grotzinger says.

On the other hand, the team also found relatively few variants associated with a higher risk of just one disease. Instead, the variants tended to fall into five groups, with particularly high overlap between schizophrenia and bipolar disorder, and between major depression, post-traumatic stress disorder and anxiety.

Many of the variants associated with schizophrenia and bipolar disorder were in genes active in excitatory neurons, which make other neurons more likely to fire, while many of the variants associated with depression, post-traumatic stress disorder and anxiety were in genes active in oligodendrocytes, the cells that produce the myelin sheaths around nerves.

Three other groups that Grotzinger and his colleagues identified were: ADHD and autism; OCD, anorexia nervosa and Tourette's disease; substance use disorders and nicotine dependence.

The findings may help explain why two-thirds of people diagnosed with a mental illness will be diagnosed with more than one during their lifetime. This can also be taken as evidence that diagnostic criteria “The ones used by psychiatrists are wrong,” Grotzinger says.

“If you went to the doctor and had a runny nose, cough and sore throat, you wouldn't want to be diagnosed with a runny nose, cough and sore throat. You would want to be diagnosed with a cold,” he says.

“We give separate labels to things that are biologically inseparable,” Grotzinger says. “But other doctors might argue that while the genetic differences are small, these things require different treatments.”

Clinicians also tend to think there is a “right” diagnosis for every person, Grotzinger says. “People may treat these diagnostic manuals like religious texts.” However, the degree of genetic overlap found in the new study suggests there is often no single correct diagnosis.

“This is an impressive article,” says Avshalom Kaspi at Duke University in North Carolina. “Many mental disorders are not isolated disorders, but share common pathways that affect neurodevelopment, cognition and emotion. This is now increasingly appreciated.”

Researchers should no longer study conditions in isolation, says Terry Moffittalso in Duke. “Funders should be much more careful when awarding grants to researchers who study one disorder at a time to avoid losing significant research resources.”

However, Moffitt believes the study is based on mental health data collected using outdated methods. People should be followed for longer periods of time to obtain more accurate data for genetic analysis, she said.

As Grotzinger and his colleagues acknowledge, the study was also largely limited to people of European descent because there was insufficient data from other groups.

Grotzinger also says we still know too little about the impact of these gene variants to begin to apply this knowledge – for example, to screening embryos during IVF. a process that raises ethical questions.

“We're getting closer, but we don't know exactly what these genes do,” he says. “It’s not that I think embryo screening is wrong; It’s bad scientifically.”