Multiple Mental Health Woes? Blame It on Genetics

Different psychiatric disorders often share the same genetic architecture, which may help explain why many individuals diagnosed with one psychiatric disorder will be diagnosed with another in their lifetime, new research suggests.

Investigators conducted a genetic analysis of 11 major psychiatric disorders, including schizophrenia and bipolar disorder.

"Our findings confirm that high comorbidity across some disorders in part reflects overlapping pathways of genetic risk," lead author Andrew Grotzinger, Department of Psychology and Neuroscience, University of Colorado at Boulder, said in a press release.

The results could lead to the development of treatments that address multiple psychiatric disorders at once and help reshape the way diagnoses are established, the researchers note.

The findings were published online May 5 in Nature Genetics.

Common Genetic Patterns

Using the massive UK Biobank and the Psychiatric Genomics Consortium, the researchers applied novel statistical genetic methods to identify common patterns across 11 major psychiatric disorders: schizophrenia, bipolar disorder, major depressive disorder, anxiety disorder, anorexia nervosa, obsessive-compulsive disorder (OCD), Tourette syndrome, post-traumatic stress disorder, problematic alcohol use, attention deficit hyperactive disorder, and autism.

The average total sample size per disorder was 156,771 participants, with a range of 9725 to 802,939 participants.

In all, the investigators identified 152 genetic variants shared across multiple disorders, including those already known to influence certain types of brain cells.

For example, they found that 70% of the genetic signal associated with schizophrenia was also associated with bipolar disorder.

Results also showed that anorexia nervosa and OCD have a strong, shared genetic architecture and that individuals with a genetic predisposition to low body mass index also tend to have a genetic predisposition to these two disorders.

Not surprisingly, the researchers note, there was a large genetic overlap between anxiety disorder and major depressive disorder.

They also observed that psychiatric disorders that tend to cluster together also tend to share genes that influence how and when individuals are physically active during the day.

For example, patients with internalizing disorders such as anxiety and depression tend to have a genetic architecture associated with low movement throughout the day. On the other hand, those with OCD and anorexia tend to have genes associated with higher movement throughout the day.

"When you think about it, it makes sense," said Grotzinger. Depressed individuals often experience fatigue or low energy while those with compulsive disorders may have a tough time sitting still, he noted.

One Treatment for Multiple Disorders?

"Collectively, these results offer key insights into the shared and disorder-specific mechanisms of genetic risk for psychiatric disease," the investigators write.

Their research is also a first step toward developing therapies that can address multiple disorders with one treatment, they add.

"People are more likely today to be prescribed multiple medications intended to treat multiple diagnoses and in some instances those medicines can have side effects," Grotzinger said.

"By identifying what is shared across these issues, we can hopefully come up with ways to target them in a different way that doesn't require four separate pills or four separate psychotherapy interventions," he added.

Grotzinger noted that, for now, the knowledge that genetics are underlying their disorders may provide comfort to some patients.

"It's important for people to know that they didn't just get a terrible roll of the dice in life — that they are not facing multiple different issues but rather one set of risk factors bleeding into them all," he said.

This research had no commercial funding. Grotzinger reported no relevant disclosures.

Nat Gen. Published online May 5, 2022. Abstract.

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