New Genetic Insights Into Overlapping Psychiatric Conditions

A global team of scientists is offering new clarity on why individuals diagnosed with one psychiatric condition frequently experience additional mental health disorders. Published today in Nature, the study presents the most comprehensive genetic analysis to date examining shared risk factors across 14 psychiatric conditions.

This landmark research was conducted by the Psychiatric Genomics Consortium’s Cross-Disorder Working Group, led by co-chairs Kenneth Kendler, M.D., professor of psychiatry at Virginia Commonwealth University School of Medicine, and Jordan Smoller, M.D., professor of psychiatry at Harvard Medical School.

Psychiatric comorbidity is widespread, with most individuals diagnosed with a mental health disorder later receiving one or more additional diagnoses. This overlap complicates diagnosis, classification, and treatment. While environmental influences and life experiences contribute to this pattern, genetic factors also play a critical role in increasing vulnerability to multiple conditions.

To better understand these genetic influences, researchers analyzed genomic data from more than six million people worldwide. Their findings revealed extensive genetic sharing across psychiatric disorders, allowing the team to group the 14 conditions into five major clusters characterized by strong genetic similarities. These results represent a major advance in understanding the biological connections underlying psychiatric illness and may help improve clinical care.

“Psychiatry remains unique among medical disciplines because it lacks objective laboratory tests,” said Kendler, a leading authority in psychiatric genetics. “We rely largely on observed symptoms rather than biological markers. Genetic research gives us a powerful framework for understanding how different disorders relate to one another. This study provides the most detailed genomic comparison ever conducted and helps explain why individuals so often experience multiple psychiatric conditions.”

The analysis included genetic data from more than one million individuals diagnosed with childhood- or adult-onset psychiatric disorders, alongside data from five million individuals without such diagnoses. By identifying genetic variants that occur more frequently in affected individuals, researchers were able to pinpoint genetic contributors to disease risk.

Using several complementary statistical and computational methods, the team examined the genetic architecture of 14 psychiatric disorders. They identified 428 genetic variants associated with multiple conditions and uncovered 101 chromosomal regions that served as shared “hot spots” for genetic risk.

Statistical modeling allowed researchers to classify the disorders into five genetically related categories:

• Compulsive disorders: obsessive-compulsive disorder, anorexia nervosa, and to a lesser extent, Tourette disorder and anxiety disorders

• Internalizing disorders: major depressive disorder, anxiety disorders, and post-traumatic stress disorder

• Neurodevelopmental disorders: autism spectrum disorder, attention-deficit/hyperactivity disorder, and to a lesser extent, Tourette disorder

• Schizophrenia and bipolar disorder

• Substance use disorders: opioid, cannabis, and alcohol use disorders, along with nicotine dependence

Notably, major depression, anxiety disorders, and post-traumatic stress disorder demonstrated particularly strong genetic overlap, sharing approximately 90% of their genetic risk factors. Schizophrenia and bipolar disorder were also closely related, sharing roughly two-thirds of their genetic markers.

The study further showed that disorders with overlapping genetic profiles also share biological characteristics, including similar patterns of gene expression across brain development and involvement of specific brain cell types. For instance, genes active in oligodendrocytes - cells essential for nervous system function - were more strongly linked to internalizing disorders, while genes expressed in excitatory neurons were more prominent in schizophrenia and bipolar disorder.

According to the researchers, these findings provide robust biological support for how psychiatric disorders are categorized and may guide future strategies to develop or repurpose treatments for conditions that frequently co-occur.

“I am deeply proud to contribute to this collaborative effort,” Kendler said. “This work demonstrates how much progress we can make - both scientifically and clinically - when we unite to address the complexities of mental illness.”

Source: Virginia Commonwealth University
ImageCredits: Freepik