One genetic map could rewrite how we understand mental health

An international team of researchers has shed light on why mental health conditions often occur together. Researchers analyzed data from more than 6 million people to explore the connections among over a dozen psychiatric disorders, including depression, anxiety, schizophrenia, bipolar disorder, ADHD, PTSD and substance use disorders.

The study, published in Nature, was co-authored by Drs. John Hettema and Brad Verhulst from the Texas A&M University Department of Psychiatry and Behavioral Sciences in the Naresh K. Vashisht College of Medicine.

The scale of the study provides the most detailed look yet at how genetic risk is distributed across conditions. Researchers examined DNA data across 14 childhood- and adult-onset psychiatric disorders from more than 1 million individuals with a disorder and 5 million individuals with none of the diagnoses. 

Genetic links between mental health disorders

“Genetic risk” describes the chance of developing a particular disease or health condition because of inherited variations in your DNA.

The team discovered that the disorders they examined share a surprising amount of genetic risk, clustered into five groups:

• Compulsive disorders (like OCD and anorexia)
• Schizophrenia and bipolar disorder
• Neurodevelopmental disorders (such as autism and ADHD)
• Internalizing disorders (depression, anxiety, PTSD)
• Substance use disorders

This means that the same genetic factors often influence multiple conditions, explaining why people frequently experience more than one mental health challenge.

These five major genetic patterns explain most of the shared risk for these disorders. Each pattern is linked to 238 genetic variants — tiny differences that influence how the brain works — offering clues about why some conditions overlap while others differ.

Several traits, including suicidality and loneliness, were genetically linked to all five factors.

“These findings help explain why mental health conditions often overlap,” said Hettema, a professor and psychiatrist, whose clinical and research expertise focuses on the epidemiology, genetics and biology of anxiety and related disorders. “By uncovering shared genetic roots, we can start thinking about treatments that target multiple disorders instead of treating each one in isolation.”

The research even pinpointed specific brain cell types linked to these genetic clusters. For the schizophrenia–bipolar group, the strongest genetic links were found in genes active in excitatory neurons, the brain cells that send “go” signals and help different regions communicate. In contrast, the risk for internalizing disorders (like depression, anxiety, PTSD) is more strongly linked to oligodendrocytes, cells that help brain signals travel faster.

“The findings suggest these ‘support cells’ might play an important role in those conditions,” said Verhulst, research assistant professor and an expert in quantitative and statistical genetics.

The big picture for mental health

Mental health affects nearly half of the population at some point in life. Current psychiatric diagnoses are based on symptoms, not biology.

“This study moves us closer to a science-based classification system for mental illness that reflects underlying genetics,” Hettema said.

“It also opens the door to new treatments that target shared biological pathways, potentially helping people with several conditions at once.”

The researchers emphasize that genetics does not “determine” someone’s outcome for psychiatric illness, as well as common medical conditions like hypertension and diabetes. Rather, it sets the stage by increasing or decreasing one’s innate risk, which then can be triggered by other factors, like stress.

The team’s work demonstrates the value of looking across diagnoses rather than within a single condition to reveal patterns that would be invisible in smaller, siloed studies.

By Lesley Henton, Texas A&M University Division of Marketing and Communications

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