Study identifies genetic loci that link brain structure and various psychiatric disorders

The development of many psychiatric disorders, including depression, schizophrenia and bipolar disorder, is known to be in great part influenced by genetics. Past research has identified various genes that appear to be associated with an increased risk of developing specific disorders, while also uncovering structural patterns commonly observed in the brains of affected individuals.

Researchers at the University of Pennsylvania, the Children’s Hospital of Philadelphia and other institutes have recently carried out a new study aimed at further exploring how variants in human DNA could simultaneously influence both the structure of cortical brain regions and increase vulnerability to psychiatric disorders. Their paper, published in Nature Mental Health, pinpoints several genetic loci (i.e., locations on a chromosome where a gene or genetic variant is found) that are linked both to the risk that an individual will develop a psychiatric condition and to specific patterns in the structure of the cortex.

“Our research started from the idea that mental disorders are strongly influenced by genetic factors, which leave detectable footprints in the brain’s structure and function,” Zhiqiang Sha, first author of the paper, told Medical Xpress.

“Even in people without a clinical diagnosis, such as first-degree relatives of patients, these genetic effects can be quite pronounced. We wanted to understand how specific regions of the genome and the brain are jointly involved in shaping this risk. By mapping these shared influences, we could reveal how brain development may deviate from typical trajectories in high-risk individuals in the future.”

As part of their study, Sha and his colleagues analyzed a large amount of genetic data that were previously collected as part of large-scale genetics projects, including the European Genomics Consortium, the UK BioBank, and the ABCD study. These projects gathered both genetic data and brain imaging scans from thousands of individuals, some of whom were diagnosed with specific psychiatric disorders.

“Using advanced statistical methods, we looked for genetic variants that influenced both brain structure and psychiatric risk,” explained Sha. “This allowed us to identify dozens of specific genomic regions that have shared effects on the brain and mental health. In essence, we connected the dots between genetics, brain anatomy, and psychiatric conditions on an unprecedented scale.”

The analyses carried out by the researchers led to the discovery of various genetic loci that were associated both with a greater risk of developing a psychiatric disorder and the structure of the cortex. Fifty-five of these genetic regions appeared to be associated with the brain’s surface area, while 29 were linked to patterns in the cortex’s thickness.

“Remarkably, these genetic variants can drive brain regions to grow larger or smaller in opposite directions, highlighting complex, not always intuitive, genetic effects,” said Sha. “This complexity means traditional genetic correlation tools might miss these shared effects, even when they’re quite strong regionally.”

The findings of this recent study could help to uncover the intricate biological pathways that increase people’s vulnerability to mental health disorders, which could in turn inform the development of both treatments and prevention strategies. Sha and his colleagues now plan to extend their analyses by also exploring how the shared genetic influences they identified unfold over the course of the brain’s development.

“We are also interested in testing whether these genetic effects can help predict early vulnerability to psychiatric disorders before clinical symptoms appear,” added Sha.

“Another important step will be to integrate other biological layers, such as gene expression and brain connectivity, to build a more complete picture. Ultimately, our goal is to translate these findings into knowledge that could guide prevention and more precise treatment strategies.”

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