Research reveals common genetic roots of multiple mental illnesses

The largest and most detailed analysis to date of how genes influence mental illness reveals that different mental illnesses have more biological similarities than previously thought.

The study, led by researchers at the University of Colorado Boulder and Massachusetts General Brigham, may inform efforts to improve the way mental disorders are diagnosed and provide insights for developing new treatments that address multiple disorders at once.

The results of this study were published in a journal on December 10th. nature.

“Currently, we diagnose mental illnesses based on what we see in the room, and many people end up being diagnosed with multiple disorders, which can be difficult to treat and discouraging patients,” said corresponding author Dr. Andrew Grotzinger, assistant professor of psychology and neuroscience at UW Boulder. “This study provides the best evidence to date that what we currently have different names for may actually be driven by the same biological process.”

Co-corresponding author Jordan Smoller, MD, Director, Center for Precision psychiatry Brigham, an associate professor at Mass General in Boston, said the findings also provide important insights into the biological pathways and gene expression in brain cell types that may underlie certain symptoms.

“These findings provide valuable clues to better understand and treat mental illnesses,” Smoller said.

5 categories

The researchers, in collaboration with the International Psychiatric Genomics Consortium's Cross-Disability Working Group, examined DNA data from more than 1 million individuals diagnosed with at least one of 14 mental illnesses and more than 5 million without a diagnosis.

They found that five fundamental “genomic factors,” including 238 genetic variations, make up the bulk of the genetic differences between people with a particular disease and those without. This paper classifies disorders into five categories, each of which has a common genetic makeup. “Internalizing conditions” such as depression, anxiety, and post-traumatic stress disorder. Substance use disorder. Neurodevelopmental conditions such as autism and attention-deficit/hyperactivity disorder (ADHD).

Remarkably, the paper places bipolar disorder and schizophrenia into a fifth category, reporting that 70% of the genetic signals associated with schizophrenia are also associated with bipolar disorder. Historically, the field of psychology has considered bipolar disorder and schizophrenia to be quite different, and clinicians typically do not diagnose individuals with both.

“We found that genetically, they are more similar than unique,” Grotzinger said.

Identifying biological pathways

The paper also points to specific biological pathways that may underlie individual groupings.

For example, research suggests that genes that affect excitatory neurons, which are involved in signal transmission between other neurons, tend to be overexpressed in both bipolar disorder and schizophrenia.

Mutations in genes that control non-neuronal cells called oligodendrocytes were common in internalizing disorders such as depression and anxiety. These specialized cells help maintain and protect the brain's wiring infrastructure.

The findings suggest that while some common genetic factors play a role very early in fetal brain development, other genetic factors may have a greater influence later in adulthood. The authors said this insight could lead to a more biological understanding of psychiatric conditions and lead to new treatment strategies.

A 2018 review found that more than half of people diagnosed with one mental illness will be diagnosed with a second or third mental illness during their lifetime. Approximately 41% will meet four or more criteria.

Grotzinger said it's too early to start piecing together diagnoses based on the findings. But he hopes new research will be considered as researchers work to update the Diagnostic and Statistical Manual of Mental Disorders (DSM), which guides the field of psychology.

“We hope that by identifying what these diseases have in common, we can come up with strategies to target them in a different way that doesn't require four separate pills or four separate drugs. psychotherapy intervention. ”