Distinct psychiatric disorders may have more in common at the genetic level than previously recognized, according to new research from the University of Colorado Boulder and Mass General Brigham. The study, published December 10 in Nature, analyzed DNA data from over 1 million people diagnosed with at least one of 14 psychiatric disorders and 5 million without diagnoses.
"Right now, we diagnose psychiatric disorders based on what we see in the room, and many people will be diagnosed with multiple disorders. That can be hard to treat and disheartening for patients," said Andrew Grotzinger, PhD, assistant professor of psychology and neuroscience at CU Boulder. "This work provides the best evidence yet that there may be things that we are currently giving different names to that are actually driven by the same biological processes."
Jordan Smoller, MD, director of the Center for Precision Psychiatry at Mass General Brigham in Boston and co-corresponding author, added: "These findings provide valuable clues for advancing our understanding and treatment of mental illness with greater precision."
Working with the international Psychiatric Genomics Consortium Cross-Disorder Working Group, researchers identified five underlying "genomic factors" involving 238 genetic variants that accounted for most genetic differences between those with a disorder and those without. The analysis grouped conditions into five categories based on shared genetics: compulsive disorders (including anorexia nervosa, Tourette disorder, obsessive-compulsive disorder), internalizing conditions (such as depression, anxiety, post-traumatic stress disorder), substance use disorders, neurodevelopmental conditions (including autism and ADHD), as well as a group combining bipolar disorder and schizophrenia.
A key finding is that about 70% of the genetic signal linked to schizophrenia also relates to bipolar disorder. Historically considered very different by clinicians—who rarely diagnose both in one individual—the research suggests a strong genetic overlap. "Genetically, we saw that they are more similar than they are unique," said Grotzinger.
The study also identified specific biological pathways associated with each grouping. Genes influencing excitatory neurons were found to be over-expressed in both bipolar disorder and schizophrenia. For internalizing disorders like depression and anxiety, gene variants affecting oligodendrocytes—cells responsible for maintaining brain wiring—were common.
Researchers suggest some shared genetic factors act early during fetal brain development while others exert influence later in adulthood. This could lead to more biologically informed approaches to diagnosis and treatment strategies for mental health conditions.
A 2018 review noted that over half of individuals diagnosed with one psychiatric condition receive a second or third diagnosis during their lives; about 41% meet criteria for four or more.
While Grotzinger cautioned against immediately changing diagnostic practices based on these findings alone, he expressed hope they would inform future updates to diagnostic manuals such as the DSM. "By identifying what is shared across these disorders, we can hopefully come up with strategies to target them in a different way that doesn't require four separate pills or four separate psychotherapy interventions."
