While most physical disorders, such as cancer or diabetes, have well-defined indicators seen in tissues, organs, and bodily fluids, mental disorders are often more difficult to diagnose as they are typically identified by thought patterns and behaviors rather than biological pathology.
In a new study, however, researchers have found that autism, schizophrenia, and bipolar disorder share some physical characteristics at the molecular level — in particular, they share patterns of gene expression in the brain. The study also identified important differences between the gene expressions of these disorders as well.
“These findings provide a molecular, pathological signature of these disorders, which is a large step forward,” said senior author Dr. Daniel Geschwind, a distinguished professor of neurology, psychiatry and human genetics and director of the University of California, Los Angeles (UCLA) Center for Autism Research and Treatment. “The major challenge now is to understand how these changes arose.”
It is well-known that certain gene variations can put people at risk for mental health disorders, but DNA alone doesn’t tell the whole story. Although every cell in the body contains the same DNA, it is the RNA molecules in different parts of the body that play a vital role in gene expression by “reading” the instructions contained within DNA.
Geschwind and the study’s lead author, Dr. Michael Gandal, hypothesized that taking a closer look at the RNA in human brain tissue would help provide a molecular profile of these psychiatric disorders. Gandal is an assistant professor of psychiatry and biobehavioral sciences at UCLA.
For the study, the researchers analyzed the RNA in 700 tissue samples from the brains of deceased people who had lived with autism, schizophrenia, bipolar disorder, major depressive disorder, or alcohol abuse disorder. They then compared these samples to other samples taken from the brains of cadavers without psychiatric disorders.
The molecular pathology findings revealed significant overlap between distinct disorders, such as autism and schizophrenia, but also specificity, with major depression showing molecular changes not seen in the other disorders.
“We show that these molecular changes in the brain are connected to underlying genetic causes, but we don’t yet understand the mechanisms by which these genetic factors would lead to these changes,” Geschwind said.
“So, although now we have some understanding of causes, and this new work shows the consequences, we now have to understand the mechanisms by which this comes about, so as to develop the ability to change these outcomes.”
The findings are published in the journal Science.