It’s often said mental illness runs in the family. But while that’s true, scientists have had very little luck actually understanding how our genes influence our risk of developing major depression or schizophrenia. New research published Friday in Science seems to provide something big needed for that greater insight: A roadmap of how genes are expressed differently in the brains of people with one of five major psychiatric disorders.
An international coalition of researchers sifted through data from earlier studies that analysed the genetic makeup of people’s brains—donated after death—who were diagnosed with either clinical depression, schizophrenia, autism spectrum disorder, alcoholism, or bipolar disorder. The studies involved 700 people in total.
The researchers specifically looked at the RNA molecules found within these people’s brain cells in the cerebral cortex, which “read” and translate the DNA packed into every cell. That allowed them to broadly see and map out how the cells actually carried out the genetic instructions they were coded with. Lastly, they used the brains of people with a non-psychiatric condition, irritable bowel disorder, as a control group.
They ultimately found lots of distinct overlaps of molecular activity between the brains of people with psychiatric disorders that weren’t found in “healthy” brains, indicating that many of the same sort of biological dysfunctions underpin them.
“These findings provide a molecular, pathological signature of these disorders, which is a large step forward,” said senior author Daniel Geschwind, a professor of neurology, psychiatry, and human genetics and director of the UCLA Center for Autism Research and Treatment, said in a statement.
The findings might even change how we conceptualise certain mental illnesses. For instance, the molecular signature seen in people’s brains with bipolar disorder was the most similar to those with schizophrenia. That came as a surprise to the researchers since the symptoms of each tend to be very different from one another.
There were also surprising key differences. The brains of people with alcoholism shared almost nothing in common with anyone else’s. That flies in the face of earlier research suggesting that depression and alcoholism are often genetically connected. And depression, too, had many patterns of molecular activity not found with the other disorders. These distinctions are important, since they might someday help scientists develop better diagnostic tests, the researchers said.
Genes are far from the only thing that influence how a cell performs (or fails at) its assigned job; the environment we spend our lives soaked in also plays a dramatic role. And there’s no single genetic mutation that will ever explain why someone is prone to depression. In fact, scientists now understand a person’s genetic risk of mental illness comes from lots of almost-insignificant genetic variations—some incredibly common, some rare—that interact with each other in ways we simply don’t have a grasp of right now.
But the findings, Geschwind and his team believe, will provide lots of new breadcrumbs for scientists to follow. And these breadcrumbs might not just lead to diagnostic tests, but actual treatments. Already, Science Magazine reports, some of the researchers are pursuing a clinical trial that will test a potential treatment for autism, based on findings in the current study and others that suggest certain brain cells called microglia seem to be overactive in the brains of people living with autism.
For the most part, though, the real work is yet to come.
“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.” [Science]