A comprehensive understanding of how diseases work is critical if they are to be treated, but that can be especially challenging when it comes to disorders of the mind. In an effort to learn more about the mechanisms that underlie them, researchers have discovered common threads and critical differences in the molecular characteristics of autism, bipolar disorder, and schizophrenia. The investigators, reporting in Science, assessed the expression patterns of several genes in the brain.
"These findings provide a molecular, pathological signature of these disorders, which is a large step forward," noted the senior author of the work, Daniel Geschwind, a distinguished professor of neurology, psychiatry and human genetics and the Director of the UCLA Center for Autism Research and Treatment. "The major challenge now is to understand how these changes arose."
Our genes are first transcribed into an intermediate molecule called RNA before being made into proteins, which carry out many of the essential functions in our bodies. While it's known that specific alterations in the genome are associated with an increased risk for psychiatric diseases, the genetics alone don't explain everything. RNA is processed and regulated in many ways before it is made into proteins, and the investigators wanted to know more about how RNA was linked to the disorders they were studying.
Geschwind and Michael Gandal, lead author and an assistant professor of psychiatry and biobehavioral sciences at UCLA, assessed the molecular profile of several brain diseases; they analyzed RNA harvested from human brain tissue.
With 700 brain tissue samples from deceased patients that had autism, bipolar disorder, major depressive disorder, alcohol abuse disorder, or schizophrenia, they could compare the molecular signatures to brain samples from people without psychiatric disorders.
The scientists found that there was a significant overlap in the molecular features of distinct diseases, like schizophrenia and autism. However, they also saw specificity. Major depression, for example, displayed molecular alterations that weren't observed in the other pathologies.
"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," said Geschwind. "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."
Dr. Geschwind recently spoke at the Allen Frontiers Symposium about how variations in our genomes contribute to differences in how we think. Check out the talk, featured in the video.