Feb 8, 2018

Similar gene activity seen across some psychiatric disorders

A mouse astrocyte.

Astrocytes (in green) are seen here in a mouse brain. Credit: NICHD

Scientists have found similar patterns of genes activity in psychiatric disorders like schizophrenia, bipolar and autism, according to a study published Thursday in Science. They've also discovered some key differences, particularly in major depressive disorder and alcohol abuse disorder.

Why it matters: Some genetic risk factors have been identified for certain psychiatric diseases, but knowing where and when a particular gene is expressed is crucial for developing better diagnostic tools and treatment.

"By understanding the molecular basis [for the disorders], one can begin to ask 'How did this arise? What is the mechanism behind this?'" says UCLA's Daniel Geschwind, a study author. In a way, he adds, the study findings help scientists "move backwards to the causation factors" and then from there new therapeutics can be created.

What they did: The team analyzed the genes expressed in 700 tissue samples from the brains of deceased patients who had one of the five psychiatric disorders and compared them with samples from brains of people without the disorders.

What they found: a "significant overlap" between some of the disorders, whereas others showed unique molecular changes.

  • Autism: They saw a strong decrease in specific neuronal signaling pathways, and an increase in cells that support the central nervous system, called microglia and astrocytes.
  • Schizophrenia had a similar, but less extensive, pattern of decreasing neuronal signaling pathways, along with a strong increase in astrocytes but not microglia.
  • Bipolar disorder had a similar but weaker pattern than schizophrenia. "Thus, there is somewhat of a gradient for these three," Geschwind says.
  • Major depressive disorder: There was a distinct pattern of genes involved in hormonal regulation and stress response.
  • Alcohol abuse disorder is further distinct from the other disorders, not showing any substantial overlap. The pattern is complex and Geschwind says they need more samples (this study only used 17 samples) and more testing to determine how strong the role of environment and exposure to alcohol plays.

"Gene expression analyses bring us one step closer to the molecular biology of these diseases and complement the genetic studies on psychiatric disorders that have been published in the last years," Harvard Medical School associate professor Kasper Lage, who was not part of this study, tells Axios.

One thing to note: These disorders are complex and studies like these can be good for finding potential genes associated with a trait or disease but can't say whether or how they are directly involved.

Sofia Frangou, a psychiatrist at the Icahn School of Medicine at Mount Sinai, is "hesitant in extrapolating the results to clinical action just yet," Ashley P. Taylor writes in The Scientist.

"Because the data come from post-mortem brains, the analysis 'doesn’t actually inform particularly about how these changes in gene expression may happen in life,'" Frangou told The Scientist.

Lage agrees but adds:

"This still represents a significant advance in our understanding of the molecular causes of disease, and provides a good starting point or a next wave of more targeted analyses of the underlying biology."

What's next: Geschwind says testing on a larger sample is needed, and in particular, he would like to examine closer the role of neuroglia like microglia and astrocytes. "This provides a framework, but there's a lot to do," he says.

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