Researchers Identify Possible Genetic Component to Loss of Brain Volume associated with Major Depressive Disorder

Severe depression and chronic stress can trigger suppression of genes responsible for building synapses in the prefrontal cortex.

According to a new release from Yale University, scientists studying the brain tissue of deceased patients who were diagnosed with major depressive disorder (MDD) have discovered that “a single genetic switch that triggers loss of brain connections in humans and depression in animal models” may contribute to the loss of brain volume often seen in patients with MDD.

The release states that “the genetic switch known as a transcription factor represses the expression of several genes that are necessary for the formation of synaptic connections between brain cells, which in turn could contribute to loss of brain mass in the prefrontal cortex.”

The study results are published in the August 12, 2012, issue of Nature Medicine. In the summary of the study, the authors wrote that they used “microarray gene profiling and electron microscopic stereology to reveal lower expression of synaptic-function—related genes” in the dorsolateral prefrontal cortex of subjects with MDD, and “a corresponding lower number of synapses.” They reported that one particular transcriptional repressor that is expressed at a higher rate in patients with MDD is, when expressed in prefrontal cortex neurons, “sufficient to decrease the expression of synapse-related genes, cause loss of dendritic spines and dendrites, and produce depressive behavior in rat models of depression.”

Senior author Ronald Duman, PhD, said the study shows that “circuits normally involved in emotion, as well as cognition, are disrupted when this single transcription factor is activated.” He said these findings indicate it may be possible to identify genetic variations that mark people as being potentially at high risk for major depressive disorder or sensitivity to stress, and that “by enhancing synaptic connections, either with novel medications or behavioral therapy, we can develop more effective antidepressant therapies.”