Depressed Woman
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According to findings published online this week in Molecular Psychiatry, researchers at the University of Pittsburgh School of Medicine found molecular-level changes in the brains of women with major depressive disorder which link two hypotheses of the biological mechanisms that lead to depression. The results also allowed the researchers to recreate the changes in a mouse model that could improve future research on depression.

Senior author Etienne Sibille, Ph.D., associate professor of psychiatry at the Pitt School of Medicine remarked that despite the fact that women are two times more likely to develop depression with more severe and frequent symptoms compared with men, very little research has focused on women or has been conducted in other female animals.

Sibille said:
"It seemed to us that if there were molecular changes in the depressed brain, we might be able to better identify them in samples that come from females. Indeed, our findings give us a better understanding of the biology of this common and often debilitating psychiatric illness."
During the study, which was funded by the National Institute of Mental Health, researchers assessed post-mortem brain tissue samples of 21 women with depression and 21 similar women with no history of the condition. They examined the amygdala, a brain region involved in sensing and expressing emotion and discovered that in contrast to women with no history in depression, those who suffered from depression showed a pattern of reduced expression of certain genes, including the one for brain-derived neurotrophic factor (BDNF), and of genes that are typically present in particular subtypes of brain cells, or neurons, that express the neurotransmitter gamma-aminobutyric acid (GABA.)

The next step of the study involved testing mice engineered to carry different mutations in the BDNF gene to study its impact on the GABA cells. The researchers discovered two mutations that led to the same deficit in the GABA subtype and that also mirrored other changes seen in the human depressed brain.

Dr. Sibille stated that research has long suspected that low levels of BDNF are linked to the development of depression, and that a hypothesis exists, that reduced GABA function is a key factor.

He summarized:
"Our work ties these two concepts together because we first show that BDNF is indeed low in depression and second that low BDNF can influence specific GABA cells in a way that reproduces the biological profile we have observed in the depressed brain."
The team continues its investigation of the molecular pathway between BDNF and GABA and others that could be significant in depression.