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Molecular-level changes in the brains of women with major depressive disorder link two hypothesis about the biological mechanisms leading to the disease. Researchers at the University of Pittsburgh School of Medicine were also able to recreate the changes in a mouse model that could enhance future research on depression.
Women are twice as likely as men to experience depression. They also more severe and frequent symptoms. Never the less, there is not a lot of research out there that isolates the female experience.
“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,” said Etienne Sibille, PhD, associate professor of psychiatry, Pitt School of Medicine. “Indeed, our findings give us a better understanding of the biology of this common and often debilitating psychiatric illness.”
Researchers looked at post-mortem brain samples of women diagnosed with depression and women who were not. The depressed women had a pattern of reduced expression of certain genes, one linked to brain-derived neurotrophic factor (BDNF) and some genes linked with the production of GABA. These two findings were made in the part of the brain that regulates emotion.
The researchers then went to the mice. They were able to engineer mice to carry different mutations in the BDNF gene to see the impact on GABA production. They found two mutations that led to the reduction in specific gene production.
Researchers have long suspected that low levels of BDNF are linked to depression. There was also the hypothesis that reduced GABA function is a key factor.
“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,” Sibille said.
Source: MedicalNewsToday, National Institute of Mental Health
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