Public Release: 

Estrogen alters memory circuit function in women with gene variant

Hormone-gene interaction may underlie sex/individual differences in mental disorders

NIH/National Institute of Mental Health

Fluctuations in estrogen can trigger atypical functioning in a key brain memory circuit in women with a common version of a gene, NIMH scientists have discovered. Brain scans revealed altered circuit activity linked to changes in the sex hormone in women with the gene variant while they performed a working memory task.

The findings may help to explain individual differences in menstrual cycle and reproductive-related mental disorders linked to fluctuations in the hormone. They may also shed light on mechanisms underlying sex-related differences in onset, severity, and course of mood and anxiety disorders and schizophrenia, which are often marked by working memory deficits. The gene-by-hormone interaction's effect on circuit function was found only with one of two versions of the gene that codes for BDNF (brain-derived neurotrophic factor), a chemical messenger operating in the circuit. This version occurs in about a fourth of white women.

The researchers experimentally manipulated estrogen levels over several months in healthy women with both versions of the gene while monitoring their brain activity as they performed a working memory task. When exposed to estrogen, an area in the brain's memory hub that is typically suppressed during such tasks instead activated in those with the uniquely human gene variant. Both PET (positron emission tomography) and fMRI (functional magnetic resonance imaging) scans showed the same atypical activation. Such gene-hormone interactions may confer risk for mental illnesses, say the researchers.

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For more information, see NIMH Science Update: https://www.nimh.nih.gov/news/science-news/2017/estrogen-alters-memory-circuit-function-in-women-with-gene-variant.shtml

REFERENCE:

Brain-derived neurotrophic factor Val66Met genotype and ovarian steroids interactively modulate working memory-related hippocampal function in women: a multimodal neuroimaging study. Wei SM, Baller EB, Kohn PD, Kippenhan JS, Kolachana B, Soldin SJ, Rubinow DR, Schmidt PJ, Berman KF. Mol Psychiatry. 2017 Apr 18. doi: 10.1038/mp.2017.72. [Epub ahead of print] PMID:28416813

About the National Institute of Mental Health (NIMH): The mission of the (NIMH) is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website http://www.nimh.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the http://www.nih.gov.

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