Women having a variant of a common gene have altered activity in the brain's memory circuit, in correspondence with fluctuations in estrogen. These findings from the National Institute of Mental Health were proved through brain scans that revealed altered circuit activity in response 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 interaction between the gene variant and estrogen fluctuation sheds light on mechanisms underlying sex-related differences in onset and severity of mood and anxiety disorders and schizophrenia often marked by working memory deficits.’
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.