Although the prevalence of bipolar disorder (BD) is similar in men and women, course and clinical features differ. Women are more likely to develop bipolar II disorder, bipolar depression and rapid-cycling than men and are at greater risk for comorbid conditions such as alcohol use problems, thyroid disease, and medication-induced obesity. However, the neurobiology of these gender differences is not completely understood.

Changes in peripheral levels of neurotrophins have been associated with mood disorders, also in interaction with early trauma. A recent study with primate model suggested that BDNF is a selective marker of early adversity in the female gender and is associated with increased levels of abnormal responses indicative of a depression-like state. In addition, pre-clinical studies showed that peer-rearing increased significantly BDNF levels only in females, which correlated with increased behavioral passivity. Preliminary results from our group suggest that women with bipolar disorder (n=16) show a greater age associated decline in BDNF levels than men (f=2.83; p=0.01), and this pattern of decline is different than in controls (p=0.04).This finding could be associated with menopause period and with a higher previous BDNF level in women.

The selective changes in BDNF levels and hormone interactions observed in females could help to explain the greater vulnerability to traumatic experiences and to mood disorders in women with BD.