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Handbook of Clinical Gender Medicine


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Certain sex-linked traits may play a role; for example, the uVNTR polymorphism of the MAOA gene on the X chromosome has been found to confer vulnerability to depression more in women than in men [15]. Similarly, estrogen receptor-beta (ER-β) appears to play a role in anxiety: Krezel et al. [16] reported an increase in anxiety-related behaviors in ER-β knockout female mice but not in males.

      Gonadal Steroids

      The increased rate of depression in women during puberty, when gonadal hormone systems are activated, suggests that hormones may contribute to sex differences in depression. Research linking affective disturbances in women with periods of hormonal change – particularly during the premenstrual and postpartum periods – further reinforces this hypothesis.

      The hormonal changes throughout the menstrual cycle have also been implicated in affective dysregulation in women. Although many women report mild-to-moderate physical or emotional symptoms during the late luteal phase of their menstrual cycle, approximately 5–10% experience significant mood disturbances in the days prior to menses. This condition, known as premenstrual dysphoric disorder, like PPD, represents a differential affective response to normal fluctuations in steroid levels in a susceptible population. Although the source of this susceptibility is unknown, controlled, double-blind studies manipulating gonadal steroid levels have clearly demonstrated a role of estradiol and progesterone in a subset of depressions in women – those related to reproductive events – thus suggesting a possible sex-dependent source of variance in the etiopathogenesis of depression.

      Integrated Model of Depression

      References