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Mood and Psychosis Symptoms During the Menopause Transition


Sarah H. Lisanby, M.D.
Division of Translational Research


Perimenopause is a window of vulnerability for the development or worsening of mood and psychotic symptoms. However, clinical recommendations on how to identify, characterize and treat mood and psychotic symptoms during the menopause transition (MT) are insufficient. Community-based prospective longitudinal studies of women transitioning through menopause document that women are at increased risk for both new-onset and recurrent depression during the MT (i.e., perimenopausal depression PMD) compared with both premenopause and several years postmenopause. Indeed, the rate of major depressive disorder and clinically meaningful elevations in depressive symptoms increases two to three-fold during MT. The MT also represents a vulnerable life phase where there is a substantial increase in the cases of first-onset schizophrenia, which is not observed in men of similar ages. Research findings also indicate that women with a previous diagnosis of schizophrenia and related disorders are at heightened risk for reemergence or exacerbation of symptoms resulting in serious functional deterioration during the MT period. Though it is known that MT represents a vulnerable life phase for mood disorders and schizophrenia and related disorders in women, research focused on deciphering the underlying biobehavioral mechanisms by which the MT enhances risk is underdeveloped. The lack of this knowledge has substantially hindered the development of treatments for perimenopausal women, for which there is an unmet need. The goal of this proposed initiative is to advance translational research to better understand the emergence and worsening of mood and psychotic disorders (e.g., PMD, generalized anxiety disorder, bipolar disorder, and schizophrenia) during the MT to identify targets for future development of novel treatment interventions.


Recent preclinical and clinical studies suggest the mechanisms for developing a mood or psychotic disorder during the MT are different during this life phase than during other developmental periods. The mechanisms, however, by which the milieu of physiological changes associated with menopause might impact mood and psychosis are poorly understood. Therefore, this concept aims to advance research on mood disorders and psychosis during the MT. Examples of study questions include but are not limited to:

  • What are the biological/neurobiological, genetic, and psychosocial/environmental risk factors, that would identify a woman as being at risk for mood and psychosis symptoms during the MT?
  • What are the proximal or distal psychological, biological, cognitive, or neuroendocrine mechanisms underlying mood and psychosis symptoms during the MT?
  • What role do changes in reproductive steroids levels play in mood and psychosis symptoms during the MT? Do mechanisms of action underlying mood and psychotic symptoms during the MT actively precipitate or otherwise predispose women to increased risk of all-cause mortality, and if so, how?
  • What biomarkers, if any, are there of mood and psychosis symptoms during the MT?