The lifetime risk for major depression in women is well known to be twice the risk in men and is especially high during the reproductive years between menarche and menopause. A subset of reproductive-age women experience depressive episodes that are triggered by hormonal fluctuations. Such "reproductive depressions" involve episodes of depression that occur specifically during the premenstrual, postpartum, and perimenopausal phases in women. These reproductive subtypes of depression can be conceptualized as a specific biological response to the effects of hormonal fluctuations in the brain. The different types of reproductive depressions are associated with each other, have unique risk factors that are distinct from nonreproductive depression episodes, and respond to both hormonal and nonhormonal interventions. This review uses a PubMed search of relevant literature to discuss clinical, animal, and genetic evidence for reproductive depression as a specific subtype of major depression. Unique treatment options, such as hormonal interventions, are also discussed, and hypotheses regarding the underlying biology of reproductive depression-including interactions between the serotonergic system and estrogen, as well as specific effects on neurosteroids-are explored. This review will provide evidence supporting reproductive depression as a distinct clinical entity with specific treatment approaches and a unique biology that is separate from nonreproductive depression.
"Tal y como plantea Ussher (1992), durante siglos se ha considerado el ciclo reproductivo femenino como un determinante principal de la conducta de las mujeres y, tanto en el discurso popular como en el académico, se ha planteado la existencia de síndromes como el premenstrual, el postnatal y el menopáusico a los que se ha considerado como las causas subyacentes de la ansiedad y depresión en las mujeres (cfrs. Payne, Palmer y Joffe, 2009), así como de una serie de síntomas físicos y de otras diferencias en salud y conducta entre mujeres y hombres. Desde esta perspectiva se ha hipotetizado la existencia de una susceptibilidad biológica planteándose que la variación cíclica neuroendocrina implicada en la reproducción femenina es vulnerable al cambio. "
"In conclusion, the findings reported here contribute to identifying the neural substrates associated with the long-standing clinical observation that changes in women's reproductive system are related to mood fluctuations and MDD symptomology (Rabin et al., 1990; Baischer et al., 1995; Rubinow and Schmidt, 1996; Harlow et al., 2003; Payne, 2003; Roca et al., 2003; Spinelli, 2005; Payne et al., 2009). Using a mild visual stress fMRI paradigm that reliably activates stress circuitry, we demonstrated a role for estradiol in modulating stress circuitry activity in healthy women and found evidence for the disruption of this hormone-brain pathway in major depression. "
[Show abstract][Hide abstract] ABSTRACT: Many regions within stress circuitry, including the anterior hypothalamus, amygdala, hippocampus and medial prefrontal cortex, are densely populated with sex steroid
receptors. Substantial evidence from animal studies indicates that the gonadal hormone 17β- estradiol impacts the structure and function of these regions, but human studies are limited. Characterizing estradiol’s role in stress circuitry in vivo in humans may have important clinical implications given the comorbidity between major depressive disorder (MDD), stress circuitry dysfunction and endocrine dysregulation. In this study, we determined estradiol’s role in modulating activity within cortical and subcortical stress circuitry regions in healthy and MDD women. Subjects were part of a neuroimaging follow-up study of a population-based birth cohort, the New England Family Study. Capitalizing on the endogenous fluctuation in 17β-estradiol (E2) during the menstrual cycle, we conducted a within-person repeated-measures functional neuroimaging study in which 15 women with recurrent MDD, in remission, and 15 healthy
control women underwent hormonal evaluations, behavioral testing and fMRI scanning on two occasions, under low and high E2 conditions. Subjects completed an fMRI scan while undergoing a mild visual stress challenge that reliably activated stress neural circuitry. Results demonstrate that E2 modulates activity aross key stress circuitry regions, including bilateral amygdala, hippocampus and hypothalamus. In healthy women, robust task-evoked BOLD signal changes observed under low E2 conditions were attenuated under high E2 conditions. This hormonal capacity to regulate activity in stress circuitry was not observed in MDD women, despite their remitted status, suggesting that dysregulation of gonadal hormone function may be a characteristic trait of the disease. These findings serve to deepen our understanding of estradiol’s actions in the healthy brain and the neurobiological mechanisms that may underlie the pronounced sex difference in MDD risk.
Neuropsychopharmacology 08/2014; in press(in press). DOI:10.1038/npp.2014.203. · 7.05 Impact Factor
"Lastly, epidemiological studies suggest stress-associated psychopathology to exhibit sex-bias and, for example, women are $2–3 times more likely to be affected by mood disorders during their reproductive years. Indirect evidence, as discussed above (Section 2.2 and 7: Payne et al., 2009; Brummelte and Galea, 2010), suggest a potential role of neurosteroids in the genderselectivity of stress-related psychopathology. Future efforts in the preclinical arena should therefore be conducted in both female and male subjects. "
[Show abstract][Hide abstract] ABSTRACT: Regulation of hypothalamic-pituitary-adrenocortical (HPA) axis activity by stress is a fundamental survival mechanism and HPA-dysfunction is implicated in psychiatric disorders. Adverse early life experiences, e.g. poor maternal care, negatively influence brain development and programs an abnormal stress response by encoding long-lasting molecular changes, which may extend to the next generation. How HPA-dysfunction leads to the development of affective disorders is complex, but may involve GABAA receptors (GABAARs), as they curtail stress-induced HPA axis activation. Of particular interest are endogenous neurosteroids that potently modulate the function of GABAARs and exhibit stress-protective properties. Importantly, neurosteroid levels rise rapidly during acute stress, are perturbed in chronic stress and are implicated in the behavioral changes associated with early-life adversity. We will appraise how GABAAR-active neurosteroids may impact on HPA axis development and the orchestration of the stress-evoked response. The significance of these actions will be discussed in the context of stress-associated mood disorders.
Frontiers in Neuroendocrinology 06/2014; 36. DOI:10.1016/j.yfrne.2014.06.001 · 7.04 Impact Factor
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