Risk for New onset of Depression in Perimenopausal Women

描述（由申请人提供）：几项流行病学研究表明，与男性相比，女性在青春期开始并持续一生的抑郁风险要大得多。此外，女性抑郁症的年龄特异性发病率在生育年龄后期达到高峰。然而，对于没有情绪障碍病史的女性来说，围绝经期在多大程度上代表了新发抑郁症的更大风险还有待确定。哈佛情绪和周期研究（HSMC）是一项基于人群的绝经前老年妇女的前瞻性研究，由于对精神疾病发病率和月经周期随时间变化的严格系统评估，因此非常适合调查这种关联。在这项研究中，大约1000名绝经前妇女（有或没有终生抑郁史）接受了为期36个月的随访，每半年进行一次精神评估、病史访谈和早期卵泡期血液标本，以测量血清中的生殖激素。我们发表的研究结果表明：1)初潮年龄和生育早期的其他事件与抑郁症的风险相关；2)与没有抑郁症史的女性相比，有重度抑郁症史的女性（尤其是那些在临近绝经期时抑郁症状更严重的女性）发生月经周期变化的风险更大，这些变化与那些预示着提前过渡到绝经期的女性相一致。3)卵泡期早期，随着绝经期的临近，抑郁女性的卵泡刺激素和黄体生成素水平高于非抑郁女性，雌二醇水平低于非抑郁女性。

DESCRIPTION (provided by applicant): Several epidemiological studies have shown that women, compared to men, are at a substantially greater risk of depression beginning in adolescence and continuing through their entire life. In addition, the age-specific incidence of depression in women peaks during the late reproductive years. However, the extent to which the perimenopause represents a time of greater risk for new onset of depression in women with no history of mood disorder is yet to be determined. The Harvard Study of Moods and Cycles (HSMC), a population-based prospective study of late premenopausal aged women, is uniquely suited to investigate this association because of the rigorous systematic assessment of psychiatric morbidity and menstrual cycle changes over time. In this study, approximately 1000 premenopausal women with and without a lifetime history of depression were followed over 36 months with semi-annual psychiatric assessments, medical history interviews, and early follicular phase blood specimens to measure reproductive hormones in serum. Our published results have shown that 1) age at menarche and other events in early reproductive life are associated with risk for depression, 2) women with a lifetime history of major depression (particularly those with more severe depressive symptoms proximate to the perimenopause) are at a greater risk of developing menstrual cycle changes consistent with those that signal an earlier transition to the perimenopause compared to women with no depression history, and 3) early follicular phase FSH and LH are higher, and estradiol levels are lower in depressed compared to non-depressed late reproductive aged women as they move toward the climacteric. Having carefully gathered prospective data on psychiatric disorders and changes in menstruation, we now have a unique opportunity to evaluate the impact of the perimenopausal transition on risk of first onset of mood disturbance. In this current submission, we plan to include approximately 500 women from the original HSMC with no lifetime history of major depression, and will enrich this sample with an additional 200 largely minority women from the general population. Our preliminary data suggest that an earlier onset to the perimenopausal transition is associated with a 3-fold risk of new onset of major depression in women with no prior history of depressive disorder. Furthermore, it appears that initiation of hormonal therapy to treat menstrual cycle changes, irregularities, or somatic symptoms attenuates this increased risk of a first onset of depressive episode. We plan to better assess the effect of onset to the perimenopause on the risk for new onset of mood disturbance independent of past depression history that clearly influences the risk of recurrent episodes. The present project is designed to confirm and expand upon these preliminary findings by using structured clinical interviews for accurate psychiatric diagnoses, and comprehensive assessments of clinical symptoms at the time of the menopausal transition.