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症风险更大。此外，妇女抑郁症的特定年龄发病率在生育后期达到高峰。然而，围绝经期在多大程度上代表了无心境障碍病史的女性新发抑郁症的更大风险尚待确定。哈佛情绪与月经周期研究（HSMC）是一项以人群为基础的前瞻性研究，研究对象为绝经后期前的老年妇女，由于对精神病发病率和月经周期随时间的变化进行了严格的系统评估，因此该研究特别适合调查这种关联。在这项研究中，大约1000名绝经前妇女，有或没有抑郁症的终身病史，随访超过36个月，每半年进行一次精神病评估，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有关，2）有严重抑郁症终身史的女性（特别是那些接近绝经期的抑郁症状更严重的患者）与未绝经的妇女相比，抑郁症病史，3）卵泡早期FSH和LH较高，雌二醇水平较低，抑郁症与非抑郁症晚期育龄妇女，因为他们走向更年期。 在仔细收集了关于精神疾病和月经变化的前瞻性数据后，我们现在有一个独特的机会来评估围月经期过渡对首次发作情绪障碍风险的影响。在本次提交的资料中，我们计划纳入来自原始HSMC的约500名无重度抑郁症终身史的女性，并将用来自普通人群的另外200名主要是少数民族女性来丰富这一样本。我们的初步数据表明，在无抑郁症既往史的女性中，较早发生围绝经期过渡与新发重性抑郁症的3倍风险相关。此外，似乎开始激素治疗来治疗月经周期变化，不规则或躯体症状，减弱了首次发作抑郁发作的风险增加。我们计划更好地评估发病至围绝经期对新发情绪障碍风险的影响，而独立于明显影响复发风险的既往抑郁史。本项目旨在通过使用结构化临床访谈进行准确的精神病诊断，并在绝经过渡期对临床症状进行全面评估，以确认和扩展这些初步研究结果。

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.