Fetal Photoperiodic Programming and Affective Disorders in Adulthood

描述（由申请人提供）：精神健康障碍的一个基本问题是生命早期经历的环境信号如何对人类疾病的发展产生长期影响。长期以来，人们一直认为光信号对特定大脑区域和功能的发展具有强大的环境影响。在动物模型中，围产期光周期通过褪黑激素信号从母亲传递给胎儿，并在生命后期对生物钟的稳定性和成年后抑郁和焦虑行为的表达产生持续影响，这表明光是一种环境信号，对大脑回路和行为具有持久的表观遗传影响。我们建议测试一组新的假设，涉及到一类疾病，其中光周期是一个关键因素-焦虑，抑郁和自杀。我们使用两个护士健康研究（NHS）队列（NHS和NHS2）作为我们的平台，其中包含约238,000名美国护士的出生日期，地点，健康概况，轮班工作历史和压力数据，我们试图确定在出生时间（根据出生日期和地点推断）暴露于光周期是否可以调节这些疾病的风险和/或与轮班工作相互作用，作为生物钟破坏的标志。此外，我们将通过评估新的假设来检验“应激素质”模型，在该假设中，胎儿光周期编程代表了一个敏感事件，使我们的研究参与者更容易在应激事件中产生情感障碍。如果情感性障碍的流行病学模式在

DESCRIPTION (provided by applicant): A fundamental question in mental health disorders is how environmental signals experienced early in life may have long-lasting effects on the development of disease in human populations. Light signals have long been recognized as a powerful environmental influence on the development of specific brain regions and functions. In animal models, perinatal light cycles are transmitted from mother to fetus through melatonin signaling, and have persistent effects later in life on stability of the biologic clock and the expression of depression and anxiety behaviors in adulthood, establishing that light is an environmental signal with enduring epigenetic effects on brain circuits and behavior. We propose to test a set of novel hypotheses in reference to a class of diseases for which light cycles are a key factor - anxiety, depression, and suicide. Using as our platform the two Nurses Health Study (NHS) cohorts, NHS and NHS2, which contain the birth dates, locations, health profiles, shift work histories and stress data of ~238,000 US nurses, we seek to determine whether exposure to light cycles around the time of birth (as inferred from birth date and location) can modulate the risk of these disorders and/or interact with shift work as a marker for disruption of the biologic clock. Further, we will test the "stress-diathesis" model by evaluating novel hypothesis in which fetal photoperiodic programming represents a sensitizing event making our study participants more vulnerable to the development of affective disorders in response to stressful events. If epidemiological patterns of affective disorders are established in this exploratory R21 study with limited budget and duration, then a follow-on R01 study could examine specific gene X environment interactions and signaling mechanisms underlying an established environmental risk factor for affective disorders. By examining light exposure in the womb, we seek to expand current research paradigms related to light signals and affective disorders, by shifting the attention to a much earlier time period in life than thus far has been studied - in utero. If our hypotheses are correct, study results will change clinical practice paradigms, as they relate to counseling of pregnant women to help guard against the development of depression and anxiety disorders in their children and translate to practical and explicit, but safe and incredibly inexpensive, interventions. Recommendations may involve the time pregnant women spend outdoors in order to increase their exposure to daylight, depending on latitude of their residence and projected birth date. Alternatively, they could entail exposure to higher-lux light lamps at specified times of the day, when indoors.