Fetal Photoperiodic Programming and Affective Disorders in Adulthood

胎儿光周期编程和成年情感障碍

• 批准号: 8843548
• 负责人: EVA S SCHERNHAMMER
• 金额: $ 26.94万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8843548
• 关键词: Adolescence; Adrenal Glands; Adult; Affect; Animal Model; Anxiety; Anxiety Disorders; Attention; Behavior; Biologic Development; Biological; Biological Clocks; Biological Rhythm; Bipolar Disorder; Birth; Brain; Brain region; Budgets; Caregiver Burden; Characteristics; Child; Childhood; Circadian Rhythms; Cohort Studies; Counseling; DNA; Data; Date of birth; Depression and Suicide; Development; Diagnosis; Dimensions; Disease; Disease susceptibility; Environment; Environmental Risk Factor; Epidemiology; Epigenetic Process; Event; Exposure to; Fetal Development; Fetus; Genes; Geographic state; Health; Human; Hypothalamic structure; Incidence; Individual; Intervention; Late Effects; Length; Life; Light; Location; Long-Term Effects; Major Depressive Disorder; Melatonin; Mental Depression; Mental Health; Mental disorders; Modeling; Mood Disorders; Mothers; Nurses; Nurses' Health Study; Observational Study; Occupations; Participant; Patient Self-Report; Pattern; Perinatal; Pharmaceutical Preparations; Phenotype; Photoperiod; Physicians; Pituitary Gland; Population; Pregnant Women; Recommendation; Recording of previous events; Research; Risk; Sampling; Schizophrenia; Signal Transduction; Specific qualifier value; Stress; Stress Tests; Stressful Event; Testing; Time; Translating; Uterus; Woman; clinical practice; cohort; depressive symptoms; disorder risk; early experience; fetal; fetal programming; follow-up; hypothalamic-pituitary-adrenal axis; in utero; insight; novel; programs; residence; response; season of birth; shift work

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.

描述(由申请人提供)：精神健康障碍的一个基本问题是，在生命早期经历的环境信号如何对人类人口中的疾病发展产生长期影响。长期以来，光信号一直被认为是对特定大脑区域和功能发育的强大环境影响。在动物模型中，围产期的光周期通过褪黑素信号从母亲传递给胎儿，并在晚年对生物钟的稳定性以及成年后抑郁和焦虑行为的表达产生持续影响，从而确立光是一种环境信号，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，参考一类疾病，光周期是一个关键因素-焦虑，抑郁，和自杀。作为我们的平台，我们使用两个护士健康研究(NHS)队列，NHS和NHS2，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，我们寻求确定出生时周围暴露于光周期(根据出生日期和地点推断)是否可以调节这些疾病的风险和/或与轮班工作相互作用，作为扰乱生物钟的标志。此外，我们将通过评估新的假说来测试“压力-素质”模型，在该假说中，胎儿光周期编程代表一种敏感事件，使我们的研究参与者更容易因应激事件而发生情感障碍。如果情感性精神障碍的流行病学模式在 这项预算和持续时间有限的探索性R21研究，然后是后续的R01研究，可以检查特定的X基因环境交互作用和潜在的情感障碍环境风险因素的信号机制。通过检查子宫中的光暴露，我们寻求扩大目前与光信号和情感障碍相关的研究范式，将注意力转移到生命中比目前研究更早的时间段--子宫内。如果我们的假设是正确的，研究结果将改变临床实践范式，因为它们与对孕妇进行咨询有关，以帮助预防她们孩子的抑郁症和焦虑症的发展，并转化为实用、明确但极其安全和廉价的干预措施。建议可能涉及孕妇在户外度过的时间，以增加她们暴露在日光下的时间，这取决于她们居住的纬度和预计的出生日期。或者，当他们在室内时，他们可能需要在一天中的特定时间暴露在更高勒度的灯光下。