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）：心理健康障碍的一个基本问题是，生命早期经历的环境信号可能会对人类疾病的发展产生长期影响。长期以来，光信号一直被认为是对特定大脑区域和功能发展的强大环境影响。在动物模型中，围产期光周期通过褪黑激素信号从母亲到胎儿传播，并在后期对生物时钟的稳定性以及成年后的抑郁症和焦虑行为的表达产生持久影响，确定光是一种环境信号，对脑电路和行为的表观遗传效应持续。我们建议对一系列新的假设进行有关一类疾病的新假设，这些疾病是光周期是关键因素 - 焦虑，抑郁和自杀。使用我们的平台，两种护士健康研究（NHS）人群，NHS和NHS2，其中包含出生日期，位置，健康概况，健康状况，工作历史和约238,000名美国护士的压力数据，我们试图确定在出生时间周围（从出生日期和位置推断出来的偏见），与这些疾病的风险相互作用，或者是将BIOLISS划定的次数与/或者相互作用。此外，我们将通过评估新的假设来测试“应力分解”模型，在这种假设中，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受到情感障碍的发展，以应对压力事件。如果在情感障碍的流行病学模式中建立 这项探索性R21研究预算有限和持续时间，然后进行后续R01研究可以检查特定的基因X环境相互作用和信号传导机制，该机制是既定的情感障碍环境风险因素。通过检查子宫中的光线暴露，我们试图扩大与光信号和情感障碍相关的当前研究范例，通过将注意力转移到生活中比到目前为止的早期生活更早的时间。如果我们的假设是正确的，研究结果将改变临床实践范例，因为它们与孕妇的咨询有关，以帮助防止子女的抑郁症和焦虑症的发展，并转化为实用，明确但安全且令人难以置信的廉价干预措施。建议可能涉及孕妇在户外度过的时间以增加日光的接触，这取决于其住所的纬度和预计的出生日期。另外，它们可能需要在室内的一天中指定的时间暴露于更高的灯灯。