Social Imprinting in the Development of Major Depression

重度抑郁症发展中的社会印记

• 批准号: 8278025
• 负责人: Stephen E Gilman
• 金额: $ 32.37万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8278025
• 关键词: Address; Adrenal Glands; Adrenal hormone preparation; Adult; Area; Attention; Behavioral Genetics; Biogenesis; Birth; Brain; CRH gene; Child; Child Sexual Abuse; Chronic; Cognitive; Cohort Studies; Data; Development; Disadvantaged; Disease; Disease susceptibility; Environment; Environmental Exposure; Environmental Risk Factor; Epidemiologist; Epidemiology; Etiology; Exposure to; Family Study; Famines; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Human; Human Chorionic Gonadotropin; Hypothalamic structure; Immune response; Immune system; Individual; Infection; Inflammatory; Interleukin-1; Interleukin-6; Investigation; Link; Longevity; Low Birth Weight Infant; Major Depressive Disorder; Mental Depression; Mental disorders; Modeling; Mood Disorders; Nature; Neurologic; New England; Pathway interactions; Performance; Perinatal Exposure; Pituitary Gland; Predisposition; Pregnancy; Psychopathology; Public Health; Recurrence; Research; Risk; Risk Factors; Role; Schizophrenia; Social Conditions; Social Environment; Stress; TNF gene; Testing; Toxicant exposure; United States National Institutes of Health; base; biological adaptation to stress; career; cohort; cytokine; early childhood; fetal; fetal programming; gene environment interaction; genetic epidemiology; health disparity; imprint; infancy; insight; lifetime risk; maternal stress; prenatal; prenatal exposure; prenatal influence; prenatal stress; psychosocial; social; socioeconomics; stressor

PROJECT SUMMARY This application seeks support to investigate the neurodevelopmental origins and etiology of major depressive disorder. Specifically, we propose to test a "fetal programming" model of depression in which adverse conditions during the fetal period-as indicated by exposure to maternal hypothalamic-pituitary-adrenal (HPA) hormones, elevated maternal pro-inflammatory cytokines; early social adversity; and genetic susceptibility, combine to contribute to a trajectory of elevated lifetime risk for major depression. This project also addresses the challenge of health disparities, which for depression are marked and persistent, and which remain an NIH priority area. We propose that the social origins of depression are, in part, neurodevelopmental in nature, and that understanding the developmental pathways to depression will not only yield significant insights into etiology, but will also advance the objective of reducing disparities. The aims of this proposal are: 1) to investigate the combined influences of atypical fetal stress-response pathways and social adversity in relation to the lifetime risk of major depressive disorder; and 2) to investigate gene-environment interactions during the prenatal period in the development of depression. The following hypotheses will be tested. 1) The long-term impact of prenatal risks-as indicated by maternal pro- inflammatory cytokines and maternal HPA activity-for major depression will be heightened under adverse social conditions. Hypothesis 1a is that the combination of maternal-fetal stress, as indicated by elevated levels of inflammatory cytokines (IL-1, IL-6, TNF-) during mid-gestation, and social adversity will be associated with an increased lifetime risk and recurrence of major depression. Hypothesis 1b is that levels of HPA hormones (increased CRH and decreased DHEAS and hCG) during mid-gestation will be associated with the lifetime risk and recurrence of major depression most strongly among individuals born in the context of social adversity 2) Social adversity during pregnancy and early infancy, in combination with genetic susceptibility to depression, with be associated with an elevated lifetime risk of depression. Hypothesis 2 is that polymorphisms in genes associated with HPA circuitry and in genes with prior replicated evidence of environmentally dependent effects on depression, will be associated with an increased risk of depression most strongly among children born in the context of social adversity. This proposal involves data from a 50-year investigation of a well-established birth cohort, the New England Family Study, which is uniquely capable of addressing the prenatal determinants of mental illness. The applicant is a social epidemiologist whose long-term career objectives are to discover the developmental pathways leading to major depression, and to identify modifiable pathways in order to reduce the public health burden of depression.

项目摘要 这个应用程序寻求支持，以调查神经发育的起源和重性抑郁症的病因。具体来说，我们建议测试一个"胎儿编程"抑郁症模型，其中胎儿期的不良条件-如暴露于母体下丘脑-垂体-肾上腺（HPA）激素，母体促炎细胞因子升高;早期社会逆境;和遗传易感性，联合收割机相结合，以提高终身患抑郁症的风险。该项目还解决了健康差距的挑战，这对抑郁症是显着的和持久的，这仍然是NIH的优先领域。我们认为抑郁症的社会根源在一定程度上是神经发育的 了解抑郁症的发展途径不仅会对病因学产生重要的见解，而且还将推进减少差异的目标。 本研究的目的是：1）研究非典型胎儿应激反应途径和社会逆境对重性抑郁症终生风险的综合影响; 2）研究产前抑郁症发生过程中基因-环境相互作用。将检验以下假设。1)产前风险的长期影响-如孕产妇亲- 炎性细胞因子和母体HPA活性在不良社会条件下会升高。假设1a是母胎压力，如妊娠中期炎性细胞因子（IL-1，IL-6，TNF-α）水平升高所示，与社会逆境的组合将与终身风险增加和抑郁症复发相关。假设1b：妊娠中期HPA激素水平（CRH升高，DHEAS和hCG降低）与抑郁症的终生风险和复发相关，在出生于社会逆境背景下的个体中最明显; 2）妊娠期和婴儿早期的社会逆境，结合遗传因素， 抑郁症的易感性，与抑郁症的终生风险增加有关。假设2是，与HPA回路相关的基因多态性和先前复制的环境依赖性对抑郁症影响的基因多态性，将与抑郁症风险增加最相关。 在社会逆境中出生的孩子中，这种情况尤为严重。 这项提案涉及的数据来自一项对一个成熟的出生队列进行的50年调查，即新英格兰家庭研究，该研究能够独特地解决精神疾病的产前决定因素。 申请人是一名社会流行病学家，其长期职业目标是发现导致重度抑郁症的发展途径，并确定可改变的途径，以减少抑郁症的公共卫生负担。

项目成果

Neurological soft signs and cognitive performance in early childhood.

• DOI: 10.1037/dev0000566
• 发表时间: 2018-11
• 期刊: Developmental psychology
• 影响因子: 4
• 作者: Alamiri B;Nelson C;Fitzmaurice GM;Murphy JM;Gilman SE
• 通讯作者: Gilman SE

Income inequality among American states and the conditional risk of post-traumatic stress disorder.

• DOI: 10.1007/s00127-017-1413-x
• 发表时间: 2017-09
• 期刊: Social psychiatry and psychiatric epidemiology
• 影响因子: 4.4
• 作者: Pabayo R;Fuller D;Goldstein RB;Kawachi I;Gilman SE
• 通讯作者: Gilman SE

Insights from life course epidemiology.

• DOI: 10.1016/j.acap.2010.03.008
• 发表时间: 2010-05
• 期刊: ACADEMIC PEDIATRICS
• 影响因子: 3.1
• 作者: Gilman, Stephen E.;McCormick, Marie C.
• 通讯作者: McCormick, Marie C.

Fetal growth and the lifetime risk of generalized anxiety disorder.

• DOI: 10.1002/da.20739
• 发表时间: 2010-11
• 期刊: DEPRESSION AND ANXIETY
• 影响因子: 7.4
• 作者: Vasiliadis, Helen-Maria;Buka, Stephen L.;Martin, Laurie T.;Gilman, Stephen E.
• 通讯作者: Gilman, Stephen E.

Psychosocial stressors and the prognosis of major depression: a test of Axis IV.

• DOI: 10.1017/s0033291712001080
• 发表时间: 2013-02
• 期刊: PSYCHOLOGICAL MEDICINE
• 影响因子: 6.9
• 作者: Gilman, S. E.;Trinh, N. -H.;Smoller, J. W.;Fava, M.;Murphy, J. M.;Breslau, J.
• 通讯作者: Breslau, J.