Reversing Impact of Childhood Adversity on MDD & Cognitive Decline in Menopause

扭转童年逆境对抑郁症的影响

• 批准号: 8797776
• 负责人: C. Neill NEILL EPPERSON
• 金额: $ 32万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8797776
• 关键词: Address; Adult; Adverse effects; Affect; Age; Aging; Alcohol consumption; Animals; Behavior; Biological Assay; Body mass index; Brain; Brain region; C-reactive protein; Childhood; Cognition; Cognitive; Cognitive aging; Cohort Studies; Data; Data Quality; Dementia; Development; Digit structure; Education; Endocrine system; Estradiol; Event; Functional disorder; Funding; Future; Health; Hippocampus (Brain); Hormones; Household; Hypogonadism; Immune system; Impaired cognition; Imprisonment; Incidence; Inflammation; Inflammatory; Interleukin-1; Interleukin-6; Investigation; Life; Life Stress; Life Style; Link; Longevity; Major Depressive Disorder; Measures; Mediating; Memory; Menopause; Mental Depression; Mental disorders; Mood Disorders; Moods; Mothers; Neuraxis; Ovarian; Ovarian hormone; Patient Self-Report; Performance; Peripheral; Pharmacotherapy; Postmenopause; Prefrontal Cortex; Premenopause; Production; Psychosocial Stress; Publishing; Questionnaires; Recording of previous events; Regulation; Relapse; Relative (related person); Reporting; Research; Research Activity; Research Personnel; Risk; Sampling; Serum; Sex Characteristics; Sexual abuse; Sleep; Smoking Status; Social support; Socioeconomic Status; Staging; Stress; Stress and Coping; Substance abuse problem; TNF gene; Testing; Time; Violence; Waxes; Woman; Women' s Health; base; biobehavior; cognitive change; cohort; cytokine; diet and exercise; divorce/separation; emotional abuse; emotional neglect; executive function; experience; inflammatory marker; nonhuman primate; physical abuse; physical neglect; processing speed; public health relevance; reproductive hormone; resilience; response; senescence

 DESCRIPTION (provided by applicant): It is well established that childhood adversity is one of the most potent predictors of adult affective disorders, particularly among women. Similarly, stress has been linked with poor cognitive aging, although the importance of the developmental stage at which such events occur is not as clear. Stress modulation of both immune and endocrine systems, directly or through their central nervous system targets, is one possible mechanism by which childhood adversity impacts both cognition and mood. In response to this RFA, we propose to utilize data collected during the 14-year long Penn Ovarian Aging Study (POAS, PI: E. Freeman) to address critical questions regarding the reversibility of early life adversity impact on risk for major depressive disorder (MDD) and sub-optimal cognitive aging, with a particular focus on the menopause transition during which reproductive hormone changes unmask vulnerability to depression and cognitive complaints in many women. Using data from the POAS cohort, we recently reported a 2-fold increased risk of new onset MDD during the menopause transition among women with a history of two or more adverse childhood experiences (ACEs). Likewise, we published the first confirmation that menopause exerts an age-independent effect on immediate and delayed verbal recall and have recently obtained preliminary evidence that ACEs may contribute an additional adverse effect in some cognitive domains. While these findings suggest an intriguing and important interaction between childhood adversity and risk for depression and cognitive decline with menopause, it would be a lost opportunity for women's health, and potentially sex difference research in affective disorders and dementia, to not utilize this cohort further to identify factors that mediate, exacerbate and/or ameliorate the negative impact of childhood adversity on mood and cognition. Moreover, there are few opportunities as rich as this to explore these factors in the presence of well-characterized ovarian hormone fluctuations over an important transition period in women's lives. This RFA is perfectly timed as funding would enable us to 1) utilize the existing biobehavioral data from the POAS cohort to determine the extent of the impact of childhood adversity on timing of depression onset, slope of the decline in cognition and trajectory of ovarian senescence; 2) conduct comprehensive assessments of life-long adversity to address whether specific "clusters" of adversity and/or a "double-hit" is necessary to observe the impact of early life stress; 3) collect more robust measures of cognition, particularly those related to executive functions and affect regulation as these are common concerns among menopausal women, and prefrontal cortex and hippocampal brain regions are a primary target of stress hormones and neuro-inflammation, and finally to 4) test the hypothesis that inflammation mediates, at least in part, the relationship between childhood adversity and the emergence of MDD and cognitive decline in the context of declining estradiol production. The extensive expertise of this collaborative group of investigators and the quality of data from the POAS cohort will insure successful completion of the proposed analyses/research activities to inform development of future studies targeting the reversible biobehavioral factors identified during the course of this 2-year R01 funding.