Adolescent trauma produces enduring disruptions in sleep architecture that lead to increased risk for adult mental illness

青少年创伤会对睡眠结构产生持久的破坏，从而导致成人精神疾病的风险增加

• 批准号: 10730872
• 负责人: Gregory I Elmer
• 金额: $ 42.49万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10730872
• 关键词: Address; Adolescence; Adolescent; Adult; Adverse event; Affect; Affective; Anxiety; Arousal; Behavior; Behavioral; Bipolar Disorder; Categories; Cell Nucleus; Charge; Circadian Rhythms; Clinical; Cognitive; Data; Diagnostic; Disease; Drug abuse; Eating; Emotional; Environmental Risk Factor; Event; Exposure to; Genetic; Goals; Health; Homosynaptic Depression; Incidence; Individual; Individual Differences; Manic; Mediating; Mediation; Mediator; Mental Depression; Mental disorders; Midbrain structure; Neurobiology; Neurons; Obsessive-Compulsive Disorder; Output; Pathway interactions; Pattern; Play; Positioning Attribute; REM Sleep; Reporting; Risk; Role; Schedule; Schizophrenia; Series; Severities; Sleep; Sleep Architecture; Sleep Deprivation; Sleep Disorders; Sleep disturbances; Stress; Symptoms; Teenagers; Tegmentum Mesencephali; Testing; Therapeutic; Trauma; Ventral Tegmental Area; adverse childhood events; adverse outcome; cognitive function; depressive symptoms; design; designer receptors exclusively activated by designer drugs; determinants of treatment resistance; drinking; emerging adult; experience; experimental study; functional disability; generalized anxiety; high risk; maladaptive behavior; negative affect; neuron development; non rapid eye movement; pediatric trauma; sex; sleep abnormalities; stress resilience; trauma exposure; virtual; young adult

Childhood trauma is one of the single greatest environmental factors known to increase risk for a broad range of adult psychiatric illnesses. The consequences of childhood trauma not only affect the risk for mental illness, but significantly alter symptom complexity and predict treatment resistance within a diagnostic category. It could be argued that sleep disturbance is the single greatest drive (others being eating, drinking, sex) known to increase risk for adult psychiatric illness. Sleep abnormalities co-occur with virtually all psychiatric illnesses and, like adolescent trauma, significantly worsens the trajectory, severity and complexity of the illness. Each component of sleep architecture contributes to cognitive, emotional and somatic health. For example, rapid-eye movement sleep (REM), plays a key role in processing affective, emotional information and is thought to be critically involved in ‘depotentiating’ the emotional charge of a stress event and ameliorating its autonomic arousal burden. A recent report strongly suggests that activation of the rostromedial tegmental nucleus (RMTg) can dramatically decrease REM sleep via its main output to the ventral tegmental area (VTA). This finding is intriguing since our lab recently implicated RMTg activation in mediating the maladaptive adult consequences of adolescent stress. RMTg activation and subsequent REM deficits during adolescence could have dramatic impact since sleep and circadian processes help drive and guide neuronal development. We will utilize adolescent exposure to an ethologically-relevant stress (live predator) to test the following hypotheses: 1) Adolescent exposure to ethologically-relevant stress results in enduring changes in component- specific sleep architecture that are associated with maladaptive behavior in adulthood, and 2) Adolescent stress- induced changes in RMTg function underly the changes in sleep architecture associated with maladaptive behavioral profiles in adulthood. The goal of AIM 1 is to determine if individual sleep profiles following adolescent stress are predictive of adult behavior in a panel of tests designed to assess depression and anxiety. We will characterize sleep architecture in adolescence and adulthood and then characterize behavior profiles in adulthood. We expect individual differences in sleep architecture following adolescent stress to be predictive of normal, maladaptive and stress-resilient adult behavioral profiles. The goal of AIM 2 is to test the functional role of the RMTg-VTA circuit in mediating disturbed sleep architecture and/or changes in adolescent stress-induced maladaptive behavior in adulthood. An intersectional chemogenetic (DREADD) approach will be used to specifically inhibit the RMTg-VTA circuit in order to test causal associations. Adolescent childhood trauma- induced sleep disturbance may be a primary factor in the trajectory towards adult mental illness. Investigating the specific alterations in sleep architecture and underlying neurobiology will help facilitate therapeutic discovery efforts.

童年创伤是已知的最大的环境因素之一，可以增加广泛的风险