Modeling sex-differences in trauma-related neural organization conferring resilience against addiction

模拟创伤相关神经组织中的性别差异，赋予其抗成瘾的能力

• 批准号: 9317079
• 负责人: George Andrew James
• 金额: $ 22.35万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9317079
• 关键词: 15 year old; Acute; Adolescent; Adult; Age; Anterior; Attention; Behavior; Behavior Control; Behavioral; Biological Neural Networks; Child Abuse and Neglect; Childhood; Clinical; Cognition; Cognitive; Conflict (Psychology); Cues; Data; Development; Disease; Dorsal; Drug Addiction; Drug Use Disorder; Drug usage; Early-life trauma; Emotional; Enrollment; Event; Exposure to; Female Adolescents; Functional Magnetic Resonance Imaging; Future; Goals; Impaired cognition; Impairment; Impulsivity; Individual; Individual Differences; Inferior; Informal Social Control; Intervention; Knowledge; Left; Life; Life Stress; Literature; Maps; Measures; Mental disorders; Modeling; Motivation; Motor; Neural Pathways; Outcome; Pattern; Predisposition; Prevention program; Preventive Intervention; Process; Psychopathology; Public Health; Recording of previous events; Recruitment Activity; Reproducibility; Research; Research Proposals; Risk; Risk Factors; Role; Sampling; Severities; Sex Characteristics; Signal Transduction; Stimulus; Stress; Symptoms; Testing; Time; Translating; Trauma; Woman; Work; addiction; assault; attentional bias; base; cingulate cortex; drug development; emotional stimulus; evidence base; frontal lobe; girls; innovation; men; motor control; neural correlate; neurobehavioral; neurodevelopment; neuromechanism; neuroregulation; pediatric trauma; potential biomarker; psychologic; psychosocial; relating to nervous system; resilience; response; sex; therapy development; young adult

ABSTRACT While childhood adversity is a recognized risk factor for the development of drug use and other psychiatric disorders, many individuals are resilient against the negative consequences of childhood trauma. Searches for the mechanisms of resilient adaptation have largely sought to characterize psychological and psychosocial protective factors. However, inhibitory motor control and its inferior frontal cortex (IFC) mechanisms represent risk and protective factors for drug use disorders. The motivation for the proposed exploratory/developmental project is our fMRI demonstration that – for women without drug use or other psychiatric disorders – an increasing severity of childhood maltreatment was associated with increasing negative modulation of dorsal anterior cingulate cortex (dACC) activity by the left IFC (LIFC). Furthermore, this LIFC to dACC influence predicted both better response inhibition for a Stop Signal task and less impaired attention/impulsivity, suggesting it may be a construct encoding resilience to trauma. Our finding stands in contrast of existing literature implicating right IFC function in inhibitory control among healthy individuals. The proposed project would use further characterize the role of IFC-dACC connectivity in encoding sex-differences in resiliency against trauma. Aim 1 would use fMRI to independently replicate this adaptive response for motor control (Stop Signal task) by comparing task responses for men and women without drug use or other disorders and with (“resilient”) and without (“control”) childhood maltreatment histories. Aim 2 would assess the generalization of this neural pathway to cognitive conflict for emotionally distracting stimuli (the emotional Stroop task). Aim 3 would explore neurodevelopment of resilience through re-enrollment of female adolescents with trauma histories whom previously underwent the Stop Signal fMRI task to associate longitudinal changes in the neural mechanisms of inhibitory control to post-trauma clinical and drug use trajectories. The proposed model-based and hypothesis-driven research plan would explore further the role of a hypothetical neural network response related to behavioral control as a mechanism of adaptive cognitive resilience and develop potential biomarkers of resilience and neurobehavioral targets for intervention in at-risk individuals.

摘要 虽然童年的逆境是吸毒和其他精神疾病发展的公认风险因素 在精神障碍方面，许多人对童年创伤的负面后果具有抵抗力。搜索 弹性适应的机制在很大程度上试图描述心理和心理社会的特征。 保护性因素。然而，抑制性运动控制及其下额叶(IFC)机制代表了 药物使用障碍的风险和保护因素。建议的探索性/发展性项目的动机 该项目是我们的fMRI演示-对于没有使用药物或其他精神疾病的女性-一个 儿童期虐待的严重程度与背部负性调节的增加有关 前扣带回皮质(DACC)的活动由左IFC(LIFC)决定。此外，这种LIFC对dACC的影响 预测停止信号任务的反应抑制更好，注意力/冲动受损更少， 这表明它可能是一种编码创伤恢复力的结构。我们的发现与现有的形成鲜明对比 文献表明，在健康个体中，右IFC在抑制控制中起作用。拟议中的项目 将使用进一步表征IFC-dACC连接在编码弹性中的性别差异方面的作用 对抗创伤。目标1将使用fMRI来独立地复制运动控制的这种适应性反应(停止 信号任务)，通过比较没有吸毒或其他障碍的男性和女性以及 (“适应力”)和无(“控制”)儿童期虐待史。目标2将评估以下方面的普遍性 这条神经通路通向情绪分散刺激的认知冲突(情绪Stroop任务)。目标3 将通过重新招收患有创伤的女性青少年来探索韧性的神经发展 既往经历停止信号功能磁共振任务以关联神经纵向变化的病史 创伤后临床和药物使用轨迹的抑制控制机制。建议的基于模型的 假说驱动的研究计划将进一步探索假想的神经网络反应的作用 与作为适应性认知弹性机制的行为控制相关，并开发潜在的生物标记物 高危个体的恢复力和神经行为目标的干预。