Rerouting towards REsilience to JUVENile stress-induced psychopAThologiEs in Adulthood: Spotlight on behavioural profiling and lifestyle interventions

重新转向对成年期青少年压力诱发的心理病理学的恢复力：聚焦行为分析和生活方式干预

• 批准号: 542950222
• 负责人: Dr. Gürsel Caliskan, Ph.D.
• 金额: --
• 依托单位: Sagol Department of Neurobiology
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/542950222?language=en
• 关键词: Rerouting; towards; REsilience; JUVENile; stress

Childhood adversities have long-lasting consequences in terms of mental health and well-being, and, exposure to childhood adversities (Juvenile stress [JS]) significantly increases vulnerability to mood and anxiety disorders later in life. Yet, not all show an increased risk of adulthood psychopathology. Some individuals develop resilience, helping them to better cope with later life challenges. Our primary objectives are (1) To elucidate mechanisms relating JS to vulnerability and resilience to stressful challenges in adulthood, and (2) To test the therapeutic/preventive potential of translational life-style interventions on the negative impact of JS later in life (i.e., boosting resilience). Our secondary objective is to systematically address sex-related differences in sensitivity, in related mechanisms underlying stress vulnerability or resilience, and in the effectiveness of life-style interventions for enhancing mental health resilience. Previous findings and our preliminary data suggest that the modulation of hippocampal functioning along its ventral-dorsal axis plays a pivotal role in mediating vulnerability or resilience following JS. Results hint to alterations of GABAergic functions, which alter excitability and immediate early gene expression, leading to alterations in memory-related engrams, and sleep patterns. We thus aim to test the following specific hypotheses: (i) JS leads to different behavioural and cognitive outcomes in resilient vs susceptible individuals. Resilience and vulnerability will be reflected in the molecular, cellular and network level process in a sex-dependent fashion. (ii) Life-style interventions can bias the outcome at the behavioural level, of JS towards resilience (intermittent fasting) or vulnerability (high-fat diet), by influencing the identified processes. The outcomes of life-style interventions are sex dependent. (iii) The long-term outcomes of JS and the effect of lifestyle interventions will be predicted by early neural and behavioural biomarkers (e.g., sleep patterns, spatial/social code in hippocampal units, maturation rate of performance in learning and social tasks). In this collaborative project, we will team advanced expertise in behavioural neuroscience together with systems, cellular and molecular methodologies to comprehensively unravel the neural bases of the impact of JS on vulnerability and resilience later in life. We will establish multimodal predictive and descriptive biomarkers that can identify risk and resilience outcomes of JS. Furthermore, we will examine the impact of life-style interventions, on behaviour and related mechanisms, with the aim of establishing such highly translational interventions as a potential approach to enhance mental health resilience following JS exposure.

童年逆境对心理健康和幸福有着长期的影响，并且，暴露于童年逆境（青少年压力[JS]）显着增加了以后生活中对情绪和焦虑症的脆弱性。然而，并非所有人都表现出成年精神病理学的风险增加。有些人发展了韧性，帮助他们更好地科普以后的生活挑战。我们的主要目标是（1）阐明JS与成年期压力挑战的脆弱性和弹性相关的机制，以及（2）测试翻译生活方式干预对JS在以后生活中的负面影响的治疗/预防潜力（即，增强恢复力）。我们的第二个目标是系统地解决与性别有关的敏感性差异，相关机制的压力脆弱性或弹性，以及生活方式干预措施的有效性，以提高心理健康的弹性。先前的研究结果和我们的初步数据表明，海马功能的调制沿着其腹背轴在介导JS后的脆弱性或弹性中起着关键作用。结果提示GABA能功能的改变，这改变了兴奋性和立即早期基因表达，导致记忆相关记忆痕迹和睡眠模式的改变。因此，我们的目标是测试以下特定的假设：（i）JS导致不同的行为和认知结果的弹性与易感个体。复原力和脆弱性将以依赖性别的方式反映在分子、细胞和网络一级的进程中。(ii)生活方式干预可以在行为水平上使JS的结果偏向于弹性（间歇性禁食）或脆弱性（高脂肪饮食），通过影响所确定的过程。生活方式干预的结果取决于性别。(iii)JS的长期结果和生活方式干预的效果将通过早期神经和行为生物标志物（例如，睡眠模式、海马单元中的空间/社会代码、学习和社会任务中的表现的成熟率）。在这个合作项目中，我们将结合行为神经科学的先进专业知识以及系统，细胞和分子方法，全面揭示JS对生命后期脆弱性和恢复力影响的神经基础。我们将建立多模态预测和描述性生物标志物，可以识别JS的风险和弹性结果。此外，我们将研究生活方式干预对行为和相关机制的影响，目的是建立这种高度转化的干预措施，作为一种潜在的方法，以提高JS暴露后的心理健康恢复力。