Lugenbühl Justina F, Viho Eva M G, Binder Elisabeth B, Daskalakis Nikolaos P
Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Department of Psychiatry and Neuropsychology, School for Mental Health, and Neuroscience, Maastricht University, Maastricht, the Netherlands.
Department Genes and Environment, Max Planck Institute of Psychiatry, Munich, Germany.
Biol Psychiatry. 2025 Feb 15;97(4):349-358. doi: 10.1016/j.biopsych.2024.09.023. Epub 2024 Oct 4.
Exposure to stressful life events is associated with a high risk of developing psychiatric disorders with a wide variety of symptoms. Cognitive symptoms in stress-related psychiatric disorders can be particularly challenging to understand, both for those experiencing them and for health care providers. To gain insights, it is important to capture stress-induced structural, epigenomic, transcriptomic, and proteomic changes in relevant brain regions such as the amygdala, hippocampus, locus coeruleus, and prefrontal cortex that result in long-lasting alterations in brain function. In this review, we will emphasize a subset of stress molecular mechanisms that alter neuroplasticity, neurogenesis, and balance between excitatory and inhibitory neurons. Then, we discuss how to identify genetic risk factors that may accelerate stress-driven or stress-induced cognitive impairment. Despite the development of new technologies such as single-cell resolution sequencing, our understanding of the molecular effects of stress in the brain remains to be deepened. A better understanding of the diversity of stress effects in different brain regions and cell types is a prerequisite to open new avenues for mechanism-informed prevention and treatment of stress-related cognitive symptoms.
暴露于应激性生活事件与出现具有多种症状的精神障碍的高风险相关。对于经历这些症状的人和医疗保健提供者而言,与应激相关的精神障碍中的认知症状可能特别难以理解。为了深入了解,重要的是捕捉应激诱导的杏仁核、海马体、蓝斑和前额叶皮质等相关脑区的结构、表观基因组、转录组和蛋白质组变化,这些变化会导致脑功能的持久改变。在这篇综述中,我们将强调改变神经可塑性、神经发生以及兴奋性和抑制性神经元之间平衡的应激分子机制的一个子集。然后,我们讨论如何识别可能加速应激驱动或应激诱导的认知障碍的遗传风险因素。尽管诸如单细胞分辨率测序等新技术有所发展,但我们对应激在大脑中的分子效应的理解仍有待深化。更好地理解应激在不同脑区和细胞类型中的效应多样性,是为基于机制的应激相关认知症状的预防和治疗开辟新途径的先决条件。