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Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

机译:单胺敏感的发育时期影响成人的情绪和认知行为。

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摘要

Development passes through sensitive periods, during which plasticity allows for genetic and environmental factors to exert indelible influence on the maturation of the organism. In the context of central nervous system development, such sensitive periods shape the formation of neurocircuits that mediate, regulate, and control behavior. This general mechanism allows for development to be guided by both the genetic blueprint as well as the environmental context. While allowing for adaptation, such sensitive periods are also vulnerability windows during which external and internal factors can confer risk to disorders by derailing otherwise resilient developmental programs. Here we review developmental periods that are sensitive to monoamine signaling and impact adult behaviors of relevance to psychiatry. Specifically, we review (1) a serotonin-sensitive period that impacts sensory system development, (2) a serotonin-sensitive period that impacts cognition, anxiety- and depression-related behaviors, and (3) a dopamine- and serotonin-sensitive period affecting aggression, impulsivity and behavioral response to psychostimulants. We discuss preclinical data to provide mechanistic insight, as well as epidemiological and clinical data to point out translational relevance. The field of translational developmental neuroscience has progressed exponentially providing solid conceptual advances and unprecedented mechanistic insight. With such knowledge at hand and important methodological innovation ongoing, the field is poised for breakthroughs elucidating the developmental origins of neuropsychiatric disorders, and thus understanding pathophysiology. Such knowledge of sensitive periods that determine the developmental trajectory of complex behaviors is a necessary step towards improving prevention and treatment approaches for neuropsychiatric disorders.
机译:发育经历敏感时期,在此期间可塑性允许遗传和环境因素对生物的成熟产生不可磨灭的影响。在中枢神经系统发育的背景下,这样的敏感时期决定了介导,调节和控制行为的神经回路的形成。这种一般机制使发展既受遗传蓝图又受环境因素的指导。在允许适应的同时,此类敏感期也是脆弱性窗口,在此期间,外部和内部因素可能通过破坏原本有弹性的发展计划而给疾病带来风险。在这里,我们回顾了对单胺信号敏感并影响与精神病学相关的成人行为的发育期。具体来说,我们回顾(1)影响传感系统发育的5-羟色胺敏感期,(2)影响认知,焦虑和抑郁相关行为的5-羟色胺敏感期,以及(3)多巴胺和5-羟色胺敏感期影响对精神刺激剂的攻击性,冲动性和行为反应。我们将讨论临床前数据以提供机制的见解,以及流行病学和临床数据以指出翻译的相关性。转化性发展神经科学领域已呈指数级发展,提供了扎实的概念进展和空前的机械洞察力。掌握了这些知识,并且正在进行重要的方法学创新,该领域有望取得突破,阐明神经精神疾病的发展起源,从而了解病理生理学。对敏感时期的了解决定了复杂行为的发展轨迹,这是改善神经精神疾病的预防和治疗方法的必要步骤。

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