Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
Transl Psychiatry. 2021 May 11;11(1):280. doi: 10.1038/s41398-021-01388-6.
Mental disorders including depression and anxiety are continuously rising their prevalence across the globe. Early-life experience of individuals emerges as a main risk factor contributing to the developmental vulnerability to psychiatric disorders. That is, perturbing environmental conditions during neurodevelopmental stages can have detrimental effects on adult mood and emotional responses. However, the possible maladaptive neural mechanisms contributing to such psychopathological phenomenon still remain poorly understood. In this review, we explore preclinical rodent models of developmental vulnerability to psychiatric disorders, focusing on the impact of early-life environmental perturbations on behavioral aspects relevant to stress-related and psychiatric disorders. We limit our analysis to well-established models in which alterations in the serotonin (5-HT) system appear to have a crucial role in the pathophysiological mechanisms. We analyze long-term behavioral outcomes produced by early-life exposures to stress and psychotropic drugs such as the selective 5-HT reuptake inhibitor (SSRI) antidepressants or the anticonvulsant valproic acid (VPA). We perform a comparative analysis, identifying differences and commonalities in the behavioral effects produced in these models. Furthermore, this review discusses recent advances on neurodevelopmental substrates engaged in these behavioral effects, emphasizing the possible existence of maladaptive mechanisms that could be shared by the different models.
精神障碍，包括抑郁和焦虑，在全球范围内的患病率持续上升。个体的早期生活经历成为导致精神障碍发育易感性的主要风险因素。也就是说，神经发育阶段的环境条件干扰会对成年期的情绪和情绪反应产生不利影响。然而，导致这种精神病理现象的可能的适应不良的神经机制仍知之甚少。在这篇综述中，我们探讨了精神障碍发育易感性的临床前啮齿动物模型，重点研究了早期生活环境干扰对与应激相关和精神障碍相关的行为方面的影响。我们将分析限制在已建立的模型中，其中 5-羟色胺（5-HT）系统的改变似乎在病理生理机制中起着关键作用。我们分析了早期生活应激和精神药物暴露（如选择性 5-羟色胺再摄取抑制剂（SSRIs）抗抑郁药或抗惊厥药丙戊酸（VPA））产生的长期行为后果。我们进行了比较分析，确定了这些模型产生的行为影响的差异和共同点。此外，该综述还讨论了神经发育基质在这些行为影响中的最新进展，强调了不同模型可能共享的适应不良机制的存在。
