Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy; Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy.
Pharmacol Ther. 2024 Aug;260:108686. doi: 10.1016/j.pharmthera.2024.108686. Epub 2024 Jul 3.
Exposure to adversities during early life stages (early life adversities - ELA), ranging from pregnancy to adolescence, represents a major risk factor for the vulnerability to mental disorders. Hence, it is important to understand the molecular and functional underpinning of such relationship, in order to develop strategies aimed at reducing the psychopathologic burden associated with ELA, which may eventually lead to a significant improvement in clinical practice. In this review, we will initially recapitulate clinical and preclinical evidence supporting the link between ELA and psychopathology and we will primarily discuss the main biological mechanisms that have been described as potential mediators of the effects of ELA on the psychopathologic risk, including the role for genetic factors as well as sex differences. The knowledge emerging from these studies may be instrumental for the development of novel therapeutic strategies aimed not only at correcting the deficits that emerge from ELA exposure, but also in preventing the manifestation of a full-blown psychopathologic condition. With this respect, we will specifically focus on adolescence as a key time frame for disease onset as well as for early therapeutic intervention. We believe that incorporating clinical and preclinical research data in the context of early life adversities can be instrumental to elucidate the mechanisms contributing to the risk for psychopathology or that may promote resilience. This will ultimately allow the identification of 'at risk' individuals who may benefit from specific forms of interventions that, by interfering with disease trajectories, could result in more benign clinical outcomes.
早期生活逆境（early life adversities - ELA）暴露，从怀孕到青春期不等，是易患精神障碍的主要危险因素。因此，了解这种关系的分子和功能基础对于开发旨在减轻与 ELA 相关的精神病理负担的策略非常重要，这最终可能导致临床实践的显著改善。在这篇综述中，我们将首先回顾支持 ELA 与精神病理学之间联系的临床和临床前证据，并将主要讨论已被描述为 ELA 对精神病理风险影响的潜在介导因素的主要生物学机制，包括遗传因素的作用以及性别差异。这些研究中出现的知识可能有助于开发新的治疗策略，这些策略不仅旨在纠正 ELA 暴露所产生的缺陷，而且还可以预防全面精神病理状况的表现。在这方面，我们将特别关注青春期，因为它是疾病发作和早期治疗干预的关键时期。我们相信，将临床和临床前研究数据纳入早期生活逆境的背景下，可以阐明导致精神病理学风险的机制，或者可以促进韧性的机制。这最终将允许识别可能受益于特定干预形式的“风险”个体，这些干预形式通过干扰疾病轨迹，可能会导致更良性的临床结果。
