The Effects of Developmental Stress on Dopaminergic Function in Adulthood: A Systematic Review and Meta-Analysis

Abstract

Aims Exposure to traumatic experiences during childhood and adolescence is a significant risk factor for the development of psychiatric disorders in adulthood. An estimated 50% of the worldwide incidence of depression and anxiety can be attributed to childhood maltreatment (Li et al., 2016). In addition, approximately one-third of psychotic experiences are attributable to a history of developmental trauma (McGrath et al., 2017). It is thought that long-lasting, trauma-induced adaptive changes in neurobiological function may lead to a predisposition towards pathophysiology (McCrory and Viding, 2015). However, the precise mechanisms through which developmental trauma exposure alters brain function on cellular and circuit levels remain poorly elucidated. Methods A systematic literature search and meta-analysis was performed to establish how dopaminergic functioning in adulthood is affected by developmental stress in rodents. Three databases, Medline®, Embase®, and PsycINFO®, were systematically searched initially on 2nd December 2023. Terms for three superordinate concepts (‘childhood’ terms, ‘trauma’ terms, and ‘dopamine’ terms) were combined. Cohen's d statistic was used for effect sizes. This protocol is pre-registered on PROSPERO® (ID: CRD42018106382). Results A total of 104 studies met our inclusion criteria. Meta-analysis indicated that developmental stress exposure leads to complex and long-lasting effects in basal and post-amphetamine extracellular dopamine concentrations in the medial prefrontal cortex, amygdala, and nucleus accumbens. In addition, there is a significant downregulation of D1 receptors and upregulation of D2 receptors in prefrontal and striatal regions involved in threat and reward processing. Effect sizes ranged from 0.36 to 1.55. Conclusion These findings strongly suggest that dopaminergic dysfunction is a mechanistic link between developmental trauma and vulnerability towards mental illness in adulthood.