Impact of Early Life Stress on Reward Circuit Function and Regulation

Abstract

Early life stress – including experience of child maltreatment, neglect, separation from or loss of a parent, and other forms of adversity – increases lifetime risk of mood, anxiety, and substance use disorders. A major component of this risk may be early life stress-induced alterations in motivation and reward processing, mediated by changes in the nucleus accumbens (NAc) and ventral tegmental area (VTA). Here, we review evidence of the impact of early life stress on reward circuit structure and function from human and animal models, with a focus on the NAc. We then connect these results to emerging theoretical models about the indirect and direct impacts of early life stress on reward circuit development. Through this review and synthesis, we aim to highlight open research questions and suggest avenues of future study in service of basic science, as well as applied insights. Understanding how early life stress alters reward circuit development, function, and motivated behaviors is a critical first step toward developing the ability to predict, prevent, and treat stress-related psychopathology spanning mood, anxiety, and substance use disorders.

Prenatal dexamethasone exposure alters effort decision making and triggers nucleus accumbens and anterior cingulate cortex functional changes in male rats

“…Prenatal stress or increased GC exposure has been shown to induce long-lasting neurobiological alterations in the reward circuit [ 22 , 27 , 44 ], leading to the emergence of motivational deficits later in life [ 2 , 45 , 46 ]. Herein, we show that animals exposed in utero to increased levels of GCs present motivational deficits in adulthood, as evaluated in the PR task.…”

Rodent models of early adversity: Impacts on developing social behavior circuitry and clinical implications

“…Although ELA impacts are brain-wide, the clinical literature has shown convergence with animal research demonstrating effects on regions processing threat and reward described above (Meyer et al, 2022 ). Examples of specific connections between adult MDD and ELA have been shown with respect to reward circuit function (Hanson et al, 2021 ) as well as amygdala and medial prefrontal cortical volume abnormalities (Heim and Binder, 2012 ; Shepard and Nugent, 2021 ). Studies have also highlighted the importance of the type and severity of adversity in producing these outcomes.…”

Early stressful experiences are associated with reduced neural responses to naturalistic emotional and social content in children

“…Supportive social relationships can have a positive effect on long-term socioemotional development ( Smith and Pollak, 2021 ). In contrast, early life stress introduces vulnerability in the development of emotional and social processes ( Hanson et al, 2021 , Herzberg and Gunnar, 2020 , Milojevich et al, 2021 ). Areas of the brain that construct emotions, including medial prefrontal cortex, anterior insula, and amygdala ( Lindquist et al, 2012 , Park et al, 2018 ), and areas involved in motivational processes, including nucleus accumbens and ventral tegmental area ( Cromwell et al, 2020 , Park et al, 2021 ), are particularly sensitive to stress.…”