Early-Life Stress Affects Stress-Related Prefrontal Dopamine Activity in Healthy Adults, but Not in Individuals with Psychotic Disorder

Early life stress may have a lasting impact on the developmental programming of the dopamine (DA) system implicated in psychosis. Early adversity could promote resilience by calibrating the prefrontal stress-regulatory dopaminergic neurotransmission to improve the individual's fit with the predicted stressful environment. Aberrant reactivity to such match between proximal and distal environments may, however, enhance psychosis disease risk. We explored the combined effects of childhood adversity and adult stress by exposing 12 unmedicated individuals with a diagnosis of non-affective psychotic disorder (NAPD) and 12 healthy controls (HC) to psychosocial stress during an [F-18]fallypride positron emission tomography. Childhood trauma divided into early (ages 0-11 years) and late (12-18 years) was assessed retrospectively using a questionnaire. A significant group x childhood trauma interaction on the spatial extent of stress-related [18F] fallypride displacement was observed in the mPFC for early (b=-8.45, t(1,23) = -3.35, p=.004) and late childhood trauma (b=7.86, t(1,23) = -2.48, p=.023). In healthy individuals, the spatial extent of mPFC DA activity under acute psychosocial stress was positively associated with the severity of early (b=7.23, t(11) = 3.06, p=.016) as well as late childhood trauma (b=-7.86, t(1,23) = -2.48, p=.023). Additionally, a trend-level main effect of early childhood trauma on subjective stress response emerged within this group (b=-.7, t(11) = -2, p=.07), where higher early trauma correlated with lower subjective stress response to the task. In the NAPD group, childhood trauma was not associated with the spatial extent of the tracer displacement in mPFC (b=-1.22, t(11) = -0.67), nor was there a main effect of trauma on the subjective perception of stress within this group (b=.004, t(11) = .01, p=.99). These findings reveal a potential mechanism of neuroadaptation of prefrontal DA transmission to early life stress and suggest its role in resilience and vulnerability to psychosis.