Overlapping Neurobiological Substrates for Early-Life Stress and Resilience to Psychosis

Early-life stress, such as childhood maltreatment, is a well-known etiological factor in psychopathology, including psychosis. Exposure to early-life stress disrupts the neurodevelopment of widespread brain systems, including key components of the hypothalamic-pituitary-adrenal axis stress response, such as the amygdala, hippocampus, and medial prefrontal cortex, as well as key components of the brain's reward system, such as the nucleus accumbens and orbitofrontal cortex. These disruptions have a considerable impact on the function of emotion and reward circuitry, which play a central role in the emergence and severity of psychosis. While this overlap may provide insight into the pathophysiology of psychosis, it also provides unique opportunities to elucidate neurobiological substrates that may promote resilience to psychosis. In this review, we discuss the hypothalamic-pituitary-adrenal axis stress response, discuss the disruption in the neurodevelopment of emotion and reward processing associated with early stress exposures, and examine how this circuitry may contribute to resilience to psychotic disorders.