Maltreatment-related childhood adversity is the leading preventable risk factor for mental illness and substance abuse. Although the association between maltreatment and psychopathology is compelling, there is a pressing need to understand how maltreatment increases the risk of psychiatric disorders. Emerging evidence suggests that maltreatment alters trajectories of brain development to affect sensory systems, network architecture and circuits involved in threat detection, emotional regulation and reward anticipation. This Review explores whether these alterations reflect toxic effects of early-life stress or potentially adaptive modifications, the relationship between psychopathology and brain changes, and the distinction between resilience, susceptibility and compensation.

Background and Scope Childhood maltreatment is the most important preventable cause of psychopathology accounting for about 45% of the population attributable risk for childhood onset psychiatric disorders. A key breakthrough has been the discovery that maltreatment alters trajectories of brain development. This review aims to synthesize neuroimaging findings in children who experienced caregiver neglect as well as from studies in children, adolescents and adults who experienced physical, sexual and emotional abuse. In doing so we provide preliminary answers to questions regarding the importance of type and timing of exposure, gender differences, reversibility and the relationship between brain changes and psychopathology. We also discuss whether these changes represent adaptive modifications or stress-induced damage. Findings Parental verbal abuse, witnessing domestic violence and sexual abuse appear to specifically target brain regions (auditory, visual and somatosensory cortex) and pathways that process and convey the aversive experience. Maltreatment is associated with reliable morphological alterations in anterior cingulate, dorsal lateral prefrontal and orbitofrontal cortex, corpus callosum and adult hippocampus, and with enhanced amygdala response to emotional faces and diminished striatal response to anticipated rewards. Evidence is emerging that these regions and interconnecting pathways have sensitive exposure periods when they are most vulnerable. Early deprivation and later abuse may have opposite effects on amygdala volume. Structural and functional abnormalities initially attributed to psychiatric illness may be a more direct consequence of abuse. Conclusion Childhood maltreatment exerts a prepotent influence on brain development and has been an unrecognized confound in almost all psychiatric neuroimaging studies. These brain changes may be best understood as adaptive responses to facilitate survival and reproduction in the face of adversity. Their relationship to psychopathology is complex as they are discernible in both susceptible and resilient individuals with maltreatment histories. Mechanisms fostering resilience will need to be a primary focus of future studies.