Hippocampal pattern separation of emotional information determining risk or resilience in individuals exposed to childhood trauma: Linking exposure to neurodevelopmental alterations and threat anticipation

Childhood adversity increases the risk of developing psychiatric symptoms later in life. However, the neuro-biological mechanisms underlying this association are unknown. This paper reviews the current literature regarding structural and functional alterations in the hippocampus and amygdala following childhood adversity, ultimately converging into a model that proposes impaired 'pattern separation' as an important underlying mechanism associated with risk or resilience for psychopathology through increased fear generalization. In the present model, decreased DG/CA3 activity and amygdala hyper-reactivity are considered to be a consequence of childhood adversity, which in turn may result in impaired pattern separation of emotional information. Impaired pattern separation is hypothesized to result in increased fear generalization, threat anticipation, and social threat interpretation, thus increasing risk for later affective, anxiety and psychotic symptoms. The proposed model provides testable hypotheses for future studies and stresses the need to stratify according to childhood adversity as an etiological factor.