Interrelated neuropsychological and anatomical evidence of hippocampal pathology in the at-risk mental state

Background. Verbal learning and memory deficits are frequent among patients with schizophrenia and correlate with reduced magnetic resonance imaging (MRI) volumes of the hippocampus in these patients. A crucial question is the extent to which interrelated structural-functional deficits of the hippocampus reflect a vulnerability to schizophrenia, as opposed to the disorder per se. Method. We combined brain structural measures and the Rey Auditory Verbal Learning Test (RAVLT) to assess hippocampal structure and function in 36 never-medicated individuals suspected to be in early (EPS) or late prodromal states (LPS) of schizophrenia relative to 30 healthy controls. Results. Group comparisons revealed bilaterally reduced MRI hippocampal volumes in both EPS and LPS subjects. In LPS subjects but not in EPS subjects, these reductions were correlated with poorer performance in RAVLT delayed recall. Conclusions. Our findings suggest progressive and interrelated structural-functional pathology of the hippocampus, as prodromal symptoms and behaviours accumulate, and the level of risk for psychosis increases. Given the inverse correlation of learning and memory deficits with social and vocational functioning in established schizophrenia, our findings substantiate the rationale for developing preventive treatment strategies that maintain cognitive capacities in the at-risk mental state.