Intact Relational Memory and Normal Hippocampal Structure in the Early Stage of Psychosis

Abstract

Previous studies indicate that the transition to psychosis is associated with dynamic changes of hippocampal integrity. Here we explored hippocampal volume and neural activation during a relational memory task in patients who were in the early stage of a psychotic illness. Forty-one early psychosis patients and 34 healthy control subjects completed a transitive inference (TI) task used previously in chronic schizophrenia patients. Participants learned to select the "winner" of two sets of stimulus pairs drawn from an overlapping sequence (A > B > C > D > E) and a nonoverlapping set (a > b, c > d, e > f, g > h). During a functional magnetic resonance imaging scan, participants were tested on the trained pairs and made inferential judgments on novel pairings that could be solved based on training (e.g., B vs. D). Hippocampal volumes were manually segmented and compared between groups. Functional magnetic resonance imaging analyses included 27 early psychosis patients and 30 control subjects who met memory training criteria. Groups did not differ on inference performance or hippocampal volume and exhibited similar activation of medial temporal regions when judging nonoverlapping pairs. However, patients who failed to meet memory training criteria had smaller hippocampal volumes. Neural activity during TI was less widespread in early psychosis patients, but between-group differences were not significant. Hippocampal activity during TI was positively correlated with inference performance only in control subjects. Our results provide evidence that relational memory impairment and hippocampal abnormalities, well established in chronic schizophrenia, are not fully present in early psychosis patients. This provides a rationale for early intervention, targeting the possible delay, reduction, or prevention of these deficits.