Elaborative Verbal Encoding and Altered Anterior Parahippocampal Activation in Adolescents and Young Adults at Genetic Risk for Schizophrenia Using fMRI

Background First-degree relatives of persons with schizophrenia are at elevated risk for the illness, demonstrate deficits in verbal memory, and exhibit structural abnormalities in the medial temporal lobe (MTL). We used functional magnetic resonance imaging (fMRI) to assess brain activity in the MTL during novel and repeated word-pair encoding. Methods Participants were 21 non-psychotic, first-degree relatives of persons with schizophrenia and 26 matched healthy controls (ages 13–28). fMRI signal change was measured using a Siemens 1.5T MR scanner, and data were analyzed using SPM-2. Verbal memory was assessed using the Miller Selfridge (MS) Context Memory test prior to scanning. Results The groups were comparable on demographics, intelligence and post-scan word recognition. Relatives at genetic risk (GR) had significantly more psychopathology than controls and worse performance on the MS test (p < .05). GR participants exhibited greater repetition suppression of activation in the left and right anterior parahippocampus (PHA, in the region of the entorhinal cortex region), after controlling for possible confounders. Controls and GR participants with above-median MS performance showed significantly greater repetition suppression of activation in left inferior frontal gyrus than those scoring below the median. Conclusions This is the first study to demonstrate an alteration of brain activity in the PHA in persons at GR for schizophrenia.