Alterations in Hippocampal Connectivity Across the Psychosis Dimension

Recent evidence demonstrates that hippocampal hyperactivity helps mediate psychosis. Using resting state functional magnetic resonance imaging (rsfMRI), we examined hippocampal connectivity alterations in individuals with psychosis (PS) versus healthy controls (HC). Because of its putative greater involvement in psychiatric disorders, we hypothesized that the anterior hippocampus network would show greater dysconnectivity in psychosis. We tested rsfMRI connectivity in 88 PS (including 21 with schizophrenia; 40 with schizoaffective disorder; 27 with psychotic bipolar I disorder) and 65 HC. Seed-based voxel-wise connectivity analyses were carried out using whole, anterior, and posterior hippocampal seeds. No significant differences in functional hippocampal connectivity were found across the three conventional diagnoses. PS were then contrasted with HC, showing strong reductions in anterior hippocampal connectivity to anterior neocortical regions, including medial frontal and anterior cingulate cortices, as well as superior temporal gyrus, precuneus, thalamus and cerebellum. Posterior hippocampal seeds also demonstrated decreased connectivity in PS, with fewer dysconnected regions and a posterior/cerebellar distribution. Whole hippocampal outcomes were consistent with anterior/posterior hippocampal connectivity changes. Connectivity alterations did not correlate with cognition, clinical symptoms, or medication effect variables. Our results suggest a psychosis network of decreased hippocampal connectivity with limbic and frontal contributions, independent of diagnostic categories.