Hippocampal Connectivity With the Default Mode Network Is Linked to Hippocampal Volume in the Clinical High Risk for Psychosis Syndrome and Healthy Individuals

Abstract

Reduced hippocampal volume is an established brain morphological feature of psychiatric conditions. Hippocampal volume is associated with brain connectivity in humans and nonhuman animals, and altered connectivity is associated with risk for psychiatric illness. Associations between hippocampal volume and connectivity are poorly characterized in humans, especially in phases of psychiatric illness that precede disease onset. This study examined associations between hippocampal volume and hippocampal functional connectivity during rest in 141 healthy control participants and 248 individuals at risk for psychosis. Significant inverse associations between hippocampal volume and hippocampal functional connectivity with the inferior parietal lobe (IPL) and thalamus were observed. Select associations between hippocampal functional connectivity and hippocampal volume were moderated by diagnostic group. Significant moderation results shifted from implicating the IPL to the temporal pole after we excluded participants on antipsychotic medication. Considered together, these findings imply that hippocampal functional connectivity with the temporoparietal junction, within a specialized subsystem of the default mode network, is sensitive to hippocampal volume.