Resting-state Functional Hypoconnectivity of Amygdala in Clinical High Risk State and First-episode Schizophrenia

Resting-state functional hypoconnectivity of the amygdala with several brain regions has been identified in patients with schizophrenia. However, little is known about it in individuals at clinical high risk state. Treatment-seeking, drug-naive young adults were recruited for the study. The participants included 33 adults at Clinical High Risk (CHRs), 31 adults with first-episode schizophrenia (FSZs), and 37 age-, gender-, and education-matched healthy controls. All the participants were subjected to resting-state functional magnetic resonance imaging scans. Seed-based voxel-wise amygdala/whole-brain functional connectivity (FC) was calculated and compared. In the CHR group, the right amygdala showed decreased FC with clusters located in the left orbital, right temporal, insular, and bilateral frontal and cingulate areas. In the FSZ group, the right amygdala showed decreased FC with clusters located in the right temporal, insular, cingulate, and frontal areas. Exactly 30% of the voxels showing decreased FC in the FSZ group coincided with those in the CHR group. No difference in FC was identified between the CHR and FSZ groups. Voxel-wise FC values with the left or right amygdala in the bilateral occipital cortex were negatively correlated with the PANSS total score in the FSZ group. Resting-state functional hypoconnectivity of the amygdala is a valuable risk phenotype of schizophrenia, and its distribution, rather than degree, distinguishes CHR state from schizophrenia. This particular hypoconnectivity in CHRs and FSZs is relatively independent of the symptomatology and may reflect a dysfunctional dopamine system.