Altered functional connectivity and low-frequency signal fluctuations in early psychosis and genetic high risk

Abstract Studying individuals at increased genetic risk for schizophrenia may generate important theories regarding the emergence of the illness. In this investigation, genetic high-risk individuals (GHR, n  = 37) were assessed with functional magnetic resonance imaging and compared to individuals in the first episode of schizophrenia (FESZ, n  = 42) and healthy comparison subjects (HCS, n  = 59). Measures of functional connectivity and the amplitude of low-frequency fluctuation (ALFF) were obtained in a global, data-driven analysis. The functional connectivity measure, termed degree centrality, assessed each voxel's connectivity with all the other voxels in the brain. GHR and FESZ displayed increased degree centrality globally and locally. On ALFF measures, GHR were indistinguishable from HCS in the majority of areas but resembled FESZ in insula, basal ganglia and hippocampus. FESZ evidenced reduced amplitude of the global neural signal as compared to HCS and GHR. Results support the hypothesis that schizophrenia diathesis involves functional connectivity and ALFF abnormalities. In addition, they further an emerging theory suggesting that increased connectivity and metabolism may be involved in schizophrenia vulnerability and early stages of the illness.