| Summary: | Abstract This study (i) conducted a meta-analysis to examine whether relatives of schizophrenia patients (FRs) have structural or functional abnormalities in the brain when compared to healthy controls, (ii) conducted original studies whether familial, genetic, or symptomatic risk for psychosis is related to physiological fluctuation in the brain, and (iii) examined whether those brain-level abnormalities at risk for psychosis overlap with the regions that exhibit abnormalities in schizophrenia patients (using the BrainMap database). In the meta-analysis, we included altogether 39 studies (1639 FRs; 1734 controls) that examined differences between FRs and healthy controls using voxel-based morphometry (VBM) or functional magnetic resonance imaging (fMRI). In the original studies, we used the Northern Finland Birth Cohort 1986 data (N=140–277). All the participants underwent fMRI scan at rest. Symptomatic risk for psychosis was assessed with a structured psychiatric interview. Familial risk for psychosis was defined on the basis of parents’ previous psychoses. Polygenic risk score for schizophrenia was computed on the basis of previous genome-wide association studies. Physiological fluctuation was measured with the coefficient of variation of the blood-oxygenation-level-dependent (BOLD) signal (CVBOLD). In the meta-analysis, no differences were found in the gray matter volume. FRs (vs. healthy controls) had higher activity in the right inferior frontal gyrus during cognitive tasks. The alterations in FRs were very restricted when compared to the brain regions affected in schizophrenia patients. In the original studies, symptomatic risk (but not familial or genetic risk) for psychosis was linked to higher physiological fluctuation in such brain regions that overlapped only slightly with the regions that exhibited alterations in schizophrenia patients in previous fMRI studies (using traditional analyzing methods). There may be functional abnormalities during cognitive tasks in FRs (vs. healthy controls) in a ...
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