A meta-analysis of fMRI studies in healthy relatives of patients with schizophrenia

Genetically at-risk yet healthy relatives of patients with schizophrenia, sharing an important part of the genetic susceptibility to the disease, allow the study of neuroimaging endophenotypes. The aim of our study was to perform a meta-analysis of whole-brain functional magnetic resonance imaging (fMRI) studies that compared adult healthy relatives of patients with schizophrenia and controls.

Twenty-one whole-brain fMRI studies were included (17 using cognitive tasks and four using emotional tasks), published between 2003 and 2013. These studies included 467 healthy relatives of patients with schizophrenia and 768 controls. To conduct the statistical analysis, we used the effect-size signed differential mapping software, a voxel-based meta-analytic approach.

In healthy relatives of patients with schizophrenia, we observed a general pattern of overactivation across the 21 fMRI studies in right-sided frontal, parietal and temporal regions compared to controls. This pattern was accompanied by an underactivation in the cingulate gyrus. Our analyses showed a very similar pattern during purely cognitive tasks; during emotional tasks, healthy relatives additionally overactivated the left parahippocampal gyrus.

This fMRI pattern of prefrontal overactivation and hypoactivation of the cingulate gyrus may represent a candidate endophenotype for schizophrenia.