LAUSR

Abstract Abnormal regional activity and functional connectivity of the default-mode network (DMN) have been reported in schizophrenia. However, previous studies may have been biased by unmatched case–control design. To limit such bias, the present study used both the family-based case–control design and the traditional case–control design to investigate abnormal regional activity of the DMN in patients with schizophrenia at rest. Twenty-eight first-episode, drug-naive patients with schizophrenia, 28 age-, sex-matched unaffected siblings of the patients (family-based controls, FBC), and 40 healthy controls (HC) underwent resting-state functional magnetic resonance imaging (fMRI) scans. The group-independent component analysis and fractional amplitude of low-frequency fluctuation (fALFF) methods were used to analyze the data. Patients with schizophrenia show increased fALFF in an overlapped region of the right superior medial prefrontal cortex (MPFC) relative to the FBC and the HC. Compared with the HC, the patients and the FBC exhibit increased fALFF in an overlapped region of the left posterior cingulate cortex/precuneus (PCC/PCu). Furthermore, the z values of the 2 overlapped regions can separate the patients from the FBC/HC, and separate the patients/FBC from the HC with relatively high sensitivity and specificity. Both the family-based case–control and traditional case–control designs reveal hyperactivity of the DMN in first-episode, drug-naive patients with paranoid schizophrenia, which highlights the importance of the DMN in the neurobiology of schizophrenia. Family-based case–control design can limit the confounding effects of environmental factors in schizophrenia. Combination of the family-based case–control and traditional case–control designs may be a viable option for the neuroimaging studies.