Interhemispheric connectivity and hemispheric specialization in schizophrenia patients and their unaffected siblings

Hemispheric integration and specialization are two prominent organizational principles for macroscopic brain function. Impairments of interhemispheric cooperation have been reported in schizophrenia patients, but whether such abnormalities should be attributed to effects of illness or familial risk remains inconclusive. Moreover, it is unclear how abnormalities in interhemispheric connectivity impact hemispheric specialization. To address these questions, we performed magnetic resonance imaging (MRI) in a large cohort of 253 participants, including 84 schizophrenia patients, 106 of their unaffected siblings and 63 healthy controls. Interhemispheric connectivity and hemispheric specialization were calculated from resting-state functional connectivity, and compared across groups. Results showed that schizophrenia patients exhibit lower interhemispheric connectivity as compared to controls and siblings. In addition, patients showed higher levels of hemispheric specialization as compared to siblings. Level of interhemispheric connectivity and hemispheric specialization correlated with duration of illness in patients. No significant alterations were identified in siblings relative to controls on both measurements. Furthermore, alterations in interhemispheric connectivity correlated with changes in hemispheric specialization in patients relative to controls and siblings. Taken together, these results suggest that lower interhemispheric connectivity and associated abnormalities in hemispheric specialization are features of established illness, rather than an expression of preexistent familial risk for schizophrenia.