Impaired rich club connectivity in unaffected siblings of schizophrenia patients

Guusje Collin*, René S. Kahn, Marcel A. De Reus, Wiepke Cahn, Martijn P. Van Den Heuvel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Schizophrenia has been conceptualized as a disorder of brain connectivity. Recent studies suggest that brain connectivity may be disproportionally impaired among the so-called rich club. This small core of densely interconnected hub regions has been hypothesized to form an important infrastructure for global brain communication and integration of information across different systems of the brain. Given the heritable nature of the illness, we hypothesized that connectivity disturbances, including abnormal rich club connectivity, may be related to familial vulnerability for schizophrenia. To test this hypothesis, both schizophrenia patients and unaffected siblings of patients were investigated. Rich club organization was examined in networks derived from diffusion-weighted imaging in 40 schizophrenia patients, 54 unaffected siblings of patients, and 51 healthy control subjects. Connectivity between rich club hubs was differentially reduced across groups (P =. 014), such that it was highest in controls, intermediate in siblings (7.9% reduced relative to controls), and lowest in patients (19.6% reduced compared to controls). Furthermore, in patients, lower levels of rich club connectivity were found to be related to longer duration of illness and worse overall functioning. Together, these findings suggest that impaired rich club connectivity is related to familial, possibly reflecting genetic, vulnerability for schizophrenia. Our findings support a central role for abnormal rich club organization in the etiology of schizophrenia.

Original languageEnglish
Pages (from-to)438-448
Number of pages11
JournalSchizophrenia Bulletin
Issue number2
Publication statusPublished - Mar 2014

Cite this