Rich club disconnectivity may be ‘core’ schizophrenia feature

By Eleanor McDermid, Senior medwireNews Reporter

The impaired “rich club” connectivity observed in the brains of patients with schizophrenia is also present in their unaffected siblings, report researchers.

Guusje Collin (University Medical Center Utrecht, the Netherlands) and colleagues found that rich club connectivity in the brains of unaffected siblings is intermediate to that in schizophrenia patients and mentally healthy controls.

This suggests that “impaired rich club connectivity in patients is likely to have a familiar, possibly genetic, component,” they write in Schizophrenia Bulletin.

Rich club connectivity involves densely interconnected central hub nodes in the brain, which are thought to play a crucial role in communication between different brain regions. The same team recently showed impairments in this connectivity in patients with schizophrenia, as reported by medwireNews.

The current study involved 40 the of same schizophrenia patients, but also 54 of their unaffected siblings and 51 mentally healthy controls who had no close family members with a lifetime psychotic disorder.

Rich club connectivity strength, measured on diffusion-weighted magnetic resonance imaging, was 7.9% lower in siblings than controls, and 19.6% lower in schizophrenia patients.

“One possible explanation may be that the observed reductions in rich club connectivity reflect a gene dosage effect, with a higher number, or expression, of schizophrenia risk alleles in patients than siblings, resulting in lower levels of rich club connectivity,” say Collin et al.

Notably, the strength of feeder connections (between rich club and peripheral nodes) did not differ between the groups, indicating that rich club connectivity specifically was affected in schizophrenia patients and siblings. Local connections (between peripheral nodes) were slightly affected by schizophrenia status, with connectivity strength reduced by 2.5% in siblings and 12.8% in patients, compared with controls.

The researchers also found the degree of impairment in rich club connectivity in patients to be related to illness duration and clinical functioning, suggesting that clinical illness could itself contribute to disconnectivity. However, they note that this is speculative owing to the cross-sectional nature of the study.

Schizophrenia patients also had reduced connectivity strength and global efficiency of the entire brain network, relative to controls, but siblings did not. Both groups had reductions in overall clustering (the likelihood that the neighbors of a node are interconnected), with the differences being greater in patients than siblings. These differences decreased after accounting for rich club connectivity, suggesting that this partly accounted for the reduced clustering.

“In all, our findings suggest that rich club dysconnectivity may be a core aspect of schizophrenia, both prior to and after the onset of illness,” concludes the team.

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