Microstructural white matter network-connectivity in individuals with psychotic disorder, unaffected siblings and controls

Background: Altered structural network-connectivity has been reported in psychotic disorder but whether these alterations are associated with genetic vulnerability, and/or with phenotypic variation, has been less well examined. This study examined i) whether differences in network-connectivity exist between patients with psychotic disorder, siblings of patients with psychotic disorder and controls, and ii) whether network-connectivity alterations vary with (subclinical) symptomatology.

Methods: Network-connectivity measures (global efficiency (GE), density, local efficiency (LE), clustering coefficient (CC)) were derived from diffusion weighted imaging (DWI) and were compared between 85 patients with psychotic disorder, 93 siblings without psychotic disorder and 80 healthy comparison subjects using multilevel regression models. In patients, associations between Positive and Negative Syndrome Scale (PANSS) symptoms and topological measures were examined. In addition, interactions between subclinical psychopathology and sibling/healthy comparison subject status were examined in models of topological measures.

Results: While there was no main effect of group with respect to GE, density, LE and CC, siblings had a significantly higher CC compared to patients (B = 0.0039, p = .002). In patients, none of the PANSS symptom domains were significantly associated with any of the four network-connectivity measures. The two-way interaction between group and SIR-r positive score in the model of LE was significant (chi(2) = 6.24, p = .01, df = 1). In the model of CC, the interactions between group and respectively SIS-r positive (chi(2) = 5.59, p = .02, df = 1) and negative symptom scores (chi(2) = 4.71, p = .03, df = 1) were significant. Stratified analysis showed that, in siblings, decreased LE and CC was significantly associated with increased SIS-r positive scores (LE: B = - 0.0049, p = .003, CC: B = - 0.0066, p = .01) and that decreased CC was significantly associated with increased SIS-r negative scores (B = - 0.012, p = .003). There were no significant interactions between group and SIS-r scores in the models of GE and density.

Conclusion: The findings indicate absence of structural network-connectivity alterations in individuals with psychotic disorder and in individuals at higher than average genetic risk for psychotic disorder, in comparison with healthy subjects. The differential subclinical symptom-network connectivity associations in siblings with respect to controls may be a sign of psychosis vulnerability in the siblings.