Voxel-based morphometry of grey and white matter volumes, low-grade inflammation, and familial liability to psychosis

BACKGROUND: Few studies have examined associations between low-grade inflammation and both grey (GMV) and white matter volumes (WMV) in early-stage psychosis in addition to their unaffected siblings, which could help disentangle illness-specific neurobiological alterations from familial vulnerability. METHODS: We performed voxel-based morphometry (VBM) analyses of total and regional GMVs and WMVs in individuals with early psychosis (n = 71), their unaffected siblings (n = 24), and community controls (n = 36). We tested for associations between total and regional brain volumes with plasma levels of interleukin (IL)-1β, IL-6, IL-4, IL-10, tumour necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, and high-sensitive C-reactive protein (hs-CRP). Analyses were adjusted for sex, age, total intracranial volume, and time interval between blood sampling and brain imaging; in early-stage psychosis, models were additionally adjusted for duration of treatment. RESULTS: After correction for multiple comparisons (Benjamini-Hochberg False Discovery Rate), GMVs in the left middle frontal gyrus showed a negative association with plasma hs-CRP levels and a positive association with IL-1β levels in early-stage psychosis. In community controls, plasma IL-6 levels showed positive associations with GMVs in the left middle frontal gyrus, left calcarine fissure, bilateral precuneus, and left middle occipital gyrus, and with WMVs in the left precuneus. No significant associations were detected in unaffected siblings. CONCLUSION: Chronic low-grade inflammation may contribute to alterations in GMV in early-stage psychosis. The sibling sample in the present study was likely underpowered to reliably detect markers of familial vulnerability. Associations between IL-6 and brain volumes observed in community controls may indicate that cytokines exert context-dependent effects on brain structure. Future studies with larger and longitudinal samples are needed to disentangle pathological from physiological immune mechanisms influencing brain structure across health and disease.