Grey matter volume patterns in thalamic nuclei are associated with familial risk for schizophrenia.

Previous evidence suggests reduced thalamic grey matter volume (GMV) in patients with schizophrenia (SCZ). However, it is not considered an intermediate phenotype for schizophrenia, possibly because previous studies did not assess the contribution of individual thalamic nuclei and employed univariate statistics. Here, we hypothesized that multivariate statistics would reveal an association of GMV in different thalamic nuclei with familial risk for schizophrenia. We also hypothesized that accounting for the heterogeneity of thalamic GMV in healthy controls would improve the detection of subjects at familial risk for the disorder. We acquired MRI scans for 96 clinically stable SCZ, 55 non-affected siblings of patients with schizophrenia (SIB), and 249 HC. The thalamus was parceled into seven regions of interest (ROIs). After a canonical univariate analysis, we used GMV estimates of thalamic ROIs, together with total thalamic GMV and premorbid intelligence, as features in Random Forests to classify HC, SIB, and SCZ. Then, we computed a Misclassification Index for each individual and tested the improvement in SIB detection after excluding a subsample of HC misclassified as patients. Random Forests discriminated SCZ from HC (accuracy=81%) and SIB from HC (accuracy=75%). Left anteromedial thalamic volumes were significantly associated with both multivariate classifications (p<0.05). Excluding HC misclassified as SCZ improved greatly HC vs. SIB classification (Cohen's d=1.39). These findings suggest that multivariate statistics identify a familial background associated with thalamic GMV reduction in SCZ. They also suggest the relevance of inter-individual variability of GMV patterns for the discrimination of individuals at familial risk for the disorder.

The role of the thalamus in schizophrenia from a neuroimaging perspective.

The thalamus is a crucial node for brain physiology and part of functional and structural pathways relevant for schizophrenia. Relatively few imaging studies on schizophrenia have focused on this brain region, yet extant evidence supports the association between this brain disorder and thalamic anomalies. Nevertheless, the mechanisms underlying this association remain largely conjectural. Here, we review imaging literature on the relationship between the thalamus and schizophrenia, focusing on critical challenges for future studies, in particular: (i) the anatomical and functional organization of the thalamus in separate nuclei, which are also differently connected with the cortex; (ii) state-dependent variables, which do not allow firm conclusions on the relevance of thalamic correlates as core phenotypes of schizophrenia and (iii) genetic variation, which affects thalamic physiology and may lead to variability of structural and functional patterns. Current evidence from the studies reviewed does not appear conclusive, although the relevance of thalamo-prefrontal interactions clearly emerges. Results from imaging genetics are beginning to cast insight on possible mechanisms of the involvement of the thalamus in schizophrenia.