Introduction: The fundamental role of the cerebellum in higher cognitive processing has recently been highlighted. However, inconsistent findings exist in schizophrenia with respect to the exact nature of cerebellar structural abnormalities and their associations with cognitive and clinical features.Materials and Methods: We undertook a detailed investigation of cerebellar lobular volumes in 40 patients with first-episode psychosis (FEP) and 40 healthy controls (HCs) using the spatially unbiased atlas template of the cerebellum (SUIT). We examined the functional significance of cerebellar structural abnormalities in relation to cognitive and clinical outcomes in patients.Results: We found that left cerebellar lobules VI and X volumes were lower in FEP patients, compared to HCs. Smaller left lobules VI and X volumes were associated with fewer number of categories completed on the Wisconsin Card Sorting Test (WCST) in patients. In addition, smaller left lobule X volume was related to performance delay on the Trail Making Test (TMT) Part B in patients.Conclusion: Our results demonstrate that cerebellar structural abnormalities are present at the early stage of schizophrenia. We suggest functional associations of cerebellar structural changes with non-verbal executive dysfunctions in FEP.
Evidence suggests that the cortico-striatalthalamo-cortical circuitry plays an important role in schizophrenia pathophysiology. Cerebellar contribution from deep cerebellar nuclei to the circuitry has not yet been examined. The authors investigated resting-state functional connectivity (RSFC) of cerebellar output nuclei with striatal-thalamiccortical regions in relation to white-matter integrity and regional gray-matter volumes in first-episode psychosis (FEP).Methods: Forty FEP patients and 40 age-and gendermatched healthy control subjects (HCs) participated. RSFC between cerebellar nuclei and striatal-thalamic-cortical regions was examined. Diffusion tensor imaging and volumetric scans were examined for possible structural constraints on RSFC. The authors also examined relationships between neuroimaging variables and cognitive and clinical measures.Results: FEP patients, compared with HCs, exhibited decreased RSFC between the left fastigial nucleus and right putamen, which was associated with poor letter fluency performance and lower global assessment of functioning scores. By contrast, patients showed widespread increased accumbens network connectivity in the left nucleus. The authors further observed both hypo-and hyper-RSFC between the cerebellar nuclei and fronto-parietal areas in patients, independent of striatal activity. Finally, the authors found impaired integrity of the left superior cerebellar peduncle and decreased bilateral putamen volume in patients, whereas structural-functional relationships found in HCs were absent in patients.
Conclusions:This study provides evidence of disordered RSFC of cerebellar output nuclei to the striatum and neocortex at the early stage of schizophrenia. Furthermore, dysfunctional cerebellar influences on fronto-parietal areas that are independent of striatal dysfunction in patients with FEP were observed. The results suggest that cortico-striatal abnormalities in patients with FEP are produced by abnormal cerebellar influences.
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