Work

Subcortical Shape Alterations in Schizophrenia: A Single-Site Validation of ENIGMA’s Meta-Analytic Findings

Year: 2026

Type: article

Abstract: Introduction: Although meta-analysis by combining samples from multiple studies increases the statistical power, differences in study designs, participant characteristics, and outcome measures can create heterogeneity. Therefore, it might be helpful to validate the results of meta-analysis in independent smaller single site samples. This study investigates the shape characteristics of subcortical structures in schizophrenia patients by replicating and extending findings from a large multi-site meta-analysis using a single-site cohort. Methods: Employing the ENIGMA shape analysis protocol, we examined the MRI images of 57 patients and 37 controls using FreeSurfer. Results: Compared with controls, schizophrenia was associated with surface contraction in the left hippocampus, bilateral thalamus, bilateral nucleus accumbens, and right amygdala, alongside surface expansion in the bilateral putamen, left caudate, and bilateral pallidum; the right caudate showed both expansion and contraction. Thickness reductions were observed in the bilateral hippocampus, bilateral thalamus, bilateral accumbens, and right amygdala, while thickening was most evident in the right pallidum; the caudate, putamen, and left pallidum showed bidirectional thickness patterns. Antipsychotic dosage showed no significant effect on shape measures. Notably, our effect sizes surpassed those observed in earlier multi-site work. Larger effect sizes observed in our study could be attributed to the higher sampling variability due to relatively smaller sample size or increased clinical severity among patients from our single center compared to the patient populations in the meta-analysis. Conclusions: Overall, these findings underscore the utility of shape-based analyses for understanding schizophrenia neuroanatomy, emphasize considering the clinical characteristics of the study sample, and highlight the importance of single-site validation-particularly for cohorts not represented in larger consortia that have higher baseline clinical severity.

Source: Nöro Psikiyatri Arşivi

DOI: 10.29399/npa.29228