Age-related alterations of local gyrification index in female patients with schizophrenia: a surface-based morphometry study

Background

Schizophrenia has been widely conceptualized as a neurodevelopmental disorder, with cortical folding abnormalities reflecting early disturbances in brain maturation. The local gyrification index (LGI), a surface-based measure derived from structural MRI, quantifies the degree of cortical folding and has been proposed as a potential biomarker of neurodevelopmental processes. While previous studies have reported reduced LGI in schizophrenia, findings have been inconsistent, particularly with regard to the influence of age. This study aimed to investigate LGI differences between female patients with schizophrenia and healthy controls and to evaluate age-related effects on LGI across cortical regions.

Methods

A total of 62 participants were included, comprising 31 female inpatients diagnosed with schizophrenia and 31 age-matched healthy controls. All participants underwent 3T MRI scanning at Chungbuk National University Hospital between January 2016 and June 2023. Cortical reconstruction and LGI computation were performed using the FreeSurfer processing pipeline (version 7.2.0), based on the Desikan–Killiany atlas, yielding 70 region-of-interest (ROI) measures. Group differences were initially assessed at the lobe level using Mann–Whitney U tests, with effect sizes quantified as rank-biserial correlations (r). ROI-level analyses were subsequently conducted to localize regional effects, applying thresholds of uncorrected p < .05 and r ≥ .30 for visualization. To disentangle age and group effects, multiple linear regression models (LGI ~ age + group) were fitted for each ROI. Partial correlation coefficients (partial r) were derived from regression t-statistics, and false discovery rate (FDR) correction was applied to control for multiple comparisons.

Results

Across the entire sample, LGI demonstrated a significant negative association with age, predominantly in right anterior cortical regions, including the frontal lobe and insula. Group comparisons revealed significantly lower LGI values in the schizophrenia group relative to controls across multiple cortical regions. At the lobe level, the largest effect sizes were observed in the occipital (r ≈ 0.59), parietal (r ≈ 0.47–0.48), and temporal lobes (r ≈ 0.43), as well as in the insula (r ≈ 0.39–0.41), indicating widespread reductions in cortical folding in patients. ROI-level analyses further localized these differences to the left occipital, parietal, temporal, and posterior cingulate regions. Regression analyses indicated that age-related LGI decline was more pronounced in the control group, whereas patients exhibited relatively stable but consistently lower LGI across age. Consequently, group differences were largest at younger ages and attenuated with increasing age.

Conclusions

These findings support the hypothesis that reduced cortical gyrification is a feature of schizophrenia consistent with neurodevelopmental disruption. The observed age-related patterns suggest that LGI alterations may be more sensitive to early developmental abnormalities rather than progressive changes over the lifespan. However, the attenuation of group differences with age highlights the importance of accounting for age effects in LGI studies. Future research should further examine the clinical utility of LGI as a biomarker by incorporating additional factors such as illness stage, treatment exposure, and longitudinal trajectories.

References

1. Schaer, M., Cuadra, M.B., Tamarit, L., Lazeyras, F., Eliez, S., Thiran, J-P., 2008, A Surface-based approach to quantify local cortical gyrification. IEEE Trans Méd Imaging 27,161–170.
2. Matsuda, Y., Ohi, K., 2018, Cortical gyrification in schizophrenia: current perspectives. Neuropsychiatr Dis Treat 14:1861–1869.
3. Madre, M., Canales-Rodríguez, E.J., Fuentes-Claramonte, P., Alonso-Lana, S., Salgado-Pineda, P., Guerrero-Pedraza, A., et al., 2019, Structural abnormality in schizophrenia versus bipolar disorder: A whole brain cortical thickness, surface area, volume and gyrification analyses. NeuroImage Clin 25:102131.