Study Reveals Subtle Brain Asymmetry Differences in Schizophrenia

A recent study published in Proceedings of the National Academy of Sciences (PNAS) I am analyzing the structural asymmetry of the brain in schizophrenia.

study: Large-scale analysis of structural brain asymmetry in schizophrenia by the ENIGMA consortium. Image credit: hutpaza / Shutterstock.com

Pathology of schizophrenia

Schizophrenia is characterized by delusions, emotional flattening, impaired executive function, disorganized speech, hallucinations, and apathy. Left-right asymmetry is an essential feature of cognitive function. People with schizophrenia show reduced left-sided verbal dominance. Non-right-handedness is also elevated in schizophrenia.

Changes in cortical asymmetry in schizophrenia have been reported in small cohort size studies. The Enhancing Neuroimaging Genetics by Meta-Analysis (ENIGMA) consortium, conducting a large-scale analysis, previously reported cortical thinning, altered subcortical volume, and reduced surface area in patients with schizophrenia compared with controls. Did. However, in these previous his ENIGMA studies, asymmetry was not assessed.

About research

In the present study, researchers measured cortical and subcortical asymmetry in schizophrenia in the largest sample from 46 different datasets. Structural magnetic resonance imaging (MRI) data were obtained from a dataset containing 5,080 affected individuals and her 6,015 controls. Controls had no past/current signs of schizophrenia. A T1-weighted brain MRI scan was performed at the study site.

Measures of cerebral surface area and cortical thickness were derived for 34 bilateral paired Desican-Killany atlas regions. Global hemisphere-level measures of mean cortical thickness and surface area were also derived.

Eight bilateral paired regional volumes were derived from a neuroanatomical atlas of subcortical structures. Measurements of the left and right hemispheres were used to estimate the asymmetry index (AI).

Univariate linear regression analysis was used to examine differences in case-control groups separately. The effect sizes of diagnoses from each dataset were meta-analyzed for brain AI in each region and projected onto Brainder’s 3D mesh of the inflated cortical/subcortical model. For statistically significant AI with group differences, we performed post hoc analyzes using linear modeling to account for asymmetry differences.

Sensitivity analyzes assessed the robustness of outlier effects, heterogeneity of dataset-handedness differences, non-linear age effects, or effects of individual datasets with intracranial volume. Secondary analyzes assessed differences in treatment groups and correlations between asymmetries and clinical variables. Finally, we performed a multivariate analysis based on the 14 datasets to determine group differences simultaneously in one model.

findings

Mean cortical thickness and surface area asymmetry across all hemispheres were not significantly different between cases and controls. However, small but significant differences were observed between cases and controls at the regional level in thickness asymmetries in the middle temporal gyrus and rostral anterior cingulate cortex. A post hoc analysis indicated that the thin left cortex in schizophrenia patients was responsible for these regional asymmetry differences.

Three datasets had outlier effects in a primary meta-analysis on thickness asymmetry in the rostral anterior cingulate cortex. Repeating the meta-analysis with these exclusions did not change the direction of group differences.

For the thickness asymmetry in the middle temporal gyrus, similar results were obtained when the two outlier datasets were excluded. Group differences in these two regional AIs were nominally significant in a model that included handedness, intracranial volume, and age.

Rostral anterior cingulate cortex thickness asymmetry did not differ between treatment groups. In contrast, a small but significant increase in mean rightward asymmetry was observed when taking first-generation antipsychotics in the middle temporal gyrus. However, these differences were not significant across multiple test fixes.

A nominally significant correlation was identified between the severity of negative symptoms and the thickness asymmetry of the rostral anterior cingulate cortex. A similar correlation was also observed between asymmetry in the thickness of the middle temporal gyrus and disease duration. However, these correlations were not significant after multiple test corrections.

In addition, there was a significant interaction between diagnosis and age for globus pallidum volume asymmetry due to mean leftward asymmetry with aging in controls but not in cases. Left and right globus pallidum volumes decreased with age in cases and controls.

A significant difference in brain asymmetry was observed in multivariate analysis of 935 cases and 1,094 controls, thus accounting for 7% of the variance of all AIs.

Conclusion

Investigators in the current study evaluated case-control differences in brain asymmetry in schizophrenia. There were subtle regional asymmetry differences in the thickness of the rostral anterior cingulate cortex and middle temporal gyrus, and differences in globus pallidus volume in the elderly.

These findings suggest that morphological changes in schizophrenia are largely similar in both brain hemispheres, with only subtle asymmetries observed at the average group level. However, 7% of the total variance across all regional asymmetries was explained by case-control group differences in the multivariate analysis. This suggests diffuse/subtle changes in brain asymmetry in schizophrenia.