Subcortical volumetric alterations in four major psychiatric disorders: a mega-analysis study of 5604 subjects and a volumetric data-driven approach for classification

Abstract

Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs. The creation of a novel diagnostic system using objective biomarkers is expected to take place. Neuroimaging studies and others reported that subcortical brain structures are the hubs for various psycho-behavioral functions, while there are so far no neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning. Prior to the main analysis, we conducted a large-scale multisite study of subcortical volumetric and lateralization alterations in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder using T1-weighted images of 5604 subjects (3078 controls and 2526 patients). We demonstrated larger lateral ventricles volume in schizophrenia, bipolar disorder, and major depressive disorder, smaller hippocampus volume in schizophrenia and bipolar disorder, and schizophrenia-specific smaller amygdala, thalamus, and accumbens volumes and larger caudate, putamen, and pallidum volumes. In addition, we observed a leftward alteration of lateralization for pallidum volume specifically in schizophrenia. Moreover, as our main objective, we clustered the 5,604 subjects based on subcortical volumes, and explored whether data-driven clustering results can explain cognitive/social functioning in the subcohorts. We showed a four-biotype classification, namely extremely (Brain Biotype [BB] 1) and moderately smaller limbic regions (BB2), larger basal ganglia (BB3), and normal volumes (BB4), being associated with cognitive/social functioning. Specifically, BB1 and BB2–3 were associated with severe and mild cognitive/social impairment, respectively, while BB4 was characterized by normal cognitive/social functioning. Our results may lead to the future creation of novel biological data-driven psychiatric diagnostic criteria, which may be expected to be useful for prediction or therapeutic selection.

The relationship between the size and asymmetry of the lateral ventricles and cortical myelin content in individuals with mood disorders

“…We also examined the relationship between the lateral ventricles size and asymmetry with the levels of cortical myelin observed in the brain regions proximal and distal to the lateral ventricles. Consistent with previous studies, the individuals with mood disorders had larger lateral ventricles than their HC counterparts (Hibar et al, 2016; Okada et al, 2023; Schmaal et al, 2016; Strakowski et al, 2002). This distinction was the most pronounced in the individuals with BD-I and MDD relative to HC rather than those with BD-II or PDD, thus reflecting the relationship between ventricular enlargement and mood disorder specificity (Edmiston et al, 2011; Grewal et al, 2023; Hauser et al, 2000; Scott et al, 1983).…”

“…For example, some studies revealed greater cortical and subcortical asymmetry in DD compared to HC (Zuo et al, 2019). However, the recent mega-analysis did not reveal significant group differences in the laterality index of the lateral ventricles in either BD or DD relative to HC (Okada et al, 2023). Considering that emotion processing and regulation were linked to hemispheric asymmetries (Bourne, 2010;Davidson, 1993;Davidson & Irwin, 1999;Turnbull & Salas, 2021) and that both are affected in mood disorders (Joormann & Gotlib, 2010;Miola et al, 2022), understanding ventricular asymmetry may shed light on neurobiological mechanisms underlying emotion dysregulation in BD and DD.…”

Cortical Similarities in Psychiatric and Mood Disorders Identified in Federated VBM Analysis via COINSTAC

“…Our findings within the hippocampus are also aligned with previous literature (Brosch et al, 2022;Lorenzetti et al, 2009;McCutcheon et al, 2023;Torres et al, 2016) that found reductions within MDD, BP, and SZ. Other cross-disorder studies found similar shared and disease-specific alterations in the hippocampus, amygdala, thalamus, accumbens of individuals with SZ, BP, and MDD (Okada et al, 2023). Future research is needed to examine these alterations in the whole-patient context to identify their relationships to cognitive and social functioning, course of illness, and medication.…”

Longitudinal reduction in brain volume in patients with schizophrenia and its association with cognitive function

“…6 The volumes of subcortical structures, including the hippocampus, amygdala, thalamus, nucleus accumbens, pallidum, and lateral ventricle, are affected by schizophrenia. [7][8][9] Cortical structures are also affected in individuals with schizophrenia. van Erp et al 10 and Matsumoto et al 11 demonstrated the widespread effects of schizophrenia on cortical structures, with larger effect sizes in the frontal and temporal cortex regions.…”