A meta‐analysis of deep brain structural shape and asymmetry abnormalities in 2,833 individuals with schizophrenia compared with 3,929 healthy volunteers via the ENIGMA Consortium

Abstract

Schizophrenia is associated with widespread alterations in subcortical brain structure.While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed moreconcave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.

Brain Asymmetry: Towards an Asymmetrical Neurovisceral Integration

“…On the other hand, the socioeconomic implications of a deeper understanding of brain asymmetry and its neurovisceral integration could predict and, when appropriate, prevent neuropathologies or behavioral deviations. The greater or lesser incidence of left or right neuropathologies can derive from alterations in the general asymmetric processing of the organism, including the asymmetric bidirectional connection between the brain and the peripheral tissues [73][74][75][76][77][78].…”

Effect of Season of Birth on Hippocampus Volume in a Transdiagnostic Sample of Patients With Depression and Schizophrenia

“…Depression as well as schizophrenia go along with significant ( Shah et al, 2017 ; Brandl et al, 2019 ; Hellewell et al, 2019 ; Huang et al, 2021 ; Liloia et al, 2021 ; Serra-Blasco et al, 2021 ; Gutman et al, 2022 ), progressive ( Vita et al, 2012 ) transdiagnostic ( Goodkind et al, 2015 ) as well as diagnosis and symptom specific ( Horn et al, 2010 ; Stegmayer et al, 2014 , 2016 ; Walther et al, 2017 ; Viher et al, 2018 ; Kindler et al, 2019 ; Schoretsanitis et al, 2019 ; Dean et al, 2020 ; Mertse et al, 2022 ) patterns of gray matter loss which may represent a hallmark of both disorders. Given the evidence for winter– and spring-birth excesses for schizophrenia, and major depression, and, as already mentioned, the suggested link with neurodevelopmental abnormalities, the question arises as to whether this seasonal birth pattern is associated with alterations in the brain.…”

Shape features of working memory-related deep-brain regions differentiate high and low community functioning in schizophrenia

“…In the SCZ group comparisons, significant inward deformation was noted in the HF-SCZ relative to LF-SCZ group only in the caudate and hippocampus; furthermore, qualitative review of the shape maps for all structures revealed a greater degree of shape abnormality in HF-SCZ relative to CON than LF-SCZ. Given that prior studies identify inward deformation of deep-brain structures as a core feature of schizophrenia ( Csernansky et al, 2002 ; Gutman et al, 2021 ; Wang et al, 2008 ), our results suggest HF-SCZ may represent a more typical neurobiological form of schizophrenia relative to LF-SCZ. Our expectation was that HF-SCZ would demonstrate brain abnormalities intermediate to CON and LF-SCZ.…”

“…The literature regarding alterations of the caudate in schizophrenia is generally consistent with our findings; however, the direction of the effect is mixed depending on method and sample composition. Inward shape deformation has been observed in multiple studies ( Cobia et al, 2021 ; Mamah et al, 2016 , Mamah et al, 2007 ), while surface expansion and thickening were noted in a recent meta-analysis of schizophrenia ( Gutman et al, 2021 ). Both SCZ groups showed greater hippocampal abnormalities relative to CON, with significant inward deformations, but additional outward deformations, in left dorsal and ventral regions for the LF-SCZ group.…”