Cortical Thickness Abnormalities at Different Stages of the Illness Course in Schizophrenia

Abstract

IMPORTANCE Questions of whether and how cortical thickness (CTh) alterations differ over the course of schizophrenia (SCZ) have yet to be resolved. OBJECTIVE To characterize CTh alterations across illness stages in SCZ.DATA SOURCES PubMed, Embase, Web of Science, and Science Direct were screened for CTh studies published before June 15, 2021.STUDY SELECTION Original studies comparing whole-brain CTh alterations from healthy controls in individuals at clinical high-risk (CHR), first episode of psychosis (FEP), and long-term illness stages of SCZ were included.DATA EXTRACTION AND SYNTHESIS This preregistered systematic review and meta-analysis followed PRISMA reporting guidelines. Separate and pooled meta-analyses were performed using seed-based d mapping. Meta-regression analyses were conducted. MAIN OUTCOMES AND MEASURESCortical thickness differences from healthy control individuals across illness stages. RESULTS Ten studies comprising 859 individuals with CHR (mean [SD] age, 21.02 [2.66] years; male, 573 [66.7%]), 12 studies including 671 individuals with FEP (mean [SD] age, 22.87 [3.99] years; male, 439 [65.4%]), and 10 studies comprising 579 individuals with long-term SCZ (mean [SD] age, 41.58 [6.95] years; male, 396 [68.4%]) were included. Compared with healthy control individuals, individuals with CHR showed cortical thinning in bilateral medial prefrontal cortex (z = −1.01; P < .001). Individuals with FEP showed cortical thinning in right lateral superior temporal cortex (z = −1.34; P < .001), right anterior cingulate cortex (z = −1.44; P < .001), and right insula (z = −1.14; P = .002). Individuals with long-term SCZ demonstrated CTh reductions in right insula (z = −3.25; P < .001), right inferior frontal cortex (z = −2.19; P < .001), and left (z = −2.37; P < .001) and right (z = −1.94; P = .002) temporal pole. There were no significant CTh differences between CHR and FEP. Individuals with long-term SCZ showed greater cortical thinning in right insula (z = −2.58; P < .001), right inferior frontal cortex (z = −2.32; P < .001), left lateral temporal cortex (z = −1.91; P = .002), and right temporal pole (z = −1.82; P = .002) than individuals with FEP. Combining all studies on SCZ, accelerated age-related CTh reductions were found in bilateral lateral middle temporal cortex and right pars orbitalis in inferior frontal cortex. CONCLUSIONS AND RELEVANCEThe absence of significant differences between FEP and CHR noted in this systematic review and meta-analysis suggests that the onset of psychosis was not associated with robust CTh reduction. The greater cortical thinning in long-term SCZ compared with FEP with accelerated age-related reduction in CTh suggests progressive neuroanatomic alterations following illness onset. Caution in interpretation is needed because heterogeneity in samples and antipsychotic treatment may confound these results.

Widespread cortical thinning, excessive glutamate and impaired linguistic functioning in schizophrenia: A cluster analytic approach

“…Thus, brain structure can provide more stable and reliable clustering solutions. Further, aberrant cortical thickness has been reported in various illness stages of schizophrenia (Zhao et al, 2022), and has been found to track the inter-individual differences in psychotic symptoms (Oertel-Knöchel et al, 2013) and Thought and Language Disorder scores in schizophrenia (Palaniyappan et al, 2020). Prior cluster analytic studies have uncovered a consistent cluster of patients with generalized reduction in cortical thickness (Dwyer et al, 2018;Chand et al, 2020;Liang et al, 2022).…”

Normative modeling of brain morphometry in Clinical High-Risk for Psychosis

“…The current study extends our understanding of the role of brain morphometry for psychosis by showing that regional neuroanatomical variation in CHR-P individuals is nested within normative variation. A small minority of CHR-PC patients had pronounced decrements in the cortical thickness and surface area of temporal regions reinforcing the relevance of these regions for psychosis risk [7][8][9] and syndromal schizophrenia. 11,12,23 Regional deviation from normative patterns in the CHR-P individuals did not show meaningful associations with the severity of positive symptoms.…”

“…6 Multiple magnetic resonance imaging (MRI) studies have focused on identifying neuroanatomical alterations in CHR-P compared to healthy individuals (HI). Two metaanalyses of these studies have highlighted cortical thickness (CT) reductions of small effect size in the frontotemporal regions of CHR individuals 7,8 while a mega-analysis of brain morphometric data from 1792 CHR-P and 1377 HI from the CHR-P Working Group of the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) Consortium found that such CT reductions were widespread (Cohen d range of -0.17 to -0.09). 9 Recently psychiatric neuroimaging has turned to normative modeling, which quantifies individual-level deviation in brain-derived phenotypes relative to a normative reference population.…”

Multiplexed and scalable cellular phenotyping toward the standardized three-dimensional human neuroanatomy

“…In addition to the thickness of the cortex, the densities of cells within the cortical laminar are also important and thought to impact brain function. For example, changes in cortical thickness and cell density have been reported in several neurological disorders (Cotter et al, 2001; Hanford et al, 2016; Thu et al, 2010; Zhao et al, 2022). However, little is known about the variability of cell densities within a gyrus/sulcus and how it is determined.…”