Cortical Thickness Abnormalities at Different Stages of the Illness Course in Schizophrenia : A Systematic Review and Meta-analysis

Key Points

Question

Are there differences in cortical thickness (CTh) alterations between clinical high-risk (CHR), first episode of psychosis (FEP), and long-term illness stages of schizophrenia (SCZ)?

Findings

In meta-analyses comprising 2109 individuals across different illness stages of SCZ (10 studies of CHR, 12 studies of FEP, and 10 studies of long-term SCZ), CTh did not differ significantly between individuals with CHR and FEP, but those with long-term illness showed more pronounced CTh reductions than individuals with FEP. Accelerated age-related CTh reductions were found in frontotemporal cortex when combining all studies.

Meaning

The findings of this systematic review and meta-analysis do not indicate an emergence of CTh alterations with illness onset but suggest a progressively increasing thinning of CTh after illness onset.

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 Measures

Cortical 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 Relevance

The 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.

Abstract

This systematic review and meta-analysis examines changes in cortical thickness in individuals during differing phases across the course of schizophrenia.