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

JAMA Psychiatry. 2022 Jun 1;79(6):560-570. doi: 10.1001/jamapsychiatry.2022.0799.


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.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortical Thinning
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Prefrontal Cortex
  • Psychotic Disorders*
  • Schizophrenia* / diagnostic imaging
  • Young Adult