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

Research output: Contribution to journalResearch articleContributedpeer-review


  • ENIGMA-Schizophrenia - (Author)
  • Division of Psychological and Social Medicine and Developmental Neurosciences
  • Department of Child and Adolescent Psychiatry and Psychotherapy
  • Illinois Institute of Technology
  • University of California at Irvine
  • Feinberg School of Medicine
  • University of Southern California
  • Duke University
  • Oregon Health and Science University
  • Boston Children's Hospital
  • University of Pennsylvania
  • University of Oslo
  • University of Maryland, Baltimore
  • University of Pennsylvania Perelman School of Medicine
  • University of Minnesota System
  • University of California at San Francisco
  • Eastern New Mexico University
  • Emory University
  • Judith Ford Mental Health
  • Bath Spa University
  • Laboratory of Neuropsychiatry
  • FIDMAG Germanes Hospitalàries Research Foundation
  • Centre for Addiction and Mental Health (CAMH)
  • Hospital Universitario Marques de Valdecilla
  • University of Basel
  • University of Lübeck
  • University of Cape Town
  • Ohio State University
  • San Filippo Neri Hospital


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 more-concave-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.


Original languageEnglish
Pages (from-to)352-372
Number of pages21
JournalHuman brain mapping
Issue number1
Publication statusPublished - Jan 2022

External IDs

PubMedCentral PMC8675416
Scopus 85114302135
ORCID /0000-0003-2132-4445/work/142236353
ORCID /0000-0002-1753-7811/work/142248160



  • Amygdala/diagnostic imaging, Corpus Striatum/diagnostic imaging, Hippocampus/diagnostic imaging, Humans, Multicenter Studies as Topic, Neuroimaging, Schizophrenia/diagnostic imaging, Thalamus/diagnostic imaging