The relationship between white matter microstructure and general cognitive ability in patients with schizophrenia and healthy participants in the ENIGMA consortium

Laurena Holleran, Sinead Kelly, Clara Alloza, Ingrid Agartz, Ole A. Andreassen, Celso Arango, Nerisa Banaj, Vince Calhoun, Dara Cannon, Vaughan Carr, Aiden Corvin, David C. Glahn, Ruben Gur, Elliot Hong, Cyril Hoschl, Fleur M. Howells, Anthony James, Joost Janssen, Peter Kochunov, Stephen M. LawrieJingyu Liu, Covadonga Martinez, Colm McDonald, Derek Morris, David Mothersill, Christos Pantelis, Fabrizio Piras, Steven Potkin, Paul E. Rasser, David Roalf, Laura Rowland, Theodore Satterthwaite, Ulrich Schall, Gianfranco Spalletta, Filip Spaniel, Dan J. Stein, Anne Uhlmann, Aristotle Voineskos, Andrew Zalesky, Theo G.M. van Erp, Jessica A. Turner, Ian J. Deary, Paul M. Thompson, Neda Jahanshad, Gary Donohoe

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Objective: Schizophrenia has recently been associated with widespread white matter microstructural abnormalities, but the functional effects of these abnormalities remain unclear. Widespread heterogeneity of results from studies published to date preclude any definitive characterization of the relationship between white matter and cognitive performance in schizophrenia. Given the relevance of deficits in cognitive function to predicting social and functional outcomes in schizophrenia, the authors carried out a meta-analysis of available data through the ENIGMA Consortium, using a common analysis pipeline, to elucidate the relationship between white matter microstructure and a measure of general cognitive performance, IQ, in patients with schizophrenia and healthy participants. Methods: The meta-analysis included 760 patients with schizophrenia and 957 healthy participants from 11 participating ENIGMA Consortium sites. For each site, principal component analysis was used to calculate both a global fractional anisotropy component (gFA) and a fractional anisotropy component for six long association tracts (LA-gFA) previously associated with cognition. Results: Meta-analyses of regression results indicated that gFA accounted for a significant amount of variation in cognition in the full sample (effect size [Hedges’ g]=0.27, CI=0.17–0.36), with similar effects sizes observed for both the patient (effect size=0.20, CI=0.05–0.35) and healthy participant groups (effect size=0.32, CI=0.18–0.45). Comparable patterns of association were also observed between LA-gFA and cognition for the full sample (effect size=0.28, CI=0.18–0.37), the patient group (effect size=0.23, CI=0.09–0.38), and the healthy participant group (effect size=0.31, CI=0.18–0.44). Conclusions: This study provides robust evidence that cognitive ability is associated with global structural connectivity, with higher fractional anisotropy associated with higher IQ. This association was independent of diagnosis; while schizophrenia patients tended to have lower fractional anisotropy and lower IQ than healthy participants, the comparable size of effect in each group suggested a more general, rather than disease-specific, pattern of association.

Original languageEnglish (US)
Pages (from-to)537-547
Number of pages11
JournalAmerican Journal of Psychiatry
Issue number6
StatePublished - Jun 2020
Externally publishedYes

ASJC Scopus subject areas

  • Psychiatry and Mental health


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