NeuroImage: Clinical (Jan 2022)

Cortico-cognition coupling in treatment resistant schizophrenia

  • Warda T. Syeda,
  • Cassandra M.J. Wannan,
  • Antonia H. Merritt,
  • Jayachandra M. Raghava,
  • Mahesh Jayaram,
  • Dennis Velakoulis,
  • Tina D. Kristensen,
  • Rigas Filippos Soldatos,
  • Shane Tonissen,
  • Naveen Thomas,
  • Karen S. Ambrosen,
  • Mikkel E. Sørensen,
  • Birgitte Fagerlund,
  • Egill Rostrup,
  • Birte Y. Glenthøj,
  • Efstratios Skafidas,
  • Chad A. Bousman,
  • Leigh A. Johnston,
  • Ian Everall,
  • Bjørn H. Ebdrup,
  • Christos Pantelis

Journal volume & issue
Vol. 35
p. 103064

Abstract

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Background: Brain structural alterations and cognitive dysfunction are independent predictors for poor clinical outcome in schizophrenia, and the associations between these domains remains unclear. We employed a novel, multiblock partial least squares correlation (MB-PLS-C) technique and investigated multivariate cortico-cognitive patterns in patients with treatment-resistant schizophrenia (TRS) and matched healthy controls (HC). Method: Forty-one TRS patients (age 38.5 ± 9.1, 30 males (M)), and 45 HC (age 40.2 ± 10.6, 29 M) underwent 3T structural MRI. Volumes of 68 brain regions and seven variables from CANTAB covering memory and executive domains were included. Univariate group differences were assessed, followed by the MB-PLS-C analyses to identify group-specific multivariate patterns of cortico-cognitive coupling. Supplementary three-group analyses, which included 23 non-affected first-degree relatives (NAR), were also conducted. Results: Univariate tests demonstrated that TRS patients showed impairments in all seven cognitive tasks and volume reductions in 12 cortical regions following Bonferroni correction. The MB-PLS-C analyses revealed two significant latent variables (LVs) explaining > 90% of the sum-of-squares variance. LV1 explained 78.86% of the sum-of-squares variance, describing a shared, widespread structure-cognitive pattern relevant to both TRS patients and HCs. In contrast, LV2 (13.47% of sum-of-squares variance explained) appeared specific to TRS and comprised a differential cortico-cognitive pattern including frontal and temporal lobes as well as paired associates learning (PAL) and intra-extra dimensional set shifting (IED). Three-group analyses also identified two significant LVs, with NARs more closely resembling healthy controls than TRS patients. Conclusions: MB-PLS-C analyses identified multivariate brain structural-cognitive patterns in the latent space that may provide a TRS signature.

Keywords