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 EbdrupChristos Pantelis

*Corresponding author af dette arbejde


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.

TidsskriftNeuroImage. Clinical
Sider (fra-til)1-12
Antal sider12
StatusUdgivet - 2022


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