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

doi:10.1016/j.nicl.2022.103064

Cortico-cognition coupling in treatment resistant schizophrenia

Neuroimage Clin. 2022:35:103064. doi: 10.1016/j.nicl.2022.103064. Epub 2022 May 28.

Authors

Warda T Syeda¹, Cassandra M J Wannan², Antonia H Merritt², Jayachandra M Raghava³, Mahesh Jayaram⁴, Dennis Velakoulis², Tina D Kristensen⁵, Rigas Filippos Soldatos⁶, Shane Tonissen², Naveen Thomas⁴, Karen S Ambrosen⁵, Mikkel E Sørensen⁵, Birgitte Fagerlund⁵, Egill Rostrup⁵, Birte Y Glenthøj⁷, Efstratios Skafidas², Chad A Bousman⁸, Leigh A Johnston⁹, Ian Everall¹⁰, Bjørn H Ebdrup¹¹, Christos Pantelis¹²

Affiliations

¹ Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Victoria, Australia. Electronic address: wtsyeda@unimelb.edu.au.
² Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Victoria, Australia.
³ Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark; Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Glostrup, Denmark.
⁴ Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Victoria, Australia; MidWest Area Mental Health Service, Sunshine Hospital, St. Albans, Victoria, Australia.
⁵ Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.
⁶ Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Victoria, Australia; First Department of Psychiatry, National and Kapodistrian University of Athens Medical School, Eginition Hospital, Athens, Greece.
⁷ Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark; Faculty of Health and Medical Sciences, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
⁸ Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Victoria, Australia; Departments of Medical Genetics, Psychiatry, and Physiology & Pharmacology, University of Calgary, Canada.
⁹ Department of Biomedical Engineering and Melbourne Brain Centre Imaging Unit, University of Melbourne, Victoria, Australia.
¹⁰ Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.
¹¹ Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Victoria, Australia; Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark; Faculty of Health and Medical Sciences, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
¹² Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Victoria, Australia; Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark; MidWest Area Mental Health Service, Sunshine Hospital, St. Albans, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health, Victoria, Australia.

Abstract

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: Brain structure; Cognition; MRI; Partial least squares correlation; Treatment-resistant schizophrenia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cognition
Cognition Disorders* / psychology
Humans
Male
Neuropsychological Tests
Schizophrenia*
Schizophrenia, Treatment-Resistant