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

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

5 Citationer (Scopus)

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.

Originalsprog	Engelsk
Artikelnummer	103064
Tidsskrift	NeuroImage. Clinical
Vol/bind	35
Sider (fra-til)	1-12
Antal sider	12
ISSN	2213-1582
DOI	https://doi.org/10.1016/j.nicl.2022.103064
Status	Udgivet - jan. 2022

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10.1016/j.nicl.2022.103064

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Syeda, W. T., Wannan, C. M. J., Merritt, A. H., Raghava, J. M., Jayaram, M., Velakoulis, D., Kristensen, T. D., Soldatos, R. F., Tonissen, S., Thomas, N., Ambrosen, K. S., Sørensen, M. E., Fagerlund, B., Rostrup, E., Glenthøj, B. Y., Skafidas, E., Bousman, C. A., Johnston, L. A., Everall, I., ... Pantelis, C. (2022). Cortico-cognition coupling in treatment resistant schizophrenia. NeuroImage. Clinical, 35, 1-12. Artikel 103064. https://doi.org/10.1016/j.nicl.2022.103064

Syeda, WT, Wannan, CMJ, Merritt, AH, Raghava, JM, Jayaram, M, Velakoulis, D, Kristensen, TD, Soldatos, RF, Tonissen, S, Thomas, N, Ambrosen, KS , Sørensen, ME , Fagerlund, B , Rostrup, E , Glenthøj, BY, Skafidas, E, Bousman, CA, Johnston, LA, Everall, I, Ebdrup, BH & Pantelis, C 2022, 'Cortico-cognition coupling in treatment resistant schizophrenia', NeuroImage. Clinical, bind 35, 103064, s. 1-12. https://doi.org/10.1016/j.nicl.2022.103064

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title = "Cortico-cognition coupling in treatment resistant schizophrenia",

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",

author = "Syeda, {Warda T} and Wannan, {Cassandra M J} and Merritt, {Antonia H} and Raghava, {Jayachandra M} and Mahesh Jayaram and Dennis Velakoulis and Kristensen, {Tina D} and Soldatos, {Rigas Filippos} and Shane Tonissen and Naveen Thomas and Ambrosen, {Karen S} and S{\o}rensen, {Mikkel E} and Birgitte Fagerlund and Egill Rostrup and Glenth{\o}j, {Birte Y} and Efstratios Skafidas and Bousman, {Chad A} and Johnston, {Leigh A} and Ian Everall and Ebdrup, {Bj{\o}rn H} and Christos Pantelis",

year = "2022",

month = jan,

doi = "10.1016/j.nicl.2022.103064",

language = "English",

volume = "35",

pages = "1--12",

journal = "NeuroImage. Clinical",

issn = "2213-1582",

publisher = "Elsevier BV",

}

TY - JOUR

T1 - Cortico-cognition coupling in treatment resistant schizophrenia

AU - Syeda, Warda T

AU - Wannan, Cassandra M J

AU - Merritt, Antonia H

AU - Raghava, Jayachandra M

AU - Jayaram, Mahesh

AU - Velakoulis, Dennis

AU - Kristensen, Tina D

AU - Soldatos, Rigas Filippos

AU - Tonissen, Shane

AU - Thomas, Naveen

AU - Ambrosen, Karen S

AU - Sørensen, Mikkel E

AU - Fagerlund, Birgitte

AU - Rostrup, Egill

AU - Glenthøj, Birte Y

AU - Skafidas, Efstratios

AU - Bousman, Chad A

AU - Johnston, Leigh A

AU - Everall, Ian

AU - Ebdrup, Bjørn H

AU - Pantelis, Christos

PY - 2022/1

Y1 - 2022/1

N2 - 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.

AB - 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.

KW - Brain structure

KW - Cognition

KW - MRI

KW - Partial least squares correlation

KW - Treatment-resistant schizophrenia

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U2 - 10.1016/j.nicl.2022.103064

DO - 10.1016/j.nicl.2022.103064

M3 - Journal article

C2 - 35689976

SN - 2213-1582

VL - 35

SP - 1

EP - 12

JO - NeuroImage. Clinical

JF - NeuroImage. Clinical

M1 - 103064

ER -

Cortico-cognition coupling in treatment resistant schizophrenia

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