Cognitive function in early-phase schizophrenia-spectrum disorder: IQ subtypes, brain volume and immune markers

Andrew J. Watson; Annalisa Giordano; John Suckling; Thomas R.E. Barnes; Nusrat Husain; Peter B. Jones; Carl R. Krynicki; Stephen M. Lawrie; Shôn Lewis; Naghmeh Nikkheslat; Carmine M. Pariante; Rachel Upthegrove; Bill Deakin; Paola Dazzan; Eileen M. Joyce

doi:10.1017/S0033291721004815

Cognitive function in early-phase schizophrenia-spectrum disorder: IQ subtypes, brain volume and immune markers

Andrew J. Watson, Annalisa Giordano, John Suckling, Thomas R.E. Barnes, Nusrat Husain, Peter B. Jones, Carl R. Krynicki, Stephen M. Lawrie, Shôn Lewis, Naghmeh Nikkheslat, Carmine M. Pariante, Rachel Upthegrove, Bill Deakin, Paola Dazzan, Eileen M. Joyce^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Evidence suggests that cognitive subtypes exist in schizophrenia that may reflect different neurobiological trajectories. We aimed to identify whether IQ-derived cognitive subtypes are present in early-phase schizophrenia-spectrum disorder and examine their relationship with brain structure and markers of neuroinflammation.

Method: 161 patients with recent-onset schizophrenia spectrum disorder (<5 years) were recruited. Estimated premorbid and current IQ were calculated using the Wechsler Test of Adult Reading and a 4-subtest WAIS-III. Cognitive subtypes were identified with k-means clustering. Freesurfer was used to analyse 3.0 T MRI. Blood samples were analysed for hs-CRP, IL-1RA, IL-6 and TNF-α.

Results: Three subtypes were identified indicating preserved (PIQ), deteriorated (DIQ) and compromised (CIQ) IQ. Absolute total brain volume was significantly smaller in CIQ compared to PIQ and DIQ, and intracranial volume was smaller in CIQ than PIQ (F(2, 124) = 6.407, p = 0.002) indicative of premorbid smaller brain size in the CIQ group. CIQ had higher levels of hs-CRP than PIQ (F(2, 131) = 5.01, p = 0.008). PIQ showed differentially impaired processing speed and verbal learning compared to IQ-matched healthy controls.

Conclusions: The findings add validity of a neurodevelopmental subtype of schizophrenia identified by comparing estimated premorbid and current IQ and characterised by smaller premorbid brain volume and higher measures of low-grade inflammation (CRP).

Original language	English
Journal	Psychological Medicine
Early online date	18 Feb 2022
DOIs	https://doi.org/10.1017/S0033291721004815
Publication status	E-pub ahead of print - 18 Feb 2022

Bibliographical note

Financial support: The study was supported by the UK MRC EME programme (reference number 10/90/04) and The Wellcome Trust (reference number 064607). Author EMJ was supported by the UCL/UCLH NIHR Biomedical Research centre.

Conflict of interest: Author TREB has been a member of an advisory board for Gedeon Richter,.outside the current work. Author CMP has received funding
from Johnson & Johnson, Boehringer Ingelheim and the Wellcome Trust, outside the current work. Author PD has received speaker fees from Janssen and Lundbeck. Other authors have no conflicts of interest to declare.

Keywords

Cognition
inflammation
neuroimaging
psychosis
schizophrenia-spectrum disorder
subtypes

ASJC Scopus subject areas

Applied Psychology
Psychiatry and Mental health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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https://www.repository.cam.ac.uk/handle/1810/334526Licence: Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND)

Cite this

Watson, A. J., Giordano, A., Suckling, J., Barnes, T. R. E., Husain, N., Jones, P. B., Krynicki, C. R., Lawrie, S. M., Lewis, S., Nikkheslat, N., Pariante, C. M., Upthegrove, R., Deakin, B., Dazzan, P., & Joyce, E. M. (2022). Cognitive function in early-phase schizophrenia-spectrum disorder: IQ subtypes, brain volume and immune markers. Psychological Medicine. Advance online publication. https://doi.org/10.1017/S0033291721004815

@article{506b048cb7a045529cd184318b6b57a2,

title = "Cognitive function in early-phase schizophrenia-spectrum disorder: IQ subtypes, brain volume and immune markers",

abstract = "Background: Evidence suggests that cognitive subtypes exist in schizophrenia that may reflect different neurobiological trajectories. We aimed to identify whether IQ-derived cognitive subtypes are present in early-phase schizophrenia-spectrum disorder and examine their relationship with brain structure and markers of neuroinflammation.Method: 161 patients with recent-onset schizophrenia spectrum disorder (<5 years) were recruited. Estimated premorbid and current IQ were calculated using the Wechsler Test of Adult Reading and a 4-subtest WAIS-III. Cognitive subtypes were identified with k-means clustering. Freesurfer was used to analyse 3.0 T MRI. Blood samples were analysed for hs-CRP, IL-1RA, IL-6 and TNF-α.Results: Three subtypes were identified indicating preserved (PIQ), deteriorated (DIQ) and compromised (CIQ) IQ. Absolute total brain volume was significantly smaller in CIQ compared to PIQ and DIQ, and intracranial volume was smaller in CIQ than PIQ (F(2, 124) = 6.407, p = 0.002) indicative of premorbid smaller brain size in the CIQ group. CIQ had higher levels of hs-CRP than PIQ (F(2, 131) = 5.01, p = 0.008). PIQ showed differentially impaired processing speed and verbal learning compared to IQ-matched healthy controls.Conclusions: The findings add validity of a neurodevelopmental subtype of schizophrenia identified by comparing estimated premorbid and current IQ and characterised by smaller premorbid brain volume and higher measures of low-grade inflammation (CRP).",

keywords = "Cognition, inflammation, neuroimaging, psychosis, schizophrenia-spectrum disorder, subtypes",

author = "Watson, {Andrew J.} and Annalisa Giordano and John Suckling and Barnes, {Thomas R.E.} and Nusrat Husain and Jones, {Peter B.} and Krynicki, {Carl R.} and Lawrie, {Stephen M.} and Sh{\^o}n Lewis and Naghmeh Nikkheslat and Pariante, {Carmine M.} and Rachel Upthegrove and Bill Deakin and Paola Dazzan and Joyce, {Eileen M.}",

note = "Financial support: The study was supported by the UK MRC EME programme (reference number 10/90/04) and The Wellcome Trust (reference number 064607). Author EMJ was supported by the UCL/UCLH NIHR Biomedical Research centre. Conflict of interest: Author TREB has been a member of an advisory board for Gedeon Richter,.outside the current work. Author CMP has received funding from Johnson & Johnson, Boehringer Ingelheim and the Wellcome Trust, outside the current work. Author PD has received speaker fees from Janssen and Lundbeck. Other authors have no conflicts of interest to declare.",

year = "2022",

month = feb,

day = "18",

doi = "10.1017/S0033291721004815",

language = "English",

journal = "Psychological Medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

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Watson, AJ, Giordano, A, Suckling, J, Barnes, TRE, Husain, N, Jones, PB, Krynicki, CR, Lawrie, SM, Lewis, S, Nikkheslat, N, Pariante, CM, Upthegrove, R, Deakin, B, Dazzan, P & Joyce, EM 2022, 'Cognitive function in early-phase schizophrenia-spectrum disorder: IQ subtypes, brain volume and immune markers', Psychological Medicine. https://doi.org/10.1017/S0033291721004815

TY - JOUR

T1 - Cognitive function in early-phase schizophrenia-spectrum disorder

T2 - IQ subtypes, brain volume and immune markers

AU - Watson, Andrew J.

AU - Giordano, Annalisa

AU - Suckling, John

AU - Barnes, Thomas R.E.

AU - Husain, Nusrat

AU - Jones, Peter B.

AU - Krynicki, Carl R.

AU - Lawrie, Stephen M.

AU - Lewis, Shôn

AU - Nikkheslat, Naghmeh

AU - Pariante, Carmine M.

AU - Upthegrove, Rachel

AU - Deakin, Bill

AU - Dazzan, Paola

AU - Joyce, Eileen M.

N1 - Financial support: The study was supported by the UK MRC EME programme (reference number 10/90/04) and The Wellcome Trust (reference number 064607). Author EMJ was supported by the UCL/UCLH NIHR Biomedical Research centre. Conflict of interest: Author TREB has been a member of an advisory board for Gedeon Richter,.outside the current work. Author CMP has received funding from Johnson & Johnson, Boehringer Ingelheim and the Wellcome Trust, outside the current work. Author PD has received speaker fees from Janssen and Lundbeck. Other authors have no conflicts of interest to declare.

PY - 2022/2/18

Y1 - 2022/2/18

N2 - Background: Evidence suggests that cognitive subtypes exist in schizophrenia that may reflect different neurobiological trajectories. We aimed to identify whether IQ-derived cognitive subtypes are present in early-phase schizophrenia-spectrum disorder and examine their relationship with brain structure and markers of neuroinflammation.Method: 161 patients with recent-onset schizophrenia spectrum disorder (<5 years) were recruited. Estimated premorbid and current IQ were calculated using the Wechsler Test of Adult Reading and a 4-subtest WAIS-III. Cognitive subtypes were identified with k-means clustering. Freesurfer was used to analyse 3.0 T MRI. Blood samples were analysed for hs-CRP, IL-1RA, IL-6 and TNF-α.Results: Three subtypes were identified indicating preserved (PIQ), deteriorated (DIQ) and compromised (CIQ) IQ. Absolute total brain volume was significantly smaller in CIQ compared to PIQ and DIQ, and intracranial volume was smaller in CIQ than PIQ (F(2, 124) = 6.407, p = 0.002) indicative of premorbid smaller brain size in the CIQ group. CIQ had higher levels of hs-CRP than PIQ (F(2, 131) = 5.01, p = 0.008). PIQ showed differentially impaired processing speed and verbal learning compared to IQ-matched healthy controls.Conclusions: The findings add validity of a neurodevelopmental subtype of schizophrenia identified by comparing estimated premorbid and current IQ and characterised by smaller premorbid brain volume and higher measures of low-grade inflammation (CRP).

AB - Background: Evidence suggests that cognitive subtypes exist in schizophrenia that may reflect different neurobiological trajectories. We aimed to identify whether IQ-derived cognitive subtypes are present in early-phase schizophrenia-spectrum disorder and examine their relationship with brain structure and markers of neuroinflammation.Method: 161 patients with recent-onset schizophrenia spectrum disorder (<5 years) were recruited. Estimated premorbid and current IQ were calculated using the Wechsler Test of Adult Reading and a 4-subtest WAIS-III. Cognitive subtypes were identified with k-means clustering. Freesurfer was used to analyse 3.0 T MRI. Blood samples were analysed for hs-CRP, IL-1RA, IL-6 and TNF-α.Results: Three subtypes were identified indicating preserved (PIQ), deteriorated (DIQ) and compromised (CIQ) IQ. Absolute total brain volume was significantly smaller in CIQ compared to PIQ and DIQ, and intracranial volume was smaller in CIQ than PIQ (F(2, 124) = 6.407, p = 0.002) indicative of premorbid smaller brain size in the CIQ group. CIQ had higher levels of hs-CRP than PIQ (F(2, 131) = 5.01, p = 0.008). PIQ showed differentially impaired processing speed and verbal learning compared to IQ-matched healthy controls.Conclusions: The findings add validity of a neurodevelopmental subtype of schizophrenia identified by comparing estimated premorbid and current IQ and characterised by smaller premorbid brain volume and higher measures of low-grade inflammation (CRP).

KW - Cognition

KW - inflammation

KW - neuroimaging

KW - psychosis

KW - schizophrenia-spectrum disorder

KW - subtypes

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U2 - 10.1017/S0033291721004815

DO - 10.1017/S0033291721004815

M3 - Article

AN - SCOPUS:85125524996

SN - 0033-2917

JO - Psychological Medicine

JF - Psychological Medicine

ER -

Cognitive function in early-phase schizophrenia-spectrum disorder: IQ subtypes, brain volume and immune markers

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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