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 journalArticlepeer-review


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 languageEnglish
JournalPsychological Medicine
Early online date18 Feb 2022
Publication statusE-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.


  • Cognition
  • inflammation
  • neuroimaging
  • psychosis
  • schizophrenia-spectrum disorder
  • subtypes

ASJC Scopus subject areas

  • Applied Psychology
  • Psychiatry and Mental health


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