Executive functioning trajectories and their prospective association with inflammatory biomarkers in schizophrenia and non-psychiatric comparison participants

David H Adamowicz; Tsung-Chin Wu; Rebecca Daly; Michael R Irwin; Dilip V Jeste; Xin M Tu; Lisa T Eyler; Ellen E Lee

doi:10.1016/j.pnpbp.2023.110866

Executive functioning trajectories and their prospective association with inflammatory biomarkers in schizophrenia and non-psychiatric comparison participants

Prog Neuropsychopharmacol Biol Psychiatry. 2024 Jan 10:128:110866. doi: 10.1016/j.pnpbp.2023.110866. Epub 2023 Sep 22.

Authors

David H Adamowicz¹, Tsung-Chin Wu², Rebecca Daly³, Michael R Irwin⁴, Dilip V Jeste⁵, Xin M Tu⁶, Lisa T Eyler⁷, Ellen E Lee⁸

Affiliations

¹ Mass General Brigham, Department of Psychiatry, Division of Geriatric Psychiatry, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA 02115, USA; Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: dadamowicz@mgb.org.
² Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: tswu@health.ucsd.edu.
³ Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA; Sam and Rose Stein Institute for Research on Aging, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: rdaly@health.ucsd.edu.
⁴ Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience, University of California, Los Angeles, CA, USA. Electronic address: mirwin1@ucla.edu.
⁵ Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA; Sam and Rose Stein Institute for Research on Aging, University of California San Diego, La Jolla, CA 92093, USA.
⁶ Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: x2tu@health.ucsd.edu.
⁷ Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA; Sam and Rose Stein Institute for Research on Aging, University of California San Diego, La Jolla, CA 92093, USA; Desert-Pacific Mental Illness Research Education and Clinical Center, Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA. Electronic address: lteyler@health.ucsd.edu.
⁸ Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA; Sam and Rose Stein Institute for Research on Aging, University of California San Diego, La Jolla, CA 92093, USA; Desert-Pacific Mental Illness Research Education and Clinical Center, Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA. Electronic address: eel013@health.ucsd.edu.

PMID: 37742747
PMCID: PMC10829566 (available on 2025-01-10)
DOI: 10.1016/j.pnpbp.2023.110866

Abstract

Background and hypothesis: Cognitive change in people with schizophrenia (PwS) is challenging to assess, but important to understand. Previous studies with limited age ranges and follow-up were subject to practice effects. Controlling for practice effects in a well-established cohort, we examined executive functioning trajectories and their association with inflammatory biomarkers, hypothesizing that PwS will have worsening executive functioning over time compared to non-psychiatric comparison participants (NCs), predicted by higher baseline inflammation with a stronger relationship in PwS than NCs.

Study design: Executive functioning was assessed in 350 participants (n = 186 PwS, 164 NCs) at 12-16-month intervals (0 to 7 follow-up visits). Inflammatory biomarkers at baseline included high sensitivity C-Reactive Protein (hs-CRP), Interferon-gamma, Tumor Necrosis Factor (TNF)-alpha, and Interleukin(IL)-6, -8, and - 10. Executive functioning trajectories across diagnostic groups were estimated using a linear mixed-effects model controlling for age, sex, race/ethnicity, and education level, with additional models to assess prediction by baseline inflammation.

Study results: Over 4.4 years average follow-up, improvements in executive functioning were attenuated in PwS and older participants. Controlling for practice effects negated improvements, revealing declines among highly educated participants regardless of diagnosis. Higher baseline hs-CRP predicted worse executive functioning only among NCs, while TNF-alpha was predictive of change in all participants only after controlling for practice effects. Only the main effect of hs-CRP on executive function was significant after adjusting for multiple comparisons. None of the other inflammatory biomarkers predicted executive functioning or trajectories of performance among study participants.

Conclusions: Systemic inflammation as reflected by baseline inflammatory biomarker levels did not predict longitudinal declines in executive functioning. Additional studies examining the temporal dynamics of inflammation and cognition in PwS will help further clarify their relationship and associated mechanisms.

Keywords: Aging; Cognition; Cytokines; Longitudinal; Psychosis.

MeSH terms

Biomarkers
C-Reactive Protein / analysis
Executive Function*
Humans
Inflammation / metabolism
Schizophrenia*
Tumor Necrosis Factor-alpha

Substances

C-Reactive Protein
Biomarkers
Tumor Necrosis Factor-alpha

Abstract

MeSH terms

Substances

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