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

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

David H Adamowicz  1 , Tsung-Chin Wu  2 , Rebecca Daly  3 , Michael R Irwin  4 , Dilip V Jeste  5 , Xin M Tu  6 , Lisa T Eyler  7 , Ellen E Lee  8
Affiliations

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

David H Adamowicz et al. Prog Neuropsychopharmacol Biol Psychiatry. .

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.

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Conflict of interest statement

Declaration of Competing Interest This work was supported, in part, by the National Institute of Mental Health (K23MH119375–01 to EEL, R01MH094151–01 to DVJ and LTE, R25MH101072 to Neal Swerdlow); the VA San Diego Healthcare System; and the Stein Institute for Research on Aging at the University of California San Diego. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
Age at study entry (baseline, black) and each of two reassessments (red, blue).
Figure 2.
Figure 2.
Age-aligned subgroups for modeling practice effect. Baseline visits are denoted in black, second visits in red, and third visits in blue.
Figure 3 –
Figure 3 –. Estimated mean and 95% confidence intervals of executive functioning by sex and diagnostic group (A), accounting for practice effects (B)
NC = non-psychiatric comparison, PwS = people with schizophrenia, F= Female, M= Male.
Figure 4–
Figure 4–. Estimated mean and 95% confidence bands of executive functioning over time by education level (A), accounting for practice effects (B).
Each panel shows the modeled trajectories of executive functioning when education is fixed at three different levels (Left panel: education level = 7 years; Middle panel: education level = 13 years; Right panel: education level =20 years). NC = non-psychiatric comparison, PwS = people with schizophrenia, F= Female, M= Male.
See this image and copyright information in PMC

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