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. 2023 Feb:252:88-95.
doi: 10.1016/j.schres.2022.12.028. Epub 2023 Jan 10.

Longitudinal study of inflammation and relapse in schizophrenia

Brian J Miller  1 , Henrique Lemos  2 , Nina R Schooler  3 , Donald C Goff  4 , Alexander Kopelowicz  5 , John Lauriello  6 , Theo Manschreck  7 , Alan Mendelowitz  8 , Del D Miller  9 , Joanne B Severe  10 , Daniel R Wilson  11 , Donna Ames  5 , Juan Bustillo  12 , John M Kane  8 , Mark H Rapaport  13 , Peter F Buckley  14
Affiliations

Longitudinal study of inflammation and relapse in schizophrenia

Brian J Miller et al. Schizophr Res. 2023 Feb.

Abstract

Introduction: The clinical course of schizophrenia is often characterized by recurrent relapses. Blood inflammatory markers are altered in acute psychosis, and may be state markers for illness relapse in schizophrenia. Few studies have investigated longitudinal, intra-individual changes in inflammatory markers as a predictor of relapse. In the present study, we explored this association in a relapse prevention trial in patients with schizophrenia.

Methods: We analyzed blood inflammatory markers in 200 subjects, with a mean 11 samples per subject, during the 30 month Preventing Relapse in schizophrenia: Oral Antipsychotics Compared to Injectable: eValuating Efficacy (PROACTIVE) trial. Associations between longitudinal changes in inflammatory markers and relapse were analyzed using a within-subjects design.

Results: 70 (35 %) of subjects relapsed during the study period. There were no significant differences in mean inflammatory marker levels based on relapse status (yes/no). Baseline levels of inflammatory markers did not predict incident relapse. Among subjects who relapsed, there was a significant decrease in mean blood IL-6 (n = 38, p = 0.019) and IFN-γ (n = 44, p = 0.012) levels from the visit before the relapse to the visit after relapse.

Conclusion: Although there was some evidence for inflammation as a potential state marker for acute psychosis, we did not find significant evidence for its utility as a relapse-predictive marker.

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Conflict of interest statement

Declaration of competing interest Dr. B. Miller served as PI on the associated National Institute of Mental Health grant. In the past 12 months, Dr. Miller received research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute; and Honoraria from Atheneum, Carlat Psychiatry, Clearview, and Psychiatric Times. Dr. Lemos declares no financial interests or potential conflicts of interest related directly or indirectly to this work. Dr. Schooler declares no financial interests or potential conflicts of interest related directly or indirectly to this work. Dr. Goff declares no financial interests or potential conflicts of interest related directly or indirectly to this work. Dr. Kopelowicz declares no financial interests or potential conflicts of interest related directly or indirectly to this work. Dr. Lauriello declares no financial interests or potential conflicts of interest related directly or indirectly to this work. Dr. Manschreck declares no financial interests or potential conflicts of interest related directly or indirectly to this work. Dr. Mendelowitz declares no financial interests or potential conflicts of interest related directly or indirectly to this work. Dr. D. Miller declares no financial interests or potential conflicts of interest related directly or indirectly to this work. Ms. Severe declares no financial interests or potential conflicts of interest related directly or indirectly to this work. Dr. Wilson declares no financial interests or potential conflicts of interest related directly or indirectly to this work. Dr. Ames declares no financial interests or potential conflicts of interest related directly or indirectly to this work. Dr. Bustillo declares no financial interests or potential conflicts of interest related directly or indirectly to this work. Dr. Kane declares no financial interests or potential conflicts of interest related directly or indirectly to this work. Dr. Rapaport served as mentor on the associated National Institute of Mental Health grant. Dr. Buckley served as mentor on the associated National Institute of Mental Health grant.

Figures

Figure 1.
Figure 1.
Flow Chart of the Study Subjects and Blood Samples
Figure 2.
Figure 2.
Longitudinal changes in blood IL-6 levels in 15 relapsed subjects Fifteen subjects had available data on IL-6 over three consecutive visits during which they relapsed (approximately 5–6 weeks between each visit). Each line shows the IL-6 levels across these visits for an individual subject. The three subjects with the highest IL-6 levels are included in the offset in the upper right corner to facilitate better visualization of IL-6 values for the other subjects. Nine of the fifteen subjects exhibited a similar pattern of changes, with a “spike” in IL-6 levels prior to relapse.
See this image and copyright information in PMC

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