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Association of baseline inflammatory markers and the development of negative symptoms in individuals at clinical high risk for psychosis.

ABSTRACT: Negative symptoms are common in individuals at clinical high-risk (CHR) for psychosis and are associated with worse functional outcomes. Inflammation may be one mechanism underlying negative symptoms. Inflammatory markers are altered in individuals at CHR and are associated with negative symptoms in patients with schizophrenia. We thus hypothesized that baseline inflammatory markers would predict the development of negative symptoms in individuals at CHR for psychosis. Thirty seven individuals from the North American Prodromal Longitudinal Study who met CHR criteria were included in the study. Inflammatory cytokines, including interferon (IFN)-?, Interleukin (IL)-1?, IL-1 receptor antagonist (IL-1RA), IL-4, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF) were measured at baseline. Negative symptoms as measured by the Scale of Prodromal Symptoms, were measured at baseline and six and twelve months. Associations between inflammatory markers and the trajectory of negative symptoms (slope) over the first year of follow-up, were assessed using linear regression models controlling for age, sex, race and depressive symptom severity (as assessed by the Calgary Depression Scale for Schizophrenia). Baseline TNF (beta?=?0.361, p?=?0.007) and IL-6 (beta?=?-0.306, p?=?0.026) predicted negative symptoms slopes, along with depressive symptom severity at baseline (beta?=?-0.596, p?=?0.000). These findings demonstrate that inflammatory cytokines may underlie the development of negative symptoms in some individuals at CHR for psychosis. TNF predicted the development of negative symptoms independent of baseline depression. Given the heterogeneity of the CHR population, the comorbidity of negative symptoms and depression in this population, and the particular challenges in treating negative symptoms, immune markers could represent potential biomarkers that underlie the development of negative symptoms, representing a potential treatment target.

SUBMITTER: Goldsmith DR

PROVIDER: S-EPMC6348114 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Project description:Meta-analytic evidence indicates that baseline exposure to antipsychotics (AP) in individuals at clinical high-risk for psychosis (CHR-P) is associated with an even higher risk of transition to psychosis. However, the temporal dynamics of such prognostic effect have not been clarified yet. This study was therefore designed to address this knowledge gap. We performed a systematic review and meta-analysis of all longitudinal studies published up to 31 December 2021 on CHR-P individuals identified according to a validated diagnostic procedure and reporting numeric data of transition to psychosis according to baseline antipsychotic exposure. 28 studies covering a total of 2405 CHR-P were included. 554 (23.0%) were exposed to AP at baseline, whereas 1851 (77.0%) were not. At follow-up (12 to 72 months), 182 individuals among AP-exposed (32.9%; 95% CI: 29.4% to 37.8%) and 382 among AP-naive CHR-P (20.6%; 18.8% to 22.8%) developed psychosis. Transition rates increased over time, with the best-fit for an ascending curve peaking at 24 months and reaching then a plateau, with a further increase at 48 months. Baseline AP-exposed CHR-P had higher transition risk at 12 months and then again at 36 and 48 months, with an overall higher risk of transition (fixed-effect model: risk ratio = 1.56 [95% CI: 1.32-1.85]; z = 5.32; p < 0.0001; Random-effect model: risk ratio = 1.56 [95% CI: 1.07-2.26]; z = 2.54; p = 0.0196). In conclusion, the temporal dynamics of transition to psychosis differ in AP-exposed vs. AP-naive CHR-P. Baseline AP exposure in CHR-P is associated with a persistently higher risk of transition at follow up, supporting the rationale for more stringent clinical monitoring in AP-exposed CHR-P. The insufficiency of more granular information in available primary literature (e.g., temporal and quantitative details of AP exposure as well as psychopathological dimensions in CHR-P) did not allow the testing of causal hypotheses on this negative prognostic association.

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Association of baseline inflammatory markers and the development of negative symptoms in individuals at clinical high risk for psychosis.

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