Cytokines, cortisol and IGF-1 in first episode psychosis and ultra high risk males. Evidence for TNF-α, IFN-γ, ΤNF-β, IL-4 deviation

Abstract

The aim of the study was to determine circulating cytokines, cortisol and Insulin-like Growth Factor (IGF)-1, known for their involvement in inflammation, in male patients with First Episode Psychosis (FEP) and subjects at Ultra High Risk (UHR) for Psychosis. The FEP group presented increased pro-inflammatory cytokines (TNF-α, IFN-γ, ΤNF-β) as well as increased anti-inflammatory cytokine (IL-4) compared with Healthy Controls (HC). The UHR group showed increased IL-4 against HC. In contrast, none of the groups did show deviation from normality in either cortisol or IGF-1 levels. These preliminary findings support the cytokines' role in the inflammatory hypothesis in psychosis.

Peripheral Biomarkers for First-Episode Psychosis—Opportunities from the Neuroinflammatory Hypothesis of Schizophrenia

“…In this meta‐analysis, the authors suggested that IL‐1β, IL‐6, and TGF‐β could be “state” markers, given their raised levels in acute episodes followed by normalization under antipsychotic treatment, while IL‐12, IFN-γ, TNF-α, and sIL‐2R were proposed to be “trait markers”, as their levels were maintained after treatment. Recently, other authors reported increased serum levels of IL-1-RA [9,34,35], IL‐1β [29,36,37], sIL‐2r [35,36,38], IL-4 [38-40], IL-6 [29,35-38,41,42], IL-8 [38], IL-10 [9,34,41,42], IL-12 [29], IL-13 [9], IL-15 [34], IFN-γ [40], and TNF-α [35-38,40-42], and decreased levels of IL-17 [39] in drug-naïve FEP patients. Increased serum levels of IL-23, a key modulator of the inflammatory response, were also found in FEP patients and acute relapses [43].…”

The psychosis risk timeline: can we improve our preventive strategies? Part 3: primary common pathways and preventive strategies

“…These findings suggest that there may be activation in different areas of the immune system once transition to psychosis has occurred (Karanikas 2017). Contrary to the work by Karanikas et al (2017), in which a raised IFN-γ was identified, a reduced level was found in the first-episode psychosis group in the work of Lizano et al (2016)). This emphasises that work is still needed to clarify the cytokine profiles more conclusively.…”

“…Karanikas et al (2017) demonstrated variation in cytokine profiles between controls, ultra-high-risk and first-episode psychosis groups. In the first-episode psychosis group there were higher pro-inflammatory cytokines (tumour necrosis factors TNF-α and TNF-β, and interferon-gamma IFN-γ) and an increase in IL-4, an anti-inflammatory cytokine.…”

Mediadores inflamatórios em perfil pródromo de psicose como potenciais biomarcadores

“…Além disso, alguns ensaios clínicos mostraram que o uso de Celecoxibe, um antiinflamatório inibidor da COX-2, associado ao uso de risperidona foi eficaz no tratamento de sintomas positivos e negativos de pacientes com esquizofrenia (MÜLLER et al, 2002(MÜLLER et al, , 2004RIEDEL et al, 2005;AKHONDZADEH et al, 2007). Além do Celecoxibe, outros antiinflamatórios como a aspirina, por exemplo, mostraram benefícios, sugerindo abordagens terapêuticas como a associação dos antiinflamatórios aos antipsicóticos para o tratamento dos sintomas psicóticos (LAAN et al, 2010;ATTARI et al, 2016) (THEODOROPOULOU et al, 2001;SONG et al, 2009;KARANIKAS et al, 2017) As limitações desse estudo foi a falta de coleta de dados como altura, peso e uso de antiinflamatórios recentes para determinar fatores confundidores como IMC. Além do viés no grupo controle partindo da mesma população dos indivíduos UHR somente controlado pelo aceite de vir até o IPQ.…”

“…quadros psicóticos posteriores, concordando com os nossos achados em indivíduos UHR(KHANDAKER et al, 2014). Em pacientes portadores de esquizofrenia crônica, já foram descritos aumentos de IL-6, IL-18 e TNF-α quando comparados aos controles saudáveis, entretanto após 6 meses de tratamento com antipsicóticos houve uma redução nos níveis deIL-6 (LUO et al, 2019).Há outros estudos reforçando nossos achados com o aumento significativo de IL-4 em indivíduos UHR(KARANIKAS et al, 2017), além disso, relatos de níveis aumentados de IL-1β, IL-4, INF-γ e TNF-α em indivíduos durante o primeiro episódio psicótico confirmando o comprometimento imunológico na fase prodrômica e ao longo da evolução da doença…”