Polymorphism in CRHR1 gene affects the IL-1b levels in suicidal attempters Clarissa R. Bastos a , Marta Gazal b , Luciana de A. Quevedo a , Joice Luisa Costa a , Carolina D. Wiener a , Karen Jansen a , Christian Loret de Mola c , Jean P. Oses a , Luciano D.M. Souza a , Luiz Valmor Portela d , Ricardo T. Pinheiro a , Ricardo A. da Silva a , Diogo R. Lara b , Gabriele Ghisleni a, * a Programa de P os-Graduaç~ ao em Saúde e Comportamento, Universidade Cat olica de Pelotas, Brazil b Biologia Celular e Molecular, Pontifícia Universidade Cat olica do Rio Grande do Sul, Brazil c Programa de P os-Graduaç~ ao em Epidemiologia, Universidade Federal de Pelotas, Brazil d Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil article info Article history: Received 4 June 2016 Received in revised form 21 October 2016 Accepted 17 November 2016 Keywords: Suicide risk HPA axis CRHR1 Polymorphism Inflammation Interleukin-1b abstract Approximately one million people commit suicide every year, being suicide attempts and ideation even more common. Changes in stress response and activation of the immune system have been associated with suicide risk. Here we investigated the interaction between immune system and HPA axis alterations in the suicide risk, looking for the influence of rs110402 CRHR1 SNP in the IL-1b levels according to suicide ideation and attempt. This study evaluated 171 subjects of which 15 had suicidal ideation, 20 had suicide attempt and 136 were controls. Genotyping was performed by real-time PCR and IL-1b levels were measured by ELISA. Our data showed that for each point increase in IL-1b levels the risk of suicide attempt increased 5% [relative risk ¼ 1.05 (95% CI: 1.0e1.10)]. After sample stratification by rs110402 SNP genotypes, we observed that in subjects carrying the A allele the risk raised to 15% [relative risk ¼ 1.15 (95% CI: 1.03e1.28)], suggesting an apparent effect modification. Thus, this study showed that alterations in CRHR1 gene were associated with higher levels of IL-1b, and increased risk for suicide, reinforcing the importance of multifactorial interactions of biological markers for psychiatric disorders. © 2016 Elsevier Ltd. All rights reserved. 1. Introduction Approximately one million people commit suicide every year (WHO, 2013), being one of the ten leading causes of death world- wide (Bertolete and Fleischmann, 2002). Suicide ideation and attempt are even more common (Tondo et al., 2007), and identi- fying risk factors in patients with psychiatric disorders is an area of increasing public health concern. The etiology of suicidal behavior is complex in that genetic, psychological and environmental factors can play a role (Correa et al., 2004). Neurobiological findings suggest that inflammation is a possible trigger for suicide behavior, independently of psychiatric disorders (Steiner et al., 2008). Studies have shown that an increase in pro- inflammatory cytokines is associated with the suicide behavior (Tonelli et al., 2008; Steiner et al., 2008), where higher levels of interleukine-1b (IL-1b) were linked to suicidal tendencies, including risk, attempt and completed suicide (Black and Miller, 2015). IL-1b is an endogenous signaling molecule released by macrophages and monocytes during the acute phase of the in- flammatory response. This pro-inflammatory cytokine is capable of modulating cerebral functions during systemic and localized inflammation, acting as a critical mediator of adaptive response to stress (John and Buckingham, 2003) by stimulation of corticotrophin-releasing hormone (CRH) release (Gadek-Michalska and Bugajski, 2010; Goshen and Yirmiya, 2009; Lopez-Castejon and Brough, 2011). In turn, CRH via corticotrophin-releasing hormone receptors (CRHR) activate the hypothalamic-pituitary-adrenal axis (HPA), promoting subsequent release of cortisol. Furthermore, HPA axis and the immune system communicate at multiple levels through the CRH, which can indirectly exert an anti- inflammatory effect via stimulation of cortisol release, and directly * Corresponding author. Programa de P os-Graduaç~ ao em Saúde e Comporta- mento, Centro de Ci^ encias da Vida e da Saúde, Universidade Cat olica de Pelotas, Rua Gonçalves Chaves 373, 96015560, Pelotas, Rio Grande do Sul, Brazil. E-mail address: ghisleni.g@gmail.com (G. Ghisleni). Contents lists available at ScienceDirect Journal of Psychiatric Research journal homepage: www.elsevier.com/locate/psychires http://dx.doi.org/10.1016/j.jpsychires.2016.11.009 0022-3956/© 2016 Elsevier Ltd. All rights reserved. Journal of Psychiatric Research 86 (2017) 34e38