Please cite this article in press as: Levandowski, M.L., et al., Distinct behavioral and immunoendocrine parame- ters during crack cocaine abstinence in women reporting childhood abuse and neglect. Drug Alcohol Depend. (2016), http://dx.doi.org/10.1016/j.drugalcdep.2016.08.010 ARTICLE IN PRESS G Model DAD-6146; No. of Pages 9 Drug and Alcohol Dependence xxx (2016) xxx–xxx Contents lists available at ScienceDirect Drug and Alcohol Dependence j ourna l h o me pa ge: www.elsevier.com/locate/drugalcdep Full length article Distinct behavioral and immunoendocrine parameters during crack cocaine abstinence in women reporting childhood abuse and neglect Mateus Luz Levandowski a,b , Thiago Wendt Viola a,c , Carine Hartmann Prado d , Andrea Wieck d , Moisés Evandro Bauer d , Elisa Brietzke e , Rodrigo Grassi-Oliveira a,b,c,∗ a Developmental Cognitive Neuroscience Lab (DCNL), Pontifical Catholic University of Rio Grande do Sul (PUCRS), RS, Brazil b Post-Graduate Program in Psychology, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre (PUCRS), RS, Brazil c Post-Graduate Program in Pediatrics and Children Health’s, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre (PUCRS), RS, Brazil d Laboratory of Immunosenescence, Institute of Biomedical Research, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre (PUCRS), RS, Brazil e Research Group in Behavioral Neuroscience of Bipolar Disorder, Departament of Psychiatry, Federal University of São Paulo Unifesp, São Paulo, SP, Brazil a r t i c l e i n f o Article history: Received 25 April 2016 Received in revised form 2 August 2016 Accepted 4 August 2016 Available online xxx Keywords: Child abuse Cocaine Cytokines Inflammation Stress Substance-use disorders a b s t r a c t Aim: To assess plasma levels of cortisol and cytokines between cocaine-dependent women with and without childhood maltreatment (CM) history during cocaine detoxification treatment. Method: We assessed immunoendocrine and clinical parameters of 108 crack cocaine female users during 3 weeks of inpatient detoxification treatment, and 24 healthy women to obtain reference values. Women with (CM+, n = 53) or without (CM-, n = 55) CM history were identified answering the Childhood Trauma Questionnaire (CTQ). Blood samples and clinical assessment were collected before lunch during the first, second and third week post-treatment admission. Flow cytometry was used to assess TNF-, IFN-, IL-2, IL-4, IL-6, IL-10, IL-17A plasma levels and ELISA assay was used to measure plasma cortisol levels. Results: At baseline, lower Th1 and Th17-related cytokines levels and higher Th2 cytokines levels were observed in crack cocaine users compared with reference values. Cytokines levels of cocaine dependents gradually became closer to reference values along detoxification treatment. However, when CM+ and CM- groups were compared, increased levels of IL-6, IL-4 and TNF- across time were observed in CM+ group only. Additionally, a Th1/Th2 immune imbalance was observed within CM+ group, which was negatively correlated with the severity of the crack withdrawal. Finally, loading trauma exposure severity, immu- noendocrine and clinical parameters in factor analysis, we identified three clusters of observed variables during detoxification: (1) systemic immunity and trauma exposure, (2) pro-inflammatory immunity and (3) behavior Conclusion: Our results suggest the existence of an immunological phenotype variant associated with CM exposure during crack cocaine detoxification of women. © 2016 Elsevier Ireland Ltd. All rights reserved. 1. ‘Introduction Substantial evidence indicates that childhood maltreatment is associated with increased risk of substance use disorders (Enoch, 2011; Giordano et al., 2014; Teicher and Samson, 2013). For exam- ple, childhood sexual abuse exposure in women increases the risk of alcohol or illicit drug dependence 6.6-fold (Kendler et al., 2000). These effects of early-life stress (ELS) exposure are particularly evi- dent in individuals with patterns of heavy substance consumption, ∗ Corresponding author at: Faculdade de Psicologia, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, Prédio 11, Sala 936, Partenon, Porto Alegre, RS Brazil. E-mail address: rodrigo.grassi@pucrs.br (R. Grassi-Oliveira). as in the case of cocaine use disorder (Shin et al., 2013). More- over, cocaine dependents with a history of childhood neglect might exhibit more severe depressive and abstinence symptoms during drug withdrawal (Francke et al., 2013; Rovaris et al., 2015), partially contributing to a complex neurobiological derangement including hypothalamo-pituitary-adrenal (HPA) axis and dopamine system dysfunctions (Gerra et al., 2009; Shin et al., 2013). Considering that ELS effects on development include the repro- gramming activity of the HPA axis and subsequently the stress response (Grassi-Oliveira et al., 2008) and the effects of stress on the immune system (Priyadarshini and Aich, 2012), a promis- ing pathway for biomarker searches regarding the link between ELS and cocaine addiction includes the identification of periph- eral immune mediators. Thus, it has been reported that childhood http://dx.doi.org/10.1016/j.drugalcdep.2016.08.010 0376-8716/© 2016 Elsevier Ireland Ltd. All rights reserved.