title: Early life stress and tumor necrosis factor superfamily in crack cocaine withdrawal.
abstract: BACKGROUND
  Both early life stress (ELS) and substance abuse, especially cocaine, have robust effects on the inflammatory system. Considering the role of the tumor necrosis factor system in inflammatory signaling and its association with ELS, the aim of the study was to compare plasma levels of TNF-alpha, its soluble receptors and ligands during early abstinence of crack cocaine.
  
  
  METHODS
  This study included 24 crack cocaine-dependent women with (CRACK-ELS) and 20 without (CRACK) a history of ELS. A healthy control group (HC), containing 25 participants, was included to provide reference values. The Childhood Trauma Questionnaire (CTQ) retrospectively assessed childhood maltreatment history of patients. Plasma levels of TNF-alpha, TNF-related weak inducer of apoptosis (TWEAK), TNF-related apoptosis-inducing ligand (TRAIL), soluble receptors TNFRI (sTNFRI) and TNFRII (sTNFRII) were assessed on the 18th day of treatment.
  
  
  RESULTS
  The CRACK-ELS group had higher TNF-alpha and lower TWEAK levels compared to the CRACK and HC groups. sTNFRII was increased, but only in comparison with the crack cocaine group and the controls. TRAIL levels were slightly higher in the CRACK-ELS group, while no differences were found for sTNFRI levels. Also, TNF-alpha plasma level was positively predicted by abstinence severity and childhood maltreatment severity, and TWEAK was negatively predicted by childhood maltreatment severity.
  
  
  CONCLUSIONS
  This is the first study to evaluate the newly secreted tumor necrosis factor superfamily ligands, TWEAK and TRAIL, during crack cocaine abstinence, supporting the association between early life stress and peripheral pro-inflammatory levels.
authors.affiliation: Centre of Studies and Research in Traumatic Stress, Pontifical Catholic University of Rio Grande do Sul, Av. Ipiranga, 6681 Prédio 11 Sala 936, Porto Alegre, RS 90619-900, Brazil.
authors.forename: Mateus Luz
authors.initials: ML
authors.lastname: Levandowski
authors.affiliation: Centre of Studies and Research in Traumatic Stress, Pontifical Catholic University of Rio Grande do Sul, Av. Ipiranga, 6681 Prédio 11 Sala 936, Porto Alegre, RS 90619-900, Brazil; Laboratory of Immunosenescence, Institute of Biomedical Research, Pontifical Catholic University of Rio Grande do Sul, Av. Ipiranga, 6690/2° floor, Porto Alegre, RS 90610-000, Brazil.
authors.forename: Thiago Wendt
authors.initials: TW
authors.lastname: Viola
authors.affiliation: Centre of Studies and Research in Traumatic Stress, Pontifical Catholic University of Rio Grande do Sul, Av. Ipiranga, 6681 Prédio 11 Sala 936, Porto Alegre, RS 90619-900, Brazil; Laboratory of Immunosenescence, Institute of Biomedical Research, Pontifical Catholic University of Rio Grande do Sul, Av. Ipiranga, 6690/2° floor, Porto Alegre, RS 90610-000, Brazil.
authors.forename: Luis Eduardo
authors.initials: LE
authors.lastname: Wearick-Silva
authors.affiliation: Laboratory of Immunosenescence, Institute of Biomedical Research, Pontifical Catholic University of Rio Grande do Sul, Av. Ipiranga, 6690/2° floor, Porto Alegre, RS 90610-000, Brazil.
authors.forename: Andréa
authors.initials: A
authors.lastname: Wieck
authors.affiliation: Centre of Studies and Research in Traumatic Stress, Pontifical Catholic University of Rio Grande do Sul, Av. Ipiranga, 6681 Prédio 11 Sala 936, Porto Alegre, RS 90619-900, Brazil.
authors.forename: Saulo Gantes
authors.initials: SG
authors.lastname: Tractenberg
authors.affiliation: Interdisciplinary Laboratory of Clinical Neuroscience, Federal University of São Paulo, Rua Machado Bittencourt, 222, Sao Paulo, SP 04044-000, Brazil.
authors.forename: Elisa
authors.initials: E
authors.lastname: Brietzke
authors.affiliation: Centre of Studies and Research in Traumatic Stress, Pontifical Catholic University of Rio Grande do Sul, Av. Ipiranga, 6681 Prédio 11 Sala 936, Porto Alegre, RS 90619-900, Brazil; Laboratory of Immunosenescence, Institute of Biomedical Research, Pontifical Catholic University of Rio Grande do Sul, Av. Ipiranga, 6690/2° floor, Porto Alegre, RS 90610-000, Brazil.
authors.forename: Moisés E
authors.initials: ME
authors.lastname: Bauer
authors.affiliation: Laboratório Interdisciplinar de Investigação Médica da Faculdade de Medicina, Universidade Federal de Minas Gerais, Avenida Professor Alfredo Balena, 190, Belo Horizonte, MG 30130-100, Brazil.
authors.forename: Antônio Lúcio
authors.initials: AL
authors.lastname: Teixeira
authors.affiliation: Centre of Studies and Research in Traumatic Stress, Pontifical Catholic University of Rio Grande do Sul, Av. Ipiranga, 6681 Prédio 11 Sala 936, Porto Alegre, RS 90619-900, Brazil; Laboratory of Immunosenescence, Institute of Biomedical Research, Pontifical Catholic University of Rio Grande do Sul, Av. Ipiranga, 6690/2° floor, Porto Alegre, RS 90610-000, Brazil. Electronic address: rodrigo.grassi@pucrs.br.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Grassi-Oliveira
mesh_terms: D000328:Adult; D016578:Crack Cocaine; D000074049:Cytokine TWEAK; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D015398:Signal Transduction / Q000502:physiology*; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D013315:Stress, Psychological / Q000209:etiology*; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000150:complications / Q000523:psychology; D011795:Surveys and Questionnaires; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D048069:Tumor Necrosis Factors / Q000097:blood; D055815:Young Adult
chemical_list: D016578:Crack Cocaine; D000074049:Cytokine TWEAK; D016207:Cytokines; C109743:TNFSF12 protein, human; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors
keywords: Child abuse; Cytokines; Inflammation; Substance-related disorders; TNF; TRAIL; TWEAK