Neurotrophic factors in women with crack cocaine dependence during early abstinence: the role of early life stress

Neurotrophic factors in women with crack cocaine dependence during early abstinence: the role of early life stress


J Psychiatry Neurosci 2014; 39(3): 206-214

Thiago Wendt Viola, BA; Saulo Gantes Tractenberg, BA; Mateus Luz Levandowski, BA; Júlio Carlos Pezzi, MS, MD; Moisés Evandro Bauer, PhD; Antonio Lúcio Teixeira, MD, PhD; Rodrigo Grassi-Oliveira, MS, MD, PhD

Viola, Tractenberg, Levandowski, Bauer, Grassi-Oliveira — Centre of Studies and Research in Traumatic Stress, Post-Graduate Program in Psychology, Pontifical Catholic University of the Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Pezzi — Post-Graduate Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Brazil; Bauer, Grassi-Oliveira — Laboratory of Immunosenescence, Institute of Biomedical Research, Pontifical Catholic University of the Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Teixeira — Neuroscience Program, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil


Background: Neurotrophic factors have been investigated in the pathophysiology of alcohol and drug dependence and have been related to early life stress driving developmental programming of neuroendocrine systems.

Methods: We conducted a follow-up study that aimed to assess the plasma levels of glial cell line–derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT3) and neurotrophin-4/5 (NT4/5) in crack users during 3 weeks of early abstinence in comparison
with healthy controls. We performed a comprehensive clinical assessment in female inpatients with crack cocaine dependence (separated into 2 groups: participants with (CSA+) and without (CSA–) a history of childhood sexual abuse) and a group of nonuser control participants.

Results: Our sample included 104 women with crack cocaine dependence and 22 controls; of the women who used crack cocaine, 22 had a history of childhood sexual abuse and 82 did not. The GDNF plasma levels in the CSA+ group increased dramatically during 3 weeks of detoxification. In contrast, those in the CSA– group showed lower and stable levels of GDNF under the same conditions. Compared with the control group, BDNF plasma levels remained elevated and NGF levels were reduced during early abstinence. We found no differences in NT3 and NT4/5 between the patients and controls. However, within-group analyses showed that the CSA+ group exhibited higher levels of NT4/5 than the CSA– group at the end of detoxification.

Limitations: Some of the participants were using neuroleptics, mood stabilizers or antidepressants; our sample included only women; memory bias could not be controlled; and we did not investigate the possible confounding effects of other forms of stress during childhood.

Conclusions: This study supports the association between early life stress and peripheral neurotrophic factor levels in crack cocaine users. During early abstinence, plasmastic GDNF and NT4/5 were the only factors to show changes associated with a history of childhood sexual abuse.

Submitted Feb. 15, 2013; Revised June 26, Sept. 11, 2013; Accepted Oct. 11, 2013.

Acknowledgements: This study was supported by CNPq, MCT/CTSaúde, DECIT/SCTIE/MS, and FAPERGS-PqG. We thank the Developmental Cognitive Neuroscience (GNCD) research team and the staff of the Sistema de Saúde Mãe de Deus for all the support regarding data collection.

Competing interests: None declared.

Contributors: T.W. Viola, J.C. Pezzi and R. Grassi-Oliveira designed the study. T.W. Viola, S.G. Tractenberg, M. Levandowski, J.C. Pezzi, A.L. Teixeira and R. Grassi-Oliveira acquired the data, which T.W. Viola, M. Levandowski, M.E. Bauer, A.L. Teixeira and R. Grassi-Oliveira analyzed. T.W. Viola, S.G. Tractenberg, M.E. Bauer and R. Grassi-Oliveira wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.130027

Correspondence to: R. Grassi-Oliveira, Av. Ipiranga, 6681, prédio 11, sala 936, Porto Alegre, RS, Brazil. 90619-900;