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

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. CONCLUSION 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.