Previous basic science research indicates brain CRF and noradrenergic upregulation during protracted abstinence in alcohol-dependent animals.6-9 Preclinical and human studies have also shown blunted/lack of HPA axis responses to stress challenge with long-term levels of alcohol consumption.8,11,13,37-39 Upregulation of central CRF and noradrenergic pathways would predict higher basal or resting-state HPA axis hormone levels, and this is consistent with higher morning basal corticotropin and higher neutral, relaxing-state corticotropin levels observed in alcohol-dependent patients compared with controls in study 1. On the other hand, unlike controls, there were no differences in corticotropin and cortisol responses to stress, cue, and neutral, relaxed conditions in alcohol-dependent patients. This lack of HPA axis response to challenge may represent a decreased physiological capacity of the HPA axis to recover to resting-state levels. Some evidence suggests that this lack of response to challenge in recovering alcohol-dependent patients may persist for at least 4 to 8 weeks’ abstinence, with documentation of partial recovery by 2 months.40 However, because a substantial number of alcoholics relapse within 2 months, an examination of whether such chronic alcohol-related effects on stress pathways contribute to relapse is of clinical significance.
