Heavy alcohol use, rather than alcohol dependence, is associated with dysregulation of the hypothalamic-pituitary-adrenal axis and the autonomic nervous system.

Background: Heavy alcohol use as well as alcohol dependence (AD) have been associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA)-axis and the autonomic nervous system (ANS). However, the relative contribution of alcohol use and AD is unclear.

Methods: Baseline data were derived from 2947 persons of the Netherlands Study of Depression and Anxiety (NESDA), including non-drinkers (n=498), moderate drinkers (n=2112) and heavy drinkers (n=337). We also distinguished between persons with no lifetime DSM-IV AD (n=2496), remitted AD (> 1 year; n = 243), and current AD (≤ 1 year; n=208). ANS measures included ECG-based heart rate (HR), respiratory sinus arrhythmia (RSA, high RSA reflecting high cardiac parasympathetic control) and pre-ejection period (PEP, high PEP reflecting low cardiac sympathetic control). HPA-axis measures included the cortisol awakening response (area under the curve with respect to the ground [AUCg] and increase [AUCi]), evening cortisol and a 0.5mg dexamethasone suppression test, all measured in saliva.

Results: Heavy drinkers showed higher basal cortisol levels (AUCg: p=.02; evening cortisol: p=.006) and increased cardiac sympathetic control (higher HR: p=.04; lower PEP: p=.04) compared to moderate drinkers. Persons with current or remitted AD did not differ from persons without lifetime AD on any of the HPA-axis or ANS indicators (all p>.33). Similar patterns of HPA-axis and ANS activity across alcohol use groups were found in persons with and without lifetime AD.

Conclusions: Our findings suggest that current heavy alcohol use, rather than current or remitted AD, is associated with hyperactivity of the HPA-axis and increased cardiac sympathetic control.