Alcohol Withdrawal Syndrome - Pathophysiology

Pathophysiology

Chronic use of alcohol leads to changes in brain chemistry especially in the GABAergic system. Various adaptations occur such as changes in gene expression and down regulation of GABA_A receptors. During acute alcohol withdrawal, changes also occur such as upregulation of alpha4 containing GABA_A receptors and down regulation of alpha1 and alpha3 containing GABA_A receptors. Neurochemical changes occurring during alcohol withdrawal can be minimized with drugs which are used for acute detoxification. With abstinence from alcohol and cross tolerant drugs these changes in neurochemistry gradually return towards normal. Adaptations to the NMDA system also occur as a result of repeated alcohol intoxication and are involved in the hyper-excitability of the central nervous system during the alcohol withdrawal syndrome. Homocysteine levels which are elevated during chronic drinking increase even further during the withdrawal state and may result in excito-neurotoxicity. Alterations in ECG, in particular an increase in QT interval, and EEG abnormalities including may occur during early withdrawal. Dysfunction of the hypothalamic–pituitary–adrenal axis and increased release of corticotropin-releasing hormone occur during both acute as well as protracted abstinence from alcohol and contribute to both acute and protracted withdrawal symptoms. Anhedonia/dysphoria symptoms, which can persist as part of a protracted withdrawal may be due to dopamine underactivity.