Scientists have known for years that heavy alcohol consumption can lead to imbalances and malfunctions in the hormones that regulate many bodily functions. Now, researchers at the National Institute on Alcohol Abuse and Alcoholism have identified a hormone which may help cause alcohol use disorder, aka alcoholism.
The hormone is aldosterone, a hormone produced in the adrenal glands, says the study, published in the journal Molecular Psychiatry. Researchers in both the U.S. and Europe participated. Aldosterone helps regulate electrolyte and fluid balance by binding to mineralocorticoid receptors (MRs), which are located throughout the body. In the brain, MRs are mainly located in the amygdala and the prefrontal cortex — two key brain areas involved in the development and maintenance of alcohol use disorder (AUD).
In AUD, amygdala dysfunction heightens activation of brain stress systems resulting in anxiety and other negative emotions, while disruption of the prefrontal cortex impairs executive control systems involved in the ability to make decisions and regulate one’s actions, emotions, and impulses.
“Previous studies, including a pilot clinical study that we published in 2008, illustrate the possible role for aldosterone in AUD,” says senior author Lorenzo Leggio, M.D., Ph.D., chief of the Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, a NIAAA intramural laboratory jointly funded with the National Institute on Drug Abuse, also part of NIH.
“Our overall hypothesis has been that aldosterone may play a role in AUD via its MR receptor and that this neuroendocrine pathway may be particularly important in anxiety, stress and stress-induced alcohol drinking.”
The new report describes three separate studies, conducted with non-human primates, rats, and humans, that investigated the potential contribution of the aldosterone/MR pathway to AUD.
In the human study, involving about 40 individuals undergoing treatment for AUD, the researchers found that blood aldosterone concentrations were higher in those who continued drinking during the 12-week period, compared with those who were abstinent during the same time frame.
For those who drank, the researchers found that aldosterone concentrations correlated with the amount of alcohol consumed during the study — higher drinking levels were associated with higher aldosterone concentrations. The researchers also found that increasing blood aldosterone concentrations correlated with increasing levels of both alcohol craving and anxiety.
Study co-author Kathleen Grant, H.D., says the amygdala’s “adaptation to aldosterone signaling due to chronic alcohol drinking illustrates fundamental adaptations across organ systems” that are part of the pathology of alcoholism. Grant is head of the Division of Neuroscience, Oregon National Primate Research Center at Oregon Health & Science University, Portland.
“This intriguing work – conducted in humans as well as two other species – provides a compelling example of how basic and preclinical research is translated into studies with direct relevance to humans,” says NIAAA Director George F. Koob, Ph.D., a co-author of the study. “It also demonstrates how interactions between the brain and the endocrine system may serve as potential targets for the development of new AUD medications.”
According to the NIAAA, about 6.2 percent or 15.1 million adults, in the United States ages 18 and older had an alcohol use disorder in 2015. Also in 2015, an estimated 623,000 adolescents ages 12 to 17 had alcohol use disorders.