Newswise — Women in early abstinence from alcohol use disorder (AUD) show important alterations in brain connectivity that could underlie anxiety-induced relapse, according to a study reported in Alcoholism: Clinical and Experimental Research. Long-term recovery from AUD is challenging, particularly through periods of stress or uncertainty. Sustained alcohol use causes alterations in brain structure and neural functioning, including in brain regions associated with anxiety, that can persist even after stopping drinking. The first few days after quitting alcohol are dominated by physical withdrawal symptoms; after this, longer-lasting effects, including the production of stress hormones and abnormal stress responses, emerge as a result of these brain alterations. This means that many people who become sober experience months or years of anxiety and stress-reactivity symptoms. In the early abstinence phase, the anxiety symptoms can be temporarily relieved by alcohol, creating a powerful motivation to resume drinking. Thus, understanding the neural changes of abstinence-related anxiety is critical for understanding, and ultimately preventing, AUD relapse.

Studies in rodents have shown that a small region inside the brain, the BNST, is critical for regulating stress responses and anxiety-like behaviors during abstinence from alcohol. Furthermore, prolonged alcohol use and subsequent abstinence alter important structural connections between the BNST and other relevant brain regions. Studying such wider brain networks is important to understand complex behaviors such as those seen in alcohol abstinence; however, no study had investigated the structural connectivity of the BNST during early abstinence in humans. In the current analysis, researchers used advanced neuroimaging methods to evaluate differences in BNST structural connectivity in people with AUD in early abstinence.

Nineteen adults with AUD who had been sober for one to six months, and 20 light drinkers who did not have AUD (control group), underwent a type of brain imaging called DTI. The researchers analyzed the brain scan data using 3D modeling techniques to identify the structural nerve tract connections of the BNST. Next, they used statistical analysis to test for differences between the AUD and control group participants in BNST network connectivity. The key finding was that women in the abstinence group showed stronger overall BNST network structural connectivity compared with women in the control group, a difference that was not seen in men. Women also showed differences compared with men in the strength of BNST structural connections to two specific brain regions. These results expand on previous findings of sex differences in the BNST, in AUD, and in abstinence – including that women are more likely than men to relapse as result of anxiety symptoms.

The study provides the first evidence of BNST network structural connectivity differences in early abstinence. The contrasting results in women and men could underlie the known sex differences in abstinence symptoms and relapse risk, and potentially inform the development of sex-specific treatments. Although it will be important to replicate the results in a larger sample, the novel findings already highlight several areas for future study – for example, to characterize differences and transitions between early and protracted abstinence, and to evaluate the functional consequences of the structural alterations in BNST connectivity. It will also be exciting to explore associations between BNST connectivity and individual characteristics such as family history, genetics, trauma history, smoking, and other substance use, to better understand their role in anxiety during abstinence. Such research could help identify subgroups of patients for whom individualized treatments could be developed to help prevent relapse.

Alterations in connectivity of the bed nucleus of the stria terminalis (BNST) during early abstinence in individuals with alcohol use disorder

A Flook, B. Feola, M. M. Benningfield, M. M. Silveri; D. G. Winder, J. Urbano Blackford (pages xxx)


Journal Link: Alcoholism: Clinical and Experimental Research