Stress triggers different brain responses in women and men with alcohol use disorder

Stress and alcohol use disorder often walk hand in hand, both affecting the brain’s neural circuits in complex ways. A recent study published in Alcoholism: Clinical and Experimental Research reveals how sudden social stress affects anxiety and brain activity in people with alcohol use disorder, with notable differences between men and women.

Alcohol use disorder (AUD) is a chronic condition characterized by an inability to control drinking despite negative consequences. People with AUD often experience a strong craving for alcohol, loss of control over drinking, and withdrawal symptoms when they stop drinking. This disorder affects millions of individuals worldwide, leading to significant health, social, and economic problems.

In the United States alone, approximately 30 million adults are affected by AUD. The disorder can lead to serious health issues, including liver disease, cardiovascular problems, and mental health disorders like depression and anxiety.

“Stress is a major cause of relapse in people with an alcohol use disorder and is a common motivator for alcohol consumption. Women have higher rates of stress-related psychopathology and show a heightened stress response,” said study author Erica N. Grodin, an adjunct assistant professor at the University of California, Los Angeles and member of the UCLA Addictions Lab.

“Alcohol use disorder and stress have common underlying neurocircuitry. Previous literature has been mixed regarding sex differences in response to acute stress and this topic had not been previously investigated in a sample of people with an alcohol use disorder. Therefore, we wanted to find out if men and women with an alcohol use disorder had differences in their subjective and neural responses to an acute stressor.”

The study involved individuals seeking treatment for moderate-to-severe alcohol use disorder, aged between 18 and 65. Participants were part of a larger clinical trial testing a neuroimmune medication, and they were required to meet specific criteria, such as consuming a minimum number of alcoholic beverages weekly and being free from other substance use disorders or severe psychiatric conditions. A total of 25 participants, including 15 men and 10 women, completed the study.

To evaluate the impact of acute social-evaluative stress, the researchers used the Montreal Imaging Stress Task (MIST). This task involved solving mental arithmetic problems under conditions designed to induce stress, such as tight time limits and negative social feedback.

During the task, participants underwent functional magnetic resonance imaging (fMRI) scans to measure brain activity. The study also included control conditions with similar arithmetic problems but without the stress-inducing elements. Participants’ anxiety and distress levels were assessed before and after the task using standardized questionnaires.

The researchers found that acute social-evaluative stress significantly increased anxiety levels in participants with alcohol use disorder. However, the increase in distress levels was not statistically significant, though there was a noticeable rise post-stress. This suggests that the stress task effectively elevated participants’ anxiety, providing a robust measure of their stress response.

The fMRI results revealed that the stress task activated several brain regions associated with stress, including the amygdala, thalamus, ventral tegmental area, and various cortical areas. There was a trend-level increase in amygdala activation during the stress condition compared to the control condition, indicating a stress response in this brain region.

The study also uncovered significant sex differences in stress responses. Women exhibited higher baseline anxiety and greater amygdala activation following the stress task compared to men. While men’s anxiety levels significantly increased after the stress task, women’s anxiety did not show a significant rise, possibly due to their higher baseline levels. Additionally, women showed increased activation in brain regions involved in affective regulation and self-referential processing, which may help them manage stress more effectively.

“Stress and negative emotionality are important motivators for alcohol use, particularly for women,” Grodin told PsyPost. “We found that even before undergoing stress, women had higher ratings of anxiety and distress than men and that women had a greater neural response to stress in the amygdala, an important brain region for stress processing compared to men. These results suggest that women may be at greater risk for stress-related alcohol use due to a heightened biological response to stress, indicated by their higher neural response to the acute stressor.”

Future research should include larger sample sizes and control groups without AUD to validate these preliminary findings. Incorporating biological measures of stress also could provide deeper insights into the mechanisms underlying stress responses in AUD. By understanding these nuances, researchers and clinicians can develop more targeted and effective treatments for individuals struggling with alcohol use disorder.

“We would like to extend upon this work in several areas,” Grodin explained. “First, we are currently investigating how acute stress impacts cognitive flexibility in a sample of individuals with and without an alcohol use disorder. This study will allow us to examine if undergoing acute stress has a greater negative impact on cognition in people with an alcohol use disorder compared to those without. We will also be examining sex differences in this work. In the future, we would like to incorporate additional hormonal assessments, including menstrual cycle, to further probe the underlying biology of these sex differences.”

The study, “Sex differences in neural response to an acute stressor in individuals with an alcohol use disorder,” was authored by Erica N. Grodin, Dylan Kirsch, Malia Belnap, and Lara A. Ray.