Prior research has demonstrated greater addiction vulnerability in women; for example, women advance from casual substance use to addiction at a faster rate, experience more severe withdrawal symptoms, exhibit higher rates of relapse, and have less treatment success than men. A new study shows that biobehavioral interactions in alcohol use disorders (AUDs) among women are cyclical in nature: women’s greater risk of personal histories of trauma coupled with a greater vulnerability to alcohol-related brain deficits can lead to more severe AUD effects.

These results and others will be shared at the 45^th annual scientific meeting of the Research Society on Alcoholism (RSA) in Orlando, Florida.

“Stress and trauma play key roles in the development of AUDs,” explained Milky Kohno, assistant professor at Oregon Health and Science University and health research scientist, VA Portland. “Abuse and trauma are more strongly associated with substance use in women than in men, likely due to greater exposure to high-impact traumatic events and repeated interpersonal trauma. Prevalence estimates indicate that approximately 80 percent of women seeking treatment for AUDs report having been exposed to sexual or physical assaults, intimate partner violence, or rape.”

Studies also show that women are more susceptible to alcohol- and drug- induced abnormalities in the peripheral immune response compared to men, she added. “Thus, coupled with an increase in inflammation related to trauma, women are particularly vulnerable to the neurobiological and immunological consequences of alcohol use.” Kohno will discuss these findings at the RSA meeting on 26 June 2022.

Her preliminary study included 30 healthy controls and 30 individuals diagnosed with an AUD. All participants completed a medical examination, provided samples for inflammatory markers and urine toxicology, and completed neurocognitive assessments and magnetic resonance (MR) scans. Childhood trauma, anxiety, and depression were assessed by various measures. Limbic system functional connectivity and markers of inflammation were also measured.

“We found that women with an AUD who experienced more childhood trauma exhibited higher levels of inflammation, while the opposite was true for men with an AUD,” said Kohno. “Trauma and stress can also affect the functioning of the emotional centers of the brain, which leads to impairments in emotion regulation. Alcohol does similar things and, coupled with a past history of trauma, these biological adaptations are further compromised and can confer greater risk for relapse.”

In other words, women will often use alcohol to cope with the negative effects of trauma, but if the emotional centers of the brain – located in the amygdala – are already compromised by trauma and inflammation, it can cause a “feed forward” loop in which the amygdala cannot function properly, more alcohol is used to cope, alcohol causes more disruption in the amygdala, and greater inflammation leads to worse emotional regulation.

“I think it is really important for people to understand that addiction is a brain disease and the reasons behind initiating and maintaining a relationship with alcohol isn’t simply about poor choices,” said Kohno. “This study highlights biological and behavioral variables that influence disease severity. Clinical trials that focus on biobehavioral interactions and sex-specific factors will yield novel outcome measures and have the potential to advance tailored treatment approaches and improve treatment efficacy.”