A Yale study supported by a Specialized Centers of Research Excellence (SCORE) grant from ORWH and the National Institute of Alcohol Abuse and Alcoholism used positron emission tomography (PET) imaging to measure microglial levels in men and women with mild to moderate alcohol use disorder (AUD). Microglia are the brain’s resident immune cells, patrolling neural pathways, clearing debris, and keeping us resilient against injury.

Healthy women exhibited higher baseline levels of microglia than healthy men. This finding aligns with women’s increased propensity for autoimmune disorders and suggests that their brains maintain a more active immune surveillance system under normal conditions. Women with mild to moderate AUD, however, showed a significant reduction in overall microglial levels compared to healthy women, whereas men with similar AUD severity did not have the same negative outcomes. This finding shows that chronic alcohol exposure may chronically activate microglia in women, leading to immune cell exhaustion and depletion over time. Among women with AUD, lower microglial density correlated with worsened mood, heightened anxiety, and impaired executive function.

Most treatments for AUD were designed around predominantly male study groups. These new findings underscore the need for women-specific interventions that bolster the brain’s immune resilience. Increasing healthy behaviors known to support immune health, such as regular exercise, restorative sleep, and a nutrient-rich diet, may complement medications to improve outcomes for women in recovery. Although it remains unclear whether microglial loss is reversible, the human brain’s inherent plasticity offers some optimism for improvement with targeted therapies.

Beyond AUD, these insights open doors to understanding why women face higher risks for conditions such as Alzheimer’s disease or multiple sclerosis. Future work could explore microglia-targeted therapies or lifestyle programs proven to rejuvenate immune cells in the brain.