Examining the Relationship and Neural Underpinnings of Mild Traumatic Brain Injury, Substance Use, and Mental Health in Emerging Adults

Abstract

Substance use is increasingly more common among emerging adults and is often linked to poor mental health, though the direction of this relationship remains unclear. Mild traumatic brain injury (mTBI) is also a known risk factor for both substance use and mood disorders, potentially due to its impact on brain regions involved in decision-making and emotional regulation. University athletes are especially vulnerable due to higher exposure to mTBI, placing them at increased risk for both substance misuse and mental health challenges. The complex interplay between these factors, along with observed sex differences, underscores the need for more targeted research and intervention. The overall objective of this research program was to examine the relationship between mTBI history and recent substance use, while exploring how mental health and mTBI interact and vary by sex and athlete status. Across four studies, important links emerged between substance use, mental health, and brain connectivity in both athletes and non-athletes. Study 1 found that in female athletes, cannabis use was associated with higher depression and altered resting-state functional connectivity (rsFC) in brain regions related to emotional regulation and self-monitoring, including reduced OFC-fusiform and increased hippocampus-cerebellum connectivity. Study 2 showed that among university athletes, mTBI and anxiety predicted alcohol and polysubstance use, with polysubstance users reporting the highest levels of depression, anxiety, and mTBI history. Study 3 extended these findings to a larger non-athlete sample, where hazardous substance use was linked to mTBI, anxiety, and depression. Sex-specific patterns emerged: in females, cannabis use was closely tied to mood symptoms, especially when combined with mTBI; in males, depression predicted both alcohol and cannabis use, with mTBI moderating alcohol use. Study 4 found that athletes with mTBI reported greater depression, anxiety, stress, and substance use, along with increased DMN-striatum connectivity related to anxiety, although no direct rsFC changes were associated with substance use. These findings emphasize the need for early screening, tailored mental health support, and integrated care. Further research into the temporal and causal relationships between mTBI, mental health, and substance use, particularly across sexes, is essential for developing effective interventions.