Study aims to explore neural, physiological mechanisms linked to substance use in adolescence experiencing anxiety

Anxiety remains one of the most diagnosed clinical symptoms in adolescence and is a potent precursor to and exacerbator of substance use disorder. In their new $3.8-million study entitled "Neurobiological Pathways from Anxiety Symptomology in Early Adolescence to Risk for Adverse Patterns of Substance Use" funded through the National Institute on Drug Abuse, UNC School of Medicine and Frank Porter Graham Child Development Institute at UNC-Chapel Hill researchers will examine the neural and physiological mechanisms associated with emergence of substance use in adolescence who experience anxiety.

Aysenil Belger, PhD, professor in the UNC Department of Psychiatry and director of the Clinical Translational Core UNC Intellectual and Developmental Disabilities Research Center; and Diana Fishbein, PhD, senior scientist and director of translational neuro-prevention research at the Frank Porter Graham Child Development Institute at UNC-Chapel Hill, are co-principal investigators leading a team of researchers to examine cognitive functions, stress physiology and brain circuits and functions that distinguish adolescents with anxiety who do and do not go on to use psychoactive substances, including alcohol, during adolescence.

Researchers will recruit children ages 12-14 who report symptoms of anxiety. The cohort will then be stratified based on a tool developed by co-PI Ty Ridenhour, PhD, senior research analyst and RTI International; the tool focuses on risk factors such as home life, peer influences, cognitive functioning, impulsivity, risk-taking, and other behaviors to determine if the child has the individual profile that places them at risk of transitioning to substance use. Researchers will compare brain function and stress physiological systems in adolescents who do and do not initiate substance use over five years.

This longitudinal study is testing participants at baseline,12 months and 24 months. Adolescents will be studied using magnetic resonance imaging (MRI) while performing tasks that measure cognitive control, impulsivity, and executive decision-making. Their physiological responses to social stressors, including heart rate, perspiration, and changes in the stress hormone, cortisol, will also be measured. In-depth surveys and toxicology screens are used to determine substance use patterns and a wide range of other child characteristics. The first goal is to first identify the predictors of adverse patterns of substance use in adolescents with anxiety symptoms and, second, to determine what neurobiological mechanisms drive this association. This information will enable the development of more targeted, personalized interventions to prevent pathways of substance use.

We have very little understanding of the biological differences that explain why some people are prone to substance use or why some children and adolescents get to the point of substance use while others don't. Once we find these biological markers, we can identify those at increased risk and what the risk factors are for that individual, and we can develop interventions that enhance cognitive skills or intervene with stress management to keep them off the adverse trajectory, using prevention science."

Aysenil Belger, PhD, Professor, UNC Department of Psychiatry

Fishbein said, "When young people experience anxiety symptoms, it can compromise the ability of interventions to prevent substance use from developing. In adding to our knowledge about biological processes that underlie anxiety and how they relate to substance use, this study will help us to identify windows of opportunity during child and adolescent development when we can most effectively intervene."

Although this study focuses on biological "risks" that may propel youth toward substance use, the researchers will also identify protective factors, such as strong connections between cognitive and emotional centers of the brain or supportive social networks that may reduce risk and lead to more positive outcomes for children with anxiety.

Given that a child's brain is very sensitive to early experiences, identifying conditions that have positive effects should reveal opportunities for strengthening those protective factors to avoid pathways to negative outcomes.

"This research is timely and important," Belger added. "Post-pandemic anxiety and mental health issues in adolescents are on the rise, and many of the same characteristics we're studying also contribute to other mental health issues like suicidality. Our study results could identify more than just risk for substance use. There are policy implications as well, including identifying social, structural, and systemic risk factors that contribute to anxiety and substance use."

Belger, who had directed the Frank Porter Graham Child Development Institute (FPG) for five years, is focused on understanding neurobiological systems, functions and mechanisms that contribute to the development of psychopathology in youth. She works on the biology of high-risk integrating multimodal methodologies such as brain imaging, electrophysiological recordings, and cognitive behavioral assessments.

Fishbein's career has centered on understanding factors that contribute to the development of psychopathology, focusing on adverse experiences that predict negative outcomes, including substance abuse. She is particularly interested in how evidence-based interventions and policies have the potential to normalize developmental trajectories, leading to positive behavioral and mental health outcomes.

Together, the work of Belger, Fishbein, and Ridenour applies technologies and findings from neuroscience to address outstanding questions in the field of prevention, leading to more effective methods and policy reforms to support the health and well-being of our young people.