Neural correlates of negative life events and their relationships with alcohol and cannabis use initiation

Abstract

Objective

Negative life events (NLEs), e.g., poor academic performance (controllable) or being the victim of a crime (uncontrollable), can profoundly affect the trajectory of one’s life. Yet, their impact on how the brain develops is still not well understood. This investigation examined the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) dataset for the impact of NLEs on the initiation of alcohol and cannabis use, as well as underlying neural mechanisms.

Methods

This study evaluated the impact of controllable and uncontrollable NLEs on substance use initiation in 207 youth who initiated alcohol use, 168 who initiated cannabis use, and compared it to 128 youth who remained substance-naïve, using generalised linear regression models. Mediation analyses were conducted to determine neural pathways of NLE impacting substance use trajectories.

Results

Dose-response relationships between controllable NLEs and substance use initiation were observed. Having one controllable NLE increased the odds of alcohol initiation by 50% (95%CI [1.18, 1.93]) and cannabis initiation by 73% (95%CI [1.36, 2.24]), respectively. Greater cortical thickness in left banks of the superior temporal sulcus mediated effects of controllable NLEs on alcohol and cannabis initiations. Greater left caudate gray-matter volumes mediated effects of controllable NLEs on cannabis initiation.

Conclusions

Controllable but not uncontrollable NLEs increased the odds of alcohol and cannabis initiation. Moreover, those individuals with less mature brain structures at the time of the NLEs experienced a greater impact of NLEs on subsequent initiation of alcohol or cannabis use. Targeting youth experiencing controllable NLEs may help mitigate alcohol and cannabis initiation.

Keywords:

• Early initiation of alcohol use
• early initiation of cannabis use
• social communication skills
• negative life events
• brain immaturity
• addictive behaviours

Acknowledgements

The authors would like to extend special thanks to Duncan B. Clark, MD, Ph.D. (Department of Psychiatry, University of Pittsburgh) for sharing critical information on negative life events.

Author’s contributions

Y.Z. and M.P.P. designed the analytic plan for this paper. Y.Z. conducted the statistical analysis and wrote the first draft of the manuscript. All authors revised, contributed to, and approved the final manuscript.

Disclosure statement

Dr. Paulus is an advisor to Spring Care, Inc., a behavioural health start-up, he has received royalties for an article about methamphetamine in UpToDate. Dr. Potenza has consulted for Opiant Therapeutics, Game Day Data, the Addiction Policy Forum, AXA, and Idorsia Pharmaceuticals; has been involved in a patent application with Yale University and Novartis; has received research support from Mohegan Sun Casino and the National Centre for Responsible Gaming; has participated in surveys, mailings or telephone consultations related to drug addiction, impulse-control disorders or other health topics; has consulted for and/or advised gambling and legal entities on issues related to impulse-control/addictive disorders; has provided clinical care in a problem gambling services program; has performed grant reviews for research-funding agencies; has edited journals and journal sections; has given academic lectures in grand rounds, CME events and other clinical or scientific venues; and has generated books or book chapters for publishers of mental health texts. The other authors do not report disclosures.

Data availability statement

The data used in this paper was retrieved on 21 October 2021, from Sage Bionetworks Synapse (https://doi.org/10.7303/syn22213272).

Additional information

Funding

We acknowledge the efforts of the NCANDA Consortium’s data analysis resource (AA021697 and AA021697-04S1), administrative resource (AA021695), and data collection sites (AA021692, AA021696, AA021681, AA021690, and AA021691) through the support of U.S. National Institute on Alcohol Abuse and Alcoholism with co-funding from the National Institute on Drug Abuse, the National Institute of Mental Health, and the National Institute Child Health and Human Development. This work was supported in part by the US National Institute on Alcohol Abuse and Alcoholism (R01AA029611), the National Institute of Mental Health (RF1MH128614), the William K. Warren Foundation, the National Institute of General Medical Sciences Centre Grant Award Number (1P20GM121312), and the National Institute on Drug Abuse (U01DA050989). The views presented in this manuscript represent those of the authors and not necessarily those of the funding agencies.