Age of onset of nicotine use and severity of nicotine addiction symptoms are associated with hippocampal volume in late adolescents and emerging adults

Background: Despite declining use of traditional combustible cigarettes, the use of nicotine and tobacco-related products (NTPs) remains high among adolescents and emerging adults largely due to the use of e-cigarettes. Adolescents and emerging adults who initiate e-cigarette use reach comparable indices of nicotine dependence as traditional cigarette smokers and can report symptoms of dependence even before developing a pattern of daily use. Symptoms such as craving, positive and negative reinforcement, and biological markers of toxicity are closely linked to the development and persistence of substance use problems. Adolescents/emerging adults may transition to dependence more quickly than adults, and the age of onset of regular NTP use is a highly predictive risk factor for future use and problems. Within the brain, the hippocampus is particularly sensitive to the effects of nicotine and may play a role in the transition from NTP initiation to more habitual and even problematic use.Methods: A cross-sectional sample of healthy, NTP-using late adolescents/emerging adults (N=86) ages 16-22 completed a structural MRI to examine whether subjective nicotine craving, stronger positive and negative reinforcement, elevated cotinine levels, and earlier age of onset of regular nicotine use would be associated with hippocampal volumes.Results: Across measures of nicotine addiction, linear regression models revealed an interaction between symptoms and age of onset of regular use. A general pattern emerged such that greater symptom severity and younger age of onset of regular use was associated with larger hippocampal volumes.Conclusions: These findings provide potential insight into the relationship between late adolescent/emerging adult brain health and a risk factor for NTP initiation and symptoms of nicotine addiction. Greater understanding of these interactions is essential for informing prevention, intervention, and public health policy.