Resting-state regional cerebral blood flow during adolescence: Associations with initiation of substance use and prediction of future use disorders

Abstract

Background Adolescence is a period of developmental flux when brain systems are vulnerable to influences of early substance use, which in turn relays increased risk for substance use disorders. Our study intent was to assess adolescent regional cerebral blood flow (rCBF) as it relates to current and future alcohol use. The aim was to identify brain-based predictors for initiation of alcohol use and onset of future substance use disorders. Methods Quantitative rCBF was assessed in 100 adolescents (age 12-15). Prospective behavioral assessments were conducted annually over a three-year follow-up period to characterize onset of alcohol initiation, future drinking patterns and use disorders. Comparisons amongst use groups (i.e., Current-, Future-, and Non-alcohol Using adolescents) identified rCBF associated with initiation of alcohol use. Regression by future drinking patterns identified rCBF predictive of heavier drinking. Survival analysis determined whether or not baseline rCBF predicted later development of use disorders. Results Baseline rCBF was decreased to the parietal cortex and increased to mesolimbic regions in adolescents currently using alcohol as well as those who would use alcohol in the future. Higher baseline rCBF to the left fusiform gyrus and lower rCBF to the right inferior parietal cortex and left cerebellum was associated with future drinking patterns as well as predicted the onset of alcohol and substance use disorders in this cohort. Conclusions Variations in resting rCBF to regions within reward and default mode or control networks appear to represent trait markers of alcohol use initiation and is predictive of future development of use disorders.

Alcohol and Drug Use and the Developing Brain

“…In a sample of 100 12– to 15-year - olds, reductions in resting-state cerebral blood flow (i.e., when participants were not performing a task) within reward and default mode networks were associated with greater alcohol consumption at a 3-year follow-up [37]. This study had a relatively small sample size, with a fifth of the sample having already initiated substance use at baseline and only a third transitioning into alcohol use by the follow-up.…”

Neurobiological signatures associated with alcohol and drug use in the human adolescent brain

“…Interestingly, adolescents that would go on to use alcohol after the baseline assessment (future users) had higher rCBF in frontal (left mid orbital gyrus) and left lingual areas and lower rCBF in bilateral temporal and parietal areas relative to non-users. Currently using adolescents, however, only differed significantly from future users in left middle temporal gyrus and left cerebellum and (higher rCBF in current users) (Ramage et al, 2015). …”

“…Non-medical use of prescription drugs, in particular, is a growing health concern in a number of countries, including the United States (UNODC, 2011). Early onset of substance use also is not only a robust predictor of increased risk for future substance use disorders (Ramage et al, 2015), adolescents and young adults with stimulant use are at particular risk (Leland et al, 2006). The use of stimulants and other drugs are concerning due to the high risk of dependence, with individuals demonstrating increased risk taking, poor decision making, and high levels of impulsivity, relative to stimulant-naïve individuals, however the neural contributions are less known.…”

Adolescence and drug use vulnerability: findings from neuroimaging

“…On tasks of visual working memory, less brain activation during early adolescence is predictive of greater substance involvement by late adolescence (17, 30). Brain activation during reward processing has also been found to predict future adolescent substance use engagement; reduced resting-state cerebral blood flow within reward and default mode networks has been associated with greater alcohol consumption during mid-to-late adolescence (31). In a large multisite European neuroimaging study, hyperactivity in superior frontal regions during reward processing at age 14 was predictive of initiation of alcohol use by age 16 (22).…”