The Timeline Followback modified to include other drugs was used to collect frequency and quantity of alcohol, marijuana, and other drug use for the six weeks prior to initiating the protocol and for the four week duration in the study.All eligible CON and HED participants who initiated study protocol were monitored for abstinence and assessed using neuropsychological tests at three time points over their four-week participation. At each time point, a 150-minute NP battery was administered by a trained neuropsychometrist. Prior to each session, all participants provided a urine sample, submitted a breathalyzer reading , and completed affective state and personality questionnaires. Upon completion of the NP battery, the participants rated their level of focus, how hard they tried, how seriously they took the session, and level of effort on a scale of 1 to 10 . Participants were compensated for their participation and abstention throughout the protocol with the largest payment at the third assessment wave to encourage study completion. At all appointments, bud trimming trays adolescents participated in a toxicology screening protocol to minimize the possibility of their substance use. HED were first studied within 14 days of heavy episodic drinking and subsequently at two 2-week intervals over four subsequent weeks of monitored abstinence . CON teens followed the same abstinence monitoring and neuropsychological testing protocol at the same time intervals.
Abstinence was monitored and facilitated through behavioral and biochemical procedures including 10-panel drug urine testing and breathalyzer. Supervised urine and breath samples were collected three times per week to assess for recent use of alcohol with ethyl glucoronide and ethyl sulfate metabolites and use of methamphetamines, cocaine, THC , benzodiazepines, methadone, barbiturates, ecstasy, opiates, PCP, and oxycodone. We utilized an observed sample collection procedure to minimize the likelihood of participant tampering. Samples were analyzed by Redwood Toxicology using cloned enzyme donor immunoassay kits. If abstinence maintenance was confirmed via subject selfreport, breathalyzer, and quantitative toxicology results, participants continued to be scheduled for neuropsychological assessments. Abstinence was also facilitated using a standardized Motivational Interviewing protocol demonstrated to encourage the maintenance of abstinence for adolescents in prior research . Eleven HED teens drank alcohol during the abstinence period and data collected after their alcohol use were excluded from the analyses. Chi-square tests and t-tests compared socio-demographic characteristics between groups. To test for HED-CON differences and changes over time, we utilized linear mixed effects models to look for group effects at time 1 and time 3, time effects, and group by time interactions.
In the mixed model analyses, the fixed variables were time point and group, the random variable was the individual subject, and the dependent variable was the standard, age-scaled, or raw score of the NP domain in question. These analyses modeled error structures among repeated dependent variables by using fixed effects, specifying a covariance structure for both between and within subjects, and fitting the means model accounting for specific covariates . Because groups differed in their CBCL externalizing behavior , family history of alcohol dependence , and lifetime marijuana use , the mixed model analyses controlled for these variables.This study examined neurocognitive differences and patterns of recovery in abstinent, adolescent heavy episodic drinkers compared to non-drinking peers. Importantly, groups had comparable California Standards Test math and language performance on standardized tests that pre-date initiation of drinking in the heavy episodic drinking group, suggesting similar functioning prior to alcohol use. We found that adolescents with histories of an average of over 200 lifetime drinking episodes who initiated heavy episodic drinking at an average age of 15.33 differed from sociodemographically similar nondrinkers across several neuropsychological domains both during the early stages of abstinence and with continued abstention. Heavy episodic drinking adolescents performed worse on prospective memory, cognitive switching, inhibition task accuracy, verbal memory, visuospatial abilities, and language and achievement.
Studies on adolescents with alcohol use disorders have consistently found deficits in executive functioning, and the current study, which focused on a nonclinical population of heavy episodic drinkers, also identified deficiencies in prospective memory, cognitive switching, and inhibition task accuracy. Prospective memory requires multiple skills: monitoring time, remembering the task to be performed, and self-initiating the task at the appropriate time. Poorer performance in prospective memory, cognitive switching, and response inhibition may apply to academic and professional settings, as goal-oriented behavior and cognitive flexibility are essential to stay on task, quickly shift mental modes, and respond accurately. Longer lasting and heavier drinking patterns among adolescents have been linked to disruptions in the hippocampus, a brain structure critical for learning and memory, with adolescent drinkers showing smaller hippocampal volumes and disturbed hippocampal white matter integrity . Our study involved youth earlier in their drinking careers and identified poorer performance in both short delay and long delay verbal memory that did not resolve within five weeks of abstinence, on average. Poorer verbal memory is likely to have a significant influence on daily functioning as recall of verbal information occurs when following instructions, remembering lists, taking exams, and other daily activities.Our finding of poorer visuospatial abilities among heavy episodic drinking adolescents is consistent with many adolescent studies reporting an association between visuospatial impairments and frequency of alcohol use and withdrawal symptoms . We found initial differences on two and three-dimensional constructions ; however, only performance on the block constructions showed improvements to levels of non-drinking peers, while complex figure reproduction remained poorer across time. This finding could suggest more recovery of mental rotation and spatial navigation functions, whereas spatial organization and fine motor skills may take longer to recover. Alcohol dependent adolescents have frequently demonstrated significantly lower verbal IQ and reading achievement scores . The present study’s finding of poorer vocabulary and reading scores in nonclinical, heavy episodic drinking youth is consistent with such prior research. Given that the drinkers and nondrinkers had comparable math and language scores in 5th grade, it is possible that the poorer vocabulary and reading skills observed in adolescence may be at least partially due to related environment, brain, or behavior changes occurring after the onset of heavy drinking. Unlike prior research, our study did not identify statistically significant deficits in verbal learning, visuospatial memory, working memory, attention, or psychomotor speed when comparing heavy episodic drinking youth, who have not yet experienced substantial alcohol related problems, to non-drinking youth. Intensity of alcohol use may not yet be severe enough to manifest in differences. Alternatively, methodological differences may also have contributed to incongruent findings. The present design allowed us to identify significant improvements across time, suggesting that both groups improved with repeated testing and that the two-week interval between neuropsychological assessments is short enough to evidence practice effects. The improvement seen across time supports the importance of including controls to compare to heavy episodic drinkers. As expected, tasks on which both groups improved with repeated testing showed greater performance increases in the heavy drinkers. Despite greater improvement from their Time 1 to Time 3 assessment, heavy drinkers did not perform to levels of nondrinkers on prospective memory, cognitive switching, inhibition task accuracy, verbal memory, cannabis trim tray or two dimensional visuospatial construction, performing approximately 5-10% lower and committing 50-100% more errors across time.
Assuming adolescents respond to initial abstinence in a similar pattern as adults, they would show an initial improvement in attention, memory, and visuospatial skills within the first two weeks of abstinence, with gradual recovery thereafter . Our study detected significant improvements in prospective memory, cognitive switching, inhibition task accuracy, and visuospatial abilities from weeks 1 to 3 of abstinence, on average. However, we only identified an improvement significant enough to bring drinkers’ performance to that of nondrinkers on the three dimensional visuospatial construction task. It may be that a longer period of recovery is needed before the expected improvements seen in adult populations become evident among adolescent drinkers. We demonstrated that we can repeatedly and intensively assess functioning of 16- to 18-year-olds with and without histories of heavy episodic drinking. Our efforts to measure sustained abstinence were sufficient for this length of time. We went to great lengths to measure continuous abstinence, including the collection of urine samples from all participants on Sunday mornings. These procedures were necessary to detect alcohol exposure in 11 heavy episodic drinking participants and to report confidently abstinence in the other drinkers. The study also provides preliminary evidence to support the success of the motivational interviewing protocol to sustain abstinence in a population of heavy episodic drinking adolescents . This study featured many design strengths but has several limitations. First, the sample was carefully selected yet modest in size, which limited our statistical power and prevented further exploration of associations between neuropsychological performance and gender, family history, or alcohol use characteristics. Second, as expected, heavy episodic drinkers had some exposure to marijuana or other drugs. While we did covary for marijuana exposure in the mixed models, it is possible that other substance use, although limited, may have contributed to group differences. Of note, the heavy episodic drinkers consumed alcohol four times more than marijuana in their lifetimes, and had an average of approximately ten lifetime experiences with other drugs. Third, while the study established a relationship between heavy episodic drinking and neurocognitive impairments among adolescents, the directionality and causality can only be determined by longitudinal studies that examine adolescents prior to any substance involvement. In summary, consistent with our hypotheses and with previous studies, 16- to 18- year-old heavy episodic drinking adolescents with recent, frequent drinking and limited other drug exposure exhibit modest but significant neurocognitive functioning differences during early abstinence and, in many cases, with sustained abstinence. Though requiring replication, we found decrements in prospective memory, cognitive switching, inhibition task accuracy, verbal memory, visuospatial abilities, and language at the first testing that improve but not to levels of non-drinking peers even after four weeks of sustained abstinence . In the present sample, scores on tasks of verbal learning, working memory, attention, and psychomotor speed did not differ as a function of youth drinking experience. Our findings, coupled with extant literature in this field, suggest that deficient neuropsychological functioning is present among adolescents with recent histories of heavy episodic drinking relative to their non-drinking peers. These cognitive differences persist across four to six weeks of abstinence, suggesting a possible alcohol-induced impact to underlying brain systems, particularly given that groups were comparable on pre-drinking academic test performance. This possibility coincides with the animal literature’s finding that adolescence is a time of enhanced sensitivity to the neurotoxic effects of alcohol. This study has the potential to contribute to improved methods for measuring changes on important neurocognitive, affective, and behavioral domains associated with heavy episodic drinking in adolescents, and monitoring and facilitating real life behavioral improvements associated with abstinence from alcohol. Poorer performance inprospective memory, cognitive switching, inhibition accuracy, verbal memory, visuospatial ability, and language may affect adolescents’ daily experiences in academic or occupational settings. With this knowledge, educators may be able to improve outcomes for these teens by considering their cognitive abilities during instruction and employing strategies of repetition and active learning to more effectively engage and instruct a population of heavy episodic drinking youth .Brain maturation during adolescence appears to mirror developments in cognition, suggesting the overwhelming importance of healthy brain maturation processes during this critical time . Given the confluence of neuromaturational activity and initiation of alcohol and marijuana use during adolescence, the potential impact of these substances on neurocognitive development is important to understand. Alcohol and marijuana are drugs of particular concern since they are the most commonly used among adolescents. Over 68% of U.S. high school seniors report having tried alcohol and 46% have tried marijuana , and in the past month, alcohol was used by 39% and marijuana by 22% . Heavy episodic drinking occurred among nearly a quarter of seniors in the prior two weeks, and 7% endorsed daily marijuana use . The extant animal literature suggests that adolescents experience heightened vulnerability to the deleterious effects of both ethanol and cannabis . In general, the animal literature suggests a more widespread impact by ethanol on the hippocampus and frontal-anteriorcortical areas , which leads to persistent structural and functional abnormalities into adulthood . Adolescent rats also show reduced sensitivity to ethanol-induced motor impairing and sedative effects , which may theoretically enable youth to drink greater quantities of alcohol and attain higher blood alcohol concentrations with less sedation than would be expected in adulthood.