The brain of an adolescent, much like teenage behavior, undergoes significant developmental changes. This neurodevelopment continues after adolescence, typically until around age 25.The maturational processes in the brain occur in stages, with more basic functions maturing first and areas such as the lateral temporal and frontal lobes, which are responsible for higher cognitive function , developing later in adolescence.Its rate of change does not plateau until the third decade of life, in concert with typical developmental trajectories of cognitive abilities, such as decision-making, attention, and cognitive control.The late maturation of the prefrontal cortex has been linked to risky behavior during adolescence, particularly if the limbic subcortical system develops earlier.Executive functioning typically matures during this developmental stage,coincident with gray matter reductions and white matter growth.Functional magnetic resonance imaging studies of executive behaviors have demonstrated increasing prefrontal activity and better inhibitory control with adolescent age.Challenges in executive functioning have been observed in adolescents with a family history of alcohol use disorder ,repeated childhood trauma experiences,and poor sleep,all of which also have been identified as risk for adolescent binge drinking and AUD.Deficits in control circuitry have been linked to impulsivity, sensation seeking, and alcohol use into early adulthood.One of the studies investigating adolescent alcohol use and its effects is coordinated by the National Consortium on Alcohol and Neurodevelopment in Adolescence , which is conducting a multisite longitudinal study supported by funding from NIAAA and other National Institutes of Health partner institutes. Launched in 2012,4×8 grow table with wheels this five-site consortium recruited a community cohort of 831 diverse adolescents ages 12 to 21 from five U.S. regions. Half the sample was enriched for key characteristics conveying risk for heavy drinking among adolescents.
Most of the sample reported very limited alcohol use at project entry; the remaining 15% exceeded typical age thresholds for alcohol at project entry in this cohort-sequential design.At project entry and annually thereafter, participants received neuroimaging , neurocognitive testing, detailed substance use and mental health interviews; provided urine samples for drug testing as well as saliva samples for genetics and pubertal hormone assays; and completed various self- and parent reports on personality, behaviors, and environment.NCANDA will continue to examine the interactive effects of typical development as well as adolescent alcohol use and executive dysfunction into early adulthood. Resting-state fMRI findings from NCANDA and other studies have shown that intrinsic functional networks sub-serving cognitive control and limbic circuitry develop across adolescence and may be influenced by adolescent heavy drinking.Moreover, the adverse effects of alcohol may be more prominent in girls than in boys.Being able to identify youth at higher risk for alcohol misuse could lead to early intervention and ultimately help reduce the significant personal and public health burden of AUD; however, relatively few studies have explored individual-level precursors of adolescent alcohol use. Prospective longitudinal studies of substance-naïve youth are uniquely positioned to identify factors predating the onset of alcohol use. Squeglia et al. identified several markers of alcohol initiation by age 18 in 137 adolescents.These markers included demographic and behavioral factors , lower executive functioning, thinner cortices, and less brain activation in diffusely distributed brain regions. NCANDA seeks to expand on these findings using a greater number of measurements in a large sample to lead to more accurate individual-level forecasting. The consortium is employing machine learning models, which can avoid multiple-comparison correction and reduce measures to a single, individual-level prediction.NCANDA developed a model that distinguished youth who drink heavily from those who drink little or no alcohol, based on patterns of macrostructural and microstructural imaging metrics in multiple brain regions.The analyses suggested delayed development of white matter connectivity among the older youth in the sample who drank heavily, as well as increased risk of subsequent heavy drinking in youth with more externalizing symptoms.
These findings fit closely with those from the IMAGEN Consortium, which found that variability in personality, cognition, life events, neural functioning, and drinking behavior features predicted Alcohol Use Disorders Identification Test scores at ages 14 and 16.Unlike white matter, gray matter volume peaks in the primary school-age years, around age 10.Squeglia et al. reported that youth who drank heavily showed accelerated reductions in gray matter volumes in cortical lateral frontal and temporal areas compared to those who drank no or little alcohol.39 These results were largely unchanged with co-use of marijuana and other drugs; also, similar patterns of developmental trajectory abnormalities existed in males and females. This finding was replicated in the NCANDA cohort, which examined the influence of alcohol use on gray matter structure in 483 adolescents ages 12 to 21 both before and 1 to 2 years after the onset of heavy drinking.For youth with no or low alcohol consumption, gray matter volumes declined throughout adolescence, with rates slowing in many brain regions in later adolescence. However, youth who initiated heavy drinking exhibited a steeper decline in frontal gray matter volumes. For both youth with no or low alcohol consumption and those with heavy drinking, cannabis use did not influence gray matter volume trajectories. These findings were confirmed in a recent analysis spanning five time points in the NCANDA study and using linear mixed effects models.A greater number of past-year binge drinking episodes was linked to greater decreases in gray matter volumes in 26 of 34 bilateral Desikan-Killiany cortical parcellations tested. The strongest effects were noted in frontal regions as well as among younger adolescents; moreover, the effects largely attenuated in later adolescence. The gray matter volumes decreased most for individuals with greater numbers of binge drinking episodes and recent binge drinking. These findings provide yet more evidence that adolescent binge drinking is linked to a greater risk of more prominent gray matter reductions during adolescence.Functional MRI studies further suggested that adolescents with histories of heavy drinking showed aberrant patterns of activation in response to cognitively challenging tasks, including tasks of working memory and inhibition. In adolescents with a history of 1 to 2 years of heavy drinking,grow tray stand the aberrant activation was not linked to detectable deficiencies in task performance.
However, if heavy drinking persisted longer, reduced task performance was often evident in the adolescents.This pattern of results suggested that the brain may be able to compensate for subtle neuronal insults for a period of time, but if drinking patterns persist and become heavier, the brain may no longer be able to compensate and may be vulnerable to the effects of repeated and sustained heavy doses of alcohol.Throughout adolescence, white matter volume increases and matures, resulting in myelination that increases speed of neuronal transmission and modulates the timing and synchrony of neuronal firing patterns that convey meaning in the brain.Squeglia et al. reported that adolescents who drank heavily showed attenuated white matter growth of the corpus callosum and pons relative to adolescents who did not drink.Pfefferbaum et al. indicated that among those in the NCANDA sample who consumed no or little alcohol, white matter regions grew at faster rates in younger age groups and slowed toward young adulthood.To examine the potential for a neurotoxic effect of alcohol use on adolescent development of white matter, Zhao et al. conducted a whole-brain analysis of fractional anisotropy of NCANDA participants ages 12 to 21 at baseline.For 63 adolescents who initiated heavy drinking, the researchers examined white matter quality before and after drinking onset and compared it to the white matter maturation trajectory of 291 adolescents with no or low alcohol consumption. Results showed deterioration of white matter integrity in youth who drank heavily compared with age- and sex-matched controls. Moreover, the slope of this reduction over time corresponded with days of drinking since the study entry.Within-subject analyses contrasted developmental trajectories of youth before and after they initiated heavy drinking. These analyses suggested that drinking onset was associated with, and appeared to precede, disrupted white matter integrity. This disruption was greater in younger adolescents than in older adolescents, and was most pronounced in the genu and body of the corpus callosum.It is possible that these brain structure changes may occur concomitantly with modifications in certain neurotransmitter and hormone secretion systems, which markedly influence the refinement of certain brain areas and neural circuits.Along with altered development and maturation of gray and white matter, studies have reported neurocognitive consequences of underage drinking, such as impairments in attention,verbal learning,visuospatial processing,and memory.Neurocognitive deficits linked to moderate to heavy drinking during this critical developmental period may lead to direct and indirect changes in neuromaturational course, with effects that may extend into adulthood. Squeglia et al. examined neurocognitive function in adolescents who drank heavily, moderately, or not at all, based on the Cahalan classification system.
Their findings suggested that initiation of moderate to heavy alcohol use and incurring hangovers during adolescence may adversely influence neurocognitive functioning. For females, more drinking days in the past year predicted a greater reduction in performance on visuospatial tasks, in particular visuospatial memory, from baseline to follow-up. For males, a tendency was seen for more hangover symptoms in the year before follow-up testing to predict a relative worsening of sustained attention.Another set of studies demonstrated that youths who drank heavily exhibited greater brain activation while viewing alcohol advertisements than while viewing ads for nonalcoholic beverages. Adolescents are exposed to alcohol advertising materials on a daily basis in many countries. As studies in adults with AUD have shown atypical responses to alcoholrelated materials,Tapert and colleagues used fMRI analyses to determine whether similar response patterns existed in adolescents who drink.The study included 15 adolescents ages 14 to 17 with AUD and 15 demographically similar adolescents who drank infrequently. The participants were shown pictures of alcoholic and nonalcoholic beverage advertisements during neuroimaging. Adolescents with histories of heavy drinking showed greatly enhanced neural activation while viewing the pictures of alcoholic beverages compared with pictures of nonalcoholic beverages. The extent of alcohol-related activation was greatest for those with the highest levels of monthly alcohol intake. In contrast, youth with limited drinking histories showed similar levels of activation while viewing the two beverage picture types. These results demonstrated pronounced alcohol cue reactivity in heavy drinking teens, particularly in reaction to alcohol advertising materials. Studies examining longer-term impacts of adolescent alcohol misuse have yielded mixed results. Some studies reported a maturing-out without significant consequences in adulthood, while others found ongoing effects on mental health, physical health, and social functioning, as well as higher levels of alcohol use and AUD.Analyses using data from the National Longitudinal Alcohol Epidemiologic Survey determined that 40% of those initiating alcohol use before age 15 were diagnosed with AUD at some point in their lives compared to only 10% of those who delayed the onset of drinking until age 21 or later.The first study of adolescents to assess the association between age of adolescent drinking onset and neurocognitive performance found that earlier age of drinking onset predicted poorer performance on tasks requiring psychomotor speed and visual attention. Similarly, an earlier age of onset of regular drinking predicted poorer performances on tests of cognitive inhibition and working memory.This study suggested that early onset of drinking increased risk for subsequent neuropsychological dysfunction.Several studies have reported that the associations between alcohol and brain structure and function differ by sex, especially in adolescents engaging in binge drinking. While not conclusive across the literature, female adolescents who engaged in binge drinking appeared to show effects such as blunted activation in frontal, temporal, and cerebellar cortices compared to females who did not drink, whereas male adolescents who engaged in binge drinking showed the opposite activation pattern.Female adolescents ages 15 to 17 meeting criteria for AUD showed larger prefrontal cortex volumes than female controls, while male adolescents with AUD had smaller prefrontal cortex volumes than male controls.A similar finding was observed for white matter.Adolescence is the peak time for both onset of substance misuse and emergence of mental illness, including anxiety disorders, bipolar disorder, major depression, eating disorders, and psychosis.The National Survey on Drug Use and Health estimated that 20% of adolescents had a mental illness that persisted into adulthood.Moreover, adolescents with a past-year major depressive episode were more likely to be current binge alcohol users.However, it remains unclear how comorbid mental health problems contribute to and exacerbate the neurobiological effects of alcohol misuse.