This study compared white matter integrity between adolescents with binge alcohol consumption relative to controls matched on age, gender, verbal IQ, ethnicity, and socioeconomic status. Despite demographic similarities, widespread reductions in FA were observed in heavy episodic drinkers, suggesting the possibility of compromised white matter integrity in major fiber tract pathways in frontal (including the corpus callosum genu and body), cerebellar, temporal, and parietal regions. These findings extend previous reports of FA diminutions observed in adults both diffusely throughout white matter (Pfefferbaum et al., 2006b
), and specifically in the corpus callosum (Harris et al., 2008
; Pfefferbaum and Sullivan, 2005
; Pfefferbaum et al., 2006a
; Schulte et al., 2005
) of individuals with alcohol use disorders, yet this is the first report to describe reduced FA in drinkers as early as mid-adolescence and in youth who do not meet criteria for alcohol abuse or dependence.
Although we only observed FA decrements, De Bellis and colleagues (2008)
found increased FA in the rostral body and isthmus of the corpus callosum among youth with an alcohol use disorder (AUD) in a region-specific study. Although the current study did not include adolescents with AUD, results here are consistent with our previous study of 8 teenagers with AUD (without concomitant psychiatric issues) compared to 8 control teens (Tapert et al., 2003
). This pilot investigation showed reduced FA in the splenium [F
(1,16) = 4.39, p
= 0.05] and marginally in the body [F
(1,16) = 3.46, p
= 0.08] of the corpus callosum. Conflicting findings could stem from dissimilarities in samples. While, here, groups were matched by age and free from psychiatric conditions, De Bellis and colleagues studied youths with an AUD who were slightly older than their comparison group (16.9 years vs. 15.9 years, p
< 0.003), and had comorbid Axis I disorders (75% cannabis use disorder, 72% lifetime major depressive episode, 69% attention deficit/hyperactivity disorder, and 63% conduct disorder) whereas such diagnoses were exclusionary for controls. These comorbid disorders have previously been linked to white matter abnormalities (Matochik et al., 2005
; McAlonan et al., 2007
; Medina et al., 2007a
; Steingard et al., 2002
). Thus, there is much difficulty extricating potential interactive effects of these conditions. However, both the present study and De Bellis and colleagues (2008)
offer interesting contributions to understanding the relationships between adolescent alcohol involvement and white matter integrity. The present study examined sub-clinical drinking to better isolate alcohol effects on typically developing teenagers. Binge drinking teens are of particular interest, as it is estimated that more than 30% of minors who begin drinking before age 16 will develop alcohol dependence (Grant and Dawson, 1997
). Indeed, studying nondisordered adolescent drinkers is of substantial import due to the increased risk for binge drinking teens to transition into an AUD by adulthood (Hawkins et al., 1992
; Viner and Taylor, 2007
). The sample in the De Bellis paper is representative of adolescents with an AUD, especially due to high rates of comorbid psychiatric disorders among such youth (Clark et al., 1997
; Viner and Taylor, 2007
White matter aberrancies were related to drinking in a dose-dependent manner. Higher estimations of peak blood alcohol concentrations were linked to poorer fiber tract quality in the corpus callosum, internal/external capsules, and posterior corona radiata. Further, teens reporting multiple hangover symptoms showed more compromised white matter in the body and genu of the corpus callosum, frontal lobe projection fibers (anterior corona radiata), and cerebellar tracts (inferior peduncle). This finding linking postdrinking effects to worse integrity is consistent with white matter deficits observed in adults with histories of alcohol withdrawal seizures (Sullivan et al., 1996
). These relationships suggest that high-dose alcohol consumption, to the extent that hangover symptomatology arises, may index adverse influences on white matter caliber, particularly since associations were not observed for drinking frequency or duration. It is also possible that hangover may be more accurately recalled than other aspects of alcohol involvement.
The results of this study align interestingly with prior evidence for alcohol-related interruption of frontocerebellar circuitry (Sullivan and Pfefferbaum, 2005
), involving network nodes pons and thalamus, which exhibit volumetric decrements among adult alcoholics (Sullivan et al., 2003
). Although we did not examine the integrity of frontocerebellar white matter connectivity specifically, we did observe lower FA in the superior cerebellar peduncle, a fiber tract that connects the thalamus to deep cerebellar nuclei (Wakana et al., 2004
). Thalamic projections also emanate from the posterior limb of the internal capsule, where reduced fiber coherence was detected. These observations of altered white matter microstructure, combined with results from other DTI, morphometric, fMRI, and neuropsychological studies, serve as converging lines of evidence pointing towards a deleterious influence of alcohol on frontocerebellar circuitry (Sullivan and Pfefferbaum, 2005
). Unlike the aforementioned studies with samples comprised of mature individuals with years of alcoholism, the sample of this exploratory analysis represents teenagers at the beginning stages of risky alcohol use, and related white matter abnormalities in these pathways detectable as early as 16 years of age.
The hippocampus is vulnerable to the effects of ethanol, particularly during adolescence (Medina et al., 2007b
; Nagel et al., 2005
). Running dorsally to the hippocampus are the fornix and stria terminalis, both compact limbic projections terminating at hippocampal and amygdala regions, respectively (Wakana et al., 2004
). Since these fibers are tightly packed together, it is difficult to ascertain whether the decreased FA observed in this area indicates altered white matter integrity to the fibers making up the fornix, terminal stria, or both. As adolescents with alcohol use disorders have demonstrated impairments in learning and memory (Tapert et al., 2002
), diminished FA in the fibers extending to the hippocampus may suggest changes in structural connectedness leading to functional aberrations in teenage drinkers. Multimodal neuroimaging studies will help solidify the nature of white matter connectivity between these regions (e.g., frontal lobe, thalamus, pons, cerebellum, insula, hippocampus, and amygdala), and elucidate the influence of heavy drinking on these networks.
Due to binge drinkers' relatively inchoate stages of alcohol use, results could alternatively highlight a premorbid white matter characteristic representing a vulnerability to risky drinking. However, the observed link between alcohol involvement (i.e., hangover) and reduced FA in this study lends support to a possible compromising influence of high-dose alcohol use on white matter quality. Several potential mechanisms could explain how FA might be reduced in heavy drinking teens. Years of alcoholism are linked to decreased N
-acetylaspartate in white matter tissue, suggesting compounding axonal insult by chronic alcohol use (Meyerhoff et al., 2004
; Schweinsburg et al., 2001
). FA decrements could represent such a chemically induced axonal injury at a microstructural level. Animal models provide additional insights to rapid, alcohol-induced neural injury. Adult rats demonstrate neurodegeneration following once-daily ethanol exposure within as little as 5 days (Collins et al., 1998
). Additionally, adolescent rats show differential sensitivity to brain damage compared to adults following 4 days of binge alcohol administration (Crews et al., 2000
). Thus, human adolescents may be especially vulnerable to the deleterious effects of alcohol on neural tissues, including white matter. Another explanation of poor white matter integrity in binge drinking adolescents could relate to a disruption of neuromaturational processes. Developmental studies of white matter coherence have demonstrated increasing FA across adolescence (Giorgio et al., 2008
; Hasan et al., 2007
), reflected here by increased FA in the corpus callosum and fornix/stria terminalis with advancing pubertal stage. Low fiber tract coherence among drinkers could be due to an innate delay or an alcohol-related impediment in normal maturational processes. It is also possible that the observed changes may relate to axonal atrophy or membrane breakdown, important in the context of adolescent neuromaturation.
This study is the first we are aware of to characterize white matter integrity in major fiber tracts throughout the cerebrum and cerebellum between subdiagnostic binge drinking teens and nondrinkers. The study is limited by its cross-sectional design and modest sample size, and serves as a preliminary characterization of white matter integrity in adolescent binge drinkers. Due to the exploratory nature of this study, the data require replication. If replicated, these results carry important public health implications as interventions targeting binge drinking behaviors could lessen the risk for developing an alcohol use disorder. Longitudinal investigations, currently underway, will also help ascertain the degree to which heavy drinking and postdrinking effects might influence the developing adolescent brain. Studies with larger sample sizes will examine gender differences, factors predating alcohol use (e.g., family history of alcoholism, personality, conduct disorder), and neuropsychological correlates of white matter abnormalities.
In sum, this study shows differences in white matter quality in adolescents with histories of heavy episodic drinking, revealing widespread areas of compromised white matter in projections to networks underlying complex cognitive abilities of learning, memory, and executive functions. Although preliminary, these results bolster the importance of elucidating the neural sequelae of heavy episodic drinking during adolescence.