Recent binge drinking predicts smaller cerebellar volumes in adolescents

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Abstract

The current study examined the effects of recent binge drinking on cerebellar morphometry in a sample of healthy adolescents. Participants were 106 teenagers (46 bingers and 60 controls) aged 16–19 who received a high-resolution magnetic resonance imaging (MRI) scan. FreeSurfer segmented and quantified the volume of each cerebellum. Maximum drinks during a binge in the past 3 months and duration since last binge were examined as predictors of cerebellar volume, after controlling for potentially confounding variables. In the 106 teens, higher peak drinks predicted smaller left hemisphere cerebellar gray and whitematter, and right hemisphere cerebellar gray matter, and marginally predicted smaller right hemisphere cerebellar white matter. Gender did not moderate these effects. More intense adolescent binge drinking is linked to smaller cerebellar volumes even in healthy teens, above and beyond variability attributable to risk factors for binge drinking. Longitudinal research is needed to see if cerebellar volumes worsen with protracted drinking and recover with abstinence. Interventions aimed at improving brain structure in adolescent binge drinkers are necessary given the high prevalence of risky drinking in youth.

Introduction

Alcohol continues to be the most widely used intoxicant among teens, with almost a third of 12th graders reporting past month binge drinking (four standard alcohol drinks on an occasion in females and five drinks for males; Johnston et al., 2011). Despite this, relatively few studies have examined the impact of binge drinking on brain structure in teens.

Alcohol exposure appears to particularly affect the cerebellum (see Sullivan and Pfefferbaum, 2005, for review) by exerting its effects on GABAergic neurons and glutamatergic granule cells (Valenzuela et al., 2010). In rats, chronic alcohol exposure has resulted in structural abnormalities in Purkinje cells (Pierce et al., 2011). The cerebellum plays a critical role in coordination and balance, affect regulation, and executive functioning (Schmahmann and Sherman, 1998), which are often disrupted in adult alcohol dependent samples (see Sullivan and Pfefferbaum, 2005, for review).

Because adolescence is a dynamic developmental stage, adult findings might not apply to teens. Several brain regions including the cerebellum continue to undergo gray matter synaptic pruning into the mid-twenties (Lenroot and Giedd, 2006), and maturation of white matter tracts appears to continue into the early thirties (Jernigan and Gamst, 2005). More specific to the current study, the cerebellum continues to functionally (e.g., Luna et al., 2001) and structurally mature through adolescence, with most studies suggesting continued pruning into the early twenties (Castellanos et al., 2002, Hill et al., 2007). Gender differences in whole brain (Lenroot and Giedd, 2010) and cerebellar (Tiemeier et al., 2010) development have also been reported, with girls peaking earlier and having relatively smaller total cerebellar volumes.

Given this neurodevelopment, the emergence of binge drinking during the teen years may differentially influence the trajectory of brain development for boys and girls. Animal studies suggest that, compared to adults, adolescents may be particularly vulnerable to the neurotoxic effects of both chronic and binge alcohol exposure (see Spear, 2010, for review). Despite the much higher prevalence of binge drinking compared to alcohol use disorders (AUD), the majority of the studies conducted thus far have specifically recruited teens with a history of AUD. Studies using magnetic resonance imaging (MRI) have revealed abnormalities in teens with AUD, including smaller left hippocampal (De Bellis et al., 2000, Nagel et al., 2005, Medina et al., 2007) and prefrontal cortex (De Bellis et al., 2005, Medina et al., 2008) volumes. Only one study investigated the cerebellum, which reported smaller cerebellar volumes in boys with AUD as compared to male controls (De Bellis et al., 2005).

More recently, studies have examined the link between hazardous alcohol use (i.e., binge drinking) and brain health in youth. Using diffusion tensor imaging, our laboratory (McQueeny et al., 2009) found that adolescent binge drinkers, compared to light drinkers, had significantly reduced white matter quality in several brain regions. Although binge drinking was not directly assessed, we (Medina et al., 2010) found that increased overall use of alcohol during the past year was significantly related to smaller cerebellar vermis volumes in substance-using teens. Taken together, these studies suggest that recent binge drinking is associated with structural brain changes, although effects on the cerebellum have not been examined. Therefore, the aim of the current study was to assess the dose-dependent effects of recent binge drinking on cerebellar volumes in a sample of 106 typically developing teenagers without comorbid psychiatric disorders. Based on adult findings, we hypothesized that higher peak binge drinking levels would be associated with smaller cerebellar volumes. Based on prior research (Medina et al., 2008, Squeglia et al., 2009, Squeglia et al.,), we also hypothesized that the relationship between binge drinking and smaller cerebellar volumes would be stronger in females than males.

Section snippets

Participants

Adolescents aged 16–19 were recruited from two projects examining youth at risk for substance use and consequences of marijuana use (McQueeny et al., 2009, Hanson et al., 2010). In both, teens were recruited via flier distribution at area schools. Studies were approved by the University of California, San Diego Human Research Protections Program, and written assent and consent were obtained from each adolescent and the adolescent's parent/legal guardian, respectively. Each teen and his/her

Demographics

Groups did not significantly differ in age (range 16–19) [F(1,105)=2.46, p=0.12], puberty stage [girls: F(1,37)=0.16, p=0.69; boys: F(1,65)=1.84, p=0.18], gender [x2(1)=0.91, p=0.34], parental socioeconomic status [F(1,105)=0.21, p=0.57], parental income [F(1,105)=0.25, p=0.62], grades completed [x2(5)=10.1, p=0.07], reading ability [F(1,105)=0.41, p=0.53], ethnicity [x2(7)=4.87, p=0.56], Hispanic/Latino composition [x2(2)=3.7, p=0.15], extent of family history of SUD (range: 0–2.25) [x2

Discussion

Our first hypothesis was supported: higher peak drinks in the past 3 months predicted smaller cerebellar volumes, for left gray and white matter and right gray matter, and marginally for right white matter compartments in a sample of 106 teens with a range of binge drinking exposure. Differences in volume were seen after controlling for the effects of gender, intracranial volume, depressive symptoms, conduct disorder diagnosis, family history of substance use disorder, recent tobacco use,

Acknowledgments

This article and much of the research presented within it were made possible through funding by the National Institute on Alcohol Abuse and Alcoholism grant R01 AA13419 and National Institute on Drug Abuse grant R01 DA021182 (PI: Tapert). During manuscript preparation, Dr. Lisdahl was supported by NIDA-funded grants R03DA027457 and R01DA030354. We would like to thank Anthony Scarlett, Diane Goldenberg, and Alejandra Infante for their assistance in establishing intracranial volumes in this

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