Reduced hippocampal volume among adolescents with alcohol use disorders without psychiatric comorbidity
Introduction
Heavy alcohol use is common in adolescence, with 31% of 12th graders reporting getting drunk in the past month (Johnston et al., 2004), and 6–10% of teens meeting diagnostic criteria for an alcohol use disorder (AUD) (Clark et al., 2002, Rohde et al., 1996). AUDs are diagnostically encompassed within other substance-related disorders, and they include both alcohol abuse, which is characterized by a “maladaptive pattern of alcohol use manifested by recurrent and significant adverse consequences related to the repeated use of alcohol”, and alcohol dependence, which is defined as “a cluster of cognitive, behavioral, and physiological symptoms indicating that the individual continues to use alcohol despite significant alcohol-related problems” (DSM-IV, 1994). Despite the high prevalence of AUD among teens, few studies have examined the effects of heavy alcohol consumption on the adolescent brain. While a wealth of literature demonstrates the deleterious effects of alcohol on the adult brain (for review, see Kril and Halliday, 1999), the adolescent brain is still actively developing (Durston et al., 2001, Giedd et al., 1999, Gogtay et al., 2004), making it difficult to draw conclusions about adolescents based on findings from adults. It is essential to understand the neuromaturational and cognitive implications of chronic alcohol use during adolescence, as neural and functional abnormalities related to maladaptive drinking differ from those of adults and could limit educational, occupational, and social opportunities.
One brain structure that has consistently demonstrated sensitivity to alcohol-related neurotoxicity is the hippocampus—a structure crucial to intact learning and memory formation (Eichenbaum, 1999, Squire, 1992). Several studies on alcoholic older adults have documented reduced hippocampal volumes (Jernigan et al., 1991, Sullivan et al., 1995) as well as verbal and spatial memory impairments (e.g., Grant, 1987, Munro et al., 2000). While the research on human adolescents is limited, rodent studies suggest that alcohol-induced hippocampal pathology and functional impairments are greater in adolescent than adult rats (for review, see White and Swartzwelder, 2004), further indicating that adolescence may be a particularly vulnerable period for alcohol-related hippocampal and associated neurocognitive dysfunction.
A few studies have examined alcohol-related neurocognitive impairments among human adolescents, and suggest that chronic alcohol use among teens is associated with lower executive functioning, visuospatial skills, attention, and verbal and nonverbal memory scores (Brown et al., 2000, Moss et al., 1994, Tapert et al., 2002). However, very few studies have examined the neural correlates of these deficits, and most investigations of adolescents with AUD have not controlled for psychiatric comorbidities, including other substance use disorders, so the unique effects of heavy drinking remain unclear.
Only one study to date has examined the structural neuropathological consequences of heavy alcohol use on the developing brain (De Bellis et al., 2000), and it revealed that even with no differences in cerebral, cortical gray and white matter, corpus callosum, and amygdala volumes, adolescents and young adults with adolescent-onset AUD had significantly smaller bilateral hippocampal volumes than case-matched controls. However, as with other previous investigations of neurocognition among AUD youths, findings may have been influenced by comorbid psychiatric disturbances, such as post-traumatic stress disorder (PTSD) and depression, which have been independently associated with hippocampal volume reduction in adults (Bremner et al., 2000, Nutt and Malizia, 2004). Polysubstance use may also be related to results, as some participants with AUD also met criteria for other substance use disorders. While that sample was largely representative of adolescents with AUD, the current study was designed to address issues of comorbidity by examining hippocampal volumes in teens with AUD but without mood, anxiety, or other substance use disorders. It was hypothesized that AUD teens would have smaller hippocampi than demographically similar controls.
Section snippets
Participants
Adolescents, ages 15 to 17, were recruited from local high schools, and included 14 teens who met DSM-IV criteria for alcohol abuse (n = 5) or dependence (n = 9) and 17 demographically similar non-abusing controls. Participants and their parents were telephone-screened for eligibility, as detailed elsewhere (Tapert et al., 2003). This study was conducted in accordance with and approved by the University of California San Diego Institutional Review Board, and written consent/assent was obtained from
Brain volumes
Adolescents with AUD had significantly smaller left hippocampal volume ratios (expressed as a ratio to intracranial volume) than healthy matched control teens (t = 2.90, df = 29, P < 0.01; Cohen's d = 1.08) (see Fig. 2), while no statistically significant differences were present between groups for right hippocampal volume ratios (Fig. 3) (t = 0.51, df = 29, P = 0.61), intracranial volume (t = − 0.67, df = 29, P = 0.51), or overall gray (t = 0.06, df = 29, P = 0.95) and white matter (t = − 1.20, df = 28, P = 0.24) volume ratios
Discussion
This study replicated and extended the results of a previous study examining brain morphology associated with AUD in adolescents. Here, we examined teens who were free from other substance use disorders and psychiatric disorder, with the exception of conduct disorder, and observed significantly smaller left hippocampal volumes among adolescents with AUD than non-abusing matched control teens. Even after exclusion of teens with comorbid AUD and conduct disorder from the analyses, teens with AUD
Acknowledgements
This work was supported by grants R21 AA12519 and R01 AA13419 from the National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (Dr. Tapert) and the UCSD Fellowship in Biological Psychiatry and Neuroscience (Dr. Nagel). The authors thank M.J. Meloy, Ph.D., Randy Notestine, Christine Fennema-Notestine, Ph.D., Korak Sarkar, and Erick Cheung for their valuable contributions to this research.
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