Hippocampal Volumes in Adolescents with and without a Family History of Alcoholism

Abstract

Background and Objectives The hippocampus may be vulnerable to the effects of heavy alcohol use during adolescence, which is a time of continued neurodevelopment. However, differences in hippocampal volume may be due to risk factors such as a family history (FH) of alcoholism. We examined hippocampal volumes in youth with and without a FH of alcoholism prior to the initiation of alcohol use. Methods Participants were demographically matched adolescents (aged 12-14) with positive (n=15; FHP) and negative (n=15; FHN) FH of alcoholism. Each group consisted of 10 males and 5 females with minimal previous substance use. Manual hippocampal tracings were completed on high-resolution magnetic resonance images by reliable raters, and intracranial volumes were controlled in analyses. Results FH groups did not differ on memory or hippocampal volumes, but group × gender interactions (p<.05) indicated that FHP males had larger left hippocampi than FHN males. Females showed greater left versus right hippocampal asymmetry, while males showed larger right versus left asymmetry. For all adolescents, larger right hippocampal volumes predicted poorer delayed visual memory (p<.01). Conclusion and Significance Alcoholism risk factors, such as family history of alcoholism, may differentially influence adolescent hippocampal development for boys as compared to girls. Results suggest that FH does not account for prior findings of reduced left hippocampal volumes in heavy drinking youth. Findings are preliminary, but suggest that future studies examining the effects of alcohol use on the adolescent brain should consider the influence of FH, especially among boys.

Family History Density of Alcoholism Relates to Left Nucleus Accumbens Volume in Adolescent Girls

“…These fi ndings are similar to another study of family history of alcoholism and GM brain volume in youth without heavy alcohol use, in which a Family History × Sex interaction was found with hippocampal volume, such that at-risk males had larger left hippocampal volumes than males without familial alcoholism (Hanson et al, 2010). It is possible that multiple neurobiological risk factors for alcoholism differ by sex in those with familial AUDs since there are also differences by sex in WM volume relationships with neuropsychological functioning in youth with and without a family history of substance abuse/dependence (Silveri et al, 2008).…”

“…Research using a region of interest (ROI) approach has found greater cerebellar volume (Hill et al, 2007(Hill et al, , 2011 and consistently smaller amygdalar and hippocampal (Benegal et al, 2007;Hanson et al, 2010;Hill et al, 2001Hill et al, , 2013b volumes in youth and young adults with familial alcoholism compared with controls. This suggests that morphometric characteristics of the brain may be particularly important markers of risk, but that structural variation related to risk may be present across brain areas.…”

“…For example, interactions with familial history risk status and externalizing disorders were reported in a study that found smaller caudate volume in youth and young adults from multiplex families with AUDs (Hill et al, 2013a). Importantly, studies that have examined brain volume in individuals with familial alcoholism have included samples of youth with little to no experience with alcohol (Benegal et al, 2007;Hanson et al, 2010) or individuals who were largely free of abuse or dependence diagnoses during childhood/adolescence (Hill et al, 2001(Hill et al, , 2007(Hill et al, , 2009(Hill et al, , 2011(Hill et al, , 2013a(Hill et al, , 2013b, thereby controlling for confounding alcohol-related neurotoxic effects on the brain.…”

“…In a study of hippocampal volume, the authors found that male youth with a family history of alcoholism (i.e., those who were family history-positive [FHP]) had larger volumes of the left hippocampus than male youth without a family history of alcoholism (i.e., those who were family history-negative [FHN]) (Hanson et al, 2010). However, no differences were observed between FHP and FHN female adolescents.…”

Family History Density of Alcoholism Relates to Left Nucleus Accumbens Volume in Adolescent Girls

“…Some of the previously published studies examined differences in brain volume between groups in a dichotomous fashion, such as comparing youth with and without familial alcoholism (Hanson et al, 2010), whereas others took a similar approach but included ultra-high-risk youth with multiplex familial AUDs in the family history group, thereby comparing high-and low-risk groups with very distinct levels of vulnerability toward AUDs (Hill et al, 2001(Hill et al, , 2007(Hill et al, , 2009(Hill et al, , 2011(Hill et al, , 2013a(Hill et al, , 2013b. However, the current study examined the degree of familial risk for alcoholism and its relationship with brain volume in a large cohort of youth all considered at risk because of the presence of at least one second-degree relative with an AUD.…”