Cerebellum volume in high-risk offspring from multiplex alcohol dependence families: Association with allelic variation in GABRA2 and BDNF

Abstract

Offspring from families with multiple cases of alcohol dependence have a greater likelihood of developing alcohol dependence (AD) and related substance use disorders. Greater susceptibility for developing these disorders may be related to structural differences in brain circuits that influence the salience of rewards or modify the efficiency of information processing and AD susceptibility. We examined the cerebellum of 71 adolescent/young adult high-risk (HR) offspring from families with multiple cases of alcohol dependence (multiplex families), and 60 low-risk (LR) controls with no family history of alcohol or drug dependence who were matched for age, gender, socioeconomic status and IQ, with attention given to possible effects of personal use of substances and maternal use during pregnancy. Magnetic resonance images were acquired on a General Electric 1.5-Tesla scanner and manually traced (BRAINS2) blind to clinical information. GABRA2 and BDNF variation were tested for their association with cerebellar volumes. High-risk offspring from multiplex AD families showed greater total volume of the cerebellum and total gray matter (GM), in comparison with LR controls. An interaction between allelic variation in GABRA2 and BDNF genes was associated with GM volumes, suggesting that inherited variation in these genes may promote early developmental differences in neuronal proliferation of the cerebellum.

Amygdala Volume in Offspring from Multiplex for Alcohol Dependence Families: The Moderating Influence of Childhood Environment and 5-HTTLPR Variation

“…Maternal alcohol dependence during pregnancy was not present. Also, maternal use of alcohol has proved to be of minimal significance in statistical analysis of cerebellar data acquired from this sample [75]. …”

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.…”

“…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.…”

Perinatal ethyl alcohol effects on the development of cerebellar cortex in albino rat

“…It was found that the continuous ethyl alcohol ingestion at high doses has risk effects on the cerebellum and its neurons especially Purkinje cells (Fitzgerald et al, 2011;Hill et al, 2011;Heaton et al, 2012). The principal aim of this study was *Corresponding author.…”