TITLE:
Caudate Volume in Offspring at Ultra High Risk for Alcohol Dependence: COMT Val158Met, DRD2, Externalizing Disorders, and Working Memory*
AUTHORS:
Shirley Y. Hill, Sarah Lichenstein, Shuhui Wang, Howard Carter, Michael McDermott
KEYWORDS:
Caudate; High-Risk; COMT; DRD2; MRI; Working Memory
JOURNAL NAME:
Advances in Molecular Imaging,
Vol.3 No.4,
October
11,
2013
ABSTRACT: Background: There is emerging evidence that the increased susceptibility to developing alcohol and substance use dis- orders in those
with a family history of Alcohol Dependence (AD) may be related to structural
differences in brain circuits that influence the salience of rewards
or modify the efficiency of information processing. Externalizing disorders of
childhood including Attention Deficit Hyperactivity Disorder, Conduct and
Oppositional Disorders are a prominent feature of those with a positive family
history. The caudate nuclei have been implicated in both the salience of
rewards and in the pathophysiology of alcohol dependence and these often
antecedent childhood disorders. Methods: Adolescent/young adult high and low-risk for AD offspring (N = 130)
were studied using magnetic resonance imaging. Volumes of the
caudate nucleus were obtained using manual tracing with BRAINS2 software and
neuropsychological functioning determined. Childhood disorders were
assessed as part of a long-term longitudinal follow-up that includes young
adult assessment. Dopaminergic variation was assessed using genotypic variation
in the catechol-O-methyltransferase (COMT) and DRD2 genes. Results: High-risk
subjects showed poorer Working Memory functioning. Caudate volume did
not differ between high and low-risk subjects, but those with externalizing
disorders of childhood showed reduced caudate volume. Variation in COMT and
DRD2 genes was associated with Working Memory performance and
caudate volume. Conclusions: Caudate volume is reduced in association with externalizing disorders
of childhood/adolescence. Working Memory deficits appear in familial high-risk
offspring and those with externalizing disorders of childhood. The dopaminergic
system appears to be involved in both working memory performance and
externalizing disorders of childhood.