Abstract
BackgroundPrevious studies have indicated that early life adversity, genetic factors and alcohol dependence are associated with reduced brain volume in adolescents. However, data on the interactive effects of early life adversity, genetic factors (e.g. p.Met66 allele of BDNF), and alcohol dependence, on brain structure in adolescents is limited. We examined whether the BDNF p.Val66Met polymorphism interacts with childhood trauma to predict alterations in brain volume in adolescents with alcohol use disorders (AUDs).MethodsWe examined 160 participants (80 adolescents with DSM-IV AUD and 80 age- and gender-matched controls) who were assessed for trauma using the Childhood Trauma Questionnaire (CTQ). Magnetic resonance images were acquired for a subset of the cohort (58 AUD and 58 controls) and volumes of global and regional structures were estimated using voxel-based morphometry (VBM). Samples were genotyped for the p.Val66Met polymorphism using the TaqMan® Assay. Analysis of covariance (ANCOVA) and post-hoc t-tests were conducted using SPM8 VBM.ResultsNo significant associations, corrected for multiple comparisons, were found between the BDNF p.Val66Met polymorphism, brain volumes and AUD in adolescents with childhood trauma.ConclusionsThese preliminary findings suggest that the BDNF p.Met66 allele and childhood trauma may not be associated with reduced structural volumes in AUD. Other genetic contributors should be investigated in future studies.
Highlights
Previous studies have indicated that early life adversity, genetic factors and alcohol dependence are associated with reduced brain volume in adolescents
In prior work we demonstrated that the two acquisition protocols produced comparable images that could be combined for analysis [8], out of an abundance of caution we match the Healthy Controls (HC) and alcohol use disorders (AUD) subjects on imaging protocol in imaging analyses reported in this paper
As an additional 2 × 2 Analysis of covariance (ANCOVA), we examined Childhood Trauma Questionnaire (CTQ) as a main effect and as an interaction with brain derived neurotrophic factor (BDNF) genotype, controlling for age, total matter volume (TMV) and alcohol life dose as covariates
Summary
Previous studies have indicated that early life adversity, genetic factors and alcohol dependence are associated with reduced brain volume in adolescents. Data on the interactive effects of early life adversity, genetic factors (e.g. p.Met allele of BDNF), and alcohol dependence, on brain structure in adolescents is limited. Studies of exposure to childhood trauma have been associated with reduced brain volumes in the prefrontal cortex [9] and the hippocampus [10,11,12] This is consistent with animal studies, which demonstrated that rats exposed to early life stress have alterations in hippocampal volume, possibly as a result of a decreased rate of synaptic development [13]. In a further analysis of our data on adolescents, we found that childhood trauma is associated with smaller left hippocampal and right precentral gyrus volumes in adolescents with exposure to alcohol [15]
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