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

Abstract

Background The increased susceptibility for developing alcohol dependence seen in offspring from families with alcohol dependence may be related to structural and functional differences in brain circuits that influence emotional processing. Early childhood environment, genetic variation in the serotonin transporter-linked polymorphic region (5-HTTLPR) of the SLCA4 gene and allelic variation in the Brain Derived Neurotrophic Factor (BDNF) gene have each been reported to be related to volumetric differences in the temporal lobe especially the amygdala Methods Magnetic resonance imaging was used to obtain amygdala volumes for 129 adolescent/young adult individuals who were either High-Risk (HR) offspring from families with multiple cases of alcohol dependence (N=71) or Low-Risk (LR) controls (N=58). Childhood family environment was measured prospectively using age-appropriate versions of the Family Environment Scale during a longitudinal follow-up study. The subjects were genotyped for Brain-Derived Neurotrophic Factor (BDNF) Val66Met and the serotonin transporter polymorphism (5-HTTLPR). Two family environment scale scores (Cohesion and Conflict), genotypic variation, and their interaction were tested for their association with amygdala volumes. Personal and prenatal exposure to alcohol and drugs were considered in statistical analyses in order to more accurately determine the effects of familial risk group differences. Results Amygdala volume was reduced in offspring from families with multiple alcohol dependent members in comparison to offspring from control families. High-Risk offspring who were carriers of the S variant of the 5-HTTLPR polymorphism had reduced amygdala volume in comparison to those with an LL genotype. Larger amygdala volume was associated with greater family cohesion but only in Low-Risk control offspring. Conclusions Familial risk for alcohol dependence is an important predictor of amygdala volume even when removing cases with significant personal exposure and covarying for prenatal exposure effects. The present study provides new evidence that amygdala volume is modified by 5-HTTLPR variation in High-Risk families.

Externalizing personality traits, empathy, and gray matter volume in healthy young drinkers

“…Hill’s group has found that the offspring of alcoholic relatives had lower [right > left] asymmetry ratios of combined gray and white orbital volume, and that orbital white matter asymmetry in these offspring correlated with greater impulsivity (Hill et al, 2009). The same group (Hill et al, 2001, 2013) and Dager et al (2015) also detected loss of right amygdala volume in the adolescent offspring of families with alcoholism. Most recently, Cservenka et al (2015) reported that family history density was related to left nucleus accumbens volume in adolescents, although only in girls.…”

Neurophysiological Correlates and Differential Drug Response in Subjects With a Family History of an Alcohol Use Disorder

“…One of the most well-replicated neuroimaging findings in FHP individuals is abnormal amygdala volume. Several studies have found that FHP individuals have smaller amygdala than FHN individuals, 9,53 whereas other studies found this difference only in the right amygdala. 15,54 Smaller amygdala have been detected as early as childhood 54 and persist after matching for IQ and socioeconomic status.…”

“…HR children who carry the short allele of 5- HTTLPR , a serotonin transporter gene implicated in alcohol dependence risk, 55 had the smallest amygdala volumes compared to long allele and LR counterparts. 53 The authors hypothesized that smaller amygdala volumes are a result of stressful childhood experiences, as family cohesion predicted larger amygdalas, and that those who had short alleles were most vulnerable to environmental influences. 53 However, some evidence suggests that smaller amygdala volumes are the result of a developmental lag rather than a static difference between FHP and FHN individuals.…”

“…53 The authors hypothesized that smaller amygdala volumes are a result of stressful childhood experiences, as family cohesion predicted larger amygdalas, and that those who had short alleles were most vulnerable to environmental influences. 53 However, some evidence suggests that smaller amygdala volumes are the result of a developmental lag rather than a static difference between FHP and FHN individuals. Sjoerds et al 56 found no differences in amygdala volumes in an adult sample, and Benegal et al 54 found that family history-related brain differences were most prominent in the younger participants in the study.…”

Does Family History of Alcohol Use Disorder Relate to Differences in Regional Brain Volumes? A Descriptive Review with New Data

“…Dager and colleagues (2015) observed significantly smaller amygdala volumes in FH+ as compared to FH− individuals, which is notable given the large sample size and correction for multiple comparisons. Hill and colleagues (2013a) similarly documented significantly smaller total, right, and left amygalar volumes in the FH+ group as compared to the FH− group. Other studies have corroborated these findings (Benegal et al 2007; Hill et al, 2001); however, other groups reported no differences in amygdalar volumes between FH groups (Cservenka et al, 2015; Sjoerds et al, 2013).…”