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

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.

Psychopathology in offspring from families of alcohol dependent female probands: a prospective study.

BACKGROUND: Despite the importance of understanding the long-term outcome for children of alcohol dependent (AD) women, the available literature is largely based on offspring of AD fathers and few have utilized prospective designs that include child, adolescent and young adult assessments. Multiplex AD families in which multiple cases of AD are present provide an ideal setting for understanding developmental variants of the adult phenotype. METHOD: Offspring from multiplex AD families identified through the mother or control families were evaluated multiple times during childhood and followed to young adulthood. Familial risk status and the presence of specific child/adolescent disorders were used as predictors of substance use disorder outcome by young adulthood. RESULTS: Offspring who were members of maternal multiplex families had elevated rates of child and young adulthood disorders. High risk offspring of alcohol dependent women were at increased risk for externalizing (Conduct Disorder and ADHD) and internalizing disorders (Major Depressive Disorder (MDD) and Anxiety Disorders). By young adulthood, offspring from these multiplex families had significantly greater odds of developing alcohol abuse or dependence (odds ratio [OR] = 3.63 [CI 1.36-9.64]) and drug abuse or dependence (OR = 4.23 [CI 1.73-10.32]). The prospective design of the study revealed that specific childhood disorders (Conduct Disorder, ADHD, MDD) increased the odds of subsequent development of substance use disorder (SUD). CONCLUSIONS: Multiplex familial risk for alcohol dependence is a significant predictor of substance use disorders by young adulthood. Familial risk and an earlier childhood disorder may set the stage for later development of SUD.

Physical activity patterns using accelerometry in the National Weight Control Registry.

The National Weight Control Registry (NWCR) was established in 1993 to examine characteristics of successful weight-loss maintainers. This group consistently self-reports high levels of physical activity. The aims of this study were to obtain objective assessments of physical activity in NWCR subjects and compare this to physical activity in both normal-weight and overweight controls. Individuals from the NWCR (n = 26) were compared to a never obese normal-weight control group matched to the NWCR group's current BMI (n = 30), and an overweight control group matched to the NWCR group's self-reported pre-weight-loss BMI (n = 34). Objective assessment of physical activity was obtained for a 1-week period using a triaxial accelerometer. Bouts of moderate-to-vigorous physical activity (MVPA) ≥10 min in duration, as well as nonbout MVPA (bouts of MVPA 1-9 min in duration) were summed and characterized. NWCR subjects spent significantly (P = 0.004) more time per day in sustained bouts of MVPA than overweight controls (41.5 ± 35.1 min/day vs. 19.2 ± 18.6 min/day) and marginally (P = 0.080) more than normal controls (25.8 ± 23.4). There were no significant differences between the three groups in the amount of nonbout MVPA. These results provide further evidence that physical activity is important for long-term maintenance of weight loss and suggest that sustained volitional activity (i.e., ≥10 min in duration) may play an important role. Interventions targeting increases in structured exercise may be needed to improve long-term weight-loss maintenance.