Carmen S. van der Zwaluw

Gene-environment interactions and alcohol use and dependence: current status and future challenges.

AIM To discuss the current status of gene-environment interaction research with regard to alcohol use and dependence. Further, we highlight the difficulties concerning gene-environment studies. METHODS Overview of the current evidence for gene-environment interactions in alcohol outcomes, and of the associated challenges in gene-environment studies. RESULTS Attention to the causative roles of gene-environment interactions in alcohol use and dependence is increasing. Studies with twin designs are beginning to examine gene-shared environment effects, and animal studies have investigated gene-environment interaction effects on alcohol intake in primates. Thirteen studies incorporated gene-environment interactions in examining alcohol use or dependence in humans. These studies held a variety of candidate genes and environmental risk factors and their heterogeneity made it impossible to draw firm general conclusions. CONCLUSIONS Challenges for future gene-environment studies are abundant, and consist of, for example, the development of clear theoretical assumptions about neurobiological mechanisms and the recruitment of large longitudinal samples that already start in childhood. Replication is essential to prevent an overload of false-positive results. Despite the difficulties, it is crucial to include gene-environment interactions in future studies in order to unravel the aetiological factors of human alcohol outcomes.

Emotional eating in adolescents: a gene (SLC6A4/5-HTT) - depressive feelings interaction analysis.

Eating in response to distress--i.e. emotional eating--is highly prevalent in (female) adults with binge eating, but has only a very low prevalence in young children. The present study addresses the emergence of emotional eating in adolescence in relation to depressive feelings. Because a reduction of food intake is considered the biologically natural response to distress, we tested whether the a-typical stress-response of emotional eating develops in interaction with genetic vulnerability. We hypothesized that the short allele of the 5-HTTLPR polymorphism in the serotonin transporter gene, which is associated with lower serotonin activity, would moderate the relation between depressive feelings and the increase in emotional eating, particularly in females. A sample of Dutch families with two adolescents was included in a longitudinal study with a four-year follow-up. A moderator effect of 5-HTTLPR genotype on the relation between depressive feelings and the increase in emotional eating was found in both sexes in the youngest siblings (n = 286). In the older siblings (n = 298), this specific moderator effect was only found in the girls. Younger adolescents and older adolescent girls showed a higher increase in emotional eating if they carried the 5-HTTLPR short allele. This is the first study that found support for a gene × depressive feelings interaction on emergence of emotional eating in (female) adolescents.

A serotonin transporter polymorphism (5-HTTLPR) predicts the development of adolescent alcohol use

BACKGROUND Because the effects of susceptibility genes on alcohol use may differ as a function of age throughout adolescence and young adulthood, prospective study designs, in addition to cross-sectional ones are needed in genetic association studies. The short, low activity allele of a polymorphism (5-HTTLPR) in the serotonin transporter gene (SLC6A4) has been related to alcohol dependence. In the current study we tested whether 5-HTTLPR genotype was associated with adolescent alcohol use both cross-sectionally and longitudinally. METHODS Non-regular drinkers (n=202) were selected from Dutch, nationwide sample of adolescents (mean age 13.4 at baseline) who were assessed across five annual waves. Latent growth curve modeling was applied to examine individual development of alcohol use over time, by estimating the initial level of alcohol use at Wave 2 (intercept), and the rate of change in alcohol use across time (slope). RESULTS The 5-HTTLPR short allele predicted adolescents growth (slope) in alcohol use over time. Adolescents with the 5-HTTLPR short allele showed larger increase in alcohol consumption than those without the 5-HTTLPR short allele. 5-HTTLPR genotype was not related to the initial level (intercept) of alcohol consumption. In all analyses we controlled for sex and personality. CONCLUSIONS To gain more insight into the etiological role of genetic determinants of adolescent alcohol use, developmental approaches that distinguish between onset and continuation of drinking should be applied.

Polymorphisms in the dopamine transporter gene (SLC6A3/DAT1) and alcohol dependence in humans: a systematic review

Dopamine neurotransmission has been a key player in attempts to identify genetic factors involved in alcohol dependence. The dopamine transporter terminates dopaminergic neurotransmission, making the gene encoding the transporter (SLC6A3/DAT1) an attractive candidate in clinical studies on alcohol dependence. We conducted a systematic review of 18 studies examining associations between polymorphisms in DAT1 and alcohol dependence. The DAT1 variable number tandem repeat, the most frequent studied polymorphism in DAT1, did not show a direct association with alcohol dependence in general. Several, but not all, studies found that the DAT1 variable number tandem repeat (9-repeat allele) was associated with alcohol-withdrawal symptoms, such as seizures and delirium tremens. We discuss shortcomings, such as lack of power and disregarding moderating variables, as well as future challenges of gene association studies.

A Variable-Number-of-Tandem-Repeats Polymorphism in the Dopamine D4 Receptor Gene Affects Social Adaptation of Alcohol Use Investigation of a Gene-Environment Interaction

Research suggests that people adapt their own drinking behavior to that of other people. According to a genetic-differences approach, some individuals may be more inclined than others to adapt their alcohol consumption level to that of other people. Using a 3 (drinking condition) × 2 (genotype) experimental design (N = 113), we tested whether susceptibility to alcohol-related cues (i.e., seeing someone drink) was related to the variable number of tandem repeats in exon 3 of the D4 dopamine receptor gene. A strong gene-environment interaction showed that participants carrying at least one copy of the 7-repeat allele consumed substantially more alcohol in the presence of a heavy-drinking individual than did participants without this allele. This study highlights that individual variability in sensitivity to other people’s drinking behavior may be attributable to genetic differences. Carrying the 7-repeat allele may increase the risk for heavy alcohol use or abuse in the company of heavy-drinking peers.

Cognitive Functioning in the Acute Phase Poststroke: A Predictor of Discharge Destination?

Cognitive dysfunction occurs in more than half of stroke survivors and can have far-reaching consequences for functioning in daily life. Assessment of cognitive function can play a major role in determining the appropriate discharge destination after a hospital stay. The present study aimed to determine the feasibility of cognitive screening in the acute phase poststroke and to investigate whether this cognitive screening can accurately predict discharge destination to either a dependent or an independent living situation. A total of 287 patients with a first-ever cerebral stroke consecutively admitted to a stroke unit of a general hospital were eligible for the study. All patients underwent neuropsychological screening, consisting of the Mini-Mental State Examination (MMSE), Cognitive Screening Test (CST), and Clock-Drawing Test, within 7 days poststroke. Screening was feasible in 73.2% of the patients. Logistic regression analysis showed that the Barthel Index (BI) score (ie, ability to perform activities of daily living) could predict the discharge destination with 47% explained variance when age and BI score were taken into account. Adding the 3 cognitive tests to the model with age and BI improved the explained variance substantially (53%), with a significant contribution of BI and CST. Cognitive screening in the acute phase poststroke appeared to be feasible and capable of supporting the decision of whether to discharge a patient to home or to a dependent living situation. Functional status improved the predictive value of the model; the MMSE was not suitable for prediction. A comprehensive set of various predictors, including cognition, is recommended to support discharge planning.

Sex differences in young adults' snack food intake after food commercial exposure

Exposure to food commercials on television is considered to be related to elevated snack food intake in front of the television. However, this assumed relation has as yet not been fully established. The present study, therefore examined the direct effects of watching television food commercials on concurrent non-advertised snack food intake in young adults. In addition, possible sex differences were investigated. Participants (N=82, 50% male) watched a movie interrupted by two commercial breaks that contained either food commercials or neutral commercials. While watching, they could freely eat crisps and chocolate coated peanuts. Afterwards, participants filled out questionnaires and were weighed and measured. Regression analyses showed that men and women were differently affected by the food commercials. Food intake in women was higher when they watched the food commercials than when they watched the neutral commercials, whereas food intake in men was lower when they watched the food commercials than when they watched the neutral commercials. The results suggest that especially women are vulnerable for eating more snack food when exposed to food commercials.

The crown of love: intimate relations and alcohol use in adolescence.

BackgroundRemarkably, little attention has been paid to the role of intimate partners and their drinking behavior in relation to adolescent alcohol use. In the current study, we examined associations between adolescent alcohol use and romantic partners’ drinking behavior.MethodsA total of 428 families, consisting of both parents and two adolescents (aged 13.4 and 15.2 at Time 1) participated in a prospective study with four annual waves. Correlations and multivariate regressions were used to examine (1) similarity in drinking behaviors of adolescents and intimate partners, (2) whether alcohol use of partners prospectively predicts adolescent alcohol consumption, and (3) whether adolescents who consume alcohol select partners over time who show similar drinking behaviors.Results(1) Frequency of alcohol consumption of adolescents and of their romantic partners correlated significantly. (2) Alcohol use of partners was not predictive of adolescent alcohol consumption over time, if previous levels of alcohol consumption were taken into account. (3) Adolescents acquired partners with similar drinking behaviors. Gender effects were found; adolescent girls, but not boys, were more likely to become involved with partners who also frequently consumed alcohol.ConclusionsRegarding alcohol consumption, adolescents and their intimate partners were relatively similar in alcohol use. This resemblance is best explained by adolescents’ selection of future partner on the basis of alcohol consumption. Less indication was found for influence effects, perhaps due to the transient nature of most adolescent romantic relationships.

Longitudinal associations between attitudes towards binge drinking and alcohol-free drinks, and binge drinking behavior in adolescence

Alcohol attitudes are often considered an important predecessor of drinking behavior, although the literature is equivocal. Lately, attention has turned to enhancing positive cognitions on alcoholic-free drinks to discourage heavy drinking. The current study was the first to longitudinally examine associations between attitudes towards binge drinking and alcohol-free drinks and binge drinking behavior in a cross-lagged path model in Mplus. Participants were 293 adolescents (131 boys, M(age)=16.1 years) who filled in two online questionnaires with a six-month interval. Binge drinking behavior and attitudes towards binge drinking and alcohol-free drinks were all significantly correlated at both waves. The multivariate model, however, showed that only higher levels of binge drinking at T1 were prospectively related to more positive binge drinking attitudes at T2, and not vice versa. Analyses were controlled for sex, educational level, and age. Findings discard the Theory of Planned Behavior, but rather seem consistent with the Theory of Cognitive Dissonance, i.e., adolescents may adapt their cognitions to their behavior. More longitudinal research with several time points and over a longer period of time is needed to further examine the development of attitudes and drinking behavior.

Testing bidirectional relationships between alcohol use and depressive symptoms: What is the role of the serotonin transporter gene?

Alcohol abuse often co-exists with a major depressive disorder. In order to understand the development of this comorbidity, it is important to concentrate on the preceding process. It has been suggested that the link between alcohol use and depressive symptoms is a result of an interaction with genetic factors. The aim of this study was to longitudinally examine the effect of the 5-HTTLPR genotype on the association between depressive symptoms and alcohol use in a Dutch community sample. Following a stepwise approach, bivariate correlations, longitudinal regression analyses, and latent growth curve analyses were separately conducted for 316 males and 321 females. A positive correlation between depressive symptoms and alcohol use was shown in female carriers of the 5-HTTLPR short allele. In addition, latent growth curve analyses showed a positive association between alcohol use and the intercept of depressive symptoms (but not the slope), but only in female carriers of the 5-HTTLPR short allele. These findings show that alcohol use may be positively related, at least cross-sectionally, to depressive symptoms in female carriers of the 5-HTTLPR S allele, and indicate that moderators such as SLC6A4 genotype and sex need to be taken into account when examining associations between depressive symptoms and drinking behavior. In order to gain insight into the longitudinal association between alcohol use and depressive symptoms, studies should concentrate on earlier stages and focus on more fine-grained research designs that allow day-to-day changes in both alcohol use and depressive symptoms.