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.

Different trajectories of adolescent alcohol use: testing gene-environment interactions.

BACKGROUND: Transitions into heavy alcohol use often already take place during adolescence and are likely to be both genetically and environmentally determined. Therefore, in a 6-wave longitudinal study, we examined the effects of DRD2 Taq1A and OPRM1 A118G genotypes and the interaction with parental rule-setting on different groups of adolescent drinkers. METHODS: Growth mixture modeling resulted in 3 distinct groups of adolescent drinkers: light drinkers (n = 346), moderate drinkers (n = 178), and heavy drinkers (n = 72). RESULTS: Multinomial regression showed that moderate drinkers carried the OPRM1 G allele and received lower levels of parental rule-setting significantly more often than the light drinking group. No other significant main effects of DRD2, OPRM1, and rule-setting were found. The interaction between OPRM1 genotype and parental rule-setting significantly distinguished the heavy drinkers from the light (p < 0.001) and moderate groups (p = 0.055): Particularly, the alcohol use of OPRM1 G allele carriers was affected by parental rule-setting, while AA genotype carriers remained largely unaffected by parental rules. CONCLUSIONS: Findings showed that different trajectories of adolescent drinking are preceded by a gene-parenting interaction. These results concur with Belsky's theory of plasticity (2009), as well as with Shanahan and Hofer's typology of a controlling and restricting gene-environment interaction (2005).

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.

The moderating effect of alcohol-specific parental rule-setting on the relation between the dopamine D2 receptor gene (DRD2), the µ-opioid receptor gene (OPRM1) and alcohol use in young adolescents.

AIMS: The main aim of the study was to test the moderating effect of two genetic polymorphisms, one in the dopamine D2 receptor gene (DRD2) and one in the mu-opioid receptor gene (OPRM1), on the link between parental rule-setting and adolescent alcohol use. METHODS: A total of 214 adolescents (M(age )=13.7, 44.9% male) provided saliva samples and completed survey items describing alcohol use and parental rule-setting. RESULTS: Findings indicated that alcohol-specific parental rule-setting was more robustly associated with alcohol use for adolescents with the DRD2 A1 risk allele and for those with the OPRM1 G-allele. CONCLUSION: This study replicates the interaction between parental rule-setting and the DRD2 risk allele on adolescent alcohol use and extends the literature by demonstrating the moderating effects of the OPRM1 risk allele on the link between parental rule-setting and adolescent alcohol use.

Best friends and alcohol use in adolescence: the role of the dopamine D4 receptor gene.

The influence of friends and peers is theoretically one of the most consistent and important factors explaining adolescent alcohol use. However, not all adolescents are equally likely to be influenced by their friends' drinking behaviors. Genetic factors may underlie these inter-individual differences in susceptibility to the drinking behavior of friends. Because the long allele (≥ 7 repeats) of the dopamine D4 receptor (DRD4) gene has been associated with susceptibility to alcohol and alcohol-related cues, we tested whether associations between best friend's and adolescent's alcohol use differed for DRD4 genotypes. A Dutch nationwide sample of 308 adolescents (age 13 at baseline) participated in a prospective, community-based study with five annual waves. A cross-lagged path analysis was carried out in Mplus to examine bi-directional relations between friends' and adolescents' weekly alcohol use (number of drinks). A multi-group approach was applied to test for moderation effects of a 48-base pair variable number of tandem repeats polymorphism in exon 3 of the DRD4 gene. Additionally, with latent growth curve models, it was examined whether the interaction between friends' drinking and DRD4 genotype predicted the development of adolescents' alcohol use. Results showed that both cross-sectionally and longitudinally higher levels of friends' alcohol use resulted in higher levels of adolescents' alcohol consumption over time (and vice versa). No significant moderation of DRD4 genotype was found: Associations between adolescents' and friends' drinking did not differ for adolescent carriers of the DRD4 long allele, when compared with adolescents without the DRD4 long allele. Because this is the first study to examine DRD4 × friends' drinking effects prospectively, replication is essential. Future longitudinal studies, possibly with observational or diary designs, are needed to increase our understanding of the interplay between genetic and environmental risk factors for adolescent alcohol use.

Risky alcohol use in adolescence: the role of genetics (DRD2, SLC6A4) and coping motives.

BACKGROUND: Drinking to cope (i.e., drinking to forget or alleviate negative feelings) has been found to be associated with adolescents' heavy drinking and alcohol-related problems. Additionally, it is widely accepted that genetic factors are involved in alcohol use and dependence. Studies are only beginning to reveal, however, which specific genotypes are related to drinking behaviors, and it is unknown whether they may interact with coping motives in predicting adolescents' risky drinking. The aim of this study was to examine relationships between the dopamine D2 receptor gene (DRD2) Taq1A polymorphism (rs1800497), a serotonin transporter gene (SLC6A4) polymorphism (5-HTTLPR), coping motives, and adolescents' binge drinking and alcohol-related problems. METHODS: Participants in this cross-sectional study were 282 Dutch adolescents (mean age 17.4, 47% men) who had consumed alcohol at least once in their life. RESULTS: Coping motives were positively related to both binge drinking and alcohol-related problems, while DRD2 and SLC6A4 genotypes were not. DRD2, but not the SLC6A4 genotype, interacted with coping motives. The link between coping motives and alcohol outcomes was stronger among those carrying the DRD2 risk (A1) allele. CONCLUSIONS: This study extends the present literature by providing additional insight into the etiological factors of adolescent drinking behavior. An interaction between a vulnerability gene (DRD2) and a cognitive factor (coping drinking) was found to be related to adolescents' binge drinking and alcohol-related problems.

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.

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) x 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.

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 adolescent's 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.

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.

Parental control and the dopamine D2 receptor gene (DRD2) interaction on emotional eating in adolescence.

The present study addresses the emergence of emotional eating in adolescence in relation to maternal or paternal psychological control. A reduction of food intake is considered the biological natural response to distress, therefore we tested whether the a-typical stress response of emotional eating develops in interaction with genetic vulnerability. Carrying the A1 allele of the dopamine D2 receptor (DRD2) gene Taq1A polymorphism (rs1800497) is associated with reduced dopamine D2 receptor availability in the brain. We hypothesized that carrying this allele would confer risk for the development of emotional eating, particularly so in adolescents with adverse rearing experiences. Participants were 279 Dutch adolescents (average age of 13.4) that participated in a prospective study with a four-year follow-up. We found a moderator effect of DRD2 genotype on the relation between both maternal and paternal psychological control and increases in emotional eating in both sexes. Adolescents showed only an increase in emotional eating in relation to high psychological control if they carried at least one DRD2 A1 allele. This study is the first to show that the relationship between adverse rearing experiences and emotional eating might be dependent on genetic make-up.

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.

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.

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

BACKGROUND: Remarkably, 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. METHODS: A 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. CONCLUSIONS: Regarding 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.

Partner effects and bidirectional parent-child effects in family alcohol use.

INTRODUCTION: The current study investigated partner effects and bidirectional parent-child effects in family alcohol use. METHODS: A full family, longitudinal design was used to test the hypotheses. Participants were 428 families, including mothers, fathers, and 2 children. Associations were measured over two waves with a 2-year interval, by means of structural equation modeling. RESULTS: Whereas alcohol use of the younger children was affected by alcohol use of both parents, alcohol use of the older children was only affected by alcohol use of mother. Moreover, although the effects were small, alcohol use of older children affected later alcohol use of both parents. CONCLUSIONS: Associations between alcohol use of parents and children seem to be bidirectional. Future studies are needed to find out whether these findings are incidental or structural. If the effects are structural, potential underlying reciprocal processes within the family play a role in the development of adolescent alcohol use.

Parental problem drinking, parenting, and adolescent alcohol use.

The present study examined whether parental problem drinking affected parenting (i.e., behavioral control, support, rule-setting, alcohol-specific behavioral control), and whether parental problem drinking and parenting affected subsequent adolescent alcohol use over time. A total of 428 families, consisting of both parents and two adolescents (mean age 13.4 and 15.2 years at Time 1) participated in a three-wave longitudinal study with annual waves. A series of path analyses were conducted using a structural equation modeling program (Mplus). Results demonstrated that, unexpectedly, parental problem drinking was in general not associated with parenting. For the younger adolescents, higher levels of both parenting and parental problem drinking were related to lower engagement in drinking over time. This implies that shared environment factors (parenting and modeling effects) influence the development of alcohol use in young adolescents. When adolescents grow older, and move out of the initiation phase, their drinking behavior may be more affected by other factors, such as genetic susceptibility, and peer drinking.

Polymorphisms in the mu-opioid receptor gene (OPRM1) and the implications for alcohol dependence in humans.

Twin and adoption studies have shown that alcohol dependence contains a substantial genetic component. In attempts to identify the genetic factors involved, association studies have linked the opioid system to alcohol dependence, with a main focus on the OPRM1 gene encoding the mu-opioid receptor. Our aim was to conduct a systematic review of the literature on the associations between polymorphisms in OPRM1 and alcohol dependence. We addressed findings of 12 studies that met our inclusion criteria. All studies employed a case-control design and included alcohol dependence as a dependent outcome measure. Our review showed that clinical studies do not unequivocally support an association between polymorphisms in OPRM1 and alcohol dependence. Factors that complicate genetic research on alcohol dependence, such as gene-environment interaction, and genetic and clinical heterogeneity, are discussed.