Preliminary evidence for a gene-environment interaction in predicting alcohol use disorders in adolescents.

BACKGROUND: Emerging research suggests that genetic influences on adolescent drinking are moderated by environmental factors. The present study builds on molecular-genetic findings by conducting the first analysis of gene-environment interactions in the association between a functional single nucleotide polymorphism (SNP) of the µ-opioid receptor (OPRM1) gene (A118G) and risk of developing an alcohol use disorder (AUD) during adolescence. Specifically, we tested whether variation in parenting practices or affiliation with deviant peers moderated the link between the OPRM1 gene and risk of an AUD. METHODS: Adolescents reporting European ancestry (N = 104), ages 12 to 19 years (M = 15.60, SD = 1.77), were interviewed to ascertain AUD diagnoses, provided a DNA sample for genetic analyses, and completed measures of parental monitoring and deviant peer affiliation. Logistic regression was used to test the effects of environmental variables and their interactions with OPRM1 genotype as predictors of AUD diagnosis while controlling for age and sex. RESULTS: Case-control comparisons showed that the proportion of youth with an AUD (n = 18) significantly differed by genotype such that 33.3% of G allele carriers met criteria for an AUD compared to 10.8% of youth who were homozygous for the A allele (p = 0.006). The OPRM1 × parental monitoring (odds ratio = 0.16) and OPRM1 × deviant peer affiliation (odds ratio = 7.64) interactions were significant predictors of AUD risk, such that G allele carriers with high levels of deviant peer affiliation or lower levels of parental monitoring had the greatest likelihood of developing an AUD (p-values <0.01). CONCLUSIONS: This study provides initial evidence that the association between the A118G SNP of the OPRM1 gene and risk of AUDs is moderated by modifiable factors. These results are limited, however, by the small sample size and require replication.

Initial evidence of an association between OPRM1 and adolescent alcohol misuse.

BACKGROUND: Considerable research efforts have attempted to identify genes associated with alcoholism among adults, yet few studies have examined adolescents. Identifying genes associated with alcohol misuse in youth is important given that the relative contribution of genetic and environmental influences on alcoholism varies across development. The purpose of this study was to examine the association between a polymorphism of the mu-opioid receptor gene (OPRM1) and alcohol misuse in a sample of youth and to test whether heightened sensitivity to the reinforcing effects of alcohol mediated this relationship. METHODS: Adolescents (n = 187; mean age = 15.4 years; 47.6% female) were genotyped for A118G (rs1799971), a single-nucleotide polymorphism (SNP) of the OPRM1 gene, and assessed for alcohol use disorder (AUD) diagnoses and other psychopathology. Alcohol misuse was also measured continuously to maximize detection of drinking problems in youth. Drinking motives were used to capture the extent to which youth consumed alcohol to enhance positive affect. RESULTS: AUD groups differed significantly in terms of allelic distributions of the A118G SNP, such that 51.9% of youth with an AUD carried at least one copy of the G allele compared to 16.3% of non-AUD controls. Those who carried the G allele endorsed drinking to enhance positive affect more strongly than those who were homozygous for the A allele and drinking to enhance positive affect mediated the association between OPRM1 and alcohol-related problems. CONCLUSIONS: These data build on findings from adult studies and provide the first evidence that a polymorphism of the OPRM1 receptor gene is associated with the development of early-onset alcohol-related problems during adolescence, in part, by heightening sensitivity to the reinforcing effects of alcohol.

Influence of antisocial and psychopathic traits on decision-making biases in alcoholics.

BACKGROUND: Although decision-making processes have become a principal target of study among addiction researchers, few studies have specifically examined decision-making among individuals with alcohol dependence (AD) and findings to date are mixed. The present study examined the relationship between AD and decision-making, and tested whether different facets of antisocial and psychopathic traits explain this association. METHODS: Participants were men with AD (n = 22), AD and comorbid antisocial personality disorder (AD + ASPD; n = 17), or a history of recreational alcohol use, but no current or lifetime symptoms of a substance use disorder, conduct disorder, or ASPD (n = 21). Decision-making was tested using the Iowa Gambling Task (IGT). RESULTS: Across groups, participants reported similar levels of awareness of the contingencies of the task, but the AD groups with and without ASPD had poorer IGT performance compared with controls (p < 0.05). A block-by-block analysis revealed that while AD had slow but steady improvement across the task, AD + ASPD exhibited initial improvement followed by a significant decrease in advantageous decision-making during the last 20 trials (p < 0.05). This was further confirmed via evidence that impulsive/antisocial personality traits but not psychopathic traits mediated poor IGT performance beyond ASPD diagnosis. CONCLUSIONS: Alcohol-dependent males favored risky choices regardless of whether they met criteria for ASPD. However, decision-making deficits were more pronounced among those with ASPD, and personality traits characterized by impulsive and antisocial tendencies mediated the relationship between AD and decision-making.

The influence of childhood sexual abuse, physical abuse, family environment, and gender on the psychological adjustment of adolescents.

OBJECTIVE: The primary aim of the current study was to examine the contributions of sexual abuse, physical abuse, family cohesion, and conflict in predicting the psychological functioning of adolescents. Additional analyses were conducted to determine whether adolescent victims of child sexual abuse and physical abuse perceive their family environments as more conflictual and less cohesive than nonabused adolescents. METHOD: Participants were 131 male and female adolescents, ages 16 years to 18 years, receiving services at a residential vocational training program. Participants completed well established psychological assessment tools to assess abuse history, family environment characteristics, and current adjustment. RESULTS: Physically abused adolescent females perceived their family environments as more conflictual and less cohesive than females without physical abuse, and sexually abused females perceived their family environments as more conflictual and less cohesive than females without sexual abuse. Physically abused adolescent males reported more conflict than males without physical abuse, but did not differ with regard to cohesion. Adolescent males with and without a sexual abuse history did not differ on the family dimensions. Multiple regression analyses revealed that both conflict and cohesion, in addition to a history of sexual and physical abuse, predicted depression and distress. Separate analyses by gender revealed these variables differentially impact adjustment in male and female adolescents. Results of a power analysis indicated sufficient power to detect these differences. CONCLUSIONS: Findings indicate that in addition to child sexual abuse and physical abuse, family conflict and cohesion are risk factors for the development of psychological distress and depression in adolescence. Implications for treatment and directions for future research are discussed.

Sexual assault and alcohol use: exploring the self-medication hypothesis.

Though a link between sexual victimization and alcohol use has been well documented, the mechanisms underlying this relationship remain unclear. The current study used path analysis to examine the role of self-reported levels of psychological distress and the function of alcohol use as indirect pathways between adult sexual assault and alcohol use. Participants were 318 undergraduate female victims and nonvictims of adult sexual assault. Results showed that a history of sexual assault was associated with increased psychological distress, which in turn contributed to alcohol use via negative reinforcement. Taken together, these findings provided support for the hypothesis that women who have been sexually assaulted consume alcohol, in part, to self-medicate. The implications for future research are discussed.

Altered emotion-modulated startle in young adults with a family history of alcoholism.

BACKGROUND: Alcoholism risk may be accompanied by poor regulation of emotions, signaling altered central nervous system processes. This study used the emotion-modulated startle paradigm to test the hypothesis that young adults with a positive paternal history of alcoholism (FH+), relative to family-history-negative persons (FH-), have altered emotional reactivity to environmental cues. METHODS: We tested 30 FH+ and 30 FH-, 15 males and 15 females in each group. Participants completed self-report instruments and interviews and had eye blink electromyograms (EMG) measured to acoustic startle probes while viewing color photographs rated as affectively pleasant, neutral, and unpleasant. RESULTS: FH- had the expected linear increase in startle magnitude, with eye blink EMG gaining in strength (F = 18, p < 0.0002) from pleasant to neutral to unpleasant slides. In contrast, FH+ did not show EMG potentiation to the unpleasant slides and therefore lacked the same linear trend (F < 1, p > 0.4). Notably, FH groups rated the emotional valence and arousal of the photographs in similar ways. Self-reported negative affect partly accounted for the lack of startle potentiation in FH+, suggesting that startle modulation differences between the groups may be associated with underlying psychological characteristics. CONCLUSIONS: These findings implicate altered limbic outputs to the startle pathway in FH+ despite normal conscious evaluation of emotional arousal and pleasantness of the slides. This method may provide a useful paradigm for testing processing of emotionally relevant stimuli in relation to risk for alcohol use disorders.

Civilian-based posttraumatic stress disorder and physical complaints: evaluation of depression as a mediator.

This study examined the role of comorbid depression in the somatic complaints of 32 individuals with civilian-based posttraumatic stress disorder (PTSD) while restricting the influence of detectable pathophysiology and additional psychiatric conditions. It was hypothesized that depressive symptomatology would mediate the relationship between PTSD and somatic symptom reporting. Participants were administered structured clinical interviews, a physical examination, and an electrocardiogram. Results of this study supported the hypothesis that depressive symptoms mediate the relationship between PTSD and physical complaints. These results add to a growing body of literature that suggests psychological factors play an influential role in the physical symptom reports of individuals with PTSD.

Altered affective modulation of the startle reflex in alcoholics with antisocial personality disorder.

BACKGROUND: Individual differences in neural circuitry that regulate emotional reactivity may be associated with alcoholism and antisocial personality disorder (ASPD), a common comorbid condition. The emotion-modulated startle reflex was used to investigate emotional reactivity among alcohol-dependent (AD) men with and without ASPD. METHODS: Sixty-two men were tested: (1) AD (n = 24), (2) AD-ASPD (n = 17), and (3) non-AD, non-ASPD controls (n = 21). Participants completed self-report instruments and clinical interviews and had eye-blink electromyograms measured in response to acoustic startle probes while viewing color photographs rated as affectively pleasant, neutral, and unpleasant. RESULTS: Startle blink magnitudes were larger during unpleasant as compared with pleasant slides for control and AD groups, resulting in significant linear trend effects (p < 0.001) and nonsignificant quadratic trend effects. In contrast, AD-ASPD did not show a significant difference in blink magnitude during unpleasant and pleasant slides and did not show a significant linear valence trend or quadratic trend effect (p > 0.6). Subjective valence and arousal ratings of the photographs were similar across groups. CONCLUSIONS: Adult male alcoholics with ASPD have abnormal emotional responsiveness to both pleasant and unpleasant stimuli relative to alcoholics without ASPD and to controls.