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VGLUT2 rs2290045 genotype moderates environmental sensitivity to alcohol-related problems in three samples of youths.

ABSTRACT: The importance of Vesicular Glutamate Transporter 2 (VGLUT2)-mediated neurotransmission has been highlighted in studies on addiction-related phenotypes. The single nucleotide polymorphism rs2290045 in VGLUT2 has been associated with alcohol dependence, but it is unknown whether or how this association is affected by environmental factors. The present study determined whether the association of alcohol-related problems with the rs2290045 in the VGLUT2 gene was modified by negative and positive environmental factors. Three samples were included: a clinical sample of 131 adolescents followed from age 17 to 22; a general population sample of 1794 young adults; and a general population sample of 1687 adolescents followed from age 14 to 17. DNA was extracted from saliva and the rs2290045 (T/C) was genotyped. Alcohol-related problems were assessed using the Alcohol Use Disorders Identification Test. Stressful life events (SLE) and parenting were assessed by questionnaires. Gene-environment interactions were investigated using a dual statistical approach. In all samples (effect sizes 0.6-6.2%), and consistent with the differential susceptibility framework, T carriers exposed to SLE reported more alcohol-related problems if they had experienced poor parenting, and lower alcohol-related problems if they had received supportive parenting. T carriers not exposed to SLE reported higher alcohol-related problems if they had received supportive parenting and lower alcohol-related problems if they had received poor parenting. Among CC carriers, alcohol-related problems did not vary as a function of negative and positive environmental factors. In conclusion, in three samples of youths, alcohol-related problems were associated with an interaction of VGLUT2 rs2290045, SLE, and parenting.

SUBMITTER: Vrettou M

PROVIDER: S-EPMC6785645 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Project description:AimsThe social environment strongly influences individual mental health. Individuals with strong social support systems tend to experience higher levels of well-being, lower levels of psychological distress and exhibit fewer psychiatric symptoms. However, there is a significant degree of individual variability as to the extent to which social support is beneficial to overall mental health. From a neurobiological perspective, it is suggested that the social hormone, oxytocin, may moderate the favorable effects of social interaction. To explore this possibility, we evaluated oxytocin genotype, social support and psychological health in a group of individuals diagnosed with DSM-IV alcohol dependence.MethodsThe associations between OXT genotype, social support and psychological health were analyzed in data from 269 adults diagnosed with DSM-IV alcohol dependence (25% female) admitted into residential treatment programs and outpatient centers in Warsaw, Poland.ResultsIn line with past observations, we noted that psychiatric distress scores were negatively correlated with social support. Extending these observations, we uncovered a significant moderating effect of OXT genotype (rs2740210) on the relationship between social support and psychiatric distress. While G carriers displayed the predicted negative relationship between social support and psychiatric distress, T homozygotes failed to exhibit such a relationship.ConclusionGenetically driven variation in oxytocin system functioning may influence the degree to which the beneficial effects of social support are felt in this population. These results have direct clinical relevance as enhancing social engagement to improve mental health may prove to be a less effective strategy in some patients owing to intrinsic factors.Short summaryThe associations between oxytocin genotype, social support, and psychological health were analyzed in data from 269 adults diagnosed with DSM-IV alcohol dependence. A significant moderating effect of OXT genotype (rs2740210) on the relationship between social support and psychiatric distress was detected.

Project description:BACKGROUND:Low sensitivity to alcohol in persons with a family history of alcoholism (FH+), compared to those without (FH-), contributes to risk for alcohol use disorder (AUD). However, sensitivity of FH+ cardiovascular response to alcohol is not well understood. This gap is significant because cardiovascular processes contribute to emotional regulation and stress response problems theorized to be central to the development and persistence of AUD. This study compared changes in heart rate (HR) and HR variability (HRV) between FH groups after consuming alcohol and control beverages and examined how these changes were moderated by emotional and alcohol-related contexts. METHODS:Young adults (N = 165) with FH+ (n = 110) or FH- (n = 55) each completed 2 sessions, separated by 1 week. They received one of 3 different beverages (alcohol, placebo, and told-no-alcohol) in each session. Electrocardiogram data were recorded during pre-beverage consumption and post-beverage consumption baselines, and then during 4 picture cue tasks (neutral, positive, negative, and alcohol-related). Generalized estimating equations were used to examine differences in cardiovascular reactivity (changes in HR and HRV power at ~ 0.1 Hz) across FH groups, beverage conditions, and picture cue tasks. RESULTS:A significant beverage condition × cue task × FH interaction effect on HRV was observed. The FH+ group, compared to the FH- group, showed (a) significantly less HRV suppression in specific cue contexts following alcohol, (b) a mixed pattern of more and less HRV suppression across cue contexts following placebo, and (c) a similar HRV reactivity pattern in the told-no-alcohol condition across cue tasks. For HR, there were no significant effects involving FH. CONCLUSIONS:Diminished cardiovascular sensitivity to oral alcohol in FH+ persons varied within a given drinking episode depending on emotional and alcohol-related features of the context, suggesting that environmental characteristics play a role in the expression of low sensitivity to alcohol among FH+ individuals.

Project description:ImportanceConcussion may exacerbate existing mental health issues. Little evidence exists on whether concussion is associated with the onset of new psychopathologies or long-term mental health problems.ObjectiveTo investigate associations between concussion and risk of subsequent mental health issues, psychiatric hospitalizations, self-harm, or suicides.Design, setting, and participantsThis population-based retrospective cohort study including children and youths aged 5 to 18 years with a concussion or orthopedic injury incurred between April 1, 2010, and March 31, 2020, in Ontario, Canada. Participants had no previous mental health visit in the year before the index event for cohort entry and no prior concussion or traumatic brain injury 5 years before the index visit. Data were collected from provincewide health administrative databases. Participants with concussion were included in the exposed cohort, and those with an orthopedic injury were included in the comparison cohort; these groups were matched 1:2, respectively, on age and sex.ExposuresConcussion or orthopedic injury.Main outcomes and measuresThe primary outcome was mental health problems, such as psychopathologies and psychiatric disorders, identified from health care visits in emergency departments, hospitalizations, or primary care settings. Secondary outcomes were psychiatric hospitalizations, self-harm health care visits, and death by suicide (identified in health care or vital statistics databases).ResultsA total of 152 321 children and youths with concussion (median [IQR] age, 13 [10-16] years; 86 423 [56.7%] male) and 296 482 children and youths with orthopedic injury (median [IQR] age, 13 [10-16] years; 171 563 [57.9%] male) were matched by age and sex. The incidence rates of any mental health problem were 11 141 per 100 000 person-years (exposed group) and 7960 per 100 000 person-years (unexposed group); with a difference of 3181 (95% CI, 3073-3291) per 100 000 person-years. The exposed group had an increased risk of developing a mental health issue (adjusted hazard ratio [aHR], 1.39; 95% CI, 1.37-1.40), self-harm (aHR, 1.49; 95% CI, 1.42-1.56), and psychiatric hospitalization (aHR, 1.47; 95% CI, 1.41-1.53) after a concussion. There was no statistically significant difference in death by suicide between exposed and unexposed groups (HR, 1.54; 95% CI, 0.90-2.61).Conclusions and relevanceAmong children and youths aged 5 to 18 years, concussion was associated with an increased risk of mental health issues, psychiatric hospitalization, and self-harm compared with children and youths with an orthopedic injury.

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VGLUT2 rs2290045 genotype moderates environmental sensitivity to alcohol-related problems in three samples of youths.

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