Alpha-5/alpha-3 nicotinic receptor subunit alleles increase risk for heavy smoking

Twin studies indicate that additive genetic effects explain most of the variance in nicotine dependence (ND), a construct emphasizing habitual heavy smoking despite adverse consequences, tolerance and withdrawal. To detect ND alleles, we assessed cigarettes per day (CPD) regularly smoked, in two European populations via whole genome association techniques. In these approximately 7500 persons, a common haplotype in the CHRNA3-CHRNA5 nicotinic receptor subunit gene cluster was associated with CPD (nominal P=6.9 x 10(-5)). In a third set of European populations (n= approximately 7500) which had been genotyped for approximately 6000 SNPs in approximately 2000 genes, an allele in the same haplotype was associated with CPD (nominal P=2.6 x 10(-6)). These results (in three independent populations of European origin, totaling approximately 15 000 individuals) suggest that a common haplotype in the CHRNA5/CHRNA3 gene cluster on chromosome 15 contains alleles, which predispose to ND

Suicidal Ideation and Suicide Attempt Across Stages of Nonmedical Prescription Opioid Use and Presence of Prescription Opioid Disorders Among U.S. Adults

Objective: This study compares the likelihood of suicidal ideation and suicide attempt across stages of nonmedical prescription opioid use and by presence of prescription opioid disorders (dependence and/or abuse) among adult respondents. Method: In the 2009 National Survey on Drug Use and Health, 37,933 adult respondents were asked if they had thought about suicide or had attempted suicide in the past year. The likelihood of ideation and attempt were compared across the following four categories: (a) those who never used prescription opioids, (b) former users, (c) persistent users, and (d) recent-onset users. Weighted multinomial logistic regressions were used to examine if these stages and presence of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for prescription opioid disorders were associated with suicidal ideation and suicide attempt. Results: Five percent of respondents (n = 2,021) reported suicidal ideation; of these, 15% (n = 310) reported attempt. Former and persistent nonmedical prescription opioid users had greater odds of suicidal ideation than those who never used these medications nonmedically. The stages of prescription opioid use were not associated with suicide attempt. Presence of prescription opioid disorders among past-year prescription opioid users was associated with suicidal ideation but not suicide attempt. Conclusions: The risk for suicidal ideation was greater in those who no longer used prescription opioids, in persistent users, and among nonmedical users who had a prescription opioid disorder compared with users without the disorder. The results suggest a need to continue monitoring for suicide risk even among those who have stopped using prescription opioids

Protocol: changes in rates of opioid overdose and poisoning events in an integrated health system following the introduction of a formulation of OxyContin® with abuse-deterrent properties

BACKGROUND: Addiction, overdoses and deaths resulting from prescription opioids have increased dramatically over the last decade. In response, several manufacturers have developed formulations of opioids with abuse-deterrent properties. For many of these products, the Food and Drug Administration (FDA) recognized the formulation with labeling claims and mandated post-marketing studies to assess the abuse-deterrent effects. In response, we assess differences in rates of opioid-related overdoses and poisonings prior to and following the introduction of a formulation of OxyContin® with abuse-deterrent properties. METHODS/DESIGN: To assess effects of this formulation, electronic medical record (EMR) data from Kaiser Permanente Northwest (KPNW) and Kaiser Permanente Northern California (KPNC) are linked to state death data and compared to chart audits. Overdose and poisoning events will be categorized by intentionality and number of agents involved, including illicit drugs and alcohol. Using 6-month intervals over a 10-year period, trends will be compared in rates of opioid-related overdoses and poisoning events associated with OxyContin® to rates of events associated with other oxycodone and opioid formulations. Qualitative interviews with patients and relatives of deceased patients will be conducted to capture circumstances surrounding events. DISCUSSION: This study assesses and tracks changes in opioid-related overdoses and poisoning events prior to and following the introduction of OxyContin® with abuse-deterrent properties. Public health significance is high because these medications are designed to reduce abuse-related behaviors that lead to important adverse outcomes, including overdoses and deaths. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40360-016-0064-y) contains supplementary material, which is available to authorized users

Identification of Dietary Supplements Associated with Blood Metabolites in the Hispanic Community Health Study/Study of Latinos Cohort Study

BACKGROUND: Metabolomics approaches have been widely used to define the consumption of foods but have less often been used to study exposure to dietary supplements. OBJECTIVES: This study aimed to identify dietary supplements associated with metabolite levels and to examine whether these metabolites predicted incident diabetes risk. METHODS: We studied 3972 participants from a prospective cohort study of 18-74-y-old Hispanic/Latino adults. At a baseline examination, we ascertained use of dietary supplements using recall methods and concurrently, a serum metabolomic panel. After adjustment for potential confounders, we identified dietary supplements associated with metabolites. We then examined the association of these metabolites with incident diabetes at the 6-y study examination. RESULTS: We observed a total of 110 dietary supplement-metabolite associations that met the criteria for statistical significance adjusted for age, sex, field center, Hispanic/Latino background, body mass index, diet, smoking, physical activity, and number of medications (adjusted P \u3c 0.05). This included 13 metabolites uniquely associated with only one dietary supplement ingredient. Vitamin C had the most associated metabolites (n = 15), including positive associations with oxalate, tartronate, threonate, and isocitrate, which were each in turn protective for the risk of incident diabetes. Vitamin C was also associated with higher N-acetylvaline level, which was an unfavorable diabetes risk factor. Other findings related to branched chain amino acid related compounds including α-hydroxyisovalerate and 2-hydroxy-3-methylvalerate, which were inversely associated with thiamine or riboflavin intake and also predicted higher diabetes risk. Vitamin B12 had an inverse association with γ-glutamylvaline, levels of which were positively associated with the risk of diabetes. CONCLUSIONS: Our data point to potential metabolite changes associated with vitamin C and B vitamins, which may have favorable metabolic effects. Knowledge of blood metabolites that can be modified by dietary supplement intake may aid understanding the health effects of dietary supplements and identify potential biological mediators

High school drinking mediates the relationship between parental monitoring and college drinking: A longitudinal analysis

<p>Abstract</p> <p>Background</p> <p>College drinking is a significant public health problem. Although parental monitoring and supervision reduces the risk for alcohol consumption among younger adolescents, few studies have investigated the impact of earlier parental monitoring on later college drinking. This study examined whether parental monitoring indirectly exerts a protective effect on college drinking by reducing high school alcohol consumption.</p> <p>Methods</p> <p>A longitudinal cohort of 1,253 male and female students, ages 17 to 19, attending a large, public, mid-Atlantic university was studied at two time points. First, data on high school parental monitoring and alcohol consumption were gathered via questionnaire during the summer prior to college entry. Second, during the first year of college, past-year alcohol consumption was measured via a personal interview. Multiple regression models tested the relationship between parental monitoring and past year alcohol use (i.e., number of drinks per drinking day).</p> <p>Results</p> <p>Holding constant demographics, SAT score, and religiosity, parental monitoring had a significant protective effect on both high school and college drinking level. However, the association between parental monitoring and college drinking level became non-significant once high school drinking level was held constant.</p> <p>Conclusion</p> <p>While parental monitoring did not directly influence college alcohol consumption, evidence for mediation was observed, whereby parental monitoring had an indirect influence on college drinking through reductions in high school drinking. Initiatives that promote effective parenting might be an important strategy to curb high-risk drinking among older adolescents. More research is needed to understand the nature and degree of parent-child communication that is necessary to extend the protective influence of parents into the college years.</p

Association between substance use and psychosocial characteristics among adolescents of the Seychelles

BACKGROUND: We examined the associations between substance use (cigarette smoking, alcohol drinking, and cannabis use) and psychosocial characteristics at the individual and family levels among adolescents of the Seychelles, a rapidly developing small island state in the African region. METHODS: A school survey was conducted in a representative sample of 1432 students aged 11-17 years from all secondary schools. Data came from a self-administered anonymous questionnaire conducted along a standard methodology (Global School-based Health Survey, GSHS). Risk behaviors and psychosocial characteristics were dichotomized. Association analyses were adjusted for a possible classroom effect. RESULTS: The prevalence of cigarette smoking, alcohol drinking and cannabis use was higher in boys than in girls and increased with age. Age-adjusted and multivariate analyses showed that several individual level characteristics (e.g. suicidal ideation and truancy) and family level characteristics (e.g. poor parental monitoring) were associated with substance use among students. CONCLUSIONS: Our results suggest that health promotion programs should simultaneously address multiple risk behaviors and take into account a wide range of psychosocial characteristics of the students at the individual and family levels

PDE8 Regulates Rapid Teff Cell Adhesion and Proliferation Independent of ICER

BACKGROUND: Abolishing the inhibitory signal of intracellular cAMP by phosphodiesterases (PDEs) is a prerequisite for effector T (Teff) cell function. While PDE4 plays a prominent role, its control of cAMP levels in Teff cells is not exclusive. T cell activation has been shown to induce PDE8, a PDE isoform with 40- to 100-fold greater affinity for cAMP than PDE4. Thus, we postulated that PDE8 is an important regulator of Teff cell functions. METHODOLOGY/PRINCIPAL FINDINGS: We found that Teff cells express PDE8 in vivo. Inhibition of PDE8 by the PDE inhibitor dipyridamole (DP) activates cAMP signaling and suppresses two major integrins involved in Teff cell adhesion. Accordingly, DP as well as the novel PDE8-selective inhibitor PF-4957325-00 suppress firm attachment of Teff cells to endothelial cells. Analysis of downstream signaling shows that DP suppresses proliferation and cytokine expression of Teff cells from Crem-/- mice lacking the inducible cAMP early repressor (ICER). Importantly, endothelial cells also express PDE8. DP treatment decreases vascular adhesion molecule and chemokine expression, while upregulating the tight junction molecule claudin-5. In vivo, DP reduces CXCL12 gene expression as determined by in situ probing of the mouse microvasculature by cell-selective laser-capture microdissection. CONCLUSION/SIGNIFICANCE: Collectively, our data identify PDE8 as a novel target for suppression of Teff cell functions, including adhesion to endothelial cells

Relationship between Maternal Clinical Factors and Mother-Reported Child Problems

Maternal depression has been associated with mothers’ elevated reports of child problems. However, it is unclear the extent to which elevations in mother ratings reflect having a depression diagnosis, having any mental illness diagnosis, or having a diagnosis vs. symptom levels. As part of a NIMH-funded, longitudinal study of mothers with serious mental illness ( N =379), we examined the relationship between mother-reported adolescent behavior problems ( N =78) and maternal depression vs. other diagnoses, as well as the effects of depression diagnosis vs. symptom levels. Mothers were recruited from the public mental health system in an urban area, and are primarily African-American and low income. We found that maternal psychiatric symptoms made a unique and significant contribution to explaining the variance in mother-reported child problems, independent of controls (e.g., teacher reports and child demographics), while maternal diagnosis did not. Implications of findings are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44321/1/10597_2005_Article_6425.pd

Drinking to ease the burden: a cross-sectional study on trauma, alcohol abuse and psychopathology in a post-conflict context

Ertl V, Saile R, Neuner F, Catani C. Drinking to ease the burden: a cross-sectional study on trauma, alcohol abuse and psychopathology in a post-conflict context. BMC Psychiatry. 2016;16(1): 202.Background It is likely that alcohol use and abuse increase during and after violent conflicts. The most prominent explanation of this phenomenon has been referred to as self-medication hypothesis. It predicts that psychotropic substances are consumed to deal with conflict-related psychic strains and trauma. In northern Uganda, a region that has been affected by a devastating civil war and is characterized by high levels of alcohol abuse we examined the associations between war-trauma, childhood maltreatment and problems related to alcohol use. Deducing from the self-medication hypothesis we assumed alcohol consumption moderates the relationship between trauma-exposure and psychopathology. Methods A cross-sectional epidemiological survey targeting war-affected families in post-conflict northern Uganda included data of male (n = 304) and female (n = 365) guardians. We used standardized questionnaires in an interview format to collect data on the guardians’ socio-demography, trauma-exposure, alcohol consumption and symptoms of alcohol abuse, PTSD and depression. Results Symptoms of current alcohol use disorders were present in 46 % of the male and 1 % of the female respondents. A multiple regression model revealed the unique contributions of emotional abuse in the families of origin and trauma experienced outside the family-context in the prediction of men’s alcohol-related symptoms. We found that alcohol consumption moderated the dose-effect relationship between trauma-exposure and symptoms of depression and PTSD. Significant interactions indicated that men who reported more alcohol-related problems experienced less increase in symptoms of PTSD and depression with increasing trauma-exposure. Conclusions The gradual attenuation of the dose-effect the more alcohol-related problems were reported is consistent with the self-medication hypothesis. Hence, the functionality of alcohol consumption has to be considered when designing and implementing addiction treatment in post-conflict contexts