DSM-V-defined substance use disorder comprises four groups of symptoms: impaired control, social impairment, risky use, and pharmacological reactions. Behavioral patterns of impaired control, ...including impulsivity and risk taking, are associated with HIV risk behaviors. Substance users with stronger craving symptoms are more likely to use drugs via intravenous injection than other routes because of the faster drug effect and the higher bioavailability; thus, they are at high risk of HIV infection. HIV risk behaviors such as unprotected sex and intravenous injection facilitate HIV disease spread. Public health policies such as Needle and Syringe Exchange Programs and medication-assisted treatment are proven to reduce HIV risk behaviors such as the frequency of intravenous injection and even the incidence of HIV infection, but both of them have limitations. While intravenous injection is a frequently discussed issue in public policies and the HIV-related literature, it is a much less frequent topic in the addiction literature. We believed that understanding the mental substrate behind impulsivity/risk taking and the possible biological mechanism of intravenous injection may help in creating more effective strategies to slow down HIV infection.
Abstract Background Two competing concepts address the development of involvement with psychoactive substances: the “gateway hypothesis” (GH) and common liability to addiction (CLA). Method The ...literature on theoretical foundations and empirical findings related to both concepts is reviewed. Results The data suggest that drug use initiation sequencing, the core GH element, is variable and opportunistic rather than uniform and developmentally deterministic. The association between risks for use of different substances, if any, can be more readily explained by common underpinnings than by specific staging. In contrast, the CLA concept is grounded in genetic theory and supported by data identifying common sources of variation in the risk for specific addictions. This commonality has identifiable neurobiological substrate and plausible evolutionary explanations. Conclusions Whereas the “gateway” hypothesis does not specify mechanistic connections between “stages”, and does not extend to the risks for addictions , the concept of common liability to addictions incorporates sequencing of drug use initiation as well as extends to related addictions and their severity, provides a parsimonious explanation of substance use and addiction co-occurrence, and establishes a theoretical and empirical foundation to research in etiology, quantitative risk and severity measurement, as well as targeted non-drug-specific prevention and early intervention.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background and aims
Cannabis, tobacco and alcohol use are prevalent among youth in the United States and may be risk factors for opioid use. The current study aimed at investigating associations ...between developmental trajectories of cannabis, tobacco and alcohol use in adolescence and opioid use in young adulthood in an urban cohort over the span of 12 years.
Design
Cohort study of adolescents originally recruited for a randomized prevention trial with yearly assessments into young adulthood.
Setting
Nine urban elementary schools in Baltimore, MD in the United States.
Participants
Participants (n = 583, 86.8% African American, 54.7% male) were originally recruited as first grade students.
Measurements
Cannabis, tobacco and alcohol use were assessed annually from ages 14–18 years and opioid use from ages 19–26. Socio‐demographics were assessed at age 6. Intervention status was also randomly assigned at age 6. Gender, race, free/reduced‐priced lunch and intervention status were included as covariates in individual and sequential growth models.
Findings
There were significant positive associations between the cannabis use intercept at age 14 and the opioid use intercept at age 19 (beta = 1.43; P = 0.028), the tobacco use intercept at age 14 and the opioid use intercept at age 19 (beta = 0.82; P = 0.042). Specifically, more frequent use of cannabis or tobacco at age 14 was associated with more frequent use of opioids at age 19.
Conclusions
Cannabis and tobacco use in early adolescence may be risk factors for opioid use in young adulthood among African Americans living in urban areas.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Considerable research suggests that suicide involves effects of genes, the environment, and their interaction. Analysis of three independent data sets of post-mortem brains revealed signs of ...increased methylation in one particular gene, SKA2, a finding that was extended to peripheral blood samples from other cohorts of prospectively followed individuals.
Objective:Reliable identification of individuals at high risk for suicide is a priority for suicide prevention. This study was conducted to identify genes exhibiting epigenetic variation associated with suicide and suicidal behaviors.Method:Genome-wide DNA methylation profiling was employed separately on neuronal and glial nuclei in a discovery set of postmortem brains from the National Institute of Child Health and Human Development to identify associations with suicide. Pyrosequencing-based validation was conducted in prefrontal cortical tissue in cohorts from the Stanley Medical Research Institute and Harvard Brain Bank at McLean Hospital and peripheral blood from three living groups. Functional associations with gene expression, stress and anxiety, and salivary cortisol were assessed.Results:The DNA methylation scan identified an additive epigenetic and genetic association with suicide at rs7208505 within the 3′ untranslated region of the SKA2 gene independently in the three brain cohorts. This finding was replicated with suicidal ideation in blood from three live cohorts. SKA2 gene expression was significantly lower in suicide decedents and was associated with genetic and epigenetic variation of rs7208505, possibly mediated by interaction with an intronic microRNA, miR-301a. Analysis of salivary cortisol measurements suggested that SKA2 epigenetic and genetic variation may modulate cortisol suppression, consistent with its implicated role in glucocorticoid receptor transactivation. SKA2 significantly interacted with anxiety and stress to explain about 80% of suicidal behavior and progression from suicidal ideation to suicide attempt.Conclusions:These findings implicate SKA2 as a novel genetic and epigenetic target involved in the etiology of suicide and suicidal behaviors.
Abstract
Introduction
Insufficient sleep is associated with all-cause mortality in the general population. Illicit drugs have pronounced effects upon sleep, and insomnia symptoms are common among ...people with HIV (PWH), suggesting persons who inject drugs (PWID) with HIV may be at higher risk of adverse outcomes from insufficient sleep.
Methods
Participants in the AIDS Linked to the IntraVenous Experience (ALIVE) study, a cohort of PWID with or without HIV, completed the Sleep Adequacy subscale of the Medical Outcomes Study (MOS) semi-annually from 2005-present. Two questions queried participants about the frequency over the past four-weeks of: 1. getting sufficient sleep to feel rested on awakening; 2. obtaining needed amount of sleep. Six-Item responses ranged from “all of the time” to “none of the time”. Participants with mean subscale scores below the sample median were considered to have insufficient sleep. Mortality data were obtained through the National Death Index through 2018. Hazards of all-cause and cause-specific mortality were evaluated using Cox-regressions accounting for repeated measurements of insufficient sleep, respectively. Models were adjusted for sociodemographics, HIV and HCV infection, severe depressive symptoms (Center for Epidemiological Studies Depression CESD≥23), number of comorbidities (0, 1, ≥2), active injection drug use, current tobacco and alcohol use.
Results
Of 2612 participants (33% HIV+), mean age at baseline was 45.8 years, 32.4% were female, 75% Black, 45% had ≥high school education, and 33% had an annual income >$5,000. At baseline, the majority were current smokers (84%), alcohol drinkers (59%), or actively injecting drugs (56%), while 25% had severe depressive symptoms and 21% had ≥2 comorbidities. After adjustment for covariates, insufficient sleep was associated with a 37% increased hazard of all-cause mortality (HR: 1.37, 95% confidence interval CI: 1.13–1.65). Insufficient sleep was associated with a 93% increased hazard of death from HIV or infectious disease-related deaths (HR: 1.93, 95% CI: 1.26–2.97).
Conclusion
Insufficient sleep was independently associated with all-cause mortality and specifically with death from HIV or infectious diseases-related causes among PWID. Interventions consider targeting sleep behaviors among PWID hold promise for improving health and longevity in this population.
Support (if any)
National Institutes of Health grants: U01-DA-036297; R01-DA-047064; R01-HL-90483; K24-AI-118591; T32-DA007292; R01-DA039408.
This study examined whether polygenic risk scores (PRS) for lifetime cannabis and alcohol use were associated with misusing opioids, and whether sex differences existed in these relations in an ...urban, African-American sample.
Data were drawn from three cohorts of participants (N = 1,103; 45% male) who were recruited in first grade as part of a series of elementary school-based, universal preventive intervention trials conducted in a Mid-Atlantic region of the U.S. In young adulthood, participants provided a DNA sample and reported on whether they had used heroin or misused prescription opioids in their lifetime. Three substance use PRS were computed based on prior GWAS: lifetime cannabis use from Pasman et al. (2018), heavy drinking indexed via maximum number of drinks from Gelernter et al. (2019), and alcohol consumption from Kranzler et al. (2019).
Higher PRS for lifetime cannabis use, greater heavy drinking, and greater alcohol consumption were associated with heightened risk for misusing opioids among the whole sample. Significant sex by PRS interactions were also observed such that higher PRS for heavy drinking and alcohol consumption were associated with a greater likelihood of opioid misuse among males, but not females.
Our findings further elucidate the genetic contributions to misusing opioids by showing that the genetics of cannabis and alcohol consumption are associated with lifetime opioid misuse among young adults, though replication of our findings is needed.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Research on environmental and genetic pathways to complex traits such as educational attainment (EA) is confounded by uncertainty over whether correlations reflect effects of transmitted parental ...genes, causal family environments, or some, possibly interactive, mixture of both. Thus, an aggregate of thousands of alleles associated with EA (a polygenic risk score; PRS) may tap parental behaviors and home environments promoting EA in the offspring. New methods for unpicking and determining these causal pathways are required. Here, we utilize the fact that parents pass, at random, 50% of their genome to a given offspring to create independent scores for the transmitted alleles (conventional EA PRS) and a parental score based on alleles not transmitted to the offspring (EA VP_PRS). The formal effect of non-transmitted alleles on offspring attainment was tested in 2,333 genotyped twins for whom high-quality measures of EA, assessed at age 17 years, were available, and whose parents were also genotyped. Four key findings were observed. First, the EA PRS and EA VP_PRS were empirically independent, validating the virtual-parent design. Second, in this family-based design, children's own EA PRS significantly predicted their EA (β = 0.15), ruling out stratification confounds as a cause of the association of attainment with the EA PRS. Third, parental EA PRS predicted the SES environment parents provided to offspring (β = 0.20), and parental SES and offspring EA were significantly associated (β = 0.33). This would suggest that the EA PRS is at least as strongly linked to social competence as it is to EA, leading to higher attained SES in parents and, therefore, a higher experienced SES for children. In a full structural equation model taking account of family genetic relatedness across multiple siblings the non-transmitted allele effects were estimated at similar values; but, in this more complex model, confidence intervals included zero. A test using the forthcoming EA3 PRS may clarify this outcome. The virtual-parent method may be applied to clarify causality in other phenotypes where observational evidence suggests parenting may moderate expression of other outcomes, for instance in psychiatry.
Anxiety disorders (ADs) are common mental disorders caused by a combination of genetic and environmental factors. Since ADs are highly comorbid with each other, partially due to shared genetic basis, ...studying AD phenotypes in a coordinated manner may be a powerful strategy for identifying potential genetic loci for ADs. To detect these loci, we performed genome-wide association studies (GWAS) of ADs. In addition, as a complementary approach to single-locus analysis, we also conducted gene- and pathway-based analyses. GWAS data were derived from the control sample of the Molecular Genetics of Schizophrenia (MGS) project (2,540 European American and 849 African American subjects) genotyped on the Affymetrix GeneChip 6.0 array. We applied two phenotypic approaches: (1) categorical case-control comparisons (CC) based upon psychiatric diagnoses, and (2) quantitative phenotypic factor scores (FS) derived from a multivariate analysis combining information across the clinical phenotypes. Linear and logistic models were used to analyse the association with ADs using FS and CC traits, respectively. At the single locus level, no genome-wide significant association was found. A trans-population gene-based meta-analysis across both ethnic subsamples using FS identified three genes (MFAP3L on 4q32.3, NDUFAB1 and PALB2 on 16p12) with genome-wide significance (false discovery rate (FDR <5%). At the pathway level, several terms such as transcription regulation, cytokine binding, and developmental process were significantly enriched in ADs (FDR <5%). Our approaches studying ADs as quantitative traits and utilizing the full GWAS data may be useful in identifying susceptibility genes and pathways for ADs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract The diagnosis of obsessive-compulsive disorder (OCD) is based on the presence of specific symptoms and their consequence in the lives of those that exhibit them. It is likely that these ...symptoms emerge from a neurocognitive vulnerability in the mental life of the individual which has a basis in neurophysiology. The prominence of doubt/uncertainty/lack of confidence∗, in the clinical presentation of many patients suffering from OCD leads to our consideration of the cognitive basis for this phenomenon. In this paper, we propose that OCD emerges from a perturbation in the decision-making process. Specifically, we hypothesize that there is diminished confidence, conviction, or certainty with regard to assimilating the information necessary to reach a decision. Recent advances in the neuroscience of decision-making provide an opportunity to further our understanding of the vulnerability underlying OCD. ∗These terms are used interchangeably in this paper
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
We examined whether the interplay between community disadvantage and a conduct disorder polygenic risk score (CD PRS) was associated with sexual health outcomes among urban women. Participants (N = ...511; 75.5% African American) were originally recruited to participate in a school-based intervention and were followed into adulthood. Community disadvantage was calculated using census data when participants were in first grade. At age 20, blood or saliva samples were collected and participants reported on their condom use, sexual partners, and sexually transmitted infections. A CD PRS was created based on a genome-wide association study conducted by Dick et al. 2010. Higher levels of community disadvantage was associated with greater sexually transmitted infections among women with a higher CD PRS. Implications of the study findings are discussed.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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