Cristie Glasheen

Influence of Mental Health and Substance Use Problems and Criminogenic Risk on Outcomes in Serious Juvenile Offenders.

OBJECTIVE To investigate the relations among certain mental health problems (MHPs; affective, anxiety, attention-deficit/hyperactivity disorder [ADHD], and substance use disorders), criminogenic risk, and outcomes in a sample of serious adolescent offenders. METHOD Using data from a longitudinal study of serious adolescent offenders (N = 949; mean age = 16 years, SD = 1.10 years; 84% male; 78% minority), we evaluated the association of MHPs with three distinct outcomes (rearrest, self-reported antisocial activity, and gainful activity), tested whether having an MHP contributed any unique explanatory power regarding these outcomes over and above criminogenic risk markers, and examined whether MHPs moderated the relationship between risk markers and outcomes. Negative binomial and ordinal regressions were used. Data for the study were derived primarily from youth self-report over a 7-year period, with parent collaterals reporting on ADHD, and official records as the source for rearrest information. RESULTS Of the sample, 57.5% met the criteria for at least one of the assessed MPHs. The presence of a substance use disorder showed consistent associations with the outcomes. After controlling for risk markers and demographic characteristics, MHPs were not associated with most outcomes. The co-occurrence of a substance use disorder and an MHP moderated the relations between several risk markers and outcomes. CONCLUSIONS Current juvenile justice policies that focus treatment efforts on both criminogenic and mental health factors (with particular emphasis on treating substance use disorders) appear to be well founded. It is unlikely that focusing solely on treating MHPs in serious offenders will have a distinct impact on later outcomes.

Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence.

We conducted a 1000 Genomes–imputed genome-wide association study (GWAS) meta-analysis for nicotine dependence, defined by the Fagerström Test for Nicotine Dependence in 17 074 ever smokers from five European-ancestry samples. We followed up novel variants in 7469 ever smokers from five independent European-ancestry samples. We identified genome-wide significant association in the alpha-4 nicotinic receptor subunit (CHRNA4) gene on chromosome 20q13: lowest P=8.0 × 10−9 across all the samples for rs2273500-C (frequency=0.15; odds ratio=1.12 and 95% confidence interval=1.08–1.17 for severe vs mild dependence). rs2273500-C, a splice site acceptor variant resulting in an alternate CHRNA4 transcript predicted to be targeted for nonsense-mediated decay, was associated with decreased CHRNA4 expression in physiologically normal human brains (lowest P=7.3 × 10−4). Importantly, rs2273500-C was associated with increased lung cancer risk (N=28 998, odds ratio=1.06 and 95% confidence interval=1.00–1.12), likely through its effect on smoking, as rs2273500-C was no longer associated with lung cancer after adjustment for smoking. Using criteria for smoking behavior that encompass more than the single ‘cigarettes per day’ item, we identified a common CHRNA4 variant with important regulatory properties that contributes to nicotine dependence and smoking-related consequences.

Exposure to Maternal Pre- and Postnatal Depression and Anxiety Symptoms: Risk for Major Depression, Anxiety Disorders, and Conduct Disorder in Adolescent Offspring

This study evaluated whether exposure to maternal pre- or postnatal depression or anxiety symptoms predicted psychopathology in adolescent offspring. Growth mixture modeling was used to identify trajectories of pre- and postnatal depression and anxiety symptoms in 577 women of low socioeconomic status selected from a prenatal clinic. Logistic regression models indicated that maternal pre- and postnatal depression trajectory exposure was not associated with offspring major depression, anxiety, or conduct disorder, but exposure to the high depression trajectory was associated with lower anxiety symptoms in males. Exposure to medium and high pre- and postnatal anxiety was associated with the risk of conduct disorder among offspring. Male offspring exposed to medium and high pre- and postnatal anxiety had higher odds of conduct disorder than did males with low exposure levels. Females exposed to medium or high pre- and postnatal anxiety were less likely to meet conduct disorder criteria than were females with lower exposure. To the best of our knowledge, this is the first study to examine the effect of pre- and postnatal anxiety trajectories on the risk of conduct disorder in offspring. These results suggest new directions for investigating the etiology of conduct disorder with a novel target for intervention.

Does Time Matter? Comparing Trajectory Concordance and Covariate Association Using Time-Based and Age-Based Assessments

Much criminological research has used longitudinal data to assess change in offending over time. An important feature of some data sources is that they contain cross-sections of different aged individuals followed over successive time periods, thereby potentially conflating age and time. This article compares the substantive conclusions about the relationship between age and offending based on trajectory modeling analyses by time-of-assessment versus age-at-assessment. Analyses of a large sample of serious youthful offenders followed for 7 years consisted of estimation of group-based offending trajectories and multinomial logistic regressions examining how risk/protective factors distinguished between offending trajectories. Findings revealed that concordance using measurement approaches was strong at relatively high and low levels of antisocial behavior, with greater ambiguity between these two offending extremes. The relation of risk/protective factors to various trajectories was substantively similar across measurement approaches.

Cis-Expression Quantitative Trait Loci Mapping Reveals Replicable Associations with Heroin Addiction in OPRM1.

BACKGROUND No opioid receptor, mu 1 (OPRM1) gene polymorphisms, including the functional single nucleotide polymorphism (SNP) rs1799971, have been conclusively associated with heroin/other opioid addiction, despite their biological plausibility. We used evidence of polymorphisms altering OPRM1 expression in normal human brain tissue to nominate and then test associations with heroin addiction. METHODS We tested 103 OPRM1 SNPs for association with OPRM1 messenger RNA expression in prefrontal cortex from 224 European Americans and African Americans of the BrainCloud cohort. We then tested the 16 putative cis-expression quantitative trait loci (cis-eQTL) SNPs for association with heroin addiction in the Urban Health Study and two replication cohorts, totaling 16,729 European Americans, African Americans, and Australians of European ancestry. RESULTS Four putative cis-eQTL SNPs were significantly associated with heroin addiction in the Urban Health Study (smallest p = 8.9 × 10(-5)): rs9478495, rs3778150, rs9384169, and rs562859. Rs3778150, located in OPRM1 intron 1, was significantly replicated (p = 6.3 × 10(-5)). Meta-analysis across all case-control cohorts resulted in p = 4.3 × 10(-8): the rs3778150-C allele (frequency = 16%-19%) being associated with increased heroin addiction risk. Importantly, the functional SNP allele rs1799971-A was associated with heroin addiction only in the presence of rs3778150-C (p = 1.48 × 10(-6) for rs1799971-A/rs3778150-C and p = .79 for rs1799971-A/rs3778150-T haplotypes). Lastly, replication was observed for six other intron 1 SNPs that had prior suggestive associations with heroin addiction (smallest p = 2.7 × 10(-8) for rs3823010). CONCLUSIONS Our findings show that common OPRM1 intron 1 SNPs have replicable associations with heroin addiction. The haplotype structure of rs3778150 and nearby SNPs may underlie the inconsistent associations between rs1799971 and heroin addiction.

Cigarette smoking behaviors among adults with serious mental illness in a nationally representative sample.

PURPOSE This study updates nationally representative information on cigarette smoking behaviors among adults with mental illness, particularly serious mental illness (SMI), to serve as a new benchmark for smoking cessation initiatives. METHODS Data are from the 2008-2012 National Surveys on Drug Use and Health. Prevalence estimates for past month daily smoking, heavy smoking, mean cigarettes consumed per day, nicotine dependence, past month quit ratio, and proportion of cigarettes consumed are presented by mental illness status. RESULTS Adults with SMI were more likely than adults with any mental illness (AMI) but not SMI and adults without mental illness to engage in smoking behaviors. Adults with AMI but not SMI were more likely to engage in all smoking behaviors compared with adults without mental illness. The past month quit ratio was significantly lower among adults with SMI and among adults with AMI but not SMI than among adults without mental illness. Adults with SMI comprised 6.9% of past month smokers but consumed 8.7% of all cigarettes. CONCLUSIONS Adults with mental illness engage in more smoking behaviors and are less likely to quit than adults without mental illness. In this high-risk population, continued efforts to promote smoking cessation are needed.

Binge drinking and the risk of suicidal thoughts, plans, and attempts

BACKGROUND Major depression is one of the strongest known risk factors for suicide. However, of the estimated 8.5 million adults with serious thoughts of suicide in the past year, only half had a major depressive episode (MDE). Identifying risk factors for suicide in the absence of depression may provide additional targets for prevention and intervention. This study uses nationally representative data to evaluate the association of binge drinking with suicidal thoughts, plans, and attempts in adults with and without MDE. METHODS Combined 2008-2012 National Survey on Drug Use and Health data were analyzed. Sex-stratified prevalence estimates of past year suicide indicators were generated by past month binge drinking and past year MDE status. Logistic regression was used to evaluate the association of binge drinking with suicide indicators by sex with and without MDE. RESULTS Unadjusted prevalence estimates for suicide indicators in males and females were higher among binge drinkers than among nonbinge drinkers, regardless of MDE status. Regression analyses indicated that binge drinking was associated with suicidal thoughts (adjusted odds ratio [aOR]=1.51, 95% confidence interval [CI]=1.28-1.79), plans (aOR=1.75, CI=1.23-2.48), and attempts (aOR=2.57, CI=1.74-3.79) in females without MDE and with suicidal thoughts in males without MDE (aOR=1.25, CI=1.04-1.49). Among males and females with MDE, binge drinking was not associated with any of the suicide indicators (p>.05). CONCLUSIONS Binge drinking in females without MDE may be an indicator for identifying at risk individuals for targeting suicide prevention activities.

The Epidemiology and Treatment of Prescription Drug Disorders in the United States

The drug problem in the United States is a complex mosaic involving different types of drugs, consumption practices, and biological and psychological responses to their effects. Over the past two decades, the fields of psychiatry and neurology have witnessed dramatic scientific breakthroughs in understanding the actions of drugs that can be used to regulate the nervous system (Nestler, Hyman, & Malenka, 2009). This has led to a dramatic increase in use of these medications for treating a wide range of physical and mental disorders (Dasgupta et al., 2006). An unintended consequence of this increased level of availability is that a large proportion of these drugs are being consumed in excess of the dosage recommended by the manufacturer or prescriber, used to self-treat illnesses instead of seeking professional medical care, and/or combined with other drugs increase the desired effects. As a result, the numbers of unintentional poisonings and emergency room visits have nearly doubled. For instance, the latest figures from the Drug Abuse Warning Network (DAWN) indicate that in 2008, that nearly half of the 2 million emergency room visits to U.S. hospitals involved prescription medications. Approximately two-thirds of those visits that involved prescription medications were for prescription pharmaceuticals only and no cooccurring illicit drug or alcohol abuse (SAMHSA, 2006). In addition to the tremendous economic costs associated with overdoses involving prescription medications, the adverse social and mental/physical health effects, though difficult to directly quantify, are considerable. The goal of this chapter is to present an overview of the current state of knowledge about the nonmedical use of prescription medications. Because of the sheer volume of the literature, this chapter cannot cover the entire breadth of this complex phenomenon. Therefore, the discussion is limited to those exhibiting features of dependence on prescription medications, as this is the most harmful pattern of use. Within the context of dependence, the goal is to present a concise review of the epidemiological data on the prevalence of dependence on prescription medications within various population subgroups (e.g. youth, those with co-occurring illicit substance use disorders, and previous history of psychiatric illness). In addition, a brief summary is provided on the pharmacological properties that are likely to confer selective use of the particular drug

Novel Genetic Locus Implicated for HIV-1 Acquisition with Putative Regulatory Links to HIV Replication and Infectivity: A Genome- Wide Association Study

Fifty percent of variability in HIV-1 susceptibility is attributable to host genetics. Thus identifying genetic associations is essential to understanding pathogenesis of HIV-1 and important for targeting drug development. To date, however, CCR5 remains the only gene conclusively associated with HIV acquisition. To identify novel host genetic determinants of HIV-1 acquisition, we conducted a genome-wide association study among a high-risk sample of 3,136 injection drug users (IDUs) from the Urban Health Study (UHS). In addition to being IDUs, HIV- controls were frequency-matched to cases on environmental exposures to enhance detection of genetic effects. We tested independent replication in the Women’s Interagency HIV Study (N=2,533). We also examined publicly available gene expression data to link SNPs associated with HIV acquisition to known mechanisms affecting HIV replication/infectivity. Analysis of the UHS nominated eight genetic regions for replication testing. SNP rs4878712 in FRMPD1 met multiple testing correction for independent replication (P=1.38x10-4), although the UHS-WIHS meta-analysis p-value did not reach genome-wide significance (P=4.47x10-7 vs. P<5.0x10-8) Gene expression analyses provided promising biological support for the protective G allele at rs4878712 lowering risk of HIV: (1) the G allele was associated with reduced expression of FBXO10 (r=-0.49, P=6.9x10-5); (2) FBXO10 is a component of the Skp1-Cul1-F-box protein E3 ubiquitin ligase complex that targets Bcl-2 protein for degradation; (3) lower FBXO10 expression was associated with higher BCL2 expression (r=-0.49, P=8x10-5); (4) higher basal levels of Bcl-2 are known to reduce HIV replication and infectivity in human and animal in vitro studies. These results suggest new potential biological pathways by which host genetics affect susceptibility to HIV upon exposure for follow-up in subsequent studies.

The role of mental illness on cigarette dependence and successful quitting in a nationally representative, household-based sample of U.S. adults

PURPOSE To begin to explore whether the association between mental illness (MI), cigarette dependence, and unsuccessful quit attempts differs across particular demographic subgroups. METHODS This study examines data from adults aged 18 years or older participating in the 2008-2012 National Surveys on Drug Use and Health. Analyses explored the moderating effects of age, gender, and race and/or ethnicity on associations between three levels of MI: (serious mental illness [SMI], any mental illness but no SMI, and no MI) and two smoking-related outcomes (cigarette dependence among current smokers and successful quitting among ever daily smokers). RESULTS After confirming that adults with MI were more likely to be dependent on cigarettes and less likely to successfully quit smoking, particularly among those with SMI, adjusted analyses indicated that age (but not gender or race/ethnicity) moderated the associations between MI and cigarette dependence and between MI. CONCLUSIONS The magnitude of the association between MI and cigarette dependence and between MI and successful quitting appears to be stronger among older adults than among younger adults. Identifying subgroups at particular high risk of cigarette dependence is paramount to targeting smoking prevention, cessation, and treatment services appropriately.