Measurement of the Risk for Substance Use Disorders: Phenotypic and Genetic Analysis of an Index of Common Liability

The inability to quantify the risk for disorders, such as substance use disorders (SUD), hinders etiology research and development of targeted intervention. Based on the concept of common transmissible liability to SUD related to illicit drugs, a method enabling quantification of this latent trait has been developed, utilizing high-risk design and item response theory. This study examined properties of a SUD transmissible liability index (TLI) derived using this method. Sons of males with or without SUD were studied longitudinally from preadolescence to young adulthood. The properties of TLI, including its psychometric characteristics, longitudinal risk assessment and ethnic variation, were examined. A pilot twin study was conducted to analyze the composition of TLI’s phenotypic variance. The data suggest that TLI has concurrent, incremental, predictive and discriminant validity, as well as ethnic differences. The data suggest a high heritability of the index in males. The results suggest applicability of the method for genetic and other etiology-related research, and for evaluation of individual risk. Handling editor: Michael Joseph Lyons. An erratum to this article can be found at     

Challenges in Genetic Studies of the Etiology of Substance Use and Substance Use Disorders: Introduction to the Special Issue

Misuse of psychoactive substances is associated with substantial costs to users and to society. A growing literature suggests individual differences in vulnerability to develop substance related problems are influenced to a large degree by genetic factors. We review the evidence from genetic epidemiologic and molecular genetic studies of problematic use of alcohol, tobacco, and other drugs, then discuss the challenges for the next generation of studies of genetic influences on substance use. These challenges are addressed in the remaining papers of this special issue. The papers cover a variety of approaches, substances, and non-human as well as human studies, but are united by their focus on going beyond heritability estimates to address the mechanisms and processes underlying the development of substance use and substance related problems, including measurement, precursors of substance abuse, stages of substance involvement, and specificity of genetic influences.     

Genetic and Environmental Influences on Gambling and Substance Use in Early Adolescence

This study examined the genetic and environmental architecture of early gambling involvement and substance use to determine whether genetic or environmental factors that contribute to substance use also put young adolescents at risk for early involvement in gambling. Self-reports of substance use and gambling involvement were collected at age 13 years from 279 Monozygotic and Dizygotic twin pairs. Univariate ACE modeling revealed that genetic and nonshared environmental factors almost equally accounted for gambling involvement, with no contribution from shared environmental factors. In contrast, both shared and nonshared environmental factors played important roles in substance use; the contribution of genetic factors was also substantial. Bivariate analyses identified a significant, albeit modest, overlap between the genetic influence on gambling involvement and the genetic influence on substance use. The results shed light on the etiology of early gambling involvement and substance use, suggesting that preventive interventions targeting common risk factors may also need to be complemented by modules that are specific to each behavior.     

Environmental Exposure and Genetic Predisposition as Risk Factors for Asthma in China

Asthma is the most common chronic pulmonary disease worldwide and places a considerable economic burden on society. China is the world''s largest developing country and has the largest population. China has undergone dramatic changes in the past few decades. The traditional lifestyle and living environment have changed in ways that directly affect the prevalence of asthma. The prevalence of asthma is lower in Chinese children and adults than in developed countries, but the prevalence has been on the rise during the past 30 years. The prevalence significantly varies among different parts of China. Polymorphisms of multiple genes, outdoor air pollution caused by PM2.5, PM10, SO₂, NO₂, environmental tobacco smoke, and coal, indoor pollution, and inhaled allergens, such as house dust mites, pollen, and cockroach particles, are risk factors for asthma.     

我国部分高发区非法成瘾物质使用第二次流行病学调查——第三部分:非法使用者社会人口特征

目的 :为系列调查报告的第三部分 ,报告了我国 1996年 6个高发区非法成瘾物质使用者社会人口学特征。方法 :整群抽样 ,挨户、线索和机构调查相结合 ,调查了 15岁及以上 673 19社区人群非法成瘾物质使用情况 ,通过单因素和多因素的分析 ,找出影响非法成瘾物质使用的相关危险因素。结果 :年龄较轻、男性、文化程度较低、无固定婚姻关系、无固定职业或流动性职业是非法使用非法成瘾物质的危险因素 ;其中 ,职业、婚姻状况及性别因素对使用非法成瘾物质影响较大。结论 :加强对青少年毒品知识的教育、提高全民素质和对毒品的意识有助于减少非法成瘾物质作用。     

Environmental and Genetic Risk Factors of Congenital Anomalies: an Umbrella Review of Systematic Reviews and Meta-Analyses

BackgroundThe prevalence of congenital anomalies in newborns in South Korea was 272.9 per 100,000 in 2005, and 314.7 per 100,000 in 2006. In other studies, the prevalence of congenital anomalies in South Korea was equivalent to 286.9 per 10,000 livebirths in 2006, while it was estimated 446.3 per 10,000 births during the period from 2008 to 2014. Several systematic reviews and meta-analyses analyzing the factors contributing to congenital anomalies have been reported, but comprehensive umbrella reviews are lacking.MethodsWe searched PubMed, Google Scholar, Cochrane, and EMBASE databases up to July 1, 2019, for systematic reviews and meta-analyses that investigated the effects of environmental and genetic factors on any type of congenital anomalies. We categorized 8 subgroups of congenital anomalies classified according to the 10th revision of the International Statistical Classification of Diseases (ICD-10). Two researchers independently searched the literature, retrieved the data, and evaluated the quality of each study.ResultsWe reviewed 66 systematic reviews and meta-analyses that investigated the association between non-genetic or genetic risk factors and congenital anomalies. Overall, 269 associations and 128 associations were considered for environmental and genetic risk factors, respectively. Congenital anomalies based on congenital heart diseases, cleft lip and palate, and others were associated with environmental risk factors based on maternal exposure to environmental exposures (air pollution, toxic chemicals), parental smoking, maternal history (infectious diseases during pregnancy, pregestational and gestational diabetes mellitus, and gestational diabetes mellitus), maternal obesity, maternal drug intake, pregnancy through artificial reproductive technologies, and socioeconomic factors. The association of maternal alcohol or coffee consumption with congenital anomalies was not significant, and maternal folic acid supplementation had a preventive effect on congenital heart defects. Genes or genetic loci associated with congenital anomalies included MTHFR, MTRR and MTR, GATA4, NKX2-5, SRD5A2, CFTR, and 1p22 and 20q12 anomalies.ConclusionThis study provides a wide perspective on the distribution of environmental and genetic risk factors of congenital anomalies, thus suggesting future studies and providing health policy implications.     

Contemplating the Use of Motivational Interviewing With Patients Who Have Schizophrenia and Substance Use Disorders

This commentary addresses four questions about using motivational interviewing (MI) with patients who have co‐occurring schizophrenia and substance use disorders: (1) Has MI passed the threshold of an “evidence‐based” approach when applied to dual diagnosis treatment? (2) How does MI work when used with patients who have psychotic disorders? (3) Which proposed MI modifications for these patients are efficacious or erroneous? (4) What are the implications for training clinicians in MI for use with this patient population? Upon contemplating the answers, the recommendation to use MI as a best dual diagnosis treatment practice may be premature.     

儿童情绪障碍相关因素的LOGISTIC回归分析

情绪障碍是儿童期常见的心理障碍之一 ,对儿童的生活和社会功能有着明显影响。本文就综合性儿科医院心理门诊中儿童情绪障碍患者的有关资料进行对照研究 ;采用Ｌｏｇｉｓｔｉｃ回归多因素分析方法 ,对引起儿童情绪障碍的相关因素作一初步分析。1　对象和方法1.1　对象病例组来源于上海医科大学儿科医院心理咨询门诊来访者 ,共 88例 ,男 :4 0例 ;女 4 8例。采用ＩＣＤ- 10精神与行为障碍分类诊断标准进行诊断。其中广泛性焦虑障碍 14例 ,惊恐障碍 6例 ,混合性焦虑抑郁障碍 9例 ,恐怖性焦虑障碍 5例 ,社交恐怖症5例 ,学校恐怖症 8例 ,分离性焦…     

Posttraumatic Stress Disorder and Co‐Occurring Substance Use Disorders: Advances in Assessment and Treatment

Posttraumatic stress disorder (PTSD) and substance use disorders (SUDs) are prevalent and frequently co‐occur. Comorbid PTSD/SUD is associated with a more complex and costly clinical course when compared with either disorder alone, including increased chronic physical health problems, poorer social functioning, higher rates of suicide attempts, more legal problems, increased risk of violence, worse treatment adherence, and less improvement during treatment. In response, psychosocial treatment options have increased substantially over the past decade and integrated approaches—treatments that address symptoms of both PTSD and SUD concurrently—are fast becoming the preferred model for treatment. This article reviews the prevalence, etiology, and assessment practices as well as advances in the behavioral and pharmacologic treatment of comorbid PTSD and SUDs.     

Examining Insomnia and PTSD Over Time in Veterans in Residential Treatment for Substance Use Disorders and PTSD

Objective/Background: Insomnia occurs in 66–90% of individuals with posttraumatic stress disorder (PTSD) and 36–72% of individuals with substance use disorder (SUD). Individuals with both PTSD and SUD are more likely to have insomnia than individuals with only one disorder. Insomnia is associated with poorer treatment outcomes for both PTSD and SUD, increased daytime symptomology for PTSD, and increased relapse for SUDs. As such, it is important to understand how sleep affects PTSD treatment among patients dually diagnosed with SUD and how sleep changes over time in a residential unit for SUDs. Participants: Participants were 40 veterans with comorbid PTSD and SUD in a 28-day Substance Abuse Residential Rehabilitation Treatment Program (SARRTP) PTSD track. Methods: Analyses used mixed models with Time (baseline, posttreatment, 3-month follow-up) to examine PTSD and insomnia severity over time. Results: Results of the longitudinal mixed model showed that PTSD symptoms improved over time but that insomnia symptoms did not. Although baseline insomnia did not affect follow-up PTSD symptoms, individuals with greater insomnia severity at the start of treatment had more severe baseline PTSD symptomatology. However, there was not an interaction of insomnia and PTSD severity over time such that baseline insomnia did not affect PTSD trajectories. Conclusions: These findings are consistent with the PTSD outpatient treatment findings and further adds evidence that insomnia is unremitting without direct intervention. Given the relationship insomnia has with PTSD severity, SUD, and relapse, directly targeting insomnia may further help improve both PTSD and SUD treatment outcomes.     

Mapping Pathways by Which Genetic Risk Influences Adolescent Externalizing Behavior: The Interplay Between Externalizing Polygenic Risk Scores,Parental Knowledge,and Peer Substance Use

Genetic predispositions and environmental influences both play an important role in adolescent externalizing behavior; however, they are not always independent. To elucidate gene–environment interplay, we examined the interrelationships between externalizing polygenic risk scores, parental knowledge, and peer substance use in impacting adolescent externalizing behavior across two time-points in a high-risk longitudinal sample of 1,200 adolescents (764 European and 436 African ancestry; M_age = 12.99) from the Collaborative Study on the Genetics of Alcoholism. Results from multivariate path analysis indicated that externalizing polygenic scores were directly associated with adolescent externalizing behavior but also indirectly via peer substance use, in the European ancestry sample. No significant polygenic association nor indirect effects of genetic risk were observed in the African ancestry group, likely due to more limited power. Our findings underscore the importance of gene–environment interplay and suggest peer substance use may be a mechanism through which genetic risk influences adolescent externalizing behavior.

     

Polygenic Risk for Aggression Predicts Adult Substance Use Disorder Diagnoses via Substance Use Offending in Emerging Adulthood and is Moderated by a Family-Centered Intervention

A substance use offense reflects an encounter with law enforcement and the court system in response to breaking the law which may increase risk for substance use problems later in life. Individuals may also be at risk for substance use offending and substance use problems based on genetic predisposition. We examined a mediation model in which polygenic risk for aggression predicted adult substance use disorder diagnoses (SUD) via substance use offending in emerging adulthood. In addition, we explored for potential attenuation of genetic influences on these outcomes by a family-based intervention, the Family Check-Up (FCU). Secondary data analyses based upon the Project Alliance 1 sample was conducted among those with genetic data (n?=?631; 322 from control and 309 from FCU intervention). The sample was ethnically diverse (30% African American, 44% European American, 6% Latinx, 4% Asian American, 3% Native American, and 13% Other). Greater polygenic risk for aggression was found to increase risk for substance use violations (age 19–23), which in turn was associated with greater likelihood of being diagnosed with SUD at age 27. A gene-by-intervention effect was found in which individuals in the control group had greater risk for SUD with increasing polygenic risk for aggression. Some convergence in results was found when replicating analyses in African American and European American subgroups. Results imply that genetic predisposition may increase risk for problematic substance use later in life via antisocial behavior, such as substance use offending, and that this can be attenuated by a family-centered intervention.

     

Adolescent Substance Use Disorders: Findings From a 14-Year Follow-Up of Speech/Language-Impaired and Control Children

Intervening on the development of adolescent addiction requires an understanding of the role of precursors. In a community sample of youth with and without early childhood speech/language (S/L) impairments, 12.7% of participants had a substance use disorder (SUD). Among these participants, 42.0% met criteria for more than 1 SUD. Interestingly, rates of SUDs did not differ by S/L status. However, S/L-impaired participants did show greater psychiatric comorbidity and poorer functioning. A total of 80% of S/L participants with SUDs had a concurrent diagnosis of antisocial personality disorder, compared with 43.8% of SUDs controls. In a logistic regression analysis, we found age 5 mother-rated problem behavior scores and an interaction between S/L status and teacher-rated conduct problem scores were predictive of SUDs. High conduct scores were predictive of SUDs development among control participants but not among S/L-impaired participants. First substance use and initial SUDs symptoms suggest that a window of opportunity exists to reach these troubled young people before they spiral into addiction.     

Psychometric and Genetic Architecture of Substance Use Disorder and Behavioral Disinhibition Measures for Gene Association Studies

Using large twin, family, and adoption studies conducted at the Minnesota Center for Twin and Family Research, we describe our efforts to develop measures of substance use disorder (SUD) related phenotypes for targets in genome wide association analyses. Beginning with a diverse set of relatively narrow facet-level measures, we identified 5 constructs of intermediate complexity: nicotine, alcohol consumption, alcohol dependence, illicit drug, and behavioral disinhibition. The 5 constructs were moderately correlated (mean r = .57) reflecting a general externalizing liability to substance abuse and antisocial behavior. Analyses of the twin and adoption data revealed that this general externalizing liability accounted for much of the genetic risk in each of the intermediate-level constructs, though each also exhibited significant unique genetic and environmental risk. Additional analyses revealed substantial effects for age and sex, significant shared environmental effects, and that the mechanism of these shared environmental effects operates via siblings rather than parents. Our results provide a foundation for genome wide association analyses to detect risk alleles for SUDs as well as novel insights into genetic and environmental risk for SUDs.     

踝关节骨折的治疗与踝关节功能预后影响因素分析

目的：探讨踝关节骨折的治疗方法及影响踝关节功能的预后因素。方法：对自2005年1月至2008年12月以来采用手法复位石膏固定和切开复位手术治疗并得到随访的40例踝关节骨折者的临床资料进行回顾分析。按Lauge—Hansen分型,旋后外旋型27例,旋后内收型3例,旋前外展型2例,旋前外旋型6例,垂直压缩型（pilon骨折）2例。采用保守治疗10例,切开复位内固定治疗30例。按照美国足踝骨科协会（AOFAS）推荐的足踝评分系统评估治疗结果。对患者年龄、性别、合并伤、受伤至治疗时间、骨折类型等5个可能的相关因素进行多因素分析。结果：40例术后均获平均15个月（6～20个月）随访。按AOFAS评分平均97分。单因素Logistic回归分析发现年龄和骨折类型的差异有统计学意义,多因素Logistic逐步回归分析发现骨折类型的差异有统计学意义。结论：影响踝关节骨折后踝关节功能的主要预后因素是骨折类型,应主要根据这个因素采取个体化的治疗方法。