Stigmata that are desired: Contradictions in addiction.

Many experts in the etiology, assessment, and treatment of substance use/addiction view stigma and stigmatization - negatively branding addiction and substance users - as obstacles to the solution of the substance misuse problem. Discussions on this topic impact research and policy, and result in oft-repeated calls to remove the stigma from substance use and users. The goal of the article is to analyze the stigmatization concept as applied to substance use/addiction. It is widely accepted in the literature that stigmatization negatively affects substance users because addiction stigma interferes in both seeking and receiving professional care. It is argued that the societal disapproval of substance use/addiction is inappropriate because it is a mental disorder, involving biological processes. Nonetheless, neither those processes nor negative attitudes to substance use affirm the concept of stigmatization as currently applied. This concept conflates potential mistreatment and malpractice with the prosocial justified societal disapproval of a lethally dangerous behavior. Consequently, the stigmatization concept suffers from internal contradictions, is either misleading or redundant, and may do more harm than the supposed mistreatment of substance users that stigmatization connotes. On the contrary, the justified disapproval of harmful behavior may be a factor raising individual resistance to substance use. Instead of mitigating the effects of that disapproval, it may need to be capitalized on. If it is employed explicitly, conscientiously, and professionally, its internalization may be one of the resistance mechanisms needed to achieve any progress in the still elusive prevention of substance use and addiction.

Transdiagnostic risk of mental disorders in offspring of affected parents: a meta-analysis of family high-risk and registry studies.

The offspring of parents with mental disorders are at increased risk for developing mental disorders themselves. The risk to offspring may extend transdiagnostically to disorders other than those present in the parents. The literature on this topic is vast but mixed. To inform targeted prevention and genetic counseling, we performed a comprehensive, PRISMA 2020-compliant meta-analysis. We systematically searched the literature published up to September 2022 to retrieve original family high-risk and registry studies reporting on the risk of mental disorders in offspring of parents with any type of mental disorder. We performed random-effects meta-analyses of the relative risk (risk ratio, RR) and absolute risk (lifetime, up to the age at assessment) of mental disorders, defined according to the ICD or DSM. Cumulative incidence by offspring age was determined using meta-analytic Kaplan-Meier curves. We measured heterogeneity with the I2 statistic, and risk of bias with the Quality In Prognosis Studies (QUIPS) tool. Sensitivity analyses addressed the impact of study design (family high-risk vs. registry) and specific vs. transdiagnostic risks. Transdiagnosticity was appraised with the TRANSD criteria. We identified 211 independent studies that reported data on 3,172,115 offspring of parents with psychotic, bipolar, depressive, disruptive, attention-deficit/hyperactivity, anxiety, substance use, eating, obsessive-compulsive, and borderline personality disorders, and 20,428,575 control offspring. The RR and lifetime risk of developing any mental disorder were 3.0 and 55% in offspring of parents with anxiety disorders; 2.6 and 17% in offspring of those with psychosis; 2.1 and 55% in offspring of those with bipolar disorder; 1.9 and 51% in offspring of those with depressive disorders; and 1.5 and 38% in offspring of those with substance use disorders. The offspring's RR and lifetime risk of developing the same mental disorder diagnosed in their parent were 8.4 and 32% for attention-deficit/hyperactivity disorder; 5.8 and 8% for psychosis; 5.1 and 5% for bipolar disorder; 2.8 and 9% for substance use disorders; 2.3 and 14% for depressive disorders; 2.3 and 1% for eating disorders; and 2.2 and 31% for anxiety disorders. There were 37 significant transdiagnostic associations between parental mental disorders and the RR of developing a different mental disorder in the offspring. In offspring of parents with psychosis, bipolar and depressive disorder, the risk of the same disorder onset emerged at 16, 5 and 6 years, and cumulated to 3%, 19% and 24% by age 18; and to 8%, 36% and 46% by age 28. Heterogeneity ranged from 0 to 0.98, and 96% of studies were at high risk of bias. Sensitivity analyses restricted to prospective family high-risk studies confirmed the pattern of findings with similar RR, but with greater absolute risks compared to analyses of all study types. This study demonstrates at a global, meta-analytic level that offspring of affected parents have strongly elevated RR and lifetime risk of developing any mental disorder as well as the same mental disorder diagnosed in the parent. The transdiagnostic risks suggest that offspring of parents with a range of mental disorders should be considered as candidates for targeted primary prevention.

Normalization of Prevention Principles and Practices to Reduce Substance Use Disorders Through an Integrated Dissemination and Implementation Framework.

Major research breakthroughs over the past 30 years in the field of substance use prevention have served to: (1) enhance understanding of pharmacological effects on the central and peripheral nervous systems and the health and social consequences of use of psychoactive substances, particularly for children and adolescents; (2) delineate the processes that increase vulnerability to or protect from initiation of substance use and progression to substance use disorders (SUDs) and, based on this understanding, (3) develop effective strategies and practices to prevent the initiation and escalation of substance use. The challenge we now face as a field is to "normalize" what we have learned from this research so that it is incorporated into the work of those involved in supporting, planning, and delivering prevention programming to populations around the world, is integrated into health and social service systems, and helps to shape public policies. But we wish to go further, to incorporate these effective prevention practices into everyday life and the mind-sets of the public, particularly parents and educators. This paper reviews the advances that have been made in the field of prevention and presents a framework and recommendations to achieve these objectives generated during several meetings of prevention and implementation science researchers sponsored by the International Consortium of Universities for Drug Demand Reduction (ICUDDR) that guides a roadmap to achieve "normalization."

The Concept of Resistance to Substance Use and a Research Approach: The Resist! Project.

Illicit substance use is dangerous in both acute and chronic forms, frequently resulting in lethal poisoning, addiction, and other negative consequences. Similar to research in other psychiatric conditions, whose ultimate goal is to enable effective prevention and treatment, studies in substance use are focused on factors elevating the risk for the disorder. The rapid growth of the substance use problem despite the effort invested in fighting it, however, suggests the need in changing the research approach. Instead of attempting to identify risk factors, whose neutralization is often infeasible if not impossible, it may be more promising to systematically reverse the perspective to the factors enhancing the aspect of liability to disorder that shares the same dimension but is opposite to risk, that is, resistance to substance use. Resistance factors, which enable the majority of the population to remain unaffected despite the ubiquity of psychoactive substances, may be more amenable to translation. While the resistance aspect of liability is symmetric to risk, the resistance approach requires substantial changes in sampling (high-resistance rather than high-risk) and using quantitative indices of liability. This article provides an overview and a practical approach to research in resistance to substance use/addiction, currently implemented in a NIH-funded project. The project benefits from unique opportunities afforded by the data originating from two longitudinal twin studies, the Virginia Twin Study of Adolescent and Behavioral Development and the Minnesota Twin Family Study. The methodology described is also applicable to other psychiatric disorders.

Physical inactivity during adolescence heightens risk for cannabis use disorder in adulthood.

The association between physical inactivity and substance use throughout adolescence was prospectively investigated in relation to developing cannabis use disorder (CUD). Physical inactivity and substance use in males (N = 462) and females (N = 178) were measured at 12-14, 16, 19, and 22 years of age in a repeated measures design. A structured diagnostic interview was administered to formulate current CUD diagnosis at 22 years of age. Mixture modeling path analysis evaluated the association between physical inactivity, substance use, and CUD. Males: Slope of physical inactivity increase spanning 12-22 years of age mediates the association between number of parents with substance use disorder (SUD) and rate of increase in substance use frequency (prodrome) which mediates the association between physical inactivity (hypothesized vulnerability) and CUD. Females: Number of SUD parents predicts slope of physical inactivity increase in daughters throughout adolescence which covaries with slope of increasing substance use frequency culminating in CUD. The association between parental SUD load (number of SUD affected parents) and CUD was found to not be mediated by physical inactivity. Rate of increase in physical inactivity during adolescence in males and females is a facet of the vulnerability for CUD. These results have ramifications for prevention considering that numerous cognitive, behavior, and emotion features of CUD vulnerability are attenuated by exercise. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A Gateway That Never Was.

This brief communication responds to the article by Rajabi et al., recently published in Behavior Genetics. To test the hypothesis of cigarette smoking as a "gateway" for subsequent opium use and contrast it with the common liability model, Mendelian randomization analysis was applied to data obtained from an Iranian sample, using CHRNA3 rs1051730 as an instrumental variable. It is doubtful, however, if the assumptions of instrumental variable analysis hold in this case. The authors misstate both the gateway hypothesis and the common liability model. The article has many other deficiencies that diminish the veracity of its categorical conclusions that accept the causal interpretation of the "gateway hypothesis" and reject the common liability model, with which the data are fully consistent.

Coupled mixed model for joint genetic analysis of complex disorders with two independently collected data sets.

BACKGROUND: In the last decade, Genome-wide Association studies (GWASs) have contributed to decoding the human genome by uncovering many genetic variations associated with various diseases. Many follow-up investigations involve joint analysis of multiple independently generated GWAS data sets. While most of the computational approaches developed for joint analysis are based on summary statistics, the joint analysis based on individual-level data with consideration of confounding factors remains to be a challenge. RESULTS: In this study, we propose a method, called Coupled Mixed Model (CMM), that enables a joint GWAS analysis on two independently collected sets of GWAS data with different phenotypes. The CMM method does not require the data sets to have the same phenotypes as it aims to infer the unknown phenotypes using a set of multivariate sparse mixed models. Moreover, CMM addresses the confounding variables due to population stratification, family structures, and cryptic relatedness, as well as those arising during data collection such as batch effects that frequently appear in joint genetic studies. We evaluate the performance of CMM using simulation experiments. In real data analysis, we illustrate the utility of CMM by an application to evaluating common genetic associations for Alzheimer's disease and substance use disorder using datasets independently collected for the two complex human disorders. Comparison of the results with those from previous experiments and analyses supports the utility of our method and provides new insights into the diseases. The software is available at https://github.com/HaohanWang/CMM .

Forecasting Opioid Use Disorder at 25 Years of Age in 16-Year-Old Adolescents.

OBJECTIVE: To evaluate the accuracy of detecting 16-year-old male (n = 465) and female (n = 162) youths who subsequently manifest opioid use disorder (OUD) at 25 years of age. We hypothesized that the combined measures of 2 components of etiology, heritable risk, and substance use, accurately detect youths who develop OUD. STUDY DESIGN: Heritable risk was measured by the transmissible liability index (TLI). Severity of the prodrome presaging OUD was quantified by the revised Drug Use Screening Inventory containing the consumption frequency index (CFI) documenting substance use events during the past month and the overall problem density (OPD) score indicating co-occurring biopsychosocial problems. Diagnosis of OUD was formulated by a clinical committee based on results of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition in conjunction with medical and social history records. RESULTS: Bivariate analysis shows that the TLI, CFI, and OPD scores at 16 years of age predict OUD at 25 years. Multivariate modeling indicates that the TLI combined with the CFI predict OUD with 86% accuracy (sensitivity = 87%; specificity = 62%). The TLI and CFI at 16 years of age mediate the association between parental substance use disorder and OUD in offspring at 25 years of age, indicating that these measures respectively evaluate risk and prodrome. CONCLUSIONS: These results demonstrate the feasibility of identifying youths requiring intervention to prevent OUD.