Background: Patterns of comorbidity suggest that the common psychiatric and substance use syndromes may be divisible into 2 broad groups of internalizing and externalizing disorders. We do not know how genetic and environmental risk factors contribute to this pattern of comorbidity or whether the etiologic structure of these groups differ in men and women. Methods: Lifetime diagnoses for 10 psychiatric syndromes were obtained at a personal interview in more than 5600 members of male-male and female-female twin pairs ascertained from a population-based registry. Multivariate twin modeling was performed using the program Mx. Results: We first fit models to the following 7 syndromes: major depression, generalized anxiety disorder, phobia, alcohol dependence, drug abuse/dependence, adult antisocial behavior, and conduct disorder. The full model, which could be constrained to equality in male and female subjects, identified 2 genetic factors. The first had strongest loadings on alcohol dependence, drug abuse/dependence, adult antisocial behavior, and conduct disorder; the second, on major depression, generalized anxiety disorder, and phobia. Alcohol dependence and drug abuse/dependence had substantial disorder-specific genetic risk factors. Shared environmental factors were most pronounced for conduct disorder and adult antisocial behavior. No clear internalizing/externalizing structure was seen for the unique environmental common factors. We then fit models to 5 internalizing syndromes. The full model, which could also be constrained to equality in men and women, revealed one genetic factor loading most heavily on major depression and generalized anxiety disorder and another loading most strongly on animal and situational phobia. Conclusions: The underlying structure of the genetic and environmental risk factors for the common psychiatric and drug abuse disorders in men and women is very similar. Genetic risk factors predispose to 2 broad groups of internalizing and externalizing disorders. Within the internalizing disorders, 2 genetic factors are seen that predispose to disorders dominated by anxious-misery and fear. Substance use disorders have disorder-specific genetic risks. The externalizing disorders of conduct disorder and adult antisocial behavior are significantly influenced by the shared environment. The pattern of lifetime comorbidity of common psychiatric and substance use disorders results largely from the effects of genetic risk factors. Arch Gen Psychiatry. 2003;60:929-937

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/207813/YOA20695.pdf

The Structure of Genetic and Environmental Risk Factors for Common Psychiatric and Substance Use Disorders in Men and Women

Impulsivity as a vulnerability marker for substance-use disorders: Review of findings from high-risk research, problem gamblers and genetic association studies

Genetic variation may partially underlie complex personality and physiological traits--such as impulsivity, risk taking and stress responsivity--as well as a substantial proportion of vulnerability to addictive diseases. Furthermore, personality and physiological traits themselves may differentially affect the various stages of addiction, defined chronologically as initiation of drug use, regular drug use, addiction/dependence and potentially relapse. Here we focus on recent approaches to the study of genetic variation in these personality and physiological traits, and their influence on and interaction with addictive diseases.

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Genetic influences on impulsivity, risk taking, stress responsivity and vulnerability to drug abuse and addiction

The addictions are common chronic psychiatric diseases that today are prevented and treated using relatively untargeted and only partially effective methods. The addictions are moderately to highly heritable, which is paradoxical because these disorders require use; a choice that is itself modulated by both genes and environment. The addictions are interrelated and related to other psychiatric diseases by common neurobiological pathways, including those that modulate reward, behavioural control and the anxiety or stress response. Our future understanding of addictions will be enhanced by the identification of genes that have a role in altered substance-specific vulnerabilities such as variation in drug metabolism or drug receptors and a role in shared vulnerabilities such as variation in reward or stress resiliency.

/pdf/the-genetics-of-addictions-uncovering-the-genes-44p2w47fg7.pdf

The genetics of addictions: Uncovering the genes

Chronic pain not caused by cancer is among the most prevalent and debilitating medical conditions but also among the most controversial and complex to manage. The urgency of patients’ needs, the demonstrated effectiveness of opioid analgesics for the management of acute pain, and the limited therapeutic alternatives for chronic pain have combined to produce an overreliance on opioid medications in the United States, with associated alarming increases in diversion, overdose, and addiction. Given the lack of clinical consensus and research-supported guidance, physicians understandably have questions about whether, when, and how to prescribe opioid analgesics for chronic pain without increasing public health risks. Here, we draw on recent research to address common misconceptions regarding the abuse-related risks of opioid analgesics and highlight strategies to minimize those risks.

https://www.nejm.org/doi/pdf/10.1056/NEJMra1507771

Opioid Abuse in Chronic Pain — Misconceptions and Mitigation Strategies

Background Previous research has demonstrated genetic and environmental influences on abuse of individual substances, but there is less known about how these factors may influence the co-occurrence of abuse of different illicit drugs. Methods We studied 3372 male twin pairs from the Vietnam Era Twin Registry. They were interviewed using the Diagnostic Interview Schedule, Version III, Revised to investigate the extent to which the abuse of different categories of drugs occurs together within an individual, as well as the possibility that genetic and environmental factors are responsible for observed co-occurrence. Co-occurrence was quantified using odds ratios and conditional probabilities. Multivariate biometrical modeling analyses were used to assess genetic and environmental influences on co-occurrence. Results Abusing any category of drug was associated with a marked increase in the probability of abusing every other category of drugs. We found evidence for a shared or common vulnerability factor that underlies the abuse of marijuana, sedatives, stimulants, heroin or opiates, and psychedelics. This shared vulnerability is influenced by genetic, family environmental, and nonfamily environmental factors, but not every drug is influenced to the same extent by the shared vulnerability factor. Marijuana, more than other drugs, was influenced by family environmental factors. Each category of drug, except psychedelics, had genetic influences unique to itself (ie, not shared with other drug categories). Heroin had larger genetic influences unique to itself than did any other drug. Conclusion There are genetically and environmentally determined characteristics that comprise a shared or common vulnerability to abuse a range of illicit drugs.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/204442/yoa7286.pdf

Thomas Doyle

Papers

Co-occurrence of Abuse of Different Drugs in Men The Role of Drug-Specific and Shared Vulnerabilities