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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.
To clarify, in a national sample, associations between risk for seven psychiatric and substance use disorders and five key transitions in Sweden's public educational system.
Methods
Swedish-born individuals (1972–1995, N = 1 997 910) were followed through 12-31-2018, at mean age 34.9. We predicted, from these educational transitions, risk for major depression (MD), obsessive-compulsive disorder (OCD), bipolar disorder (BD), schizophrenia (SZ), anorexia nervosa (AN), alcohol use disorder (AUD), and drug use disorder (DUD), assessed from Swedish national registers, by Cox regression, censoring individuals with onsets ⩽17. We also predicted risk from the deviation of grades from family-genetic expectations (deviation 1) and from changes in grades from ages 16 to 19 (deviation 2).
Results
We observed four major risk patterns across transitions in our disorders: (i) MD and BD, (ii) OCD and SZ, (iii) AUD and DUD, and (iv) AN. Failing early educational transitions had the greatest impact on risk for OCD and SZ while for other disorders, not progressing from basic to upper high school had the largest effect. Completing vocational v. college-prep upper high school was strongly associated with risk for AUD and DUD, had little relation with MD, OCD, BD, and SZ risk, and was protective for AN. Deviation 1 predicted risk most strongly for SZ, AN, and MD. Deviation 2 predicted risk most strongly for SZ, AUD, and DUD.
Conclusions
The pattern of educational transitions and within family and within person development deviations are strongly and relatively specifically associated with future risk for seven psychiatric and substance-use disorders.
The causal impacts of recreational cannabis legalization are not well understood due to the number of potential confounds. We sought to quantify possible causal effects of recreational cannabis legalization on substance use, substance use disorder, and psychosocial functioning, and whether vulnerable individuals are more susceptible to the effects of cannabis legalization than others.
Methods
We used a longitudinal, co-twin control design in 4043 twins (N = 240 pairs discordant on residence), first assessed in adolescence and now age 24–49, currently residing in states with different cannabis policies (40% resided in a recreationally legal state). We tested the effect of legalization on outcomes of interest and whether legalization interacts with established vulnerability factors (age, sex, or externalizing psychopathology).
Results
In the co-twin control design accounting for earlier cannabis frequency and alcohol use disorder (AUD) symptoms respectively, the twin living in a recreational state used cannabis on average more often (βw = 0.11, p = 1.3 × 10−3), and had fewer AUD symptoms (βw = −0.11, p = 6.7 × 10−3) than their co-twin living in an non-recreational state. Cannabis legalization was associated with no other adverse outcome in the co-twin design, including cannabis use disorder. No risk factor significantly interacted with legalization status to predict any outcome.
Conclusions
Recreational legalization was associated with increased cannabis use and decreased AUD symptoms but was not associated with other maladaptations. These effects were maintained within twin pairs discordant for residence. Moreover, vulnerabilities to cannabis use were not exacerbated by the legal cannabis environment. Future research may investigate causal links between cannabis consumption and outcomes.
Parkinson’s disease (PD) is a neurologic degenerative condition with complex neuropsychiatric manifestations which can be challenging to manage and greatly impact quality of life and prognosis.
Objectives
The description of this case aims to highlight the complex interaction between PD, drug-abuse and impulse control disorder (ICD).
Methods
Clinical information was obtained through patient interviewing and medical records consulting. A literature review on the topic was conducted.
Results
We report the case of a 52-years-old male with PD diagnosed at the age of 45, presenting with rigidity of right limbs and freezing of gait. He had a history of multiple substance-abuse: hashish, heroin and cocaine, with cessation of all substances by the age of 40. The patient responded well to antiparkinsonian medication initially, but needed frequent adjustments and developed ICD secondary to dopamine agonists, presenting pathological gambling and hypersexuality. At 47 he restarted using cocaine stating that it diminished the motor symptoms. Motor symptoms worsened and became partially responsive to medication. Pharmacologic options were limited due to ICD. He developed dopamine dysregulation syndrome, abusing dopaminergic drugs and requesting multiple prescriptions. Deep brain stimulation surgery was proposed, but the patient was deemed unfit for the procedure after two separate psychiatric evaluations, mainly because of behaviour and social problems in relation to sustained cocaine abuse and personality disorder. Attempts to stop drug abuse were unsuccessful despite several interventions by addiction psychiatry.
Conclusions
Co-occurrence of PD, substance-abuse and personality disorder poses as a therapeutic challenge conditioned by pharmacological iatrogenesis and behavioural disturbances, requiring a multidisciplinary and individualized approach.
This chapter reviews what is known about the developmental antecedents of adult antisocial personality. It addresses the question of why it is that, while many people may have personality difficulties, a minority develop a severe and persistent dysfunction of personality that is more or less life-long, leading them into a pattern of chronic antisocial behaviour. Findings reviewed in this chapter suggest that the route to adult antisociality is marked by a cascade of developmental roadblocks and insults arising during childhood and adolescence. The authors emphasise the importance of adolescence as a period when things can go seriously awry and personality can deviate from a normal track. They further emphasise the critical importance of substance abuse, particularly the misuse of alcohol, in the genesis of life-course-persistent antisociality. Two possible developmental pathways are described, one predominantly male, the other predominantly female, through which adult antisociality results from adverse circumstances in childhood and adolescence.
Valid diagnostic standards are important for both the treatment and scientific study of SUD. Primary features of SUD are uncontrolled compulsive drug use, and harmful consequences of drug use. The DSM-5, a successor to the DSM-IV, lists diagnostic criteria for SUD, and its use is the standard for diagnosis of the disorder. Physiological withdrawal symptoms are only 1 of 11 possible criteria, so are neither necessary nor sufficient for a positive diagnosis. Differences among individuals in gender, psychiatric disorders, and other factors can influence the diagnosis of SUD. Less severe cases may be difficult to distinguish from heavy but non-pathological use of drugs, including alcohol. Screening tests cannot provide a diagnosis, but can identify individuals whose drug use warrants a full diagnostic interview. For those with an SUD, the diagnostic interview can be the initial phase of treatment by establishing a therapeutic relationship with a mental health professional. A skilled clinician can often counteract the denial and defensiveness that can prevent an accurate diagnosis of SUD.
Non-medical opioid use (NMOU) is a growing crisis. Cancer patients at elevated risk of NMOU (+risk) are frequently underdiagnosed. The aim of this paper was to develop a nomogram to predict the probability of +risk among cancer patients receiving outpatient supportive care consultation at a comprehensive cancer center.
Method
3,588 consecutive patients referred to a supportive care clinic were reviewed. All patients had a diagnosis of cancer and were on opioids for pain. All patients were assessed using the Edmonton Symptom Assessment Scale (ESAS), Screener and Opioid Assessment for Patients with Pain (SOAPP-14), and CAGE-AID (Cut Down-Annoyed-Guilty-Eye Opener) questionnaires. “+risk” was defined as an SOAPP-14 score of ≥7. A nomogram was devised based on the risk factors determined by the multivariate logistic regression model to estimate the probability of +risk.
Results
731/3,588 consults were +risk. +risk was significantly associated with gender, race, marital status, smoking status, depression, anxiety, financial distress, MEDD (morphine equivalent daily dose), and CAGE-AID score. The C-index was 0.8. A nomogram was developed and can be accessed at https://is.gd/soappnomogram. For example, for a male Hispanic patient, married, never smoked, with ESAS scores for depression = 3, anxiety = 3, financial distress = 7, a CAGE score of 0, and an MEDD score of 20, the total score is 9 + 9+0 + 0+6 + 10 + 23 + 0+1 = 58. A nomogram score of 58 indicates the probability of +risk of 0.1.
Significance of results
We established a practical nomogram to assess the +risk. The application of a nomogram based on routinely collected clinical data can help clinicians establish patients with +risk and positively impact care planning.
Addiction to various substances, including drugs and alcohol, probably arises from a combination of environmental and genetic factors. The genetic vulnerability to drug addiction is supported by several familial, adoption and twin studies. However, as in other mental disorders, the genetic vulnerability to drug addiction appears complex: these disorders do not follow the rules of Mendelian inheritance. Instead, they are probably influenced by multiple susceptibility genes, each of which contributes to the disorder. The more genes necessary for a disorder, the harder it is to detect any of them. This difficulty is magnified by the role of environmental factors. Association studies using the candidate gene approach can identify susceptibility genes for drug abuse supported by the pathophysiological hypothesis of the illness. This review will focus on the clinical and molecular genetic studies in drug abuse.
Two clinical observations of mianserin abuse by psychiatric out-patients are described. A previous history of substance dependence was found in both cases. Mianserin should be used with caution in predisposed patients, before further studies on the subject are carried out.
is HIV-positive andHIV-negative injection drug addicts.
The Methods of the research
– study of social functioning, quality of life and alienation of injection drug addicts with HIV-infection and without HIV-infection with establishment ofinterrelation of factors of clinical and psychosocial characteristics and further development of the evaluation methods of the alienation level and treatment efficacy of injection drug addicts.
Results
While performing the research were studied the regularities of drug addiction spread in the Republic of Belarus, developmentof epidemical HIV-infection process and the state of immune system among injection drug addicts. It is shown, that the spread of drug abuse and HIV-infection is followed by the increase of HIV-positive injection drug addicts, who has shown the symptoms of immune deficiency, which are marked with comorbidity with HIV-infection.
Conclusion
Were developed and clinically tested diagnostic technique of alienation level of injection drug addicts and evaluation method ofefficiency treatment of drug addicts, which distinguishes the main criterion of conducted research and its research and practice importance.
We seek to identify factors that facilitate or inhibit transmission of drug abuse (DA) from high-risk parents to their children. In 44,250 offspring of these parents, ascertained from a Swedish national sample for having a mother and/or father with DA, we explored, using Cox models, how the prevalence of DA was predicted by potentially malleable risk factors in these high-risk parents, their spouses and the rearing environment they provided. Analyses of offspring of discordant high-risk siblings and offspring of discordant sibling-in-laws and step-parents aided causal inference. Risk for DA in the children was associated with high-risk and married-in parental externalizing psychopathology, a range of other features of these parents (e.g., low education and receipt of welfare), and aspects of the rearing environment (e.g., neighborhood deprivation and number of nearby drug dealers). Offspring of discordant high-risk siblings, siblings-in-laws and step-parents suggested that nearly all these associations were partly causal. A multivariate analysis utilizing offspring of discordant high-risk siblings identified the six most significant potentially malleable risk factors for offspring DA: (1) criminal behavior (CB) in married-in parent, (2) community peer deviance, (3) broken family, (4) DA in high-risk parent, (5) CB in high-risk parent and (6) number of family moves. Children in the lowest decile of risk had a 50% reduction in their DA prevalence, similar to that seen in the general population. We conclude that transmission of DA from high-risk parents to children partly results from a range of potentially malleable risk factors that could serve as foci for intervention.
We sought to quantify and investigate the causal nature of the association between resilience at age 18 and future drug abuse (DA).
Method
In a national sample of Swedish men (n = 1 392 800), followed for a mean of 30.3 years, resilience was assessed during military conscription and DA defined from medical, criminal and pharmacy registers. For causal inference, we utilized three methods: (i) instrumental variable analyses with the month of birth as the instrument; (ii) co-relative analyses using the general population, cousins, siblings and monozygotic twins; and (iii) propensity scoring on a subsample (n = 48 548) with strong resilience predictors. Cox proportional hazards models were utilized to examine survival time till DA diagnosis.
Results
Low resilience was most robustly predicted from internalizing symptoms. Lower levels of standardized resilience strongly predicted the risk for DA (HR = 2.31, 95% CIs 2.28–2.33). In instrumental, co-relative, and propensity score analyses, the association between resilience and DA was estimated at HR = 3.06 (2.44–3.85), 1.34 (1.28–1.39), and 1.40 (1.28–1.53), respectively. Sensitivity analyses suggested that our instrument was weak and, despite our large sample, likely under-estimated confounding.
Conclusions
Low resilience strongly predicts DA risk. Three different causal analysis methods, with divergent assumptions, concurred in estimating that an appreciable proportion of this association was causal, probably around 40%, with the remainder arising from confounding variables many of which are likely familial. Consistent with prior interventions focused on substance use prevention, our results suggest that prevention programs that increase resilience in adolescence should meaningfully reduce the long-term risk for DA.
Addressing important problems and processes in the assessment of substance use disorders (SUDs), this chapter reviews the types of information necessary for a formal diagnosis of a DSM-5 SUD. In addition, the chapter discusses seven assessment areas that must be examined if a given case is to be well evaluated. These include clinical history, strength of dependence syndrome, impaired volitional control, craving, neuroadaptation, negative consequences and pathological patterns, and stage of change. The origin and research background of each of these constructs are briefly outlined, a favored assessment tool for each is reviewed in detail, and alternative measures are also suggested. The assessment of SUDs is a multidimensional, complex process for which many excellent tools have been, and are still being, developed.
Can drug abuse (DA) be transmitted psychologically between adult siblings consistent with a social contagion model?
Methods
We followed Swedish sibling pairs born in 1932–1990 until one of them, sibling1 (S1), had a first DA registration. We then examined, using Cox regression, the hazard rate for a first registration for DA in sibling2 (S2) within 3 years of a first DA registration in S1 as a function of their geographical proximity. We examined 153 294 informative pairs. To control for familial confounding, we repeated these analyses in sibships containing multiple pairs, comparing risk in different siblings with their proximity to S1. DA was recorded in medical, criminal or pharmacy registries.
Results
The best-fit model predicted risk for DA in S2 as a function of the log of kilometres between S1 and S2 with parameter estimates (±95% confidence intervals) of 0.94 (0.92; 0.95). Prediction of DA included effects of cohabitation and an interaction of proximity and time since S1 registration with stronger effects of proximity early in the follow-up period. Proximity effects were stronger for smaller S1–S2 age differences and for same- v. opposite-sex pairs. Sibship analyses confirmed sibling-pair results.
Conclusions
Consistent with a social contagion model, the probability of transmission of a first registration for DA in sibling pairs is related to their geographical proximity and similarity in age and sex. Such effects for DA are time-dependent and include cohabitation effects. These results illustrate the complexity of the familial aggregation of DA and support efforts to reduce their contagious spread within families in adulthood.
We introduce and apply an elegant, contrastive genetic-epidemiological design – Maternal Half-Sibling Families with Discordant Fathers – to clarify cross-generational transmission of genetic risk to alcohol use disorder (AUD), drug abuse (DA) and major depression (MD).
Method
Using Swedish national registries, we identified 73 108 eligible pairs of reared together maternal half-siblings and selected those whose biological fathers were discordant for AUD, DA and MD, and had minimal contact with the affected father. We examined differences in outcome in half-siblings with an affected v. unaffected father.
Results
For AUD, DA and MD, the HR (95% confidence intervals) for the offspring of affected v. unaffected fathers were, respectively, 1.72 (1.61; 1.84), 1.55 (1.41; 1.70) and 1.51 (1.40; 1.64). Paternal DA and AUD, but not MD, predicted risk in offspring for attention deficit hyperactivity disorder, conduct disorder, and poor educational performance and attainment. Offspring of affected v. unaffected fathers had poorer pregnancy outcomes, with the effect strongest for DA and weakest for MD. A range of potential biases and confounders were examined and were not found to alter these findings substantially.
Conclusion
Reared together maternal half-siblings differ in their paternal genetic endowment, sharing the same mother, family, school and community. They can help clarify the nature of paternal genetic effects and produce results consistent with other designs. Paternal genetic risk for DA and AUD have effects on offspring educational achievement, child and adult psychopathology, and possibly prenatal development. The impact of paternal genetic risk for MD is narrower in scope.
Although all the international instruments (treaties, conventions, etc), that shape criminal policy concerning drug trafficking in the Latin American region, converge and given the commitment of the states to go in the same direction, nevertheless it is quite difficult to conduct good research in the subject. This is due to multiple, and constant, reforms in the local legislation, the use of different legal terms and the context of the right to privacy in each country. This article, written by Gloria Orrego Hoyos and Esteban Pizá, addresses the main legal instruments applicable to the general topic of drug trafficking, and concerning personal consumption or minimum dose, and highlights the problems and obstacles faced with regard to conducting research about drug trafficking in the Latin American region.
Cannabis use has been linked to impairments in neuropsychological functioning across a large and continually expanding body of research. Yet insight into underlying causal relations remains limited due to the historically cross-sectional nature of studies in this area. Recently, however, studies have begun to use more informative design strategies to delineate these associations. The aim of this article is to provide a critical evaluation and review of research that uses longitudinal designs to examine the link between cannabis use and neuropsychological functioning. In summarizing the primary findings across these studies, this review suggests that cannabis use leads to neuropsychological decline. However, across most studies, these associations were modest, were present only for the group with the heaviest cannabis use, and were often attenuated (or no longer significant) after controlling for potential confounding variables. Future studies with neuropsychological data before and after initiation of cannabis use, along with careful measurement and control of “shared risk factors” between cannabis use and poorer neuropsychological outcomes, are needed to better understand who, and under what conditions, is most vulnerable to cannabis-associated neuropsychological decline. (JINS, 2017, 23, 893–902)
Relapse from drug abuse (DA) is common, but has rarely been studied in general population samples using a wide range of objective predictors.
Method
Using nationwide registries, we ascertained 44 523 subjects first registered for DA between the ages of 15 and 40 in 1998 to 2004 and followed for 8 years. We predicted relapse in subjects defined as a second DA registration. We also predicted DA relapse in relative pairs concordant for DA but discordant for relapse.
Results
In multivariate regression analyses, the strongest predictors for relapse were prior criminal behavior, male sex, being on social welfare, low school achievement, prior alcoholism, and a high-risk father. A risk index trained from these analyses on random split-halves demonstrated a risk ratio of 1.11 [95% confidence intervals (CIs) 1.10–1.11] per decile and an ROC value of 0.70 (0.69–0.71). Co-relative analyses indicated that a modest proportion of this association was causal, with the remainder arising from familial confounders. A developmental structural equation model revealed a complex interviewing of risk pathways to DA with three key mediational hubs: low educational attainment, early age at first registration, and being on social welfare.
Conclusions
In a general population sample, using objective registry information, DA relapse is substantially predictable. However, the identified risk factors may not be valid targets for interventions because many index familial risk and may not impact causally on probability of relapse. Risk for DA relapse may reflect an inter-weaving, over developmental time, of genetic–temperamental vulnerability, indices of externalizing behaviors and social factors reflecting deprivation.