Developing Substance Use Research Articles

Maladaptive Decision Making in Adults with a History of Adolescent Alcohol use, in a Preclinical Model, Is Attributable to the Compromised Assignment of Incentive Value during Stimulus-Reward Learning.

According to recent WHO reports, alcohol remains the number one substance used and abused by adolescents, despite public health efforts to curb its use. Adolescence is a critical period of biological maturation where brain development, particularly the mesocorticolimbic dopamine system, undergoes substantial remodeling. These circuits are implicated in complex decision making, incentive learning and reinforcement during substance use and abuse. An appealing theoretical approach has been to suggest that alcohol alters the normal development of these processes to promote deficits in reinforcement learning and decision making, which together make individuals vulnerable to developing substance use disorders in adulthood. Previously we have used a preclinical model of voluntary alcohol intake in rats to show that use in adolescence promotes risky decision making in adulthood that is mirrored by selective perturbations in dopamine network dynamics. Further, we have demonstrated that incentive learning processes in adulthood are also altered by adolescent alcohol use, again mirrored by changes in cue-evoked dopamine signaling. Indeed, we have proposed that these two processes, risk-based decision making and incentive learning, are fundamentally linked through dysfunction of midbrain circuitry where inputs to the dopamine system are disrupted by adolescent alcohol use. Here, we test the behavioral predictions of this model in rats and present the findings in the context of the prevailing literature with reference to the long-term consequences of early-life substance use on the vulnerability to develop substance use disorders. We utilize an impulsive choice task to assess the selectivity of alcohol’s effect on decision-making profiles and conditioned reinforcement to parse out the effect of incentive value attribution, one mechanism of incentive learning. Finally, we use the differential reinforcement of low rates of responding (DRL) task to examine the degree to which behavioral disinhibition may contribute to an overall decision-making profile. The findings presented here support the proposition that early life alcohol use selectively alters risk-based choice behavior through modulation of incentive learning processes, both of which may be inexorably linked through perturbations in mesolimbic circuitry and may serve as fundamental vulnerabilities to the development of substance use disorders.

Child maltreatment and age of alcohol and marijuana initiation in high-risk youth

IntroductionYouth with a history of child maltreatment use substances and develop substance use disorders at rates above national averages. Thus far, no research has examined pathways from maltreatment to age of substance use initiation for maltreated youth. We examined the longitudinal impact of maltreatment in early childhood on age of alcohol and marijuana use initiation, and whether internalizing and externalizing behaviors at age 8 mediates the link between maltreatment and age of substance use initiation. Materials and methodsData were drawn from the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN) at ages 4, 8, 12, and 18. Maltreatment was assessed through reviews of administrative records and youth self-reports. Behavior problems were assessed with the Child Behavior Checklist. Age of substance use initiation was assessed with the Young Adult version of the Diagnostic Interview Schedule for Children. ResultsPath analyses indicated mediated effects from a history of maltreatment to age at first alcohol and marijuana use through externalizing behaviors. Considering type of maltreatment, direct effects were found from physical abuse to age of alcohol initiation, and mediated effects were found from sexual abuse and neglect to initial age of alcohol and marijuana use through externalizing behaviors. Direct effects for marijuana use initiation and indirect effects through internalizing behavior problems were not significant for either substance. ConclusionsExternalizing behavior is one pathway from childhood maltreatment to age of substance use initiation. Services for maltreated youth should incorporate substance use prevention, particularly among those with early externalizing problems.

Medical Disease or Moral Defect? Stigma Attribution and Cultural Models of Addiction Causality in a University Population.

This study examines the knowledge individuals use to make judgments about persons with substance use disorder. First, we show that there is a cultural model of addiction causality that is both shared and contested. Second, we examine how individuals' understanding of that model is associated with stigma attribution. Research was conducted among undergraduate students at the University of Alabama. College students in the 18-25 age range are especially at risk for developing substance use disorder, and they are, perhaps more than any other population group, intensely targeted by drug education. The elicited cultural model includes different types of causes distributed across five distinct themes: Biological, Self-Medication, Familial, Social, and Hedonistic. Though there was cultural consensus among respondents overall, residual agreement analysis showed that the cultural model of addiction causality is a multicentric domain. Two centers of the model, the moral and the medical, were discovered. Differing adherence to these centers is associated with the level of stigma attributed towards individuals with substance use disorder. The results suggest that current approaches to substance use education could contribute to stigma attribution, which may or may not be inadvertent. The significance of these results for both theory and the treatment of addiction are discussed.

Assessment and Treatment for Persons with Coexisting Ability and Substance Use Issues: A Review and Analysis of the Literature.

Persons with ability issues are at considerably higher risk to develop substance use problems when compared to the general population. Yet, little is known about the current status of substance use treatment for this population. A comprehensive search of the literature revealed a need for (a) population-specific instruments for screening and assessment of the use of alcohol and drugs, including the misuse of prescription medication; (b) tailored treatment methods and individualized treatment plans that meet diverse literacy or cognitive needs;

Life course persistent and adolescence limited conduct disorder in a nationally representative US sample: prevalence, predictors, and outcomes.

The course of conduct disorder (CD) is heterogeneous. Moffitt proposed the heuristic of life course persistent (LCP) and adolescence limited (AL) to differentiate etiologically distinct forms of antisocial behavior (AB), each with distinct predictors and consequences, although a few studies have assessed this demarcation within the context of CD. The objective of this study was to apply Moffitt's taxonomy in a nationally representative US sample to investigate the prevalence, predictors, and outcomes of LCP and AL CD. Data come from the Collaborative Psychiatric Epidemiology Studies, a set of population-based nationally representative cross-sectional surveys (N = 20,130). Predictors included harsh discipline, maternal and paternal closeness, poverty in childhood, history of learning disability, parental deviance, and nativity. Outcomes included substance use, employment status, education attainment, marital status, income level, and self-rated mental and physical health. The prevalence of LCP and AL CD was 0.5 and 4.6%, respectively, for females, and 1.9 and 5.1%, respectively, for males. Low childhood SES [Odds Ratio (OR) = 3.49], lack of maternal closeness (OR = 2.50), and history of harsh discipline (OR = 2.17) increased odds of LCP group membership. The LCP group had higher odds of developing substance use disorders (OR = 2.00) relative to AL. LCP CD is more strongly influenced by childhood environment and confers increased odds for substance use problems in adulthood relative to AL CD.

Neuroimaging the neural correlates of increased risk for substance use disorders in attention-deficit/hyperactivity disorder-A systematic review

Children with attention-deficit/hyperactivity disorder (ADHD) are nearly three times more likely to develop substance use disorders (SUD) than their typically developing peers. Our objective was to review the existing neuroimaging research on high-risk ADHD (ie, ADHD with disruptive behavior disorders, familial SUD and/or early substance use), focusing on impulsivity as one possible mechanism underlying SUD risk. A PubMed literature search was conducted using combinations of the keywords "ADHD," "substance use," "substance use disorder," "SUD," "addiction," "dependence," "abuse," "risk," "brain" "MRI," "imaging" and "neuroimaging." Studies had to include cohorts that met diagnostic criteria for ADHD; studies of individuals with ADHD who all met criteria for SUD were excluded. Eight studies met the search criteria. Individuals with high-risk ADHD have hyperactivation in the motivation-reward processing brain network during tasks of impulsive choice, emotion processing, and risky decision-making. During response inhibition tasks, they have hypoactivation in the inhibitory control brain network. However, studies focusing on this latter circuit found hypoactivation during inhibitory control tasks, decreased white matter microstructure coherence and reduced cortical thickness in ADHD independent of substance use history. An exaggerated imbalance between the inhibitory control network and the motivation-reward processing network is theorized to distinguish individuals with high-risk ADHD. Preliminary findings suggest that an exaggerated aberrant reward processing network may be the driving neural correlate of increased SUD risk in ADHD. Neural biomarkers of increased SUD risk in ADHD could help clinicians identify which patients may benefit most from SUD prevention. Thus, more neuroimaging research on this vulnerable population is needed. (Am J Addict 2017;26:99-111).

Maternal Separation Impairs Cocaine-Induced Behavioural Sensitization in Adolescent Mice.

Adverse early-life conditions induce persistent disturbances that give rise to negative emotional states. Therefore, early life stress confers increased vulnerability to substance use disorders, mainly during adolescence as the brain is still developing. In this study, we investigated the consequences of maternal separation, a model of maternal neglect, on the psychotropic effects of cocaine and the neuroplasticity of the dopaminergic system. Our results show that mice exposed to maternal separation displayed attenuated behavioural sensitization, while no changes were found in the rewarding effects of cocaine in the conditioned place preference paradigm and in the reinforcing effects of cocaine in the self-administration paradigm. The evaluation of neuroplasticity in the striatal dopaminergic pathways revealed that mice exposed to maternal separation exhibited decreased protein expression levels of D2 receptors and increased levels of the transcriptional factor Nurr1. Furthermore, animals exposed to maternal separation and treated with cocaine exhibited increased DA turnover and protein expression levels of DAT and D2R, while decreased Nurr1 and Pitx3 protein expression levels were observed when compared with saline-treated mice. Taken together, our data demonstrate that maternal separation caused an impairment of cocaine-induced behavioural sensitization possibly due to a dysfunction of the dopaminergic system, a dysfunction that has been proposed as a factor of vulnerability for developing substance use disorders.

Choosing Opioid Policies Our Patients Can Live With.

In 1997, the American Academy of Pain Medicine and the American Pain Society jointly issued recommendations regarding the care of patients with chronic pain.(1) Several years later, the Joint Commission on Accreditation of Healthcare Organizations issued pain management standards "recommending" that hospitals identify patients with pain upon initial screening and collect data to monitor the effectiveness of pain management.(2) Nearly two decades later, we find ourselves in the midst of a opioid epidemic triggered, in part, by excessive utilization of opioid pain medications.(3) We now find ourselves playing "catch up," as we try to undo some of the practices of the past, and change the culture to better balance benefit and risk. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved. Language: en

Early Adolescent Trajectories of Impulsiveness and Sensation Seeking in Children of Fathers with Histories of Alcohol and Other Substance Use Disorders.

Problem substance use often begins in adolescence. This vulnerability likely stems, at least partially, from relatively rapid increases in sensation seeking occurring in early to mid-adolescence and more gradual improvements in impulse control occurring through later adolescence. Better understanding how these processes develop in high-risk youth may lead to enhanced substance use disorder treatment and prevention strategies. We characterized trajectories of self-reported impulsivity and sensation seeking in 305 FH+ youths who at minimum had a father with a history of alcohol or other drug use disorders and 81 youths with no family histories of substance use disorders (FH-). Assessments started at ages 10 to 12 and continued at 6-month intervals for up to 42months. In addition, a subset of 58 FH+ youths who began alcohol or other drug use before age 15 (FH+ Users) were compared to 58 FH+ propensity-matched adolescents who did not initiate substance use before age 15 (FH+ Non-Users). Compared to FH- youths at preadolescence, FH+ youths reported higher general impulsivity and higher impulsivity related to poor planning and attention. Over time, there were no differential effects of FH status on changes in impulsivity or sensation seeking across adolescence. FH+ Users had smaller decreases in general impulsivity and impulsivity related to restlessness and fidgeting across adolescence than FH+ Non-Users. FH+ Users also had greater increases in sensation seeking across adolescence than FH+ Non-Users. Increased impulsivity in FH+ youths may make them less able to regulate sensation seeking drives that peak in adolescence, which may contribute to their high risk for developing substance use disorders. Additionally, FH+ adolescents who initiate early use may be at increased risk in part due to increased impulsivity coupled with greater increases in sensation seeking.

22.4 REDUCING RISK FOR SUBSTANCE USE PROBLEMS AMONG ADOLESCENTS WITH A CHILD MALTREATMENT HISTORY

Youth who have experienced childhood maltreatment, such as sexual abuse, physical abuse, and witnessing violence, are more than twice as likely to develop substance use problems during adolescence than youth who have not had such experiences. Despite this elevated risk, few trauma-informed interventions targeting substance use risk reduction have been rigorously evaluated for adolescents. The purpose of this presentation is to report results from an NIH NIDA-funded stage 2 randomized controlled trial for a psychosocial treatment (risk reduction through family therapy, RRFT) targeting co-occurring substance use problems and maltreatment-related psychopathology among teenagers.

Anxiety Symptoms and Coping Motives: Examining a Potential Path to Substance Use-Related Problems in Adolescents With Psychopathic Traits

ABSTRACTBackground: Although the relation between impulsive-irresponsible psychopathic traits and substance use is well-documented, the path to developing substance use problems is less understood in adolescents with these characteristics. Objectives: To examine the associations between psychopathy, anxiety, and substance use motives and a mechanism by which anxiety and alcohol and marijuana coping motives mediate the relation between psychopathic traits and substance use-related problems. Methods: A sample of 185 at-risk adolescent males from a residential military-style program reporting past alcohol or marijuana use (M age = 16.74) participated in the study. Results: Impulsive-Irresponsible psychopathic traits were uniquely and incrementally predictive of alcohol and marijuana use-related problems and anxiety. Anxiety and coping motives appeared to partially explain the association between impulsivity-irresponsibility and substance use-related problems. Conclusions/Importance: Findings suggest that youth expressing impulsive-irresponsible psychopathic traits may engage in problematic substance use at least partly as a function of heightened anxiety and a subsequent desire to alleviate distress by using alcohol or marijuana to cope.

The Associations of Age and Ethnicity on Substance Use Behaviors of Adolescent and Young Adult Childhood Cancer Survivors.

The aim of this study was to examine the associations between age and ethnicity on the development of substance use behaviors among Hispanic and non-Hispanic White (NHW) adolescent and young adult (AYA) childhood cancer survivors. Participants were recruited from a single institution through the CHOC Children's Hospital Cancer Registry and included 55 Hispanic and 61 NHW AYA childhood cancer survivors, ages 12 to 33years (Mean age±SD: 19±4.2). Smoking, alcohol, and drug use were measured using the Child Health Illness Profile - Adolescent Edition. Hispanic AYA survivors were less likely to be medically insured and reported lower household income than their NHW counterparts (P<0.001 and P<0.001, respectively). After controlling for socioeconomic differences and gender, age and ethnicity were significant predictors of substance use among AYA survivors. Hispanic survivors reported less lifetime use of cigarette smoking compared with NHW survivors (OR 0.17, 95% CI, 0.03-0.80). Older age, for both Hispanic and NHW survivors, was found to be a risk factor for lifetime substance use and current alcohol/hard liquor consumption and binge drinking (P<0.05). Young adult childhood cancer survivors and NHW survivors are at greatest risk for developing substance use behaviors. The frequency of substance use among AYA survivors appears to increase as they transition into adulthood. These findings emphasize the need to improve long-term health behavior screening and develop effective interventions on reducing substance use behaviors in this vulnerable population.

Childhood Maltreatment and Development of Substance Use Disorders

Exposure to childhood maltreatment (CM) is associated with increased risk for developing substance use disorders (SUDs). CM exerts negative effects on cognitive abilities including intellectual performance, memory, attention, and executive function. Parallel cognitive impairments have been observed in SUDs. Hence, limited studies have examined the mediating effect of cognitive impairments in the relationship between CM and SUDs. In addition, most studies used concurrent self-report assessments in adult populations. Longitudinal studies that investigated the long-term consequences of CM on psychopathology, including SUDs, throughout childhood, adolescence, and adulthood are rare. Thus, the underlying developmental pathways between CM and SUDs are not clearly understood. In this article, we review the evidence that cognitive impairments mediate, at least in part, the relationship between CM and development of SUDs and propose a model that explains how CM increases the risk for SUDs through the development of a cognitive framework of vulnerability.

Interactions between Early Life Stress, Nucleus Accumbens MeCP2 Expression, and Methamphetamine Self-Administration in Male Rats.

Early life stress (ELS) is highly related to the development of psychiatric illnesses in adulthood, including substance use disorders. A recent body of literature suggests that long-lasting changes in the epigenome may be a mechanism by which experiences early in life can alter neurobiological and behavioral phenotypes in adulthood. In this study, we replicate our previous findings that ELS, in the form of prolonged maternal separation, increases adult methamphetamine self-administration (SA) in male rats as compared with handled controls. In addition, we show new evidence that both ELS and methamphetamine SA alter the expression of the epigenetic regulator methyl CpG-binding protein 2 (MeCP2) in key brain reward regions, particularly in the nucleus accumbens (NAc) core. In turn, viral-mediated knockdown of MeCP2 expression in the NAc core reduces methamphetamine SA, as well as saccharin intake. Furthermore, NAc core MeCP2 knockdown reduces methamphetamine, but not saccharin, SA on a progressive ratio schedule of reinforcement. These data suggest that NAc core MeCP2 may be recruited by both ELS and methamphetamine SA and promote the development of certain aspects of drug abuse-related behavior. Taken together, functional interactions between ELS, methamphetamine SA, and the expression of MeCP2 in the NAc may represent novel mechanisms that can ultimately be targeted for intervention in individuals with adverse early life experiences who are at risk for developing substance use disorders.

Developmental stress elicits preference for methamphetamine in the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder.

BackgroundDevelopmental stress has been hypothesised to interact with genetic predisposition to increase the risk of developing substance use disorders. Here we have investigated the effects of maternal separation-induced developmental stress using a behavioural proxy of methamphetamine preference in an animal model of attention-deficit/hyperactivity disorder, the spontaneously hypertensive rat, versus Wistar Kyoto and Sprague–Dawley comparator strains.ResultsAnalysis of results obtained using a conditioned place preference paradigm revealed a significant strain × stress interaction with maternal separation inducing preference for the methamphetamine-associated compartment in spontaneously hypertensive rats. Maternal separation increased behavioural sensitization to the locomotor-stimulatory effects of methamphetamine in both spontaneously hypertensive and Sprague–Dawley strains but not in Wistar Kyoto rats.ConclusionsOur findings indicate that developmental stress in a genetic rat model of attention-deficit/hyperactivity disorder may foster a vulnerability to the development of substance use disorders.

Substance use disorders: Relationship with intermittent explosive disorder and with aggression, anger, and impulsivity

BackgroundA relationship between substance use and aggression has been noted for decades. While substance use appears to be associated with an increased risk of aggressive behavior, no study has yet reported on the pattern of comorbidity and temporal relationship between impulsive aggression (i.e., intermittent explosive disorder) and substance use disorders (SUD), specifically. MethodsTo specify these relationships, we examined DSM-5 diagnosis data from diagnostic interviews of 1355 adults who met one of five non-overlapping diagnostic subgroups: those with intermittent explosive disorder (IED; n = 339), those with SUD (n = 136), IED+SUD (n = 280), adults with psychiatric disorders but no SUD or IED (n = 320), and healthy Controls: HC, n = 282). ResultsOccurrence of lifetime SUD was elevated in IED vs. all Non-IED subjects (Odds Ratio: 3.61 [95% CI: 2.82–4.63]) and onset of IED preceded SUD in 80% of comorbid IED+SUD cases. Examination of the severity of impulsive aggression and SUD revealed that IED increased SUD severity but the presence of SUD did not increase severity of IED core features, including aggression, anger, or impulsivity. ConclusionsSubjects with IED are at increased risk of developing substance use disorder, compared to those without IED. This suggests that history of recurrent, problematic, impulsive aggression is a risk factor for the later development of SUD rather than the reverse. Thus, effective treatment of impulsive aggression, before the onset of substance misuse, may prevent or delay the development of SUD in young individuals.

The risk of offspring developing substance use disorders when exposed to one versus two parent(s) with alcohol use disorder: A nationwide, register-based cohort study

AimFew population-based, family studies have examined associations between exposure to one vs. two parent(s) with alcohol use disorder (AUD) and the risk of offspring developing substance use disorder (SUD). Moreover, these studies have focused solely on the development of AUD, and not SUD, in offspring. The purpose of this study was to investigate whether exposure to one vs. two parent(s) with AUD increases the risk of offspring developing SUD. MethodsA population-based, cohort study was conducted in which offspring born in Denmark between 1983 and 1989 were followed through national registries until 2011. Register-based data were obtained from the: Psychiatric Central Research Register, National Patient Registry, Civil Registration System, Fertility Database, and Cause of Death Register. Adjusted hazard ratios were calculated using multivariate Cox-regression models. FindingsA total of 398,881 offspring were included in this study. Of these, 3.9% had at least one parent with AUD. Parental AUD was significantly associated with the development of SUD in offspring. Having one parent with AUD was linked to a 1.44-fold increased risk (95% CL, 1.29–1.61), while having two parents with AUD was linked to a 2.29-fold increased risk (95% CI, 1.64–3.20). No significant differences were found in relation to either parental or offspring gender. ConclusionsExposure to parental AUD is linked to an increased risk of offspring developing SUD. This risk is additive for offspring exposed to double parental AUD. The findings have important implications for clinical assessment and intervention strategies, as well as the management of offspring exposed to parental AUD.

Personality and trajectories of posttraumatic psychopathology: A latent change modelling approach

BackgroundSurvivors of traumatic events may develop a range of psychopathology, across the internalizing and externalizing dimensions of disorder and associated personality traits. However, research into personality-based internalizing and externalizing trauma responses has been limited to cross-sectional investigations of PTSD comorbidity. Personality typologies may present an opportunity to identify and selectively intervene with survivors at risk of posttraumatic disorder. Therefore this study examined whether personality prospectively influences the trajectory of disorder in a broader trauma-exposed sample. MethodsDuring hospitalization for a physical injury, 323 Australian adults completed the Multidimensional Personality Questionnaire—Brief Form and Structured Clinical Interview for DSM-IV, with the latter readministered 3 and 12 months later. Latent profile analysis conducted on baseline personality scores identified subgroups of participants, while latent change modelling examined differences in disorder trajectories. ResultsThree classes (internalizing, externalizing, and normal personality) were identified. The internalizing class showed a high risk of developing all disorders. Unexpectedly, however, the normal personality class was not always at lowest risk of disorder. Rather, the externalizing class, while more likely than the normal personality class to develop substance use disorders, were less likely to develop PTSD and depression. ConclusionsResults suggest that personality is an important mechanism in influencing the development and form of psychopathology after trauma, with internalizing and externalizing subtypes identifiable in the early aftermath of injury. These findings suggest that early intervention using a personality-based transdiagnostic approach may be an effective method of predicting and ultimately preventing much of the burden of posttraumatic disorder.

Sleep mediates the link between resiliency and behavioural problems in children at high and low risk for alcoholism.

Children of alcoholic parents are at greater risk for developing substance use problems. Having a parent with any mental illness increases the risk for sleep disorders in children. Using actigraphy, this study characterized sleep in children of alcoholics and community controls over a period of 1 week. This study further examined whether sleep characteristics of the children mediated the relationship between self-regulation indices (i.e. undercontrol and resiliency) and outcome measures of function (e.g. problem behaviours and perceived conflict at home). Eighty-two children (53 boys, 29 girls, 7.2-13.0years old) were recruited from the ongoing Michigan Longitudinal Study. Seventeen participants had no parental history of alcohol abuse or dependence family history negative (FH-), 43 had at least one parent who was a recovered alcoholic, and 22 had at least one parent who met diagnostic criteria within the past 3years. Sleep was assessed with actigraphy and sleep diaries for 1 week, and combined with secondary analysis of data collected for the longitudinal study. FH- children had more objectively measured total sleep time. More total sleep time was associated with greater resiliency and behavioural control, fewer teacher-reported behavioural problems, and less child-reported conflict at home. Further, total sleep time partially mediated the relationship between resiliency and perceived conflict, and between resiliency and externalizing problems. These findings suggest that in high-risk homes, the opportunity to obtain sufficient sleep is reduced, and that insufficient sleep further exacerbates the effects of impaired dispositional self-regulatory capacity on behavioural and emotional regulation.

Aggression as a Predictor of Early Substance Use Initiation among Youth with Family Histories of Substance Use Disorders.

Aggression as a Predictor of Early Substance Use Initiation among Youth with Family Histories of Substance Use Disorders.