Including Substance Use Disorders Research Articles

Pharmacology and Therapeutic Potential of Benzothiazole Analogues for Cocaine Use Disorder.

Pharmacological targeting of the dopamine D4 receptor (D4R)─expressed in brain regions that control cognition, attention, and decision-making─could be useful for several neuropsychiatric disorders including substance use disorders (SUDs). This study focused on the synthesis and evaluation of a novel series of benzothiazole analogues designed to target D4R. We identified several compounds with high D4R binding affinity (Ki ≤ 6.9 nM) and >91-fold selectivity over other D2-like receptors (D2R, D3R) with diverse partial agonist and antagonist profiles. Novel analogue 16f is a potent low-efficacy D4R partial agonist, metabolically stable in rat and human liver microsomes, and has excellent brain penetration in rats (AUCbrain/plasma > 3). 16f (5-30 mg/kg, i.p.) dose-dependently decreased iv cocaine self-administration in rats, consistent with previous results produced by D4R-selective antagonists. Off-target antagonism of 5-HT2A or 5-HT2B may also contribute to these effects. Results with 16f support further efforts to target D4R in SUD treatment.

Tobacco/nicotine dependence as a risk factor for substance use disorders and related mental health conditions among cancer patients.

Cancer patients often face multiple comorbidities and are at risk for various mental health conditions and substance use disorders. Tobacco/nicotine dependence (TND) is a known risk factor for poor health outcomes and has been associated with psychiatric disorders including substance use disorder. However, the specific relationship between TND and the risk of substance use disorder and mental health conditions among cancer patients remains underexplored. This study aimed to assess the association between TND and the risk of comorbid conditions among cancer patients. Data were obtained from a database of electronic health records for patients from the University of California health system. The odds for every condition among cancer patients with TND were calculated and compared with those for cancer patients without TND. ORs were adjusted for gender, ethnicity, and race. Three thousand seven hundred and ninety-one cancer patients with TND had 252,619 total conditions, and 51,711 cancer patients without TND had 2,310,880 conditions. After adjusting for confounders, the condition for which TND most exacerbated risk was psychoactive substance-induced organic anxiety disorder (OR=16.3, p<0.001). This appeared consistent with the second, third, and fifth most-exacerbated conditions: stimulant use disorder (OR=12.8, p<0.001), cocaine induced mental disorder (OR=11.0, p<0.001), and cocaine use disorder (OR=11.0, p<0.001). Different conditions exacerbated by TND include acute alcoholic intoxication (OR=11.4, p<0.001), opioid use disorder (OR=7.6, p<0.001), schizoaffective disorder (OR=7.4, p<0.001), and cannabis use disorder (OR=6.3, p<0.001). Our findings reveal a strong association between TND and an increased risk of substance use disorder and mental health conditions among cancer patients. Specifically, cancer patients with TND were at an elevated risk for psychoactive substance-induced organic anxiety disorder, stimulant use disorder, and cocaine-related disorders. Additionally, TND was associated with an increased risk of acute alcoholic intoxication, opioid use disorder, schizoaffective disorder, and cannabis use disorder. These findings underscore the need for comprehensive screening and interventions to address TND and comorbid conditions among cancer patients.

Effects of Mindfulness-Based Interventions on Gray Matter Volume in Patients with Opioid Dependence

Introduction: Recently, several mindfulness-based programs showed promising clinical effects in the treatment of psychiatric disorders including substance use disorders. However, very little is known about the effects of mindfulness-based interventions (MBIs) on brain structure in such patients. Methods: This study aimed to detect changes in gray matter volume (GMV) in opioid-dependent patients receiving MBI during their first month of treatment. Thirty patients were assigned to either 3 weeks of MBI (n = 16) or treatment as usual (TAU, n = 14) and were investigated using structural magnetic resonance imaging before and after treatment. Longitudinal pipeline of the Computational Anatomy Toolbox for SPM (CAT12) was used to detect significant treatment-related changes over time. The identified GMV changes following treatment were related to clinically relevant measures such as impulsivity, distress tolerance, and mindfulness. Results: After treatment, increased mindfulness scores were found in individuals receiving MBI compared to TAU. In the MBI group, there were also significant differences with respect to distress tolerance and impulsivity. Effects on mindfulness, distress tolerance, and impulsivity were also found in the TAU group. Longitudinal within-group analysis revealed increased left anterior insula GMV in individuals receiving MBI. Anterior insula volume increase was associated with decreased impulsivity levels. In the TAU group, significant GMV changes were found in the right lingual gyrus and right entorhinal cortex. Discussion/Conclusion: MBI can yield significant clinical effects during early abstinence from opioid dependence. MBI is particularly associated with increased insula GMV, supporting an important role of this region in the context of MBI-induced neural changes.

The N40D Variant Presents Distinct Trafficking and Signaling Properties to the Mu‐Opioid Receptor

The opioid overdose crisis has continued to increase over the past few years resulting in about 1.7 million people battling substance use disorder related to prescription opioid pain relievers. Individual susceptibility to opioid overdose and addiction is largely determined by genetic variation. One gene that shows genetic variation is OPRM1, the gene for the mu-opioid receptor (MOR), the primary target of all clinically used and abused opioids. OPRM1 is susceptible to several naturally occurring single nucleotide polymorphisms (SNPs), such as A118G (or N40D). N40D is the most prevalent SNP and causes an Asn to Asp switch leading to the removal of an N-glycosylation site. N40D is associated with various disorders including substance use disorder and alcoholism. However, how N40D and other SNPs change MOR function at molecular and cellular levels are still unknown. To address this gap, we examined the effect of the N40D mutation on two key aspects of receptor function: trafficking and signaling. Our results suggest that N40D variant receptor shows steady state localization and trafficking that is distinct from the MOR, leading to differences in downstream consequences of receptor signaling from the same agonist. These results have profound implications to understanding the pharmacogenetics of opioid physiology and developing personalized care in the future.

Genomic relationships across psychiatric disorders including substance use disorders

BackgroundA recent study investigated the genetic associations and latent genetic structure among eight psychiatric disorders using findings from genome-wide association studies (GWASs). No data from substance use disorders were included, while these represent an important category of mental disorders and could influence the latent genetic structure. We extended the original paper by recreating the genetic relationship matrix, graph, and latent genetic factor structure, including additional data from substance use disorders. MethodsWe used GWAS summary statistics of 11 psychiatric disorders, including alcohol dependence, nicotine dependence, and cannabis use disorder. We estimated genetic correlations between all traits in Linkage Disequilibrium-Score Regression. A graph was created to illustrate the network of genetic correlations. We then used the genetic relationships to model a latent genetic factor structure. ResultsAlcohol and nicotine dependence showed significant genetic correlations with several other psychiatric disorders, including ADHD, schizophrenia, and major depression. Cannabis use disorder was only significantly associated with ADHD. The addition of substance use disorders resulted in some changes in the latent structure of the factor model when compared to the original model including eight disorders. All substance use disorders contributed mostly to Factor 3, a heterogeneous factor with also loadings from ADHD, major depression, Autism Spectrum Disorders, and Tourette Syndrome. ConclusionsAlcohol and nicotine dependence show widespread genetic correlations with other psychiatric disorders. Including substance use disorders in the factor analysis results in some changes in the underlying genetic factor structure. Given the instability of such models, identified structures should be interpreted with caution.

Turning the 'Tides on Neuropsychiatric Diseases: The Role of Peptides in the Prefrontal Cortex.

Recent advancements in technology have enabled researchers to probe the brain with the greater region, cell, and receptor specificity. These developments have allowed for a more thorough understanding of how regulation of the neurophysiology within a region is essential for maintaining healthy brain function. Stress has been shown to alter the prefrontal cortex (PFC) functioning, and evidence links functional impairments in PFC brain activity with neuropsychiatric disorders. Moreover, a growing body of literature highlights the importance of neuropeptides in the PFC to modulate neural signaling and to influence behavior. The converging evidence outlined in this review indicates that neuropeptides in the PFC are specifically impacted by stress, and are found to be dysregulated in numerous stress-related neuropsychiatric disorders including substance use disorder, major depressive disorder (MDD), posttraumatic stress disorder, and schizophrenia. This review explores how neuropeptides in the PFC function to regulate the neural activity, and how genetic and environmental factors, such as stress, lead to dysregulation in neuropeptide systems, which may ultimately contribute to the pathology of neuropsychiatric diseases.

We should address residential relocation to improve patient care.

Moving, or residential relocation, occurs frequently in childhood and adolescence as well as in adulthood, yet little scientific consensus exists on its impact upon health outcomes. This paper summarises the available literature on this broad topic and explores the currently known factors of importance surrounding residential relocation. There is already evidence to support an increased risk of suicidal ideation, psychiatric disorders including substance use disorders, functional impairments and future general medical health impairments in children, adolescents and adults with histories of residential relocation. Intrapersonal factors, such as personality type and the availability of coping skills, as well as interpersonal factors, such as family composition and system strengths, attenuate risk and are integral to additionally assess. While there is support for the contribution of residential relocation in the onset of youth psychopathology that warrant consideration of residential relocation in the standard assessment of a patient, further studies are needed to better explore this factor in select populations.

Are pre-existing psychiatric disorders the only reason for involuntary holds in the emergency department?

ObjectivesTo determine the role of previous psychiatric disorders including substance use disorders on emergency department (ED) patients on involuntary holds and compare presentations, treatment, and outcomes based on cause.MethodsWe conducted a retrospective study of patients ≥ 18 years old on involuntary holds in the ED of a tertiary care center from January 1, 2013, to November 30, 2015. Demographic and clinical information were collected. Those with and without prior psychiatric disorder including substance use disorder were compared.ResultsWe identified 251 patients of which 129 (51.4%) had a psychiatric disorder, 23 (9.2%) had a substance use disorder, and 86 (34.3%) had both. Thirteen patients (5.2%) had no psychiatric disorder or substance use disorder and the majority 10 (76.9%) were on involuntary holds due to suicidal threats related to pain or another medical problem. Patients without a psychiatric or substance use disorder were older (55 years [17.8] vs 42 [19]; P = 0.01), more likely to be married (10 [76.9%] vs 64 [26.9%]; P < 0.001), and had more medical comorbidities (10 [76.9%] vs 114 [47.9%]; P = 0.049) compared with those without a psychiatric or substance use disorder.ConclusionPatients on involuntary holds most commonly have pre-existing psychiatric disorder including substance use disorder. Patients on involuntary holds without history of psychiatric disorder often have severe pain or other active medical conditions which may contribute to suicidal thoughts. Addressing these underlying medical issues may be crucial in preventing further psychiatric decompensation.

Reward and immune responses in adolescent females following experimental traumatic brain injury

The pathology of traumatic brain injury (TBI) adversely affects many brain regions, often resulting in the development of comorbid psychiatric disorders including substance use disorders (SUD). Although traditionally thought to be an epidemic that predominantly affects males, recent clinical studies report females have higher rates of concussions and longer recovery times than males. Yet, how neurotrauma, particularly deep within the brain, between the sexes is differentially manifested remains largely unknown. The risk of TBI peaks during adolescence when neuronal networks that regulate reward behaviors are not fully developed. Previously, using the conditioned place preference (CPP) assay, we found that adolescent TBI increased susceptibility to the rewarding effects of cocaine in male mice. Further, we observed augmented inflammatory profiles, increased microglial phagocytosis of neuronal proteins, and decreased neuronal spine density in the NAc. Notably, the extent of sex differences in SUD susceptibility following TBI has not be investigated. Thus, here we ask the central question of whether the adolescent TBI-induced neuroinflammatory profile at reward centers is divergent in a sex-dependent manner. Using the CPP assay, we found that female mice with high levels of female sex hormones at the time of adolescent TBI demonstrated neuroprotection against increased sensitivity to the rewarding effects of cocaine. These studies also provide evidence of significantly reduced microglial activation and phagocytosis of neuronal proteins within the NAc of females. Overall, our results offer crucial insight into how adolescent TBI impacts the reward pathway in a sex depending manner that could explain a vulnerability to addiction-like behavior.

In Vivo and In Vitro Analyses of Novel Peptidomimetic Disruptors for the Serotonin 5-HT2C Receptor Interaction With Phosphatase and Tensin Homolog.

Hypofunction of the serotonin (5-HT) 5-HT2C receptor (5-HT2CR) has been implicated in a variety of disorders including substance use disorders. As such, approaches to enhance 5-HT2CR signaling display therapeutic potential. In the present study, we show that disruption of the 5-HT2CR interaction with the protein phosphatase and tensin homolog (PTEN) via peptidomimetics enhances 5-HT2CR-mediating signaling in vitro and potentiates selective 5-HT2CR agonists in behavioral rodent models. Overall, the present study provides further evidence that 5-HT2CR activity can be modulated through an allosteric protein–protein interaction. This work provides the groundwork for the continued exploration of protein–protein interactions that can allosterically modulate this critical receptor and other important G protein-coupled receptors (GPCRs) for new therapeutic development through mechanisms that may display clinical utility.

The Underlying Structure of Comorbid Mental Health and Substance Use Disorders in Prison Populations

Background: High rates of mental disorders have been reported for prison populations. Understanding patterns of comorbidity may be essential for the development of adequate treatment interventions. The present study aimed to assess the underlying structure of comorbidity between mental health and substance use disorders in prison populations. Methods: Current mental disorders were assessed using the Mini-International Neuropsychiatric Interview in a cross-sectional observational study of 427 individuals consecutively committed to prison facilities in Santiago, Chile. Five alternative structural models were tested using confirmatory factor analysis (CFA). Latent class analysis of comorbid mental health and substance use disorders was carried out. Results: CFA indicated the best fit for a bifactor model with a general psychopathology P factor and specific internalizing and externalizing factors. Borderline personality disorder loaded highest on the P factor (0.85). The latent comorbidity structure showed a four-class solution representing one class without relevant comorbidities (48% prevalence) and three classes representing the following comorbidities: (1) externalizing disorders including substance use and antisocial personality disorder (31%), (2) internalizing disorders including anxiety disorders (10%), and (3) all types of disorders co-occurring (11%). Major depression and borderline personality disorder were present across all three latent classes of comorbidity. Conclusions: Prison mental health services need to serve a highly comorbid population. Specific approaches may be useful for an externalizing and an internalizing spectrum of disorders. An important group of individuals with all types of mental disorders co-occurring may need new approaches in treatment development.

Promoting Wellness in Older Adults with Mental Illnesses and Substance Use Disorders: Call to Action to All Stakeholders

There are two faces of aging. One face, which reflects the common perception of aging, associates it with an increase in morbidity and mortality and a progressive decline in independence and autonomy. The other face, much less acknowledged despite growing evidence, associates aging with improved mental health including life satisfaction, happiness, and wisdom. It is important to consider both aspects to develop plans for promoting wellness and healthy aging among people with mental disorders including substance use disorders. This article summarizes the current information base, identifies gaps in knowledge, and presents recommendations for a research agenda in this arena.

GABAA Negative Modulation Selectively Attenuates Cocaine Self‐Administration In Rats

GABAA receptors are critical to normal CNS functioning, abundant in brain areas involved in motivational processes and have been implicated in neurological disorders including substance use disorders. Modulation of GABAA receptors can alter the effects of abused drugs including those which do not directly interact with GABAA receptors. Our previous data showed that a low efficacy benzodiazepine‐site negative GABAA modulator will attenuate both toluene and methamphetamine‐facilitated intracranial self‐stimulation in mice and attenuate methamphetamine‐stimulated extracellular dopamine levels in the nucleus accumbens of mice in vivo. Given the critical placement of GABAA receptor populations within dopaminergic drug reward pathways, the current study investigated the hypothesis that negative allosteric modulation of GABAA receptors selectively alters reward circuitry to reduce the abuse‐related effects of cocaine. The effects of the negative GABAA modulator Ro 15,4513 on cocaine self‐administration was examined in adult male Sprague‐Dawley rats. Two groups of rats were trained on a fixed‐ratio 5 (FR5) schedule to self‐administer intravenous injections of 0.1 or 0.3 mg/kg/infusion cocaine in daily 2‐hr sessions. To further assess the selectivity of GABAA negative modulation for altering cocaine's effects, a third group of rats was trained to respond under a FR5 schedule for 45‐mg food pellets. After reaching stable levels of performance the rats were pretreated with vehicle, 0.3, 1 or 3 mg/kg intraperitoneal Ro15‐4513 prior to the 2‐hr operant test sessions. Each test session was separated by at least 3 days of training to allow Ro 15‐4313 washout and reestablish stable baseline rates of lever pressing behavior. Ro15‐4513 dose‐dependently attenuated cocaine self‐administration at both the 0.1 and 0.3 mg/kg/infusion cocaine self‐administration doses with responding almost completely eliminated by 3 mg/kg Ro 15‐4513. In contrast, the same doses of Ro15‐4513 had minimal effects on rates of food reinforced lever‐pressing. These data demonstrate that negative GABAA receptor modulation will attenuate intravenous cocaine self‐administration in male rats at doses that do not impact food‐maintained performance. Overall, our studies and prior data suggest negative modulation of the benzodiazepine‐site on GABAA receptors may be a promising pathway for the development of novel broad spectrum pharmacotherapeutics for substance abuse treatment.

Genetic and Modeling Approaches Reveal Distinct Components of Impulsive Behavior.

Impulsivity is an endophenotype found in many psychiatric disorders including substance use disorders, pathological gambling, and attention deficit hyperactivity disorder. Two behavioral features often considered in impulsive behavior are behavioral inhibition (impulsive action) and delayed gratification (impulsive choice). However, the extent to which these behavioral constructs represent distinct facets of behavior with discrete biological bases is unclear. To test the hypothesis that impulsive action and impulsive choice represent statistically independent behavioral constructs in mice, we collected behavioral measures of impulsivity in a single cohort of mice using well-validated operant behavioral paradigms. Mice with manipulation of serotonin 1B receptor (5-HT1BR) expression were included as a model of disordered impulsivity. A factor analysis was used to characterize correlations between the measures of impulsivity and to identify covariates. Using two approaches, we dissociated impulsive action from impulsive choice. First, the absence of 5-HT1BRs caused increased impulsive action, but not impulsive choice. Second, based on an exploratory factor analysis, a two-factor model described the data well, with measures of impulsive action and choice separating into two independent factors. A multiple-indicator multiple-causes analysis showed that 5-HT1BR expression and sex were significant covariates of impulsivity. Males displayed increased impulsivity in both dimensions, whereas 5-HT1BR expression was a predictor of increased impulsive action only. These data support the conclusion that impulsive action and impulsive choice are distinct behavioral phenotypes with dissociable biological influences that can be modeled in mice. Our work may help inform better classification, diagnosis, and treatment of psychiatric disorders, which present with disordered impulsivity.

Text messaging interventions for individuals with mental health disorders including substance use: A systematic review

We completed a systematic review of the literature to characterize the impact of text messaging interventions on medication adherence or mental health related outcomes in people with mental health disorders including substance use. Four electronic databases were searched from January 1999 to October 2015. Seven studies met our inclusion criteria: three studies evaluated text messaging in patients with schizophrenia or schizoaffective disorder diagnosis, two studies evaluated text messaging in patients with chronic alcohol dependence, and two studies reviewed text messaging in patients with mood disorders. Six studies were randomized controlled trials and one was a prospective pilot study with pre-post intervention design. Text messaging frequency ranged from once weekly to twelve per day. The effect of text messaging on medication adherence was measured in five studies; one study reporting significant improvements in the text messaging intervention group. The effect of text messaging on mental health related outcomes was measured in all seven studies, with five studies showing significant improvements in a variety of psychiatric and social functioning assessments. Collectively, these studies suggest text messaging is a promising tool to support management of patients with mental illness. Further research examining theory-based text messaging interventions in larger samples of patients is required.

The effects of intranasal oxytocin in opioid-dependent individuals and healthy control subjects: a pilot study.

There has been an explosion of research on the potential benefits of the social neuropeptide oxytocin for a number of mental disorders including substance use disorders. Recent evidence suggests that intranasal oxytocin has both direct anti-addiction effects and pro-social effects that may facilitate engagement in psychosocial treatment for substance use disorders. We aimed to assess the tolerability of intranasal oxytocin and its effects on heroin craving, implicit association with heroin and social perceptual ability in opioid-dependent patients receiving opioid replacement therapy (ORT) and healthy control participants. We performed a randomized, double-blind, placebo-controlled, within- and between-subjects, crossover, proof-of-concept trial to examine the effects of oxytocin (40 international units) on a cue-induced craving task (ORT patients only), an Implicit Association Task (IAT), and two social perception tasks: the Reading the Mind in the Eyes Task (RMET) and The Awareness of Social Inference Test (TASIT). Oxytocin was well tolerated by patients receiving ORT but had no significant effects on craving or IAT scores. There was a significant reduction in RMET performance after oxytocin administration versus placebo in the patient group only, and a significant reduction in TASIT performance after oxytocin in both the patient and healthy control groups. A single dose of intranasal oxytocin is well tolerated by patients receiving ORT, paving the way for future investigations. Despite no significant improvement in craving or IAT scores after a single dose of oxytocin and some evidence that social perception was worsened, further investigation is required to determine the role oxytocin may play in the treatment of opioid use disorder. Methadone Oxytocin Option. ClinicalTrials.gov identifier: NCT01728909.

Basal regulation of HPA and dopamine systems is altered differentially in males and females by prenatal alcohol exposure and chronic variable stress.

Effects of prenatal alcohol exposure (PAE) on central nervous system function include an increased prevalence of mental health problems, including substance use disorders (SUD). The hypothalamic-pituitary-adrenal (HPA) and dopamine (DA) systems have overlapping neurocircuitries and are both implicated in SUD. PAE alters both HPA and dopaminergic activity and regulation, resulting in increased HPA tone and an overall reduction in tonic DA activity. However, effects of PAE on the interaction between HPA and DA systems have not been investigated. The present study examined PAE effects on basal regulation of central stress and DA systems in key brain regions where these systems intersect. Adult Sprague-Dawley male and female offspring from prenatal alcohol-exposed (PAE), pairfed (PF), and ad libitum-fed control (C) groups were subjected to chronic variable stress (CVS) or remained as a no stress (non-CVS) control group. Corticotropin releasing hormone (CRH) mRNA, as well as glucocorticoid and DA receptor (DA-R) expression were measured under basal conditions 24h following the end of CVS. We show, for the first time, that regulation of basal HPA and DA systems, and likely, HPA-DA interactions, are altered differentially in males and females by PAE and CVS. PAE augmented the typical attenuation in weight gain during CVS in males and caused increased weight loss in females. Increased basal corticosterone levels in control, but not PAE, females suggest that PAE alters the profile of basal hormone secretion throughout CVS. CVS downregulated basal CRH mRNA in the prefrontal cortex and throughout the bed nucleus of the stria terminalis (BNST) in PAE females but only in the posterior BNST of control females. PAE males and females exposed to CVS exhibited more widespread upregulation of basal mineralocorticoid receptor mRNA throughout the hippocampus, and an attenuated decrease in DA-R expression throughout the nucleus accumbens and striatum compared to CVS-exposed control males and females. Overall, these findings enhance our understanding of PAE effects on the cross-talk between HPA and DA systems, and provide insight into possible mechanisms underlying mental health problems that are related to stress and DA signaling, including SUD, which have a high prevalence among individuals with FASD.

The association between delusional-like experiences, and tobacco, alcohol or cannabis use: a nationwide population-based survey

BackgroundPrevious population-based studies have found that delusional-like experiences (DLE) are prevalent in the community, and are associated with a wide range of mental health disorders including substance use. The aim of the study was to explore the association between DLE and three commonly used substances - tobacco, alcohol and cannabis.MethodsSubjects were drawn from the Australian National Survey of Mental Health and Wellbeing 2007. The Composite International Diagnostic Interview was used to identify DLE, common psychiatric disorders, and substance use. We examined the relationship between the variables of interest using logistic regression, adjusting for potential confounding factors.ResultsOf 8 773 participants, 8.4% (n = 776) subjects endorsed one or more DLE. With respect to tobacco use, compared to nonusers, DLE were more common in those who (a) had daily use, (b) commenced usage aged 15 years or less, and (c) those who smoked heavily (23 or more cigarettes per day). Participants with cannabis use disorders were more likely to endorse DLE; this association was most prominent in those with an onset of 16 years or younger. In contrast, the pattern of association between DLE versus alcohol use or dependence was less consistent, however those with early onset alcohol use disorders were more likely to endorse DLE probe items.ConclusionsWhile cannabis use disorders have been previously linked with DLE, our findings linking alcohol and tobacco use and DLE suggest that the influence of these substances on psychosis-related outcomes warrants closer scrutiny in longitudinal prospective studies.

Incidence of psychopathology in a cohort of young heroin and/or cocaine users

A prospective study was carried out in Barcelona, Spain, to determine the incidence of mental disorders including substance use disorders (SUDs). From a cohort of 288 young adult (aged 18–30 years) cocaine and/or heroin users recruited in nonclinical settings, 158 were reinterviewed 18 months later using the Psychiatric Research Interview for Substance and Mental Disorders. During follow-up, 18% of subjects presented a new SUD, and nearly 11% a new non-SUD Axis I disorder. Incidence was highest for mood disorders (8%). Being a woman, a lower frequency of substance use at baseline, a younger age of heroin first use, and a worsening of SUD were associated with a higher likelihood of presenting a new Axis I disorder. Having received drug treatment ever (at baseline) or during follow-up was not associated with progress of SUD. An overall improvement in the psychiatric status of these young substance users was observed.

Trauma and Substance Use Disorders in Rural and Urban Veterans

Disparities in the prevalence, morbidity, and mortality of multiple mental health conditions have been described between rural and urban populations. However, there is limited information regarding differences in exposure to trauma and trauma-related mental health conditions in these populations. Given the number of veterans who are returning to rural communities after serving in Operation Enduring Freedom and Operation Iraqi Freedom, differences in trauma exposure are of particular relevance. Trauma exposure is related to a variety of mental health disorders including substance use disorders (SUD). The objectives of this preliminary study were to describe lifetime military and nonmilitary trauma and to compare trauma history between rural and urban veterans in SUD treatment. Sixty adults in SUD treatment were enrolled at 3 Veterans Health Administration sites in Nebraska over a 3-month period in 2008. Subjects completed an interview with study staff, which assessed SUD diagnoses and childhood, lifetime, and military trauma. Rural or urban status was determined by self-report of childhood residence. Childhood trauma, lifetime trauma, and response to military trauma were compared between rural and urban veterans. Although there were no significant differences in trauma exposure between rural and urban groups, there was an association between specific types of trauma and measures typically associated with increased substance abuse severity and poorer SUD treatment outcome. This is the first study, to our knowledge, which compared trauma exposure between rural and urban veterans and identified an association between childhood trauma exposure and multiple SUD treatment attempts.