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Illicit methamphetamine abuse represents a major problem in many countries worldwide, including the United States. Prolonged regular smoking or injection of methamphetamine can cause a psychosis, typically characterized by paranoid delusions and auditory hallucinations and often associated with disturbances in mood. These symptoms may persist long after methamphetamine is discontinued and may prove refractory to antipsychotic medications. The authors describe a patient who developed a typical methamphetamine psychosis that persisted despite months of abstinence from methamphetamine and weeks of treatment with antipsychotic medication but that responded promptly to electroconvulsive therapy (ECT) on two separate occasions: on initial presentation and again a year later when the patient relapsed into methamphetamine abuse and developed psychosis again. The authors review the large international literature on methamphetamine psychosis, much of which is from Japan and has not previously been summarized in English. Persistent methamphetamine psychosis has been widely reported in Japan for more than 50 years but is rarely discussed in the American literature, possibly because some such cases are misdiagnosed in the United States as primary psychotic disorders. Given the growing public health problem of methamphetamine abuse in the United States, the distinction between persistent methamphetamine psychosis and a primary psychotic disorder has grown increasingly important. Thus, American clinicians should be alert to the possibility of methamphetamine psychosis and may wish to consider ECT in refractory cases. [ABSTRACT FROM AUTHOR]

People with HIV and comorbid substance use problems may be among those who benefit most from long-acting HIV antiretroviral treatment, but they are routinely excluded from Phase 3 clinical trials. Their inclusion would permit an examination of the clinical value of long-acting therapies for people with adherence problems and an exploration of syndemic interactions between HIV, mental health conditions, and substance use problems, which compound into a major challenge in the efforts to end the HIV epidemic., Competing Interests: Competing interest’s statement The authors declare no conflicts of interest.

Objectives: People with HIV (PWH) have high rates of depression and neurocognitive impairment (NCI) despite viral suppression on antiretroviral therapy (ART). Mounting evidence suggests that immunometabolic disruptions may contribute to these conditions in some PWH. We hypothesized that metabolic dysfunction in astrocytes is associated with depressive symptoms and cognitive function in PWH., Methods: Human astrocytes were exposed to sera from PWH ( n =40) with varying degrees of depressive symptomatology and cognitive function. MitoTracker TM Deep Red FM (MT) was used to visualize mitochondrial activity and glial fibrillary acidic protein (GFAP) as an indicator of astrocyte reactivity using the high-throughput fluorescent microscopy and image analyses platform, CellInsight CX5 (CX5). The Seahorse platform was used to assess glycolytic and mitochondrial metabolism., Results: More severe depression, as indexed by higher Beck's Depression Inventory (BDI-II) scores, was associated with lower MT signal measures. Better cognitive function, as assessed by neuropsychiatric testing t-scores, was associated with increased MT signal measures. GFAP intensity negatively correlated with several cognitive t-scores. Age positively correlated with (higher) MT signal measures and GFAP intensity. Worse depressive symptoms (higher BDI-II scores) were associated with decreased oxygen consumption rate and spare respiratory capacity, concomitant with increased extracellular acidification rate in astrocytes., Conclusions: These findings show that factors in the sera of PWH alter mitochondrial activity in cultured human astrocytes, suggesting that mechanisms that alter mitochondrial and astrocyte homeostasis can be detected peripherally. Thus, in vitro cultures may provide a model to identify neuropathogenic mechanisms of depression or neurocognitive impairment in PWH and test personalized therapeutics for neurologic and psychiatric disorders., Competing Interests: Competing interests: UCSD (inventor: Jerel Adam Fields) has a patent pending related to this work., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Importance: With increasing medicinal and recreational cannabis legalization, there is a public health need for effective and unbiased evaluations for determining whether a driver is impaired due to Δ9-tetrahydrocannabinol (THC) exposure. Field sobriety tests (FSTs) are a key component of the gold standard law enforcement officer-based evaluations, yet controlled studies are inconclusive regarding their efficacy in detecting whether a person is under the influence of THC., Objective: To examine the classification accuracy of FSTs with respect to cannabis exposure and driving impairment (as determined via a driving simulation)., Design, Setting, and Participants: This double-blind, placebo-controlled parallel randomized clinical trial was conducted from February 2017 to June 2019 at the Center for Medicinal Cannabis Research, University of California, San Diego. Participants were aged 21 to 55 years and had used cannabis in the past month. Data were analyzed from August 2021 to April 2023., Intervention: Participants were randomized 1:1:1 to placebo (0.02% THC), 5.9% THC cannabis, or 13.4% THC cannabis smoked ad libitum., Main Outcome and Measures: The primary end point was law enforcement officer determination of FST impairment at 4 time points after smoking. Additional measures included officer estimation as to whether participants were in the THC or placebo group as well as driving simulator data. Officers did not observe driving performance., Results: The study included 184 participants (117 [63.6%] male; mean [SD] age, 30 [8.3] years) who had used cannabis a mean (SD) of 16.7 (9.8) days in the past 30 days; 121 received THC and 63, placebo. Officers classified 98 participants (81.0%) in the THC group and 31 (49.2%) in the placebo group as FST impaired (difference, 31.8 percentage points; 95% CI, 16.4-47.2 percentage points; P < .001) at 70 minutes after smoking. The THC group performed significantly worse than the placebo group on 8 of 27 individual FST components (29.6%) and all FST summary scores. However, the placebo group did not complete a median of 8 (IQR, 5-11) FST components as instructed. Of 128 participants classified as FST impaired, officers suspected 127 (99.2%) as having received THC. Driving simulator performance was significantly associated with results of select FSTs (eg, ≥2 clues on One Leg Stand was associated with impairment on the simulator: odds ratio, 3.09; 95% CI, 1.63-5.88; P < .001)., Conclusions and Relevance: This randomized clinical trial found that when administered by highly trained officers, FSTs differentiated between individuals receiving THC vs placebo and driving abilities were associated with results of some FSTs. However, the high rate at which the participants receiving placebo failed to adequately perform FSTs and the high frequency that poor FST performance was suspected to be due to THC-related impairment suggest that FSTs, absent other indicators, may be insufficient to denote THC-specific impairment in drivers., Trial Registration: ClinicalTrials.gov Identifier: NCT02849587.

Background: Cannabis is increasingly used both medically and recreationally. With widespread use, there is growing concern about how to identify cannabis-impaired drivers., Methods: A placebo-controlled randomized double-blinded protocol was conducted to study the effects of cannabis on driving performance. One hundred ninety-one participants were randomized to smoke ad libitum a cannabis cigarette containing placebo or delta-9-tetrahydrocannabinol (THC) (5.9% or 13.4%). Blood, oral fluid (OF), and breath samples were collected along with longitudinal driving performance on a simulator (standard deviation of lateral position [SDLP] and car following [coherence]) over a 5-hour period. Law enforcement officers performed field sobriety tests (FSTs) to determine if participants were impaired., Results: There was no relationship between THC concentrations measured in blood, OF, or breath and SDLP or coherence at any of the timepoints studied (P > 0.05). FSTs were significant (P < 0.05) for classifying participants into the THC group vs the placebo group up to 188 minutes after smoking. Seventy-one minutes after smoking, FSTs classified 81% of the participants who received active drug as being impaired. However, 49% of participants who smoked placebo (controls) were also deemed impaired at this same timepoint. Combining a 2 ng/mL THC cutoff in OF with positive findings on FSTs reduced the number of controls classified as impaired to zero, 86 minutes after smoking the placebo., Conclusions: Requiring a positive toxicology result in addition to the FST observations substantially improved the classification accuracy regarding possible driving under the influence of THC by decreasing the percentage of controls classified as impaired., (© American Association for Clinical Chemistry 2023.)

Objectives: People living with HIV (PWH) with substance or alcohol use often have unsuppressed plasma HIV viral loads (pVL). The degree to which substance and alcohol use effects on HIV viral suppression are mediated through medication nonadherence is incompletely understood., Methods: We included PWH prescribed antiretroviral therapy and receiving care at an academic HIV clinic between 2014 and 2018 who completed both patient-reported outcomes (PRO) questionnaires and had subsequent pVL measurements. Measures included assessments of alcohol use (AUDIT-C), drug use (NIDA-ASSIST), and self-reported adherence measured using four different methods. Substances found in bivariate analysis to predict detectable pVL were modeled separately for mediation effects through adherence. We report natural direct (NDE) and indirect effect (NIE), marginal total effect (MTE), and percentage mediated., Results: Among 3125 PWH who met eligibility criteria, 25.8% reported hazardous alcohol use, 27.1% cannabis, 13.1% amphetamines, 1.9% inhalants, 5.3% cocaine, 4.5% sedative-hypnotics, 2.9% opioids, and 2.3% hallucinogens. Excellent adherence was reported by 58% of PWH, and 10% had detectable pVL. Except for sedatives, using other substances was significantly associated with worse adherence. Bivariate predictors of detectable pVL were [OR (95% CI)]: amphetamine use 2.4 (1.8-3.2) and opioid use 2.3 (1.3-4.0). The percent of marginal total effect mediated by nonadherence varied by substance: 36% for amphetamine use, 27% for opioid use, and 39% for polysubstance use., Conclusion: Use of amphetamines, opioids, and multiple substances predicted detectable pVL. Up to 40% of their effects were mediated by self-reported nonadherence. Confirmation using longitudinal measurement models will strengthen causal inference from this cross-sectional analysis., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: EC received research grant funding paid to the Regents of the University of California from Gilead and Merck, and consulting fees for an advisory board from Gilead for unrelated projects. The other authors have no reported conflicts of interest., (© 2023 The Authors.)

Importance: Expanding cannabis medicalization and legalization increases the urgency to understand the factors associated with acute driving impairment., Objective: To determine, in a large sample of regular cannabis users, the magnitude and time course of driving impairment produced by smoked cannabis of different Δ9-tetrahydrocannabinol (THC) content, the effects of use history, and concordance between perceived impairment and observed performance., Design, Setting, and Participants: This double-blind, placebo-controlled parallel randomized clinical trial took place from February 2017 to June 2019 at the Center for Medicinal Cannabis Research, University of California San Diego. Cannabis users were recruited for this study, and analysis took place between April 2020 and September 2021., Interventions: Placebo or 5.9% or 13.4% THC cannabis smoked ad libitum., Main Outcomes and Measures: The primary end point was the Composite Drive Score (CDS), which comprised key driving simulator variables, assessed prior to smoking and at multiple time points postsmoking. Additional measures included self-perceptions of driving impairment and cannabis use history., Results: Of 191 cannabis users, 118 (61.8%) were male, the mean (SD) age was 29.9 (8.3) years, and the mean (SD) days of use in the past month was 16.7 (9.8). Participants were randomized to the placebo group (63 [33.0%]), 5.9% THC (66 [34.6%]), and 13.4% THC (62 [32.5%]). Compared with placebo, the THC group significantly declined on the Composite Drive Score at 30 minutes (Cohen d = 0.59 [95% CI, 0.28-0.90]; P < .001) and 1 hour 30 minutes (Cohen d = 0.55 [95% CI, 0.24-0.86]; P < .001), with borderline differences at 3 hours 30 minutes (Cohen d = 0.29 [95% CI, -0.02 to 0.60]; P = .07) and no differences at 4 hours 30 minutes (Cohen d = -0.03 [95% CI, -0.33 to 0.28]; P = .87). The Composite Drive Score did not differ based on THC content (likelihood ratio χ24 = 3.83; P = .43) or use intensity (quantity × frequency) in the past 6 months (likelihood ratio χ24 = 1.41; P = .49), despite postsmoking blood THC concentrations being higher in those with the highest use intensity. Although there was hesitancy to drive immediately postsmoking, increasing numbers (81 [68.6%]) of participants reported readiness to drive at 1 hour 30 minutes despite performance not improving from initial postsmoking levels., Conclusions and Relevance: Smoking cannabis ad libitum by regular users resulted in simulated driving decrements. However, when experienced users control their own intake, driving impairment cannot be inferred based on THC content of the cigarette, behavioral tolerance, or THC blood concentrations. Participants' increasing willingness to drive at 1 hour 30 minutes may indicate a false sense of driving safety. Worse driving performance is evident for several hours postsmoking in many users but appears to resolve by 4 hours 30 minutes in most individuals. Further research is needed on the impact of individual biologic differences, cannabis use history, and administration methods on driving performance., Trial Registration: ClinicalTrials.gov Identifier: NCT02849587.

Objectives: The COVID-19 pandemic and the resulting social changes have made unprecedented changes in our lifetime with unknown repercussions on children with autism spectrum disorders. We sought to assess the effect of the COVID-19 pandemic and resulting social changes on boys with autism spectrum disorder., Methods: We conducted a survey using the CRISIS-AFAR questionnaire of caregivers of a population of boys ( n  = 40) with moderate to severe autism spectrum disorder for changes in environment and behavior before and after the pandemic., Results: We found several interesting findings, including an increase in self-injurious behaviors after the start of the pandemic, but not in the level of hyperactivity, anxiety, or aggressive behavior, or amount and frequency of stereotypies/repetitive behaviors in the children before and after the start of the pandemic. There was an increased difficulty in adjusting to new daily routines after the pandemic, as well as increased difficulty falling asleep., Conclusions: The study showed that a majority of boys with moderate/severe autism in our study were negatively affected by the pandemic across several domains. Additionally, this study highlights the need for educational and mental health resources to be prepared for similar events in the future., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022.)

Increased prevalence of cannabis consumption and impaired driving are a growing public safety concern. Some states adopted per se driving laws, making it illegal to drive with more than a specified blood concentration of ∆9-tetrahydrocannabinol (THC) in a biological fluid (typically blood). Blood THC concentrations decrease significantly (∼90%) with delays in specimen collection, suggesting the use of alternative matrices, such as oral fluid (OF). We characterized 10 cannabinoids' concentrations, including THC metabolites, in blood and OF from 191 frequent and occasional users by liquid chromatography with tandem mass spectrometry for up to 6 h after ad libitum smoking. Subjects self-titrated when smoking placebo, 5.9 or 13.4% THC cannabis. Higher maximum blood THC concentrations (Cmax) were observed in individuals who received the 5.9% THC versus the 13.4% THC plant material. In blood, the Cmax of multiple analytes, including THC and its metabolites, were increased in frequent compared to occasional users, whereas there were no significant differences in OF Cmax. Blood THC remained detectable (≥5 ng/mL) at the final sample collection for 14% of individuals who smoked either the 5.9 or 13.4% THC cigarette, whereas 54% had detectable THC in OF when applying the same cutoff. Occasional and frequent cannabis users' profiles were compared, THC was detectable for significantly longer duration in blood and OF from frequent users. Detection rates between frequent and occasional users at multiple per se cutoffs showed larger differences in blood versus OF. Understanding cannabinoid profiles of frequent and occasional users and the subsequent impact on detectability with current drug per se driving limits is important to support forensic interpretations and the development of scientifically supported driving under the influence of cannabis laws., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Proving driving under the influence of cannabis (DUIC) is difficult. Establishing a biomarker of recent use to supplement behavioral observations may be a useful alternative strategy. We determined whether cannabinoid concentrations in blood, oral fluid (OF) or breath could identify use within the past 3 h-likely the period of the greatest impairment. In a randomized trial, 191 frequent (≥4/week) and occasional (<4/week) cannabis users smoked one cannabis (placebo [0.02%], or 5.9% or 13.4% Δ9-tetrahydrocannabinol [THC]) cigarette ad libitum. Blood, OF and breath samples were collected prior to and up to 6 h after smoking. Samples were analyzed for 10 cannabinoids in OF, 8 in blood and THC in breath. Frequent users had more residual THC in blood and were more likely to be categorized as 'recently used' prior to smoking; this did not occur in OF. Per se limits ranging from undetectable to 5 ng/mL THC in blood offered limited usefulness as biomarkers of recent use. Cannabinol (CBN, cutoff = 1 ng/mL) in blood offered 100% specificity but only 31.4% sensitivity, resulting in 100% positive predictive value (PPV) and 94.0% negative predictive value (NPV) at 4.3% prevalence; however, CBN may vary by cannabis chemovar. A 10 ng/mL THC cutoff in OF exhibited the overall highest performance to detect its use within 3 h (99.7% specificity, 82.4% sensitivity, 92.5% PPV and 99.2% NPV) but was still detectable in 23.2% of participants ∼4.4 h post-smoking, limiting specificity at later time points. OF THC may be a helpful indicator of recent cannabis intake, but this does not equate to impairment. Behavioral assessment of impairment is still required to determine DUIC. This study only involved cannabis inhalation, and additional research evaluating alternative routes of ingestion (i.e., oral) is needed., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

HIV-associated neurocognitive disorders (HAND) persist despite the advent of antiretroviral therapy (ART), suggesting underlying systemic and central nervous system (CNS) inflammatory mechanisms. The endogenous cannabinoid receptors 1 and 2 (CB 1 and CB 2 ) modulate inflammatory gene expression and play an important role in maintaining neuronal homeostasis. Cannabis use is disproportionately high among people with HIV (PWH) and may provide a neuroprotective effect for those on ART due to its anti-inflammatory properties. However, expression profiles of CB 1 and CB 2 in the brains of PWH on ART with HAND have not been reported. In this study, biochemical and immunohistochemical analyses were performed to determine CB 1 and CB 2 expression in the brain specimens of HAND donors. Immunoblot revealed that CB 1 and CB 2 were differentially expressed in the frontal cortices of HAND brains compared to neurocognitively unimpaired (NUI) brains of PWH. CB 1 expression levels negatively correlated with memory and information processing speed. CB 1 was primarily localized to neuronal soma in HAND brains versus a more punctate distribution of neuronal processes in NUI brains. CB 1 expression was increased in cells with glial morphology and showed increased colocalization with an astroglial marker. These results suggest that targeting the endocannabinoid system may be a potential therapeutic strategy for HAND.

Introduction: To end the HIV epidemic, HIV prevention and pre-exposure prophylaxis (PrEP) promotion efforts must reach young men who have sex with men (YMSM) at greatest risk for HIV. This study qualitatively explored whether common metrics used by clinicians, scientists, and public health officials to objectively assess HIV risk align with how YMSM conceptualize their risk for HIV and the factors that shape YMSM's risk perceptions., Methods: Interviews with a racially/ethnically diverse sample of HIV-negative YMSM (ages 19-24 years, 60% Latinx; n = 20) examined conceptualizations of HIV risk within the context of repeat HIV testing. Iterative, applied thematic analysis examined how participants conceptualized and constructed their HIV risk, and compared participants' descriptions of their risk with a validated quantitative assessment of HIV risk that reliably predicts HIV seroconversion in this group., Results: Objective quantitative assessments of HIV risk poorly aligned with participants' perceived HIV risk. Participants described their current risk in relative terms (relative to past risk and relative to friends'/peers' risk) and described age/developmental stage and changes in knowledge about HIV prevention as key factors in risk changes over time. Other factors included substance use and trust/mistrust in sexual partners and scientific advances in HIV prevention (eg, U = U and PrEP). Factors that influenced participants' perceived HIV risk were similar regardless of objective risk assessment., Conclusions: Quantitative assessments of risk may poorly align with risk perception among YMSM. Although objective metrics can effectively target YMSM at greatest risk for HIV transmission, interventions to improve prevention behaviors and PrEP uptake may be more effective when tailored to bridge the disconnection between objective HIV risk assessments and YMSM's constructions of risk., Competing Interests: Research reported in this article was supported by NIMH R21MH113477 (PI: M.H.). J.K.F. was supported by the California Tobacco-Related Disease Research Program grant T29FT0265 and National Institute on Drug Abuse (NIDA) grant T32DA023356. M.L.M. was supported by NIDA grants T32DA023356 and 3R01DA040648-02S1. L.R.S. was supported by National Institute of Mental Health (NIMH) grant R01MH123282. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health/NIDA/NIMH or the California Tobacco-Related Disease Research Program. K.R.A. reports an educational grant from Gilead Sciences through the University of Michigan completed in 2018; D.J.G. consulted for Greenwich Bioscience, Inc.; M.H. received research funding from Gilead and Pfizer. L.R.S. is a co-investigator on a research study supported by Gilead Sciences. The other authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

HIV infection and methamphetamine (METH) use are highly comorbid and represent a significant public health problem. Both conditions are known to negatively impact a variety of brain functions. One brain function that may be affected by HIV and METH use is sensorimotor gating, an automatic, pre-conscious filtering of sensory information that is thought to contribute to higher order cognitive processes. Sensorimotor gating is often measured using prepulse inhibition (PPI), a paradigm that can be conducted in both humans and animals, thereby enabling cross-species translational studies. While previous studies suggest HIV and METH may individually impair PPI, little research has been conducted on the effects of combined HIV and METH on PPI. The goal of this cross-species study was to determine the effects of METH on PPI in the inducible Tat (iTat) mouse model of HIV and in people with HIV. PPI was measured in the iTat mouse model before, during, and after chronic METH treatment and after Tat induction. Chronic METH treatment decreased PPI in male but not female mice. PPI normalized with cessation of METH. Inducing Tat expression decreased PPI in male but not in female mice. No interactions between chronic METH treatment and Tat expression were observed in mice. In humans, HIV was associated with decreased PPI in both men and women. Furthermore, PPI was lowest in people with HIV who also had a history of METH dependence. Overall, these results suggest HIV and METH may additively impair early information processing in humans, potentially affecting downstream cognitive function., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We examined the joint effects of depressive symptoms (Beck Depression Inventory-II (BDI-II)) and systemic inflammation (plasma C-reactive protein (CRP)) on longitudinal profiles of neurocognition in a cohort of 143 people with HIV (PWH) on antiretroviral therapy. Global neurocognition, processing speed, motor skills, and attention/working memory all worsened as CRP increased but only among PWH who, on average, exhibited moderate to severe depressive symptoms (BDI-II > 22). Findings suggest that some PWH with chronically elevated depressive symptoms may have an inflammatory subtype of depression and a particular vulnerability to neurocognitive changes that may respond to drugs targeting inflammation or its neural sequelae.

Background: HIV-related neuroinflammation has been proposed as a catalyst for dopaminergic dysregulation in mesocortical pathways, which may contribute to the pathogenesis of depression. Abnormalities in dopaminergic neurotransmission and depression are common in people with HIV (PWH), however the link between dopamine (DA) and depression in PWH is poorly characterized. This study investigated CSF dopaminergic biomarkers, specifically DA and its metabolite, homovanillic acid (HVA), and examined their relationship with depressive symptoms and CSF neuroinflammatory markers in PWH and HIV-seronegative (HIV-) individuals., Methods: Participants were 102 HIV- individuals and 123 PWH (mean age = 42) who underwent neuropsychiatric evaluations and lumbar puncture. Current depression severity was classified using the Beck Depression Inventory-II (BDI-II). CSF was assayed for DA and HVA using high performance liquid chromatography and neuroinflammatory markers using immunoassays. Linear regressions modelled BDI-II scores as a function of HIV, dopaminergic biomarker z-scores, and their interaction, controlling for psychosocial factors. Correlational analyses examined dopaminergic and neuroinflammatory relationships., Results: PWH had significantly higher BDI-II scores than HIV- participants. DA and HVA were not associated with HIV status but both significantly moderated the effect of HIV on BDI-II scores, such that PWH exhibited higher depressive symptoms than HIV- participants only at lower concentrations of HVA (z ≤ 0.06) and DA (z ≤ 0.11). In PWH only, lower HVA significantly correlated with higher BDI-II scores and higher neuroinflammation, including higher MCP-1 and IP-10., Conclusions: Results suggest that the pathophysiology of depression in PWH differs from that in HIV- individuals. Specifically, lower central dopaminergic activity was selectively associated with greater depressive symptoms and neuroinflammation in PWH. With the rise in consideration of DA agonists for the treatment of depression, these results suggest that PWH may show a greater response to these agents than their HIV- peers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Whoonga is a smoked heroin-based street drug that first emerged in South Africa a decade ago. While previous scientific reports suggest that use is growing and youth are particularly vulnerable, trajectories of initiation are not well characterized., Methods: In 2015, 30 men undergoing residential addiction treatment for this smoked heroin drug in KwaZulu-Natal, South Africa participated in semi-structured interviews about their experiences using the drug. Interview data were coded using qualitative content analysis., Results: Participant trajectories to initiating smoked heroin were "vertical" in the context of marijuana use or "horizontal" in the context of other hard drug use. Participants reporting vertical trajectories began smoking heroin as youth at school or in other settings where people were smoking marijuana. Several participants with horizontal trajectories started smoking heroin to address symptoms of other drug or alcohol addiction. Social influences on initiation emerged as an overarching theme. Members of participants' social networks who were smoking or distributing heroin figured prominently in initiation narratives. Surprisingly, references to injection drug use were absent from initiation narratives. Participants reported people who smoke heroin differ from those who inject heroin by race., Conclusion: Consistent with theories implicating social and structural influences on substance use initiation, people who started smoking heroin had social contacts who smoked heroin and frequented places where substance use was common. Smoked heroin initiation for several participants with horizontal trajectories may have been averted if they accessed evidence-based treatments for stimulant or alcohol use disorders. With increasing reports of heroin use across Africa, a coordinated approach to address this growing epidemic is needed. However, because smoked heroin and injection heroin use occur in distinct risk environments, interventions tailored to people who use smoked heroin will be needed to prevent smoked heroin use, prevent transition to injection use, and mitigate other social harms., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: The HIV infection may predispose perinatally HIV-infected (PHIV+) adolescents to mental illness. Adolescence can be when mental health disorders manifest for the first time. This study investigates the prevalence of mental illness in PHIV+ and HIV-uninfected adolescents in Soweto., Methods: PHIV+ adolescents aged 13-19 years were recruited from an antiretroviral treatment program, whereas HIV-uninfected controls were recruited from the community in Soweto, South Africa, between October 2016 and April 2017. The Patient Health Questionnaire for Adolescents, Child Post-Traumatic Stress Disorder (PTSD) Checklist, and Millon Adolescent Clinical Inventory tools assessed components of mental health. Sociodemographic and virological data were collected. Risk factors for suicidality were determined by logistic regression., Results: One hundred and sixty-two adolescents (50% PHIV+, 61% female) with a median age of 16 years (interquartile range: 15-18) were enrolled. A depressive disorder was found in 14% of all adolescents, 35% had suicidal ideation, and 22% had PTSD symptoms. Risk factors for suicidality were female gender, HIV-positive status, repeating a grade at school and a history of physical and/or sexual abuse., Conclusions: These findings show a high prevalence of suicidality and PTSD symptoms in adolescents from South Africa and highlight the importance of screening for mental illness, specifically suicidality, in HIV-positive adolescents. Adolescents from a disadvantaged socioeconomic background appear to be at risk, posing a challenge because of the lack of health seeking behaviors in young people and lack of adolescent-friendly health facilities. Interventions specific to adolescents in low- and middle-income countries are needed to improve emotional and psychiatric symptoms and functioning., (Copyright © 2020 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Higher cumulative burden of depression among people with HIV (PWH) is associated with poorer health outcomes; however, longitudinal relationships with neurocognition are unclear. This study examined hypotheses that among PWH, (1) higher cumulative burden of depression would relate to steeper declines in neurocognition, and (2) visit-to-visit depression severity would relate to fluctuations in neurocognition within persons., Setting: Data were collected at a university-based research center from 2002 to 2016., Methods: Participants included 448 PWH followed longitudinally. All participants had >1 visit (M = 4.97; SD = 3.53) capturing depression severity (Beck Depression Inventory-II) and neurocognition (comprehensive test battery). Cumulative burden of depression was calculated using an established method that derives weighted depression severity scores by time between visits and total time on study. Participants were categorized into low (67%), medium (15%), and high (18%) depression burden. Multilevel modeling examined between- and within-person associations between cumulative depression burden and neurocognition over time., Results: The high depression burden group demonstrated steeper global neurocognitive decline compared with the low depression burden group (b = -0.100, P = 0.001); this was driven by declines in executive functioning, delayed recall, and verbal fluency. Within-person results showed that compared with visits when participants reported minimal depressive symptoms, their neurocognition was worse when they reported mild (b = -0.12, P = 0.04) or moderate-to-severe (b = -0.15, P = 0.03) symptoms; this was driven by worsened motor skills and processing speed., Conclusions: High cumulative burden of depression is associated with worsening neurocognition among PWH, which may relate to poor HIV-related treatment outcomes. Intensive interventions among severely depressed PWH may benefit physical, mental, and cognitive health.

Background The widespread availability of cannabis raises concerns regarding its effect on driving performance and operation of complex equipment. Currently, there are no established safe driving limits regarding ∆9-tetrahydrocannabinol (THC) concentrations in blood or breath. Daily cannabis users build up a large body burden of THC with residual excretion for days or weeks after the start of abstinence. Therefore, it is critical to have a sensitive and specific analytical assay that quantifies THC, the main psychoactive component of cannabis, and multiple metabolites to improve interpretation of cannabinoids in blood; some analytes may indicate recent use. Methods A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed to quantify THC, cannabinol (CBN), cannabidiol (CBD), 11-hydroxy-THC (11-OH-THC), (±)-11-nor-9-carboxy-Δ9-THC (THCCOOH), (+)-11-nor-Δ9-THC-9-carboxylic acid glucuronide (THCCOOH-gluc), cannabigerol (CBG), and tetrahydrocannabivarin (THCV) in whole blood (WB). WB samples were prepared by solid-phase extraction (SPE) and quantified by LC-MS/MS. A rapid and simple method involving methanol elution of THC in breath collected in SensAbues® devices was optimized. Results Lower limits of quantification ranged from 0.5 to 2 μg/L in WB. An LLOQ of 80 pg/pad was achieved for THC concentrations in breath. Calibration curves were linear (R2>0.995) with calibrator concentrations within ±15% of their target and quality control (QC) bias and imprecision ≤15%. No major matrix effects or drug interferences were observed. Conclusions The methods were robust and adequately quantified cannabinoids in biological blood and breath samples. These methods will be used to identify cannabinoid concentrations in an upcoming study of the effects of cannabis on driving.

Background: The Zanmi Lasante Depression Symptom Inventory (ZLDSI) is a screening tool for major depression used in 12 primary care clinics in Haiti's Central Plateau. Although previously validated in a clinic-based sample, the present study is the first to evaluate the validity and clinical utility of the ZLDSI for depression screening in a school-based population in central Haiti., Methods: We assessed depressive symptoms in a school-based sample of transitional age youth (18-22 years; n  = 120) with the ZLDSI. Other mental health-related assessments included a modified Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID) for current Major Depressive Episode, the Center for Epidemiologic Studies Depression Scale, and selected items adapted from the Global School-Based Health Survey mental health module. Diagnostic assignments of major depressive episode (MDE) were based on modified SCID interviews., Results: The ZLDSI demonstrated good overall accuracy in identifying current MDE (Area under the Curve = .92, 95% CI = .86, .98, p  < .001). We ascertained ≥12 as the optimal cut-off point to screen for depression with a sensitivity of 100% and a specificity of 73.9%. In addition, the ZLDSI was associated with other measures of depressive symptoms, suggesting that it demonstrates construct validity., Conclusions: Study findings support that the ZLDSI has clinical utility for screening for depression among school-going transitional age youth., Competing Interests: Competing interestsMEG is currently employed by Sage Therapeutics, Inc. The other authors declare that they have no competing interests., (© The Author(s). 2020.)

Objective: Despite potential for dependence and adverse neurological effects, long-term benzodiazepine (BZD) use is common among people living with HIV (PLWH). As PLWH are at risk for central nervous system dysfunction, we retrospectively examined the association between BZD use and HIV-associated neurocognitive impairment (NCI)., Methods: Three hundred six PLWH underwent comprehensive neurobehavioral evaluations. Current BZD use (BZD+) was determined through self-report. Using propensity scores, 153 BZD- individuals were matched to 153 BZD+ participants on demographics and medical comorbidities. Multiple regression models examined NCI and demographically adjusted neurocognitive T-scores as a function of BZD status, adjusting for estimated premorbid ability, current affective symptoms, and nadir CD4 count. Secondary analyses explored neurocognitive correlates of positive BZD urine toxicology screens (TOX+) and specific BZD agents., Results: Median duration of BZD use was 24 months. Current BZD use related to higher likelihood of NCI (odds ratio = 2.13, P = 0.003) and poorer global (d = -0.28, P = 0.020), processing speed (d = -0.23, P = 0.047), and motor T-scores (d = -0.32, P = 0.008). Compared with BZD-/TOX-, BZD+/TOX+ exhibited additional decrements in executive function (d = -0.48, P = 0.013), working memory (d = -0.49, P = 0.011), and delayed recall (d = -0.41, P = 0.032). For individual agents, diazepam, lorazepam, and alprazolam were most strongly associated with NCI (odds ratios >2.31)., Discussion: BZD use may elevate risk for NCI in PLWH, potentially through diffuse neurocognitive slowing and acute compromise of recall and higher-order capacities. These effects are robust to psychosocial and HIV-specific factors and occur in comparison with a tightly matched BZD- group. Prospective and interventional studies should evaluate causal associations between NCI and BZD use and explore treatment alternatives to BZDs in PLWH.

Background: Chronicity of depression among people living with HIV (PLWH) is associated with poorer viral suppression and mortality risk. The extent to which suicidal ideation (SI) and other baseline characteristics predict a prolonged duration of depressive illness among PLWH is not known but could help identify PLWH most at risk., Methods: Data were drawn from a sample of 1002 depressed PLWH engaged in primary care at a metropolitan HIV clinic from 2007-2018, representing 2,569 person-years. Depression characteristics were derived from the Patient Health Questionnaire 9 (PHQ-9), administered during routine screening. Other characteristics were derived from clinic data. Unadjusted and covariate-adjusted survival analyses compared the time to depression remission between depressed participants with and without SI at their initial screening., Results: At baseline, 38.4% of depressed PLWH endorsed SI. Depressed PLWH with SI took significantly longer to achieve remission from depression than those without SI. The association appeared to be mediated by depression symptom severity. When adjusted for age, depression diagnosis, any recent drug use, and depression symptom severity, baseline SI no longer predicted remission hazard., Limitations: Participants were assessed for depression with variable frequency. The analysis assumed all patients received comparable treatment for their depression. Some variables were based on clinic measurements that may be subject to misclassification bias., Conclusions: These data suggest that depressed PLWH with SI are at risk for greater chronicity of depression because their depression is more severe. Accordingly, PLWH should be urgently engaged in psychiatric care in the event of SI or severe depressive symptoms., (Copyright © 2019. Published by Elsevier B.V.)

Background: South Africa has the highest number of people living with HIV (PLWH) and one of the largest antiretroviral therapy (ART) programs globally. High rates of substance use comorbidity exist, including speculation of recreational ART use (i.e., mixing ART with other illicit drugs). Recreational ART use may affect viral load among PLWH due to ART nonadherence and/or viral resistance; however, prior quantitative research has not examined rates of recreational ART use, nor associations with HIV treatment outcomes longitudinally., Methods: Data were drawn from a prospective, observational cohort study (n = 500) of ART-eligible adults recruited from two HIV voluntary counseling and testing centers in Cape Town, and Johannesburg, South Africa. Multiple logistic regression models assessed recreational ART use as a predictor of ART initiation over six months and viral load suppression over nine months, above and beyond other substance use (binge drinking and illicit drug use)., Results: Approximately 5% (n = 24) reported recreational ART use, which was less frequent in Cape Town compared to Johannesburg (AOR = 0.025; 95%CI: 0.003-0.19; p < 0.001). Recreational ART use was not significantly associated with ART initiation or viral suppression. Other substance use, but not recreational ART use, was significantly associated with lower odds of ART initiation (AOR = 0.54; 95%CI: 0.33-0.87; p = .01) and viral suppression (AOR = 0.47; 95%CI: 0.25-0.89; p = .02)., Conclusions: Recreational ART use was infrequent and not uniquely associated with ART initiation or viral suppression. Findings suggest that comorbid use of other substances is ultimately what may make recreational ART use problematic for ongoing engagement in care and viral suppression., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A liquid chromatography tandem mass spectrometry method was developed for quantifying ten cannabinoids in oral fluid (OF). This method utilizes OF collected by the Quantisal™ device and concurrently quantifies cannabinol (CBN), cannabidiol (CBD), Δ 9 -tetrahydrocannabinol (THC), 11-hydroxy-Δ 9 -THC (11-OH-THC), 11-nor-9-carboxy-Δ 9 -THC (THC-COOH), 11-nor-9-carboxy-Δ 9 -THC glucuronide (THC-COOH-gluc), Δ 9 -THC glucuronide (THC-gluc), cannabigerol (CBG), tetrahydrocannabiverin (THCV), and Δ 9 -tetrahydrocannabinolic acid A (THCA-A). Solid phase extraction was optimized using Oasis Prime HLB 30 mg 96-well plates. Cannabinoids were separated by liquid chromatography over a BEH C18 column and detected by a Waters TQ-S micro tandem mass spectrometer. The lower limits of quantification (LLOQ) were 0.4 ng/mL for CBN, CBD, THC, 11-OH-THC, THC-gluc, and THCV; and 1.0 ng/mL for THC-COOH, THC-COOH-gluc, CBG and THCA-A. Linear ranges extended to 2000 ng/mL for THC and 200 ng/mL for all other analytes. Inter-day analytical bias and imprecision at three levels of quality control (QC) was within ±15%. Mean extraction efficiencies ranged from 26.0-98.8%. Applicability of this method was tested using samples collected from individuals randomly assigned to smoke either a joint containing <0.1%, 5.9%, or 13.4% THC content. This method was able to identify and calculate the concentration of 6 of 10 cannabinoids validated in this method., (Published by Elsevier B.V.)

Background: A recent meta-analysis affirmed the benefit of medicinal cannabis for chronic neuropathic pain, a disabling and difficult-to-treat condition. As medicinal cannabis use is becoming increasingly prevalent among Americans, an exploration of its economic feasibility is warranted. We present this cost-effectiveness analysis of adjunctive cannabis pharmacotherapy for chronic peripheral neuropathy. Materials and Methods: A published Markov model comparing conventional therapies for painful diabetic neuropathy was modified to include arms for augmenting first-line, second-line (if first-line failed), or third-line (if first- and second-line failed) therapies with smoked cannabis. Microsimulation of 1,000,000 patients compared the cost (2017 U.S. dollars) and effectiveness (quality-adjusted life years [QALYs]) of usual care with and without adjunctive cannabis using a composite of third-party and out-of-pocket costs. Model efficacy inputs for cannabis were adapted from clinical trial data. Adverse event rates were derived from a prospective study of cannabis for chronic noncancer pain and applied to probability inputs for conventional therapies. Cannabis cost was derived from retail market pricing. Parameter uncertainty was addressed with one-way and probabilistic sensitivity analysis. Results: Adding cannabis to first-line therapy was incrementally less effective and costlier than adding cannabis to second-line and third-line therapies. Third-line adjunctive cannabis was subject to extended dominance, that is, the second-line strategy was more effective with a more favorable incremental cost-effectiveness ratio of $48,594 per QALY gained, and therefore, third-line adjunctive cannabis was not as cost-effective. At a modest willingness-to-pay threshold of $100,000/QALY gained, second-line adjunctive cannabis was the strategy most likely to be cost-effective. Conclusion: As recently proposed willingness-to-pay thresholds for the United States health marketplace range from $110,000 to $300,000 per QALY, cannabis appears cost-effective when augmenting second-line treatment for painful neuropathy. Further research is warranted to explore the long-term benefit of smoked cannabis and standardization of its dosing for chronic neuropathic pain., Competing Interests: No competing financial interests exist.

Little is known about disparities in depression prevalence, treatment, and remission by psychiatric comorbidities and substance use among persons living with HIV (PLWH). We conducted a cross-sectional analysis in a large cohort of PLWH in routine care and analyzed conditional probabilities of having an indication for depression treatment, receiving treatment, receiving indicated treatment adjustments, and achieving remission, stratified by alcohol use, illicit drug use, and panic symptoms. Overall, 34.7% (95% CI 33.9-35.5%) of participants had an indication for depression treatment and of these, 55.3% (53.8-56.8%) were receiving antidepressants. Among patients receiving antidepressants, 33.0% (31.1-34.9%) had evidence of remitted depression. In a subsample of sites with antidepressant dosage data, only 8.8% (6.7-11.5%) of patients received an indicated treatment adjustment. Current drug users (45.8%, 95% CI 43.6-48.1%) and patients reporting full symptoms of panic disorder (75.0%, 95% CI 72.9-77.1%) were most likely to have an indication for antidepressant treatment, least likely to receive treatment given an indication (current drug use: 47.6%, 95% CI 44.3-51.0%; full panic symptoms: 50.8%, 95% CI 48.0-53.6%), or have evidence of remitted depression when treated (22.3%, 95% CI 18.5-26.6%; and 7.3%, 95% CI 5.5-9.6%, respectively). In a multivariable model, drug use and panic symptoms were independently associated with poorer outcomes along the depression treatment cascade. Few differences were evident by alcohol use. Current drug users were most likely to have an indication for depression treatment, but were least likely to be receiving treatment or to have remitted depression. These same disparities were even more starkly evident among patients with co-occurring symptoms of panic disorder compared to those without. Achieving improvements in the depression treatment cascade will likely require attention to substance use and psychiatric comorbidities.

The association between earthquakes and youth post-traumatic stress disorder (PTSD) has been well described, but little is known about the relationship between other stressful life events (SLEs) and PTSD among earthquake-affected youth. This study examines a variety of SLEs, including earthquake, and their association with PTSD among school-going Haitian youth following a major earthquake in 2010. In 2013, we assessed 120 students ages 18-22 for PTSD and other SLEs using a modified Structured Clinical Interview for DSM-IV (SCID)-based interview and the Stressful Life Events Checklist (SLE Checklist). Only 51.7% of participants on the SLE Checklist and 31.7% in the interview endorsed being affected by the earthquake or another disaster. Sexual assault showed the strongest association with PTSD in multivariable logistic regression. Contrary to our hypothesis, exposure to earthquake or another disaster was not significantly associated with current PTSD. In this population, exposure to interpersonal violence may have had a greater impact on PTSD risk than exposure to natural disaster. These data underscore the need to examine and reduce both acute and chronic stressors among disaster-affected youth., (Copyright © 2018. Published by Elsevier B.V.)

This study evaluates the use of a mental health mobile clinic to overcome two major challenges to the provision of mental healthcare in resource-limited settings: the shortage of trained specialists; and the need to improve access to safe, effective, and culturally sound care in community settings. Employing task-shifting and supervision, mental healthcare was largely delivered by trained, non-specialist health workers instead of specialists. A retrospective chart review of 318 unduplicated patients assessed and treated during the mobile clinic's first two years (January 2012 to November 2013) was conducted to explore outcomes. These data were supplemented by a quality improvement questionnaire, illustrative case reports, and a qualitative interview with the mobile clinic's lead community health worker. The team evaluated an average of 42 patients per clinic session. The most common mental, neurological, or substance abuse (MNS) disorders were depression and epilepsy. Higher follow-up rates were seen among those with diagnoses of bipolar disorder and neurological conditions, while those with depression or anxiety had lower follow-up rates. Persons with mood disorders who were evaluated on at least two separate occasions using a locally developed depression screening tool experienced a significant reduction in depressive symptoms. The mental health mobile clinic successfully treated a wide range of MNS disorders in rural Haiti and provided care to individuals who previously had no consistent access to mental healthcare. Efforts to address these common barriers to the provision of mental healthcare in resource-limited settings should consider supplementing clinic-based with mobile services., Competing Interests: The authors have declared that no competing interests exist.

Background: Prescription records, manual chart review, and patient self-report are each imperfect measures of depression treatment in HIV-infected adults., Methods: We compared antidepressant prescription records in an electronic data warehouse with antidepressant treatment and psychotherapy identified via manual chart review and self-report for patients at 6 academic HIV treatment centers. We examined concordance among these three sources, and used latent class analysis (LCA) to estimate sensitivity and specificity of each measure., Results: In our charts sample (n = 586), 59% had chart indication of "any depression treatment" and 46% had a warehouse prescription record. Antidepressant use was concordant between charts and data warehouse for 77% of the sample. In our self-report sample (n = 677), 52% reported any depression treatment and 43% had a warehouse prescription record. Self-report of antidepressant treatment was consistent with prescription records for 71% of the sample. LCA estimates of sensitivity and specificity for "any depression treatment" were 67% and 90% (warehouse), 87% and 75% (self-report), and 96% and 77% (chart)., Limitations: There is no gold standard to measure depression treatment. Antidepressants may be prescribed to patients for conditions other than depression. The results may not be generalizable to patient populations in non-academic HIV clinics. Regarding LCA, dependence of errors may have led to overestimation of sensitivity and specificity., Conclusions: Prescription records were largely concordant with self-report and chart review, but there were discrepancies. Studies of depression in HIV-infected patients would benefit from using multiple measures of depression treatment or correcting for exposure misclassification., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Importance: Depression commonly affects adults with HIV and complicates the management of HIV. Depression among individuals with HIV tends to be chronic and cyclical, but the association of this chronicity with HIV outcomes (and the related potential for screening and intervention to shorten depressive episodes) has received little attention., Objective: To examine the association between increased chronicity of depression and multiple HIV care continuum indicators (HIV appointment attendance, treatment failure, and mortality)., Design, Setting, and Participants: The study comprised an observational clinical cohort of 5927 patients with 2 or more assessments of depressive severity who were receiving HIV primary care at 6 geographically dispersed US academic medical centers from September 22, 2005, to August 6, 2015., Main Outcomes and Measures: Missing a scheduled HIV primary care visit, detectable HIV RNA viral load (≥75 copies/mL), and all-cause mortality. Consecutive depressive severity measures were converted into a time-updated measure: percentage of days with depression (PDD), following established methods for determining depression-free days., Results: During 10 767 person-years of follow-up, the 5927 participants (5000 men, 926 women, and 1 intersex individual; median age, 44 years [range, 35-50 years]) had a median PDD of 14% (interquartile range, 0%-48%). During follow-up, 10 361 of 55 040 scheduled visits (18.8%) were missed, 6191 of 28 455 viral loads (21.8%) were detectable, and the mortality rate was 1.5 deaths per 100 person-years. Percentage of days with depression showed a dose-response relationship with each outcome. Each 25% increase in PDD led to an 8% increase in the risk of missing a scheduled appointment (risk ratio, 1.08; 95% CI, 1.05-1.11), a 5% increase in the risk of a detectable viral load (risk ratio, 1.05; 95% CI, 1.01-1.09), and a 19% increase in the mortality hazard (hazard ratio, 1.19; 95% CI, 1.05-1.36). These estimates imply that, compared with patients who spent no follow-up time with depression (PDD, 0%), those who spent the entire follow-up time with depression (PDD, 100%) faced a 37% increased risk of missing appointments (risk ratio, 1.37; 95% CI, 1.22-1.53), a 23% increased risk of a detectable viral load (risk ratio, 1.23; 95% CI, 1.06-1.43), and a doubled mortality rate (hazard ratio, 2.02; 95% CI, 1.20-3.42)., Conclusions and Relevance: Greater chronicity of depression increased the likelihood of failure at multiple points along the HIV care continuum. Even modest increases in the proportion of time spent with depression led to clinically meaningful increases in negative outcomes. Clinic-level trials of protocols to promptly identify and appropriately treat depression among adults living with HIV should be conducted to understand the effect of such protocols on shortening the course and preventing the recurrence of depressive illness and improving clinical outcomes.

Background: Task-sharing with teachers to promote youth mental health is a promising but underdeveloped strategy in improving care access in low-income countries., Aims: To assess feasibility, acceptability and utility of the teacher accompaniment phase of a school-based Teacher- Accompagnateur Pilot Study (TAPS) in Haiti., Methods: We assigned student participants, aged 18-22 years ( n = 120), to teacher participants ( n = 22) within four Haitian schools; we instructed participants to arrange meetings with their assigned counterparts to discuss mental health treatment, academic skills, and/or well-being. We measured student and teacher perceived feasibility, acceptability and utility of meetings with self-report Likert-style questions. We examined overall program feasibility by the percentage of students with a documented meeting, acceptability by a composite measure of student satisfaction and utility by the percentage with identified mental health need who discussed treatment with a teacher., Results: Favorable ratings support feasibility, acceptability and utility of teacher- accompagnateur meetings with students. The majority of students (54%) met with a teacher. Among students with an identified mental disorder, 43.2% discussed treatment during a meeting., Conclusion: This accompaniment approach to mental health task-sharing with teachers provided a school-based opportunity for students with mental health need to discuss treatment and has potential relevance to other low-income settings.

Background: The mental health treatment gap for youth in low- and middle-income countries (LMICs) is substantial; strategies for redress are urgently needed to mitigate the serious health and social consequences of untreated mental illness in youth., Aims: To estimate the burden of major depressive episode (MDE) and posttraumatic stress disorder (PTSD) as well as utilization of care among Haitian youth in order to describe the mental health treatment gap in a LMIC setting., Methods: We estimated the point prevalence of MDE, PTSD, and subthreshold variants in a school-based sample of youth ( n = 120, ages 18-22 years) using a modified Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID)-based interview and examined treatment utilization among those receiving one of these diagnoses. We assessed additional psychopathology with self-report measures to examine validity of study diagnostic assignments., Results: The combined prevalence of full-syndrome or subthreshold MDE or PTSD was high (36.7%). A large majority of affected individuals (88.6%) had accessed no mental health services in the health sector, and 36.4% had accessed no care of any kind in either the health or folk sectors in the past year., Conclusion: Findings demonstrate a high mental health burden among Haiti's youth and that many youth with MDE and PTSD are not accessing mental health care.

Background: Engagement and training of educators in student mental health holds promise for promoting access to care as a task sharing strategy but has not been well-studied in low-income regions., Methods: We used a prospective and convergent mixed methods design to evaluate a customized school mental health 2½ day training for teachers in rural Haiti ( n  = 22) as the initial component of formative research developing a school-based intervention to promote student mental health. Training prepared teachers to respond to student mental health needs by providing psychoeducational and practical support to facilitate access to care. We examined level of participation and evaluated feasibility, acceptability, and perceived effectiveness by calculating mean scores on self-report Likert-style items eliciting participant experience. We examined effectiveness of the training on improving mental health knowledge and attitudes by comparing mean scores on an assessment administered pre- and post-training. Finally, we examined self-report written open-ended responses and focus group discussion (FGD) interview data bearing on perceived feasibility, acceptability, and effectiveness to contextualize participant ratings of training and to identify recommendations for enhancing the utility of mental health training locally for educators., Results: Mean scores of knowledge and attitudes significantly improved between the pre-test and post-tests; e.g., knowledge improved from 58% correct at baseline to 68% correct on the second post-test ( p  = 0.039). Mean ratings of the training were favorable across all categories and FGD data demonstrated widespread participant endorsement of training acceptability and effectiveness; participants recommended extending the duration and number of training sessions., Conclusions: Findings support feasibility, acceptability, and a limited scope of effectiveness of brief mental health training for secondary school teachers in Haiti. Further development of approaches to engage teachers in promoting school mental health through training is warranted.

Depression and substance use are significant obstacles to effective HIV care. Using data derived from a randomized controlled trial of persons with HIV who are homeless or marginally housed, this study assesses the utility of antidepressant treatment among persons with HIV, depression, and active substance use. Participants were diagnosed with depressive disorders and randomly assigned to receive directly observed therapy with fluoxetine or a referral to community mental health treatment. Assessments, conducted at baseline and every 3 months over a 9-month period, included the Hamilton Rating Scale for Depression, the Beck Depression Inventory II, and self-report of alcohol, crack, cocaine, heroin, or methamphetamine use in the past 90 days. To investigate the effect of antidepressant treatment in the setting of active substance use, the authors fit mixed-effects linear regression models to estimate the effect of directly observed fluoxetine on depressive symptom severity after stratifying by any alcohol use or any illicit drug use. To investigate whether alcohol use or illicit drug use moderated the antidepressant treatment response, the authors examined the interaction terms. The effect of directly observed fluoxetine treatment on depression symptom severity was statistically significant irrespective of alcohol use status. When stratified by illicit drug use status, the effect of directly observed fluoxetine treatment on depression symptom severity was statistically significant only among persons who did not use illicit drugs. The interaction terms were not statistically significant. This study found a benefit of antidepressant treatment in persons with HIV, depression, and alcohol use. In addition, this study found no evidence that either alcohol use or illicit drug use moderates the antidepressant treatment response. Altogether, these findings support the use of antidepressant medication in this population. The public health impact of research in this area is significant given the known adverse effects of depression on HIV-related health outcomes. ClinicalTrials.gov Identifier: NCT00338767.

Background: Worldwide, there is a gap between the burden of mental distress and disorder and access to mental health care. This gap is particularly large in low- and middle-income countries (LMICs). After the 2010 earthquake in Haiti, the international health care organizations Partners in Health and Zanmi Lasante worked to expand local mental health services in rural Haiti., Objective: The aims of this study are to describe clinical characteristics of the patients served during a pilot project to deliver community-based psychiatric services in rural Haiti and to show how this experience complements the Mental Health Gap Action Programme ("mhGAP"), a tool developed by the World Health Organization to support mental health care delivery by nonspecialists in LMICs., Methods: The pilot was conducted in March 2011. A visiting psychiatrist traveled to rural Haiti and paired with local clinicians to evaluate patients and to support quality improvement practices in psychiatric care. Patients received a standard neuropsychiatric evaluation. mhGAP was an important clinical reference. To assess the experience, we conducted a retrospective chart review of outpatient encounters., Findings: Sixty-five patients presented with a wide range of common psychiatric, neurologic, and general medical conditions. Forty-nine of these patients (75%) reported primary problems subsumed by an mhGAP module. Fifteen patients (23%) reported headache as their chief complain, a condition that is not currently covered by mhGAP. Surprisingly, only 3 patients (5%), reported earthquake-related distress., Conclusions: Our clinical data reinforce the need for provision of standard psychiatric and neurologic services in LMICs. Such services ought to accompany interventions targeted specifically at disaster-related problems. Clinical situations falling outside existing mhGAP modules inspired the development of supplemental treatment protocols. These observations informed coordinated efforts at Zanmi Lasante to build a sustainable, integrated mental health system in Haiti that may be relevant to other resource-limited settings., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Young adults in South Africa are at the epicenter of the HIV epidemic. The prevalence of HIV among young people in the province of KwaZulu-Natal (KZN) is particularly high. This study characterizes inkwari (Zulu word for raves or weekend-long parties) in eThekwini District, KZN and explored how these place-based dynamics shape the risk environment for the young adult attendees. In 2011, 13 qualitative interviews were conducted with men and women between 18 and 30 years-old who reported unprotected sex with at least one casual partner in the prior 3 months and attended an inkwari in the same time period. Interviews were analyzed using qualitative content analysis. Nine key informant interviews helped to triangulate these data. Five women and eight men were interviewed and the mean age was 25 years (SD 3.24). Ten reported meeting a sexual partner at an inkwari. Inkwari were characterized as sexualized settings with limited adult supervision. Participants attended inkwari to socialize with peers, use drugs and alcohol, and meet sexual partners. Sexual and physical violence also occurred at inkwari. Given the convergence of social, sexual, and substance-using networks at inkwari, further inquiry is needed to determine how this place may potentiate HIV transmission risk in an endemic setting.

Developing mental health care capacity in postearthquake Haiti is hampered by the lack of assessments that include culturally bound idioms Haitians use when discussing emotional distress. The current paper describes a novel emic-etic approach to developing a depression screening for Partners in Health/Zanmi Lasante. In Study 1 Haitian key informants were asked to classify symptoms and describe categories within a pool of symptoms of common mental disorders. Study 2 tested the symptom set that best approximated depression in a sample of depressed and not depressed Haitians in order to select items for the screening tool. The resulting 13-item instrument produced scores with high internal reliability that were sensitive to culturally informed diagnoses, and interpretations with construct and concurrent validity (vis-à-vis functional impairment). Discussion focuses on the appropriate use of this tool and integrating emic perspectives into developing psychological assessments globally. The screening tool is provided as an Appendix., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Objective: The catatonic syndrome ("catatonia") is characterized by motor and motivation dysregulation and is associated with a number of neuropsychiatric and medical disorders. It is recognizable in a variety of clinical settings. We present observations from the treatment of four individuals with catatonia in Haiti and Rwanda and introduce a treatment protocol for use in resource-limited settings., Methods: Four patients from rural Haiti and Rwanda with clinical signs of catatonia and a positive screen using the Bush-Francis Catatonia Rating Scale were treated collaboratively by general physicians and mental health clinicians with either lorazepam or diazepam. Success in treatment was clinically assessed by complete remittance of catatonia symptoms., Results: The four patients in this report exhibited a range of characteristic and recognizable signs of catatonia, including immobility/stupor, stereotypic movements, echophenomena, posturing, odd mannerisms, mutism and refusal to eat or drink. All four cases presented initially to rural outpatient general health services in resource-limited settings. In some cases, diagnostic uncertainty initially led to treatment with typical antipsychotics. In each case, proper identification and treatment of catatonia with benzodiazepines led to significant clinical improvement., Conclusion: Catatonia can be effectively and inexpensively treated in resource-limited settings. Identification and management of catatonia are critical for the health and safety of patients with this syndrome. Familiarity with the clinical features of catatonia is essential for health professionals working in any setting. To facilitate early recognition of this treatable disorder, catatonia should feature more prominently in global mental health discourse., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Media reports have described recreational use of HIV antiretroviral medication in South Africa, but little has been written about this phenomenon in the scientific literature. We present original, qualitative data from eight semi-structured interviews that characterize recreational antiretroviral use in Soweto, South Africa. Participants reported that antiretrovirals, likely efavirenz, are crushed, mixed with illicit drugs (in a mixture known as whoonga), and smoked. They described medications being stolen from patients and expressed concern that antiretroviral abuse jeopardized the safety of both patients and users. Further studies are needed to understand the prevalence, patterns, and consequences of antiretroviral abuse and diversion.

Whoonga is a drug cocktail in South Africa rumored to contain illicit drugs and HIV antiretroviral (ARV) medication. Although its use may adversely impact adherence to HIV treatment and may have the potential to generate ARV resistance, there is a paucity of research characterizing whoonga. We learned of whoonga during semi-structured interviews about substance abuse and HIV risk at "club-events" known as inkwaris in an urban township of Durban, South Africa. Whoonga was an emerging theme spontaneously identified as a problem for the community by 17 out of 22 informants. Perceptions of whoonga suggest that it is highly addictive, contains ARVs (notably efavirenz), is used by individuals as young as 14, and poses a threat to the health and safety of those who use it, including increasing the risk of HIV infection. Our informants provide preliminary evidence of the dangers of whoonga and reinforce the need for further study.

Uncovering the etiology of a bowel obstruction in a patient with a hernia represents a diagnostic dilemma. Although the hernia is often initially the presumptive cause of the bowel obstruction, obstructive carcinoma or another pathological process hidden by the hernia are important considerations. Here we describe a case of a man with an obstructing neoplasm of the colon within a large ventral hernia, whose constipation was initially attributed to incarceration of the hernia.

Abnormal hypoactivation in the amygdala and fusiform gyrus, brain areas that participate in face processing and social cognition, has consistently been demonstrated in persons with autism. We investigated activity in these areas in a boy with autism, DD, who had a special interest in "Digimon" cartoon characters. DD individuates Digimon faster than familiar faces and objects, but he individuates familiar faces no faster than objects. In contrast, a typically developing boy with an interest in "Pokemon" cartoon characters is equally fast at individuating faces and Pokemon and faster at individuating faces and Pokemon than objects and Digimon. In addition, using functional magnetic resonance imaging (fMRI), we show that DD activates his amygdala and fusiform gyrus for perceptual discriminations involving Digimon but not for those involving familiar or unfamiliar faces. This pattern of activation is not seen in the typically developing control with an interest in Pokemon or in a second comparison case who has autism but no interest in Digimon. These results have important implications for our understanding of autism, cortical face specialization, and the possible role of the amygdala in the development of perceptual expertise.

A region in the lateral aspect of the fusiform gyrus (FG) is more engaged by human faces than any other category of image. It has come to be known as the 'fusiform face area' (FFA). The origin and extent of this specialization is currently a topic of great interest and debate. This is of special relevance to autism, because recent studies have shown that the FFA is hypoactive to faces in this disorder. In two linked functional magnetic resonance imaging (fMRI) studies of healthy young adults, we show here that the FFA is engaged by a social attribution task (SAT) involving perception of human-like interactions among three simple geometric shapes. The amygdala, temporal pole, medial prefrontal cortex, inferolateral frontal cortex and superior temporal sulci were also significantly engaged. Activation of the FFA to a task without faces challenges the received view that the FFA is restricted in its activities to the perception of faces. We speculate that abstract semantic information associated with faces is encoded in the FG region and retrieved for social computations. From this perspective, the literature on hypoactivation of the FFA in autism may be interpreted as a reflection of a core social cognitive mechanism underlying the disorder.

Investigations of face processing in persons with an autism spectrum disorder (ASD) inform upon theories of the development of "normal" face processing, and the story that emerges challenges some models of the nature and origin of cortical face specialization. Individuals with an ASD possess deficits in face processing and a lack of a fusiform face area (FFA). Evidence from studies of ASD can be conceptualized best using an expertise framework of face processing rather than models that postulate a face module in the fusiform gyrus. Because persons with an ASD have reduced social interest, they may fail to develop cortical face specialization. Face specialization may develop in normal individuals because they are socially motivated to regard the face, and such motivation promotes expertise for faces. The amygdala is likely the key node in the system that marks objects as emotionally salient and could be crucial to the development of cortical face specialization., (Copyright 2002 Wiley Periodicals, Inc.)