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At-home rapid antigen tests provide a convenient and expedited resource to learn about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection status. However, low sensitivity of at-home antigen tests presents a challenge. This study examines the accuracy of at-home tests, when combined with computer-facilitated symptom screening.The study used primary data sources with data collected during 2 phases at different periods (phase 1 and phase 2): one during the period in which the alpha variant of SARS-CoV-2 was predominant in the United States and another during the surge of the delta variant. Four hundred sixty-one study participants were included in the analyses from phase 1 and 374 subjects from phase 2. Phase 1 data were used to develop a computerized symptom screening tool, using ordinary logistic regression with interaction terms, which predicted coronavirus disease-2019 (COVID-19) reverse transcription polymerase chain reaction (RT-PCR) test results. Phase 2 data were used to validate the accuracy of predicting COVID-19 diagnosis with (1) computerized symptom screening; (2) at-home rapid antigen testing; (3) the combination of both screening methods; and (4) the combination of symptom screening and vaccination status. The McFadden pseudo-R2 was used as a measure of percentage of variation in RT-PCR test results explained by the various screening methods.The McFadden pseudo-R2 for the first at-home test, the second at-home test, and computerized symptom screening was 0.274, 0.140, and 0.158, respectively. Scores between 0.2 and 0.4 indicated moderate levels of accuracy. The first at-home test had low sensitivity (0.587) and high specificity (0.989). Adding a second at-home test did not improve the sensitivity of the first test. Computerized symptom screening improved the accuracy of the first at-home test (added 0.131 points to sensitivity and 6.9% to pseudo-R2 of the first at-home test). Computerized symptom screening and vaccination status was the most accurate method to screen patients for COVID-19 or an active infection with SARS-CoV-2 in the community (pseudo-R2 = 0.476).Computerized symptom screening could either improve, or in some situations, replace at-home antigen tests for those individuals experiencing COVID-19 symptoms.

Although at-home coronavirus disease-2019 (COVID-19) testing offers several benefits in a relatively cost-effective and less risky manner, evidence suggests that at-home COVID-19 test kits have a high rate of false negatives. One way to improve the accuracy and acceptance of COVID-19 screening is to combine existing at-home physical test kits with an easily accessible, electronic, self-diagnostic tool. The objective of the current study was to test the acceptability and usability of an artificial intelligence (AI)-enabled COVID-19 testing tool that combines a web-based symptom diagnostic screening survey and a physical at-home test kit to test differences across adults from varying races, ages, genders, educational, and income levels in the United States.A total of 822 people from Richmond, Virginia, were included in the study. Data were collected from employees and patients of Virginia Commonwealth University Health Center as well as the surrounding community in June through October 2021. Data were weighted to reflect the demographic distribution of patients in United States. Descriptive statistics and repeated independent t tests were run to evaluate the differences in the acceptability and usability of an AI-enabled COVID-19 testing tool.Across all participants, there was a reasonable degree of acceptability and usability of the AI-enabled COVID-19 testing tool that included a physical test kit and symptom screening website. The AI-enabled COVID-19 testing tool demonstrated overall good acceptability and usability across race, age, gender, and educational background. Notably, participants preferred both components of the AI-enabled COVID-19 testing tool to the in-clinic testing.Overall, these findings suggest that our AI-enabled COVID-19 testing approach has great potential to improve the quality of remote COVID testing at low cost and high accessibility for diverse demographic populations in the United States.

Study Objectives In adult populations, women are more likely than men to be prescribed benzodiazepines. However, such disparities have not been investigated in people with opioid use disorder (OUD) and insomnia receiving buprenorphine, a population with particularly high sedative/hypnotic receipt. This retrospective cohort study used administrative claims data from Merative MarketScan Commercial and MultiState Medicaid Databases (2006–2016) to investigate sex differences in the receipt of insomnia medication prescriptions among patients in OUD treatment with buprenorphine. Methods We included people aged 12–64 years with diagnoses of insomnia and OUD-initiating buprenorphine during the study timeframe. The predictor variable was sex (female versus male). The primary outcome was receipt of insomnia medication prescription within 60 days of buprenorphine start, encompassing benzodiazepines, Z-drugs, or non-sedative/hypnotic insomnia medications (e.g. hydroxyzine, trazodone, and mirtazapine). Associations between sex and benzodiazepine, Z-drug, and other insomnia medication prescription receipt were estimated using Poisson regression models. Results Our sample included 9510 individuals (female n = 4637; male n = 4873) initiating buprenorphine for OUD who also had insomnia, of whom 6569 (69.1%) received benzodiazepines, 3891 (40.9%) Z-drugs, and 8441 (88.8%) non-sedative/hypnotic medications. Poisson regression models, adjusting for sex differences in psychiatric comorbidities, found female sex to be associated with a slightly increased likelihood of prescription receipt: benzodiazepines (risk ratio [RR], RR = 1.17 [1.11–1.23]), Z-drugs (RR = 1.26 [1.18–1.34]), and non-sedative/hypnotic insomnia medication (RR = 1.07, [1.02–1.12]). Conclusions Sleep medications are commonly being prescribed to individuals with insomnia in OUD treatment with buprenorphine, with sex-based disparities indicating a higher prescribing impact among female than male OUD treatment patients.

The causes of substance use disorders (SUDs) are largely unknown and the effectiveness of their treatments is limited. One crucial impediment to research and treatment progress surrounds how SUDs are classified and diagnosed. Given the substantial heterogeneity among individuals diagnosed with a given SUD (e.g., alcohol use disorder [AUD]), identifying novel research and treatment targets and developing new study designs is daunting.In this article, we review and integrate two recently developed frameworks, the National Institute on Drug Abuse's Phenotyping Assessment Battery (NIDA PhAB) and the Hierarchical Taxonomy of Psychopathology (HiTOP), that hope to accelerate progress in understanding the causes and consequences of psychopathology by means of deep phenotyping, or finer-grained analysis of phenotypes.NIDA PhAB focuses on addiction-related processes across multiple units of analysis, whereas HiTOP focuses on clinical phenotypes and covers a broader range of psychopathology. We highlight that NIDA PhAB and HiTOP together provide deep and broad characterizations of people diagnosed with SUDs and complement each other in their efforts to address widely known limitations of traditional classification systems and their diagnostic categories. Next, we show how NIDA PhAB and HiTOP can be integrated to facilitate optimal rich phenotyping of addiction-related phenomena. Finally, we argue that such deep phenotyping promises to advance our understanding of the neurobiology of SUD and addiction, which will guide the development of personalized medicine and interventions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

PURPOSE OF REVIEW: Opioid-related deaths are a leading cause of mortality during pregnancy through 12 months postpartum. Buprenorphine use during pregnancy is increasing, yet expert opinion on its dosing through the perinatal period is limited. We provide a review of the current clinical literature on buprenorphine dosing during pregnancy through 12 months postpartum. and present data from a retrospective chart review of patients at our institution describing trends in buprenorphine dosing during pregnancy and postpartum. Utilizing this information, we synthesize findings to provide clinical recommendations for providers. RECENT FINDINGS: Existing literature during pregnancy reflects how many women increase and split total daily buprenorphine doses as gestational age advances. SUMMARY: We present data from a retrospective chart review of patients at our institution describing trends in buprenorphine dosing during pregnancy and postpartum. Utilizing this information, we synthesize findings to provide clinical recommendations for providers. Changes in the total daily dose of buprenorphine used across pregnancy and through 12 months postpartum at the individual level do not follow consistent patterns, highlighting substantial individual variability. Altogether, buprenorphine dosing should be individualized through pregnancy and postpartum with frequent evaluations by providers and solicited input from patients.

Background: The differential utility of neurocognitive impulsivity and externalizing/ internalizing traits as putative endophenotypes for dependence on heroin vs. amphetamine is unclear. Objective: This exploratory study aims to determine: (1) whether neurocognitive impulsivity dimensions and externalizing/internalizing traits are correlated between siblings discordant for heroin and amphetamine dependence; and (2) which of these associations are common across substances and which are substance- specific. Methods: Pearson correlations between individuals with ‘pure’ heroin and amphetamine dependence and their unaffected biological siblings (n = 37 heroin sibling pairs; n = 30 amphetamine sibling pairs) were run on 10 neurocognitive measures, 6 externalizing measures, and 5 internalizing measures. Sibling pair effects were further examined using regression. Results: Siblings discordant for heroin dependence were significantly correlated on delay aversion on the Cambridge Gambling Task, risk-taking on the Balloon Analogue Risk Task, sensation seeking, and hopelessness. Siblings discordant for amphetamine dependence were significantly correlated on the quality of decision-making on the Cambridge Gambling Task, discriminability on the Immediate Memory Task, commission errors on the Go/No Go Task, trait impulsivity, ADHD and anxiety sensitivity. Conclusion: Dimensions of impulsivity and externalizing/internalizing traits appear to aggregate among siblings discordant for substance dependence. Risk-taking propensity, sensation seeking and hopelessness were specific for heroin sibling pairs. Motor/action impulsivity, trait impulsivity, and anxiety sensitivity were specific to amphetamine sibling pairs. Decisional/choice impulsivity was common across both heroin and amphetamine sibling pairs. These findings provide preliminary evidence for the utility of neurocognitive impulsivity and externalizing/ internalizing traits as candidate endophenotypes for substance dependence in general and for substance-specific dependencies.

BackgroundChronic substance use and its effects on brain function and structure has long been of interest to clinicians and researchers. Prior cross-sectional comparisons of diffusion tensor imaging (DTI) metrics have suggested deleterious effects of chronic substance use (i.e., cocaine use) on white matter integrity (WM). However, it is unclear how these effects may replicate with improving DTI technologies to enhance detection of substance use-related WM decrements. In this study, we sought to conduct a replication of previous work in this area and determine whether there are any patterns of persistent differences in WM microstructure between individuals with a history of Cocaine Use Disorder (CocUD, according to DSM-IV) and healthy controls. Method46 participants (21 healthy controls, 25 chronic cocaine users) were recruited from the Richmond, Virginia metropolitan area. Information regarding past and current substance use was collected from all participants. Participants also completed structural and DTI scans.ResultsConsistent with previous DTI studies, significant differences between CocUD and controls were found in FA and AD between groups, with CocUD showing lower FA and AD in the right inferior and superior longitudinal fasciculus; the genu, body, and splenium of the corpus callosum; and the anterior, posterior, and superior corona radiata, among several other regions. These differences were not significant for other diffusivity metrics. Lifetime alcohol consumption was greater in the CocUD group, but lifetime alcohol consumption did not show a significant linear relationship with any of the DTI metrics in within-group regression analyses.ConclusionsThese data align with previously reported declines in WM integrity in chronic cocaine users. However, it is less clear whether comorbid alcohol consumption results in an additive deleterious effect on WM microstructure.

Past investigations utilizing diffusion tensor imaging (DTI) have demonstrated that cocaine use disorder (CUD) yields white matter changes, primarily in the corpus callosum. By applying Bayesian model averaging using multiple linear regression in DTI, we demonstrate there may exist relationships between the impaired white matter and glutamic acid decarboxylase (GAD) polymorphisms. This work explored the two-way and three-way interactions between GAD1a (SNP: rs1978340) and GAD1b (SNP: rs769390) polymorphisms and years of cocaine use (YCU). GAD1a was associated with more frontal white matter changes on its own but GAD1b was associated with more midbrain and cerebellar changes as well as a greater increase in white matter changes in the context of chronic cocaine use. The three-way interaction GAD1a|GAD1b|YCU appeared to be roughly an average of the polymorphism two-way interactions GAD1a|YCU and GAD1b|YCU. The three-way interaction demonstrated multiple regions including corpus callosum which featured fewer significant voxel changes, perhaps suggesting a small protective effect of having both polymorphisms on corpus callosum and cerebellar peduncle.

Cocaine use disorder (CUD) patients display heterogenous symptoms and unforeseeable responses to available treatment approaches, highlighting the need to identify objective, accessible biobehavioral signatures to predict clinical trial success in this population. In the present experiments, we employed a task-based behavioral and pharmacogenetic-fMRI approach to address this gap. Craving, an intense desire to take cocaine, can be evoked by exposure to cocaine-associated stimuli which can trigger relapse during attempted recovery. Attentional bias towards cocaine-associated words is linked to enhanced effective connectivity (EC) from the anterior cingulate cortex (ACC) to hippocampus in CUD participants, an observation which was replicated in a new cohort of participants in the present studies. Serotonin regulates attentional bias to cocaine and the serotonergic antagonist mirtazapine decreased activated EC associated with attentional bias, with greater effectiveness in those CUD participants carrying the wild-type 5-HT2CR gene relative to a 5-HT2CR single nucleotide polymorphism (rs6318). These data suggest that the wild-type 5-HT2CR is necessary for the efficacy of mirtazapine to decrease activated EC in CUD participants and that mirtazapine may serve as an abstinence enhancer to mitigate brain substrates of craving in response to cocaine-associated stimuli in participants with this pharmacogenetic descriptor. These results are distinctive in outlining a richer “fingerprint” of the complex neurocircuitry, behavior and pharmacogenetics profile of CUD participants which may provide insight into success of future medications development projects.

Food intake is essential for survival, but maladaptive patterns of intake, possibly encoded by a preexisting vulnerability coupled with the influence of environmental variables, can modify the reward value of food. Impulsivity, a predisposition toward rapid unplanned reactions to stimuli, is one of the multifaceted determinants underlying the etiology of dysregulated eating and its evolving pathogenesis. The medial prefrontal cortex (mPFC) is a major neural director of reward-driven behavior and impulsivity. Compromised signaling between the mPFC and nucleus accumbens shell (NAcSh) is thought to underlie the cognitive inability to withhold prepotent responses (motor impulsivity) and binge intake of high-fat food (HFF) seen in binge eating disorder. To explore the relationship between motor impulsivity and binge-like eating in rodents, we identified high (HI) and low impulsive (LI) rats in the 1-choice serial reaction time task and employed a rat model of binge-like eating behavior. HFF binge rats consumed significantly greater calories relative to control rats maintained on continual access to standard food or HFF. HI rats repeatedly exhibited significantly higher bingeing on HFF vs. LI rats. Next, we employed dual viral vector chemogenetic technology which allows for the targeted and isolated modulation of ventral mPFC (vmPFC) neurons that project to the NAcSh. Chemogenetic activation of the vmPFC to NAcSh pathway significantly suppressed motor impulsivity and binge-like intake for high-fat food. Thus, inherent motor impulsivity and binge-like eating are linked and the vmPFC to NAcSh pathway serves as a 'brake' over both behaviors.

Attentional function in substance use disorder (SUD) is not well understood. To probe attentional function in SUD as a function of primary substance of abuse, we administered the attentional network task (ANT) to 44 individuals with Cocaine Use Disorder (CoUD), 49 individuals with Cannabis Use Disorder (CaUD), 86 individuals with Opioid Use Disorder (OUD), and 107 controls with no SUD, along with the stop-signal task (SST). The ANT quantifies the effects of (temporal) alerting cues and (spatial) orienting cues to reduce reaction time (RT) to targets, as well as probing how conflicting (target-incongruent) stimuli slow RT. The SST quantifies individuals' ability to inhibit already-initiated motor responses. After controlling for sex representation and age, OUD and CaUD participants showed blunted alerting effects compared to controls, whereas CaUD and CoUD participants showed greater stimulus conflict (flanker) effects. Finally, CoUD participants showed a trend toward increased orienting ability. In SST performance, no SUD group showed a prolonged stop-signal reaction compared to controls. However, the OUD group (and CoUD group at trend level) showed prolonged "go" RT to targets and reduced hit rates. These data indicate differences in attentional function in persons with SUD as a function of the primary substance use.

Positive social connections are crucial for recovery from Substance Use Disorder (SUD). Of interest is understanding potential social information processing (SIP) mediators of this effect. To explore whether persons with different SUD show idiosyncratic biases toward social signals, we administered an emotional go-nogo task (EGNG) to 31 individuals with Cocaine Use Disorder (CoUD), 31 with Cannabis Use Disorder (CaUD), 79 with Opioid Use Disorder (OUD), and 58 controls. Participants were instructed to respond to emotional faces (Fear/Happy) but withhold responses to expressionless faces in two task blocks, with the reverse instruction in the other two blocks. Emotional faces as non-targets elicited more “false alarm” (FA) commission errors as a main effect. Groups did not differ in overall rates of hits (correct responses to target faces), but participants with CaUD and CoUD showed reduced rates of hits (relative to controls) when expressionless faces were targets. OUD participants had worse hit rates [and slower reaction times (RT)] when fearful faces (but not happy faces) were targets. CaUD participants were most affected by instruction effects (respond/“go” vs withhold response/“no-go” to emotional face) on discriminability statistic A. Participants were faster to respond to happy face targets than to expressionless faces. However, this pattern was reversed in fearful face blocks in OUD and CoUD participants. This experiment replicated previous findings of the greater salience of expressive face images, and extends this finding to SUD, where persons with CaUD may show even greater bias toward emotional faces. Conversely, OUD participants showed idiosyncratic behavior in response to fearful faces suggestive of increased attentional disruption by fear. These data suggest a mechanism by which positive social signals may contribute to recovery.

Background and objectives Current methods of classifying individuals with substance use disorder (SUD) result in vast heterogeneity among persons within a given diagnosis. These approaches, while clinically allowing for distinctions between patient groups, are less than ideal when attempting to recruit a neurobehaviorally defined subset of subjects into clinical trials. To address this gap, alternative strategies have been proposed, including behavioral phenotyping. The NIDA Phenotyping Assessment Battery (PhAB) is a modular package of assessments and neurocognitive tasks that was developed for use in clinical trials. The goal of the present study is to assess the feasibility of the NIDA PhAB with regard to ease of administration and time burden. Methods Healthy controls, persons with cocaine use disorder (CocUD), opioid use disorder (OUD), cannabis use disorder (CanUD), and combined opioid and cocaine use disorder (OCUD) were recruited from various sources (N = 595). Participants completed screening and one to three assessment visits. Time to complete the measures was recorded and a satisfaction interview was administered. Results Of the participants enrolled, 381 were deemed eligible. The majority of eligible participants (83%) completed all assessments. The average completion time was 3 hours. High participant satisfaction ratings were noted, with over 90% of participants endorsing a willingness to participate in a similar study and recommend the study to others. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: These findings corroborate the ease with which the PhAB may be easily incorporated into a study assessment visit without undue participant burden. The PhAB is an efficient method for behavioral phenotyping in addiction clinical trials. (Am J Addict 2021;00:00-00).

Geostatistical modeling for continuous point-referenced data has extensively been applied to neuroimaging because it produces efficient and valid statistical inference. However, diffusion tensor imaging (DTI), a neuroimaging technique characterizing the brain's anatomical structure, produces a positive-definite (p.d.) matrix for each voxel. Currently, only a few geostatistical models for p.d. matrices have been proposed because introducing spatial dependence among p.d. matrices properly is challenging. In this paper, we use the spatial Wishart process, a spatial stochastic process (random field), where each p.d. matrix-variate random variable marginally follows a Wishart distribution, and spatial dependence between random matrices is induced by latent Gaussian processes. This process is valid on an uncountable collection of spatial locations and is almost-surely continuous, leading to a reasonable way of modeling spatial dependence. Motivated by a DTI data set of cocaine users, we propose a spatial matrix-variate regression model based on the spatial Wishart process. A problematic issue is that the spatial Wishart process has no closed-form density function. Hence, we propose an approximation method to obtain a feasible Cholesky decomposition model, which we show to be asymptotically equivalent to the spatial Wishart process model. A local likelihood approximation method is also applied to achieve fast computation. The simulation studies and real data application demonstrate that the Cholesky decomposition process model produces reliable inference and improved performance, compared to other methods.

BACKGROUND. Takotsubo syndrome (TS) is an acute, reversible form of heart failure, often mimicking an acute coronary syndrome (ACS). Data regarding racial differences in TS are inconsistent. The aim is to assess clinical features associated with unfavorable in-hospital outcomes between African American (AA) and Caucasian (CAU) patients. METHODS. A retrospective electronic health record query identified 44 AA patients and 110 CAU patients with a diagnosis of TS. Our primary outcome was a composite of death, stroke, and cardiogenic shock during hospitalization. Variables associated with an increased risk of the primary composite outcomes were included in a logistic regression model. RESULTS. Compared to CAU patients, AA patients were a more comorbid population, and presented a higher prevalence of history of illicit drug use (27.3% vs 13.6% p=0.044). There were no significant differences regarding in-hospital complication rates between AA and CAU patients. In the logistic regression model, infection was associated with greater risk of developing the primary outcome in AA patients (OR=7.26 95% CI [1.22–43.17], p=0.029), whereas angina was a protective factor (OR=0.11 95% CI [0.02–0.65], p=0.015). In CAU patients, severely depressed ejection fraction and worse peak creatinine during hospitalization increased risk of developing the primary outcome (OR=5.88 95% CI [2.01–17.17], p

The rate at which the coronavirus disease (COVID-19) spread required a rapid response across many, if not all, industries. Academic medical centers had to rapidly evaluate, prioritize, and coordinate the multiple requests for clinical trial participation. This involved redirecting resources and developing a collaborative system for assessment, decision making, and implementation. Our institution formed a team with diverse representation from multiple stakeholders to review and prioritize all research protocols related to COVID-19. To accomplish this, a prioritization matrix was developed to help determine the order in which the protocols should be placed for consideration by the treating clinician. The purpose of the team was to review the COVID-19 clinical trials in the pipeline, prioritize those trials that best met the needs of our patients, oversee training and resource needs, and lead the formulation of procedures for integration with clinical care. Resources from the Clinical Research Unit were then allocated to support the swift execution of such studies. This manuscript describes that process, the challenges encountered, and the lessons learned on how to make all clinical trials more successful in a complex and dynamic environment.

This study compares the numbers of nonfatal, unintentional opioid-related opioid overdoses presenting to a US urban emergency department during the early months of the coronavirus disease 2019 (COVID-19) pandemic (March-June 2020) vs 2019, overall and by age, race/ethnicity, and insurance status.

Background Marijuana use increases cardiac sympathetic activity within minutes of its use and this effect may begin to decrease as soon as one hour after marijuana use. However, the cardiovascular effects of marijuana use more than an hour after use is poorly characterized. The purpose of the current study is to compare heart rate, a marker of cardiac sympathetic activity, across recent marijuana use groups (never used=63; recent use [in the past 24 hours; subacute] = 13; in the past 7 days, but not in the past 24 hours = 17). Overall, the current sample included 93 African American/Black college students, with a mean age of 20.03 (SD = 2.21). Methods Participants completed a demographic form, a brief battery of psychological questionnaires, and had their heart rate assessed at baseline. Results Analysis of covariance showed that heart rate was statistically significantly lower in the recent use group (M = 62.38) compared with the non-users group (M = 73.92). This difference persisted before and after statistically adjusting for demographic covariates. Conclusions These results suggest that there may be a cardiovascular process that occurs when using marijuana that results in a compensatory, reduced heart rate.

Contemporary research has enriched our knowledge of mechanisms involved in the generation and persistence of the debilitating disorders characterized by an “addictive dimensionality,” such as substance use disorders and binge eating disorder. Personalized treatment strategies for addictive disorders might include one or a combination of medications at important stages in detoxification and recovery to reduce craving, assist in establishing a substance-free state, and open the optimal window to allow cognitive restructuring and enhanced inhibitory control of substance-seeking. The overlapping neural systems and brain circuitry involved across addictive disorders have elevated interest in the metabolic and neural regulators serotonin (5-hydroxytryptamine; 5-HT) and ghrelin. This chapter focuses on these systems as examples of how we can broaden our horizons for advancing future therapeutic and biomarker initiatives.

There is a growing clinical literature linking impulsivity to drug cue reactivity in individuals with substance misuse. Evidence supporting this link comes from studies using a variety of behavioral laboratory measures of impulsivity and drug cue reactivity. This link is not surprising considering the nature of impulsivity and drug cue reactivity, which both have elements of a stimulus driven reaction to the environment. This chapter describes in detail the literature supporting this link and discusses the potential neurobiology of the overlap based on brain imaging. Last, some potential treatments that target both impulsivity and drug cue reactivity are discussed.

Relapse during abstinence in cocaine use disorder (CUD) is often hastened by high impulsivity (predisposition toward rapid unplanned reactions to stimuli without regard to negative consequences) and high cue reactivity (e.g., attentional bias towards drug reward stimuli). A deeper understanding of the degree to which individual biological differences predict or promote problematic behaviors may afford opportunities for clinical refinement and optimization of CUD diagnostics and/or therapies. Preclinical evidence implicates serotonin (5-HT) neurotransmission through the 5-HT2A receptor (5-HT2AR) as a driver of individual differences in these relapse-related behaviors. Regulation of 5-HT2AR function occurs through many mechanisms, including DNA methylation of the HTR2A gene, an epigenetic modification linked with the memory of gene-environment interactions. In the present study, we tested the hypothesis that methylation of the HTR2A may associate with relapse-related behavioral vulnerability in cocaine-dependent participants versus healthy controls. Impulsivity was assessed by self-report (Barratt Impulsiveness Scale; BIS-11) and the delay discounting task, while levels of cue reactivity were determined by performance in the cocaine-word Stroop task. Genomic DNA was extracted from lymphocytes and the bisulfite-treated DNA was subjected to pyrosequencing to determine degree of methylation at four cytosine residues of the HTR2A promoter (-1439, -1420, -1224, -253). We found that the percent methylation at site -1224 after correction for age trended towards a positive correlation with total BIS-11 scores in cocaine users, but not healthy controls. Percent methylation at site -1420 negatively correlated with rates of delay discounting in healthy controls, but not cocaine users. Lastly, the percent methylation at site -253 positively correlated with attentional bias toward cocaine-associated cues. DNA methylation at these cytosine residues of the HTR2A promoter may be differentially associated with impulsivity or cocaine-associated environmental cues. Taken together, these data suggest that methylation of the HTR2A may contribute to individual differences in relapse-related behaviors in CUD.

Impulsivity and the attentional orienting response to cocaine-associated cues (cue reactivity) promote relapse in cocaine-use disorder (CUD). A time-dependent escalation of cue reactivity (incubation) occurs during extended, forced abstinence from cocaine self-administration in rats. The investigational serotonin (5-HT) 5-HT2A receptor (5-HT2AR) antagonist/inverse agonist M100907 suppresses impulsive action, or the inability to withhold premature responses, and cocaine-seeking behaviors. The present preclinical study was designed to establish the potential for repurposing the Food and Drug Administration–approved selective 5-HT2AR antagonist/inverse agonist pimavanserin as a therapeutic agent to forestall relapse vulnerability in CUD. In male Sprague-Dawley rats, pimavanserin suppressed impulsive action (premature responses) measured in the 1-choice serial reaction time (1-CSRT) task, similarly to M100907. We also used the 1-CSRT task to establish baseline levels of impulsive action before cocaine self-administration and evaluation of cue reactivity (lever presses reinforced by the discrete cue complex previously paired with cocaine delivery). We observed an incubation of cocaine cue reactivity between day 1 and day 30 of forced abstinence from cocaine self-administration. Baseline levels of impulsive action predicted incubated levels of cocaine cue reactivity in late abstinence. We also found that baseline impulsive action predicted the effectiveness of pimavanserin to suppress incubated cue reactivity in late abstinence from cocaine self-administration at doses that were ineffective in early abstinence. These data suggest that integration of clinical measures of impulsive action may inform refined, personalized pharmacotherapeutic intervention for the treatment of relapse vulnerability in CUD.

Stress cardiomyopathy is an acute reversible heart failure syndrome initially believed to represent a benign condition due to its self-limiting clinical course, but now recognized to be associated with a non-negligible rate of serious complications such as ventricular arrhythmias, systemic thromboembolism, and cardiogenic shock. Due to an increased awareness and recognition, the incidence of stress cardiomyopathy has been rising (15-30 cases per 100,000 per year), although the true incidence is unknown as the condition is likely underdiagnosed. Stress cardiomyopathy represents a form of neurocardiogenic myocardial stunning, and while the link between the brain and the heart is established, the exact pathophysiological mechanisms remain unclear. We herein review the proposed risk factors and triggers for the syndrome and discuss a practical approach to diagnosis and treatment of the patients with stress cardiomyopathy, highlighting potential challenges and unresolved questions.