Discriminating cocaine use from other sympathomimetics using wearable electrocardiographic (ECG) sensors.

Background: Our group has established the feasibility of using on-body electrocardiographic (ECG) sensors to detect cocaine use in the human laboratory. The purpose of the current study was to test whether ECG sensors and features are capable of discriminating cocaine use from other non-cocaine sympathomimetics.

Methods: Eleven subjects with cocaine use disorder wore the Zephyr BioHarness™ 3 chest band under six experimental (drug and non-drug) conditions, including 1) laboratory, intravenous cocaine self-administration, 2) after a single oral dose of methylphenidate, 3) during aerobic exercise, 4) during tobacco use (N=7 who smoked tobacco), and 5) during routine activities of daily inpatient living (unit activity).

Genome-wide meta-analysis of alcohol use disorder in East Asians.

Alcohol use disorder (AUD) is a leading cause of death and disability worldwide. Genome-wide association studies (GWAS) have identified ~30 AUD risk genes in European populations, but many fewer in East Asians. We conducted GWAS and genome-wide meta-analysis of AUD in 13,551 subjects with East Asian ancestry, using published summary data and newly genotyped data from five cohorts: (1) electronic health record (EHR)-diagnosed AUD in the Million Veteran Program (MVP) sample; (2) DSM-IV diagnosed alcohol dependence (AD) in a Han Chinese-GSA (array) cohort; (3) AD in a Han Chinese-Cyto (array) cohort; and (4) two AD Thai cohorts.

Lower prefrontal cortical synaptic vesicle binding in cocaine use disorder: An exploratory C-UCB-J positron emission tomography study in humans.

Preclinical studies have revealed robust and long-lasting alterations in dendritic spines in the brain following cocaine exposure. Such alterations are hypothesized to underlie enduring maladaptive behaviours observed in cocaine use disorder (CUD). The current study explored whether synaptic density is altered in CUD.

Reliability and validity of DSM-IV and DSM-5 methamphetamine use disorder diagnoses using the Chinese Version of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA).

Background: The Semi-structured Assessment for Drug Dependence and Alcoholism (SSADDA) was developed to assess substance-use disorders and other psychiatric traits. We translated the SSADDA into Chinese and evaluated its inter-rater reliability and concurrent validity in diagnosing DSM-IV methamphetamine (MA) dependence and DSM-5 MA-use disorder (MUD).

Methods: The sample comprised 231 participants who were interviewed using the Chinese SSADDA and the Mini-International Neuropsychiatric Interview (Chinese MINI) for concurrent validation.

Testing the effects of the GLP-1 receptor agonist exenatide on cocaine self-administration and subjective responses in humans with cocaine use disorder.

Background: Preclinical rodent studies have demonstrated reduced cocaine taking after administration of glucagon-like peptide 1 (GLP-1) analogues. We investigated effects of a GLP-1 analogue (exenatide) on behavioral and subjective effects of cocaine in individuals with cocaine use disorder (CUD).

Methods: Non-treatment-seeking CUD subjects underwent two human laboratory cocaine self-administration test sessions following an acute 3 -h pre-treatment with exenatide (5 mcg; subcutaneously) or placebo.

Dopamine D receptor availability in cocaine use disorder individuals with obesity as measured by [C]PHNO PET.

Background: Positron emission tomography (PET) work with the dopamine D3 receptor (DR) preferring ligand [C]PHNO in obese individuals has demonstrated higher binding and positive correlations with body mass index (BMI) in otherwise healthy individuals. These findings implicated brain reward areas including the substantia nigra/ventral tegmental area (SN/VTA) and pallidum. In cocaine use disorder (CUD), similar SN/VTA binding profiles have been found compared to healthy control subjects.

Multimodal investigation of dopamine D/D receptors, default mode network suppression, and cognitive control in cocaine-use disorder.

Stimulant-use disorders have been associated with lower availability of dopamine type-2 receptors (D2R) and greater availability of type-3 receptors (D3R). Links between D2R levels, cognitive performance, and suppression of the default mode network (DMN) during executive functioning have been observed in healthy and addicted populations; however, there is limited evidence regarding a potential role of elevated D3R in influencing cognitive control processes in groups with and without addictions. Sixteen individuals with cocaine-use disorder (CUD) and 16 healthy comparison (HC) participants completed [C]-(+)-PHNO PET imaging of D2R and D3R availability and fMRI during a Stroop task of cognitive control.

Simplified Quantification of C-UCB-J PET Evaluated in a Large Human Cohort.

C-UCB-J (()-1-((3-(C-methyl-C)pyridin-4-yl)methyl)-4-(3,4,5-trifluorophenyl)pyrrolidin-2-one) is a PET tracer for synaptic vesicle glycoprotein 2A, which may be a marker of synaptic density. To simplify the scan protocol, SUV ratios (SUVRs) were compared with model-based nondisplaceable binding potential () to select the optimal time window in healthy and neuropsychiatric subjects. In total, 141 scans were acquired for 90 min.

Genomewide Association Study of Alcohol Dependence and Related Traits in a Thai Population.

Background: Alcohol use (both quantity and dependence) is moderately heritable, and genomewide association studies (GWAS) have identified risk genes in European, African, and Asian populations. The most reproducibly identified risk genes affect alcohol metabolism. Well-known functional variants at the gene encoding alcohol dehydrogenase B and other alcohol dehydrogenases affect risk in European and African ancestry populations.

Shared microstructural features of behavioral and substance addictions revealed in areas of crossing fibers.

Background: Similarities between behavioral and substance addictions exist. However, direct neurobiological comparison between addictive disorders is rare. Determination of disorder-specificity (or lack thereof) of alterations within white-matter microstructures will advance understanding of the pathophysiology of addictions.

Gray-matter relationships to diagnostic and transdiagnostic features of drug and behavioral addictions.

Alterations in neural structure have been reported in both cocaine-use disorder and gambling disorder, separately, suggesting similarities across addiction diagnoses. Individual variation in neural structure has also been associated with impulsivity, a dimensional construct implicated in addictions. This study combines categorical (diagnosis-based) and dimensional (transdiagnostic) approaches to identify neural structural alterations linked to addiction subtypes and trait impulsivity, respectively, across individuals with gambling disorder (n = 35), individuals with cocaine-use disorder (n = 37) and healthy comparison individuals (n = 37).

Regional and source-based patterns of [C]-(+)-PHNO binding potential reveal concurrent alterations in dopamine D and D receptor availability in cocaine-use disorder.

Dopamine type 2 and type 3 receptors (DR/DR) appear critical to addictive disorders. Cocaine-use disorder (CUD) is associated with lower DR availability and greater DR availability in regions primarily expressing DR or DR concentrations, respectively. However, these CUD-related alterations in DR and DR have not been concurrently detected using available dopaminergic radioligands.

Domain Adaptation Methods for Improving Lab-to-field Generalization of Cocaine Detection using Wearable ECG.

Mobile health research on illicit drug use detection typically involves a two-stage study design where data to learn detectors is first collected in lab-based trials, followed by a deployment to subjects in a free-living environment to assess detector performance. While recent work has demonstrated the feasibility of wearable sensors for illicit drug use detection in the lab setting, several key problems can limit lab-to-field generalization performance. For example, lab-based data collection often has low ecological validity, the ground-truth event labels collected in the lab may not be available at the same level of temporal granularity in the field, and there can be significant variability between subjects.

The Connecticut Mental Health Center: Celebrating 50 Years of a Successful Partnership Between the State and Yale University.

September 28, 2016, marked the 50th anniversary of the Connecticut Mental Health Center, a state-owned and state-operated joint venture between the state and Yale University built and sustained with federal, state, and university funds. Collaboration across these entities has produced a wide array of clinical, educational, and research initiatives, a few of which are described in this column. The missions of clinical care, research, and education remain the foundation for an organization that serves 5,000 individuals each year who are poor and who experience serious mental illnesses and substance use disorders.

Sex Differences in Methamphetamine Use and Dependence in a Thai Treatment Center.

Background And Objective: Males and females who use methamphetamine (MA) differ in sociodemographics, MA diagnoses, comorbidities, and brain activity. The objective of this study was to investigate sex differences in the characteristics of MA use and dependence in patients at a Thai substance treatment center.

Methods: Demographic, MA use, and diagnostic data for 782 MA users were obtained by using the Semi-Structured Assessment for Drug Dependence and Alcoholism-Thai version.

Cocaine dependence and thalamic functional connectivity: a multivariate pattern analysis.

Cocaine dependence is associated with deficits in cognitive control. Previous studies demonstrated that chronic cocaine use affects the activity and functional connectivity of the thalamus, a subcortical structure critical for cognitive functioning. However, the thalamus contains nuclei heterogeneous in functions, and it is not known how thalamic subregions contribute to cognitive dysfunctions in cocaine dependence.

Elevated Dopamine D Receptor Availability in Obese Individuals: A PET Imaging Study with [C](+)PHNO.

Most prior work with positron emission tomography (PET) dopamine subtype 2/3 receptor (DR) non-selective antagonist tracers suggests that obese (OB) individuals exhibit lower DRs when compared with normal weight (NW) individuals. A D-preferring DR agonist tracer, [C](+)PHNO, has demonstrated that body mass index (BMI) was positively associated with DR availability within striatal reward regions. To date, OB individuals have not been studied with [C](+)PHNO.

Age-related changes in binding of the D2/3 receptor radioligand [(11)C](+)PHNO in healthy volunteers.

Objective: Previous imaging studies with positron emission tomography (PET) have reliably demonstrated an age-associated decline in the dopamine system. Most of these studies have focused on the densities of dopamine receptor subtypes D2/3R (D2R family) in the striatum using antagonist radiotracers that are largely nonselective for D2R vs. D3R subtypes.

Modafinil and sleep architecture in an inpatient-outpatient treatment study of cocaine dependence.

Objective: To determine whether the increase in slow-wave sleep associated with modafinil treatment in chronic cocaine users mediates improved clinical outcomes.

Method: 57 cocaine dependent participants were randomized to receive modafinil 400mg or placebo daily during a period of inpatient treatment followed by six weeks of outpatient treatment. Participants underwent polysomnographic sleep recording during inpatient treatment prior to and after starting modafinil.

A preliminary study of dopamine D2/3 receptor availability and social status in healthy and cocaine dependent humans imaged with [(11)C](+)PHNO.

Background: Previous work in healthy non-human primates and humans has shown that social status correlates positively with dopamine 2/3 receptor (D2/3R) availability imaged with antagonist radioligands and positron emission tomography (PET). Further work in non-human primates suggests that this relationship is disrupted by chronic cocaine administration. This exploratory study examined the relationship between social status and D2/3R availability in healthy (HH) and cocaine dependent (CD) humans using the D3-preferring, agonist radioligand, [(11)C](+)PHNO.

Brain Activity During Cocaine Craving and Gambling Urges: An fMRI Study.

Although craving states are important to both cocaine dependence (CD) and pathological gambling (PG), few studies have directly investigated neurobiological similarities and differences in craving between these disorders. We used functional magnetic resonance imaging (fMRI) to assess brain activity in 103 participants (30 CD, 28 PG, and 45 controls) while they watched videos depicting cocaine, gambling, and sad scenarios to investigate the neural correlates of craving. We observed a three-way urge type × video type × diagnostic group interaction in self-reported craving, with CD participants reporting strong cocaine cravings to cocaine videos, and PG participants reporting strong gambling urges to gambling videos.

Ancestry informative markers for distinguishing between Thai populations based on genome-wide association datasets.

The main purpose of this work was to identify a set of AIMs that stratify the genetic structure and diversity of the Thai population from a high-throughput autosomal genome-wide association study. In this study, more than one million SNPs from the international HapMap database and the Thai depression genome-wide association study have been examined to identify ancestry informative markers (AIMs) that distinguish between Thai populations. An efficient strategy is proposed to identify and characterize such SNPs and to test high-resolution SNP data from international HapMap populations.

Deficits in prefrontal cortical and extrastriatal dopamine release in schizophrenia: a positron emission tomographic functional magnetic resonance imaging study.

Importance: Multiple lines of evidence suggest a deficit in dopamine release in the prefrontal cortex (PFC) in schizophrenia. Despite the prevalence of the concept of prefrontal cortical hypodopaminergia in schizophrenia, in vivo imaging of dopamine release in the PFC has not been possible until now, when the validity of using the positron emission tomographic D2/3 radiotracer carbon 11-labeled FLB457 in combination with the amphetamine paradigm was clearly established.

Objectives: To (1) test amphetamine-induced dopamine release in the dorsolateral PFC (DLPFC) in drug-free or drug-naive patients with schizophrenia (SCZ) and healthy control (HC) individuals matched for age, sex, race/ethnicity, and familial socioeconomic status;(2) test blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging activation during a working memory task in the same participants; and (3) examine the relationship between positron emission tomographic and functional magnetic resonance imaging outcome measures.