Faculty Bibliography

Individuals with alcohol use disorders show white matter abnormality relative to normal samples, but differences in white matter profiles have not yet been investigated as a function of abstinence. Individuals with current alcohol use disorders (AUD-C; n = 10), individuals with alcohol use disorders in remission for at least 1 year (AUD-R; n = 9), and healthy control participants (HC; n = 15) matched to alcohol groups on age and smoking status underwent MRI. Diffusion tensor imaging (DTI) data were analyzed using tract-based spatial statistics (TBSS). Compared with HC, AUD-C showed reduced axial diffusivity in bilateral frontal and temporal white matter. In AUD-R, lower fractional anisotropy relative to HC was widespread in bilateral parietal regions. A combined AUD-C and AUD-R group had decreased fractional anisotropy primarily in the fornix and thalamus. In conclusion, AUD-R manifested damage in parietal regions integral to processing of visuospatial information and self-awareness whereas AUD-C showed abnormal diffusivity in fronto-temporal regions that regulate impulsivity, attention, and memory. As a combined group, AUD individuals exhibited abnormality in subcortical areas associated with sensory processing and memory. White matter differences in individuals with AUD may be attributable to premorbid vulnerability or persisting effects of alcohol abuse, but the pattern of abnormality across groups suggests that these abnormalities may be secondary to alcohol use.

PURPOSE: To identify individual- and neighborhood-level correlates of membership within high HIV prevalence drug networks. METHODS: We recruited 378 New York City drug users via respondent-driven sampling (2006-2009). Individual-level characteristics and recruiter-recruit relationships were ascertained and merged with 2000 tract-level U.S. Census data. Descriptive statistics and population average models were used to identify correlates of membership in high HIV prevalence drug networks (>10.54% vs. <10.54% HIV). RESULTS: Individuals in high HIV prevalence drug networks were more likely to be recruited in neighborhoods with greater inequality (adjusted odds ratio [AOR], 5.85; 95% confidence interval [CI], 1.40-24.42), higher valued owner-occupied housing (AOR, 1.48; 95% CI, 1.14-1.92), and a higher proportion of Latinos (AOR, 1.83; 95% CI, 1.19-2.80). They reported more crack use (AOR, 7.23; 95% CI, 2.43-21.55), exchange sex (AOR, 1.82; 95% CI, 1.03-3.23), and recent drug treatment enrollment (AOR, 1.62; 95% CI, 1.05-2.50) and were less likely to report cocaine use (AOR, 0.40; 95% CI, 0.20-0.79) and recent homelessness (AOR, 0.32; 95% CI, 0.17-0.57). CONCLUSIONS: The relationship between exchange sex, crack use, and membership within high HIV prevalence drug networks may suggest an ideal HIV risk target population for intervention. Coupling network-based interventions with those adding risk-reduction and HIV testing/care/adherence counseling services to the standard of care in drug treatment programs should be explored in neighborhoods with increased inequality, higher valued owner-occupied housing, and a greater proportion of Latinos.

At stake in the May 2013 publication of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), are billions of dollars in insurance payments and government resources, as well as the diagnoses and treatment of millions of patients. We argue that the most recent revision process has missed social determinants of mental health disorders and their diagnosis: environmental factors triggering biological responses that manifest themselves in behavior; differing cultural perceptions about what is normal and what is abnormal behavior; and institutional pressures related to such matters as insurance reimbursements, disability benefits, and pharmaceutical marketing. In addition, the experts charged with revising the DSM lack a systematic way to take population-level variations in diagnoses into account. To address these problems, we propose the creation of an independent research review body that would monitor variations in diagnostic patterns, inform future DSM revisions, identify needed changes in mental health policy and practice, and recommend new avenues of research. Drawing on the best available knowledge, the review body would make possible more precise and equitable psychiatric diagnoses and interventions.

RATIONALE: Chronic food restriction (FR) increases rewarding effects of abused drugs and persistence of a cocaine-conditioned place preference (CPP). When there is a single daily meal, circadian rhythms are correspondingly entrained, and pre- and postprandial periods are accompanied by different circulating levels of metabolic hormones that modulate brain dopamine function. OBJECTIVES: The present study assessed whether rewarding effects of d-amphetamine, cocaine, and persistence of cocaine-CPP differ between FR subjects tested in the pre- and postprandial periods. MATERIALS AND METHODS: Rats were stereotaxically implanted with intracerebral microinjection cannulae and an electrode in lateral hypothalamus. Rewarding effects of d-amphetamine and cocaine were assessed using electrical self-stimulation in rats tested 1-4 or 18-21 h after the daily meal. Nonimplanted subjects acquired a cocaine-CPP while ad libitum fed and then were switched to FR and tested for CPP at these same times. RESULTS: Rewarding effects of intranucleus accumbens (NAc) d-amphetamine, intraventricular cocaine, and persistence of cocaine-CPP did not differ between rats tested 18-21 h food-deprived, when ghrelin and insulin levels were at peak and nadir, respectively, and those tested 1-4 h after feeding. Rats that expressed a persistent CPP had elevated levels of p-ERK1, GluA1, and p-Ser845-GluA1 in NAc core, and the latter correlated with CPP expression. CONCLUSIONS: Psychostimulant reward and persistence of CPP in FR rats are unaffected by time of testing relative to the daily meal. Further, NAc biochemical responses previously associated with enhanced drug responsiveness in FR rats are associated with persistent CPP expression.

The mechanisms by which natural rewards such as sugar affect synaptic transmission and behavior are largely unexplored. Here, we investigate regulation of nucleus accumbens synapses by sucrose intake. Previous studies have shown that AMPA receptor (AMPAR) trafficking is a major mechanism for regulating synaptic strength, and that in vitro, trafficking of AMPARs containing the GluA1 subunit takes place by a two-step mechanism involving extrasynaptic and then synaptic receptor transport. We report that in rat, repeated daily ingestion of a 25% sucrose solution transiently elevated spontaneous locomotion and potentiated accumbens core synapses through incorporation of Ca(2+)-permeable AMPA receptors (CPARs), which are GluA1-containing, GluA2-lacking AMPARs. Electrophysiological, biochemical, and quantitative electron microscopy studies revealed that sucrose training (7 d) induced a stable (>24 h) intraspinous GluA1 population, and that in these rats a single sucrose stimulus rapidly (5 min) but transiently (<24 h) elevated GluA1 at extrasynaptic sites. CPARs and dopamine D1 receptors were required in vivo for elevated locomotion after sucrose ingestion. Significantly, a 7 d protocol of daily ingestion of a 3% solution of saccharin, a noncaloric sweetener, induced synaptic GluA1 similarly to 25% sucrose ingestion. These findings identify multistep GluA1 trafficking, previously described in vitro, as a mechanism for acute regulation of synaptic transmission in vivo by a natural orosensory reward. Trafficking is stimulated by a chemosensory pathway that is not dependent on the caloric value of sucrose.

Social discrimination may isolate drug users into higher risk relationships, particularly in disadvantaged neighborhood environments where drug trade occurs. We used negative binomial regression accounting for clustering of individuals within their recruitment neighborhood to investigate the relationship between high-risk drug ties with various forms of social discrimination, neighborhood minority composition, poverty and education. Results show that experiencing discrimination due to drug use is significantly associated with more drug ties in neighborhoods with fewer blacks. Future social network and discrimination research should assess the role of neighborhood social cohesion.

Recent developments in the study of classic hallucinogens, combined with a re-appraisal of the older literature, have led to a renewal of interest in possible therapeutic applications for these drugs, notably their application in the treatment of addictions. This article will first provide a brief review of the research literature providing direct and indirect support for the possible therapeutic effects of classic hallucinogens such as psilocybin and lysergic acid diethylamide (LSD) in the treatment of addictions. Having provided a rationale for clinical investigation in this area, we discuss design issues in clinical trials using classic hallucinogens, some of which are unique to this class of drug. We then discuss the current status of this field of research and design considerations in future randomized trials.

Background: Although opioid substitution therapy is an effective clinical tool used to manage opioid abuse and dependence, concerns regarding the current FDA-approved medications have lead to a search for efficacious, non-opioid medications. Preclinical data indicate that neurokinin 1 (NK1) receptor activity may modulate opioid effects and withdrawal. This investigation sought to examine the ability of the NK1 antagonist aprepitant to alter the effects of methadone as well as withdrawal symptoms induced by brief methadone discontinuation. Methods: This blinded, placebo-controlled, within-subjects study consisted of placebo and aprepitant conditions. Experimental assessments occurred on the first three days (days 1-3: placebo or aprepitant + methadone) and again on days 8-10 (aprepitant or placebo + methadone). Fifteen methadone-maintained patients completed the investigation. Outcome measures were the assessments of opioid withdrawal, as well as subjective measures of opioid-like effects. Results: Statistical trends indicated that aprepitant may reduce opioid withdrawal symptoms. When an active dose of aprepitant was administered an hour before methadone, participants reported less desire to use methadone. However, ratings of methadone "Liking" also appeared to increase. Conclusions: These data tentatively suggest that aprepitant has some ability to alleviate withdrawal following methadone abstinence, but also appears to increase subjective indicators of methadone's abuse liability. Since few of the differences between aprepitant and placebo reached statistical significance, these data should only be viewed as preliminary. Findings from other studies indicate that higher doses of aprepitant may be more clinically effective. Further clinical investigations are needed in order to determine whether aprepitant is useful for alleviating opioid withdrawal.

Many individuals diagnosed with a substance use disorder are also diagnosed with another psychiatric disorder. Little is known regarding which treatments are efficacious for these dually diagnosed individuals (DDI). Characterizing the psychometric properties of assessments used with DDI samples is essential to efficacy studies with DDI. This study examined the internal consistency and test-retest reliability of self-report instruments among DDI. Most subscales demonstrated high test-retest reliability; one subscale demonstrated poor reliability. Internal consistency was similar to that of non-DDI samples. This exploratory study suggests that, while some instruments should be interpreted cautiously, DDI samples can be accurately assessed with self-report measures.

Discrimination can influence risk of disease by promoting unhealthy behaviors (e.g., smoking, alcohol use). Whether it influences the formation of high-risk social ties that facilitate HIV transmission is unclear. Using cross-sectional data from a cohort of illicit drug users, this study examined the association between discrimination based on race, drug use and prior incarceration and risky sex and drug ties. Negative binomial regression models were performed. Participants who reported discrimination based on race and drug use had significantly more sex and drug-using ties. But, after accounting for both racial and drug use discrimination, only racial discrimination was associated with increased sex, drug-using, and injecting ties. Drug users who experience discrimination and subsequently develop more sex and drug-using ties, increase their risk of contracting HIV. Future longitudinal studies illuminating the pathways linking discrimination and social network development may guide intervention development and identify drug-using subpopulations at high risk for disease transmission.