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Objective: To increase the number of physician-scientists in research, the Drug Abuse Research Training (DART) program at the Medical University of South Carolina offers a 2-year research track for psychiatry residents and a 10-week summer fellowship for students. The goal of this study was to examine program outcomes and alumni diversity levels over DART’s 15-year history. Methods: To date, 215 trainees (44 residents, 171 summer fellows) have completed the program. An anonymous online survey was sent to the 143 program alumni with valid contact information. Survey data included demographic characteristics, post-program research involvement, and self-reported barriers to continued research engagement. Results: Overall survey completion response was 83.5% (N= 122). The alumni included 59.0% women, and 36.1% of respondents identified as a member of a minority racial/ethnic group. Following program completion, 77.0% of the alumni reported continued research involvement. More than half of the alumni reported scientific publications (57.4%) and conference presentations (63.1%) since completing DART. Among respondents who did not subsequently engage in research, the most common modifiable barriers included difficulty finding a mentor, self-perceived deficits in statistical skills and research methodology, and overall lack of confidence in research ability. Conclusions: Over the past 15 years, the DART program has established a diverse research training program that now spans the educational spectrum from undergraduate to residency training. Future program goals include additional training to address self-reported modifiable research barriers. This program provides a model for other training programs designed to cultivate research interests and promote the diversity of clinical researchers.

Alcohol Use Disorder (AUD) is characterized by loss of control over drinking. Behavioral control is mediated, in part, by cortical dopamine signaling. Inhibition of catechol-O-methyltransferase (COMT), the enzyme primarily responsible for cortical dopamine inactivation, may increase cortical dopamine, especially among individuals with genetically mediated lower dopaminergic tone, such as COMTrs4680 (val158met) val-allele homozygotes. This study was a randomized, placebo-controlled, pharmacogenetic trial of the COMT inhibitor tolcapone. Ninety non-treatment-seeking AUD individuals were prospectively genotyped for rs4680 and randomized to tolcapone (200 mg t.i.d.) or placebo for 8 days. At baseline and on day 7, peripheral COMT activity was assayed, and participants completed an fMRI alcohol cue-reactivity task; on day 8, they completed a bar-lab paradigm. Primary outcomes were: (1) natural drinking during the medication period; (2) alcohol self-administration in the bar lab; and (3) alcohol cue-elicited cortical (right inferior frontal gyrus [rIFG]) and ventral striatal activation. At baseline, the rs4680 val-allele had an additive effect on COMT activity. Tolcapone, relative to placebo, reduced COMT activity in all genotype groups. COMTgenotype moderated tolcapone’s effect on drinking during the medication period and in the bar lab, such that tolcapone, relative to placebo, reduced drinking only among val-allele homozygotes. Tolcapone did not affect cue-elicited ventral striatal activation but reduced rIFG activation; less rIFG activation on day 7 was associated with less drinking during the medication period. Taken together, these data suggest that COMT inhibition may reduce drinking specifically among individuals genetically predisposed to excessive COMT activity and potentially low cortical dopamine tone.

While the opiate antagonist, naltrexone, is approved for treating alcohol use disorder (AUD), not everyone who receives the medication benefits from it. This study evaluated whether the OPRM1SNP rs1799971 interacts with the dopamine transporter gene DAT1/SLC6A3VNTR rs28363170 or the catechol‐O‐methyltransferase (COMT) gene SNP rs4680 in predicting naltrexone response. Individuals who met DSM‐IV alcohol dependence were randomly assigned to naltrexone (50 mg/d) or placebo based on their OPRM1genotype (75 G‐allele carriers and 77 A‐allele homozygotes) and also genotyped for DAT1VNTR (9 vs. 10 repeats) or COMTSNP (val/val vs. met carriers). Heavy drinking days (%HDD) were evaluated over 16 weeks and at the end of treatment. Effect sizes (d) for naltrexone response were calculated based on genotypes. Naltrexone, relative to placebo, significantly reduced %HDD among OPRM1G carriers who also had DAT110/10 (p= 0.021, d= 0.72) or COMTval/val genotypes (p= 0.05, d= 0.80), and to a lesser degree in those OPRM1A homozygotes who were also DAT19‐repeat carriers (p= 0.09, d= 0.70) or COMTmet carriers (p= 0.03, d= 0.63). All other genotype combinations showed no differential response to naltrexone. Diarrhea/abdominal pain was more prominent in OPRM1A homozygotes who were also DAT9 or COMTmet carriers. These results suggest that individuals with AUD with a more opioid‐responsive genotype (OPRM1G carriers) respond better to naltrexone if they have genotypes indicating normal/less dopamine tone (DAT110,10 or COMTval,val), while those with a less responsive opioid‐responsive genotype (OPRM1A homozygotes) respond better to naltrexone if they have genotypes indicating greater dopamine tone (DAT19‐repeat or COMTmet carriers). These results could lead to more personalized AUD treatments. Measuring individual genetic variation could improve AUD naltrexone treatment. When mu opioid receptor gene (OPRM1 A118G) “high brain opioid function” G allele carriers also have “normal or low dopamine brain function” gene polymorphisms i.e. dopamine transporter (DAT 10R) or catechol‐o‐methyl transferase (COMT 158 Val/Val), they respond better to naltrexone. However, OPRM1 AA common variant “normal brain opioid function” individuals respond better to naltrexone if they also have DAT 9R or COMT met alleles indicating “greater brain dopamine” functionality.

CASE Ms A is a 64-year-old retired schoolteacher who is referred to a psychiatrist by her primary care physician. She reports that she does not have a psychiatric problem, but [...]

The opioid antagonist naltrexone is not efficacious for every alcohol treatment seeker. However, various individual factors, such as genetic differences and nicotine‐use/smoking status, have been suggested as predictors of naltrexone response. In a randomized clinical trial, we previously reported that nicotine‐use/smoking status might be a stronger predictor of naltrexone efficacy than OPRM1A118G single nucleotide polymorphism (SNP) genotype. In this report, we further characterize the nicotine‐users in that trial, examine other drinking outcomes, examine the influence of smoking change on naltrexone effects on drinking, and validate the result in smokers with disialo carbohydrate‐deficient transferrin (%dCDT) change as an independent biomarker of response. Individuals (n= 146) meeting DSM‐IVcriteria for alcohol dependence who were genotyped for the OPRM1A118G SNPand who did, or did not, use nicotine/cigarettes were randomized, in a balanced fashion, to naltrexone (50 mg/d) or placebo and provided medical management (MM) over a 16‐week clinical trial. Alcohol use and smoking during the trial were assessed and analyzed. Nicotine‐use/smoking status significantly interacted with medication in reducing percent heavy drinking days (PHDD) during the trial (p= 0.003), such that nicotine‐users/smokers showed significantly lower PHDDon naltrexone versus placebo (p= 0.0001, Cohen's d= 0.89), while nonusers showed no significant difference between naltrexone and placebo (p= 0.95, Cohen's d= 0.02). Similar effects were shown for drinks per day and percent days drinking. The superiority of naltrexone over placebo on PHDDreduction in nicotine‐users/smokers was confirmed with %dCDT(Cohen's drange 0.3 to 0.9 over the study). Naltrexone did not significantly change cigarette use in smokers, and change in use did not influence naltrexone's effect on PHDD. These data confirm past findings that naltrexone is more efficacious in those who use nicotine/cigarettes. Compared to previous work on the OPRM1A118G SNP, it appears that nicotine‐use might be a more salient predictor of naltrexone treatment response. While naltrexone did not change cigarette use during the study, and smoking change was not related to alcohol reduction, it should be noted that participants were not seeking smoking cessation and MM did not address this issue. In this clinical trial of Alcohol Dependent (AUD) individuals, those that used nicotine/smoked had much reduced drinking when taking the opioid antagonist naltrexone compared to non‐nicotine users. Results were confirmed with the specific marker of heavy drinking, %dCDT. The effect on reduced drinking was independent of any effect of naltrexone on nicotine use/smoking, or the amount of pre‐treatment drinking. This data suggests that nicotine might enhance alcohol's neurobiological effects (dopamine reward?) and that those effects might predispose to successful naltrexone intervention.

Naltrexone reduces drinking among individuals with alcohol use disorders (AUDs), but it is not effective for everyone. Variability in its effects on reward-related brain activation, genetic variation, and/or cigarette smoking may account for this mixed response profile. This randomized clinical trial tested the effects of naltrexone on drinking and alcohol cue-elicited brain activation, evaluated whether OPRM1 A118G genotype or smoking moderated these effects, and explored whether the effects of medication on cue-elicited activation predicted subsequent drinking. One hundred and fifty-two treatment-seeking individuals with alcohol dependence, half preselected to carry at least one A118G G (Asp) allele, were randomized to naltrexone (50 mg) or placebo for 16 weeks and administered an fMRI alcohol cue reactivity task at baseline and after 2 weeks of treatment. Naltrexone, relative to placebo, significantly reduced alcohol cue-elicited activation of the right ventral striatum (VS) between baseline and week 2 and reduced heavy drinking over 16 weeks. OPRM1 genotype did not significantly moderate these effects, but G-allele carriers who received naltrexone had an accelerated return to heavy drinking after medication was stopped. Smoking moderated the effects of medication on drinking, such that naltrexone was superior to placebo only among smokers. The degree of reduction in right VS activation between scans interacted with medication in predicting subsequent drinking, such that individuals with greater reduction in activation who received naltrexone, but not placebo, experienced the least heavy drinking during the following 14 weeks. These data replicate previous findings that naltrexone reduces heavy drinking and reward-related brain activation among treatment-seeking individuals with AUDs, and indicate that smoking and the magnitude of reduction in cue-elicited brain activation may predict treatment response.

Because psychiatric illnesses and problematic alcohol use frequently co-occur and heavy alcohol use can exacerbate depression and anxiety, mental health clinicians should perform alcohol-use screenings. The aim of this study was to determine if psychiatric patients would be accepting of their mental health clinician screening them for heavy alcohol use. Using a written survey, patients rated their levels of agreement with 9 statements regarding opinions about alcohol screening by their mental-health providers. They also completed the Alcohol Use Disorders Identification Test-C (AUDIT-C), a screening instrument for heavy alcohol use. One hundred fifty-four patients were surveyed in 2 psychiatric outpatient clinics. Nearly 40% screened positively for heavy alcohol use on the AUDIT-C. Nearly 8 out of 10 psychiatric patients were in favor of being screened for alcohol use by either self-report or biomarkers, independent of AUDIT-C status and gender. Thus, mental health clinicians should not be deterred from alcohol screening by perceived negative attitudes from patients.

Alcohol Use Disorder (AUD) is associated with elevated brain response to cues. Recent studies have suggested that theta burst stimulation (TBS) to the MPFC can decrease reactivity to cues in a transdiagnostic manner. The goal of this clinical trial was to evaluate the effect of continuous TBS as a tool to decrease drinking behavior and brain reactivity to alcohol cues among individuals with AUD.

Background: Individuals with social anxiety disorder and co‐occurring alcohol problems report using alcohol to cope with anxiety symptoms. Interventions that reduce both social anxiety and drinking are needed. Paroxetine, an FDA‐approved medication to treat social anxiety disorder, reduces anxiety in individuals with co‐occurring alcohol problems.

There have been many recent developments in the pharmacological management of alcohol withdrawal and alcohol dependence. Although previous treatments had included benzodiazepines as their mainstay, the use of these agents in the alcoholic population is problematic. Benzodiazepines are themselves addictive and they may increase the risk of alcohol relapse. Non-benzodiazepine anticonvulsants such as carbamazepine, valproic acid, gabapentin, vigabatrin and topiramate have been shown to be excellent treatments of both alcohol withdrawal and the prevention of alcohol relapse. Although none of these agents have yet been approved by the FDA, there is growing evidence in the literature to support their use.

Patients with social phobia who responded well to 6 months of open-label treatment with clonazepam were assigned to receive either continuation treatment (CT) with clonazepam for another 5 months, or to undergo discontinuation treatment (DT) using a clonazepam taper at the rate of 0.25 mg every 2 weeks, with double-blind placebo substitution. Clinical efficacy was compared between the CT and DT groups using three different social phobia scales. Benzodiazepine withdrawal symptoms were also measured. Relapse rates were 0 and 21.1% in the CT and DT groups, respectively. Subjects in the CT group generally showed a more favorable clinical response at midpoint and/or endpoint, although even in the DT group clinical response remained good. With respect to withdrawal symptoms, the rates were low in both groups (12.5% for CT and 27.7% for DT) with no real evidence suggesting significant withdrawal difficulties. At the end of 11 months of treatment with clonazepam, however, a more rapid withdrawal rate was associated with greater distress. This study offers preliminary evidence to suggest that continuation therapy with clonazepam in the treatment of social phobia is safe and effective, producing a somewhat greater clinical benefit than a slow-taper discontinuation regime. However, even in the DT group, withdrawal symptoms were not found to be a major problem. The study can be taken as supportive of benefit for long-term clonazepam treatment in social phobia, as well as being compatible with a reasonably good outcome after short-term treatment and slow taper. (J Clin Psychopharmacol 1998;18:373-378)