Shirley H. Leong

Naltrexone vs Placebo for the Treatment of Alcohol Dependence: A Randomized Clinical Trial.

IMPORTANCE Alcohol use disorder is one of the leading causes of disability worldwide. While effective pharmacological treatments exist, they are efficacious only in certain individuals, contributing to their limited use. Secondary analysis of clinical trial data suggests that a functional polymorphism (rs1799971, Asn40Asp) of the µ-opioid receptor gene (OPRM1) is associated with the risk of relapse to heavy drinking following treatment with the opioid antagonist naltrexone. OBJECTIVE To prospectively examine whether rs1799971 is predictive of naltrexone treatment response. DESIGN, SETTING, AND PARTICIPANTS We conducted a 12-week, double-blind, randomized clinical trial of naltrexone vs placebo in individuals with alcohol dependence (intent-to-treat analysis). Participants were randomly assigned to study treatment based on the presence of 1 or 2 copies of the Asp40 allele compared with those homozygous for the Asn40 allele (2 × 2 cell design). Recruitment occurred between January 2009 and September 2013. All participants were seen in an outpatient clinical setting. A convenience sample of participants (n = 221) was recruited from 5 sites. All participants met DSM-IV criteria for alcohol dependence, with no concurrent psychotic or manic symptoms, no use of concurrent psychotropic medications, and no current dependence on illicit substances. INTERVENTIONS The study drug was naltrexone (50 mg) given once daily or corresponding placebo. MAIN OUTCOMES AND MEASURES The primary study outcome measure was relapse to heavy drinking measured using the timeline follow-back method. RESULTS There was no evidence of a genotype × treatment interaction on the primary outcome of heavy drinking (P = .32). In the Asn40 group, the observed effect of naltrexone was similar to that in previous trials (odds ratio, 0.69; 95% CI, 0.41-1.18; P = .17), with a very small naltrexone effect in the Asp40 group (odds ratio, 1.10; 95% CI, 0.52-2.31; P = .80), contrary to the pattern expected a priori. A significant reduction in heavy drinking occurred across all groups (P = .001). Other drinking outcomes, and all secondary outcomes, demonstrated similar time effects, with no genotype × treatment interaction. CONCLUSIONS AND RELEVANCE The results of this study do not support the hypothesis that the Asp40 allele moderates the response to naltrexone treatment. It is premature to use the Asn40Asp polymorphism as a biomarker to predict the response to naltrexone treatment of alcohol dependence. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00831272.

Boundaries of Schizoaffective Disorder: Revisiting Kraepelin

IMPORTANCE Established nosology identifies schizoaffective disorder as a distinct category with boundaries separating it from mood disorders with psychosis and from schizophrenia. Alternative models argue for a single boundary distinguishing mood disorders with psychosis from schizophrenia (kraepelinian dichotomy) or a continuous spectrum from affective to nonaffective psychosis. OBJECTIVE To identify natural boundaries within psychotic disorders by evaluating associations between symptom course and long-term outcome. DESIGN, SETTING, AND PARTICIPANTS The Suffolk County Mental Health Project cohort consists of first-admission patients with psychosis recruited from all inpatient units of Suffolk County, New York (72% response rate). In an inception cohort design, participants were monitored closely for 4 years after admission, and their symptom course was charted for 526 individuals; 10-year outcome was obtained for 413. MAIN OUTCOMES AND MEASURES Global Assessment of Functioning (GAF) and other consensus ratings of study psychiatrists. RESULTS We used nonlinear modeling (locally weighted scatterplot smoothing and spline regression) to examine links between 4-year symptom variables (ratio of nonaffective psychosis to mood disturbance, duration of mania/hypomania, depression, and psychosis) and 10-year outcomes. Nonaffective psychosis ratio exhibited a sharp discontinuity-10 days or more of psychosis outside mood episodes predicted an 11-point decrement in GAF-consistent with the kraepelinian dichotomy. Duration of mania/hypomania showed 2 discontinuities demarcating 3 groups: mania absent, episodic mania, and chronic mania (manic/hypomanic >1 year). The episodic group had a better outcome compared with the mania absent and chronic mania groups (12-point and 8-point difference on GAF). Duration of depression and psychosis had linear associations with worse outcome. CONCLUSIONS AND RELEVANCE Our data support the kraepelinian dichotomy, although the study requires replication. A boundary between schizoaffective disorder and schizophrenia was not observed, which casts further doubt on schizoaffective diagnosis. Co-occurring schizophrenia and mood disorder may be better coded as separate diagnoses, an approach that could simplify diagnosis, improve its reliability, and align it with the natural taxonomy.

Prevalence and correlates of suicidal ideation and suicide attempts among veterans in primary care referred for a mental health evaluation.

BACKGROUND The Veterans Health Administration has made concerted efforts to increase mental health services offered in primary care. However, few studies have evaluated correlates of suicidal ideation and suicide attempt in veterans in primary care-mental health integration (PCMHI). The purpose of the present study is to examine associations between suicidal ideation and suicide attempts as dependent variables and demographic and clinical factors as the independent variables. METHODS Veterans (n=3004) referred from primary care to PCMHI were contacted for further assessment, which included past-year severity of suicidal thoughts (none, low, high) and attempts using the Paykel Suicide Scale, mental health disorders, and illicit drug use. Multinomial logistic regression models were used to identify correlates of suicidal ideation and suicide attempts. RESULTS Thoughts of taking ones life was endorsed by 24% of participants and suicide attempts were reported in 2%. In adjusted models, depression, psychosis, mania, PTSD and generalized anxiety disorder were associated with high severity suicidal ideation, but not suicide attempt. Illicit drug use was not associated with suicidal ideation, but was the only variable associated with suicide attempt. LIMITATIONS The study was cross-sectional, focused on one clinical setting, and the suicide attempt analyses had limited power. CONCLUSIONS PCMHI is a critical setting to assess suicidal ideation and suicide attempt and researchers and clinicians should be aware that the differential correlates of these suicide-related factors. Future research is needed to identify prospective risk factors and assess the utility of follow-up care in preventing suicide.

A Cross-Sectional Study of Attitudes About the Use of Genetic Testing for Clinical Care Among Patients with an Alcohol Use Disorder

AIM Modification and individualization of medical treatments due to genetic testing has the potential to revolutionize healthcare delivery. As evidence mounts that genetic testing may improve treatment decisions for patients with alcohol use disorder (AUD), we explored patient concerns and attitudes toward genetic testing. METHODS Subjects of two USA cross-sectional AUD studies were surveyed regarding their attitudes regarding the use of genetic testing for AUD treatment. RESULTS Four hundred and fifty-seven participants were surveyed. Overall, subjects showed a high degree of willingness to provide DNA for clinical use and recognized genetics as important to the pathophysiology of a number of disorders including AUD. There were, however, significant concerns expressed related to insurance denial or employment problems. CONCLUSION We found that patients enrolled in AUD studies had some concerns about use of genetic testing. The patients in these two samples were, however, willing and knowledgeable about providing DNA samples.

Preliminary support for the role of reward relevant effort and chronotype in the depression/insomnia comorbidity

BACKGROUND The presence of insomnia in the context of depression is linked to a number of poor outcomes including reduced treatment response, increased likelihood of relapse, and greater functional impairment. Given the frequent co-occurrence of depression and insomnia, research into systems and processes relevant to both disorders, specifically reward processing and circadian rhythm disruption, may help parse this complex comorbidity. METHODS A pilot study was conducted on a sample of 10 veterans with clinically significant depression and insomnia symptoms. Participants completed objective (actigraphy) and subjective (sleep diary) assessments of sleep, self-reports of chronotype, and behavioral tasks assessing reward relevant effort before and after 6 sessions of Cognitive Behavioral Therapy for Insomnia. RESULTS Insomnia and depression significantly improved following CBT-I. Subjective sleep parameters significantly improved with large effect sizes. Actigraphy results were nonsignificant, but effect sizes for sleep efficiency and onset latency were in the medium range. Chronotype shifted significantly toward morningness following CBT-I, and an earlier chronotype at baseline was associated with increased reward effort following treatment. Changes in chronotype, depression and insomnia were not associated with changes in effort. LIMITATIONS Findings are limited by small sample size and lack of randomized control group. CONCLUSIONS Findings should be interpreted as hypothesis generating in the service of furthering research aimed at uncovering potential mechanisms underlying the depression/insomnia comorbidity. Analyses of sleep data in extant datasets of reward processing impairments in depression as well as original projects aimed at exploring potential sleep, circadian rhythm, and reward interactions in depression are encouraged.

The associations between suicidality and mental health factors and pain interference in veterans being referred to primary care mental health integration

In veterans being referred to a primary care-mental health integration (PCMHI) program, the Behavioral Health Laboratory, we sought to identify correlates of suicidal ideation severity and suicide attempts using the ideation-to-action framework among pain interference, psychiatric disorders, and treatment factors. Veterans (n = 17,176) referred to the Behavioral Health Laboratory received a structured assessment that included past-year suicidal thoughts and behaviors, psychiatric symptoms, substance use, psychotropic medication use, and mental health treatment utilization. Nearly 50% of participants reported at least passive suicidal ideation. While psychiatric symptoms differentiated passive ideators, active ideators, and suicide attempters from non-suicide ideators, there were no significant differences among active ideators and attempters. Additionally, attempters differed from passive ideators in terms of drug use, mental health treatment, psychotropic medication use, mania, and psychosis. Pain interference was significantly associated with suicidal ideation severity in bivariate analyses, but not for the adjusted analyses. PCMHI is a setting seeing a high rate of suicidal ideation and may serve as a critical setting to implement suicide prevention efforts.

Factors Associated With Long-term Benzodiazepine Use Among Older Adults

LESS IS MORE Factors Associated With Long-term Benzodiazepine Use Among Older Adults Benzodiazepine use among older adults is common despite evidence for many potential risks. While treatment guidelines recommend short-term use of benzodiazepines, up to one-third of use is long term, which is most common among older adults.1 To reduce benzodiazepine prescribing to older adults, one potential point for intervention is at the transition from new to long-term use, yet little is known about the factors that predict conversion to long-term use.2,3

Socioeconomic Disparities and Metabolic Risk in Veterans with Serious Mental Illness

Socioeconomic disparities were assessed in predicting metabolic risk among veterans with serious mental illness. Veterans with schizophrenia, schizoaffective, or bipolar disorders were identified in VISN 4 facilities from 10/1/2010 to 9/30/2012. Differences between patients with and without metabolic syndrome were compared using t-tests, Chi square tests and multivariate logistic regressions. Among 10,132 veterans with mental illness, 48.8% had metabolic syndrome. Multivariate logistic regression analysis confirmed that patients with metabolic syndrome were significantly more likely to be older, male, African-American, married, and receiving disability pensions but less likely to be homeless. They were more likely to receive antipsychotics, antidepressants, or anticonvulsants. Bivariate cross-sectional analysis revealed that patients with metabolic syndrome had higher rates of coronary artery disease, cerebrovascular disease, and mortality, and that metabolic syndrome was more often associated with emergency visits and psychiatric or medical hospitalizations. Demographics, socioeconomic status and medications are independent predictors of metabolic syndrome and should be considered in broader screening of risk factors in order to provide preventive interventions for metabolic syndrome.

Association between drug use and suicidal ideation and attempt among at-risk primary care patients

epidemiology of substance use. The results are consistent and extend to those of the general and immigrant populations. It is imperative to develop and evaluate strategies to detect the at-risk women population as early as possible and offer them preventive strategies. The primary care centers are places for early detection and implementing prevention services, especially for women where drug use prevention should be included as part of routine reproductive healthcare. Financial support: NIDA DA 022445, NIDA 3P30DA02782802S1 and -02S2.