Improved Depressive Symptoms in Adults with Schizophrenia During a Smoking Cessation Attempt with Varenicline and Behavioral Therapy.

OBJECTIVE: Smoking prevalence rates are elevated in individuals with schizophrenia spectrum disorders (SSD) compared with the general population, with attendant disproportionate smoking-related morbidity and mortality. Pharmacotherapies that improve abstinence rates in this population are underutilized, partly due to concerns about neuropsychiatric safety, particularly for those with comorbid depression or prior suicide attempt. Prospective assessment of the psychiatric safety profile of varenicline in those with SSD is needed. METHODS: Adult smokers with SSD entered a 12-week trial of varenicline and behavioral therapy for smoking cessation. Depressive symptoms were assessed with the Calgary Depression Scale for Schizophrenia (CDSS) at baseline and weekly thereafter. Participants with baseline and one or more postbaseline CDSS assessments, n = 179, were included in a secondary analysis of change in depressive symptoms with varenicline treatment, adjusting for abstinence status and baseline depressive symptoms. RESULTS: Twenty-seven percent of participants had a CDSS score at baseline consistent with current major depressive disorder, and more than half had a prior suicide attempt. Forty-one percent (74/179) achieved two or more weeks of continuous abstinence at the end of treatment. CDSS scores declined 31% during the 12-week treatment period. Controlling for baseline CDSS scores, depressive symptoms declined over time in those who completed the trial, independent of abstinence status, and either declined or remained unchanged in those with major depressive disorder or prior suicide attempt or who were taking antidepressant medication. Those who did not complete the trial had no change in depressive symptoms. DISCUSSION: Depressive symptoms declined in adults with schizophrenia during 12 weeks of varenicline treatment and cognitive behavioral therapy, independent of tobacco abstinence. Smokers with SSD who have significant depressive symptoms may be successful in smoking cessation attempts with pharmacotherapeutic aids such as varenicline while maintaining stable psychiatric symptoms. This is a secondary analysis of data collected as part of a clinical trial registered as NCT00621777, at www.clinicaltrials.gov .

Traumatic brain injury and bipolar psychosis in the Genomic Psychiatry Cohort.

Approximately three million individuals in the United States sustain traumatic brain injury (TBI) every year, with documented impact on a range of neurological and psychiatric disturbances including mania, depression, and psychosis. Identification of subsets of individuals that may demonstrate increased propensity for posttraumatic symptoms and who may share genetic vulnerabilities for gene-environment interactions can enhance efforts to understand, predict, and prevent these phenomena. A sample of 11,489 cases from the Genomic Psychiatry Cohort (GPC), a NIMH-managed data repository for the investigation of schizophrenia and bipolar disorder, was used for this study. Cases were excluded if TBI was deemed causal to their mental illness. A k-means clustering algorithm was used to probe differences between schizophrenia and bipolar disorder associated with variables including onset age, hallucinations, delusions, head injury, and TBI. Cases were separated into an optimum number of seven clusters, with two clusters including all cases with brain injury. Bipolar disorder with psychosis and TBI were significantly correlated in one cluster in which 72% of cases were male and 99.2% sustained head injury. This cluster also carried the longest average period of unconsciousness. This study demonstrates an association of TBI with psychosis in a subset of bipolar cases, suggesting that traumatic stressors may have the ability to impact gene expression in a vulnerable population, and/or there is a heightened occurrence of TBI in individuals with underlying psychosis. Further studies should more closely examine the interplay between genetic variation in bipolar disorder and susceptibility to psychosis following TBI. © 2015 Wiley Periodicals, Inc.

Olfactory performance segregates effects of anhedonia and anxiety on social function in patients with schizophrenia.

BACKGROUND: Social dysfunction is common among individuals with schizophrenia. While often attributed to anhedonia, social dysfunction could also result from unrecognized anxiety. We examined the contributions of anhedonia and anxiety to social function using olfactory function to examine whether the domains had separate underpinnings. METHODS: We assessed anhedonia, anxiety and social function as well as olfactory function in well-characterized patients with schizophrenia or schizoaffective disorder and healthy controls. RESULTS: We included 56 patients and 37 controls in our study. Patients exhibited significantly higher levels of anhedonia and anxiety than controls, and the domains were highly correlated in patients. The combination of anhedonia and anxiety more strongly predicted social dysfunction than either measure alone. Smell identification was differentially related to the symptoms, with better performance predicting less anhedonia but more social fear in male patients. LIMITATIONS: The use of self-report measures precludes differentiation between recollected or recounted experience. Aside from smell identification and odour threshold, additional measures of olfaction may be considered for future studies. CONCLUSION: Anhedonia and anxiety were strongly correlated and both negatively impacted social function. The olfactory biomarker results support the conclusion that these domains are separate. Social function in patients with schizophrenia may improve with interventions for anxiety, even in the presence of marked negative symptoms.

Achieving Smoking Cessation in Individuals with Schizophrenia: Special Considerations.

Premature mortality due to cardiovascular disease in those with schizophrenia is the largest lifespan disparity in the US and is growing; adults in the US with schizophrenia die, on average, 28 years earlier than those in the general population. The rate of smoking prevalence among individuals with schizophrenia is estimated to be from 64 to 79%. Smokers with schizophrenia have historically been excluded from most large nicotine-dependence treatment studies. However, converging evidence indicates that a majority of smokers with schizophrenia want to quit smoking, and that available pharmacotherapeutic smoking cessation aids are well tolerated by this population of smokers and are effective when combined with behavioral treatment. The aim of this review is to present updated evidence for safety and efficacy of smoking cessation interventions for those with schizophrenia spectrum illness. We also highlight implications of the very low abstinence rates for smokers with schizophrenia who receive placebo plus behavioral treatment in randomized trials, and review treatment approaches to address the high rate of rapid relapse observed upon pharmacologic treatment discontinuation in this population. Recommendations for monitoring for treatment-emergent nicotine withdrawal symptoms, side effects, and effects of cessation on antipsychotic medication are also provided. Smokers with schizophrenia spectrum disorders should be encouraged to quit smoking and should receive varenicline, bupropion with or without nicotine replacement therapy (NRT), or NRT, all in combination with behavioral treatment for at least 12 weeks. Maintenance pharmacotherapy may reduce relapse and improve sustained abstinence rates. Controlled trials in smokers with schizophrenia consistently show no greater rate of neuropsychiatric adverse events with pharmacotherapeutic cessation aids than with placebo.

Predictors of tobacco abstinence in outpatient smokers with schizophrenia or bipolar disorder treated with varenicline and cognitive behavioral smoking cessation therapy.

BACKGROUND: The estimated mortality gap between those with and without serious mental illness (SMI) is increasing, now estimated at 28years, which is largely due to smoking-related diseases. AIMS: We sought to identify predictors of 14-day continuous abstinence in stable outpatient smokers with SMI. METHOD: Adult smokers with schizophrenia spectrum (n=130) or bipolar disorder (n=23) were enrolled in a 12-week course of varenicline and cognitive-behavioral therapy for smoking cessation. RESULTS: Independent predictors of abstinence included reduction in withdrawal symptoms prior to the quit day, fewer cigarettes smoked per day at baseline, better baseline attention, remitted alcohol dependence, and lower expectation of peer support to aid quitting. CONCLUSIONS: Interventions that consider these targets may improve smoking cessation outcomes in those with SMI.

Maintenance pharmacotherapy normalizes the relapse curve in recently abstinent tobacco smokers with schizophrenia and bipolar disorder.

OBJECTIVE: To compare the effect of maintenance pharmacotherapy on sustained abstinence rates between recently abstinent smokers with schizophrenia and bipolar disorder (SBD) and general population smokers without psychiatric illness. METHOD: We performed a person-level, pooled analysis of two randomized controlled trials of maintenance varenicline, conducted in adult smokers with SBD and general population smokers, controlling for severity of dependence. Smokers abstinent after 12-weeks of open varenicline treatment were randomly assigned to ≥12-weeks maintenance varenicline or identical placebo. RESULTS: In those assigned to maintenance placebo, the abstinence rate at week-24 was lower in those with SBD than for those without psychiatric illness (29.4±1.1% vs. 61.8±0.4%, OR:0.26, 95% CI: 0.13, 0.52, p<0.001). In smokers assigned to maintenance pharmacotherapy, however, there was no effect of diagnosis on abstinence rates at week-24 (87.2±0.8% vs. 81.9±0.2%, OR: 1.68, 95% CI: 0.53, 5.32, p=0.38). Time to first lapse was shortest in those with SBD assigned to maintenance placebo (Q1=12days, 95%CI: 4, 16), longer in those without psychiatric illness assigned to maintenance placebo (Q1=17days, 95%CI: 17, 29), still longer in general-population smokers assigned to maintenance varenicline (Q1=88, 95% CI:58,91, and longest in those with SBD who received maintenance varenicline (Q1>95days, 95%CI:non-est), (Χ23df=96.99, p<0.0001; all pairwise comparisons p<0.001). CONCLUSIONS: Following a standard 12-week course of pharmacotherapy, people with schizophrenia and bipolar disorder were more likely to relapse to smoking without maintenance varenicline treatment. Maintenance pharmacotherapy could improve longer-term tobacco abstinence rates and reduce known smoking-related health disparities in those with SMI.

Frequent Comorbidity and Predictors of Social Anxiety in Persons With Schizophrenia: A Retrospective Cohort Study.

OBJECTIVE: To determine if symptoms of social anxiety are distinct from negative symptoms of schizophrenia. METHOD: Fifty-three patients with schizophrenia or schizoaffective disorder (diagnosed per DSM-IV criteria) and 37 healthy controls were examined with the Liebowitz Social Anxiety Scale (LSAS) for social anxiety disorder and for the severity of social anxiety. The Positive and Negative Syndrome Scale (PANSS) and the Chapman scales for physical and social anhedonia were also administered. Data were collected from 2005 to 2010 from inpatient and outpatient research centers at the New York State Psychiatric Institute, New York. RESULTS: Social anxiety disorder was elevated more than 10-fold in schizophrenia patients than in controls (37.7% of patients vs 2.9% of controls, P ≤ .001). Social anxiety and social fear were unrelated to the PANSS with few exceptions. A family history of psychosis was also a significant independent predictor of social anxiety as measured by LSAS total (P = .004) and the social fear subscale (P = .007). CONCLUSIONS: These data confirm social anxiety disorder as a prominent comorbid disorder in patients with schizophrenia. Future studies should focus on treatment trials of this phenomenon. Social anxiety cannot be explained by the negative symptomatology of the disease. This study suggests that a family history of psychosis is a significant predictor of social anxiety.

Current trends in the management of recurrent anterior shoulder instability.

The glenohumeral joint is innately complex and comprised of both static and dynamic stabilizers. Anterior glenohumeral instability has been estimated to have an incidence of 11.2 cases per 100,000 persons and typically follows a traumatic injury. Although there are specific instances when conservative management is advocated, a majority of these patients are treated with operative stabilization. Recent advancements in arthroscopy have created a shift from the traditional open stabilization procedures towards more minimally invasive arthroscopic stabilization procedures. This comprehensive review will summarize current concepts involved in evaluating patients with anterior glenohumeral instability and specifically focus on those patients who suffer from recurrent instability.

Low vitamin D levels predict clinical features of schizophrenia.

Vitamin D plays crucial roles in neuroprotection and neurodevelopment, and low levels are commonly associated with schizophrenia. We considered if the association was spurious or causal by examining the association of Vitamin D with Leukocyte Telomere Length (LTL), a marker of cellular aging. Vitamin D levels in 22 well-characterized schizophrenia cases were examined with respect to symptoms, cognition, and functioning. LTL was assessed using quantitative polymerase chain reaction (qPCR). The results showed that 91% (20) had deficient or insufficient Vitamin D levels, which were associated with excitement and grandiosity, social anhedonia, and poverty of speech. Sex-specific analyses showed strong associations of hypovitamintosis D to negative symptoms and decreased premorbid adjustment in males, and to lesser hallucinations and emotional withdrawal, but increased anti-social aggression in females. In females LTL was furthermore associated with Vitamin D levels. This study demonstrates a relationship of low vitamin D levels with increased cellular aging in females. It is also the first study to demonstrate potential sex-specific profiles among schizophrenia cases with hypovitaminosis.

In vivo effects of single intra-articular injection of 0.5% bupivacaine on articular cartilage.

BACKGROUND: Single intra-articular injections of local anesthetics are commonly used clinically. Recent in vitro studies have demonstrated chondrotoxic effects of local anesthetics, with the greatest emphasis on bupivacaine toxicity. This in vivo study was conducted to determine whether a single intra-articular injection of 0.5% bupivacaine results in chondrocyte morbidity and rapid chondrolysis. METHODS: Forty-eight Sprague-Dawley rats received a 100-microL injection of sterile 0.9% saline solution (negative control) into one stifle joint and 100 microL of either preservative-free 0.5% bupivacaine (experimental group) or 0.6 mg/mL monoiodoacetate (positive control) into the contralateral joint. The rats were killed at one week, four weeks, twelve weeks, or six months. Live and dead cells were quantified with use of three-dimensional confocal reconstructions of fluorescent-stained tissues at standardized locations on the distal part of the femur. Histological findings were graded with use of a modified Mankin score, and cell density was quantified with use of custom image-analysis software. RESULTS: In the specimens injected with bupivacaine, the chondral surfaces remained intact as seen with gross and histological examination. No differences in superficial chondrocyte viability or modified Mankin scores were observed between the saline-solution and bupivacaine groups at any location or time point (p > 0.05). Quantitative histological analysis of the bupivacaine-treated knees at six months revealed an up to 50% reduction in chondrocyte density compared with that of the saline-solution-treated knees (p < or = 0.01). Monoiodoacetate injection resulted in death of up to 87% of the superficial chondrocyte cells at one week and chondrolysis at six months. Despite severe histological abnormalities by four weeks after monoiodoacetate injection, cartilage injury was not evident on gross inspection until six months. CONCLUSIONS: This in vivo study showing reduced chondrocyte density without cartilage tissue loss six months after a single intra-articular injection of 0.5% bupivacaine suggests bupivacaine toxicity. The effects of bupivacaine were milder than those of an injection of 0.6% monoiodoacetate, which resulted in chondrolysis over the same time period.