Erin L. Reutenauer

A preliminary study of the effects of cigarette smoking on prepulse inhibition in schizophrenia : Involvement of nicotinic receptor mechanisms

BACKGROUND Schizophrenics exhibit deficits in prepulse inhibition (PPI) of the startle response, and have high rates of cigarette smoking. We evaluated the effects of cigarette smoking on PPI deficits in schizophrenia, and the role of nicotinic acetylcholine receptors (nAChRs) in mediating cigarette smoking-related PPI enhancement. METHODS PPI was assessed at baseline, after overnight abstinence, and after smoking reinstatement during three separate test weeks in nicotine-dependent schizophrenia (n=15) and control (n=14) smokers pre-treated with the nAChR antagonist mecamylamine (MEC; 0.0, 5.0 or 10.0 mg/day). RESULTS PPI was comparable between schizophrenia and control smokers after ad lib cigarette smoking. Overnight smoking abstinence significantly reduced PPI, while smoking reinstatement reversed abstinence-induced worsening of PPI deficits in schizophrenia. However, acute abstinence and reinstatement did not alter PPI in controls. PPI enhancement by smoking reinstatement in schizophrenia was dose-dependently blocked by MEC, whereas MEC had no effect on PPI in control smokers. CONCLUSIONS These results suggest that: 1) Non-deprived smokers with schizophrenia have comparable levels of PPI to non-deprived smoking controls; 2) In schizophrenia, PPI is impaired by smoking abstinence and improved by acute smoking reinstatement, and; 3) enhancement of PPI by cigarette smoking in schizophrenia is mediated by stimulation of central nAChRs. Our findings may contribute to understanding the increased vulnerability to nicotine dependence in schizophrenia, with implications for treatment of PPI deficits in this disorder.

Gender Differences in Associations between Lifetime Alcohol, Depression, Panic Disorder, and Posttraumatic Stress Disorder and Tobacco Withdrawal

This study examined the interaction of gender and lifetime psychiatric status on the experience of nicotine withdrawal using retrospective data from the National Comorbidity Survey (NCS; N = 816). Multiple regression analyses were performed to examine the main and interactive effects of gender and major depression, alcohol abuse/dependence, panic disorder, and PTSD on indices of withdrawal. Major depression and alcohol abuse/dependence were associated with longer duration of withdrawal symptoms in women. Women also showed stronger associations between major depression and recurrent withdrawal symptoms and PTSD and smoking relapse to alleviate withdrawal. Men showed a stronger association between alcohol abuse/dependence and smoking relapse to alleviate withdrawal. When developing and providing smoking cessation interventions, it is important to consider the gender-specific effects of lifetime psychiatric status on withdrawal.

Obese Schizophrenia Spectrum Patients Have Significantly Higher 10-Year General Cardiovascular Risk and Vascular Ages than Obese Individuals without Severe Mental Illness

BACKGROUND Individuals with schizophrenia have a life expectancy that is 20 years less than the general population, along with high rates of obesity and cardiovascular disease (CVD) mortality. OBJECTIVE This study assessed the 10-year general CVD risk and vascular ages of 106 obese schizophrenia spectrum patients and 197 demographically matched obese controls without severe mental illness (SMI) from the National Health and Nutrition Examination Survey (NHANES). METHODS Vascular age and general CVD risk were calculated using the Framingham global CVD calculator, which incorporates age, sex, total and HDL cholesterol levels, systolic blood pressure, smoking status, and diabetes or hypertension treatment. RESULTS Obese schizophrenia spectrum patients had a mean vascular age that was 14.1 years older than their mean actual age, whereas obese NHANES participants had only a 6.7-year difference. The probability of experiencing a CVD event within the next 10 years was 10.7% for obese patients and 8.5% for obese NHANES participants. CONCLUSION These findings suggest that schizophrenia spectrum patients experience increased metabolic risk independent of weight. Primary care clinicians can utilize general CVD risk and vascular age scores to communicate metabolic risk more easily and to help make treatment decisions.

Association of prescription H1 antihistamine use with obesity: results from the National Health and Nutrition Examination Survey.

The incidence of obesity in the United States has reached epidemic proportions. Previous research has shown several medications exert noticeable effects on body‐weight regulation. Histamine‐1 (H1) receptor blockers commonly used to alleviate allergy symptoms are known to report weight gain as a possible side effect. Therefore, we investigated the association between prescription H1 antihistamine use and obesity in adults using data from the 2005–2006 National Health and Nutrition Examination Survey (NHANES). Adults taking prescription H1 antihistamines were matched by age and gender with controls and compared on the basis of body measurements, plasma glucose, insulin concentrations, and lipid levels. Prescription H1 antihistamine users had a significantly higher weight, waist circumference, and insulin concentration than matched controls. The odds ratio (OR) for being overweight was increased in prescription H1 antihistamine users. H1 antihistamine use may contribute to the increased prevalence of obesity and the metabolic syndrome in adults given these medications are also commonly used as over‐the‐counter remedies.

The effect of dietary and physical activity pattern on metabolic profile in individuals with schizophrenia: a cross-sectional study

OBJECTIVE With the rate of obesity on the rise worldwide, individuals with schizophrenia represent a particularly vulnerable population. The aim of this study was to assess the metabolic profile of individuals with schizophrenia in relation to dietary and physical activity habits compared with healthy controls. METHODS Dietary and physical activity habits of 130 individuals with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia or schizoaffective disorder were compared with 250 body mass index-, age-, and sex-matched and racially matched controls from the 2005-2008 National Health and Nutrition Examination Surveys using a 24-hour diet recall and a self-report physical activity questionnaire. RESULTS Individuals with schizophrenia had significantly higher levels of glycosylated hemoglobin and insulin compared with matched controls. In addition, these individuals had an increased waist circumference and diastolic blood pressure than did the comparison group. Daily energy intake was not different between groups; however, individuals with schizophrenia consumed significantly greater amounts of sugar and fat. Individuals with schizophrenia reported engaging in moderate physical activity less frequently compared with the National Health and Nutrition Examination Surveys group, but there was no difference in reported vigorous physical activity. CONCLUSIONS These findings suggest that the dietary and physical activity habits of individuals with schizophrenia contribute to an adverse metabolic profile. Increased opportunities for physical activity and access to healthy foods for individuals with schizophrenia may ease the burden of disease.

A double-blind, placebo-controlled, randomized clinical trial of oral selegiline hydrochloride for smoking cessation in nicotine-dependent cigarette smokers

AIM The primary aim of this study was to determine the safety and efficacy of the monoamine oxidase-B (MAO-B) inhibitor selegiline hydrochloride (SEL, l-Deprenyl; Eldepryl) as an aid for smoking cessation in cigarette smokers. METHODS One hundred and one nicotine-dependent adult cigarette smokers without current psychiatric or substance use disorders participated in this 8-week randomized, double-blind, placebo-controlled trial. Participants received either SEL (5mg bid, n=51) or placebo (PLO, n=50), in combination with brief (<10 min) manualized smoking cessation counseling. The main smoking outcome measures were 7-day point prevalence abstinence at end of trial (EOT), 4-week continuous smoking abstinence at end of trial (CA), and 7-day point prevalence abstinence at 6-month follow-up (6MFU). Abstinence was determined by an absence of self-reported cigarette smoking and biochemically verified by expired breath carbon monoxide and plasma cotinine levels. RESULTS Rates of smoking abstinence did not differ by medication group (EOT: SEL=16%, PLO=20%, p=0.57; CA: SEL=14%, PLO=18%, p=0.56; 6MFU: SEL=12%, PLO=16%, p=0.54). Adverse events were modest and comparable between medication groups. Participants receiving SEL were more likely than those receiving PLO to report dry mouth (25.5% versus 8.2%, p<0.05). CONCLUSIONS Our results suggest that SEL was safe and well-tolerated by adult cigarette smokers, but did not improve smoking abstinence rates compared to PLO.

Survey of Clinician Attitudes Toward Smoking Cessation for Psychiatric and Substance Abusing Clients

Abstract The current study examined mental health clinician attitudes regarding smoking cessation for psychiatric and substance abusing patients. Participants included n = 15 never smokers, n = 12 former smokers, and n = 7 current smokers. There was a trend (p = 0.08) for current smokers as compared to former and never smokers to be less likely to encourage their clients to stop smoking. Overall, clinicians strongly agreed that an individuals motivation is the most important determinant of success in quitting. Clinicians were concerned that smoking cessation would initiate a relapse to substance abuse. We suggest that mental health clinicians can be instrumental in providing information, encouragement, and opportunities for their patients to attempt smoking cessation.

The impact of eszopiclone on sleep and cognition in patients with schizophrenia and insomnia: A double-blind, randomized, placebo-controlled trial

BACKGROUND Insomnia is frequent in schizophrenia and may contribute to cognitive impairment as well as overuse of weight inducing sedative antipsychotics. We investigated the effects of eszopiclone on sleep and cognition for patients with schizophrenia-related insomnia in a double-blind placebo controlled study, followed by a two-week, single-blind placebo phase. METHODS Thirty-nine clinically stable outpatients with schizophrenia or schizoaffective disorder and insomnia were randomized to either 3mg eszopiclone (n=20) or placebo (n=19). Primary outcome measure was change in Insomnia Severity Index (ISI) over 8 weeks. Secondary outcome measure was change in MATRICS Consensus Cognitive Battery (MATRICS). Sleep diaries, psychiatric symptoms, and quality of life were also monitored. RESULTS ISI significantly improved more in eszopiclone (mean=-10.7, 95% CI=-13.2; -8.2) than in placebo (mean=-6.9, 95% CI=-9.5; -4.3) with a between-group difference of -3.8 (95% CI=-7.5; -0.2). MATRICS score change did not differ between groups. On further analysis there was a significant improvement in the working memory test, letter-number span component of MATRICS (mean=9.8±9.2, z=-2.00, p=0.045) only for subjects with schizophrenia on eszopiclone. There were improvements in sleep diary items in both groups with no between-group differences. Psychiatric symptoms remained stable. Discontinuation rates were similar. Sleep remained improved during single-blind placebo phase after eszopiclone was stopped, but the working memory improvement in patients with schizophrenia was not durable. CONCLUSIONS Eszopiclone stands as a safe and effective alternative for the treatment of insomnia in patients with schizophrenia. Its effects on cognition require further study.

An open-label pilot trial of alpha-lipoic acid for weight loss in patients with schizophrenia without diabetes.

UNLABELLED A possible mechanism of antipsychotic-induced weight gain is activation of hypothalamic monophosphate-dependent kinase (AMPK) mediated by histamine 1 receptors. Alpha-lipoic acid (ALA), a potent antioxidant, counteracts this effect and may be helpful in reducing weight for patients taking antipsychotics. The objective of this open-label study was to assess the efficacy of ALA (1,200 mg) on twelve non-diabetic schizophrenia patients over ten weeks. Participants lost significant weight during the intervention (-2.2 kg±2.5 kg). ALA was well tolerated and was particularly effective for individuals taking strongly antihistaminic antipsychotics (-2.9 kg±2.6 kg vs. -0.5 kg±1.0 kg). CLINICAL TRIAL REGISTRATION NCT01355952.

Investigating the safety and efficacy of naltrexone for anti-psychotic induced weight gain in severe mental illness: study protocol of a double-blind, randomized, placebo-controlled trial.

BackgroundObesity is a growing health problem leading to high rates of mortality and morbidity in patients with severe mental illness (SMI). The increased rate of obesity is largely attributed to antipsychotic use. The effect of antipsychotic medications on H1 and 5HT2 receptors has been associated with weight gain, but there is also a substantial amount of evidence showing that D2 receptor blockade may be responsible for weight gain by interacting with the dopamine-opioid system. Unfortunately, current available medications for weight loss have limited efficacy in this population. Naltrexone, an opioid receptor antagonist, may be a promising agent to reduce antipsychotic induced weight gain by decreasing food cravings. We aim to investigate the safety and efficacy of two doses of naltrexone (25 mg & 50 mg) versus placebo for weight and health risk reduction in overweight and obese individuals (BMI ≥ 28) with SMI, who gained weight while being treated with antipsychotics.Methods and designOne hundred and forty four patients will be recruited throughout the greater New Haven area. The participants will be randomized to naltrexone 25 mg/day, naltrexone 50 mg/day, or placebo in a 1:1:1 ratio. Participants will be on the study medication for 52 weeks, and assessed weekly for the first 4 weeks and bi-weekly thereafter. The primary outcome measurements are weight reduction and percentage achieving clinically significant weight loss (5% of total body weight). Waist circumference, body mass index, serum lipid profile, fasting glucose, and glycosylated hemoglobin are the secondary outcome measures. The effect of naltrexone on other outcome measurements such as schizophrenia symptoms, depression, dietary consumption, quality of life, cognitive functioning, physical activity, metabolism/inflammation markers, serum leptin, ghrelin, peptide YY, adinopectin, high sensitivity CRP, interleukin 6, interleukin-1B, interleukin-18, and tumor necrosis factor alpha (TNF-α) will be evaluated. The data will be analyzed by applying linear mixed effect models.DiscussionThis is the first large scale study investigating the safety and efficacy of naltrexone in antipsychotic induced weight gain; and hopefully, this may lead to a novel pharmacological option for management of this major health problem.Trial registrationThis trial is registered in http://www.clinicaltrials.gov as NCT01866098