Alcohol and nicotine dependence are common in schizophrenia. Varenicline is effective in smoking cessation and has also been shown to decrease alcohol consumption in smokers. The present pilot study assessed the safety and effectiveness of varenicline for treatment of concurrent nicotine and alcohol dependence in schizophrenia. Outpatients with schizophrenia or schizoaffective disorder and concurrent alcohol and nicotine dependence were enrolled in this 8-week, double-blind, randomized, placebo-controlled trial. Alcohol use and smoking were assessed using self-report (Timeline Follow-Back) and biological measures. Adverse events were recorded. Changes in the number of standard drinks per week and cigarettes per week were compared in the 2 groups. Because of safety concerns or loss to follow-up, of 55 patients enrolled, only 10 started study medication, 5 each on varenicline and placebo. Gastrointestinal adverse effects, such as severe abdominal pain, limited study completion to only 4 subjects. Number of standard alcoholic drinks consumed per week decreased by [mean (SD)] 16.6 (20.1) in the varenicline group and by 2.4 (27.4) in the placebo group. Mean (SD) number of cigarettes smoked per week decreased by 66 (65) in the varenicline group and by 47 (77) in the placebo group. Varenicline treatment of concurrent alcohol and nicotine dependence in schizophrenia may be problematic because of safety concerns limiting recruitment and poor tolerability (gastrointestinal adverse effects) limiting retention. There was no increased number of serious neuropsychiatric adverse events in the varenicline group. Based on this small sample, concurrent alcohol and nicotine dependence in schizophrenia may present special obstacles to successful treatment with varenicline.

BackgroundAlcohol use disorders (AUDs) lead to alterations in central nervous system (CNS) architecture along with impaired learning and memory. Previous work from our group and that of others suggests that one mechanism underlying these changes is alteration of cell proliferation, apoptosis, and DNA-repair in neural stem cells (NSCs) produced as a consequence of ethanol-induced effects on the expression of genes related to p53-signaling. This study tests the hypothesis that changes in the expression of p53-signaling genes represent biomarkers of ethanol abuse which can be identified in the peripheral blood of rat drinking models and human AUD subjects and posits that specific changes may be correlated with differences in neuropsychological measures and CNS structure.ResultsRemarkably, microarray analysis of 350 genes related to p53-signaling in peripheral blood leukocytes (PBLs) of binge-drinking rats revealed 190 genes that were significantly altered after correcting for multiple testing. Moreover, 40 of these genes overlapped with those that we had previously observed to be changed in ethanol-exposed mouse NSCs. Expression changes in nine of these genes were tested for independent confirmation by a custom QuantiGene Plex (QGP) assay for a subset of p53-signaling genes, where a consistent trend for decreased expression of mitosis-related genes was observed. One mitosis-related gene (Pttg1) was also changed in human lymphoblasts cultured with ethanol. In PBLs of human AUD subjects seven p53-signaling genes were changed compared with non-drinking controls. Correlation and principal components analysis were then used to identify significant relationships between the expression of these seven genes and a set of medical, demographic, neuropsychological and neuroimaging measures that distinguished AUD and control subjects. Two genes (Ercc1 and Mcm5) showed a highly significant correlation with AUD-induced decreases in the volume of the left parietal supramarginal gyrus and neuropsychological measures.ConclusionsThese results demonstrate that alcohol-induced changes in genes related to proliferation, apoptosis, and DNA-repair are observable in the peripheral blood and may serve as a useful biomarker for CNS structural damage and functional performance deficits in human AUD subjects.

The goal of the present study was to identify predictors of smoking severity in patients with schizophrenia and co-occurring alcohol use disorders (AUD). Our hypothesis was that negative symptoms of schizophrenia, severity of depression, male gender, drinking severity and recreational drug use were associated with increased smoking. Clinical data, including demographic variables, alcohol and substance use severity, psychiatric medications, severity of depression, positive and negative symptoms of schizophrenia were analyzed in a cohort of 90 patients with schizophrenia or schizoaffective disorder and AUD. 88% of participants were smokers; they smoked an average of 15 cigarettes/day. Zero-inflated negative binomial regression analyses demonstrated that alcohol use severity, gender and severity of negative symptoms were not predictive of the number of cigarettes smoked. Smoking severity was positively related to Caucasian race, psychosis severity (PANSS general score) and medications (conventional antipsychotics). Subjects, who used recreational drugs, smoked less. In summary, severe, treatment resistant schizophrenia, and conventional antipsychotic treatment is associated with heavy smoking in patients with schizophrenia and AUD regardless of gender, or alcohol use.

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Background Schizophrenia and alcohol dependence (AD) are both major risk factors for a variety of medical problems, yet little is known about the medical status of patients in whom both conditions coexist. Objective To assess accuracy of self-reported medical problems and to compare the accuracy reports in patients with schizophrenia or schizoaffective disorder and co-occurring AD compared to patients with AD only and to controls. Our hypothesis was that medical problems are under-reported in patients with co-occurring disorders, possibly due to the combination of alcohol use and symptoms of schizophrenia. Methods Self-reported medical diagnoses were recorded and compared to medical records obtained from all area hospitals in 42 patients with schizophrenia and AD, 44 patients with schizoaffective disorder and AD, 41 patients with AD only, and 15 control subjects. Patients underwent a medical history, physical examination, and review of medical records. Results Patients with schizophrenia or schizoaffective disorder and co-occurring AD underreported their medical problems significantly more than patients with AD only and controls. Accuracy of self report was significantly lower in patients with schizophrenia-spectrum disorders plus co-occurring alcohol dependence than in AD alone or in controls. The most commonly underreported diagnoses included coronary artery disease, chronic renal failure, seizure disorder, hyperlipidemia, asthma and hypertension. Discussion In order to detect potentially unreported medical conditions in patients with co-occurring schizophrenia/schizoaffective disorder and alcohol dependence, the use of targeted screening questionnaires is recommended in addition to physical examination and thorough review of medical records.