Varenicline treatment of concurrent alcohol and nicotine dependence in schizophrenia: a randomized, placebo-controlled pilot trial.

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.

Evaluation of cell proliferation, apoptosis, and DNA-repair genes as potential biomarkers for ethanol-induced CNS alterations.

BACKGROUND: Alcohol 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. RESULTS: Remarkably, 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. CONCLUSIONS: These 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 COVID-19 Pandemic and Adolescents' Psychological Distress: A Multinational Cross-Sectional Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has continued for more than two years, and the impact of this pandemic on mental health has become one of the most important research topics in psychiatry and psychology. The aim of the present study was to assess psychological distress in adolescents across five countries (Sweden, Morocco, Serbia, Vietnam, and the United States of America) during the COVID-19 pandemic. METHODS: Using nonparametric analyses we examined the impact of COVID-19 on distress, measured by the Brief Symptom Inventory, in a sample of 4670 adolescents. RESULTS: Our results showed that the association between the COVID-19 impact and psychological distress in adolescents' lives was positive and moderate in Morocco and Serbia, positive and weak in Vietnam and the United States of America, and negative and weak in Sweden. We also found that female adolescents reported higher distress levels than male adolescents. CONCLUSIONS: COVID-19 impacted adolescents and their psychological distress differently depending on their residence.

Measurement properties of the life history of aggression in adolescents: Data from Morocco, Serbia, Sweden, Vietnam, and the USA.

The Life History of Aggression (LHA) is a frequently used scale for assessing trait aggression, but its psychometric properties have not been evaluated among adolescents. The aim of this study was to evaluate the psychometric properties of the LHA among high school students from Morocco, Serbia, Sweden, Vietnam, and the United States of America (USA). The total sample included 4867 adolescents, aged 15-19 years, from Morocco (n = 508), Serbia (n = 1067), Sweden (n = 1570), Vietnam (n = 1401), and the USA (n = 321). A two-factor, nine-item model containing an aggression factor (5 items) and a consequences/antisocial behavior factor (4 items) was created. The two-factor model had an acceptable-to-good model fit for the data for the total sample and all five countries, including gender. Cronbach's alpha (α) was satisfactory across countries. Still, the construct was noninvariant across countries and genders. The LHA with nine items in two subscales showed sound construct validity and internal consistency and can be used for group-level or within-group assessments of trait aggression in adolescents by either gender or country. However, it should not be used for cross-gender or cross-country comparisons due to a lack of measurement invariance.

Predictors of smoking severity in patients with schizophrenia and alcohol use disorders.

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. Eighty-eight percent of participants were smokers, they smoked an average of 15 cigarettes/day. Zero-inflated negative binomial (ZINB) 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 (Positive and Negative Syndrome Scale [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.

Psychiatric symptoms in systemic lupus erythematosus: a systematic review.

OBJECTIVE: Systemic lupus erythematosus (SLE) presents with psychiatric symptoms in most patients that often remain undiagnosed and untreated. This study evaluates the prevalence of psychiatric symptoms in SLE on the basis of clinical trials that fulfilled diagnostic criteria specified by the American College of Rheumatology (ACR). Current hypotheses explaining the pathogenesis of psychiatric symptoms of lupus are reviewed to gain new insights into the neuroimmune pathogenesis of other psychiatric disorders. DATA SOURCE: A MEDLINE search of the literature (English language only) from April 1999 to August 2011 was performed using the search terms lupus and psychiatric to identify studies of neuropsychiatric SLE. STUDY SELECTION: Of 163 publications, 18 clinical studies were selected that focused on psychiatric symptoms, had a sample size of at least 20, and included patients of any age or gender as long as they fulfilled ACR criteria for neuropsychiatric SLE. DATA EXTRACTION: The following data were extracted: author name, year of publication, psychiatric diagnostic method, total number of patients with SLE, and percentage of patients with individual psychiatric diagnoses. The point prevalence of psychiatric symptoms was calculated for neuropsychiatric SLE diagnoses in every study included. RESULTS: Psychiatric symptoms are present in the majority of patients with SLE. Depression (in up to 39% of patients) and cognitive dysfunction (up to 80%) are the most common psychiatric manifestations. Genetic and environmental factors (eg, ultraviolet light, retroviruses, and medications) may play a role in the pathogenesis. In addition, the patient's reaction to the illness may result in anxiety (up to 24%) and depression. Currently known biomarkers are nonspecific for neuropsychiatric SLE and indicate inflammation, microglial activation, ischemia, oxidative stress, mitochondrial dysfunction, and blood-brain barrier dysfunction. CONCLUSIONS: Identification of lupus-specific biomarkers of psychiatric symptoms is a high priority. Our current diagnostic assessment methods need improvement. Development of evidence-based guidelines is needed to improve diagnosis, prevention, and treatment of disabling psychiatric complications in lupus.

Accuracy of self-reported medical problems in patients with alcohol dependence and co-occurring schizophrenia or schizoaffective disorder.

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: The objectives of this study are 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 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.