Bo-Geum Kong

Adjunctive varenicline treatment with antipsychotic medications for cognitive impairments in people with schizophrenia: a randomized double-blind placebo-controlled trial.

The aim of this study is to examine the effects of treatment with varenicline, a partial agonist at the α4β2 and full agonist at the α7 nicotine acetylcholine receptor, on cognitive impairments in people with schizophrenia. In all, 120 clinically stable people with schizophrenia participated in randomized, double-blind, placebo-controlled 8-week trial. Antipsychotic and concomitant medication doses remained fixed throughout the study. Varenicline was titrated up to 1 mg twice daily for weeks 2–8. Neuropsychological, clinical, and safety assessments were administered at baseline and weeks 1, 2, 4, and 8. In the primary analyses of neurocognitive differences at week 8, no varenicline–placebo differences were significant. In secondary longitudinal analyses, varenicline improved compared with placebo on the Digital Symbol Substitution Test (p=0.013) and the Wisconsin Card Sorting Test non-perseverative errors (p=0.043). Some treatment effects were different between smokers and non-smokers. In smokers, Continuous Performance Test hit reaction time (p=0.008) and Stroop Interference (p=0.004) were reduced for varenicline compared with placebo, while there were no treatment differences in non-smokers. No significant treatment main effects or interactions were noted for total scores on the Positive and Negative Syndrome Scale or the Scale for the Assessment for Negative Symptoms. Our findings suggest beneficial effects of adjunctive varenicline treatment with antipsychotics for some cognitive impairments in people with schizophrenia. In some cases, effects of treatment varied between smokers and non-smokers. Further study is required to assess the functional significance of these changes.

Bone mineral density and osteoporosis risk in older patients with schizophrenia.

Objective: People with schizophrenia are at a higher risk for osteoporosis. The authors investigated the prevalence of low bone density and its risk factors in older Korean patients with schizophrenia. Method: In cross-sectional study, 327 inpatients with schizophrenia were screened. Among them, 229 patients older than 50 years participated in this study. The control group consisted of healthy volunteers who were of similar ages (n = 125). Bone density was measured in the lumbar spine and the neck, trochanter, and ward regions of the right proximal femur by dual-energy x-ray absorptiometry. Clinical variables such as alcohol use, cigarette smoking, and fracture history were obtained. The Student t test, Pearson &khgr;2 test, Wilcoxon rank sum test, and logistic regression analysis were used. Results: The prevalence of osteoporosis was significantly higher in patients with schizophrenia compared with healthy controls (34.9% vs 18.4%, P = 0.0043). Within the schizophrenia group, female subjects had a significantly higher prevalence of osteoporosis than male subjects (48.4% vs 25.7%, P = 0.0014); however, no sex differences were identified in the healthy control group. The actual bone density and t scores in patients with schizophrenia were significantly lower in all sites than in healthy controls. Among patients with schizophrenia, smokers and alcohol abuser showed lower bone density compared with those who did not smoke or drink. The lifetime prevalence of fracture was significantly higher in patients with schizophrenia (24.0%) compared with healthy controls (5.6%; P = 0.001). Conclusions: Our results emphasize that older patients with schizophrenia are at risk for low bone density. Cigarette smoking and alcohol abuse are associated with low bone density in patients with schizophrenia.

The Relationship between Language Ability and Cognitive Function in Patients with Schizophrenia.

Objective Cognitive dysfunction is common in people with schizophrenia, and language disability is one of the most notable cognitive deficits. This study assessed the use and comprehension ability of the Korean language in patients with schizophrenia and the correlations between language ability and cognitive function. Methods Eighty-six patients with schizophrenia and a group of 29 healthy controls were recruited. We assessed both clinical symptoms and cognitive functions including Korean language ability. For clinical symptoms, the Positive and Negative Syndrome Scale, Clinical Global Impression-Schizophrenia Scale, and Social and Occupational Functioning Assessment Scale were used. For the Korean language ability assessment, a portion of the Korean Broadcasting System (KBS) Korean Language Test was used. The Short-form of Korean-Wechsler Adult Intelligence Scale, the Korean version of the University of California San Diego (UCSD) Performance-based Skills Assessment (K-UPSA), and the Wisconsin Card Sorting Test (WCST) were used to assess cognitive functions. Results Schizophrenic patients had significantly lower scores in the language and cognitive function tests both in the total and subscale scores. Various clinical scores had negative correlations with reading comprehension ability of the KBS Korean Language Test. The WCST and a part of the K-UPSA had positive correlations with multiple domains of the language test. Conclusion A significant difference was found between schizophrenic patients and controls in language ability. Correlations between Korean language ability and several clinical symptoms and cognitive functions were demonstrated in patients with schizophrenia. Tests of cognitive function had positive correlations with different aspects of language ability.

Adjunctive varenicline treatment for smoking reduction in patients with schizophrenia: A randomized double-blind placebo-controlled trial

OBJECTIVES Smoking is more common among patients with schizophrenia than it is in the general population. Varenicline, a partial and full agonist at the α4β2 and α7 nicotine acetylcholine receptors, respectively, has been shown to be an effective anti-smoking treatment. This study examined the effects of varenicline treatment on smoking reduction in patients with schizophrenia. METHODS Sixty smokers with schizophrenia were recruited and randomized to receive either varenicline or placebo. Smoking behavior was assessed with the Minnesota Nicotine Withdrawal Scale (mNWS), Brief Questionnaire of Smoking Urge (QSU-brief), and Modified Cigarette Evaluation Questionnaire (mCEQ). Exhaled carbon monoxide was also measured to assess smoking dependency and status. Data were analyzed with the two-tailed Students t-test, χ(2) test, and repeated measures ANOVA. RESULTS During the 8-week study, there was a significant time×group interaction, which showed that smoking decreased over time in the varenicline group. Expired CO levels also decreased in the varenicline group, showing a significant time effect, group effect, and time×group interaction. Total mCEQ scores decreased in the varenicline group, demonstrating a significant time×group interaction. Among the five domains of the mCEQ, the smoking satisfaction, psychological reward, and enjoyment of respiratory tract sensation domains showed significant time×group interactions in the varenicline group. The QSU-brief and mNWS demonstrated a significant time effect, but not significant time×group interactions. Adjunctive varenicline treatment with antipsychotics was generally well-tolerated and safe. CONCLUSIONS Varenicline showed significant efficacy in reducing smoking in people with schizophrenia.

Differences in cognitive function and daily living skills between early- and late-stage schizophrenia.

Objectives. Cognitive dysfunction is a core feature of schizophrenia; deficits often manifest prior to diagnosis and persist throughout the course of the illness. This study was performed to assess the difference in cognitive function and daily living skills between the early- and late-stage schizophrenia. Methods. Fifty-five clinically stable patients with schizophrenia were recruited (25 with < 5-year and 30 with > 5-year disease durations). We evaluated subjects’ clinical states, cognitive function, and psychosocial factors. The Korean versions of MATRICS Consensus Cognitive Battery and UCSD Performance-based Skills Assessment were used for evaluating cognitive function and daily living skills. Chi-square, Wilcoxon rank sum, and t-tests were used to analyze the data. Results. The two groups did not differ for most demographic variables. No significant differences between groups were found for clinical symptoms, psychosocial factors, or non-social cognitive domains. However, the early-stage group had higher social cognition domain scores than the late-stage group (p = 0.01). Early-stage patients scored significantly higher than those in the late-stage group did in the communication and comprehension/planning domains (p = 0.037 and 0.027, respectively), and total score (p = 0.003) of the Performance-based Skills Assessment. Conclusions. We observed significant differences between patients with early- and late-stage illness with regard to social cognition and performance-based skills.

Rim1α and Neurexin3 Regulate Synaptosomal Dopamine Release

Neurotransmitter release is regulated by various proteins of the active zone in the presynaptic nerve terminals. Dopamine (DA) is an essential neurotransmitter associated with the pathophysiology of diverse behavioral and mental illness such as schizophrenia and drug addiction. We measured synaptosomal DA release of knockout (KO) mice which lacked major genes related to neurotransmitter release. Synaptosomal DA uptake and release were performed and measured using [³H]-DA and superfusion experiments. 3 of the 17 KO mice exhibited altered DA release compared to their littermate controls. In Rim1α KO, [³H]-DA release evoked by membrane depolarization significantly decreased. Both basal (physiological buffer-evoked) and membrane depolarization-evoked DA release significantly decreased in dopaminergic conditional KO of Rim1αβ. Dopaminergic conditional KO of neurexin3 demonstrated a significant increase of membrane depolarization-evoked DA release. These data explain the similarities and distinctions between DA and other classical neurotransmitters such as glutamate and GABA (γ-aminobutyric acid) release. In conclusion, Rim1α and neurexin3 may be important regulators of presynaptic DA release and related to disorders of the nervous system.