Efficacy of Transcranial Direct Current Stimulation to Improve Insight in Patients With Schizophrenia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND AND HYPOTHESIS: Impaired insight into the illness and its consequences is associated with poor outcomes in schizophrenia. While transcranial direct current stimulation (tDCS) may represent a potentially effective treatment strategy to relieve various symptoms of schizophrenia, its impact on insight remains unclear. To investigate whether tDCS would modulate insight in patients with schizophrenia, we undertook a meta-analysis based on results from previous RCTs that investigated the clinical efficacy of tDCS. We hypothesize that repeated sessions of tDCS will be associated with insight improvement among patients. STUDY DESIGN: PubMed and ScienceDirect databases were systematically searched to identify RCTs that delivered at least 10 tDCS sessions in patients with schizophrenia. The primary outcome was the change in insight score, assessed by the Positive and Negative Syndrome Scale (PANSS) item G12 following active tDCS sessions as opposed to sham stimulation. Effect sizes were calculated for all studies and pooled using a random-effects model. Meta-regression and subgroup analyses were conducted. STUDY RESULTS: Thirteen studies (587 patients with schizophrenia) were included. A significant pooled effect size (g) of -0.46 (95% CI [-0.78; -0.14]) in favor of active tDCS was observed. Age and G12 score at baseline were identified as significant moderators, while change in total PANSS score was not significant. CONCLUSIONS: Ten sessions of active tDCS with either frontotemporoparietal or bifrontal montage may improve insight into the illness in patients with schizophrenia. The effect of this treatment could contribute to the beneficial outcomes observed in patients following stimulation.

Evaluation of the correlation between gaze avoidance and schizophrenia psychopathology with deep learning-based emotional recognition.

OBJECTIVE: To investigate the correlation between gaze avoidance and psychopathology in patients with schizophrenia through eye movement measurements in real-life interpersonal situations. METHODS: We enrolled 52 clinically stable patients with schizophrenia. Psychopathology was evaluated using the Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale, and Hamilton Anxiety Rating Scale. After presenting a visual stimulus, eye movements were measured with Tobii Pro Wearable Glasses 2, and deep learning-based emotional recognition using the residual masking network was used for neutral stimulus verification. Statistical analyses were performed using Pearson's correlation and regression analyses. RESULTS: Data of 45 participants with verified stimulus neutrality by deep learning image recognition were used for analysis. The first dwelling time was negatively correlated with the PANSS positive syndrome subscale (p = 0.028), general psychopathology subscale (p = 0.008), total score (p = 0.008), 5-factor positive symptoms (p = 0.035), and 5-factor depression/anxiety symptoms (p = 0.043). The baseline-area of interest (AOI) pupil diameter change was positively correlated with PANSS 5-factor positive symptom scores (p = 0.039). After adjusting for additional variables, the same items had a significant effect on the first dwelling time and baseline-AOI pupil diameter change. CONCLUSIONS: Psychopathology, particularly positive symptoms, was associated with gaze avoidance and pupil diameter in patients with schizophrenia. Evaluating the characteristics of eye movements in patients with schizophrenia will enable better understanding of their symptoms.

Relationship between disability self-awareness and cognitive and daily living function in schizophrenia.

We investigated the relationship between disability self-awareness and cognitive and daily living functions in 49 patients with schizophrenia. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS) self-report was used to identify patient-rated global function. A clinician-rated measure of global function was obtained using the Personal and Social Performance Scale (PSP); disability self-awareness was calculated using two global function scores. The Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS) were used to evaluate clinical symptoms, while the MATRICS consensus cognitive battery (MCCB) and the UCSD Performance-based Skills Assessment (UPSA) were applied to assess cognitive and daily living functionality, respectively. The WHODAS scores correlated significantly with the MCCB verbal learning, visual learning, and social cognition domains, and with the UPSA communication domain. The PSP correlated significantly with all MCCB and UPSA domains. Disability self-awareness demonstrated positive correlation with most domains of MCCB and UPSA. The findings of this study indicate that the lower the cognitive and daily living function in patients with schizophrenia, the more positively they perceive their own disability.

Association between Dialysis Adequacy and Cognition in Patients with Peritoneal Dialysis.

OBJECTIVE: Cognition of peritoneal dialysis patients is influenced by various factors including dialysis adequacy such as fractional urea clearance (Kt/V) and relative overhydration (RelOH). This study aimed to discover the potential contribution of dialysis adequacy to cognitive function in patients undergoing peritoneal dialysis. METHODS: Fifty-nine patients undergoing peritoneal dialysis were recruited. Demographic information, comorbidities, and clinical lab findings were retrospectively collected, and dialysis adequacy was determined by the Kt/V and RelOH calculation. Cognition and depression were measured with Digit Symbol Substitution Test, Hopkins Verbal Learning Test, Wechsler memory scale (spatial span), Wisconsin Card Sorting Test, and Beck's depression inventory. Partial correlation test was used to explore the correlation of dialysis adequacy with cognitive function. RESULTS: RelOH showed significant correlation with some of the Wisconsin Card Sorting test results. The categories achieved showed negative correlation (r=-0.32, p=0.02) and trials to complete first category showed positive correlation (r=0.31, p=0.02) with RelOH. Other tasks showed no significant correlation with RelOH. Kt/V. CONCLUSION: Our study demonstrates that peritoneal dialysis adequacy, measured by RelOH, seems to be significantly correlated with the occurrence of cognitive impairment. The outcome suggests that RelOH may have the potential to clarify the role of cognitive impairment in peritoneal dialysis patients.

Correlation between Performance-Based and Interview-Based Cognitive Measurements in Patients with Schizophrenia.

OBJECTIVE: The Measurement and Treatment Research to improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) is used to measure the cognitive function of patients with schizophrenia. In some situations, interview-based measures such as the Schizophrenia Cognition Rating Scale (SCoRS) may be appropriate. In this study, we analyzed the correlation between performance- and interview-based measurements in patients with schizophrenia. METHODS: Fifty-six clinically stable patients were recruited. To evaluate cognitive function, we used the MCCB performance-based measure and the SCoRS interview-based measure. Measurements were taken at baseline, and 2 weeks and 3 months later. Spearman correlations were computed between each SCoRS item's interviewer rating and each MCCB score. RESULTS: The correlation between the MCCB overall T score and the SCoRS global score was the strongest (r=-0.52), while the SCoRS total score and the MCCB Speed of Processing score also correlated (r=-0.48). The SCoRS global score showed statistically significant correlations with all seven MCCB domains and the overall T score. CONCLUSION: This study reveals correlations between MCCB domains and SCoRS items. Since we find that interview-based measurements are highly correlated with performance-based measurements, we suggest them as a useful cognitive function evaluation tool that can easily be applied in clinical settings.

Effects of an extrinsic motivator on the evaluation of cognitive and daily living functions in patients with schizophrenia.

We investigated the effect of an extrinsic motivator on the MATRICS Consensus Cognitive Battery (MCCB) and UCSD Performance-Based Skills Assessment (UPSA) scores, which assess cognitive and daily living functions, in patients with schizophrenia. We enrolled 60 clinically stable patients with schizophrenia and allocated them to the motivator or control group. We conducted baseline assessments of cognitive function using the MCCB, daily living function using the UPSA, clinical symptoms, and psychosocial characteristics in both groups. In the retrial, we initially evaluated clinical symptoms. Next, we assigned an extrinsic motivator to the motivator group and again assessed cognitive function and daily living function using the MCCB and UPSA. Statistical analyses were performed using t-tests, Chi-square tests, Fisher's exact test, repeated measures analysis of variance, and logistic regression analysis. We found significant time × group interactions in processing speed, verbal learning, visual learning, and composite scores of MCCB. There were no significant interactions in UPSA scores. The meaningful change rates of social cognition and composite scores in MCCB were significantly higher in the motivator group than in the control group. After adjusting for additional variables, the extrinsic motivator had a significant effect on the meaningful MCCB composite score change. Conclusively, our findings suggest beneficial effects of extrinsic motivator on the MCCB score in patients with schizophrenia. In the future, the implementation and interpretation of the MCCB considering the motivation is necessary.

Developing clinical cut-off scores for the university of California San Diego performance-based skills assessment in patients with schizophrenia.

This study aimed to obtain University of California San Diego Performance-based Skill Assessment (UPSA) cut-off scores for the purpose of severity classification and to expand the clinical utility of the UPSA for the evaluation of cognitive function in patients with schizophrenia. In total, 191 patients with schizophrenia were recruited. The UPSA, Positive and Negative Symptom Scale (PANSS), Clinical Global Impression-Schizophrenia Scale (CGI-SCH), and Global Assessment Functioning Scale (GAF) were used for the evaluation. The cognitive symptoms item of the CGI-SCH was used as a reference and the subjects were divided into three groups: mild, moderate, and severe. The sensitivity and specificity of the UPSA were analyzed by receiver operating characteristic curves. There were significant differences in the UPSA, CGI-SCH, PANSS, and GAF scores among the groups. In the mild and moderate groups, a UPSA score of 59 was identified as the optimal cut-off score, and a score of 41 was identified as the optimal cut-off score in the moderate and severe groups. Severity can be classified using the UPSA score as follows: ≥ 60 for mild, 41-59 for moderate, and ≤ 40 for severe. The UPSA could be used to assess the degree of daily living dysfunction in patients with schizophrenia.

The effect of anticholinergic burden on cognitive and daily living functions in patients with schizophrenia.

OBJECTIVE: This study aimed to explore the association between medication-associated anticholinergic burden and cognitive and daily living functions in patients with schizophrenia. METHODS: Sixty patients with schizophrenia were recruited. We used the Anticholinergic Drug Scale (ADS) for evaluating medication-associated anticholinergic burden. The MATRICS Consensus Cognitive Battery (MCCB) and the University of California San Diego Performance-based Skills Assessment (UPSA) were used for evaluating cognitive and daily living functions. To assess clinical symptoms, psychiatrists conducted interviews using the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. RESULTS: Subjects were divided into low (n = 31) and high (n = 29) anticholinergic burden based on ADS scores of 3 or more. The "high ADS" group had poorer cognitive (composite MCCB score, p < 0.001) and daily living functions (total UPSA score, p = 0.001) than the "low ADS" group. Medication-associated anticholinergic burden was negatively correlated with cognitive functions (composite MCCB score, r = -0.512, p < 0.001) and daily living functions (total UPSA score, r = -0.355, p = 0.005). A regression analysis showed that anticholinergic burden significantly explained the decline in cognitive functions (composite MCCB score, R2 = 0.262, p < 0.001) and daily living functions (total UPSA score, R2 = 0.126, p = 0.005). Explanatory power was reduced after a covariate adjustment, but the effects of the composite MCCB score (p = 0.013) and of the transportation domain score of the UPSA (p = 0.048) remained significant. CONCLUSIONS: Our analysis shows that anticholinergic burden reduces cognitive and daily living functions in patients with schizophrenia. A drug strategy with minimal anticholinergic burden may be helpful to patients if it does not adversely affect clinical symptoms.

Usefulness of the University of California San Diego Performance-Based Skills Assessment for the evaluation of cognitive function and activities of daily living function in patients with cognitive impairment.

OBJECTIVES: To assess the usefulness of the University of California San Diego Performance-Based Skills Assessment (UPSA) as a new diagnostic method and tool for the assessment of cognitive function and activities of daily living function in patients with cognitive impairment. METHOD: In total, 35 patients with cognitive impairment and 35 healthy controls were recruited for this study. The Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Global Deterioration Scale (GDS) were used for the evaluation of cognitive function, while the Barthel Activities of Daily Living Index (BADL), Instrumental Activities of Daily Living Index (IADL), and UPSA were used for the evaluation of activities of daily living function. RESULTS: UPSA scores were significantly lower in patients with cognitive impairment than in controls. The UPSA total score was significantly correlated with MMSE, CDR, GDS, and IADL scores. With regard to the detection of cognitive impairment, UPSA exhibited a greater determination power (R2 = 0.593) compared with BADL (R2 = 0.149) and IADL (R2 = 0.423) and higher sensitivity and specificity compared with IADL. CONCLUSION: Our results suggest that UPSA is a useful tool for the evaluation of cognitive function and activities of daily living function in patients with cognitive impairment.

Increased Bone Mineral Density after Abstinence in Male Patients with Alcohol Dependence.

OBJECTIVE: This study aimed to compare the bone mineral density of male patients with alcohol dependence with that in healthy controls and to assess changes in bone density after abstinence. METHODS: Forty-four inpatients with confirmed the Diagnostic and Statistical Manual of Mental Disorders, fourth edition diagnosis of alcohol abuse and 42 controls were recruited. Bone density was determined with dual-energy X-ray absorptiometry in the lumbar spine as well as in the femoral neck, trochanter, and Ward's triangle regions of the proximal right femur. RESULTS: There were no significant differences in age and body mass index between patients with alcohol dependence and healthy controls. In the alcohol dependence group, osteopenia and osteoporosis were found in 54.5% and 34.1% of the patients, respectively, whereas in the control group, the corresponding values were 45.2% and 11.9% (p=0.001). Although the actual bone density in the femur and the corresponding T-scores were significantly lower in the alcohol dependence group, no significant differences were found in the lumbar spine. In both groups, body mass index showed a significant correlation with bone mineral density in all areas. After 3 to 4 years of abstinence, bone density significantly increased in the lumbar and femur. CONCLUSION: We conclude that bone mineral density in patients with alcohol dependence was significantly lower than that in healthy controls, and the rates of osteopenia and osteoporosis are higher. Importantly, abstinence from alcohol increases bone density.

Associations Among Plasma Stress Markers and Symptoms of Anxiety and Depression in Patients with Breast Cancer Following Surgery.

OBJECTIVE: The objective of present study is to analyze the prevalence of depression and anxiety following breast cancer surgery and to assess the factors that affect postoperative psychological symptoms. METHODS: The Hamilton Rating Scale for Depression (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Body Image Scale (BIS), and Rosenberg Self Esteem Scale (RSES) were used to assess the psychological states of patients who had been diagnosed with and had undergone surgery for breast cancer. Blood concentrations of the stress markers adrenocorticotropic hormone, cortisol, arginine-vasopressin, and angiotensin-converting enzyme were measured. Pearson's correlation analysis and multilinear regression analysis were used to analyse the data. RESULTS: At least mild depressive symptoms were noted in 50.5% of patients, while 42.4% of patients exhibited at least mild anxiety symptoms. HAM-D score was positively correlated with HAM-A (r=0.83, p<0.001) and BIS (r=0.29, p<0.001) scores and negatively correlated with RSES score (r=-0.41, p<0.001). HAM-A score was positively correlated with BIS score (r=0.32, p<0.001) and negatively correlated with RSES score (r=-0.27, p<0.001). There were no statistically significant associations between stress markers and depression/anxiety. CONCLUSION: Patients with breast cancer frequently exhibit postoperative depression and anxiety, which are related to low levels of self-esteem and distorted body image.

Adjunct transcranial direct current stimulation improves cognitive function in patients with schizophrenia: A double-blind 12-week study.

OBJECTIVES: Cognitive impairment is a common symptom of schizophrenia that has significant effects on quality of life and the activities of daily living. The present study examined the ability of transcranial direct current stimulation (tDCS) to improve cognitive function and clinical symptoms in patients with schizophrenia. METHODS: Fifty-six patients with schizophrenia were randomized to real-tDCS and sham-tDCS groups. The participants were stable for a period of 3months before study enrollment. Each group received 30min of active 2-mA tDCS or sham stimulation over the left dorsolateral prefrontal cortex (anode F3, cathode F4) once per day for 10 consecutive weekdays. The Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) and Wisconsin Card Sorting Test (WCST) were used to evaluate cognitive function, and the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Schizophrenia scale (CGI-SCH), and Calgary Depression Scale for Schizophrenia (CDSS) were used to evaluate symptoms at baseline, after 10 sessions, and at 3-month follow-up. RESULTS: There was a significant time×group interaction, indicating that MCCB working memory (P=0.008) and overall scores (P=0.031) improved over time in the real-tDCS group compared to the sham-tDCS group. There was also a significant time×group interaction for depressive symptoms as evaluated by the CGI-SCH, which decreased over time in the real-tDCS group (P=0.041). tDCS treatment combined with antipsychotic medication was generally well-tolerated and safe. CONCLUSIONS: Adjunct tDCS treatment is safe and effective for improving cognitive status in patients with schizophrenia.

The Korean Version of the University of California San Diego Performance-based Skills Assessment: Reliability and Validity.

OBJECTIVE: The study's aim was to develop and standardize a Korean version of the University of California San Diego Performance-based Skills Assessment (K-UPSA), which is used to evaluate the daily living function of patients with schizophrenia. METHODS: Study participants were 78 patients with schizophrenia and 27 demographically matched healthy controls. We evaluated the clinical states and cognitive functions to verify K-UPSA's reliability and validity. For clinical states, the Positive and Negative Syndrome Scale, Clinical Global Impression-Schizophrenia scale, and Social and Occupational Functioning Assessment Scale and Schizophrenia Quality of Life Scale-fourth revision were used. The Schizophrenia Cognition Rating Scale, Short-form of Korean-Wechsler Adult Intelligence Scale, and Wisconsin Card Sorting Test were used to assess cognitive function. RESULTS: The K-UPSA had statistically significant reliability and validity. The K-UPSA has high internal consistency (Cronbach's alpha, 0.837) and test-retest reliability (intra-class correlation coefficient, 0.381-0.792; p＜0.001). The K-UPSA had significant discriminant validity (p＜0.001). Significant correlations between the K-UPSA's scores and most of the scales and tests listed above demonstrated K-UPSA's concurrent validity (p＜0.001). CONCLUSION: The K-UPSA is useful to evaluate the daily living function in Korean patients with schizophrenia.

The Korean Version of the Schizophrenia Cognition Rating Scale: Reliability and Validity.

OBJECTIVE: This study's aim was to develop and standardize a Korean version (SCoRS-K) of the Schizophrenia Cognition Rating Scale (SCoRS), which is used to evaluate the degree of cognitive dysfunction affecting the everyday functioning of people with schizophrenia. METHODS: Eighty-four schizophrenia patients with stable symptoms who were receiving outpatient treatment and rehabilitation therapy, and 29 demographically matched non-patient controls, participated in the study. Demographic data were collected, and clinical symptoms, cognitive function, and social function were evaluated to verify SCoRS-K's reliability and validity. Clinical symptoms were evaluated using the Positive and Negative Syndrome Scale and the Clinical Global Impression-Schizophrenia Scale. Cognitive function was evaluated using a short form of the Korean Wechsler Adult Intelligence Scale and the Wisconsin Card Sorting Test (WCST). Social function was evaluated using the Social and Occupational Functioning Assessment Scale, the Schizophrenia Quality of Life Scale, and the Social Functioning Scale. RESULTS: Data analysis demonstrated SCoRS-K's statistically significant reliability and validity. SCoRS-K has high internal consistency (Cronbach's alpha; patient 0.941, informant 0.905, interviewer 0.964); test-retest reliability [patient 0.428 (p=0.003), informant 0.502 (p<0.001), interviewer 0.602 (p<0.001); and global rating 0.642 (p<0.001)]. The mean scores of subjects were significantly higher than those of the controls (p<0.001), demonstrating SCoRS-K's discriminant validity. Significant correlations between the total scores and global rating score of SCoRS-K and those of the scales and tests listed above (except WCST) support SCoRS-K's concurrent validity. CONCLUSION: SCoRS-K is a useful instrument for evaluating the degree of cognitive dysfunction in Korean schizophrenia patients.

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 α4ß2 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 Student's 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.

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.

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.

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 α4ß2 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 χ2 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.

Adjunctive treatment with a dopamine partial agonist, aripiprazole, for antipsychotic-induced hyperprolactinemia: a placebo-controlled trial.

OBJECTIVE: Hyperprolactinemia and associated side effects often occur with antipsychotics. The authors investigated the effect of adjunctive treatment with aripiprazole on hyperprolactinemia and psychopathology in patients with schizophrenia maintained with haloperidol. METHOD: Fifty-six patients with hyperprolactinemia taking haloperidol were enrolled. Haloperidol dose was fixed; aripiprazole was dosed at 15 mg/day for the first 4 weeks, then 30 mg/day for the following 4 weeks. Serum prolactin, haloperidol, and aripiprazole levels were measured. Symptoms and side effects were assessed with the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms, Clinical Global Impression symptom scale, Simpson-Angus Rating Scale, and Barnes Akathisia Rating Scale at weeks 1, 2, 4, 6, and 8. RESULTS: Prolactin levels of patients receiving aripiprazole significantly decreased over time, demonstrating a significant time effect and a time-by-group interaction. In the aripiprazole group, 88.5% of patients at week 8 had prolactin levels normalize compared to 3.6% of patients receiving placebo. Among 11 female patients with menstrual disturbances randomly assigned to aripiprazole, seven patients regained menstruation during the study, whereas none receiving placebo did. Plasma levels of haloperidol were not significantly altered. No significant time effect and time-by-group interactions on BPRS, Scale for the Assessment of Negative Symptoms, and Simpson-Angus Rating Scale scores were noted. CONCLUSIONS: Adjunctive aripiprazole treatment reversed hyperprolactinemia in both sexes, resulting in reinstatement of menstruation in female patients, with no significant effects on psychopathology and extrapyramidal symptoms. Aripiprazole has higher affinity to dopamine D(2) receptors than haloperidol, which is the likely cause of this observation.