Individualized prediction of cognitive test scores from functional brain connectome in patients with first-episode late-life depression.

BACKGROUND: In the realm of cognitive screening, the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are widely utilized for detecting cognitive deficits in patients with late-life depression (LLD), However, the interindividual variability in neuroimaging biomarkers contributing to individual-specific symptom severity remains poorly understood. In this study, we used a connectome-based predictive model (CPM) approach on resting-state functional magnetic resonance imaging data from patients with LLD to establish individualized prediction models for the MoCA and the MMSE scores. METHODS: We recruited 135 individuals diagnosed with first-episode LLD for this research. Participants underwent the MMSE and MoCA tests, along with resting-state functional magnetic resonance imaging scans. Functional connectivity matrices derived from these scans were utilized in CPM models to predict MMSE or MoCA scores. Predictive precision was assessed by correlating predicted and observed scores, with the significance of prediction performance evaluated through a permutation test. RESULTS: The negative model of the CPM procedure demonstrated a significant capacity to predict MoCA scores (r = -0.309, p = 0.002). Similarly, the CPM procedure could predict MMSE scores (r = -0.236, p = 0.016). The predictive models for cognitive test scores in LLD primarily involved the visual network, somatomotor network, dorsal attention network, and ventral attention network. CONCLUSIONS: Brain functional connectivity emerges as a promising predictor of personalized cognitive test scores in LLD, suggesting that functional connectomes are potential neurobiological markers for cognitive performance in patients with LLD.

Executive function deficits and medial temporal lobe atrophy in late-life depression and Alzheimer's disease: a comparative study.

Objectives: Alzheimer's disease (AD) and late-life depression (LLD) frequently exhibit executive function deficits (EFD) and medial temporal lobe atrophy (MTA) as shared characteristics. The objective of this research was to examine the utility of the Trail Making Test (TMT) and the MTA scale in distinguishing between LLD and AD. Methods: A study of 100 patients, 50 with AD and 50 with LLD, was conducted using a cross-sectional design. The individuals were subjected to clinical evaluations to assess their level of depression and overall cognitive abilities, which included the Geriatric Depression Scale (GDS), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). We evaluated executive function deficits (EFD) through the use of the TMT, which includes both TMT-A and TMT-B. MTA was measured using magnetic resonance imaging. To evaluate the ability of TMT and MTA scale to distinguish between the two groups, a receiver operating characteristic (ROC) curve was utilized. To investigate the connections between MTA and neuropsychological measures, a correlation analysis was performed. Results: AD patients exhibited notably reduced MMSE, MoCA, and GDS scores, as well as an increased MTA total scores, time spent on TMT-A, and TMT-B compared to LLD patients (p < 0.05). TMT-A and TMT-B both exhibited excellent discriminatory power between AD and LLD, achieving area under curve (AUC) values of 92.2 and 94.2%, respectively. In AD patients, there was a negative correlation between MMSE and MoCA scores and MTA scores, while in LLD patients, there was a positive correlation between time spent on TMT-A and GDS scores and MTA scores. Conclusion: AD patients experience more severe EFD and MTA than LLD patients. The differential diagnosis of AD and LLD can be aided by the useful tool known as TMT. It is important to acknowledge that TMT is capable of capturing only a fraction of the executive function, thus necessitating a cautious interpretation of research findings.

The cognitive effects of adjunctive repetitive transcranial magnetic stimulation for late-onset depression: a randomized controlled trial with 4 week follow-up.

Objectives: Cognitive impairment is common and linked to poor outcomes in patients with late-onset depression (LOD). The cognitive effects of repetitive transcranial magnetic stimulation (rTMS) for LOD are not well understood. This study aimed to investigate the effects of rTMS on cognitive function in elderly patients with LOD. Methods: In total, 58 elderly patients (aged 60 to 75 years) with depression were enrolled and randomly assigned to an active rTMS group or a sham group. The participants received active or sham rTMS over the left dorsolateral prefrontal cortex for 4 weeks, 5 days a week, at a frequency of 10 Hz rTMS and 120% of the motor threshold (MT). Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at baseline, the end of the 4 week treatment period, and at the 4 week follow-up. Results: The active rTMS group showed significant improvements in immediate memory and attention scores on the RBANS compared to the sham group. However, no significant differences were observed between the two groups in other cognitive domains assessed by the RBANS. No serious adverse events related to rTMS treatment were observed. Conclusion: Treatment with 120% MT rTMS was associated with improvement in cognitive defects related to the active phase of LOD. These findings suggest that rTMS could provide early improvements in cognitive function in clinical settings for elderly patients with LOD.Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=40698, identifier ChiCTR1900024445.

Simultaneous measurement of amino acid enantiomers in the serum of late-life depression patients using convenient LC-MS/MS method with Nα-(5-fluoro-2,4-dinitrophenyl)-l-leucinamide Derivatization.

D-amino acids may be indicators of late-life depression but separation and quantification of enantiomers which differ only by optical rotation sign remain challenging due to their identical physical and chemical properties. A convenient LC-MS/MS method was developed for the simultaneous measurement of l- and d-amino acids based on the chiral derivatization reagent, Nα-(5-fluoro-2,4-dinitrophenyl)-L-leucinamide, and conventional octadecylsilane reversed-phase column. Methanol was used as the extraction solvent and a single-step derivatization reaction using volatile triethylamine eliminated the requirement for desalination prior to LC-MS/MS. Simultaneous separation and identification of 21 amino acids and the enantiomeric compositions of the 18 chiral proteogenic entities were achieved. Low limits of detection (0.03-4.0 nM), wide linear range (0.01-20 µM), good precision (RSDs < 10 %) and negligible matrix effects indicated the suitability of the method. Application of the method to the quantification of serum chiral amino acids in late-life depression patients (n = 40) and controls (n = 35) found a total of 17 L-amino acids, 14 D-amino acids, DL-asparagine, glycine and γ-aminobutyric acid. The statistical evaluation showed significant differences of glycine, L-threonine and D-methionine between late-life depression patients and controls, indicating that these are potential biomarkers of late-life depression.

Altered topological properties of functional brain networks in patients with first episode, late-life depression before and after antidepressant treatment.

Objectives: To preliminarily explore the functional activity and information integration of the brains under resting state based on graph theory in patients with first-episode, late-life depression (LLD) before and after antidepressant treatment. Methods: A total of 50 patients with first-episode LLD and 40 non-depressed controls (NCs) were recruited for the present research. Participants underwent the RBANS test, the 17-item Hamilton depression rating scale (HAMD-17) test, and resting-state functional MRI scans (rs-fMRI). The RBANS test consists of 12 sub-tests that contribute to a total score and index scores across the five domains: immediate memory, visuospatial/constructional, language, attention, and delayed memory. Escitalopram or sertraline was adopted for treating depression, and the dosage of the drug was adjusted by the experienced psychiatrists. Of the 50 LLD patients, 27 cases who completed 6-month follow-ups and 27 NCs matched with age, sex, and education level were included for the final statistical analysis. Results: There were significant differences in RBANS total score, immediate memory, visuospatial/constructional, language, attention, and delayed memory between LLD baseline group and NCs group (P < 0.05). Considering the global attribute indicators, the clustering coefficient of global indicators was lower in the LLD baseline group than in the NCs group, and the small-world attribute of functional brain networks existed in all three groups. The degree centrality and node efficiency of some brains were lower in the LLD baseline group than in the NCs group. After 6 months of antidepressant therapy, the scores of HAMD-17, immediate memory, language, and delayed memory in the LLD follow-up group were higher than those in the LLD baseline group. Compared with the LLD baseline group, the degree centrality and node efficiency of some brains in the cognitive control network were decreased in the LLD follow-up group. Conclusions: The ability to integrate and divide labor of functional brain networks declines in LLD patients and linked with the depression severity. After the relief of depressive symptoms, the small-world attribute of functional brain networks in LLD patients persists. However, the information transmission efficiency and centrality of some brain regions continue to decline over time, perhaps related to their progressive cognitive impairment.

Prediction of Antidepressant Efficacy by Cognitive Function in First-Episode Late-Life Depression: A Pilot Study.

The response rate of treatment for late-life depression (LLD) is only 25-60%. The cognitive impairment associated with LLD often affects the effectiveness of antidepressants and may has the potential ability to predict response. This study seeks a biomarker for baseline cognitive function to predict efficacy of antidepressants. Sixty patients diagnosed with LLD received escitalopram or sertraline treatment for 8 weeks. Clinical symptom was measured using Hamilton Depression Rating Scale-17 (HAMD-17) and cognitive function was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Trail Making Test (TMT) before and after 8-week treatment. Patients were divided into treatment effective group (TE) and treatment ineffective group (TI) according to reduction rate in scores of HAMD-17 after treatment. Thirty-eight matched healthy controls (HC) were assessed using RBANS and TMT. There was significant decrease of score of RBANS and increase of score of TMT in patients with LLD compared with HC. Regression analysis revealed that change in HAMD-17 score was significantly positively associated with baseline score of picture naming, figure copy, digit span, and delayed memory. The preliminary findings suggested that working memory, attention, visuospatial, language function, and delayed memory should be examined further as a means of providing the useful objective biomarkers of treatment response. Clinical Trials Registration: [www.ClinicalTrials.gov], identifier [ChiCTR2100042370].

Altered Intrinsic Brain Activity in Patients With Late-Life Depression: A Resting-State Functional MRI Study.

Objectives: To investigate the altered intrinsic brain activity (IBA) in patients suffering from late-life depression (LLD) using a percent amplitude of fluctuation (PerAF) method. Methods: In total, fifty patients with LLD and 40 non-depressed controls (NCs) were recruited for the present research. Participants underwent the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test and resting-state functional MRI (rs-fMRI) scans. The RBANS test consists of 12 sub-tests that contribute to a total score and index scores across the following five domains: immediate memory, visuospatial/constructional, language, attention, and delayed memory. The PerAF method was used for data analysis to detect changes in neural activity in the relevant brain regions. A receiver operating characteristic (ROC) curve was conducted to evaluate the ability of the RBANS test and proposed the PerAF method in distinguishing the two groups. The relationships between altered IBA and neuropsychologic deficits were determined by the Pearson correlation analysis. Results: A significant difference existed in RBANS total score, immediate memory, visuospatial/constructional, language, attention, and delayed memory between groups (P < 0.05). Compared with the NCs group, the LLD group demonstrated decreased PerAF differences in the bilateral superior frontal gyrus, orbital part (Frontal_Sup_Orb), and bilateral anterior cingulate cortex (ACC). The PerAF method and RBANS test exhibited an excellent discriminatory power with the area under curve (AUC) values in distinguishing the two groups. In addition, the attention score of the RBANS test positively correlated with the PerAF values of the bilateral Frontal_Sup_Orb and bilateral ACC. Conclusion: The changes of PerAF in the bilateral Frontal_Sup_Orb and bilateral ACC are related to an increased risk of developing LLD. Moreover, the PerAF method could be used as an underlying sensitivity biomarker to identify the psychiatric disorder.

Risk factors for suicidal behavior in late-life depression: A retrospective preliminary clinical study.

AIM: To explore the risk factors associated with suicidal behavior (SB) using logistic regression analysis and the propensity score matching (PSM) method among Chinese patients suffering from late-life depression (LLD). METHOD: Patient information sheets were retrieved with the International Classification of Diseases, Tenth Revision (ICD-10) code from an electronic database that comprised patient medical information. Herein, we set SB as a dependent variable, and gender, marital status, monthly income, quality of interpersonal relationships, hobbies, impulsivity, severity of depression, psychiatric symptoms or not, and having histories of smoking, drinking, major mental trauma as independent variables according to clinical experience and previous findings. For uncertain independent risk factors associated with SB generated by logistic regression analysis, PSM was performed for further verification. RESULTS: The differences between the SB group and non-SB group for marital status, severity of depression, a history of drinking, and a history of major mental trauma were found to be statistically significant in univariate comparisons (P < 0.05); binary logistic regression analysis and PSM analysis showed that the severity of depression, a history of drinking, and a history of major mental trauma were independent risk factors associated with SB of patients with LLD with an odds ratio greater than one. CONCLUSION: The severity of depression, a history of drinking, and a history of major mental trauma were independently associated with the occurrence of SB of patients with LLD in China. Further longitudinal and prospective studies are warranted to examine the dynamic changes of confounding risk factors. Geriatr Gerontol Int 2021; 21: 849-854.

A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer's dementia.

BACKGROUND: New therapies are urgently needed for Alzheimer's disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. METHODS: We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. RESULTS: A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was - 2.15 points (95% confidence interval, - 3.07 to - 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group. CONCLUSIONS: GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. TRIAL REGISTRATION: ClinicalTrials.gov, NCT0229391 5. Registered on November 19, 2014.

Relationship Between Alzheimer's Disease and Retinal Choroidal Thickness: A Cross-Sectional Study.

BACKGROUND: The choroid is involved directly or indirectly in many pathological conditions such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). OBJECTIVE: The objective of this study was to investigate the association between retinal choroidal properties and the pathology of AD by determining choroidal thickness, hippocampus volume, cognitive functions, and plasma BACE1 activity. METHODS: In this cross-sectional study, 37 patients with AD and 34 age-matched controls were included. Retinal choroidal thickness was measured via enhanced depth imaging optical coherence tomography. Hippocampal volume was measured via 3.0T MRI. Cognitive functions were evaluated using the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog). Plasma BACE1 activity was analyzed using a fluorescence substrate-based plasma assay, and regression model were to analyze the data. RESULTS: Retinal choroidal thickness was significantly thinner in the AD group than in the control group [(114.81±81.30) µm versus (233.79±38.29) µm, p < 0.05]. Multivariable regression analysis indicated that the ADAS-cog scores (ß=-0.772, p = 0.000) and age (ß=-0.176, p = 0.015) were independently associated with choroidal thickness. The logistic regression model revealed that the subfoveal choroidal thickness was a significant predictor for AD (OR = 0.984, 95% CI: 0.972-0.997). CONCLUSION: There was a general tendency of choroid thinning as the cognitive function declined. Although choroidal thickness was not a potential indicator for early stage AD, it was valuable in monitoring AD progression.

Efficacy of Group Reminiscence Therapy on Cognition, Depression, Neuropsychiatric Symptoms, and Activities of Daily Living for Patients With Alzheimer Disease.

The current study aimed to investigate the effects of group reminiscence therapy on cognitive function, depression, neuropsychiatric symptoms, and activities of daily living in patients with mild-to-moderate Alzheimer disease (AD). A single-blind randomized parallel-design controlled trial was conducted between May 1, 2017, and April 30, 2018. Ninety patients with mild-to-moderate AD recruited from Beijing Geriatric Hospital were randomly allocated into intervention (n = 45) and control groups (n = 45). In the intervention group, group-based reminiscence therapy was performed in two 30- to 45-minute sessions weekly for 12 weeks. Control participants received only conventional drug treatments and routine daily care. Alzheimer disease-related symptoms were evaluated using the Alzheimer's Disease Assessment Scale-Cognitive section, the Cornell Scale for Depression in Dementia (CSDD), the Neuropsychiatric Inventory, and the Barthel Index. Four time points were set for data collection: baseline (before treatment), 4 weeks (during treatment), 12 weeks (end of treatment), and 24 weeks (12 weeks posttreatment). χ2 Tests, independent t tests, repeated-measures analysis of variance, and Bonferroni tests were used for data analysis. Significant improvements in depressive and neuropsychiatric symptoms were found in the intervention group compared to the control group (P < .05). Mean CSDD scores in the intervention group were improved at all 3 time points compared to baseline and showed the greatest effect at 12 weeks (t = 2.076, P = .041) and 24 weeks follow-up (t = 3.834, P = .000) compared to controls. Group reminiscence therapy was effective for improving depressive symptoms and was beneficial for treating neuropsychiatric symptoms in patients with AD.

Nonsteroidal anti-inflammatory drugs use and risk of Parkinson disease: A dose-response meta-analysis.

Previous studies have indicated that nonsteroidal anti-inflammatory drugs (NSAIDs) use is associated with Parkinson disease risk, but presented controversial results.Medline, Embase, Web of Science, and the Cochrane Database were searched update to November 2017. Key data were extracted from eligible studies. A dose-response meta-analysis was conducted for synthesizing data from eligible studies.Fifteen eligible studies were included in this meta-analysis. NSAIDs use was not associated with Parkinson disease risk [relevant risk (RR): 0.06; 95% confidence interval (95% CI), 0.91-1.02]. Subgroup analysis showed that aspirin use (RR: 1.14; 95% CI, 0.98-1.30) or ibuprofen use (RR: 1.01; 95% CI, 0.88-1.17) was not associated with Parkinson disease risk; however, the use of non-aspirin NSAIDs was significantly associated with Parkinson disease risk (RR:0.91; 95% CI, 0.84-0.99). Furthermore, NSAIDs use was not associated with the risk of Parkinson disease in female (RR: 0.99; 95% CI, 0.83-1.17) and male (RR: 1.01; 95% CI, 0.88-1.16). In addition, a dose-response showed per 1 number of prescription incremental increase in NSAIDs use was not associated with the risk of Parkinson disease (RR: 0.96; 95% CI, 0.91-1.02), per 1 year of duration of NSAIDs use incremental increase was not associated with the risk of Parkinson disease (RR: 0.98; 95% CI, 0.92-1.03), and per 1 dosage of NSAIDs use incremental increase was not associated with the risk of Parkinson disease (RR: 0.98; 95% CI, 0.95-1.02).NSAIDs use was not associated with the risk of Parkinson disease. The potency and the cumulative NSAIDs use did not play critical roles.

Association between COMT gene polymorphisms, clinical symptoms, and cognitive functions in Han Chinese patients with schizophrenia.

AIM: Catechol-O-methyltransferase (COMT) gene variants may be involved in the pathogenesis of psychotic symptoms, and associated especially with negative symptom in schizophrenia, but their roles in cognitive function and treatment response remain unclear. The aim of this study was to explore the association between COMT gene polymorphisms, clinical symptoms (including cognitive function), and treatment response to antipsychotic medications in patients with schizophrenia. PATIENTS AND METHODS: A total of 200 Han Chinese inpatients with schizophrenia were recruited in accordance with Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV). In total, 96 of them completed assessments at baseline and after 8 weeks of antipsychotic treatment. Clinical symptoms were assessed using the Positive And Negative Syndrome Scale (PANSS), and cognitive function was evaluated using the Verbal Fluency Test, Trail Making Test A-B, Stroop Color-Word Test, and Wisconsin Card Sorting Test. Two single nucleotide polymorphisms, rs4680 and rs165599, on the COMT gene were genotyped. RESULTS: At baseline, we found no significant genotypic association between rs4680 and clinical symptoms or cognitive function. After 8 weeks of antipsychotic treatment, compared with patients with GG genotype, patients with AA/AG genotypes at rs4680 showed significantly higher scores on PANSS total, both at baseline and at the end of 8 weeks, especially in negative and general psychopathology symptoms. Patients with GG at rs165599 scored significantly higher on the Stroop test, suggesting better cognitive performance after 8 weeks of treatment. No significant association was found between rs165599 genotype and psychiatric symptoms as assessed by the PANSS and cognitive function tests at baseline. CONCLUSION: Our findings suggest that the COMT gene polymorphisms may influence the response to antipsychotic treatment in Han Chinese patients with schizophrenia.

Associations between the DBH gene, plasma dopamine ß-hydroxylase activity and cognitive measures in Han Chinese patients with schizophrenia.

The dopamine (DA) and norepinephrine (NE) systems modulate cognitive function. Dopamine ß-hydroxylase (DßH) converts DA to NE, and its activity is under strong genetic control. This study examines the association of plasma DßH (pDßH) activity, DBH gene polymorphisms (-1021C>T, rs1611115 and 444G>A, rs1108580) and cognitive deficits in Han Chinese patients with schizophrenia. We assessed pDßH activity and cognitive function using the Verbal Fluency Test (VFT), Trail Making Test (TMT) A-B, Stroop color-word test and Wisconsin Card Sorting Test (WCST) in 200 patients with schizophrenia before and after 8weeks of antipsychotic treatment (96 patients completed assessments at baseline and post-treatment). We found that rs1611115 was significantly associated with pDßH activity, and there was strong LD between rs1611115 and rs1108580 polymorphisms. Correlation analysis indicated that pDßH activity correlated nominally with improvement in VFT score after 8weeks antipsychotic treatment. Moreover, there was a significant genotype effect of the rs1108580 on VFT: the VFT score of patients with AA genotype was higher than that of patients with AG/GG genotype either at baseline or the end of 8 weeks after treatment. However, this difference was not observed for rs1611115. Our findings confirm a strong association between genotype at rs1611115 and pDßH activity in Chinese patients with schizophrenia. Our data also suggest the rs1108580 polymorphism may influence some aspects of cognitive function in schizophrenia.

Effects of risperidone on glucose metabolism in Chinese patients with schizophrenia: a prospective study.

BACKGROUND: While most of the second generation antipsychotic agents are associated with abnormal glucose metabolism, previous studies have shown that risperidone has relatively little effect upon blood glucose levels. This study aimed to explore the effect of risperidone on the glucose-regulating mechanism of patients with schizophrenia by using the oral glucose tolerance test (OGTT), measuring insulin and C-peptide levels. METHODS: Thirty inpatients with schizophrenia taking risperidone were studied. All the patients were given a simplified OGTT at baseline and six weeks after treatment. Plasma glucose, insulin, and C-peptide concentrations were measured at fasting, then 1 and 2h after OGTT respectively. Other data, including demographic characteristics and plasma drug concentrations, were also recorded. RESULTS: (1) There was no significant increase in the proportion of patients demonstrating abnormal plasma glucose levels compared with baseline (p=1.000, McNemar test); (2) risperidone was associated with elevated insulin concentrations (p=0.013), C-peptide levels (p=0.020), insulin/glucose ratio (p=0.020) and BMI (p<0.01); (3) no sex differences in glucose-related measures were observed. CONCLUSION: Risperidone treatment may be associated with alterations in glucose-regulating mechanisms in patients with schizophrenia.

Escitalopram in major depressive disorder: a multicenter, randomized, double-blind, fixed-dose, parallel trial in a Chinese population.

Escitalopram, the S-enantiomer of citalopram and the most selective of the selective serotonin reuptake inhibitor (SSRI) has been shown to be efficacious in the treatment of major depression in white populations. Our aim in this study was to investigate the efficacy and tolerability of escitalopram in Chinese patients with moderate to severe major depression. Patients who met DSM-IV criteria for a major depressive episode were enrolled in this multicenter, randomized, double-blind, fixed-dose comparison trial. Patients were given escitalopram 10 mg/day or fluoxetine 20 mg/day for 8 weeks. All patients were assessed with the 17-item Hamilton Depression Rating Scale (HAM-D-17) and the Montgomery-Asberg Depression Rating Scale (MADRS). Tolerability was assessed on the basis of adverse effects (measured with a locally developed checklist), regular biochemical tests, and electrocardiograph (ECG) assessments. Two hundred forty patients were enrolled and randomized to escitalopram (123 patients) or fluoxetine (117 patients). The HAM-D-17 total scores of both groups decreased significantly from baseline, but there was no significant difference at week 8 between the two groups (15.8 for escitalopram and 14.7 for fluoxetine; P >.05). There were no significant differences in response rates at all visits after treatment based on either HAM-D-17 or MADRS. A post hoc analysis indicated that escitalopram was superior to fluoxetine on two items of the HAM-D-17: "depressed mood" (P =.023) and "work and interest" (P =.024). The adverse events reported in the escitalopram and fluoxetine groups were comparable, and most were mild to moderate. Both drugs showed good compliance profiles. Escitalopram 10 mg/day is at least as efficacious as fluoxetine 20 mg/day and well tolerated in Chinese patients with major depression, with possible superiority in some core symptoms such as "depressed mood" and "work and interest."

Gender differences in 542 Chinese inpatients with schizophrenia.

OBJECTIVE: To investigate gender differences in the onset and other clinical features of Han Chinese inpatients with schizophrenia. METHODS: Five-hundred-and-forty-two Han Chinese inpatients with DSM-IV schizophrenia were assessed with the Positive and Negative Symptoms Scale (PANSS), the Brief Psychiatric Rating Scale (BPRS), the Global Assessment of Function scale (GAF) and locally-developed standardized data collection forms. Comparisons were made between male and female patients. RESULTS: This is the largest study of gender differences in schizophrenia to be conducted in a Chinese population. In our sample, we found that schizophrenia onset occurred at a significantly earlier age in male patients compared to female patients and that late-onset schizophrenia (as defined by onset> or =45 years) was significantly more common in female patients. The paranoid subtype of schizophrenia was less common in male patients, males received higher daily doses of antipsychotics and demonstrated a different pattern of antipsychotic usage, being less likely to be treated with SGAs. Further, cigarette smoking was more common in male patients and male patients were more likely to be single or never married. By contrast, female patients showed a different pattern of ongoing symptoms and severity, being more likely to have persistent positive symptoms, more severe positive and affective symptoms, and a greater number of suicide attempts whereas male patients were more likely to show severe deterioration over time. CONCLUSIONS: There are notable gender differences in the age at onset, treatment and a range of other clinical features in Han Chinese patients with schizophrenia. Such differences were largely consistent with those reported in Western studies. These gender differences need to be considered in the assessment and management of Chinese patients with schizophrenia.

Gender, age, smoking behaviour and plasma clozapine concentrations in 193 Chinese inpatients with schizophrenia.

AIM: To study the relationship between age, gender, cigarette smoking and plasma concentrations of clozapine (CLZ) and its metabolite, norclozapine (NCLZ) in Chinese patients with schizophrenia. METHODS: Data from a therapeutic drug monitoring programme were analysed retrospectively. One hundred and ninety-three Chinese inpatients with schizophrenia were assessed using clinical data forms. Steady-state plasma concentrations of CLZ and NCLZ were assayed using high-performance liquid chromatography. Comparisons of dosage and plasma CLZ concentrations were undertaken between males (n = 116) and females (n = 77), younger (40 years, n = 111) and current male smokers (n = 50) and nonsmokers (n = 66). RESULTS: (i) Plasma CLZ concentrations demonstrated large interindividual variability, up to eightfold at a given dose; (ii) there were significant effects of gender on plasma CLZ concentrations (relative to dose per kg of body weight) with female patients having significantly higher concentrations than males (30.09 +/- 24.86 vs. 19.87 +/- 3.55 ng ml(-1) mg(-1) day(-1) kg(-1); P < 0.001); (iii) there were no significant differences in plasma CLZ concentrations between those patients 40 years; and (iv) there were no significant differences in plasma CLZ concentrations between male smokers and nonsmokers, despite the CLZ dosage for smokers being significantly higher. CONCLUSIONS: Plasma CLZ concentrations vary up to eightfold in Chinese patients. Among the patient-related factors investigated, only gender was significant in affecting CLZ concentrations in Chinese patients with schizophrenia, with female patients having higher levels.

Antipsychotic drug use in 503 Chinese inpatients with schizophrenia.

Objective. To determine current patterns of antipsychotic medication use and metabolic complications among hospitalized Chinese patients with schizophrenia. Method. A total of 503 inpatients who met ICD-10 diagnostic criteria for schizophrenia were enrolled. Demographic features and records of current treatment (medication, dose, duration of treatment) were collected through cross-sectional chart review along with biophysical parameters (body mass index and laboratory findings). Results. (1) Most patients (457/503, 90.9%) were found to receive antipsychotic monotherapy; (2) clozapine was the most common medication used (152/507, 30.2%); (3) the subset of patients treated within the course of a first episode psychosis, or with less than 5 years of illness, were more likely to be treated with second-generation antipsychotics (SGAs) than with conventional antipsychotic medications or clozapine; (4) patients treated with clozapine or conventional antipsychotics were more likely to manifest metabolism-related physical conditions than those receiving SGAs. Conclusion. Conventional antipsychotics and clozapine constitute the current mainstream of schizophrenia treatment in China where a lower percentage of patients receive SGAs other than clozapine than in developed countries. The high incidence of treatment-related metabolic complications in this population suggests that these issues are under-appreciated based on current patterns of medication use.

Cigarette smoking in Chinese male inpatients with schizophrenia: a cross-sectional analysis.

Given the high rates of cigarette smoking in schizophrenia in many published studies from around the world, we studied the relationship between smoking status and clinical characteristics in male Chinese schizophrenic inpatients. Two hundred seventy-nine schizophrenic inpatients were assessed using clinical data forms to ascertain historical, demographic and treatment variables and collateral information was also collected from case records and interviews with patients and family members. Current smokers (N=112) were compared with non-smokers (N=167) on clinical variables by independent sample t-tests and chi(2) tests, with adjustment for confounding variables using ANCOVA and binary logistic regression analysis. Compared to non-smokers, current smokers were significantly more likely to be divorced, have lower educational attainment, a more episodic course, have a greater number of previous psychotic relapses and more likely to be treated with clozapine. There was no correlation, however, between smoking consumption and schizophrenic psychopathology. Accordingly, cigarette smoking may be associated with certain clinical features in schizophrenic patients, and should be carefully screened for when making treatment and rehabilitation plans.