Sex differences in prevalence and clinical correlates of insomnia in Chinese patients with chronic schizophrenia.

OBJECTIVE: It is generally recognized that there are sex differences in many aspects of schizophrenia. The main purpose of this study was to investigate the sex differences in the prevalence and clinical correlates of insomnia in patients with chronic schizophrenia. METHODS: A total of 957 patients who met the DSM-IV diagnostic criteria for schizophrenia were recruited in this cross-sectional study (male/female = 630/327). Demographic, clinical, and insomnia data were collected using self-reported questionnaires. Fasting blood samples were collected to evaluate the status of blood lipids. Psychopathological symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS: The prevalence rate of insomnia in female patients with schizophrenia was significantly higher than that in male patients (17.3% for males and 26.3% for females; χ2 = 10.74, p = 0.001). Regression analysis showed that in male patients, insomnia was independently associated with severe PANSS positive symptoms, severe PANSS depressive factor, and high levels of low-density lipoprotein levels, while in female patients, insomnia was associated with low education level, high PANSS depressive factor, and high levels of apolipoprotein B levels. CONCLUSION: This study illustrates that insomnia is more frequent in female than male schizophrenia patients, and that there are differences in the clinical correlates of insomnia by sex, suggesting that sex differences should be considered in prevention and treatment strategies for coexisting insomnia in schizophrenia patients.

Association of P50 with social function, but not with cognition in patients with first-episode schizophrenia.

Functional deficits including cognitive impairment and social dysfunction are the core symptoms of schizophrenia (SCZ), and sensory gating (SG) deficits may be involved in the pathological mechanism of functional deficits in SCZ. This study was to investigate the relationship between defective P50 inhibition and functional deficits in first-episode drug naïve (FEDN) SCZ patients. A total of 95 FEDN SCZ patients and 53 healthy controls (HC) were recruited. The Chinese version of UCSD Performance-Based Skills (UPSA), MATRICS Consensus Cognitive Battery (MCCB), and EEG system were used to assess the social function, cognitive performance, and P50 inhibition, respectively. The MCCB total score and eight domain scores were significantly lower in patients with FEDN SCZ than those in HC (all p < 0.05). The UPSA total score and financial skills scores were also significantly lower in SCZ patients than that in the HC (all p < 0.05). Compared with HC, patients with FEDF SCZ had a higher P50 ratio (all p < 0.05). There was no correlation between P50 components and MCCB scores in patients with FEDF SCZ. However, there was only a correlation between the P50 ratio and UPSA financial skills, communication skills, or total score in patients (all p < 0.05). Defective P50 inhibition in FEDN SCZ patients may be associated with social dysfunction but not cognitive impairment, suggesting that the social dysfunction and cognitive impairment of patients with FEDN SCZ may have different pathogenic mechanisms.

Sex difference in association between cognitive and P50 deficits in patients with chronic schizophrenia.

A large number of studies have reported that sensory gating disorders represented by P50 inhibition may be involved in the pathophysiological process of schizophrenia. However, few studies have explored the relationship between sensory gating disorders and cognitive dysfunction in patients with schizophrenia. This study aimed to explore sex differences in the relationship between cognitive and P50 deficits in patients with chronic schizophrenia, which has not been reported. A total of 183 chronic schizophrenia patients (128 males and 55 females) and 166 healthy controls (76 males and 90 females) participated in this study. The MATRICS Consensus Cognitive Battery (MCCB) was measured for cognitive function and P50 components for the sensory gating in all participants. The Positive and Negative Syndrome Scales (PANSS) was used to assess the psychopathological symptoms in patients. Female patients performed significantly better than male patients in several cognitive domains of MCCB (all p < 0.01). There were no significant differences in P50 components between male and female patients (all p > 0.05). Further analysis showed that in female patients, latency of S2 was negatively correlated with reasoning and problem-solving domain of MCCB (p < 0.05), and P50 ratio was negatively correlated with social cognition domain of MCCB (p < 0.05). In male patients, there was no any correlation between P50 and cognitive domains of MCCB. Our results suggest that there is a sex difference in the association between P50 deficiency and cognitive impairment in Chinese Han patients with schizophrenia.

Demographics, clinical characteristics and cognitive symptoms of heavy smokers and non-heavy smokers in Chinese male patients with chronic schizophrenia.

Many studies have shown a high smoking rate and cognitive impairment in patients with schizophrenia. The effects of smoking and nicotine intake on cognitive function in schizophrenia are still controversial. In this study, we divided patients into heavy smoking and non-heavy smoking groups and compared the clinical characteristics and cognitive symptoms between the two groups in Chinese male patients with schizophrenia. A total of 154 heavy smoking patients and 372 non-heavy smoking patients were recruited. They completed a detailed questionnaire including general and socio-demographic data. Positive and Negative Syndrome Scale (PANSS) was rated for psychopathology. The Fagerstrom Test for Nicotine Dependence (FTND) was used to assess the degree of nicotine dependence. Heavy smokers were younger, started smoking earlier and had a higher FTND total score than non-heavy smoking patients. Moreover, we found that heavy smokers had significantly lower negative symptom scores and cognitive factor scores than non-heavy smokers. Logistic regression analysis showed that cognitive factor score and age of initial smoking were significantly associated with heavy smoking. Linear regression analysis showed that cognitive factor score, age of initial smoking and dose of antipsychotics were significant predictors of the amount of smoking. Our findings suggest that there are significant differences in some demographic and clinical variables between heavy and non-heavy smokers in Chinese male patients with chronic schizophrenia. Moreover, heavy smokers have less cognitive symptoms, suggesting that heavy smoking may be beneficial for cognition of patients with schizophrenia.

Macrophage migration inhibitory factor as a potential novel biomarker for cognitive function in patients with first-episode schizophrenia.

OBJECTIVE: Cognitive impairment is prevalent in schizophrenia. Macrophage migration inhibitory factor which is released into the circulation under stress or inflammation, is associated with cognition and also plays an important role in immunity. However, no study has investigated the relationship between macrophage migration inhibitory factor and cognitive function in first-episode schizophrenia patients at baseline or after treatment. This study investigated the pre- and post-risperidone treatment correlations between serum macrophage migration inhibitory factor levels and cognitive function in first-episode schizophrenia patients. METHODS: A total of 83 first-episode schizophrenia patients who received risperidone monotherapy and 57 healthy controls - matched for sex, age, smoking status, education (years), marital status and waist-to-hip ratio - were included. Macrophage migration inhibitory factor levels were measured before and 10 weeks after treatment in the patient group and at baseline in the controls. Pre- and post-treatment cognitive functions in patients were assessed using the MATRICS Consensus Cognitive Battery. RESULTS: At baseline, macrophage migration inhibitory factor levels were significantly higher in first-episode schizophrenia patients than those in healthy controls (p < 0.01) and decreased in patients after 10 weeks of risperidone treatment compared with baseline (p < 0.05). The MATRICS Consensus Cognitive Battery total score and the sub-scores for the Trail Making Test, Symbol Coding, Letter Number Sequence, Maze and Brief Visuospatial Memory Test-Revised improved significantly after risperidone treatment. After controlling for age, sex, education, waist-to-hip ratio and smoking status, partial correlation analysis showed a positive correlation between baseline macrophage migration inhibitory factor levels and patients' baseline MATRICS Consensus Cognitive Battery verbal memory scores (r = 0.29, p = 0.01). Macrophage migration inhibitory factor changes correlated negatively with verbal memory changes (r = -0.26, p = 0.04). Multiple linear regression analysis identified a definite correlation between the changes in word memory test score and macrophage migration inhibitory factor level (ß = -0.09, p = 0.04). CONCLUSION: Macrophage migration inhibitory factor may be involved in the process of cognitive impairment in first-episode schizophrenia and repair mechanisms following risperidone treatment.

Treatment response prediction and individualized identification of first-episode drug-naïve schizophrenia using brain functional connectivity.

Identifying biomarkers in schizophrenia during the first episode without the confounding effects of treatment has been challenging. Leveraging these biomarkers to establish diagnosis and make individualized predictions of future treatment responses to antipsychotics would be of great value, but there has been limited progress. In this study, by using machine learning algorithms and the functional connections of the superior temporal cortex, we successfully identified the first-episode drug-naive (FEDN) schizophrenia patients (accuracy 78.6%) and predict their responses to antipsychotic treatment (accuracy 82.5%) at an individual level. The functional connections (FC) were derived using the mutual information and the correlations, between the blood-oxygen-level dependent signals of the superior temporal cortex and other cortical regions acquired with the resting-state functional magnetic resonance imaging. We also found that the mutual information and correlation FC was informative in identifying individual FEDN schizophrenia and prediction of treatment response, respectively. The methods and findings in this paper could provide a critical step toward individualized identification and treatment response prediction in first-episode drug-naive schizophrenia, which could complement other biomarkers in the development of precision medicine approaches for this severe mental disorder.

Glucose disturbances, cognitive deficits and white matter abnormalities in first-episode drug-naive schizophrenia.

Disturbance of glucose metabolism may be implicated in cognitive deficits of schizophrenia in its early phases. Many studies have reported the important role of widespread disruption of white matter (WM) connectivity in pathogenesis, cognitive deficit and psychopathology of schizophrenia. However, no study has investigated their inter-relationships in drug-naive first episode (DNFE) patients with schizophrenia. Glucose metabolism parameters including fasting glucose, insulin and homeostasis model of assessment-insulin resistance (HOMA-IR) index, cognitive performance on the MATRICS Consensus Cognitive Battery (MCCB) and the voxel-wised WM fractional anisotropy (FA) values were examined using DTI in 39 DNFE schizophrenia and 31 control subjects. The Positive and Negative Syndrome Scale was utilized for clinical symptoms. The patients showed significantly greater fasting plasma levels of glucose and insulin and HOMA-IR, and poorer cognitive scores, together with widespread reduced FA values in five brain areas, including left and right corpus callosum, superior longitudinal fasciculus, posterior thalamic radiation, and corona radiata (all p < 0.05). Association analysis showed that glucose level was positively associated with Digital Sequence Test and Continuous Performance Test, but negatively with FA values in posterior thalamic radiation and left corpus callosum in patients (all p < 0.05). Furthermore, multiple regression analysis revealed that the interactions of glucose × FA in left corpus callosum, longitudinal fasciculus and corona radiata were independent contributors to the Brief Visuospatial Memory Test (BVMT) of MCCB, while the interaction of glucose × FA in left corpus callosum, or in longitudinal fasciculus was associated with MCCB mazes and Trail Making A Test, respectively. Therefore, abnormal glucose metabolism, cognitive impairment and widespread disruption of WM structure occur in an early course of schizophrenia onset. An interaction between glucose metabolism abnormality and the WM dysconnectivity may lead to cognitive impairment.

Correction: Glucose disturbances, cognitive deficits and white matter abnormalities in first-episode drug-naive schizophrenia.

A correction to this paper has been published and can be accessed via a link at the top of the paper.

Relationship between TNF-α levels and psychiatric symptoms in first-episode drug-naïve patients with schizophrenia before and after risperidone treatment and in chronic patients.

BACKGROUND: The influence of antipsychotic drugs on tumor necrosis factor-α (TNF-α) levels is unclear, and there is no consensus on the association between TNF-α and psychotic symptoms. This study aimed to investigate the differences in TNF-α levels and clinical correlations in first-episode drug-naïve (FEDN) patients with schizophrenia before and after treatment and in chronic patients. METHODS: A total of 103 (51 FEDN and 52 chronic) patients and 114 healthy controls were recruited. Demographic and clinical data, including TNF-α levels, were recorded. We used the Positive and Negative Syndrome Scale (PANSS) to measure the psychopathology of all patients. RESULTS: TNF-α levels before treatment were significantly higher in FEDN patients than in chronic patients and healthy controls. No significant sex differences were found in the TNF-α levels of patients with schizophrenia. The TNF-α levels before treatment were significantly positively related to changes in PANSS negative symptoms in FEDN patients. The TNF-α levels in chronic patients were significantly negatively correlated with the general psychopathology subscales and PANSS total scores. CONCLUSIONS: Increased TNF-α levels in FEDN patients and their correlation with psychopathology indicate that inflammatory cytokines may play a crucial role in the etiopathogenesis of schizophrenia, and inflammation-directed therapy may, therefore, improve negative symptoms.

Association of negative symptoms with cognitive impairment in Chinese Han patients with chronic schizophrenia.

OBJECTIVE: Cognitive impairment is an essential feature of schizophrenia; however, the relationship between clinical psychiatric symptoms with cognitive impairment is still unclear. Therefore, we aimed to assess cognitive deficits and the relationship between clinical symptoms and cognitive function in patients with chronic schizophrenia, which provide a reference guide for psychiatrists. METHODS: We compared the cognitive function in 312 schizophrenia inpatients and 397 healthy controls by using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The positive and negative symptom scale (PANSS) was used to assess the clinical symptoms of the patients. RESULTS: Analysis of covariance showed that the RBANS total and four index scores (all p < 0.001) were significantly lower in patients than healthy controls. After Bonferroni correction, Pearson correlation analysis showed that there was a significant negative association between PANSS negative symptom subscale and RBANS total score and all 5 domain scores (all p < 0.01). Further regression analysis showed that negative symptoms, age, age of onset, and antipsychotic dose were important independent predictors of cognitive deficits. CONCLUSIONS: Our findings suggest that patients with chronic schizophrenia exhibit cognitive deficits compared with healthy people. Negative symptoms and some clinical variables are associated with cognitive impairment in patients with schizophrenia.KEYPOINTSThis study indicates that patients with chronic schizophrenia have extensive cognitive impairment shown on RBANS except for the visuospatial/constructional domain.Cognitive impairment in patients is associated with age, negative symptoms, age of onset, and antipsychotic dose.There is a significant negative association between cognitive deficits and negative symptoms in patients with chronic schizophrenia.The results of this study need to be confirmed in future studies with longitudinal designs with a large and sex-balanced sample in first-episode drug naïve patients with schizophrenia.

The prevalence, risk factors, and clinical characteristics of insulin resistance in Chinese patients with schizophrenia.

BACKGROUND: Studies have shown that patients with schizophrenia are at a high risk of developing insulin resistance (IR). We investigated the prevalence of IR and its clinical correlates in hospitalized Chinese patients with schizophrenia. METHODS: A total of 193 patients with schizophrenia (113 males and 80 females) were recruited for the study. We collected their demographic and clinical data, including data on their plasma glucose and lipid levels. All patients were rated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess cognitive function, while Positive and Negative Syndrome Scale (PANSS) was used to assess psychopathology. The cut-off value for the homeostasis model assessment of insulin resistance (HOMA-IR) was set at 1.7. RESULTS: The prevalence of IR was 37.82% (73/193). The IR patients had significantly higher waist-to-hip ratio and body mass index (BMI), and higher fasting plasma glucose (FPG), triglyceride (TG), and low density lipoprotein (LDL) levels compared to non-IR patients (all p<.05). Binary logistic regression analysis showed that smoking, BMI, and TG and LDL levels are significant predictors of IR. In addition, correlation analysis showed that IR was significantly correlated with the waist-to-hip ratio, BMI, and LDL level (Bonferroni corrected p<.05). The multivariable linear regression analysis indicated that the BMI and FPG are associated with the IR index. There was no significant difference in IR index between patients who were taking different antipsychotics. CONCLUSION: We found a high prevalence of IR and its risk factors in Chinese patients with schizophrenia. Active weight control to reduce the BMI and waist circumference and reducing the number of cigarettes consumed, may be essential to decrease the incidence of IR in patients with schizophrenia.

Interaction of BDNF with cytokines in chronic schizophrenia.

Brain-derived neurotrophic factor (BDNF) interacts with cytokines. Although both BDNF and cytokines occur at abnormal levels in schizophrenia patients, their interactions have not yet been examined. We therefore compared serum BDNF, TNF-α, interleukin (IL)-2, IL-6, and IL-8 levels in 92 chronically medicated schizophrenia patients and 60 healthy controls. We correlated these serum levels within these subject groups with each other and with clinical symptoms assessed according to the Positive and Negative Syndrome Scale (PANSS). Compared to the control group, the schizophrenia patients had significantly lower BDNF and TNF-α levels, and higher IL-2, IL-6, and IL-8 levels. The patients also showed a significant positive correlation between BDNF and both IL-2 and IL-8 levels, and low BDNF and TNF-α levels together were associated with poor performance on the PANSS cognitive factor. Thus, an interaction between cytokines and neurotrophic factors may be implicated in the pathophysiology of chronic schizophrenia. In particular, the cytokine TNF-α may interact with BNDF causing cognitive impairment.

Association of the manganese superoxide dismutase gene Ala-9Val polymorphism with age of smoking initiation in male schizophrenia smokers.

Schizophrenia patients exhibit higher smoking rates than the general population. A growing body of evidence suggests that cigarette smoke impairs the antioxidant defense mechanisms, leading to oxidative damage. Manganese superoxide dismutase (MnSOD) is the major antioxidant in the mitochondria, catalyzing the metabolism of superoxide radicals to form hydrogen peroxide. Since the identification of a well-characterized functional polymorphism, Ala-9Val of MnSOD, a number of studies have evaluated the association between Val-9Ala and schizophrenia or cancer. In this study, we hypothesized that the functional polymorphism of MnSOD Ala-9Val was associated with smoking in patients with schizophrenia. This polymorphism was genotyped in 666 chronic male schizophrenia patients (smoker/never-smoker = 507/159) and 660 male controls (smoker/never-smoker = 360/300) using a case-control design. The cigarettes smoked per day (CPD) and smoking behaviors were evaluated by clinician-administered questionnaires and the Fagerstrom Test for Nicotine Dependence (FTND). The results showed no significant differences in MnSOD Ala-9Val genotype and allele distributions between the patients and healthy controls or between smokers and never-smokers in either patients or healthy controls alone. The smokers with the Ala allele started smoking significantly earlier (19.9 ± 5.8 vs. 21.7 ± 6.5 years, P = 0.005) only in patients. These results suggest that the MnSOD Ala-9Val polymorphism may not influence smoking status in a Chinese male schizophrenia population, but may influence the age at which smoking is started among schizophrenia smokers.

Efficacy and safety of prolonged-release trazodone in major depressive disorder: a multicenter, randomized, double-blind, flexible-dose trial.

OBJECTIVE: To investigate the efficacy, safety, and clinical benefit of prolonged-release trazodone (Trittico) in the treatment of major depressive disorder (MDD). METHODS: In this study, 363 Chinese patients with MDD were randomized 1:1 to receive either prolonged-release trazodone (150-450 mg) or placebo treatment for 6 weeks. The primary efficacy measurement was the change of the 17-item Hamilton Depression Rating Scale (HAMD-17) total score from baseline to the end of the study. The secondary efficacy measurements were the response and remission rates, the Clinical Global Impression - Improvement of Illness (CGI-I) score at the end of the study, and the change of the HAMD-14 total score and quality of sleep [evaluated by the Pittsburgh Sleep Quality Index (PSQI) scale] during the study period. RESULTS: The mean maximum daily dose was 273.11 mg for the trazodone group and 290.92 mg for the placebo group. At the end of the study, there was a significant difference between the two groups in the HAMD-17 change score (trazodone vs. placebo: -11.07 vs. -8.29, p < 0.001). Trazodone showed advantages at 1 week of treatment, and the effect lasted until the end of the study (week 6). The response and remission rates of the trazodone group were significantly higher than those in the placebo group (response rate: 59.6 vs. 37.2%, p < 0.001; remission rate: 35.5 vs. 22.2%, p = 0.005). The majority of the adverse reactions of trazodone were mild to moderate, and the most frequent adverse reactions (≥5%) were dizziness, dry mouth, somnolence, and nausea. CONCLUSIONS: Prolonged-release trazodone was more effective than placebo in MDD and was well tolerated.

A double-blind, randomized controlled study of the effects of celecoxib on clinical symptoms and cognitive impairment in patients with drug-naïve first episode schizophrenia: pharmacogenetic impact of cyclooxygenase-2 functional polymorphisms.

Chronic low-grade peripheral and central nervous system inflammation may have a role in the pathogenesis of schizophrenia (SCZ). Inhibition of cyclooxygenase-2 (COX2), the arachidonic acid pathway, may inhibit cytokine responses and minimize inflammation. In this study, we added the COX2 inhibitor celecoxib to risperidone monotherapy to examine its efficacy on clinical symptoms and cognitive deficits in drug-naïve first episode (DNFE) SCZ patients. First, we genotyped two polymorphisms (rs5275 and rs689466) in the COX-2 gene in a case-control study of 353 SCZ patients and 422 healthy controls. Ninety patients participated in a 12-week, double-blind, randomized, placebo-controlled trial of celecoxib 400 mg/day. We used the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess clinical symptoms and cognition. Our results show that the COX2 rs5275 polymorphism was significantly correlated with SCZ and positive symptoms. After 12-week treatment, celecoxib significantly improved the PANSS total and three subscale scores of SCZ patients. Furthermore, patients with the rs5275 TT genotype had greater improvement in PANSS total score than patients carrying the C allele. However, no significant difference in RBANS total and subscale scores existed between the celecoxib and placebo groups at week 12. Our findings suggest that COX2 inhibitors may be promising therapeutics for clinical symptoms rather than cognitive impairment in first episode SCZ patients. COX2 rs5275 gene polymorphism may be implicated in the development and the efficacy of treating clinical symptoms in SCZ.Trial Registration Number: The trial was registered with www.clinicaltrials.gov (NCT00686140).

Association between suicidal behavior and impaired glucose metabolism in first-episode drug-naïve patients with schizophrenia.

BACKGROUND: Schizophrenia (SZ) patients have been reported to have comorbid suicidal behavior (SB) and impaired glucose metabolism in early psychosis, but it is unclear whether impaired glucose metabolism plays a role in the occurrence of SB in patients with first-episode drug-naïve (FEDN) SZ. Therefore, our main aim was to examine the relationship between SB and glucose metabolism in FEDN SZ patients. METHODS: We recruited 319 FEDN SZ patients and collected information on their sociodemographic characteristics, clinical data, and glucose metabolism parameters. Participants' psychotic and depressive symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HAMD), respectively. Fasting plasma glucose and insulin levels were also measured. RESULTS: The percentage of FEDN SZ patients with SB was 45.5% (145/319). Compared to SZ patients without SB, SZ patients with SB exhibited higher scores on HAMD, PANSS positive subscale, as well as higher levels of fasting plasma glucose, fasting plasma insulin, and homeostasis model assessment of insulin resistance index (all p<0.05). Logistic regression analysis indicated that increased levels of insulin resistance (adjusted OR = 1.920), body mass index (adjusted OR = 0.931), and PANSS general psychopathology (adjusted OR = 1.041) were independently associated with SB. The Receiver Operating Characteristic Curve showed an Area Under Curve value of 0.732 for the combination of three factors in regression model to distinguish between SB and non-SB. CONCLUSIONS: Our results indicate that fasting glucose, fasting insulin, and insulin resistance are strongly associated with SB in FEDN SZ patients, suggesting that glucose metabolism abnormalities may be potential biomarkers of SB in SZ patients. Regular monitoring of glucose metabolism variables is essential for suicide prevention.

Ginkgo biloba for Tardive Dyskinesia and Plasma MnSOD Activity: Association with MnSOD Ala-9Val Variant.

BACKGROUND: Excessive free radicals are implicated in the pathophysiology of tardive dyskinesia (TD), and Ginkgo biloba extract (EGb761) scavenges free radicals, thereby enhancing antioxidant enzymes such as mitochondrial manganese superoxide dismutase (MnSOD). This study examined whether EGb761 treatment would improve TD symptoms and increase MnSOD activity, particularly in TD patients with specific MnSOD Val-9Ala genotype. METHODS: An EGb761 (240 mg/day) 12-week double-blind clinical trial with 157 TD patients was randomized. The severity of TD was measured by the Abnormal Involuntary Movement Scale (AIMS) and plasma MnSOD activity was assayed before and after 12 weeks of treatment. Further, in an expanded sample, we compared MnSOD activity in 159 TD, 227 non-TD and 280 healthy controls, as well as the allele frequencies and genotypes for the MnSOD Ala-9Val polymorphism in 352 TD, 486 non-TD and 1150 healthy controls. RESULTS: EGb761 significantly reduced TD symptoms and increased MnSOD activity in TD patients compared to placebo (both p < 0.01). Moreover, we found an interaction between genotype and treatment response (p < 0.001). Furthermore, in the EGb761 group, patients carrying the Ala allele displayed a significantly lower AIMS total score than patients with the Val/Val genotype. In addition, MnSOD activity was significantly lower at baseline in TD patients compared with healthy controls or non-TD patients. CONCLUSION: EGb761 treatment enhanced low MnSOD activity in TD patients and produced greater improvement in TD symptoms in patients with the Ala allele of the MnSOD Ala-9Val polymorphism.

Sex difference in association between tardive dyskinesia and cognitive deficits in patients with chronic schizophrenia.

BACKGROUND: Tardive dyskinesia (TD), a side effect due to long-term use of antipsychotic medication, is associated with cognitive impairment. Several studies have found sex differences in cognitive impairment in schizophrenia patients, while whether there are sex differences in cognitive performance in schizophrenia patients with TD has not been reported. METHODS: A total of 496 schizophrenia inpatients and 362 healthy controls were recruited for this study. We used the Positive and Negative Syndrome Scale (PANSS) to assess patients' psychopathological symptoms and the Abnormal Involuntary Movement Scale (AIMS) to assess the severity of TD. Cognitive function was measured in 313 of these inpatients and 310 of healthy controls using the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). RESULTS: Patients with schizophrenia performed worse in all cognitive domains than healthy controls(all p < 0.001). Compared to patients without TD, patients with TD had higher PANSS total, PANSS negative symptom subscale and AIMS scores (all p < 0.001), while RBANS total, visuospatial/constructional and attention subscale scores were significantly lower (all p < 0.05). In addition, the visuospatial/constructional and attention indices remained significantly lower in male patients with TD than those without TD (both p < 0.05), but these results were not observed in female patients. Moreover, visuospatial/constructional and attention indices were negatively correlated with total AIMS scores only in male patients (both p < 0.05). CONCLUSION: Our results suggest that there may be sex differences in cognitive impairment in schizophrenia patients with comorbid TD, indicating that female gender may have a protective effect on cognitive impairment in schizophrenia patients caused by TD.

Diabetes mellitus in patients with chronic bipolar disorder: prevalence, clinical correlates and relationship with homocysteine.

Comorbid diabetes mellitus in patients with bipolar disorder may contribute to increased morbidity and mortality. To determine the prevalence of diabetes mellitus in bipolar disorder patients and its clinico-demographic and homocysteine correlates, we conducted a cross-sectional survey of 195 bipolar disorder inpatients. They received questionnaires, clinical measurements and laboratory tests to assess demographic characteristics, anthropometric variables, clinical variables and plasma homocysteine levels. The prevalence of diabetes mellitus (including type 1, type 2 and special types) in Chinese bipolar disorder patients was 14.9%. Analysis of variance or chi-square test showed that compared with non-diabetic bipolar disorder patients, diabetic bipolar disorder patients were older, more often married, had a longer duration of disease, took less olanzapine and had a higher frequency of hypertension. However, there were no significant differences in body mass index (BMI) and homocysteine levels between diabetic and non-diabetic bipolar disorder patients. Logistic regression analysis showed that marital status and duration of disease were independently associated with diabetes mellitus in patients with bipolar disorder after controlling for age, use of olanzapine, presence of hypertension, BMI and homocysteine levels. These findings shed light on the clinico-demographic correlates of the increased prevalence of diabetes mellitus in bipolar disorder patients, rather than the correlation with some metabolic risk factors.

P50 sensory gating, cognitive deficits and depressive symptoms in first-episode antipsychotics-naïve schizophrenia.

OBJECTIVE: Sensory gating P50 (SG-P50) may be involved in the pathophysiological mechanisms of impaired cognition in schizophrenia (SCZ). Comorbid depressive symptoms are common in SCZ patients and are also found to be associated with their cognitive impairment. However, it is unclear whether SG-P50 is abnormal in first episode antipsychotics naïve (FEAN) SCZ patients with depressive symptoms. Our aimed to investigate the relationships between SG-P50, depressive symptoms and neurocognition in FEAN-SCZ patients. METHODS: We recruited 103 FEAN-SCZ patients (depression: n = 63; non-depression: n = 40) and 55 healthy controls. SG-P50 was measured using the standard auditory dual-click (S1&S2) paradigm. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale-17 (HDRS-17). Cognitive performance was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). RESULTS: Compared with non-depressive patients, depressive patients had a significantly larger S2 amplitude (p = 0.005) and a higher S2/S1 ratio at trend level (p = 0.075) after corrected. There were significant differences in the scores of CPT-IP and Mazes (NAB) between depressive and non-depressive FEAN-SCZ patients (both p values < 0.05). For all patients, the SG-P50 S2/S1 ratio was significantly correlated with HDRS-17 score (r = 0.23, p = 0.020) and MCCB-Symbol coding (r = -0.16, p = 0.043). For depressive FEAN-SCZ patients, S2 amplitude was an independent predictor of the MCCB-Mazes (NAB) (ß = -0.31, t = -2.52, p = 0.015). CONCLUSIONS: SG-P50 deficit may be an informational biomarker for depressive symptoms and neurocognitive impairments in FEAN-SCZ patients.