Prevalence, clinical features and prescription patterns of psychotropic medications for patients with psychotic depression in China.

OBJECTIVE: To investigate the prevalence of psychotic depression and the differences in sociodemographic and clinical characteristics and prescription patterns of psychotropic medications between patients with psychotic depression (PD) and patients with nonpsychotic depression (NPD) in China. METHODS: We conducted a cross-sectional study in 13 major psychiatric hospitals or the psychiatric units of general hospitals in China from September 1, 2010, to February 28, 2011. PD was defined according to the psychotic disorder section of the Mini International Neuropsychiatric Interview (MINI). The sociodemographic and clinical characteristics and the prescription patterns of psychotropic medications were compared between the PD and NPD groups. Multivariate logistic regression analysis was used to investigate factors associated with an increased likelihood of PD. RESULTS: Among 1172 MDD patients, the prevalence of psychotic features was 9.2% in the present study. The logistic regression analysis indicated that unmarried (OR = 2.08, p < 0.001), frequent depressive episodes (OR = 2.10, p = 0.020), depressive episodes with suicidal ideation and attempts (OR = 1.91, p = 0.004), and patients who were prescribed any antipsychotics (OR = 2.94, p < 0.001) were associated with psychotic features in patients with MDD. LIMITATIONS: Cross-sectional design, retrospective recall of some data CONCLUSION: The prevalence of PD is high in China, and there were some differences in demographic and clinical characteristics between patients with PD and patients with NPD. Clinicians should regularly assess psychotic symptoms and consider intensive treatment and close monitoring when treating subjects with PD.

Association of serum uric acid levels with suicide risk in female patients with major depressive disorder: a comparative cross-sectional study.

BACKGROUND: Individuals with major depressive disorder (MDD) have a high suicide risk. Some evidence suggests that uric acid (UA) may be involved in the pathophysiology of MDD. The purpose of this study was to evaluate whether serum UA levels were associated with suicide risk in MDD patients. METHODS: One hundred four female patients with MDD (52 patients with suicide risk and 52 patients without suicide risk) and 52 healthy individuals were included in this study. The suicide risk was evaluated by Mini International Neuropsychiatric Interview (M.I.N.I.). Fasting serum levels of UA, as well as glucose, lipid and renal function indicators were measured. RESULTS: Serum UA levels in MDD patients with suicide risk (245.01 ± 55.44 µmol/L) were significantly lower than those in MDD patients without suicide risk (274.17 ± 72.65 µmol/L) (p = 0.017) and healthy controls (271.42 ± 55.25 µmol/L) (p = 0.030). There was no difference in serum UA levels between the MDD patients without suicide risk and healthy controls (p = 0.821). Binary logistic regression analysis revealed a significant relationship between suicide risk and decreased serum UA levels (OR = 0.989, p = 0.010) in MDD patients. CONCLUSION: Decreased serum UA levels were associated with suicide risk in MDD patients. Purinergic system dysfunction may be involved in the neurobiological basis of suicide risk in these patients.

Choroid Plexus Enlargement and Allostatic Load in Schizophrenia.

Although schizophrenia is a brain disorder, increasing evidence suggests that there may be body-wide involvement in this illness. However, direct evidence of brain structures involved in the presumed peripheral-central interaction in schizophrenia is still unclear. Seventy-nine previously treatment-naïve first-episode schizophrenia patients who were within 2-week antipsychotics initial stabilization, and 41 age- and sex-matched healthy controls were enrolled in the study. Group differences in subcortical brain regional structures measured by MRI and the subclinical cardiovascular, metabolic, immune, and neuroendocrine biomarkers as indexed by allostatic load, and their associations were explored. Compared with controls, patients with schizophrenia had significantly higher allostatic load (P = .001). Lateral ventricle (P < .001), choroid plexus (P < .001), and thalamus volumes (P < .001) were significantly larger, whereas amygdala volume (P = .001) was significantly smaller in patients. The choroid plexus alone was significantly correlated with higher allostatic load after age, sex, education level, and the total intracranial volume were taken into account (t = 3.60, P < .001). Allostatic load was also significantly correlated with PANSS positive (r = 0.28, P = .016) and negative (r = -0.31, P = .008) symptoms, but in opposite directions. The peripheral multisystemic and central nervous system abnormalities in schizophrenia may interact through the choroid plexus during the early stage of the illness. The choroid plexus might provide a sensitive structural biomarker to study the treatment and prevention of brain-periphery interaction abnormalities in schizophrenia.

Patients With Drug-Naive Bipolar Disorder in Remission After 8 Weeks of Treatment Had Decreased Serum Uric Acid Concentrations.

Background: Evidence indicates that the serum concentration of uric acid (UA) in patients may relate both to the pathophysiology and therapeutics of bipolar disorder (BPD). The purpose of this study was to examine the changes and clinical significance of serum UA concentrations in first-episode manic patients suffering from BPD. Methods: Seventy-six drug-naive patients with first-episode bipolar mania and 76 age- and gender-matched healthy subjects were recruited. Young Mania Rating Scale and Hamilton Depression Rating Scale were used to assess clinical symptoms. We tested serum UA concentrations by sandwich enzyme-linked immunosorbent assay at baseline and at the end of 8-week treatment in BPD patients and in the control group. Results: After 8-week quetiapine and sodium valproate treatment, this study revealed that the serum UA concentrations in remitted patients were significantly lower than nonremitted patients; however, those remitted patients still had higher serum UA than healthy controls. We discovered that the baseline UA concentration was higher in nonremitted than remitted patients after 8 weeks of treatment. Finally, a positive association was found between serum UA and symptom relief in the first episode of manic disorder patients. Conclusion: Patients with first-episode BPD had high levels of serum UA, which responds to treatment mainly in remitted patients. Our results suggest that serum UA concentrations might present potentially a trait marker in bipolar patients.

Brain Abnormalities in Different Phases of Working Memory in Schizophrenia: An Integrative Multi-Modal MRI Study.

The current study aimed to examine both gray matter and functional activity changes in schizophrenia by combing both structural and task-related functional magnetic resonance imaging (fMRI). Nineteen patients with schizophrenia and 17 controls were recruited. The fMRI scan was performed while performing a working memory (WM) task. In terms of task performance, accuracy did not differ between groups, but there were significant differences in reaction time. Compared with controls, patients exhibited decreased functional activation in prefrontal areas, insula, lingual gyrus, and superior temporal gyrus during different phases of WM. The subcallosal cortex showed increased activation. Intriguingly, a structural-functional correlation was found in the left dorsolateral prefrontal cortex, anterior cingulate cortex, and subcallosal cortex in patients when performing high-load WM task. This study demonstrated both impaired gray matter volume and functional activation during WM in schizophrenia, suggesting structural and functional impairments. The structural-functional correlation in schizophrenia suggested that structural damage in schizophrenia might induce a decreased ability to modulate functional response in accordance with increasing task difficulty.

Prescription practices in the treatment of agitation in newly hospitalized Chinese schizophrenia patients: data from a non-interventional naturalistic study.

BACKGROUND: Data on the pharmacological management of acute agitation in schizophrenia are scarce. The aim of this study is to investigate the prescription practices in the treatment of agitation in Chinese patients with schizophrenia. METHODS: We conducted a large, multicenter, observational study in 14 psychiatry hospitals in China. Newly hospitalized schizophrenia patients with the PANSS-EC total score ≥ 14 and a value ≥4 on at least one of its five items were included in the study. Their drug treatments of the first 2 weeks in hospital were recorded by the researchers. RESULTS: Eight hundred and 53 patients enrolled in and 847 (99.30%) completed the study. All participants were prescribed antipsychotics, 40 (4.72%) were prescribed benzodiazepine in conjunction with antipsychotics and 81 were treated with modified electric convulsive therapy (MECT). Four hundred and 12 (48.64%) patients were prescribed only one antipsychotic, in the order of olanzapine (120 patients, 29.13%), followed by risperidone (101 patients, 24.51%) and clozapine (41 patients, 9.95%). About 435 (51.36%) participants received antipsychotic polypharmacy, mostly haloperidol + risperidone (23.45%), haloperidol+ olanzapine (17.01%), olanzapine+ ziprasidone (5.30%), haloperidol + clozapine (4.37%) and haloperidol + quetiapine (3.90%). Binary logistic regression analysis suggests that a high BARS score (OR 2.091, 95%CI 1.140-3.124), severe agitation (OR 1.846, 95%CL 1.266-2.693), unemployment or retirement (OR 1.614, 95%CL 1.189-2.190) and aggressiveness on baseline (OR 1.469, 95%CL 1.032-2.091) were related to an increased antipsychotic polypharmacy odds. Male sex (OR 0.592, 95%CL 0.436-0.803) and schizophrenia in older persons (age ≥ 55 years, OR 0.466, 95%CL 0.240-0.902) were less likely to be associated with antipsychotic polypharmacy. CONCLUSION: The present study demonstrates that monotherapy and polypharmacy display equally common patterns of antipsychotic usage in managing agitation associated with schizophrenia in China. The extent and behavioral activities of agitation and several other factors were associated with polypharmacy.

Interaction of BDNF and cytokines in executive dysfunction in patients with chronic schizophrenia.

Multiple lines of evidence indicate that patients with chronic schizophrenia (SCZ) display executive dysfunction across the illness course. However, the potential molecular pathophysiologic mechanisms remain poorly elucidated. Neurodevelopmental changes caused by alterations of inflammatory mediators and neurotrophins have been shown to occur in the earliest stages of SCZ, and be associated with executive dysfunction (ED) in SCZ. Therefore, the current study was to investigate whether the interplay between BDNF and inflammatory mediators was involved in the disruption of executive function of long-term hospitalized patients with chronic SCZ. Serum cytokines and BDNF levels were measured in 112 long-term hospitalized patients with chronic SCZ and 44 healthy normal controls. Executive functions were assessed by verbal fluency tests (VFT), the Stroop word-color test (Stroop), and the Wisconsin card sorting tests (WCST).The results showed that the patients had higher IL-2, IL-6, IL-8, but lower TNF-α and BDNF compared to control subjects. In the patient group, BDNF was positively associated with IL-2 and IL-8 levels, while lower BDNF levels were correlated with ED measured by VFT and WCST tests. Multiple stepwise regression analyses confirmed that BDNF × IL-8 and BDNF × TNF-α were factors influencing the total score of VFT, while BDNF × IL-8 and BDNF × TNF-α were recognized as influencing factors for WCST scores. Our results suggest complex interactions between BDNF and cytokines were involved in the pathophysiology of executive function impairments in patients with SCZ.

Prevalence and clinical features of atypical depression among patients with major depressive disorder in China.

BACKGROUND: Little is known about the demographic and clinical features of the atypical subtype of major depressive disorder (MDD) patients in China. This study set out to investigate the prevalence of atypical depression in MDD patients in China, and identify its demographic and clinical features. METHODS: The study was conducted in 13 major psychiatric hospitals or in the psychiatric units of general hospitals in China, and recruited a sample of 1172 patients diagnosed with MDD. The patients' demographic and clinical features and prescriptions of psychotropic drugs were collected using a standardized questionnaire designed for the study. RESULTS: The prevalence of atypical depression was 15.3%. In multiple logistic regression analyses, compared to the non-atypical depression patients, the atypical depression patients were more likely to have depressive episodes with suicide ideation and attempts (OR = 1.49, 95% CI = 1.06, 2.10, P = 0.023), depressive episodes with psychotic features (OR = 2.15, 95% CI = 1.43, 3.22, P < 0.001), seasonal depressive episodes (OR = 1.77, 95% CI = 1.12, 2.78, P = 0.014), an earlier age of onset (OR = 0.98, 95% CI = 0.96, 0.99, P = 0.001), and lifetime depressive episodes (OR = 1.07, 95% CI = 1.01, 1.13, P = 0.020). LIMITATIONS: The assessment of atypical features was not based on a validated rating scale. CONCLUSION: Our results indicate that atypical depression is common in Chinese patients with MDD. MDD with atypical features may be more severe and debilitating than patients with non-atypical features.

Risk Factors for Recent Suicide Attempts in Major Depressive Disorder Patients in China: Results From a National Study.

Objective: To analyze the factors associated with recent suicide attempts including socio-demographic and clinical characteristics in major depressive disorder (MDD) patients in China. Methods: The data were from a nationwide sample from 13 major psychiatric hospitals or the psychiatric units of general hospitals in China, from September 1, 2010 to February 28, 2011. Melancholic features and suicide attempts in the past month were defined according to the melancholic feature module and the suicide module of the Mini International Neuropsychiatric Interview (MINI). Socio-demographic and clinical characteristics were compared between MDD patients with and without recent suicide attempts. Further analyses regarding the factors associated with recent suicide attempts in MDD patients were performed via multivariate logistic regression analysis. Results: Among 1,172 MDD patients, 57 (4.9%) were reported to have made a suicide attempt in the past month. Compared to the MDD patients without recent suicide attempt, significantly higher percentage of patients in the recent suicide attempters group had previous suicide attempts (χ2 = 171.861, p < 0.001) and depressive episodes with melancholic features (χ2 = 22.837, p < 0.001). Logistic regression analysis indicated that previous suicide attempts (OR = 20.81, 95% CI: 11.12-38.94, p < 0.001) and depressive episodes with melancholic features (OR = 4.43, 95% CI: 2.09-9.43, p < 0.001) were independently associated with recent suicide attempts in MDD patients. Limitations: Cross-sectional design, retrospective recall of suicide attempt data. Conclusion: Recent suicide attempts are associated with melancholic features and previous suicide attempts in MDD patients in China. These data may help clinicians to identify MDD patients at high risk of suicide attempt behavior.

P50 suppression deficits and psychopathology in Han Chinese patients with schizophrenia.

OBJECTIVE: Numerous studies have reported P50 gating deficits in schizophrenia, though with mixed results. Moreover, few studies have explored the association between P50 gating deficits and psychopathology in Chinese patients with schizophrenia. In the present study, we investigated the P50 auditory sensory gating patterns and their correlations with clinical symptoms in a large sample of Han Chinese patients with schizophrenia. METHODS: We assessed P50 sensory gating with a 64-channel electroencephalography system in 133 patients with schizophrenia and 148 healthy controls. The schizophrenia symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS). RESULTS: Patients with schizophrenia had a significantly higher P50 gating ratio (p<0.001), longer S1 latency (p<0.05), lower S1 amplitude (p<0.01), and lower P50 difference (p<0.001) than did controls. No significant correlations were found between the P50 gating measures and the PANSS total score or subscale scores in patients with schizophrenia. CONCLUSIONS: These findings suggest that the P50 sensory gating deficits identified in Chinese patients with schizophrenia may not be involved in the psychopathology of the illness.

Treatment satisfaction with paliperidone extended-release tablets: open-label study in schizophrenia patients dissatisfied with previous antipsychotic medication.

OBJECTIVE: The aim of this study was to evaluate the changes in treatment satisfaction after switching to paliperidone extended-release (ER) in Chinese schizophrenia patients dissatisfied with their previous antipsychotic treatment. METHODS: In this 8-week, open-label, single-arm, multicenter, prospective study, 1,693 patients dissatisfied with previous antipsychotic medication were enrolled and switched to paliperidone ER tablets (3-12 mg/d) based on clinical judgment. The primary efficacy end point was change in Medication Satisfaction Questionnaire (MSQ) score from baseline to week 8. The secondary end points included percentage of patients with MSQ score ≥4, as well as changes in Clinical Global Improvement-Severity (CGI-S) and Personal and Social Performance (PSP) scores. RESULTS: MSQ scores increased significantly from baseline (mean [standard deviation {SD}]: 2.48 [0.55]) to week 8 (5.47 [0.89], P<0.0001; primary end point, full analysis set). The percentage of patients with MSQ score ≥4 was 95.9% at week 8, indicating that most of the patients were satisfied with their treatment. Significant (P<0.0001) improvements from baseline to week 8 were noted in CGI-S score (2.37 [1.20]) and PSP score (25.5 [15.0]). A total of 174 (10.28%) patients experienced adverse events (AEs). The most common (>10 patients) events were extrapyramidal disorder (n=84, 4.96%), poor quality sleep (n=18, 1.06%) and akathisia (n=13, 0.77%). The majority of AEs were mild to moderate in severity. No deaths occurred. CONCLUSION: Treatment satisfaction improved after switching to paliperidone ER from the previous antipsychotic in Chinese patients with schizophrenia.

Association of catechol-O-methyltransferase Val(108/158) Met genetic polymorphism with schizophrenia, P50 sensory gating, and negative symptoms in a Chinese population.

Catechol-O-methyltransferase (COMT), an enzyme involved in the degradation and inactivation of the neurotransmitter dopamine, is associated with the sensory gating phenomenon, protecting the cerebral cortex from information overload. The COMT Val(108/158)Met polymorphism is essential for prefrontal cortex processing capacity and efficiency. The current study was designed to investigate the role of COMT Val(108/158)Met polymorphism in development, sensory gating deficit, and symptoms of schizophrenia in Han Chinese population. P50 gating was determined in 139 schizophrenic patients and 165 healthy controls. Positive and Negative Syndrome Scale (PANSS) was used to assess the clinical symptomatology in 370 schizophrenic subjects. COMT Val(108/158)Met polymorphism was genotyped by PCR-restriction fragment length polymorphism (PCR-RFLP). No significant differences in COMT allele and genotype distributions were observed between schizophrenic patients and control groups. Although P50 deficits were present in patients, there was no evidence for an association between COMT Val(108/158)Met polymorphism and the P50 biomarker. Moreover, PANSS negative subscore was significantly higher in Val allele carriers than in Met/Met individuals. The present findings suggest that COMT Val(108/158)Met polymorphism may not contribute to the risk of schizophrenia and to the P50 deficits, but may contribute to the negative symptoms of schizophrenia among Han Chinese.

Ginkgo biloba and vitamin E ameliorate haloperidol-induced vacuous chewingmovement and brain-derived neurotrophic factor expression in a rat tardive dyskinesia model.

Neurodegeneration may be involved in the development of tardive dyskinesia (TD), and low levels of brain-derived neurotrophic factor (BDNF) may play a role. Ginkgo biloba (EGb761), a potent antioxidant, may have neuroprotective effects. We hypothesized that there would be decreased BDNF expression in TD, but that treatment with EGb761 would increase BDNF expression and reduce TD manifestations in a rat model. Forty rats were treated with haloperidol (2mg/kg/day via intraperitoneal injections) for 5weeks. EGb761 (50mg/kg/day) and vitamin E (20mg/kg/day) were then administered by oral gavage for another 5weeks, and we compared the effects of treatment with EGb761 or vitamin E on haloperidol-induced vacuous chewing movements (VCMs) and BDNF expression in four brain regions: prefrontal cortex (PFC), striatum (ST), substantia nigra (SNR), and globus pallidus (GP). Our results showed that haloperidol administration led to a progressive increase in VCMs, but both EGb761 and vitamin E significantly decreased VCMs. Haloperidol also decreased BDNF expression in all four brain regions, but both EGb761 and vitamin E administration significantly increased BDNF expression. Our results showed that both EGb761 and VE treatments exerted similar positive effects in a rat model of TD and increased BDNF expression levels in the four tested brain regions, suggesting that both EGb761 and vitamin E improve TD symptoms, possibly by enhancing BDNF in the brain and/or via their free radical-scavenging actions.

Smoking and Serum Lipid Profiles in Schizophrenia.

Schizophrenia is associated with a high prevalence of cigarette-smoking and abnormal lipid profiles. The purpose of this study was to determine whether the profiles differ between schizophrenic smokers and non-smokers and whether the lipid profiles are related to psychopathological symptoms. Serum lipid profiles were measured in 130 male inpatients with DSM-IV-defined schizophrenia: 104 smokers and 26 non-smokers. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Our results showed that positive PANSS symptoms were fewer in smokers than in non-smokers, while the negative symptoms were fewer in those who smoked more cigarettes. Total protein and globulin levels were significantly lower in the smokers than in the non-smokers. However, there was no significant difference in total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol, apolipoprotein A1, or apolipoprotein B between the smokers and non-smokers. However, the PANSS positive subscale had a significant negative correlation with the HDL-c levels (a protective factor) in the smokers but not in the non-smokers. Our findings suggest that schizophrenic patients who smoke have fewer psychotic symptoms, but contrary to expectation, smoking does not alter lipid profile levels.

Altered interleukin-18 levels are associated with cognitive impairment in chronic schizophrenia.

The pathophysiology of cognitive deficits in schizophrenia may involve the neuroinflammation mediated by cytokines. This study examined the IL-18 levels, the cognitive function, and their association in schizophrenia. We recruited 70 chronic patients and 75 normal controls and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and IL-18 levels. Positive and Negative Syndrome Scale (PANSS) was assessed in chronic patients. IL-18 levels were increased in chronic patients as compared to normal controls (p < 0.01). RBANS total score and the subscales of immediate memory and delayed memory were lower in patients than controls (all p < 0.001). In patients, IL-18 levels were positively associated with RBANS total score and the subscales of immediate and delayed memory (all p < 0.05). Multiple regression analysis further confirmed that IL-18 was an independent contributor to RBANS total score and the aforementioned two indexes (all p < 0.05). Our data demonstrate that immune responses may play an important role in cognitive deficits in schizophrenia and the abnormal levels of IL-18 reflecting the disturbed balance of proinflammatory and anti-inflammatory mechanisms may be relevant to cognitive deficits of this disorder.

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.

Effects of cigarette smoking and alcohol use on neurocognition and BDNF levels in a Chinese population.

OBJECTIVE: Few studies have examined the potential interactive effect of both smoking and drinking on cognition. Brain-derived neurotrophic factor (BDNF) plays a critical role in cognition. This is the first study to examine the neurocognitive consequences of cigarette smoking combined with chronic alcohol consumption and their relationship to serum BDNF levels in a Chinese Han population. MATERIALS AND METHODS: We recruited 191 healthy male subjects, including 47 isolated smokers, 31 isolated chronic alcohol users, 58 combined smokers and chronic alcohol users, and 55 non-smokers and non-alcohol users. We then compared the repeatable battery for the assessment of neuropsychological status (RBANS) scores and serum BDNF levels in these four groups. RESULTS: When compared to the non-smoking + non-alcohol-using group, the smoking group performed worse on immediate memory, attention, language, and RBANS total score. There were no significant differences in the RBANS scores between the alcohol-using group and non-smoking + non-alcohol-using group, or between the smoking group and smoking + alcohol-using group. We did not find an association between BDNF and smoking or drinking status or between BDNF and cognitive performance. In the smoking group, there was a significant correlation between BDNF and carbon monoxide concentration, and between BDNF and the Fagerstrom Test for Nicotine Dependence (FTND) total score. CONCLUSIONS: Our results suggest that smoking is associated with cognitive decline, but not with BDNF levels in a normal population. However, smoking severity is positively associated with BDNF levels. Concomitant alcohol use does not worsen the cognitive decline caused by smoking.

Diurnal neurobiological alterations after exposure to clozapine in first-episode schizophrenia patients.

BACKGROUND: Irregular circadian rhythm and some of its most characteristic symptoms are frequently observed in patients with schizophrenia. However, changes in the expression of clock genes or neuropeptides that are related to the regulation of circadian rhythm may influence the susceptibility to recurrence after antipsychotic treatment in schizophrenia, but this possibility has not been investigated. METHODS: Blood samples were collected from 15 healthy male controls and 13 male schizophrenia patients at 4h intervals for 24h before and after treatment with clozapine for 8 weeks. The outcome measures included the relative expression of clock gene mRNA PERIOD1 (PER1), PERIOD2 (PER2), PERIOD3 (PER3) and the levels of plasma cortisol, orexin, and insulin. RESULTS: Compared with healthy controls, schizophrenia patients presented disruptions in diurnal rhythms of the expression of PER1, PER3, and NPAS2 and the release of orexin, accompanied by a delayed phase in the expression of PER2, decreases in PER3 and NPAS2 expression, and an increase in cortisol levels at baseline. Several of these disruptions (i.e., in PER1 and PER3 expression) persisted after 8 weeks of clozapine treatment, similar to the decreases in the 24-h expression of PER3 and NPAS2. Clozapine treatment for 8 weeks significantly decreased the 24-h levels of PER2 and increased the 24-h levels of insulin. CONCLUSION: These persistent neurobiological changes that occur after 8 weeks of clozapine treatment may contribute to the vulnerability to recurrence and efficacy of long-term maintenance treatment in schizophrenia.

Beneficial effects of EGb761 and vitamin E on haloperidol-induced vacuous chewing movements in rats: Possible involvement of S100B mechanisms.

Tardive dyskinesia (TD) is a serious side effect induced by the long-term administration of typical antipsychotics. The pathophysiology of TD remains unclear, but experimental evidence suggests that neurodegeneration caused by free radicals may play an important role in TD development. S100B is considered a potential biomarker of structural neural and glial damage. This study investigated S100B expression in TD-related brain regions and assessed the effect of antioxidants Gingko biloba leaf extract (EGb761) and vitamin E (VE) on S100B in TD rats. A total of 32 rats were randomly divided into 4 study groups: saline control (saline), haloperidol alone group (Hal), EGb761-haloperidol (EGb-Hal), and vitamin E-haloperidol (VE-Hal). Rats were treated with haloperidol intraperitoneal injections (2mg/kg/day) each day for 5 weeks. EGb761 (50mg/kg/day) and VE (20mg/kg/day) were then administered during a 5-week withdrawal period. We performed behavioral assessments and immunohistochemically analyzed S100B expression in four TD-related brain regions. Our findings demonstrated that haloperidol administration led to a progressive increase in VCMs and in S100B expression in all four brain regions. Both EGb761 and VE reversed these changes, and there were no group differences between the EGb761 and VE groups. Our results indicated that long-term administration of haloperidol may induce VCMs and increase S100B expression in TD-related brain regions, and S100B may be a significant biomarker related to TD pathophysiology. Moreover, the antioxidant capacity of EGb761 and VE coupled with the possible neuroprotective effects of S100B may account for their success in improving the symptoms of haloperidol-induced TD.

Risk Factors for Anxiety in Major Depressive Disorder Patients.

OBJECTIVE: To analyze the sociodemographic and clinical factors related to anxiety in patients with major depressive disorder (MDD). METHODS: This study involved a secondary analysis of data obtained from the Diagnostic Assessment Service for People with Bipolar Disorders in China (DASP), which was initiated by the Chinese Society of Psychiatry (CSP) and conducted from September 1, 2010 to February 28, 2011. Based on the presence or absence of anxiety-related characteristics, 1,178 MDD patients were classified as suffering from anxious depression (n=915) or non-anxious depression (n=263), respectively. RESULTS: Compared with the non-anxious group, the anxious-depression group had an older age at onset (t=-4.39, p<0.001), were older (t=-4.69, p＜0.001), reported more lifetime depressive episodes (z=-3.24, p=0.001), were more likely to experience seasonal depressive episodes (χ(2)=6.896, p=0.009) and depressive episodes following stressful life events (χ2=59.350, p <0.001), and were more likely to have a family history of psychiatric disorders (χ(2)=6.091, p=0.014). Their positive and total scores on the Mood Disorder Questionnaire (MDQ) and the 32-item Hypomania Checklist (HCL-32) (p<0.05) were also lower. The logistic regression analysis indicated that age (odds ratio [OR]=1.03, p<0.001), a lower total MDQ score (OR=0.94, p=0.011), depressive episodes following stressful life events (OR=3.04, p<0.001), and seasonal depressive episodes (OR=1.75, p=0.039) were significantly associated with anxious depression. CONCLUSION: These findings indicate that older age, fewer subclinical bipolar features, an increased number of depressive episodes following stressful life events, and seasonal depressive episodes may be risk factors for anxiety-related characteristics in patients with MDD.