Xiaoduo Fan

Elevated serum levels of C-reactive protein are associated with more severe psychopathology in a subgroup of patients with schizophrenia

The present study examined the hypothesis that elevated serum levels of C-reactive protein (CRP) would be associated with more severe clinical symptoms in patients with schizophrenia. Twenty-six inpatients with schizophrenia or schizoaffective disorder were enrolled. Serum levels of CRP were measured, and each patient was assessed with the Positive and Negative Syndrome Scale (PANSS). Subjects with CRP levels above the normal range (CRP>0.50 mg/dl, elevated CRP group, N=5) scored significantly higher than those with CRP levels in the normal range (CRP<or=0.50 mg/dl, normal CRP group, N=21) on the PANSS total score, negative symptom subscale score and general psychopathology subscale score. There was no significant difference between the two groups on the PANSS positive symptom subscale score. An inflammatory process, as reflected by elevated serum levels of CRP, might be associated with more severe psychopathology in a subgroup of patients with schizophrenia.

Aripiprazole added to overweight and obese olanzapine-treated schizophrenia patients.

Olanzapine treatment has been associated with clinically meaningful weight increases, hypertriglyceridemia, insulin resistance, and diabetes mellitus. There are few options for olanzapine responders who fail other antipsychotic agents. Aripiprazole is a potent (high-affinity) partial agonist at D2 and 5-HT1A receptors and a potent antagonist at 5-HT2A receptor and is associated with less weight gain than olanzapine. We report the results of a 10-week placebo-controlled, double-blind crossover study that examined 15 mg/d aripiprazoles effects on weight, lipids, glucose metabolism, and psychopathology in overweight and obese schizophrenia and schizoaffective disorder subjects treated with a stable dose of olanzapine. During the 4 weeks of aripiprazole treatment, there were significant decreases in weight (P = 0.003) and body mass index (P = 0.004) compared with placebo. Total serum cholesterol (P = 0.208), high-density lipoprotein cholesterol (HDL-C; P = 0.99), HDL-2 (P = 0.08), HDL-3 (P = 0.495), and low-density lipoprotein cholesterol (P = 0.665) did not change significantly comparing aripiprazole treatment to placebo treatment. However, total serum triglycerides (P = 0.001), total very low-density lipoprotein cholesterol (VLDL-C; P = 0.01), and VLDL-1C and VLDL-2C (P = 0.012) decreased significantly during the aripiprazole treatment phase. The VLDL-3C tended lower during aripiprazole, but the decrease was not significant (P = 0.062). There was a decrease in C-reactive protein comparing aripiprazole treatment to placebo, although it did not reach significance (P = 0.087). The addition of aripiprazole to a stable dose of olanzapine was well tolerated and resulted in significant improvements on several outcome measures that predict risk for medical morbidity.

Inflammation and schizophrenia

Previous research has demonstrated that prenatal infections with bacterial or viral agents during pregnancy are associated with an increased risk of schizophrenia in the offspring during adulthood. Furthermore, there has been evidence linking obstetric complications to schizophrenia. In parallel, there is a separate body of evidence relating subclinical chronic inflammation and schizophrenia in individuals, usually in their adulthood, who have already developed schizophrenia. On the other hand, unequivocal experimental, epidemiological and clinical evidence has emerged during the past decade linking inflammation to the development of insulin resistance and metabolic disturbances, which are common in the schizophrenic population. Inflammation might be an important common pathophysiological process related to both schizophrenia psychopathology and metabolic disturbances seen in patients with schizophrenia. Future studies targeting proinflammatory cytokines and their molecular signaling pathways may lead to novel pharmacological intervention strategies treating both psychopathology and medical comorbidity in patients with this devastating mental illness.

Modafinil for clozapine-treated schizophrenia patients: a double-blind, placebo-controlled pilot trial.

BACKGROUND Patients with schizophrenia often suffer from cognitive deficits and negative symptoms that are poorly responsive to antipsychotics including clozapine. Clozapine-induced sedation can worsen cognition and impair social and occupational functioning. OBJECTIVES To evaluate the efficacy, tolerability, and safety of modafinil for negative symptoms, cognition, and wakefulness/fatigue in DSM-IV-diagnosed schizophrenia patients treated with clozapine. METHOD A double-blind, placebo-controlled, flexible-dosed 8-week pilot trial was conducted between September 2003 and September 2007, adding modafinil up to 300 mg/d to stabilized schizophrenia outpatients receiving clozapine. Psychopathology, cognition, and wakefulness/fatigue were assessed with standard rating scales. RESULTS Thirty-five patients were randomly assigned to treatment with study drug and included in the analysis. Modafinil did not reduce negative symptoms or wakefulness/fatigue or improve cognition compared to placebo. Modafinil was well tolerated and did not worsen psychosis. CONCLUSIONS Results of this pilot trial do not support routine use of modafinil to treat negative symptoms, cognitive deficits, or wakefulness/fatigue in patients on clozapine. However, given our limited power to detect a treatment effect and the clear possibility of a type II error, larger trials are needed to resolve or refute a potential therapeutic effect of uncertain magnitude. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00573417.

Higher white blood cell counts are associated with an increased risk for metabolic syndrome and more severe psychopathology in non-diabetic patients with schizophrenia.

BACKGROUND Unequivocal evidence has emerged linking inflammation to the risk of metabolic problems. Previous research also has suggested a relationship between inflammation and schizophrenia. The present study examined whether white blood cell count (WBC), a marker of systemic inflammation, is associated with metabolic syndrome and psychiatric symptoms in non-diabetic patients with schizophrenia. METHODS Outpatients 19 to 75 years old diagnosed with schizophrenia or schizoaffective disorder participated in a multi-center, cross-sectional study. Vital signs and anthropometric measures were obtained. Fasting blood samples were collected to determine levels of glucose, lipids and WBC. Psychiatric symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). RESULTS In the sample of 199 patients, multiple logistic regression showed that WBC (log transformed) strongly predicted the condition of metabolic syndrome after potential confounding variables including age, gender, race, age of illness onset, family history of diabetes, smoking status and antipsychotic agent used were taken into consideration (odds ratio 47.2, 95% CI 3.4-658.7, p=0.004). On the other hand, significant correlations were found between WBC (log transformed) and BPRS-total score (r=0.18, p=0.014), negative symptom score (r=0.15, p=0.039) as well as anxious depression factor score (r=0.21, p=0.004) after potential confounding variables were taken into consideration. CONCLUSION This study suggested that WBC, a simple, readily available and inexpensive measure, may potentially be a useful marker to predict an increased risk for metabolic syndrome and more severe psychiatric symptoms in non-diabetic patients with schizophrenia.

A double‐blind, placebo‐controlled trial of sibutramine for clozapine‐associated weight gain

Objective:  This study sought to examine the effectiveness of sibutramine, a weight loss agent, on clozapine‐associated weight gain.

Elevated levels of adiponectin and other cytokines in drug naïve, first episode schizophrenia patients with normal weight☆

OBJECTIVE The study was to examine the levels of adiponectin (APN) and other cytokines, and body metabolism in drug naïve, first episode schizophrenia patients with normal weight. METHODS Ninety-six drug naïve, first episode schizophrenia patients with normal weight (SZ group), 60 healthy individuals with normal weight (control group), and 60 overweight or obese but otherwise healthy individuals (obesity group) were enrolled in the study. Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and APN were measured using enzyme linked immunosorbent assay (ELISA). Glucose oxidase was used to measure plasma glucose level. Lipid levels were measured using the enzymatic colorimetric method. RESULTS Serum levels of IL-1β, IL-6 and TNF-α in both the SZ group and the obesity group were significantly higher than those in the control group (ps<0.001). There were no significant differences between the SZ group and the obesity group on those cytokines (ps>0.05). In addition, the levels of APN were significantly higher in the SZ group (p<0.001), and significantly lower in the obesity group (p<0.01) compared with the control group. Further, there were significant positive relationships between levels of APN and levels of other cytokines within the SZ group (ps<0.05); in contrast, there were significant negative relationships between levels of APN and levels of other cytokines within the obesity group (ps<0.05). Fasting serum levels of glucose, LDL, triglycerides and total cholesterol were significantly higher, and fasting serum levels of HDL were significantly lower in the obesity group compared with the other two groups (ps<0.01). There were no significant differences in any of the metabolic parameters between the control group and the SZ group (ps>0.05). CONCLUSIONS Drug naïve, first episode schizophrenia patients with normal weight seem to present an up-regulated inflammatory status as reflected by elevated levels of IL-1β, IL-6, and TNF-α. APN may play a unique pro-inflammatory role in this patient population. Implications of the findings in relation to the pathogenesis of schizophrenia and the vulnerability for metabolic problems were discussed.

Activation of Th17 cells in drug naïve, first episode schizophrenia.

OBJECTIVE The present study was to examine the role of pro-inflammatory T helper 17 (Th17) cells in drug naïve, first episode schizophrenia. METHOD Patients with normal weight, drug naïve, first episode schizophrenia and healthy controls were enrolled in the study. Flow cytometric analysis was performed to analyze the proportion of Th17 cells among the CD4(+) T cells. Plasma levels of interleukin-17 (IL-17), interferon-γ (IFN-γ) and interleukin-6 (IL-6) were examined using enzyme-linked immunosorbent assay (ELISA). Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). All measures were repeated for the patient group after 4 weeks of risperidone treatment. RESULTS Sixty-nine patients with normal weight, drug naïve, first episode schizophrenia and 60 healthy controls were enrolled. At baseline, the patient group hadz significantly higher proportions of Th17 cells and plasma levels of IFN-γ and IL-6 compared with the control group (ps<0.01). Within the patient group, there were significant positive relationships between the proportion of Th17 cells, plasma levels of IL-17, IFN-γ, IL-6 and the PANSS total score after controlling for potential confounding variables (ps<0.05). After 4weeks of risperidone treatment, the proportion of Th17 cells decreased significantly (p <0.001), and there was a significant positive relationship between the PANSS total score change rate and the change in proportion of Th17 cells (p = 0.039). CONCLUSIONS Patients with normal weight, drug naïve, first episode schizophrenia present activation of Th17 cells, which might be associated with therapeutic response after risperidone treatment.

Posttraumatic stress disorder, cognitive function and quality of life in patients with schizophrenia

The purpose of the present study was to assess posttraumatic stress disorder (PTSD), cognitive function, and quality of life in patients with schizophrenia who had a self-reported history of trauma exposure. Outpatients diagnosed with schizophrenia or schizoaffective disorder were referred to the study. Each patient was assessed with the Positive and Negative Syndrome Scale (PANSS), the Harvard Trauma Questionnaire (HTQ), a cognitive assessment battery, Heinrichs Quality of Life Scale (QLS), and the Behavior and Symptom Identification Scale (BASIS). Eighty-seven subjects who reported experiencing at least one traumatic event were included in the study. Fifteen of 87 (17%) met the DSM-IV criteria for PTSD. The PTSD group had significantly worse overall cognitive performance than the non-PTSD group, especially in the domains of attention, working memory and executive function. In addition, the PTSD group showed significantly worse self-rated quality of life as measured by the BASIS total score. The development of PTSD is associated with poor cognitive function and subjectively, but not objectively, rated low quality of life in patients with schizophrenia. Evaluating PTSD in patients with schizophrenia could have important implications from both clinical and research perspectives.

Sexual functioning, psychopathology and quality of life in patients with schizophrenia

OBJECTIVE The present study was to characterize relationships among sexual functioning, schizophrenia symptoms and quality of life measures. In addition, sexual functioning was compared among patients treated with different antipsychotic agents. METHODS Outpatient subjects were assessed using the Positive and Negative Symptom Scale (PANSS), the Changes in Sexual Functioning Questionnaire (CSFQ) and the Hamilton Rating Scale for Depression (HAMD). Quality of life was assessed using two different instruments: observer-rated Heinrichs Quality of Life Scale (QLS) and self-rated The Behavior and Symptom Identification Scale (BASIS). RESULTS One hundred twenty-four patients with schizophrenia or schizoaffective disorder were enrolled in the study. Eight-six patients (69%) completed at least part of the CSFQ assessment, which generated at least one valid subscale score. High rates of sexual impairment were found in both male and female patients (65%-94% across different subscales). For males, higher scores on the PANSS-positive subscale were associated with a lower frequency of sexual activity (p=0.04). For females, higher scores on the PANSS-positive subscale and PANSS-general psychopathology subscale were significantly associated with more difficulty in both sexual arousal and orgasm (ps<0.05). For both males and females, there were no significant relationships between any CSFQ subscale measures and the quality of life measures (ps>0.05). No significant differences were found among three antipsychotic treatment groups (clozapine, olanzapine or typical agents) on any CSFQ subscale measures or quality of life measures after controlling for PANSS total scores (ps>0.05). CONCLUSIONS Effective treatment strategies still need to be developed to address sexual dysfunction and quality of life in patients with schizophrenia.