ALDH2 polymorphism,associated with attenuating negative symptoms in patients with schizophrenia treated with add-on dextromethorphan

ObjectiveIncreasing the evidence of inflammation's contribution to schizophrenia; using anti-inflammatory or neurotrophic therapeutic agents to see whether they improve schizophrenia treatment. Dextromethorphan (DM), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, might protect monoamine neurons. Whether treating schizophrenia with risperidone plus add-on DM is more effective than risperidone (RISP) alone, and the association between the ALDH2 polymorphism and treatment response were investigated.MethodsA double-blind study in which patients with schizophrenia were randomly assigned to the RISP + DM (60 mg/day; n = 74) or the RISP + Placebo (n = 75) group. The Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) scores were used to evaluate clinical response during weeks 0, 1, 2, 4, 6, 8, and 11. The genotypes of the ALDH2 polymorphism were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. A generalized estimating equation was used to analyze the effects of ALDH2 polymorphism on the clinical performance of DM.ResultsPANSS and SANS scores were significantly lower in both groups after 11 weeks of treatment. SANS total scores were significantly lower in the RISP + DM group in patients with the ALDH2*2*2 genotype.ConclusionsRISP plus add-on DM treatment reduced negative schizophrenia symptoms in patients with the ALDH2 polymorphism.     

Actigraphic monitoring of activity and rest in schizophrenic patients treated with olanzapine or risperidone

Metabolic disturbances are a growing concern for the treatment of schizophrenia. As decreased activity and poor sleep quality are risk factors for metabolic disturbances, we investigated the activity and sleep patterns of schizophrenic patients using actigraphy. Seventy-three patients with schizophrenia spectrum disorder (mean age 29.2 ± 10.2 years, 27 females) treated with olanzapine (n = 54) or risperidone (n = 19) and 36 age- and sex-matched healthy controls were examined. Actigraphic recordings were obtained throughout seven consecutive days. The Athens Insomnia Scale (AIS) and Epworth Sleepiness Scale (ESS) were used to assess sleep and daytime sleepiness. Drug side effects were evaluated with the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale and Barnes Akathisia Rating Scale (BARS). Mental status was rated with the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS). The patients had lower mean 24 h-activity (p < 0.001) and mean 10 h-daytime-activity (p < 0.001), and longer time in bed (p < 0.001). Higher PANSS scores, especially in the negative symptoms scale, were related to lower activity (r_s = −0.508, p < 0.001). Higher depressive symptoms were related to lower mean 24 h-activity (r_s = −0.233, p = 0.049), longer time in bed (r_s = 0.315, p = 0.007) and higher AIS (r_s = 0.377, p = 0.001) and ESS scores (r_s = 0.321, p = 0.006). Healthy females presented higher activity than healthy males (p < 0.001). Similar but not significant gender differences were observed in the patients. These findings show that patients with schizophrenia treated with olanzapine or risperidone exhibit low physical activity and altered sleep pattern which may promote metabolic side effects. These changes are linked to negative and depressive symptoms.     

Quetiapine has equivalent efficacy and superior tolerability to risperidone in the treatment of schizophrenia with predominantly negative symptoms

Atypical antipsychotics are generally thought to be more effective than conventional agents in treating the negative symptoms of schizophrenia; however, there have been few direct comparisons among atypicals. We therefore investigated risperidone and quetiapine with respect to their efficacy against negative symptoms in a 12–week,double–blind, comparative pilot study involving 44 patients with schizophrenia with predominantly negative symptoms, as defined by Positive and Negative Syndrome Scale (PANSS) scores. Other efficacy measures included the Scale for the Assessment of Negative Symptoms (SANS) and the Clinical Global Impression (CGI) rating scale. Antipsychotic tolerability was assessed using the Simpson–Angus Scale (SAS) and various laboratory measures. Mean doses were 589.7 mg/ day quetiapine and 4.9 mg/day risperidone (observed cases). Both antipsychotics produced significant decreases in PANSS total, positive and negative scores, and SANS scores. Patients receiving risperidone were significantly more likely to experience extrapyramidal symptoms (EPS) [p <0.05], or to require anticholinergic medication (p <0.05), and had significantly higher prolactin levels (p <0.001) than quetiapine–treated patients. In conclusion, there is no significant difference in efficacy between quetiapine and risperidone in alleviating the negative symptoms of schizophrenia. Quetiapine is also well tolerated, with a lower incidence of EPS and prolactin increase than risperidone.     

米诺环素辅助治疗精神分裂症阴性症状的效果及对免疫因子的影响

目的探讨米诺环素辅助治疗精神分裂症阴性症状的效果及免疫学机制。方法将92例符合美国《精神疾病诊断与统计手册(第4版)》(DSM-IV)诊断标准、以阴性症状为主且单一利培酮治疗的精神分裂症患者随机分为米诺环素组(n=46)或安慰剂对照组(n=46),治疗周期为16周。于入组及出组时以阴性症状评定量表(SANS)、阳性和阴性症状量表(PANSS)评定疗效,测定治疗前后白介素1-β(IL-1β)、肿瘤坏死因子-α(TNF-α)、一氧化氮(NO)浓度变化。结果 PANSS阴性症状评分和总评分与安慰剂组相比,减分差异有统计学意义(P0.01);两组治疗前后除NO外其余两个因子的浓度变化均无统计学意义(P0.05)。结论米诺环素辅助治疗精神分裂症的阴性症状有效,但作用机制仍不明,是否通过抑制NO浓度的变化尚需进一步的研究。     

Decreased serum BDNF levels in chronic institutionalized schizophrenia on long-term treatment with typical and atypical antipsychotics

Accumulating evidence showed that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia. Decreased BDNF levels have been found in the serum of schizophrenic patients with mixed results. In the present study, we assessed serum BDNF levels in a large group of 364 schizophrenic patients (157 on clozapine, 89 on risperidone and 118 on typical antipsychotics), compared to 323 healthy control subjects matched for age and gender. The schizophrenia symptomatology was assessed by the Positive and Negative Syndrome Scale (PANSS), and serum BDNF levels were measured by sandwich ELISA. The results showed that BDNF levels were significantly lower in chronic patients with schizophrenia than in healthy control subjects (9.9 ± 2.0 ng/ml vs.11.9 ± 2.3 ng/ml, p < 0.0001). Lower BDNF levels were observed in patients treated with risperidone (9.3 ± 2.3 ng/ml) compared to those with clozapine (10.2 ± 2.0 ng/ml, p < 0.001) and typical antipsychotics (10.0 ± 2.1 ng/ml, p < 0.01). Furthermore, a stepwise multiple regression analysis identified types of antipsychotic drugs (beta = − 0.37, t = − 3.15, p = 0.001) and BDNF levels (beta = − 0.26, t = − 2.51, p = 0.014) as the influencing factor for the positive symptom subscore of PANSS. In addition, there was a sex difference in BDNF levels in patients with schizophrenia (9.7 ± 1.9 ng/ml for males vs.10.4 ± 2.1 ng/ml for female, p < 0.005), but not in normal controls. Our findings indicated decreased BDNF serum levels in chronic patients with schizophrenia, which may be related to clinical phenotypes, including gender, antipsychotic treatment and the severity of psychotic symptoms.     

Selective Serotonin 3 Receptor Antagonist Treatment for Schizophrenia: Meta-analysis and Systematic Review

Double-blinded, randomized, placebo-control trials of selective serotonin 3 receptor antagonists (5-HT₃R-ANTs) for schizophrenia have differed in outcome. This meta-analysis tests the hypothesis that 5-HT₃R-ANTs are effective for the treatment for schizophrenia. We searched PubMed, the Cochrane Library database, and PsycINFO up to June 15, 2013. We conducted a systematic review and meta-analysis of individual patient data from randomized controlled trials comparing 5-HT₃R-ANTs add-on therapy with placebo. The risk ratio (RR), 95 % confidence intervals (CI), and standardized mean difference (SMD) were calculated. A random-effects model was used. Six studies (total n = 311) were identified. These included one granisetron plus risperidone study, one ondansetron plus risperidone study, one ondansetron plus haloperidol, and three tropisetron plus risperidone studies. The statistically significant effects of 5-HT₃R-ANTs add-on therapy on Positive and Negative Syndrome Scale (PANSS) total scores were SMD = ?1.03, CI = ?1.70 to ?0.36, p = 0.003 (I ² = 82 %, 5 studies, n = 261); on negative scores were SMD = ?1.10, CI = ?1.82 to ?0.39, p = 0.002 (I ² = 84 %, 5 studies, n = 261); and on PANSS general scores were SMD = ?0.70, CI = ?1.23 to ?0.17, p = 0.01 (I ² = 73 %, 5 studies, n = 261). However, 5-HT₃R-ANTs add-on therapy was not superior to placebo in PANSS positive scores (SMD = ?0.12, p = 0.33). Dropout due to all cause (RR = 0.80, p = 0.50), inefficacy (RR = 0.76, p = 0.65), or adverse events (RR = 0.84, p = 0.75) was similar in both groups. Constipation occurred significantly more often with 5-HT₃R-ANTs than placebo (RR = 2.05, CI = 1.07–3.91, p = 0.03, NNH = 11, p = 0.02). 5-HT₃R-ANTs add-on therapy is more beneficial on the psychopathology (especially negative symptoms) than controls in patients with schizophrenia, and 5-HT₃R-ANTs seem to be well-tolerated treatments.     

Effects of risperidone and quetiapine on cognition in patients with schizophrenia and predominantly negative symptoms

Evidence suggests that neurocognitive impairment is a key factor in the pathology of schizophrenia and is linked with the negative symptoms of the disease. In this study the effects of the atypical antipsychotics quetiapine and risperidone on cognitive function in patients with schizophrenia and with predominantly negative symptoms were compared. Patients were randomly assigned to double-blind treatment with quetiapine or risperidone for 12 weeks. Cognitive function was assessed at baseline, Week 6 and Week 12. Efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) at baseline, Week 6 and Week 12. Extrapyramidal side-effects were assessed each week using the Simpson-Angus Scale (SAS), adverse events were recorded as additional indicators of tolerability throughout the trial. In total, 44 patients were enrolled in the study. Data from the 34 patients who completed cognitive assessments at two or more time points out of three (baseline, Week 6 and Week 12) are analysed here. Quetiapine improved significantly global cognitive index z-scores at both Week 6 (p < 0.001 vs. baseline) and Week 12 (p < 0.01 vs. baseline), whereas risperidone improved significantly global cognitive index z-scores at Week 12 (p < 0.05). Between-group comparisons at Week 6 showed significantly greater improvements in working memory and verbal memory with quetiapine than risperidone (p < 0.05) and a significantly greater improvement in reaction quality/attention with quetiapine than risperidone at Week 12 (p<0.05). Quetiapine and risperidone produced significant improvements from baseline in PANSS total (p<0.001) and subscale scores at Week 12. Significant improvements in SANS total score were also seen in both the quetiapine (p < 0.001) and risperidone (p < 0.01) groups at Week 12 compared with baseline. SAS scores, measuring the incidence of extrapyramidal side-effects, were higher in patients receiving risperidone compared with those receiving quetiapine, and significant differences were seen at Weeks 3, 4, 5 and 7. Both quetiapine and risperidone improved cognition according to changes in cognitive index scores from baseline to Week 12. These results suggest that quetiapine and risperidone provide valuable treatment options for patients with schizophrenia with predominantly negative symptoms. Also, the improvements in cognition following treatment with quetiapine and risperidone may enhance long-term outcomes for these patients.     

A preliminary analysis of association between the down-regulation of microRNA-181b expression and symptomatology improvement in schizophrenia patients before and after antipsychotic treatment

Despite the growing evidences on the relation of altered expression of miRNAs and schizophrenia, most schizophrenia subjects have an extensive antipsychotic treatment history and the pharmacological effects on miRNA expression are largely unknown. This study aimed to investigate the change of plasma microRNA-181b level and improvement of symptomatology before and after six-week antipsychotic treatment in schizophrenia patients, and explore their association. A total of 20 schizophrenia patients absent of antipsychotics and 20 age-and gender-matched normal controls were enrolled, and tested for 9 schizophrenia-associated microRNA (miR-30e, miR-34a, miR-181b, miR-195, miR-346, miR-432, miR-7, miR-132 and miR-212) expression levels in plasma using quantitative RT-PCR and for symptomatology improvement using Positive And Negative Syndrome Scale (PANSS) before and after treatment (olanzapine, quetiapine, ziprasidone and risperidone) for the patients only. Compared with the normal control group, the expression levels of miRNA-181b, miRNA-30e, miRNA-34a and miRNA-7 of the patients group were significantly higher (p < 0.05). Compared with those before treatment in the patient group, the symptomatology scores were significantly lower (p < 0.001), and the expression level of microRNA-181b was significantly down-regulated after treatment (p < 0.05). The change of miRNA-181b expression was positively correlated with the improvement of negative symptoms and lack of response symptoms (r = 0.502 and 0.557, P < 0.05, accounting for 20.2% and 26.4% respectively), and their therapeutic effects with OR being 11.283 and 5.119 respectively. We conclude that miRNA-181b, miRNA-30e, miRNA-34a and miRNA-7 are probably involved in pathogenesis of SZ, and the significant down-regulation of miRNA-181b expression predicts improvement of negative symptoms to treatment, and thus can serve as a potential plasmamolecular marker for antipsychotic responses.     

Disentangling the symptoms of schizophrenia: Network analysis in acute phase patients and in patients with predominant negative symptoms

BackgroundThe Positive and Negative Syndrome Scale (PANSS) is widely used in schizophrenia and has been divided into distinct factors (5-factor models) and subfactors. Network analyses are newer in psychiatry and can help to better understand the relationships and interactions between the symptoms of a psychiatric disorder. The aim of this study was threefold: (a) to evaluate connections between schizophrenia symptoms in two populations of patients (patients in the acutely exacerbated phase of schizophrenia and patients with predominant negative symptoms [PNS]), (b) to test whether network analyses support the Mohr 5 factor model of the PANSS and the Kahn 2 factor model of negative symptoms, and finally (c) to identify the most central symptoms in the two populations.MethodsUsing pooled baseline data from four cariprazine clinical trials in patients with acute exacerbation of schizophrenia (n = 2193) and the cariprazine–risperidone study in patients with PNS (n = 460), separate network analyses were performed. Network structures were estimated for all 30 items of the PANSS.ResultsWhile negative symptoms in patients with an acute exacerbation of schizophrenia are correlated with other PANSS symptoms, these negative symptoms are not correlated with other PANSS symptoms in patients with PNS. The Mohr factors were partially reflected in the network analyses. The two most central symptoms (largest node strength) were delusions and uncooperativeness in acute phase patients and hostility and delusions in patients with PNS.ConclusionsThis network analysis suggests that symptoms of schizophrenia are differently structured in acute and PNS patients. While in the former, negative symptoms are mainly secondary, in patients with PNS, they are mainly primary. Further, primary negative symptoms are better conceptualized as distinct negative symptom dimensions of the PANSS.     

Auditory and visual P300 reflecting cognitive improvement in patients with schizophrenia with quetiapine: A pilot study

We recorded event-related potentials (ERPs) in patients with schizophrenia before and after treatment with quetiapine, to investigate this drug's effects on cognitive function. Auditory and visual oddball stimulus discrimination paradigms were presented to patients with schizophrenia (N = 20) before and after 3 months' treatment with quetiapine. The 2-stimulus auditory oddball paradigm used a standard tone (1000 Hz, 75 dB, 80%) and a target tone (2000 Hz, 75 dB, 20%). The 2-stimulus visual oddball paradigm used a standard stimulus (small circle, 80%) and a target stimulus (large circle, 20%). Patients' severity of psychopathology was initially evaluated with the Positive and Negative Syndrome Scale (PANSS) and was likewise re-evaluated after treatment. After treatment with quetiapine, patients' P300 amplitudes increased over baseline for both tasks (auditory stimuli, P < 0.01; visual stimuli, P < 0.01) and their P300 latencies for both target stimuli decreased significantly (auditory stimuli, P < 0.001; visual stimuli, P < 0.01). Visual P300 amplitude was negatively correlated with the severity of positive symptoms at the Fz electrode before the treatment (r = − 0.45, P < 0.05). After treatment with quetiapine, there were no significant correlations between severity of positive or negative symptoms and visual P300 amplitudes for midline electrodes. These findings suggest that the reduced and delayed P300 may be a state marker for schizophrenia, which may in turn be modulated by positive symptoms, and also suggest that the amplitude and latency for both auditory and visual tasks may be decreased by quetiapine treatment. Based on these results, we suggest that the atypical antipsychotic quetiapine may improve some aspects of cognitive domains in patients with schizophrenia.     

A double-blind, placebo-controlled study of traditional Chinese medicine sarsasapogenin added to risperidone in patients with negative symptoms dominated schizophrenia

Objective

To identify whether sarsasapogenin, a sapogenin from the Chinese medicinal herb Anemarrhena Asphodeloides Bunge, would augment the efficacy of risperidone and significantly improve cognitive functions in patients with negative symptoms dominated schizophrenia.

Methods

The trial was a double-blind, placebo-controlled, parallel-group design. The eligible patients were randomized into 2 treatment groups: sarsasapogenin group (sarsasapogenin plus risperidone for 8 weeks, n = 41) and placebo group (risperidone only for 8 weeks, n = 39). At the baseline, as well as at weeks 2, 4 and 8 of treatment, the therapeutic response was measured by using scales including Positive and Negative Symptoms Scale (PANSS), Wechsler Memory Scale (WMS), modified Chinese Wechsler Adult Intelligence Scale (mWAIS), Clinical Global Impression (CGI) and Brief Psychiatry Rating Scale (BPRS). The study period for each subject was 8 weeks and duration of overall trial was 2 years.

Results

Patients treated with sarsasapogenin plus risperidone demonstrated no statistically significant differences in changes in PANSS, WMS or mWAIS score at the end-point of the trial compared with patients treated with placebo plus risperidone. The incidence of treatment-emergent adverse events in patients treated with sarsasapogenin was not different from that observed in placebo group.

Conclusion

Sarsasapogenin did not augment the efficacy of risperidone in treating negative symptoms dominated schizophrenia. Sarsasapogenin at a dosage of 200 mg per day added to a flexible dosage of risperidone at 2–4 mg per day is safe and well tolerated by patients with negative symptoms dominated schizophrenia.     

Brief PANSS to assess and monitor the overall severity of schizophrenia

Aims: The aim of the present study was to develop a subscale of the Positive and Negative Syndrome Scale (PANSS) that would be brief and sensitive to changes in the clinical features of schizophrenia (i.e. the Brief PANSS, or bPANSS). Methods: The PANSS before and after treatment, and the Clinical Global Impression–Change (CGI‐C) was rated for 714 schizophrenia patients. Of these, Clinical Global Impression–Severity (CGI‐S) was also evaluated in 30 of these patients. The bPANSS items were extracted from full PANSS items based on the following aims: (i) to develop a brief scale; (ii) to develop a scale sensitive to changes resulting from antipsychotic treatment; and (iii) to reflect the broad spectrum of schizophrenia symptoms. Results: The following six items were extracted to serve as the bPANSS: delusion, suspiciousness, emotional withdrawal, passive/apathetic social withdrawal, tension, and unusual thought content. The coefficients of correlation between the bPANSS and full PANSS before and after treatment were 0.86 and 0.92, respectively (both P < 0.001). The coefficient of correlation between the degrees of change in the scores for the bPANSS and the full PANSS was 0.93 (P < 0.001), and that between delta bPANSS and CGI‐C was 0.73 (P < 0.001). Conclusions: bPANSS is able to capture the overall clinical features of schizophrenia within a short assessment period.     

C-reactive protein serum level in drug-free male Egyptian patients with schizophrenia

Despite the growing research interest in the role of immunological markers in schizophrenia, few studies, with conflicting results, have focused on the association between high sensitivity C-reactive protein (hs-CRP) levels and clinical characteristics in schizophrenia. In this cross-sectional case-control study, a sample of 200 antipsychotic-free male Egyptian schizophrenia patients was assessed by the Positive and Negative Syndrome Scale (PANSS) and compared with 200 healthy controls as regards serum hs-CRP level using an immunoturbidimetric method. CRP level for patients (geometric mean = 3.3 mg/L) was significantly (P = 0.000) higher than that for controls (geometric mean = 1.4 mg/L). PANSS scores and patients' data, which significantly correlated with serum hs-CRP level, were entered into a stepwise multiple regression analysis. Results of this analysis showed that PANSS negative symptom score was second only to the waist circumference, with which they explained 54.7 % of the variation in serum hs-CRP. Comparable results were obtained when patients, controls and the relevant confounders were included in one multivariate analysis. We concluded that in Egyptian men, waist circumference and schizophrenia diagnosis are strong predictors of raised CRP level independent of a number of potentially confounding variables. In antipsychotic-free patients, CRP level is higher than in healthy controls and is positively correlated with the severity of the psychopathology as measured by PANSS. This relationship is especially notable in negative, but not positive symptoms.     

Association between subjective well-being and depressive symptoms in treatment-resistant schizophrenia before and after treatment with clozapine

Background

We examined the relationship between subjective well-being and depressive symptoms in patients with treatment-resistant schizophrenia before and after treatment with clozapine to contribute to the growing body of research regarding the determinants of patients' perspective of their own well-being in schizophrenia.

Methods

Forty patients with treatment-resistant schizophrenia were comprehensively evaluated for subjective well-being, schizophrenic symptoms, and depressive symptoms before and 8 weeks after the initiation of treatment with clozapine. Correlation analysis and Fisher's z-transformation statistics were performed.

Results

There were significant improvements in all Positive and Negative Syndrome Scale (PANSS) factor scores and Beck Depression Inventory (BDI) score over the treatment period (P < .05). Before clozapine administration, the subjective well-being score had significant negative correlations with the PANSS depression factor score (P < .05) and the BDI score (P < .05). After clozapine treatment, the subjective well-being score still had significant negative correlations with the PANSS depression factor score (P < .05) and the BDI score (P < .05) and no new associations emerged with treatment. Fisher's z-transformation statistics revealed that the correlations between the subjective well-being score and the depression score were not significantly different before and after clozapine treatment.

Conclusions

These results indicate that depressive symptoms are significantly associated with low subjective well-being in patients with treatment-resistant schizophrenia. The association was equally significant before and after treatment with clozapine, suggesting that the relationship does not change with clozapine treatment, even when depressive symptoms improve significantly, and that there may be a common pathophysiological basis for depressive symptoms and the subjective appraisal of well-being in schizophrenia.     

Effect of self-consistency group intervention for adolescents with schizophrenia: An inpatient randomized controlled trial

ObjectiveThe aim of the study was to explore the efficacy of structural group therapy on the self-consistency and congruence of inpatient adolescents with a diagnosis of schizophrenia.MethodSixty inpatient adolescents with schizophrenia were randomly assigned to an intervention group (n = 30) and a control group (n = 30). The intervention group was provided with a 12-session structural group therapy program for six weeks (1 h, two times per week), while the control group participated in a handicraft group. All patients were assessed with the Self-Consistency and Congruence Scale (SCCS) and the Positive and Negative Syndrome Scale (PANSS) at pretest, posttest, three-month and one-year follow-up. The results were analyzed using t-test and repeated measures ANOVA.FindingsThe two groups had no significant difference at the pre-test of outcome measures (p > 0.05). Significant differences existed between the two groups in ego-dystonic, self-flexibility, SCCS scores, positive syndrome, general psychopathology and PANSS scores after the intervention (p < 0.05). At the three-month follow-up, ego-dystonic, self-flexibility and PANSS scores were also found to be significantly different between the two groups (p < 0.05). But the outcome measures were not significantly different between the two groups at the one-year follow-up.ConclusionStructural group therapy in a mental health setting had a positive effect on improving self-consistency and congruence, positive symptoms and general psychopathology of inpatient adolescents with a diagnosis of schizophrenia.     

Factors involved in the level of functioning of patients with schizophrenia according to latent variable modeling

PurposeThis study aimed at using latent variable modelling to explore the significantly contributing variables to functioning in schizophrenia patients.MethodsThe study cohort comprised 296 schizophrenia patients evaluated once for demographic characteristics, functioning (FROGS, SWN-K, QLS) and symptomatology (Positive and Negative Syndrome Scale [PANSS]). First exploratory multivariate analyses were conducted and then a model with functioning as a latent variable was proposed and tested with the data.ResultsSymptomatology as negative, cognitive and excitation factor are significant predictors of functioning assessed through FROGS (P < 0.0001), SWN-K and QLS (P < 0.001). The model was constructed with functioning defined as a latent variable, indicators are subscores on FROGS, SWN-K, QLS and exogenous variable included symptomatology, Duration of Untreated Psychosis (DUP) and educational level.ConclusionUsing the five clinical dimensions of the PANSS, (Positive, Negative, Cognitive, Anxiety/Depression and Excitation) the negative and cognitive dimensions are highly correlated via the latent variable to the three dimensions of functioning evaluated by the FROGS: “daily life”, “social functioning” and “treatment” and the QLS subscores (interpersonnal, common object, instrumental role). Educationnal level is positively linked to functioning but not DUP. The model emphasizes the need for treatment strategies that have an effect on cognitive-factors, to improve functioning in schizophrenia.     

Increase in thalamic binding of [C]PE2I in patients with schizophrenia: A positron emission tomography study of dopamine transporter

Previous in vivo imaging studies reported no difference in dopamine transporter (DAT) bindings in the striatum between control subjects and patients with schizophrenia. However, as the signals of radioligands with moderate affinity were insufficient for allowing the evaluation of small amounts of DAT, DAT binding in extrastriatal regions has not been determined. Positron emission tomography scanning using [¹¹C]PE2I was performed on eight patients with schizophrenia and twelve normal control subjects. Binding potential (BP_ND) for DAT in the caudate, putamen, thalamus and substantia nigra was calculated, using the cerebellum as reference region. In patients with schizophrenia, clinical symptoms were evaluated by Positive and Negative Syndrome Scale (PANSS). BP_ND in the thalamus of patients with schizophrenia was significantly higher than in control subjects (P = 0.044). In patients with schizophrenia, there were significantly positive correlations between BP_ND in the thalamus and total (r = 0.75), positive (r = 0.78) and negative PANSS scores (r = 0.82). Altered DAT in the thalamus might be related to the pathophysiology and clinical symptoms of schizophrenia.     

The importance of self-determined motivation towards physical activity in patients with schizophrenia

There is a need for theoretically-based research on the motivational processes linked to the commencement and continuation of physical activity in patients with schizophrenia. Within the Self-Determination Theory (SDT) framework, we investigated the SDT tenets in these patients by examining the factor structure of the Behavioral Regulation in Exercise Questionnaire-2 (BREQ-2) and by investigating associations between motivation and PA. The secondary aim was to study differences in motivation according to gender, educational level, treatment setting and disease stage. A total of 129 patients (44♀) with schizophrenia agreed to participate. Exploratory factor analysis showed sufficient convergence with the original factor for amotivation, external and introjected regulation, while identified and intrinsic regulations loaded on a single factor which we labeled “autonomous regulation”. Significant positive correlations were found between the total physical activity score and the subscales amotivation (r=−0.44, P<0.001), external regulation (r=−0.27, P<0.001), and autonomous regulation (r=0.57, P<0.001). Outpatients reported more external (P<0.05) and introjected (P<0.05) regulations than inpatients. Our results suggest that patients' level of self-determination may play an important role in the adoption and maintenance of health promoting behaviors in patients with schizophrenia.     

利培酮合并赛来昔布治疗精神分裂症首次发病患者的随机双盲对照研究

目的 评估利培酮合并赛来昔布对精神分裂症首次发病(以下简称首发)患者的临床疗效及安全性.方法 符合美国精神障碍诊断与统计手册第4版诊断标准的精神分裂症首发住院患者90例,随机分到利培酮+赛来昔布组(研究组,46例)或利培酮+空白剂组(对照组,44例),观察时间均为12周.以阳性和阴性症状量表(PANSS)、临床疗效总评量表(CGI)、汉密尔顿抑郁量表(HAMD)评定临床疗效,以治疗中需处理的不良反应量表(TESS)、Simpson锥体外系副反应量表(SEPS)、异常不自主运动评定量表(MMS)评定药物不良反应和锥体外系副反应.结果 两组患者治疗前后比较,PANSS总分及各分量表分均明显下降(P均<0.05);研究组PANSS总分、分量表分、HAMD评分较对照组的降低更为明显,差异均有统计学意义(P均<0.05).研究组总有效率(66%)明显高于对照组(26%);X2=16.1,P=0.001.治疗第12周末,两组TESS、SEPS、MMS评分的差异均无统计学意义(P均>0.05);研究组患者体质量的增加(4±5)kg,明显高于对照组(1±4)kg,t=2.6,P<0.05.结论 赛来昔布可以提高利培酮对首发精神分裂症的疗效.     

Efficacy of risperidone versus olanzapine in patients with schizophrenia previously on chronic conventional antipsychotic therapy: a switch study

The objective of the study was to examine whether patients with schizophrenia who were judged to be stable on long-term treatment with conventional antipsychotic medications would further benefit from a switch to an atypical antipsychotic drug. Thirty-six subjects with schizophrenia spectrum disorder, on conventional antipsychotic medication therapy for at least 2 years, were randomized in double-blind fashion to risperidone versus olanzapine. Patients were titrated up to 6 mg risperidone or 15 mg olanzapine as tolerated, followed by tapering and discontinuation of conventional antipsychotic medication. Atypical antipsychotic agents were then administered alone (monotherapy) for 12 weeks. Efficacy and tolerability were assessed using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale, and Simpson Angus Scale. Body weight was measured at each visit. Both treatment groups exhibited marked and similar improvement in the total PANSS score from baseline to study endpoint (22 weeks) [risperidone: baseline=59.3 (SE 3.1), 22 weeks=44.3 (SE 2.3) (p<0.001); olanzapine: baseline=55.9 (SE 3.3), 22 weeks=46.9 (SE 3.2) (p<0.001). Both groups also exhibited significant reductions in PANSS factor scores for positive and negative symptoms and disorganized thoughts. Only risperidone-treated patients exhibited significant decreases in uncontrolled hostility/excitement and anxiety and depression. Of note, while positive factor scores exhibited the majority of change within the first 10 weeks, negative factor scores continued to decline significantly in both treatment groups throughout the study. Tolerability assessments did not differ between groups. The results indicate that both atypical antipsychotic medications provided significant additional improvement in symptom severity in patients with schizophrenia previously on conventional antipsychotic agents.