| 1 | Clin Ther 2005 Dec 27: 1930-41 |
|---|---|
| PMID | 16507379 |
| 标题 | Effects of switching from olanzapine to risperidone on the prevalence of the metabolic syndrome in overweight or obese patients with schizophrenia or schizoaffective disorder: analysis of a multicenter, rater-blinded, open-label study. |
| Abstract | A major contributor to mortality inpatients withschizophreniaor schizoaffective disorder is cardiovascular disease, an important risk factor for which is the cluster of clinical abnormalities that define the metabolic syndrome (eg, abdominal/visceral obesity, hypertriglyceridemia, impaired glucose tolerance). The aim of this article was to examine the effects of switching from the antipsychotic olanzapine to risperidone on the prevalence of the metabolic syndrome in high-risk overweight or obese patients withschizophreniaor schizoaffective disorder. This post hoc analysis was based on data from a previous 2-phase, 20-week, multicenter (19 US sites), rater-blinded, open-label study. High-risk overweight or obese (body mass index [BMI], >26 kg/m(2)) patients aged 18 to 65 years withschizophreniaor schizoaffective disorder whose treatment was switched from olanzapine to risperidone were enrolled. Patients who entered the phase 1 switch from olanzapine to risperidone (6 weeks) and the phase 2 extension (14 weeks) were included in the assessment. The primary end point was the difference from baseline in the prevalence of the metabolic syndrome at week 20, determined using measurements of weight, BMI, waist circumference, and systolic and diastolic blood pressure (SBP/DBP). Baseline assessments for the metabolic syndrome were available from 121 of 123 patients recruited for phase 1 of the study (61 men, 60 women; mean [SD] age, 41.1 [10.2] years; mean [SD] BMI, 33.9 [6.9] kg/m(2)); 71 patients entered phase 2 (29 men, 42 women; mean [SD] age, 40.2 [10.3] years; mean [SD] BMI, 35.1 [7.3] kg/m(2)), of whom 39 (54.9%) ere diagnosed withschizophrenia，有32（45.1％）患有精神分裂症。在研究进入时，在63名（52.1％）患者中发现了代谢综合征。在71例基线和第20周可获得的数据（使用最后一次观察方法）中，代谢综合征的患病率从基线时的38名（53.5％）患者降低到研究端的26（36.6％）（McNemar）CHI（2）= 8.0，p <0.005）。在平均体重（P = 0.031），BMI（P = 0.002），腰围（P = 0.003），SBP（P = 0.006）和DBP(P = 0.010). There was no significant difference in the reduction in the prevalence of the metabolic syndrome between patients who did or did not receive the behavioral therapy for weight loss. In this post hoc analysis of switching from the antipsychotic olanzapine to risperidone on the prevalence of the metabolic syndrome in high-risk overweight or obese patients withschizophreniaor schizoaffective disorder, the metabolic syndrome was highly prevalent at baseline. Switching from olanza- pine to risperidone was associated with a significant reduction in this prevalence. |
| SCZ关键字 | schizophrenia, schizophrenic, schizophrenics |
| 2 | J Psychiatr Res 2005 Sep 39: 509-18 |
| PMID | 15992560 |
| 标题 | 精神分裂症中对情绪图片的生理反应。 |
| Abstract | schizophrenic在e患者已知经验困难motional information processing, yet knowledge of their physiological responsivity to emotional stimuli is limited. The purpose of this study was to investigate the physiological reactions ofschizophrenicpatients to emotional stimuli. We presented pictures selected from the International Affective Picture System (IAPS) to patients and controls, while assessing their subjective evaluations in terms of valence and arousal scores and measuring their responses of heart rate (HR), breathing rate (BR), skin conductance level (SCL) and diastolic (DBP）和收缩压（SBP）。为了分析生理数据，形成了三个情绪图像类别：阳性（色情含量），阴性（身体伤害）和中性（景观）。患者和对照在对图片的主观评估上没有差异。同样，对于患者和对照组，SCL和DBPresponses to positive emotional pictures were larger as compared to negative and neutral pictures. However, the patients did show significantly increased HR responses to the positive emotional pictures as compared to controls, possibly as a result of a decreased parasympathetic activity. Only for the BR response to the positive emotional pictures did we observe significant positive correlations with the PANSS scores. These first data suggest that altered physiological responsivity to emotional pictures inschizophreniais limited to those with positive emotional content. Further studies will need to refine the dynamics of this stimulus category in relation to clinical state and medication effects. |
| SCZ关键字 | schizophrenia, schizophrenic, schizophrenics |
| 3 | J Psychiatr Res 2005 Sep 39: 509-18 |
| PMID | 15992560 |
| 标题 | 精神分裂症中对情绪图片的生理反应。 |
| Abstract | schizophrenic在e患者已知经验困难motional information processing, yet knowledge of their physiological responsivity to emotional stimuli is limited. The purpose of this study was to investigate the physiological reactions ofschizophrenicpatients to emotional stimuli. We presented pictures selected from the International Affective Picture System (IAPS) to patients and controls, while assessing their subjective evaluations in terms of valence and arousal scores and measuring their responses of heart rate (HR), breathing rate (BR), skin conductance level (SCL) and diastolic (DBP）和收缩压（SBP）。为了分析生理数据，形成了三个情绪图像类别：阳性（色情含量），阴性（身体伤害）和中性（景观）。患者和对照在对图片的主观评估上没有差异。同样，对于患者和对照组，SCL和DBPresponses to positive emotional pictures were larger as compared to negative and neutral pictures. However, the patients did show significantly increased HR responses to the positive emotional pictures as compared to controls, possibly as a result of a decreased parasympathetic activity. Only for the BR response to the positive emotional pictures did we observe significant positive correlations with the PANSS scores. These first data suggest that altered physiological responsivity to emotional pictures inschizophreniais limited to those with positive emotional content. Further studies will need to refine the dynamics of this stimulus category in relation to clinical state and medication effects. |
| SCZ关键字 | schizophrenia, schizophrenic, schizophrenics |
| 4 | 精神分裂。res。2008 Apr 101: 266-72 |
| PMID | 18262771 |
| 标题 | Metabolic syndrome in first episode schizophrenia - a randomized double-blind controlled, short-term prospective study. |
| Abstract | 虽然治疗schizophrenia可以说，当今最具破坏性的疾病之一，由于第二代抗精神病药的出现而得到了极大的帮助，它们以相当大的代价 - 代谢综合征（Mets）。已经用几种抗精神病药描述了这种不良反应，范围为20％-60％，至少是普通人群患病率的两倍。 All consecutive patients with first episodeschizophreniaat our referral psychiatric hospital were recruited in an extensive prospective randomized, double-blind controlled study including measures of waist circumference (WC), blood pressure (SBP/DBP), triglyceride (TGL), high-density lipoproteins (HDL) and fasting blood sugar (FBS) levels and randomized to receive either, haloperidol, olanzapine or risperidone. The prevalence of MetS was assessed based on two criteria- ATP IIIA and criteria of International Diabetes Federation (IDF). This was compared with a gender, age, exercise and diet matched healthy control group. The analysis of 99 patients showed a prevalence of MetS as 10.1% and 18.2% as assessed by ATP IIIA and IDF criteria respectively. The prevalence of MetS in our sample of patients withschizophreniais at least five times as high when compared to the matched healthy control group. Olanzapine had maximum prevalence of MetS at 20-25% followed by risperidone at 9-24% and haloperidol at 0-3%. Metabolic syndrome is highly prevalent among treated patients with first episodeschizophrenia。Early monitoring of patients on atypical antipsychotics can possibly play an important role in early detection and hence prevention of the metabolic syndrome. |
| SCZ关键字 | schizophrenia, schizophrenic, schizophrenics |
| 5 | 翻译精神病学2011 -1 1：E9 |
| PMID | 22832404 |
| 标题 | Convergent functional genomics of anxiety disorders: translational identification of genes, biomarkers, pathways and mechanisms. |
| Abstract | Anxiety disorders are prevalent and disabling yet understudied from a genetic standpoint, compared with other major psychiatric disorders such as bipolar disorder andschizophrenia。The fact that they are more common, diverse and perceived as embedded in normal life may explain this relative oversight. In addition, as for other psychiatric disorders, there are technical challenges related to the identification and validation of candidate genes and peripheral biomarkers. Human studies, particularly genetic ones, are susceptible to the issue of being underpowered, because of genetic heterogeneity, the effect of variable environmental exposure on gene expression, and difficulty of accrual of large, well phenotyped cohorts. Animal model gene expression studies, in a genetically homogeneous and experimentally tractable setting, can avoid artifacts and provide sensitivity of detection. Subsequent translational integration of the animal model datasets with human genetic and gene expression datasets can ensure cross-validatory power and specificity for illness. We have used a pharmacogenomic mouse model (involving treatments with an anxiogenic drug--yohimbine, and an anti-anxiety drug--diazepam) as a discovery engine for identification of anxiety candidate genes as well as potential blood biomarkers. Gene expression changes in key brain regions for anxiety (prefrontal cortex, amygdala and hippocampus) and blood were analyzed using a convergent functional genomics (CFG) approach, which integrates our new data with published human and animal model data, as a translational strategy of cross-matching and prioritizing findings. Our work identifies top candidate genes (such as FOS, GABBR1, NR4A2, DRD1, ADORA2A, QKI, RGS2, PTGDS, HSPA1B, DYNLL2, CCKBR andDBP), brain-blood biomarkers (such as FOS, QKI and HSPA1B), pathways (such as cAMP signaling) and mechanisms for anxiety disorders--notably signal transduction and reactivity to environment, with a prominent role for the hippocampus. Overall, this work complements our previous similar work (on bipolar mood disorders andschizophrenia) conducted over the last decade. It concludes our programmatic first pass mapping of the genomic landscape of the triad of major psychiatric disorder domains using CFG, and permitted us to uncover the significant genetic overlap between anxiety and these other major psychiatric disorders, notably the under-appreciated overlap withschizophrenia。PDE10A, TAC1 and other genes uncovered by our work provide a molecular basis for the frequently observed clinical co-morbidity and interdependence between anxiety and other major psychiatric disorders, and suggest schizo-anxiety as a possible new nosological domain. |
| SCZ关键字 | schizophrenia, schizophrenic, schizophrenics |
| 6 | 精神分裂。res。2014 Aug 157: 244-8 |
| PMID | 24934904 |
| 标题 | 血清脑源性神经之间的关系trophic factor (BDNF) and cardiometabolic indices in schizophrenia. |
| Abstract | Brain derived neurotrophic factor (BDNF), which has been implicated in the pathogenesis ofschizophrenia, has been recently shown to be involved in the regulation of metabolism and energy homeostasis. This study seeks to examine the relationship between BDNF, metabolic indices and cardiovascular (CVD) risk in patients withschizophrenia。收集了61名参与者的医学历史，人口统计信息和人体测量测量schizophrenia。Fasting glucose and lipids were measured in a central laboratory, and serum BDNF was analyzed using commercially available enzyme-linked immunosorbent assay (ELISA). The 10-year CVD risk for each participant was computed using the Framingham risk score (FRS). Linear regressions were performed to examine the relationships between serum BDNF with body mass index (BMI), blood pressure (BP), triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-C) and glucose. To examine the relationship between serum BDNF and FRS, serum BDNF was categorized into quartiles, and a multiple regression was performed. After adjusting for age, gender and current smoking status, diastolic BP (DBP) (p=0.045) and TG (p=0.015) were found to be significantly associated with serum BDNF. Participants in the highest quartile of serum BDNF had a 3.3 times increase in FRS over those in the lowest quartile. Our findings support the possible regulatory role of BDNF in metabolism and cardiovascular homeostasis among patients withschizophreniasimilar to that observed among the non-mentally ill. Serum BDNF not only present itself as a candidate biomarker ofschizophreniabut also might be a viable marker of metabolic co-morbidities associated withschizophrenia。 |
| SCZ关键字 | schizophrenia, schizophrenic, schizophrenics |
| 7 | Transl Psychiatry 2014 -1 4: e391 |
| PMID | 24844177 |
| 标题 | Genetic risk prediction and neurobiological understanding of alcoholism. |
| Abstract | We have used a translational Convergent Functional Genomics (CFG) approach to discover genes involved in alcoholism, by gene-level integration of genome-wide association study (GWAS) data from a German alcohol dependence cohort with other genetic and gene expression data, from human and animal model studies, similar to our previous work in bipolar disorder andschizophrenia。小组的名义上重要的假定值SNPs in the top candidate genes discovered by CFG� (n=135 genes, 713 SNPs) was used to generate a genetic� risk prediction score (GRPS), which showed a trend towards significance (P=0.053) in separating� alcohol dependent individuals from controls in an independent German test cohort. We then validated and prioritized our top findings from this discovery work, and�subsequently tested them in three independent cohorts, from two continents. A panel of all the nominally significant P-value single-nucleotide length polymorphisms (SNPs) in the top candidate genes discovered by CFG (n=135 genes, 713 SNPs) were used to generate a Genetic Risk Prediction Score (GRPS), which showed a trend towards significance (P=0.053) in separating alcohol-dependent individuals from controls in an independent German test cohort. In order to validate and prioritize the key genes that drive behavior without some of the pleiotropic environmental confounds present in humans, we used a stress-reactive animal model of alcoholism developed by our group, the D-box binding protein (DBP）敲除小鼠，与Koob及其同事提出的成瘾理论的过度相符。一个较小的面板（n = 11个基因，66个SNP），用于酒精中毒，交叉验证并通过这种应激反应性动物模型优先级，在独立的德国测试队列中表现出更好的预测能力（P = 0.041）。在最初发现步骤中，酗酒的最高CFG评分基因是在应力反应性动物模型交叉验证之后，突触核蛋白α（SNCA）仍然是最高基因。我们还在来自美国的另外两个独立的测试队列中测试了这一小基因，一个基因具有酒精依赖性（P = 0.00012），另一个具有酒精滥用（酒精中毒形式不太严重； p = 0.0094）。SNCA本身能够将酒精中毒与酒精依赖人群中的对照组分开（p = 0.000013）和酒精滥用队列（p = 0.023）。从较小程度和/或在整个队列中宽广的，来自11个基因的小组中的其他八个基因也是如此。SNCA，GRM3和MBP在严格的Bonferroni校正中得以进行多次比较。综上所述，这些结果表明我们的压力反应性DBPanimal model helped to validate and prioritize from the CFG-discovered genes some of the key behaviorally relevant genes for alcoholism. These genes fall into a series of biological pathways involved in signal transduction, transmission of nerve impulse (including myelination) and cocaine addiction. Overall, our work provides leads towards a better understanding of illness, diagnostics and therapeutics, including treatment with omega-3 fatty acids. We also examined the overlap between the top candidate genes for alcoholism from this work and the top candidate genes for bipolar disorder,schizophrenia, anxiety from previous CFG analyses conducted by us, as well as cross-tested genetic risk predictions. This revealed the significant genetic overlap with other major psychiatric disorder domains, providing a basis for comorbidity and dual diagnosis, and placing alcohol use in the broader context of modulating the mental landscape. |
| SCZ关键字 | schizophrenia, schizophrenic, schizophrenics |
| 8 | 精神分裂。res。2016年4月1日：-1 |
| PMID | 27132483 |
| 标题 | Altered circadian clock gene expression in patients with schizophrenia. |
| Abstract | Impaired circadian rhythmicity has been reported in several psychiatric disorders.schizophreniais commonly associated with aberrant sleep-wake cycles and insomnia. It is not known ifschizophreniais associated with disturbances in molecular rhythmicity. We cultured fibroblasts from skin samples obtained from patients with chronicschizophreniaand from healthy controls, respectively, and analyzed the circadian expression during 48h of the clock genes CLOCK, BMAL1, PER1, PER2, CRY1, CRY2, REV-ERB? andDBP。In fibroblasts obtained from patients with chronicschizophrenia，我们发现与健康对照细胞相比，CRY1和PER2的节奏表达丧失。我们还估计了这些患者的睡眠质量，发现与健康对照相比，大多数患者的睡眠不佳。在另一个患者样本中，我们分析了来自schizophreniaexperiencing their first episode of psychosis, and found decreased expression of CLOCK, PER2 and CRY1 compared to blood cells from healthy controls. These novel findings show disturbances in the molecular clock inschizophrenia并在我们对这种疾病中报道的异常节奏的理解中具有重要意义。 |
| SCZ关键字 | schizophrenia, schizophrenic, schizophrenics |