A path-analytical approach to differentiate between direct and indirect drug effects on negative symptoms in schizophrenic patients

The hypothesis that differences in drug effects of risperidone and haloperidol on negative symptoms in schizophrenia are secondary to effects on positive, extrapyramidal, and depressive symptoms was investigated by means of an analysis of the data from the USA-Canada risperidone double-blind randomized clinical trial of 523 chronic schizophrenic patients. Regression analyses in the total sample and within treatment groups confirmed a strong relationship between changes in negative symptoms and the other variables studied (R²=0.50–0.51,p<0.001). Only depressive symptoms did not contribute significantly to these results (p>0.10). Path analysis showed that the greater mean change (p<0.05) of negative symptoms with risperidone compared to haloperidol could not be fully explained by correlations with favourable effects on positive and extrapyramidal symptoms. The relationship between shift in extrapyramidal symptoms and shift in negative symptoms failed to reach statistical significance; however, there was a clear tendency in the expected direction in both treatment groups.     

待分类的精神病性和非精神病性精神障碍与精神分裂症的对比分析

目的 探讨待分类的精神病性和非精神病性精神障碍临床特征。方法 对待分类的精神病性和非精神病性精神障碍与精神分裂症临床资料进行对比分析。结果 待分类的精神病性障碍与精神分裂症在发病年龄、复发率、阳性家族史、治疗和疗效上无显著性差异；待分类的非精神病性精神障碍在复发率、阳性家族史及治愈率上与前两者有显著性差异。结论 待分类的精神病性障碍与精神分裂症可能具有同源性，部分非精神病性精神障碍与两者可能不同源。     

一次和多次住院精神分裂症患者再住院分析

目的 :比较 1次和≥ 2次住院精神分裂症患者出院后的再住院率 ,初步探讨影响再住院的相关因素。　方法 :1999年度出院的 833例住院精神分裂症患者纳入调查 ,使用自制的再住院及其相关因素调查表 ,于 2 0 0 3年 12月底前电话或入户调查出院后至少 4 8个月的情况。　结果 :6 6 4例完成调查 ,分为 1次住院组 (333例 )和多次住院组 (331例 )。用生存分析 (Kaplan Meier公式 )比较两组未再住院率 ,12个月末 (分别为 6 7 0 %和 6 1 6 % )、2 4个月末 (5 6 2 %和 4 8 9% )、36个月末 (4 6 0和 35 1% )和 4 8个月末 (4 1 1%和 2 8 7% )。Cox回归风险比例模型分析影响再住院的相关因素显示 ,与药物依从性、生活事件、自知力和家庭照顾相关 (P <0 0 5 ) ,药物依从性对再住院的贡献值 (1 719)最大。　结论 :1次住院精神分裂症患者出院后的再住院率较多次住院者低。药物依从性是影响再住院的主要因素     

A sexually dimorphic ratio of orbitofrontal to amygdala volume is altered in schizophrenia.

BACKGROUND: Neuroanatomic sexual dimorphisms have been correlated with behavioral differences between healthy men and women. We have reported higher orbitofrontal cortex to amygdala ratio (OAR) in women than men. Although gender differences in schizophrenia are evident clinically and correlate with neuroanatomic measures, their relationship to OAR has not been examined. METHODS: Magnetic resonance imaging was performed in 31 neuroleptic-na?ve schizophrenic patients (16 men) and 80 healthy volunteers (34 men), aged less than 50 years. An automated tissue segmentation procedure was combined with expert-guided parcellation of orbitofrontal and amygdala volumes. RESULTS: Men with schizophrenia had increased OAR relative to healthy men, whereas women had decreased OAR. Increased OAR in men with schizophrenia reflected abnormally low amygdala volumes, whereas decreased OAR in women reflected abnormally low orbitofrontal volumes. Less severe negative symptoms were associated with increased OAR in men but with decreased OAR in women. In men, increased amygdala volume was associated with greater symptom severity, whereas in women higher volumes of both amygdala and orbitofrontal regions were associated with lesser severity of negative symptoms. CONCLUSIONS: These opposite OAR abnormalities, whereby men show feminization and women masculinization, suggest gender-mediated effects of the underlying neuropathologic processes. The correlations with symptom severity suggest that neuroanatomic abnormalities in OAR reflect compensatory brain changes.     

An alternative mechanism of actions for neuroleptic and antidepressant drugs

It has earlier been proposed by the author that the aetiology of schizophrenic symptomatology may be due to the presence of abnormally connected interhemispheric fibres which link specialised functions in the brains of schizophrenics that are not connected in normal subjects, and that the neuroleptic drugs may produce their action through a local anaesthetic-like effect in suppression of conduction in these fibres. This line of thought has been extended here to consider the possible mechanism of action of the neuroleptic drugs in more detail, as well as that of the tricyclic antidepressant drugs which are derivatives of the phenothiazine group. Pharmacological similarities with the local anaesthetics both structurally and functionally have been considered, as well as the effects that these drug groups may have in common with the lithium salts. It has been suggested that these drugs all produce their primary effect on cell membranes, though not necessarily at the synapse, that the time course of their clinical effect may correlate with their incorporation into various cell membranes within the CNS, and that they may thus bring about a fundamental alteration in cell membrane microstructure. The possible role of electroconvulsive therapy has also been considered. The corollary of this argument is that the affective disorders may be genetically determined diseases of cell membrane microstructure.     

Retroviruses and schizophrenia in Jamaica

Reports of an 18-fold higher incidence of schizophrenia among second-generation Afro-Caribbeans, and especially Jamaican migrants in the United Kingdom were soon called “an epidemic of schizophrenia,” with the inference that a novel virus, likely to be perinatally transmitted, was a possible etiological agent. This intriguing observation led us to explore a possible link with human T-cell lymphotropic virus type one (HTLV-I), because it is a virus that is endemic in the Caribbean Islands, is perinatally transmitted, known to be neuropathogenic, and the cause of a chronic myelopathy (tropical spastic paraparesis/ HTLV-I associated myelopathy). We therefore examined inpatients at the Bellevue Mental Hospital, Kingston, Jamaica and did standard serological tests for retroviruses HTLV-I and HTLV-II and HIV-I and HIV-II on 201 inpatients who fulfilled ICD-9 and DSM III-R criteria for schizophrenia. Our results produced important negative data, since the seropositivity rates for HTLV-I, the most likely pathogen, were no greater than the seropositivity range for HTLV-I carriers in this island population, indicating that HTLV-I and the other retroviruses tested do not play a primary etiological role in Jamaican schizophrenics.     

Length of hospital stay and associated costs for olanzapine vs. haloperidol in the treatment of schizophrenia relapse in Germany

We examined the number of days spent in hospital due to a relapse of schizophrenia and the associated costs for patients treated with olanzapine or haloperidol. Twenty-one German psychiatric hospitals participated in this retrospective study. Data on the last hospitalisation following a relapse of schizophrenia were documented for equal numbers of patients on olanzapine and haloperidol. Matching for time since diagnosis and severity of symptoms was performed. Data were collected on 136 matched pairs. Total length of time spent in hospital was the same on average for patients in both groups (median about 5 weeks), but olanzapine patients spent nearly 1 week less in the in-patient setting than haloperidol patients, resulting in a saving of Euro 411 per patient. Our findings are consistent with those of randomised clinical trials in concluding that olanzapine is preferable to haloperidol in terms of the direct cost of treating schizophrenia. Andrea Spannheimer Kendle GmbH & Co. GMI KG, Stefan-George-Ring 6, 81929 Munich, Germany, e-mail: spannheimer.andrea@kendle.com     

利培酮治疗与细胞色素P4502D6/C188T酶基因多态性的关联分析

目的　研究利培酮临床效应的个体差异与其代谢酶细胞色素P4 5 0 2D6 (cytochromeP4 5 02D6 ,CYP2D6 )酶基因多态性的相关性。方法　对 88例符合CCMD 3精神分裂症诊断标准的患者和 96例健康对照者作病例 -对照分析。精神分裂症患者给予利培酮治疗 8周 ,用阳性和阴性症状量表 (posi tiveandnegativesymptomscale ,PANSS)评分评价利培酮疗效。采用聚合酶链反应扩增及限制性片段长度多态性 (PCR RFLP)技术对CYP2D6exonⅠ的C188T位点突变进行检测 ,分析利培酮临床效应与其主要代谢酶CYP2D6 /C188T酶基因多态性的相关性。结果　中国上海地区人群的CYP2D6 /C188T突变率(弱代谢型 )为 36 .3% ,病例组和正常对照组间基因型频率总体分布比较无显著差异 (χ2 =1.15 ,df=2 ,P >0 .0 5 ) ,两组间的等位基因频率之间比较也无显著性差异 (χ2 =0 .78,df=1,P >0 .0 5 )。进行性别及有否家族史分组后分析 ,亦无差异存在 ,且CYP2D6 /C188T突变与利培酮临床效应之间并无相关性 (χ2 =1.12 ,df=2 ;χ2 =0 .0 3,df=1,P >0 .0 5 )。结论　未发现中国人CYP2D6 /C188T多态性与利培酮临床效应的个体差异有相关性。