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.     

Efficacy of Lung Cancer Screening; Comparison of Results from a Case-Control Study and a Survival Analysis

A case-control study to evaluate the efficacy of lung cancer screening conducted by us showed that lung cancer screening may reduce the mortality of the disease up to 28%. Assuming this efficacy is unbiased, and that the screening rate is 51.6%, which was observed in the control group in the above study, the number of lung cancer deaths prevented by screening in the study period was calculated to be 47 for males and females combined. In the same study population, screen-detected lung cancer patients (N = 207) in the same study period were followed and the 7-year survival rate (46.9%) was compared to the 5-year survival rate (11.3%) obtained by the Osaka Cancer Registry, in which screen-detected lung cancer patients were only 1.8%. The number of lung cancer deaths prevented by screening, estimated by the difference in the above two survival rates, was 74 (95% confidence interval; 55–93). The number of lung cancer deaths prevented by screening estimated from the case-control study was significantly lower than that estimated from the survival analysis. This indicates that the efficacy of lung cancer screening estimated by the case-control study was within the range that could be explained by the actual long-term survivors among the screen-detected patients in the study population.     

The Effect of Quisqualic Acid-Induced Lesions of the Nucleus Basalis Magnocellularis on Latent Inhibition

Latent inhibition (LI) is a reduction in the rate of acquisition of a Pavlovian conditioned response that results from prior nonreinforced preexposure to a conditioned stimulus (CS). LI has been suggested to reflect the operation of mechanisms involved in stimulus selection for subsequent cognitive processing. The present experiment was conducted to assess the effect of bilateral lesions of the nucleus basalis magnocellularis (NBM) on LI employing a conditioned emotional response paradigm. Bilateral lesions of the NBM were produced by administration of 0.12 M quisqualic acid and resulted in decreased cortical acetylcholinesterase staining, as well as a 40% reduction in cortical choline acetyltransferase activity. Following lever press training, preexposed animals received 40 presentations of a 60-s tone CS. Nonpreexposed animals received no tone presentations. Acquisition of conditioned suppression was then assessed over the course of 4 tone-shock (0.6 mA, 0.5 s) pairings. Control, preexposed animals displayed a retarded rate of acquisition in comparison to nonpreexposed controls, thereby demonstrating that the parameters used in the present experiment produced LI. In contrast, lesioned animals preexposed to the CS acquired conditioned suppression as readily as non-preexposed lesioned animals. However, the acquisition of conditioned suppression in both lesioned groups was found to be similar to that displayed in the preexposed control group. This pattern of results was interpreted as being attributable to a lesion-induced impairment in the ability to maintain stimulus processing, rather than a deficit in the ability to filter a stimulus. Copyright © 1996 Elsevier Science Inc.     

Effects of bombesin and gastrin-releasing peptide on memory processing

We have previously shown that feeding mice immediately following training enhances memory retention and that one of the gastrointestinal hormones released during a meal, cholecystokinin, also enhances retention after peripheral administration. In the studies reported here we demonstrate that another gastrointestinal peptide, gastrin-releasing peptide (GRP), enhances retention after peripheral administration, as does its amphibian counterpart, bombesin. GRP_14–27 had the same effect as the intact peptide, while GRP_1–16 was ineffective at enhancing retention. The dose-response curves showed a characteristic inverted U-shape with high doses of both GRP and bombesin being amnestic. The effect of both peptides was time-dependent and both reversed amnesia induced by the anticholinergic, scopolamine. I.c.v. administration of the peptides required higher doses to produce an effect on memory retention. suggesting that the effect was mediated predominantly through a peripheral mechanism. Doses of the peptides that enhanced memory retention after peripheral administration failed to increase serum glucose, suggesting that glucose modulation was not the mechanism by which GRP and bombesin modulate memory processing. Vagotomy inhibited the memory-enhancing effects of both GRP and bombesin, suggesting that these peptides produced their effect by stimulating ascending vagal pathways. These studies, together with our previous study with cholecystokinin, suggest the existence of a gastrointestinal hormonal system, which is activated by the passage of food through the intestine, that enhances memory retention.     

Disconjugate memory-guided saccades to disparate targets: evidence for 3D sensitivity

The saccadic system has been traditionally regarded as two-dimensional (horizontal, vertical) and basically conjugate in the two eyes. However, saccades to disparate targets (e.g., targets in real three-dimensional space that are located in different directions and at different distances) are naturally disconjugate. We report here that memory-guided saccades to a disparate target flashed 1 s earlier become disconjugate following repeated trials. After 15 min of repetition, the disconjugacy persists even when the target to be remembered is no longer disparate. This suggests fast memory-based learning. Learning, however, fails to occur if, during the repetition trials, the memory delay is 2 s. These findings suggest that the saccadic system has access to a 3D representation of targets and is gifted with 3D short-term memory and learning capacity. Received: 7 July 1997 / Accepted: 25 May 1998     

不同记忆负荷对事件相关电位—P300的影响

我们研究了不同记忆负荷条件下,ERP-P_(300)变化的规律性和特点及ERP-P_(300)与脑力负荷难度之间的关系。在三种脑力作业时,要求受试者记忆2、4、6位随机数字。结果表明,1、随着记忆数字增加,P_(300)波幅相应增大,三种记忆作业P_(300)波幅之间均有显著性差异。2、记忆错误率和记忆难度主观评价值,亦随着记忆数字增加而增大,且在三种记忆作业之间均有显著性差异。3、P_(300)波幅和记忆难度主观评价值之间相关分析表明呈正相关(P<0.01)。我们建议,P_(300)波幅测量可以作为评价脑力负荷的一项客观指标。     

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     

Glucocorticoids Decrease Hippocampal and Prefrontal Activation during Declarative Memory Retrieval in Young Men

Glucocorticoids (GCs, cortisol in human) are associated with impairments in declarative memory retrieval. Brain regions hypothesized to mediate these effects are the hippocampus and prefrontal cortex (PFC). Our aim was to use fMRI in localizing the effects of GCs during declarative memory retrieval. Therefore, we tested memory retrieval in 21 young healthy males in a randomized placebo-controlled crossover design. Participants encoded word lists containing neutral and emotional words 1 h prior to ingestion of 20 mg hydrocortisone. Memory retrieval was tested using an old/new recognition paradigm in a rapid event-related design. It was found that hydrocortisone decreased brain activity in both the hippocampus and PFC during successful retrieval of neutral words. These observations are consistent with previous animal and human studies suggesting that glucocorticoids modulate both hippocampal and prefrontal brain regions that are crucially involved in memory processing. Electronic Supplementary Material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

项目记忆和源记忆的功能磁共振成像研究

目的探讨项目记忆和源记忆的神经基础及其是否存在性别差异。方法健康男女各8名，实验材料为504个高频双汉字词，项目记忆和源记忆实验任务，Block设计，GE1．5T采集功能磁共振成像（mRI）数据，用SPM99分析，得到男女脑功能激活图（P〈0．002，体素块〉20）。结果在P〈0．002，体素块〉20时，女性项目记忆激活双前额叶背外侧BA6（激活数目左右侧分别为62和11个），源记忆较多激活左前额叶背外侧BA6／46（激活数目为59个）；男性项目记忆激活右前额叶背外侧BA6／46（激活数目为64个），源记忆激活双前额叶背外侧BA6（左右侧分别为9和40个）。结论项目记忆更多激活右侧前额叶背外侧，而源记忆更多激活左侧前额叶背外侧。女性较多地引起左前额叶背外侧激活；而男性较多地引起右前额叶背外侧激活。     

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。