抗精神病药物引起高催乳素血症的机制

催乳素(PRL)升高是抗精神病药物常见的不良反应,可以引起性功能障碍、泌乳、月经不调、骨质疏松以及乳腺癌等多种临床结局.本文综述了精神分裂症患者的血清催乳素水平、抗精神病药物对精神分裂症患者血清催乳素水平的影响及机制的探讨,为临床科研以及临床用药提供循证医学依据.     

抗精神病药物所致高催乳素血症的遗传因素研究进展

高催乳素血症是抗精神病药物治疗中常见的不良反应，可引起月经紊乱、溢乳、男性乳房女性化、性功能障碍以及乳腺癌等多种临床结局，降低精神分裂症患者服药依从性和生活质量，影响预后。本文对与抗精神病药物所致催乳素升高的遗传因素的研究进展进行综述，旨在为抗精神病药物临床个体化用药和未来临床研究提供参考依据。     

氯氮平、利培酮和奥兰扎平的5-HT_2和DA_2受体占有率

众所周知,抗精神病药阻断了多巴胺(DA2)受体,虽然未证实这与抗精神病药效果一定有因果关系,但两者之间的关系不容否认。已证实DA2受体占有率与抗精神病效果存在阈值关系,为60%或70%。当占有率超过80%时,锥体外系副作用(EPS)发生率明显上升;而且催乳素水平的升高也可能与DA2受体占有率存在阈值关系。因此DA2受体占有率可能是抗精神病药治疗效果、锥体外系副作用及催乳素升高的可靠指标。非经典抗精神病药较少引起EPS和催乳素升高。本研究的主要目的是比较氯氮平、利培酮和奥兰扎平在治疗范围内、多剂量和稳态使用时DA2受体的占有率。…     

阿立哌唑对抗精神病药物所致的老年精神分裂症患者高催乳素血症的影响

目的:探讨阿立哌唑对抗精神病药物所致的老年精神分裂症患者高催乳素血症的影响.方法:63例抗精神病药所致高催乳素血症的老年精神分裂症患者随机分为研究组(33例)和对照组(30例).两组沿用原有抗精神病药物,研究组加用阿立哌唑5 mg/d持续12周.分别于入组前、入组4、8、12周末检测血清催乳素水平,同时采用简明精神病评定量表(BPRS)和治疗中出现的症状量表(TESS)评定精神病性症状及药物不良反应. 结果:入组4、8、12周末研究组血清催乳素水平较入组前及对照组显著降低(P均＜0.05);对照组入组前后血清催乳素水平差异无统计学意义(P均＞0.05).两组人组前后BPRS、TESS评分差异无统计学意义(P均＞0.05). 结论:阿立哌唑可有效降低抗精神病药物所致老年精神分裂症患者血清催乳素水平增高,且并未增加药物不良反应.     

抗精神病药对妊娠和哺乳的影响

精神分裂症和双相障碍妇女都可能服抗精神病药治疗,而抗精神病药对妊娠和哺乳有何影响,一直是精神科医生所关心的问题,本文综述了抗精神病药对妊娠和哺乳的影响。1高催乳素血症1.1机制抗精神病药强效阻断垂体前叶D2受体,迅速增加催乳素分泌,引起高催乳素血症（定义为血浆催乳素浓度〉20μg/L）.1.2机率引起高催乳素血症的率利培酮最高（88%,记作90%）,典型抗精神病药次之（48%,记作50%）,     

非典型抗精神病药物对患者体质量的影响

非典型抗精神病药物对代谢的影响包括体质量增加、血糖升高、血脂代谢异常、催乳素水平升高等。目前对瘦素的研究于进一步揭示非典型抗精神病药物对体质量增加的作用机制具有意义。     

5-HT和DA的相互影响与氯氮平的作用机制

氯氮平及其它非经典抗精神病药物对5-HT_2受体的亲和力强于对D_2受体,这一作用机制决定了这类药物区别于经典抗精神病药物。本文从5-HT与DA的相互影响阐述了氯氮平的有关作用机制。     

抗精神病药物治疗时的神经内分泌试验

Ⅰ氟哌啶醇兴奋试验时血浆催乳素变化血浆中催乳素(PRL)浓度与抗精神病药物阻断多巴胺受体的功能有关。由于接受治疗剂量的抗精神病药物后,每例患者血中PRL 的浓度各不相同,所以药物治疗有效时,血中 PRL 的浓度是否达到最高值?抑或达到同样血浓度的 PRL 时,是否阻断同量的多巴胺受体?这是饶有兴趣的问题,本试验拟探讨血浆中 PRL 浓度与药物疗效及阻断多巴胺受体之间的关系。     

抗精神病药所致的高催乳素血症--读者来信

编辑先生: 高催乳素血症是抗精神病药常见的不良反应.我们想了解不同种抗精神病药对精神障碍患者催乳素水平的影响.请予以指教,谢谢!     

多巴胺受体与抗精神病药的副作用北大核心CSCD

目前上市的抗精神病药均作用于多巴胺D2样受体。D2受体的阻断既能改善幻觉妄想等阳性症状,也会带来锥体外系综合征和高催乳素血症等副作用。5-羟色胺2A受体阻断、D2受体的快速解离和D3受体的选择性,均在一定程度上减轻锥体外系反应,故而成就了第2代抗精神病药的"非典型"特征。药物不易透过血脑屏障导致的垂体蓄积及其D2受体占有率高,则有助于解析高催乳素血症的产生。     

Environmental factors in the development and progression of late-onset Alzheimer＇s disease

Late-onset Alzheimer＇s disease （LOAD） is an age-related neurodegenerative disorder characterized by gradual loss of synapses and neurons, but its pathogenesis remains to be clarified. Neurons live in an environment constituted by neurons themselves and glial cells. In this review, we propose that the neuronal degeneration in the AD brain is partially caused by diverse environmental factors. We first discuss various environmental stresses and the corresponding responses at different levels. Then we propose some mechanisms underlying the specific pathological changes, in particular, hypothalamic-pituitary adrenal axis dysfunction at the systemic level; cerebrovascular dysfunction, metal toxicity, glial activation, and Aβ toxicity at the intercellular level; and kinase-phosphatase imbalance and epigenetic modification at the intracellular level. Finally, we discuss the possibility of developing new strategies for the prevention and treatment of LOAD from the perspective of environmental stress. We conclude that environmental factors play a significant role in the development of LOAD through multiple pathological mechanisms.     

Disrupted structural and functional brain connectomes in mild cognitive impairment and Alzheimer＇s disease

Alzheimer＇s disease （AD） is the most common type of dementia, comprising an estimated 60-80% of all dementia cases. It is clinically characterized by impairments of memory and other cognitive functions. Previous studies have demonstrated that these impairments are associated with abnormal structural and functional connections among brain regions, leading to a disconnection concept of AD. With the advent of a combination of non-invasive neuroimaging （structural magnetic resonance imaging （MRI）, diffusion MRI, and functional MRI） and neurophysiological techniques （electroencephalography and magnetoencephaJography） with graph theoretical analysis, recent studies have shown that patients with AD and mild cognitive impairment （MCI）, the prodromal stage of AD, exhibit disrupted topological organization in large-scale brain networks （i.e., connectomics） and that this disruption is significantly correlated with the decline of cognitive functions. In this review, we summarize the recent progress of brain connectomics in AD and MCI, focusing on the changes in the topological organization of large-scale structural and functional brain networks using graph theoretical approaches. Based on the two different perspectives of information segregation and integration, the literature reviewed here suggests that AD and MCI are associated with disrupted segregation and integration in brain networks. Thus, these connectomics studies open up a new window for understanding the pathophysiological mechanisms of AD and demonstrate the potential to uncover imaging biomarkers for clinical diagnosis and treatment evaluation for this disease.     

Edema and neuronal apoptosis in the hippocampus and cortex of elderly rats following transient cerebral ischemia/reperfusion injury

BACKGROUND： Previous studies of cerebral ischemia have used young animals, with an ischemic time greater than 5 minutes （safe time limit）. Despite an increased understanding of neuronal apoptosis, it remains uncertain whether brief cerebral ischemic events of 5 minutes or less damage brain tissue in elderly rodents. OBJECTIVE： To investigate the effects of transient cerebral ischemia （5 minutes）/reperfusion injury on brain cortical and hippocampal edema, aquaporin-4 （AQP-4） expression, and neuronal apoptosis in aged rats, and to compare ischemic sensitivity between cortex and hippocampus. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Institute of Cerebrovascular Disease, Qingdao University Medical School from April 2008 to March 2009. MATERIALS： Rabbit anti-AQP-4 polyclonal antibody, TUNEL kit, and SABC immunohistochemistry kit were purchased from Wuhan Boster Bioengineering, China. METHODS： A total of 160 healthy, male, aged 19-21 months, Wistar rats were randomly assigned to 4 groups： sham-surgery, and ischemia 1-, 3-, and 5-minute groups, with 40 rats in each group. The global cerebral ischemia model was established using the Pusinelli four-vessel occlusion, and the three cerebral ischemia groups were subdivided into reperfusion 12-hour, 1-, 2-, 3-, and 7-day subgroups, with 8 rats in each subgroup. The sham-surgery group was subjected to exposure of the first cervical bilateral alar foramina and bilateral common carotid arteries. MAIN OUTCOME MEASURES： The dry-wet weight assay was used to measure brain water content and histopathology of the cortex and hippocampus was observed following hematoxylin-eosin staining. In addition, cortical and hippocampal AQP-4 expression was detected by streptavidin-biotin complex immunohistochemistry, and neuronal apoptosis was detected by the TUNEL method. RESULTS： There was no significant difference in brain water content or AQP-4 expression in the cortex and hippocampus between ischemia 1- and 3-minute groups and the sham-surgery group or brain water content or AQP-4 expression in the cortex between ischemia 5-minute group and sham-surgery group （P 〉 0.05）. However, brain water content and AQP-4 expression in the hippocampus after 5 minutes of cerebral ischemia were significantly increased compared with the sham-surgery group （P 〈 0.05 or P 〈 0.01）. Several TUNEL-positive cells were observed in the cortex and hippocampus of the sham-surgery group and ischemia 1-minute group, as well as in the cortex of the ischemia 3-minute group. In addition, the number of apoptotic neurons in the hippocampus of ischemia 3-minute group and in the cortex and hippocampus of ischemia 5-minute group was significantly increased （P 〈 0.05 or P 〈 0.01 ）. Neuronal apoptosis was increased after 12 hours of ischemia/reperfusion, and it reached a peak by 2 days （P 〈 0.01）. CONCLUSION： Transient cerebral ischemia （5 minutes） resulted in increased hippocampal edema, AQP-4 expression, and neuronal apoptosis. Moreover, cerebral ischemia had a greater effect on neuronal apoptosis than brain edema or AQP-4 expression, and the hippocampus was more sensitive than the cortex.     

Total saponins of Panax ginseng effects on proliferation and differentiation of human embryonic neural stem cells and in a Parkinson’s disease mouse model

BACKGROUND： Total saponins of Panax ginseng （TSPG） exhibits neuroprotection against Parkinson＇s disease in the substantia nigra. OBJECTIVE： To investigate the effects of TSPG on human embryonic neural stem cells （NSCs） proliferation and differentiation into dopaminergic neurons using in vitro studies, and to observe NSC differentiation in a mouse model of Parkinson＇s disease, as well as behavioral changes before and after transplantation. DESIGN, TIME AND SETTING： In vitro neural cell biology trial and in vivo randomized, controlled animal trial were performed at the Institute of Basic Medical Sciences, Chongqing Medical University between September 2004 and December 2007. MATERIALS： TSPG （purity 〉 95%） was isolated, extracted, and identified by Chongqing Academy of Chinese Materia Medica. Recombinant human basic fibroblast growth factor （bFGF） and recombinant human epidermal growth factor （EGF） were purchased from PeproTech, USA. A total of 25 C57/BL6J mice, aged 18-20 weeks were included. Twenty were used to establish a Parkinson＇s disease model with i.p. injection of MPTP （1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine） and TSPG alone or combined with interleukin-1 （IL-1）-treated NSCs prior to transplantation into the corpus striatum. The remaining five mice were pretreated for 3 days with TSPG prior to MPTP injection, serving as the TSPG prevention group. METHODS： Primary NSCs were isolated, cultured and purified from embryonic cerebral cortex. Immunocytochemistry was employed to detect specific antigen expression in the NSCs. In vitro experiment： （1） to induce proliferation, NSCs were treated with TSPG, EGF＋bFGF, or TSPG＋EGF＋bFGF, respectively; （2） to induce dopaminergic neuronal differentiation, NSCs were treated with TSPG, IL-1, or TSPG＋IL-1, respectively. MAIN OUTCOME MEASURES： In vitro experiment： the effects of TSPG on NSCs proliferation were evaluated with flow cytometry and MTT assay. Tyrosine hydroxylase expression was determined by immunocytochemistry assay to observe effects of TSPG on dopaminergic neuronal differentiation. In vivo experiment： differentiation of grafted NSCs in the mouse brain was determined by immunohistochemical staining. Behavioral changes were evaluated by spontaneous activity frequency, memory function, and score of paralysis agitans. RESULTS： （1） NSCs were cultured and passaged for more than three passages. Immunocytochemistry revealed positive nestin staining, as well as neurofilament protein and glial fibrillary acidic protein. （2） TSPG significantly increased NSC proliferation, in particular when combined with EGF and bFGF, which was twice as effective as FGF or bFGF alone. TSPG also induced dopaminergic differentiation in NSCs, in particular when TSPG was added together with IL-1, resulting in an effect five times greater than that of IL-1 alone. （3） At day 30 following transplantation, most NSCs in the TSPG prevention group differentiated into dopaminergic neurons, and the scores of paralysis agitans, spontaneous activity, and memory function were significantly increased compared with TSPG alone or TSPG＋IL-1 groups （P 〈 0.05）. CONCLUSION： TSPG stimulated NSC proliferation, in particular when combined with FGF and bFGF. TSPG significantly induced dopaminergic neuronal differentiation of NSCs, and the effect was greater when combined with IL-1. In addition, TSPG greatly improved behavior in the Parkinson＇s disease mouse model following NSC transplantation. Following NSC transplantation, TSPG pretreatment exhibited superior efficacy over either TSPG alone or TSPG in combination with IL-1, in terms of behavioral improvements in the Parkinson＇s disease mouse model.     

墨蝶呤还原酶基因与精神分裂症相关性的研究进展

墨蝶呤还原酶（SPR）催化四氢生物蝶呤（BH4）从头合成途径的最后一步反应。SPR基因遗传缺陷或突变可导致BH。的合成紊乱,影响单胺类神经递质（如多巴胺、5-羟色胺及谷氨酸等）的合成或释放,进而参与包括精神分裂症在内的多种神经精神系统疾病的发生发展过程。此外,SPR基因敲除小鼠表现出持续增强的自主活动等类精神分裂症症状,说明该基因在精神分裂症的发病中扮演重要的角色。进一步研究SPR基因及其单核苷酸多态性的功能,可为阐明精神分裂症的发病机制提供重要的线索,也为新一代抗精神病药物的研制及开发开拓新的视野。现对SPR基因与精神分裂症的相关研究做一综述。     

Neuronal failure in Alzheimer＇s disease： a view through the oxidative stress looking-glass

Considerable debate and controversy surround the cause（s） of AIzheimer＇s disease （AD）. To date, several theories have gained notoriety, however none is universally accepted. In this review, we provide evidence for the oxidative stress-induced AD cascade that posits aged mitochondria as the critical origin of neurodegeneration in AD.     

癫痫与自杀

自杀而导致死亡被为是增加癫痫患者死亡率的最重要原因之一。国外许多研究报道都表明癫痫患者的自杀率比普通人群的自杀率高几倍到二十几倍。可能导致癫痫患者自杀的危险性因素是有多方面的,本文将从5-HT、抗癫痫药及癫痫手术治疗、精神病理等方面对癫痫患者可能存在自杀危险因素进行综述,并希望在癫痫的综合治疗中对这些危险因素能加以考虑。     

Wnt信号通路与骨髓间充质干细胞增殖及分化的关系

骨髓间充质干细胞（bonemarrow—derived mesenchymal stem cells,BMSCs）是骨髓中不同于造血干细胞的一类细胞,其来源丰富,取材简便,易分离、纯化、培养,在一定的条件下可以迅速体外扩增,具有多向分化潜能,可以通过不同的方法被诱导分化成骨细胞、软骨细胞、肌细胞、神经胶质细胞、神经元细胞等,而且它具有低免疫源性,向病变部位迁移的能力,     

Cerebrospinal fluid biomarkers of Alzheimer＇s disease

Alzheimer＇s disease （AD） is a fatal neurodegenerative disorder that takes about a decade to develop, making early diagnosis possible. Clinically, the diagnosis of AD is complicated, costly, and inaccurate, so it is urgent to find specific biomarkers. Due to its multifactorial nature, a panel of biomarkers for the multiple pathologies of AD, such as cerebral amyloidogenesis, neuronal dysfunction, synapse loss, oxidative stress, and inflammation, are most promising for accurate diagnosis. Highly sensitive and high-throughput proteomic techniques can be applied to develop a panel of novel biomarkers for AD. In this review, we discuss the metabolism and diagnostic performance of the well-established core candidate cerebrospinal fluid （CSF） biomarkers （β-amyloid, total tau, and hyperphosphorylated tau）. Meanwhile, novel promising CSF biomarkers, especially those identified by proteomics, updated in the last five years are also extensively discussed. Furthermore, we provide perspectives on how biomarker discovery for AD is evolving.     

焦虑与心血管疾病的相关性分析

近年来,我国所患心血管疾病的人口比例越来越高,而焦虑症作为伴发心血管疾病的常见性疾病,对其识别与否以及处理的是否得当将对心血管疾病的预后产生重大影响,但目前国内外对此的研究还相对欠缺,现对此做一综述,综合相关文献,对此方面的问题进行研究。