| 1 | Alcohol. Clin. Exp. Res. 2011 May 35: 963-75 |
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| PMID | 21314694 |
| 标题 | Genomewide association analysis of symptoms of alcohol dependence in the molecular genetics of schizophrenia (MGS2) control sample. |
| Abstract | 尽管遗传对酒精依赖性（AD）的影响是实质的，但在鉴定影响风险的个体遗传变异方面的进展很困难。 我们对基于人群的分子遗传学的3169名饮酒受试者进行了全基因组的关联研究schizophrenia（MGS2）控制样本。询问受试者的7个有关AD症状的问题，这些问题通过验证性因素分析分析。使用Affymetrix 6.0阵列进行基因分型。分别针对欧美（EA，n = 2,357）和非裔美国人（AA，n = 812）主题进行了三组分析：单个单核苷酸多态性（SNP），候选基因和富集途径（GO）类别（GO）。 AD的症状形成了高度连贯的单个因素。没有SNP接近全基因组的意义。在EA样品中，最显着的基因内SNP是在KCNMA1中，KCNMA1是秀丽隐杆线虫中Slo-1基因的人类同源物。具有显着SNP的簇的基因包括AKAP9，磷脂酰肌醇锚固生物合成，G类（PIGG）和KCNMA1。在AA样品中，最显着的基因内SNP是CEACAM6，并且显示出具有经验意义的SNP的基因包括KCNQ5，SLC35B4和MGLL。在基于候选基因的分析中，最重要的发现是ADH1C，B细胞1（NFKB1）中的Kappa光多肽基因增强子的核因子（NFKB1）和Ankyrin重复蛋白重复和激酶结构域中包含1（ANKK1）的EA样品和ADH5，和ADH5，和ADH5，和ADH5，和pomc, and CHRM2 in the AA sample. The ALIGATOR program identified a significant excess of associated SNPs within and near genes in a substantial number of GO categories over a range of statistical stringencies in both the EA and AA sample. While we cannot be highly confident about any single result from these analyses, a number of findings were suggestive and worthy of follow-up. Although quite large samples will be needed to obtain requisite power, the study of AD symptoms in general population samples is a viable complement to case-control studies in identifying genetic risk variants for AD. |
| SCZ关键字 | schizophrenia, schizophrenic, schizophrenics |
| 2 | PLoS ONE 2011 -1 6: e20571 |
| PMID | 21695181 |
| 标题 | 奥氮平诱导的心晶状体和体重增加与甲状腺肿下丘脑神经肽信号传导相关，而无需伴随AMPK磷酸化。 |
| Abstract | 抗精神病药治疗在患者中的成功schizophreniais limited by the propensity of these drugs to induce hyperphagia, weight gain and other metabolic disturbances, particularly evident for olanzapine and clozapine. However, the molecular mechanisms involved in antipsychotic-induced hyperphagia remain unclear. Here, we investigate the effect of olanzapine administration on the regulation of hypothalamic mechanisms controlling food intake, namely neuropeptide expression and AMP-activated protein kinase (AMPK) phosphorylation in rats. Our results show that subchronic exposure to olanzapine upregulates neuropeptide Y (NPY) and agouti related protein (AgRP) and downregulates proopiomelanocortin (pomc）在下丘脑（ARC）的弧形核中。这种效果在饲喂自随意的大鼠和成对的大鼠中都显而易见。值得注意的是，尽管体重增加并增加了神经肽的表达，但奥氮平的亚慢性施用降低了AMPK磷酸化水平。急性施用奥氮平或氯氮平后，未观察到AMPK的这种减少。总体而言，我们的数据表明，奥氮平诱导的心晶片是通过下丘脑神经肽的适当变化而介导的，并且这种作用不需要伴随的AMPK激活。我们的数据为抗精神病药诱导的心脏和体重增加的下丘脑机制提供了新的启示，并为控制能量平衡的替代靶标提供了基础。 |
| SCZ关键字 | schizophrenia, schizophrenic, schizophrenics |
| 3 | Front Neurosci 2011 -1 5: 107 |
| PMID | 21991243 |
| 标题 | 成年海马神经发生和可塑性在苔藓纤维投影的甲状腺膜束中：I。通过活性进行共同调节。 |
| Abstract | BESIDES THE MASSIVE PLASTICITY AT THE LEVEL OF SYNAPSES, WE FIND IN THE HIPPOCAMPUS OF ADULT MICE AND RATS TWO SYSTEMS WITH VERY STRONG MACROSCOPIC STRUCTURAL PLASTICITY: adult neurogenesis, that is the lifelong generation of new granule cells, and dynamic changes in the mossy fibers linking the dentate gyrus to area CA3. In particular the anatomy of the infrapyramidal mossy fiber tract (IMF) changes in response to a variety of extrinsic and intrinsic stimuli. Because mossy fibers are the axons of granule cells, the question arises whether these two types of plasticity are linked. Using immunohistochemistry for markers associated with axonal growth and pro-opiomelanocortin (pomc)-GFP mice to visualize the post-mitotic maturation phase of adult hippocampal neurogenesis, we found that newly generated mossy fibers preferentially but not exclusively contribute to the IMF. The neurogenic stimulus of an enriched environment increased the volume of the IMF. In addition, the IMF grew with a time course consistent with axonal outgrowth from the newborn neurons after the induction of neurogenic seizures using kainate. These results indicate that two aspects of plasticity in the adult hippocampus, mossy fiber size and neurogenesis, are related and may share underlying mechanisms. In a second part of this study, published separately (Krebs et al., 2011) we have addressed the question of whether there is a shared genetics underlying both traits. |
| SCZ关键字 | schizophrenia, schizophrenic, schizophrenics |
| 4 | PLoS ONE 2012 -1 7: e33548 |
| PMID | 22438946 |
| 标题 | 与奥氮平诱导的体重增加有关的黑色皮质素能，GABA能和大麻素神经传递的改变。 |
| Abstract | Second generation antipsychotics (SGAs) are used to treatschizophrenia但可能会引起严重的代谢副作用，例如肥胖和糖尿病。这项研究检查了低剂量的奥氮平对下丘脑和脑干中食欲/代谢调节信号的影响，以阐明奥氮平诱导的肥胖症的基础机制。 促蛋白聚糖素的水平（pomc），神经肽Y（NPY）和谷氨酸脱羧酶（GAD（65），用于GABA合成的酶）mRNA表达和大麻素CB1受体（CB1R）结合密度（使用[（3）SR-141716A）在在0.25、0.5、0.5、0.5、1.0或2.0 mg/kg Olanzapine或媒介物（3年，14天，14天）之后，雌性Sprague Dawley大鼠的弧形核（ARC）和背部迷走神经复合物（DVC）。与其体重增加责任一致，奥氮平显着降低了厌食症pomc并以剂量敏感的方式在电弧中以剂量敏感的方式增加了甲状腺素的mRNA表达。GAD（65）mRNA表达增加，CB1R结合密度在ARC和DVC中降低。大脑中神经传递信号的改变与体重和肥胖显着相关。诱导大鼠体重增加所需的最小剂量阈值为0.5 mg/kg奥氮平。 奥氮平诱导的体重增加与抑制食欲减少有关pomc并增加了NPY。这项研究还支持CB1R和GABA在体重增加副作用的机制中的作用，可能通过改变pomctransmission. Metabolic dysfunction can be modelled in the female rat using low, clinically-comparable olanzapine doses when administered in-line with the half-life of the drug. |
| SCZ关键字 | schizophrenia, schizophrenic, schizophrenics |
| 5 | Neuroscience 2013 Sep 249: 172-91 |
| PMID | 23298853 |
| 标题 | 精神病出现的压力和神经发育过程。 |
| Abstract | The notion that stress plays a role in the etiology of psychotic disorders, especiallyschizophrenia是长期存在的。然而,只是在最近years that the potential neural mechanisms mediating this effect have come into sharper focus. The introduction of more sophisticated models of the interplay between psychosocial factors and brain function has expanded our opportunities for conceptualizing more detailed psychobiological models of stress in psychosis. Further, scientific advances in our understanding of adolescent brain development have shed light on a pivotal question that has challenged researchers; namely, why the first episode of psychosis typically occurs in late adolescence/young adulthood. In this paper, we begin by reviewing the evidence supporting associations between psychosocial stress and psychosis in diagnosed patients as well as individuals at clinical high risk for psychosis. We then discuss biological stress systems and examine changes that precede and follow psychosis onset. Next, research findings on structural and functional brain characteristics associated with psychosis are presented; these findings suggest that normal adolescent neuromaturational processes may go awry, thereby setting the stage for the emergence of psychotic syndromes. Finally, a model of neural mechanisms underlying the pathogenesis of psychosis is presented and directions for future research strategies are explored. |
| SCZ关键字 | schizophrenia, schizophrenic, schizophrenics |
| 6 | World J. Biol. Psychiatry 2014 Apr 15: 251-8 |
| PMID | 24564533 |
| 标题 | 在抗精神病药诱导的体重增加中，黑色皮质素系统基因变异的研究。 |
| Abstract | The use of second-generation antipsychotic medications may result in substantial weight gain in a subset ofschizophreniapatients. Distinct populations of neurons expressed in the hypothalamus, including the cocaine- and amphetamine-regulated transcript (CART), the polypeptide pro-opiomelanocortin (pomc)和agouti-related蛋白质(AGRP) regulatory roles in weight control and energy homeostasis. Thus, we investigated the potential role of CART,pomcand AGRP genetic variants in antipsychotic-induced weight gain (AIWG). 五个卡车单核苷酸多态性（SNP）（RS10515115，RS3763153，RS3857384，RS11575893，RS16871471），三个），三个pomcSNP（RS6713532，RS1047521，RS3754860）和一个AGRP SNP（RS1338993）在218例抗精神病药治疗的患者中进行了基因分型。schizophreniaand evaluated for AIWG. We compared weight change (%) across genotypic groups using analysis of covariance. None of the SNPs inpomc, CART, AGRP were significantly associated with AIWG in the refined samples stratified by ethnicity and medication treatment. In this exploratory study, we observed thatpomc, CART and AGRP gene variants are not a major contributor to AIWG. However larger samples are required to completely rule out their effect on AIWG. |
| SCZ关键字 | schizophrenia, schizophrenic, schizophrenics |
| 7 | prog。神经心理药物。生物。精神病学2014年1月48日：287-94 |
| PMID | 23085507 |
| 标题 | Immune system and glucose metabolism interaction in schizophrenia: a chicken-egg dilemma. |
| Abstract | Impaired glucose metabolism and the development of metabolic syndrome contribute to a reduction in the average life expectancy of individuals withschizophrenia。It is unclear whether this association simply reflects an unhealthy lifestyle or whether weight gain and impaired glucose tolerance in patients withschizophrenia直接归因于非典型抗精神病药物或疾病的疾病的副作用。此外，许多先前的研究强调了患者免疫系统的改变schizophrenia。Increased concentrations of interleukin (IL)-1, IL-6, and transforming growth factor-beta (TGF-?) appear to be state markers, whereas IL-12, interferon-gamma (IFN-?), tumor necrosis factor-alpha (TNF-?), and soluble IL-2 receptor (sIL-2R) appear to be trait markers ofschizophrenia。此外，单核吞噬细胞系统（MPS）和小胶质细胞激活参与了疾病的早期过程。这篇综述说明了“鸡蛋的困境”，目前尚不清楚脑葡萄糖利用受损是否会导致周围葡萄糖代谢的次要疾病，心血管并发症的风险增加，以及随附的患者促脑血管变化的风险schizophrenia或免疫机制是否可能参与schizophrenia, which leads to disturbances in glucose metabolism such as metabolic syndrome. Alternatively, shared underlying factors may be responsible for the co-occurrence of immune system and glucose metabolism disturbances inschizophrenia。 |
| SCZ关键字 | schizophrenia, schizophrenic, schizophrenics |
| 8 | PLOS ONE 2014 -1 9：E104160 |
| PMID | 25084453 |
| 标题 | Preventing olanzapine-induced weight gain using betahistine: a study in a rat model with chronic olanzapine treatment. |
| Abstract | Olanzapine is the one of first line antipsychotic drug forschizophreniaand other serious mental illness. However, it is associated with troublesome metabolic side-effects, particularly body weight gain and obesity. The antagonistic affinity to histamine H1 receptors (H1R) of antipsychotic drugs has been identified as one of the main contributors to weight gain/obesity side-effects. Our previous study showed that a short term (2 weeks) combination treatment of betahistine (an H1R agonist and H3R antagonist) and olanzapine (O+B) reduced (-45%) body weight gain induced by olanzapine in drug-na�ve rats. A key issue is that clinical patients suffering withschizophrenia, bipolar disease and other mental disorders often face chronic, even life-time, antipsychotic treatment, in which they have often had previous antipsychotic exposure. Therefore, we investigated the effects of chronic O+B co-treatment in controlling body weight in female rats with chronic and repeated exposure of olanzapine. The results showed that co-administration of olanzapine (3 mg/kg, t.i.d.) and betahistine (9.6 mg/kg, t.i.d.) significantly reduced (-51.4%) weight gain induced by olanzapine. Co-treatment of O+B also led to a decrease in feeding efficiency, liver and fat mass. Consistently, the olanzapine-only treatment increased hypothalamic H1R protein levels, as well as hypothalamic pAMPK?, AMPK? and NPY protein levels, while reducing the hypothalamicpomc，UCP1和PGC-1？棕色脂肪组织（BAT）中的蛋白质水平。奥氮平诱导下丘脑H1R，PAMPK？，BAT UCP1和PGC-1的变化？可以通过O+b的共同处理来逆转。这些结果支持进一步的临床试验，以测试O+B共同处理以控制体重增加/肥胖副作用的有效性schizophreniawith chronic antipsychotic treatment. |
| SCZ关键字 | schizophrenia, schizophrenic, schizophrenics |
| 9 | Psychoneuroendocrinology 2014 Oct 48: 77-86 |
| PMID | 24992721 |
| 标题 | Betahistine ameliorates olanzapine-induced weight gain through modulation of histaminergic, NPY and AMPK pathways. |
| Abstract | Olanzapine is widely used to treatschizophreniaand other disorders, but causes adverse obesity and other metabolic side-effects. Both animal and clinical studies have shown that co-treatment with betahistine (a histaminergic H1 receptor agonist and H3 receptor antagonist) is effective for ameliorating olanzapine-induced weight gain/obesity. To reveal the mechanisms underlying these effects, this study investigated the effects of co-treatment of olanzapine and betahistine (O+B) on expressions of histaminergic H1 receptor (H1R), AMP-activated protein kinase (AMPK), neuropeptide Y (NPY), and proopiomelanocortin (pomc）在与减少奥氮平诱导的体重增加有关的下丘脑中。与仅奥氮平治疗组相比，奥氮平显着上调了H1R的mRNA和蛋白质表达，而O+B共同处理显着下调了H1R水平。Olanzapine显着增强了NPY mRNA的表达，但通过O+B共处理可以显着逆转。下丘脑H1R表达与总食物摄入和NPY表达呈正相关。奥氮平还增加了AMPK吗？通过AMPK测量激活？磷酸化（PAMPK？）/ampk？与对照组相比，比率是O+B共同处理降低了PAMPK？/ampk？比率，与仅奥氮平治疗相比。pampk？/ampk？ ratio was positively correlated with total food intake and H1R expression. Although olanzapine administration decreased thepomcmRNA水平，该水平不受O+B共同处理的影响。因此，这些结果表明，与贝特阿希碱的共同治疗可能会通过H1R-NPY和H1R-PAMPK逆转奥氮平诱导的体重增加吗？途径。 |
| SCZ关键字 | schizophrenia, schizophrenic, schizophrenics |
| 10 | 脑部。2015年1月1596年：146-55 |
| PMID | 25449893 |
| 标题 | Effects of risperidone treatment on the expression of hypothalamic neuropeptide in appetite regulation in Wistar rats. |
| Abstract | Although the use of atypical antipsychotic drugs has been successful in the treatment ofschizophrenia，它们可能会在长期使用中引起一些并发症，包括体重增加。使用这些药物的患者往往主要是由于副作用而破坏治疗的。非典型抗精神病药机制调节精神病患者大脑中的许多高度破坏的神经递质途径，但也可能导致不同大脑区域的神经激素途径受损。在这项研究中，我们研究了与食欲调节有关的下丘脑神经激素的循环水平。神经肽Y（NPY）;α黑素细胞刺激激素（？-MSH）;可卡因和苯丙胺调节的转录本（CART）；与Agouti相关的肽（AGRP）；雄性Wistar大鼠的瘦素，用5-羟色胺拮抗剂的利培酮治疗了四个星期。还分析了下丘脑中这些候选基因的mRNA表达水平的改变。 We hypothesized that risperidone treatment might alter both hypothalamic and circulating levels of neuropeptides through serotonergic antagonism, resulting in weight gain. Gene expression studies revealed that the mRNA expression levels of proopiomelanocortin (pomc), AgRP, and NPY decreased as well as their plasma levels, except for NPY. Unexpectedly, CART mRNA levels increased when their plasma levels decreased. Becausepomcneurons express the serotonin receptor (5HT2C), the serotonergic antagonism of risperidone onpomcneurons may cause an increase in appetite and thus increase food consumption even in a short-term trial in rats. |
| SCZ关键字 | schizophrenia, schizophrenic, schizophrenics |