| 1 | PLOS ONE 2011 -1 6：E20571 |
|---|---|
| PMID | 21695181 |
| Title | 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。 |
| 抽象的 | 抗精神病药治疗在患者中的成功schizophrenia受这些药物诱导应激，体重增加和其他代谢障碍的倾向的限制，尤其是奥氮平和氯氮平。然而，参与抗精神病药诱导的心形的分子机制尚不清楚。在这里，我们研究了奥氮平的给药对控制食物摄入的下丘脑机制的影响，即神经肽的表达和AMP激活的蛋白激酶（AMPK）在大鼠中的磷酸化。我们的结果表明，亚氮平的亚慢性暴露会上调神经肽Y（NPY）和Agouti相关蛋白（AGRP) and downregulates proopiomelanocortin (POMC) in the arcuate nucleus of the hypothalamus (ARC). This effect was evident both in rats fed ad libitum and in pair-fed rats. Of note, despite weight gain and increased expression of orexigenic neuropeptides, subchronic administration of olanzapine decreased AMPK phosphorylation levels. This reduction in AMPK was not observed after acute administration of either olanzapine or clozapine. Overall, our data suggest that olanzapine-induced hyperphagia is mediated through appropriate changes in hypothalamic neuropeptides, and that this effect does not require concomitant AMPK activation. Our data shed new light on the hypothalamic mechanism underlying antipsychotic-induced hyperphagia and weight gain, and provide the basis for alternative targets to control energy balance. |
| SCZ Keywords | schizophrenia |
| 2 | J Clin Psychopharmacol 2012 12月32日：767-72 |
| PMID | 23131879 |
| Title | Trajectories of agouti-related protein and leptin levels during antipsychotic-associated weight gain in patients with schizophrenia. |
| 抽象的 | 但并不是所有的第二代抗精神病药物can induce considerable weight gain and metabolic syndrome. Although the exact biochemical mechanisms for these adverse effects are unclear, appetite-regulating neuropeptides of the central nervous system are thought to be implicated in this process. The hypothalamic mediator Agouti-related protein (AGRP) is inhibited by leptin and was shown to increase food intake. The aim of the present study was to investigate the trajectory ofAGRPlevels during antipsychotic-induced weight gain. 作为对照前瞻性临床研究的一部分，我们确定了体内脂肪质量的指标AGRP，16例患者的瘦素水平schizophrenia用Ziprasidone治疗和21例患者schizophreniatreated with olanzapine. Measurements by enzyme-linked immunosorbent assay were obtained before treatment (T0), after 4 weeks (T1), and after 3 months (T2) of treatment. 与接受Ziprasidone治疗的患者相比，奥氮平治疗的患者的体重指数和瘦素水平升高AGRPlevels did not differ among the treatment groups and did not change over time. Associations betweenAGRP在奥氮平治疗的患者中破坏了脂肪肿块以及食欲，但在Ziprasidone组中没有破坏。 Future studies are needed to test whether the lack of a decrease inAGRP用奥氮平治疗的患者体重增加的水平会使不良代谢长期作用永存。 |
| SCZ Keywords | schizophrenia |
| 3 | World J. Biol. Psychiatry 2014 Apr 15: 251-8 |
| PMID | 24564533 |
| Title | 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。 |
| 抽象的 | The use of second-generation antipsychotic medications may result in substantial weight gain in a subset ofschizophrenia患者。在下丘脑中表达的神经元的不同种群，包括可卡因和苯丙胺调节的转录本（CART），多肽促蛋白酶素（POMC）和AGOUTI相关蛋白（AGRP），在体重控制和能量稳态中具有调节作用。因此，我们研究了CART，POMC和AGRPgenetic variants in antipsychotic-induced weight gain (AIWG). Five CART single nucleotide polymorphisms (SNPs) (rs10515115, rs3763153, rs3857384, rs11575893, rs16871471), three POMC SNPs (rs6713532, rs1047521, rs3754860) and oneAGRPSNP (rs1338993), were genotyped in 218 patients treated with antipsychotics for chronicschizophreniaand evaluated for AIWG. We compared weight change (%) across genotypic groups using analysis of covariance. pomc，购物车中的SNP中没有一个SNPAGRPwere significantly associated with AIWG in the refined samples stratified by ethnicity and medication treatment. 在这项探索性研究中，我们观察到POMC，CART和AGRP基因变体不是AIWG的主要贡献者。但是，需要较大的样本才能完全排除其对AIWG的影响。 |
| SCZ Keywords | schizophrenia |
| 4 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2014 Jan 48: 287-94 |
| PMID | 23085507 |
| Title | Immune system and glucose metabolism interaction in schizophrenia: a chicken-egg dilemma. |
| 抽象的 | 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直接归因于的副作用吗typical antipsychotic medications or disease-inherent derangements. In addition, numerous previous studies have highlighted alterations in the immune system of patients withschizophrenia。白介素（IL）-1，IL-6和转化生长因子β（TGF-？）的浓度增加似乎是状态标记，而IL-12，IL-12，干扰素 - γ（IFN-？），肿瘤坏死因子 - α（TNF-？），可溶性IL-2受体（SIL-2R）似乎是特征标记schizophrenia。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 Keywords | schizophrenia |
| 5 | 脑部。2015年1月1596年：146-55 |
| PMID | 25449893 |
| Title | 利培酮治疗对Wistar大鼠食欲调节中下丘脑神经肽表达的影响。 |
| 抽象的 | Although the use of atypical antipsychotic drugs has been successful in the treatment ofschizophrenia, they can cause some complications in the long-term use, including weight gain. Patients using these drugs tend to disrupt treatment primarily due to side effects. The atypical antipsychotic mechanism of action regulates a number of highly disrupted neurotransmitter pathways in the brains of psychotic patients but may also cause impairment of neurohormonal pathways in different brain areas. In this study, we investigated the circulating levels of hypothalamic neurohormones, which are related to appetite regulation; neuropeptide Y (NPY); alpha melanocyte stimulating hormone (?-MSH); cocaine and amphetamine regulated transcript (CART); agouti-related peptide (AGRP); and leptin in male Wistar rats, which were treated with risperidone, a serotonin antagonist, for four weeks. Alterations in the mRNA expression levels of these candidate genes in the hypothalamus were also analyzed. 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除NPY外，NPY及其血浆水平均下降。出乎意料的是，当卡车水平降低时，CART mRNA水平升高。由于POMC神经元表达5-羟色胺受体（5HT2C），因此利培酮对POMC神经元的血清素能拮抗作用可能会导致食欲增加，因此即使在大鼠的短期试验中，食物消耗也会增加。 |
| SCZ Keywords | schizophrenia |
| 6 | METAB BRAIN DIS 2015 APR 30：529-35 |
| PMID | 25034457 |
| Title | 氯氮平单一疗法的精神分裂症患者的AGRP蛋白水平。 |
| 抽象的 | Agouti-related peptide (AGRP) is one of the hypothalamic hormones that works by increasing appetite and decreasing metabolism, thus leading to weight gain. The aim of the study was to find out ifAGRP受试者的水平schizophrenia与健康对照组相比，氯氮平单一疗法上的单一疗法更高。 我们确定了空腹血清AGRP24个受试者的水平schizophreniaon clozapine monotherapy and 24 healthy, age- and sex-matched controls. Biochemical and anthropometric measurements were combined with body composition analysis. There was no difference forAGRP服用氯氮平和对照组的患者之间的水平（15.00.65 vs. 15.33.6.82 pg/ml，p？= 0.37）。我们发现之间的负相关AGRP整个研究组和氯氮平组的水平和总体脂肪（R？= -0.34和-0.48）和与瘦体重的正相关（分别为R？= 0.38和0.49）在整个研究组和氯氮平组中分别为0.49），整个研究组和氯氮平组的体水（R？= 0.34和0.49）和基础代谢率（氯氮平和对照组中的R？= 0.42）。与年龄，身高，体重，体重指数，脂肪质量指数，腹部，腰部或髋关节圆周，腰椎比，血压，总胆固醇，HDL，LDL，LDL，甘油三酸酯，尿酸，葡萄糖，葡萄糖，胰岛素，胰岛素，胰岛素，胰岛素，胰岛素，胰岛素，胰岛素，胰岛素，胰岛素，胰岛素，胰岛素，胰岛素，胰岛素，胰岛素，胰岛素，胰岛素，胰岛素，血压比，脂肪比率，血压比，血压比率，血压比，血压总数，总和，较重氯氮平剂量或治疗持续时间，抗精神病药的治疗时间和胰岛素抵抗的标记。 We cannot conclude that treatment with clozapine is associated with increased level ofAGRP。我们没有发现先前描述的差异AGRPlevels between obese and non-obese subjects or associations betweenAGRP和各种代谢参数。 |
| SCZ Keywords | schizophrenia |