| 1 | Subcell. Biochem. 2008 -1 49: 241-68 |
|---|---|
| PMID | 18751914 |
| Title | Altered lipid metabolism in brain injury and disorders. |
| Abstract | 放松管制的脂质代谢对于中枢神经系统损伤和疾病可能特别重要，因为该器官的脂质浓度最高，毗邻脂肪组织。动脉粥样硬化（缺血性中风的危险因素）是由LDL衍生脂质在动脉壁中积累的结果。促炎细胞因子（TNF-Alpha和IL-1），分泌磷脂酶A2 IIA和脂蛋白-PLA2与血管炎症有关。这些炎症反应促进了动脉粥样硬化的斑块，可以诱导缺血性中风的血凝块的形成和释放。TNF-Alpha和IL-1改变了脂质代谢，并刺激eicosanoids，神经酰胺和活性氧的产生，可增强CNS损伤和某些神经系统疾病。胆固醇是脂质组织的重要调节剂，也是神经类似生物合成的前体。在许多脑部病理中，神经类固醇水平较低与预后不良有关。载脂蛋白E是大脑中的主要胆固醇载体蛋白，编码变体载脂蛋白E4的基因是阿尔茨海默氏病的重要危险因素。帕金森氏病在某种程度上是由磷脂酶激活引起的脂质过氧化引起的。Niemann-Pick疾病A和B是由于酸性鞘磷脂酶缺乏症引起的，导致鞘磷脂的积累，而Niemann-Pick疾病C是由于NPC1或NPC1的突变引起的NPC2把基因,导致有缺陷的胆固醇t and cholesterol accumulation. Multiple sclerosis is an autoimmune inflammatory demyelinating condition of the CNS. Inhibiting phospholipase A2 attenuated the onset and progression of experimental autoimmune encephalomyelitis. The endocannabinoid system is hypoactive in Huntington's disease. Ethyl-eicosapetaenoate showed promise in clinical trials. Amyotrophic lateral sclerosis causes loss of motorneurons. Cyclooxygenase-2 inhibition reduced spinal neurodegeneration in amyotrophic lateral sclerosis transgenic mice. Eicosapentaenoic acid supplementation provided improvement inschizophreniapatients, while the combination of (eicosapentaenoic acid + docosahexaenoic acid) provided benefit in bipolar disorders. The ketogenic diet where >90% of calories are derived from fat is an effective treatment for epilepsy. Understanding cytokine-induced changes in lipid metabolism will promote novel concepts and steer towards bench-to-bedside transition for therapies. |
| SCZ Keywords | schizophrenia |
| 2 | BMC Pharmacol. 2009 -1 9: 10 |
| PMID | 19715613 |
| Title | Psychotropic drugs up-regulate the expression of cholesterol transport proteins including ApoE in cultured human CNS- and liver cells. |
| Abstract | Disturbances in lipid homeostasis and myelination have been proposed in the pathophysiology ofschizophrenia和躁郁症。我们先前已经表明，几种抗精神病药和抗抑郁药通过激活固醇调节元素结合蛋白（SREBP）转录因子增加脂质生物合成，从而控制了与脂肪酸和胆固醇生物合成的许多基因的表达。本原则研究的目的是研究此类药物是否还影响培养的人类中枢神经系统和肝细胞中的脂质转运和输出途径。 Quantitative PCR and immunoblotting were used to determine the level of lipid transport genes in human glioblastoma (GaMg) exposed to clozapine, olanzapine, haloperidol or imipramine. The effect of some of these drugs was also investigated in human astrocytoma (CCF-STTG1), neuroblastoma (SH-SY5Y) and hepatocellular carcinoma (HepG2) cells. We found significant transcriptional changes of cholesterol transport genes (ApoE, ABCA1, NPC1,NPC2, NPC1L1), which are predominantly controlled by the Liver X receptor (LXR) transcription factor. The up-regulation was observed after 24 to 48 hours of drug exposure, which is markedly delayed as compared to the drug-induced SREBP-controlled stimulation of lipid biosynthesis seen after 6 hours. 我们的数据表明，两亲性精神药物对细胞脂质生物合成的刺激之后是胆固醇转运和外排途径的转录激活。这种作用可能与精神药物的治疗作用和代谢不良影响有关。 |
| SCZ Keywords | schizophrenia |
| 3 | Encephale 2013年10月39日：315-9 |
| PMID | 23928063 |
| Title | [成人发作Niemann-Pick型C疾病和精神病：文献评论]。 |
| Abstract | Niemann-Pick type C disease (NPC) is a rare hereditary disease, which psychiatrists do not face often in France. Indeed, only a couple of articles specifically describing the psychiatric-disorders in the adult form have been published. And for the most part, they were not written by psychiatrists. This comprehensive international literature review aims at providing knowledge on this disease to French psychiatrists. To achieve this literature review, we used the "PubMed" search engine, looking for the following keywords: Niemann-Pick type C AND (schizophreniaOR psychosis). Niemann-Pick type C disease (NPC) is a rare, neurovisceral, autosomal recessive disease, with an extremely heterogeneous clinical presentation. It is characterized by a wide range of symptoms that are not specific, such as neurological, systemic or psychiatric symptoms. The adult form of the disease concerns a small proportion (5 %) of the people affected and is usually expressed as a neurological form. A variety of progressive and disabling symptoms are encountered, mainly cerebellar signs (cerebellar ataxia, impaired gait, dysarthria), but also movement disorders, cataplexy, seizures and dysphagia. Patients face constant cognitive deterioration, which can result in severe dementia. Abnormal saccadic eye movement is often the first manifestation of the disease. Supranuclear gaze palsy is considered to be a specific sign and should be systematically searched for. In terms of systemic signs, the usual infantile hepatosplenomegaly is very fickle in the adult form; if present, it is usually asymptomatic. Non-specific psychiatric symptoms are often associated with NPC disease. For one third of cases, it can also express as an isolated psychiatric-disorder form, such asschizophrenia- 诸如精神病（偏执妄想，听觉幻觉，解释性思想和混乱），抑郁症，躁郁症，强迫性行为和行为问题（睡眠障碍，多动，躁动，侵略性或自我保障）。该精神病学概述主要是非典型的，伴随着视觉幻觉，混乱，症状波动，治疗耐药性或因神经肌肉药物的加重，卡塔托尼亚，进行性认知能力下降，但也癫痫发作。神经系统表现的晚期出现通常错误地归因于抗精神病药的作用，抗精神病药物会产生迟到的诊断。大多数NPC影响患者过早死亡。NPC诊断基于对皮肤活检以及NPC1和NPC1的测序的成纤维细胞培养的菲律宾测试。NPC2genes. Routine laboratory biochemistry profiles are generally normal. The early diagnosis is fundamental to deploy the best follow-up care. The patient should therefore be in contact with a reference centre. Until recently, NPC treatment consisted in supportive therapies and symptomatic drugs, useful, however, with variable efficacy. The recent discovery of a medicine called Miglustat (N-butyldeoxynojirimycin; NB-DJN; Zavesca(�), Actelion Pharmaceuticals Ltd.) which improves the disease evolution, should encourage psychiatrists to look for it in every atypical psychosis. |
| SCZ Keywords | schizophrenia |
| 4 | Encephale 2015 Jun 41: 238-43 |
| PMID | 25238906 |
| Title | [Niemann-Pick type C disease and psychosis: Two siblings]. |
| Abstract | Niemann-Pick type C disease (NPC) is a rare, neurovisceral, autosomal recessive disease, with an extremely heterogeneous clinical presentation. The adult form of the disease is usually expressed as a neurological form. Non-specific psychiatric symptoms are often associated with NPC. For some cases, it can also be expressed as an isolated psychiatric disorder form. Since 2009, the launching of a medicine called miglustat has helped to improve the disease evolution. We report two siblings followed-up in the same department of psychiatry and with an atypical psychotic symptomatology. Case 1 is a 27-year-old French male. He was hospitalised several times due to disordered behaviour, psychomotor excitation, mood instability and wandering. He was originally diagnosed withschizophrenia．然而,病人的精神病证明refractory to treatment. He also exhibited a number of neurological signs (pyramidal signs and abnormal movements of the hands, head and limbs), which were considered related to his antipsychotic medication. Three years later, a full physical, neurological and neuropsychological examination revealed various neurological and visceral symptoms. He was diagnosed with NPC based on a classical biochemical NPC-phenotype following filipin staining in cultured skin fibroblasts. NPC1 gene sequencing revealed that he was a compound heterozygote for the p.S954L and p.N1156S mutations. The patient's psychiatric and neurological symptoms are currently stabilized by miglustat, allowing the patient to cease antipsychotic medication. Case 2 is the elder sister of Case 1. She was hospitalised several times due to acute delirium, hallucinations and suicidal tendencies. She was diagnosed with paranoidschizophreniaat 22 years of age. She has received a variety of typical and atypical antipsychotics. Many of these drugs proved initially effective but the patient's symptoms repeatedly returned. The patient shows persistent and worsening gait disorder and abnormal arm movements. A follow-up neurological examination at age 29 did not detect any ataxia, cataplexy or vertical supra-nuclear gaze palsy. Direct NPC1 gene sequencing detected a mutant NPC1 allele held in common with her brother, but full sequencing of both the NPC1 andNPC2基因和多重连接依赖性探针扩增（MLPA）未检测到任何其他病原突变或其他异常。 由于NPC是一种常染色体隐性疾病，因此仅携带一个因果基因突变的杂合子通常无症状。因此，尽管公认的智慧表明患者2不受这种疾病的影响，但有趣的是考虑为什么她像她的兄弟一样患有神经系统和精神病。讨论了几种假设：杂合遗传因素中的心理表达易于schizophrenia, comorbidity or fortuitous association. It is not currently known whether a patient with a single NPC gene mutation can express NPC in full, partially, or perhaps just to a minimal degree. This case of a patient with a heterozygous "carrier" NPC genotype and neuropsychiatric disorders suggestive of the disease raises the possibility that symptomatic heterozygous NPC patients may exist. On the other hand, if the heterozygous genotype of patient 2 does not give rise to symptomatic disease, it is pertinent to question whether it could be a predisposing factor for the development of psychiatric pathologies. There are currently no published data on the occurrence of heterozygous NPC1 orNPC2非典型精神病患者之间的突变与神经系统症状相结合。相反，没有公开的数据表明受NPC影响的家庭的精神疾病频率增加。最后，鉴于这个家庭的精神疾病史，精神病可能只是与患者1中的有症状NPC同时发生，并且偶然地发生了schizophrenia在患者2中与无症状的NPC携带者基因型同时发生。为了进一步调查，NPC患者的携带者家族成员（父母和兄弟姐妹）应完全筛选出暗示该疾病的迹象。 |
| SCZ Keywords | schizophrenia |
| 5 | Rinsho Shinkeigaku 2016 5月1日：-1 |
| PMID | 27181747 |
| Title | A case of variant biochemical phenotype of Niemann-Pick disease type C accompanying savant syndrome. |
| Abstract | A 40-year-old man was referred to our hospital because of vertical supranuclear gaze palsy, frequent sudden loss of muscle tonus and ataxia for several years. He had a history of prolonged neonatal jaundice. He was given a diagnosis of autism in his childhood, followed by a diagnosis ofschizophrenia在他的十几岁。他还开发了一项经验丰富的日历计算技能。（123）I-Imp-spect在左额颞叶中的脑血流量降低，因为在Savant综合征中经常看到。尽管NPC1和NPC2revealed no pathogenic mutation, filipin staining of cultured fibroblasts from his biopsied skin revealed a certain amount of intracellular cholesterol storage pattern, indicating a variant biochemical phenotype of Niemann-Pick disease type C (NPC). The diagnosis of adulthood onset NPC is difficult and challenging, especially for neurologists, because the symptoms and signs are not as clear as those in the classical childhood onset NPC and this subtype is not yet widely known. However, the diagnosis can be made by a combination of filipin staining of fibroblast and/or gene analysis. As a disease-specific therapy for NPC has been approved in Japan, the diagnosis of NPC is of significance. |
| SCZ Keywords | schizophrenia |