| 1 | Rev. Neurol. (Paris) 2005 Mar 161: 318-22 |
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| PMID | 15800453 |
| Title | [Presentation of Niemann-Pick type C disease with psychiatric disturbance in an adult]. |
| Abstract | Niemann-Pick Type C disease (NPC) is an autosomal recessive neurovisceral lysosomal lipid storage disorder. A 31-year-old right-handed woman had suffered fromschizophrenia13年。在25岁的时候，她患有步态障碍，患有静态和动力学小脑综合征，构音障碍，垂直的近视凝视性麻痹和认知障碍。脑MRI正常。由于高胆固醇血症和转氨酶升高，进行了腹部超声检查，并揭示了肝肾上腺全球，与其他体征和症状结合使用，这表明NPC的诊断。通过证明未酯化胆固醇（菲律宾染色）的溶酶体储存以及LDL诱导的胆固醇酯化率降低来证实该诊断。含义NPC1gene was assessed by genetic complementation analysis. NPC的表型呈现非常可变。稀有的成人发言形式的渐进式课程。精神病表现通常是突出的，可能是神经系统症状之前的。暴露于神经动物学会延迟NPC的诊断。 与小脑综合征，垂直核凝视麻痹和脾肿大相关的精神病表现非常暗示NPC疾病，可以通过菲律宾染色可靠地在培养的皮肤成纤维细胞上可靠地诊断出来。 |
| SCZ Keywords | schizophrenia |
| 2 | Subcell. Biochem. 2008 -1 49: 241-68 |
| PMID | 18751914 |
| Title | 脂质代谢改变了脑损伤和疾病。 |
| Abstract | Deregulated lipid metabolism may be of particular importance for CNS injuries and disorders, as this organ has the highest lipid concentration next to adipose tissue. Atherosclerosis (a risk factor for ischemic stroke) results from accumulation of LDL-derived lipids in the arterial wall. Pro-inflammatory cytokines (TNF-alpha and IL-1), secretory phospholipase A2 IIA and lipoprotein-PLA2 are implicated in vascular inflammation. These inflammatory responses promote atherosclerotic plaques, formation and release of the blood clot that can induce ischemic stroke. TNF-alpha and IL-1 alter lipid metabolism and stimulate production of eicosanoids, ceramide, and reactive oxygen species that potentiate CNS injuries and certain neurological disorders. Cholesterol is an important regulator of lipid organization and the precursor for neurosteroid biosynthesis. Low levels of neurosteroids were related to poor outcome in many brain pathologies. Apolipoprotein E is the principal cholesterol carrier protein in the brain, and the gene encoding the variant Apolipoprotein E4 is a significant risk factor for Alzheimer's disease. Parkinson's disease is to some degree caused by lipid peroxidation due to phospholipases activation. Niemann-Pick diseases A and B are due to acidic sphingomyelinase deficiency, resulting in sphingomyelin accumulation, while Niemann-Pick disease C is due to mutations in either theNPC1or NPC2 genes, resulting in defective cholesterol transport 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 |
| 3 | 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 ofschizophreniaand bipolar disorder. We have previously shown that several antipsychotic and antidepressant drugs increase lipid biosynthesis through activation of the Sterol Regulatory Element-Binding Protein (SREBP) transcription factors, which control the expression of numerous genes involved in fatty acid and cholesterol biosynthesis. The aim of the present proof-of-principle study was to investigate whether such drugs also affect lipid transport and export pathways in cultured human CNS and liver cells. 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. Our data show that stimulation of cellular lipid biosynthesis by amphiphilic psychotropic drugs is followed by a transcriptional activation of cholesterol transport and efflux pathways. Such effects may be relevant for both therapeutic effects and metabolic adverse effects of psychotropic drugs. |
| SCZ Keywords | schizophrenia |
| 4 | Encephale 2013 Oct 39: 315-9 |
| PMID | 23928063 |
| Title | [Adult onset Niemann-Pick type C disease and psychosis: literature review]. |
| 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型C疾病（NPC）是一种罕见的神经扮演，常染色体隐性疾病，具有极为异质的临床表现。它的特征是多种特异性的症状，例如神经，全身或精神病症状。该疾病的成年形式涉及受影响的人的一小部分（5％），通常以神经系统形式表示。遇到了各种进行性和残疾症状，主要是小脑体征（小脑共济失调，步态受损，构造障碍），但还运动障碍，脱氧，癫痫发作，癫痫发作和吞咽困难。患者面临恒定的认知恶化，可能导致严重的痴呆。异常的saccadic眼球运动通常是该疾病的第一个表现。前凝视性麻痹被认为是一个特定的符号，应系统地搜索。就系统性迹象而言，通常的婴儿肝肾上腺全脂肿大在成年形式中非常善变。如果存在，通常是无症状的。非特异性精神病症状通常与NPC疾病有关。 For one third of cases, it can also express as an isolated psychiatric-disorder form, such asschizophrenia-like psychosis (paranoid delusions, auditory hallucinations, interpretative thoughts, and disorganization), depression, bipolar disorder, obsessive-compulsive behaviour and behavioural problems (sleep disorders, hyperactivity, agitation, aggressiveness or self-mutilations). This psychiatric overview is mostly atypical and is accompanied by visual hallucinations, confusion, symptom fluctuations, treatment resistance or aggravation with neuroleptic drugs, catatonia, progressive cognitive decline, but also seizures. The late appearance of neurological manifestations is often wrongfully attributed to the effects of antipsychotic medication, which generates tardy diagnosis. Most of NPC affected patients die prematurely. NPC diagnosis is based on a filipin test on a fibroblast culture from a skin biopsy and also on a sequencing of theNPC1and NPC2 genes. 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 |
| 5 | Encephale 2015 Jun 41: 238-43 |
| PMID | 25238906 |
| Title | [Niemann-Pick type C disease and psychosis: Two siblings]. |
| Abstract | Niemann-pick型C疾病（NPC）是一种罕见的神经扮演，常染色体隐性疾病，具有极为异质的临床表现。该疾病的成年形式通常表示为神经系统形式。非特异性精神症状通常与NPC有关。在某些情况下，它也可以表示为孤立的精神疾病形式。自2009年以来，一种名为Miglustat的药物的推出有助于改善疾病的进化。 我们报告两个兄弟去探究在相同的管理artment 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. However, the patient's psychosis proved 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.NPC1gene 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 paranoidschizophrenia22岁的。她已经收到了各种各样的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. DirectNPC1基因测序检测到突变体NPC1等位基因在与她的哥哥,但是full sequencing of both theNPC1and NPC2 genes and multiplex ligation-dependent probe amplification (MLPA) did not detect any other pathogenic mutation or other anomalies. 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 heterozygousNPC1or NPC2 mutations among patients with atypical psychiatric presentations combined with neurological symptoms. Conversely, there are no published data demonstrating an increased frequency of psychiatric disorders in families affected by NPC. Finally, in view of the history of psychiatric disorders in this family, it is possible that psychosis simply occurred concomitantly with symptomatic NPC in patient 1 by chance, and thatschizophreniaoccurred simultaneously with an asymptomatic NPC carrier genotype in patient 2. To investigate this further, NPC patients' carrier family members (parents and siblings) should be fully screened for signs suggestive of the disease. |
| SCZ Keywords | schizophrenia |
| 6 | 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 | 一名40岁的男子因垂直的近视凝视性麻痹而被转诊到我们的医院，经常突然突然损失肌肉和共济失调。他有长期的新生儿黄疸病史。他在童年时期被诊断为自闭症，然后诊断schizophrenia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。虽然遗传分析NPC1NPC2没有发现致病性突变，他的活检皮肤中培养的成纤维细胞的菲律宾染色显示出一定量的细胞内胆固醇储存模式，表明NIEMANN-PICK型C型C型（NPC）的变异生化表型（NPC）。成年发作的诊断NPC既困难又具有挑战性，尤其是对于神经科医生而言，因为症状和体征并不像经典儿童期NPC那样清晰，并且这种亚型尚不广为人知。但是，可以通过成纤维细胞和/或基因分析的菲律宾染色结合进行诊断。由于日本已批准了针对NPC的疾病特异性疗法，因此NPC的诊断具有重要意义。 |
| SCZ Keywords | schizophrenia |