| 1 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2004 Jul 128B: 19-20 |
|---|---|
| PMID | 15211623 |
| Title | Polymorphisms in the MAOA, MAOB, and COMT genes and aggressive behavior in schizophrenia. |
| 抽象的 | 一些研究报道了COMT和MAO基因型与侵略性之间的关联，尽管结果不一致。我们检查了公开侵略量表（OAS）分数与MAOA和MAOA之间的关系MAOB346名受试者的驱动良好样本中的多态性精神分裂症。我们还检查了150个个人的II期复制样本中的COMT，并将这些结果与我们先前报道的COMT结果结合在一起。我们没有发现OAS等级与在不同遗传模型下研究的任何多态性之间的任何关联的证据。没有证据表明MAOA和COMT在OAS分数上的同义相互作用。这些结果无法支持以下理论：MAOA内的功能多态性，MAOB, or COMT genes, as determinants of catecholamine enzymatic activity, are risk factors for aggressive behavior. |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症 |
| 2 | Psychiatry Res 2004 Jun 127: 1-7 |
| PMID | 15261699 |
| Title | Polymorphisms of dopamine degradation enzyme (COMT and MAO) genes and tardive dyskinesia in patients with schizophrenia. |
| 抽象的 | 几条证据表明，迟发性运动障碍（TD）可能与多巴胺能神经传递改变有关。我们假设，通过改变中枢神经系统中多巴胺能神经传递的改变，混乱的多巴胺降解酶活性可能与对TD的敏感性有关。在本研究中，我们研究了三种多巴胺降解酶和TD的基因多态性之间的关系。我们基于Catechol-O-O-甲基转移酶（COMT）基因的密码子108/158的Valine/蛋氨酸多态性，在单单胺氧化酶A（MAOA）基因中的启动子中的30 bp重复多态性以及A/GLOCHEE的启动子中的30 bp重复多态性，以及A/GLOCHEN的A/GLOLISPORISP。单胺氧化酶B的内含子13（MAOB）206名日本患者的基因精神分裂症。No significant difference was found in total scores on the Abnormal Involuntary Movement Scale (AIMS) among the subject groups, sorted according to the COMT, MAOA andMAOB基因型。此外，对于任何多态性，TD患者与没有TD的患者之间的等位基因频率没有发现显着差异。由于COMT和MAO基因都参与降解儿茶酚胺，因此我们还寻求证据表明添加剂和上皮效应，但没有观察到。因此，我们的数据不支持COMT，MAOA和MAOB基因单独或组合涉及TD的易感性。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症 |
| 3 | 精神分裂。res。2009年4月109日：94-7 |
| PMID | 19268543 |
| Title | Polymorphisms in SLC6A4, PAH, GABRB3, and MAOB and modification of psychotic disorder features. |
| 抽象的 | 我们测试了四个基因[苯丙氨酸羟化酶（PAH），5-羟色胺转运蛋白（SLC6A4），单胺氧化酶B（MAOB), and the gamma-aminobutyric acid A receptor beta-3 subunit (GABRB3)] for their impact on five精神分裂症症状因素：妄想，幻觉，躁狂，抑郁和负面症状。在爱尔兰高密度研究的90个家庭子集中精神分裂症PAH 232 BP微卫星等位基因使用QTDT（F = 8.0，P = .031）和QPDTPHase（Chi-square = 12.54，p = .028）表现出与妄想因子的显着关联。同样，使用qpdtphase（Chi-square = 15.51，p = .030）检测到GABRB3 191 bp等位基因与幻觉因子之间的显着关联，但不能检测到QTDT（Chi-square = 2.07，p = .560）。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症 |
| 4 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2009 Apr 150B: 369-74 |
| PMID | 18553363 |
| Title | Recent adaptive selection at MAOB and ancestral susceptibility to schizophrenia. |
| 抽象的 | The ancestral susceptibility hypothesis has been proposed to explain the existence of susceptibility alleles to common diseases. Some ancestral alleles, reflecting ancient adaptations, may be poorly adapted to the more contemporary environmental conditions giving rise to an increased risk to suffer some common disorders. In order to test this hypothesis in精神分裂症, we focused on the monoamine oxidase B gene (MAOB）。该基因参与了几种单胺的脱氨基，包括几种食物中存在的异生胺以及多巴胺等神经递质。此外，基于I期HAPMAP数据的初步分析表明，最近的自然选择已在该基因座上作用。我们进一步探讨了这种近期阳性选择的存在，该测试是基于将链接不平衡（LD）扩展到特定选定单倍型的大距离的测试，从HAPMAP II期获取数据，并搜索祖先单倍型与祖先单倍型的关联精神分裂症in a sample of 532精神分裂症来自西班牙的患者和597个对照。我们的分析表明存在MAOB受近期选择的约束。与祖先的敏感性假设一致，患者的祖先单倍型显着过多（P = 0.047）。这些单倍型赋予了增加的风险精神分裂症，仅限于男性（P = 0.024，OR = 1.41，95％CI 1.01-1.90）。因此，在复制研究之前，MAOB似乎适合祖先的敏感性模型，验证了一种新的策略以寻找常见精神分裂症susceptibility genes by focusing in those functional candidate genes subject to recent positive selection. |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症 |
| 5 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2009 Apr 150B: 369-74 |
| PMID | 18553363 |
| Title | Recent adaptive selection at MAOB and ancestral susceptibility to schizophrenia. |
| 抽象的 | The ancestral susceptibility hypothesis has been proposed to explain the existence of susceptibility alleles to common diseases. Some ancestral alleles, reflecting ancient adaptations, may be poorly adapted to the more contemporary environmental conditions giving rise to an increased risk to suffer some common disorders. In order to test this hypothesis in精神分裂症, we focused on the monoamine oxidase B gene (MAOB）。该基因参与了几种单胺的脱氨基，包括几种食物中存在的异生胺以及多巴胺等神经递质。此外，基于I期HAPMAP数据的初步分析表明，最近的自然选择已在该基因座上作用。我们进一步探讨了这种近期阳性选择的存在，该测试是基于将链接不平衡（LD）扩展到特定选定单倍型的大距离的测试，从HAPMAP II期获取数据，并搜索祖先单倍型与祖先单倍型的关联精神分裂症in a sample of 532精神分裂症来自西班牙的患者和597个对照。我们的分析表明存在MAOB受近期选择的约束。与祖先的敏感性假设一致，患者的祖先单倍型显着过多（P = 0.047）。这些单倍型赋予了增加的风险精神分裂症，仅限于男性（P = 0.024，OR = 1.41，95％CI 1.01-1.90）。因此，在复制研究之前，MAOB似乎适合祖先的敏感性模型，验证了一种新的策略以寻找常见精神分裂症susceptibility genes by focusing in those functional candidate genes subject to recent positive selection. |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症 |
| 6 | Hum Psychopharmacol 2010 Jul 25: 397-403 |
| PMID | 20589923 |
| Title | 抗精神病药诱导的腿综合征和单胺氧化酶基因的多态性之间的关联研究。 |
| 抽象的 | This study aimed to investigate whether the monoamine oxidase (MAO) A and B genes are associated with antipsychotic-induced restless legs syndrome (RLS) in精神分裂症。 We assessed antipsychotic-induced RLS symptoms in 190 Korean精神分裂症patients and divided the subjects into two groups: those with RLS symptoms (n = 96) and those without RLS symptoms (n = 94). Genotyping was performed for the variable number of tandem repeat (VNTR) polymorphism of the MAOA gene and A644G polymorphism of theMAOBgene. There was no significant difference in the genotype and allele frequencies of all polymorphisms investigated between these two groups. However, the result of global haplotype analysis showed a significant difference in haplotype frequencies between male subjects with and without RLS symptoms (p = 0.013). The interaction between two polymorphisms had a significant effect on the RLS scores of both male (p = 0.047) and female (p = 0.028) patients. These data do not suggest that the MAOA gene VNTR andMAOB基因A644G多态性与抗精神病药诱导的RLS症状有关精神分裂症。但是，我们发现男性之间的单倍型频率有所不同精神分裂症patients with and without RLS symptom and the interaction between the two polymorphisms had a significant influence on the RLS scores of patients with精神分裂症。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症 |
| 7 | Hum Psychopharmacol 2010 Jul 25: 397-403 |
| PMID | 20589923 |
| Title | 抗精神病药诱导的腿综合征和单胺氧化酶基因的多态性之间的关联研究。 |
| 抽象的 | This study aimed to investigate whether the monoamine oxidase (MAO) A and B genes are associated with antipsychotic-induced restless legs syndrome (RLS) in精神分裂症。 We assessed antipsychotic-induced RLS symptoms in 190 Korean精神分裂症patients and divided the subjects into two groups: those with RLS symptoms (n = 96) and those without RLS symptoms (n = 94). Genotyping was performed for the variable number of tandem repeat (VNTR) polymorphism of the MAOA gene and A644G polymorphism of theMAOBgene. There was no significant difference in the genotype and allele frequencies of all polymorphisms investigated between these two groups. However, the result of global haplotype analysis showed a significant difference in haplotype frequencies between male subjects with and without RLS symptoms (p = 0.013). The interaction between two polymorphisms had a significant effect on the RLS scores of both male (p = 0.047) and female (p = 0.028) patients. These data do not suggest that the MAOA gene VNTR andMAOB基因A644G多态性与抗精神病药诱导的RLS症状有关精神分裂症。但是，我们发现男性之间的单倍型频率有所不同精神分裂症patients with and without RLS symptom and the interaction between the two polymorphisms had a significant influence on the RLS scores of patients with精神分裂症。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症 |
| 8 | Behav Brain功能2011 -1 7：42 |
| PMID | 21978760 |
| Title | 汉族中文中单胺氧化酶A/B基因和精神分裂症的关联研究。 |
| 抽象的 | Monoamine oxidases (MAOs) catalyze the metabolism of dopaminergic neurotransmitters. Polymorphisms of isoforms MAOA andMAOBhave been implicated in the etiology of mental disorders such as精神分裂症。Association studies detected these polymorphisms in several populations, however the data have not been conclusive to date. Here, we investigated the association of MAOA andMAOBpolymorphisms with精神分裂症in a Han Chinese population. Two functional single nucleotide polymorphisms (SNPs), rs6323 of MAOA and rs1799836 ofMAOB, were selected for association analysis in 537 unrelated精神分裂症patients and 536 healthy controls. Single-locus and Haplotype associations were calculated. No differences were found in the allelic distribution of rs6323. The G allele of rs1799836 was identified as a risk factor in the development of精神分裂症（p = 0.00001）。风险单倍型RS6323T-RS1799836G与精神分裂症in female patients (P = 0.0002), but the frequency difference was not significant among male groups. Our results suggest thatMAOBis a susceptibility gene for精神分裂症。In contrast, no significant associations were observed for the MAOA functional polymorphism with精神分裂症in Han Chinese. These data support further investigation of the role of MAO genes in精神分裂症。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症 |
| 9 | BMC Neurosci 2012 -1 13: 95 |
| PMID | 22867132 |
| Title | Testosterone regulation of sex steroid-related mRNAs and dopamine-related mRNAs in adolescent male rat substantia nigra. |
| 抽象的 | Increased risk of精神分裂症in adolescent males indicates that a link between the development of dopamine-related psychopathology and testosterone-driven brain changes may exist. However, contradictions as to whether testosterone increases or decreases dopamine neurotransmission are found and most studies address this in adult animals. Testosterone-dependent actions in neurons are direct via activation of androgen receptors (AR) or indirect by conversion to 17?-estradiol and activation of estrogen receptors (ER). How midbrain dopamine neurons respond to sex steroids depends on the presence of sex steroid receptor(s) and the level of steroid conversion enzymes (aromatase and 5?-reductase). We investigated whether gonadectomy and sex steroid replacement could influence dopamine levels by changing tyrosine hydroxylase (TH) protein and mRNA and/or dopamine breakdown enzyme mRNA levels [catechol-O-methyl transferase (COMT) and monoamine oxygenase (MAO) A and B] in the adolescent male rat substantia nigra. We hypothesized that adolescent testosterone would regulate sex steroid signaling through regulation of ER and AR mRNAs and through modulation of aromatase and 5?-reductase mRNA levels. 我们找到了er吗？在青春期雄性大鼠中脑多巴胺神经元中的AR，表明多巴胺神经元准备对循环性类固醇做出反应。我们报告说，雄激素（T和DHT）会增加蛋白质并增加COMT，MAOA和MAOB青春期男性大鼠黑质中的mRNA。我们报告，所有三种性类固醇都会增加AR mRNA。用ER对ER途径的差异作用？mRNA下调和ER？发现睾丸激素上调mRNA。5？通过AR激活增加还原酶-1 mRNA，芳香酶mRNA通过腺苷切除术降低。 我们得出的结论是，青春期睾丸激素增加可以通过促进T向DHT转化并增加AR mRNA来改变性类固醇信号的平衡，从而有利于雄激素反应。此外，睾丸激素可能会增加局部多巴胺的合成和代谢，从而改变黑质尼格拉内多巴胺的调节。我们表明，通过AR和ERS的睾丸激素作用均通过改变正常青少年男性黑质中的AR和ER mRNA水平来调节性类固醇受体的合成。青春期大脑中的性类固醇增加可能会改变尼格拉多巴胺途径，从而增加了心理病理发展的脆弱性。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症 |
| 10 | 精神病学水库2012年7月198日：202-6 |
| PMID | 22414661 |
| Title | Investigating association of four gene regions (GABRB3, MAOB, PAH, and SLC6A4) with five symptoms in schizophrenia. |
| 抽象的 | Recently, microsatellite polymorphisms have been reported to be associated with four genes, GABRB3,MAOB，PAH和SLC6A4及其关系已被测试到五个症状因素：幻觉，妄想，负面症状，躁狂和抑郁症。这些因素经常存在于精神分裂症spectrum disorders in the Irish Study of High Density精神分裂症带有诊断的概率的家庭（ISHDSF）精神分裂症(Bergen et al., 2009). Of these, GABRB3 and PAH were reported to be significantly associated with hallucinations and delusions in a 90-family subset of the ISHDSF, respectively. In this study, we tested the association of genetic markers from these four gene regions with the approximate five clinical symptoms, based upon 256精神分裂症patients, with genotypic data obtained by higher resolution single nucleotide polymorphism (SNP) genotyping. We found one GABRB3 SNP (rs1426891, 70.8kb downstream of this gene) and haplotype constructed by three SNPs (rs1426891, rs2912602, and rs2912600) were significantly associated with hallucinations in Caucasians after Bonferroni correction for multiple testing (Bonferroni corrected P: 0.032 and 0.016, respectively). Additionally, we found one haplotype constructed by two SNPs, rs5905587-rs37615860, inMAOB/NDP基因区域与所有测试样品中的妄想显着相关（Bonferroni校正了P：0.048）。这些结果提供了其他证据，表明GABRB3和MAOB/NDP基因区域可能构成幻觉和妄想的风险因素精神分裂症。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症 |
| 11 | ISRN Psychiatry 2012 -1 2012: 852949 |
| PMID | 23738213 |
| Title | Monoamine oxidase a and B gene polymorphisms and negative and positive symptoms in schizophrenia. |
| 抽象的 | Given that精神分裂症是一种异质性疾病，对临床特征的分析可能有助于鉴定可能与遗传研究相关的均质表型。联系与关联研究表明，一个基因座倾向于精神分裂症可能位于XP11中。我们分析了UVNTR和RS1137070，来自MAOA的多态性和RS1799836的多态性MAOB在344个样本中执行单个SNP病例对照关联研究的基因精神分裂症患者和124名对照受试者。UVNTR，RS1137070和RS1799836 SNP的单一多态性分析未显示病例和对照之间的统计差异。临床特征的多元方差分析分析显示MAOB/rs1799836 and affective flattening scores (F = 4.852, P = 0.009), and significant association between MAOA/uVNTR and affective flattening in female精神分裂症患者(F = 4.236, P = 0.016) Bonferroni之后correction. Our preliminary findings could suggest that severity of affective flattening may be associated by modifier variants of MAOA andMAOBgenes in female Mexican patients with精神分裂症。但是，应分析使用基于定量症状的表型和几种候选变体的进一步的大规模研究，以获得最终的结论。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症 |
| 12 | Psychiatr. Genet. 2012 Feb 22: 42-5 |
| PMID | 21610556 |
| Title | Associations of MAOA-VNTR or 5HTT-LPR alleles with attention-deficit hyperactivity disorder symptoms are moderated by platelet monoamine oxidase B activity. |
| 抽象的 | 单胺系统已经建议去玩a role in the biological basis of attention-deficit hyperactivity disorder (ADHD) symptoms. Thus, polymorphisms, for example, in the monoamine oxidase A (MAOA) and the serotonin transporter (5HTT) genes have been associated with ADHD-like phenotypes. Furthermore, platelet monoamine oxidase B (MAOB）活动经常与冲动相关的特征有关。在这项研究中，我们研究了有关血小板的组合的ADHD症状MAOBactivity and MAOA-variable number of tandem repeats (VNTR) or 5HTT-LPR genotype. The study group consisted of 156 adolescent twin pairs, that is, 312 individuals, who participated in a previous study. ADHD symptoms were scored with a structured clinical interview of both the twins and a parent using Kiddie Schedule for Affective Disorders and精神分裂症for School-Age Children-Present and Lifetime Version. The presence of a short 5HTT-LPR or short MAOA-VNTR allele, in combination with high levels of plateletMAOBenzyme activity was associated with higher scores of ADHD-like problems (P<0.001 and 0.01, respectively). This re-examination of ADHD scores in a nonclinical sample suggests that effects of MAOA-VNTR and 5HTT-LPR are moderated by plateletMAOBactivity. |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症 |
| 13 | Behav Brain功能2014 -1 10：26 |
| PMID | 25073638 |
| Title | Polymorphisms in genes implicated in dopamine, serotonin and noradrenalin metabolism suggest association with cerebrospinal fluid monoamine metabolite concentrations in psychosis. |
| 抽象的 | 同性恋酸（HVA），5-羟基丁乙酸（5-HIAA）和3-甲氧基-4-羟基苯基甘油醇（MHPG）是中枢神经系统中的主要单胺代谢物（CNS）。它们的脑脊液（CSF）浓度反映了中枢神经系统中单胺的转换率，部分在遗传影响下，并且与精神分裂症。We have hypothesized that CSF monoamine metabolite concentrations represent intermediate steps between single nucleotide polymorphisms (SNPs) in genes implicated in monoaminergic pathways and psychosis. We have searched for association between 119 SNPs in genes implicated in monoaminergic pathways [tryptophan hydroxylase 1 (TPH1), TPH2, tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), dopamine beta-hydroxylase (DBH), catechol-O-methyltransferase (COMT），单胺氧化酶A（MAOA）和MAOB] and monoamine metabolite concentrations in CSF in 74 patients with psychotic disorder. There were 42 nominally significant associations between SNPs and CSF monoamine metabolite concentrations, which exceeded the expected number (20) of nominal associations given the total number of tests performed. The strongest association (p = 0.0004) was found betweenMAOBrs5905512, a SNP previously reported to be associated with精神分裂症in men, and MHPG concentrations in men with psychotic disorder. Further analyses in 111 healthy individuals revealed that 41 of the 42 nominal associations were restricted to patients with psychosis and were absent in healthy controls. 本研究表明，中枢神经系统中的单胺转换率的改变反映了SNP与精神病之间关联的中间步骤。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症 |
| 14 | Eur. Psychiatry 2014 Jun 29: 304-6 |
| PMID | 24630741 |
| Title | Psychosis-proneness correlates with expression levels of dopaminergic genes. |
| 抽象的 | Psychosis-proneness or精神分裂症是一个人格组织，反映个人的风险精神分裂症-发展。据信是一个完全尺寸的构造精神分裂症，它已成为基本精神病研究的越来越有前途的工具。beplay苹果手机能用吗尽管许多研究表明遗传共同点精神分裂症and精神分裂症，从未在基因表达调控的变化中检查精神分裂症before. We therefore extracted RNA from the blood, a valid surrogate for brain tissue, of a large sample of 67 healthy male volunteers and correlated the activities of all genes relevant for dopaminergic neurotransmission with the positive精神分裂症- O-Life的规模。我们发现有关基因的表达的显着负相关，MAOB, DRD4, DRD5 and FOS, indicating that increased精神分裂症coincides with higher levels of dopaminergic dysregulation on the mRNA-level. Considering the advantages of this method, we suggest that it be applied more often in fundamental psychosis-research. |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症 |
| 15 | Eur. Psychiatry 2014 Jun 29: 304-6 |
| PMID | 24630741 |
| Title | Psychosis-proneness correlates with expression levels of dopaminergic genes. |
| 抽象的 | Psychosis-proneness or精神分裂症是一个人格组织，反映个人的风险精神分裂症-发展。据信是一个完全尺寸的构造精神分裂症，它已成为基本精神病研究的越来越有前途的工具。beplay苹果手机能用吗尽管许多研究表明遗传共同点精神分裂症and精神分裂症，从未在基因表达调控的变化中检查精神分裂症before. We therefore extracted RNA from the blood, a valid surrogate for brain tissue, of a large sample of 67 healthy male volunteers and correlated the activities of all genes relevant for dopaminergic neurotransmission with the positive精神分裂症- O-Life的规模。我们发现有关基因的表达的显着负相关，MAOB, DRD4, DRD5 and FOS, indicating that increased精神分裂症coincides with higher levels of dopaminergic dysregulation on the mRNA-level. Considering the advantages of this method, we suggest that it be applied more often in fundamental psychosis-research. |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症 |
| 16 | Mol. Psychiatry 2015 Nov 20: 1266-85 |
| PMID | 26283638 |
| Title | 使用合并的基因组和临床风险评估方法理解和预测自杀性。 |
| 抽象的 | Worldwide, one person dies every 40 seconds by suicide, a potentially preventable tragedy. A limiting step in our ability to intervene is the lack of objective, reliable predictors. We have previously provided proof of principle for the use of blood gene expression biomarkers to predict future hospitalizations due to suicidality, in male bipolar disorder participants. We now generalize the discovery, prioritization, validation, and testing of such markers across major psychiatric disorders (bipolar disorder, major depressive disorder, schizoaffective disorder, and精神分裂症) in male participants, to understand commonalities and differences. We used a powerful within-participant discovery approach to identify genes that change in expression between no suicidal ideation and high suicidal ideation states (n=37 participants out of a cohort of 217 psychiatric participants followed longitudinally). We then used a convergent functional genomics (CFG) approach with existing prior evidence in the field to prioritize the candidate biomarkers identified in the discovery step. Next, we validated the top biomarkers from the prioritization step for relevance to suicidal behavior, in a demographically matched cohort of suicide completers from the coroner's office (n=26). The biomarkers for suicidal ideation only are enriched for genes involved in neuronal connectivity and精神分裂症,生物标志物还为自杀behav验证ior are enriched for genes involved in neuronal activity and mood. The 76 biomarkers that survived Bonferroni correction after validation for suicidal behavior map to biological pathways involved in immune and inflammatory response, mTOR signaling and growth factor regulation. mTOR signaling is necessary for the effects of the rapid-acting antidepressant agent ketamine, providing a novel biological rationale for its possible use in treating acute suicidality. Similarly,MAOB, a target of antidepressant inhibitors, was one of the increased biomarkers for suicidality. We also identified other potential therapeutic targets or biomarkers for drugs known to mitigate suicidality, such as omega-3 fatty acids, lithium and clozapine. Overall, 14% of the top candidate biomarkers also had evidence for involvement in psychological stress response, and 19% for involvement in programmed cell death/cellular suicide (apoptosis). It may be that in the face of adversity (stress), death mechanisms are turned on at a cellular (apoptosis) and organismal level. Finally, we tested the top increased and decreased biomarkers from the discovery for suicidal ideation (CADM1, CLIP4, DTNA, KIF2C), prioritization with CFG for prior evidence (SAT1, SKA2, SLC4A4), and validation for behavior in suicide completers (IL6, MBP, JUN, KLHDC3) steps in a completely independent test cohort of psychiatric participants for prediction of suicidal ideation (n=108), and in a future follow-up cohort of psychiatric participants (n=157) for prediction of psychiatric hospitalizations due to suicidality. The best individual biomarker across psychiatric diagnoses for predicting suicidal ideation was SLC4A4, with a receiver operating characteristic (ROC) area under the curve (AUC) of 72%. For bipolar disorder in particular, SLC4A4 predicted suicidal ideation with an AUC of 93%, and future hospitalizations with an AUC of 70%. SLC4A4 is involved in brain extracellular space pH regulation. Brain pH has been implicated in the pathophysiology of acute panic attacks. We also describe two new clinical information apps, one for affective state (simplified affective state scale, SASS) and one for suicide risk factors (Convergent Functional Information for Suicide, CFI-S), and how well they predict suicidal ideation across psychiatric diagnoses (AUC of 85% for SASS, AUC of 89% for CFI-S). We hypothesized a priori, based on our previous work, that the integration of the top biomarkers and the clinical information into a universal predictive measure (UP-Suicide) would show broad-spectrum predictive ability across psychiatric diagnoses. Indeed, the UP-Suicide was able to predict suicidal ideation across psychiatric diagnoses with an AUC of 92%. For bipolar disorder, it predicted suicidal ideation with an AUC of 98%, and future hospitalizations with an AUC of 94%. Of note, both types of tests we developed (blood biomarkers and clinical information apps) do not require asking the individual assessed if they have thoughts of suicide, as individuals who are truly suicidal often do not share that information with clinicians. We propose that the widespread use of such risk prediction tests as part of routine or targeted healthcare assessments will lead to early disease interception followed by preventive lifestyle modifications and proactive treatment. |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症 |
| 17 | 掠夺。Neuropsychopharmacol。医学杂志。精神病学2016Aug 69: 131-46 |
| PMID | 26851573 |
| Title | 精神病患者的单胺氧化酶和搅动。 |
| 抽象的 | Subjects with精神分裂症或进行障碍表现出反社会，侵略性和暴力行为和躁动的终生模式。单胺氧化酶（MAO）是一种参与各种单胺神经递质和神经调节剂的降解的酶，因此在各种精神病和神经退行性疾病和病理行为中起作用。血小板MAO-B活动与精神病和侵略性相关性格特征有关，而MAOA和MAOA的变体MAOBgenes have been associated with diverse clinical phenotypes, including aggressiveness, antisocial problems and violent delinquency. The aim of the study was to evaluate the association of platelet MAO-B activity,MAOBrs1799836 polymorphism and MAOA uVNTR polymorphism with severe agitation in 363 subjects with精神分裂症and conduct disorder. The results demonstrated significant association of severe agitation and smoking, but not diagnosis or age, with platelet MAO-B activity. Higher platelet MAO-B activity was found in subjects with severe agitation compared to non-agitated subjects. Platelet MAO-B activity was not associated withMAOBRS1799836多态性。这些结果表明血小板MAO-B活性增加与严重搅动之间的关联。在严重的搅动和MAOA UVNTR之间未发现显着关联或MAOBrs1799836 polymorphism, revealing that these individual polymorphisms in MAO genes are not related to severe agitation in subjects with精神分裂症and conduct disorder. As our study included 363 homogenous Caucasian male subjects, our data showing this negative genetic association will be a useful addition to future meta-analyses. |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症，精神分裂症 |