| H01649 | |
| H number | H01649 |
| Name | Schizophrenia |
| Description | Schizophrenia (SCZD) is a common serious psychotic illness that typically emerges in late adolescence and early adulthood. It is characterized by hallucinations and delusions (commonly known as positive symptoms), social withdrawal, alogia, and flat affect (negative symptoms), and cognitive disabilities. While treatments exist for the psychotic symptoms of schizophrenia, there is no effective therapy to prevent the cognitive impairments. The disorder is substantially heritable, but expression of the clinical phenotype is likely to involve the interplay of multiple susceptibility variants, epigenetic factors, and environmental influences. Although it has been suggested that many of the promising candidate genes are involved in the development and maintenance of synaptic function, the most of them remains to be identified. The pathogenic mechanisms underlying schizophrenia are unknown, but observers have repeatedly noted pathological features involving excessive loss of gray matter and reduced numbers of synaptic structures on neurons. Recently, it has been found that alleles of the C4 genes are associated with schizophrenia in proportion to their tendency to promote greater expression of C4A in the brain. |
| Category | Mental and behavioural disorder |
| Network | - |
| Gene | (SCZD4) PRODH [HSA:5625] [KO:K00318] (SCZD6) NRG1 [HSA:3084] [KO:K05455] (SCZD9) DISC1 [HSA:27185] [KO:K16534] (SCZD15) SHANK3 [HSA:85358] [KO:K15009] (SZCD17) NRXN1 [HSA:9378] [KO:K07377] (SCZD18) SLC1A1 [HSA:6505] [KO:K05612] (SCZD19) RBM12 [HSA:10137] [KO:K24526] MTHFR [HSA:4524] [KO:K25004] CHI3L1 [HSA:1116] [KO:K17523] SYN2 [HSA:6854] [KO:K19941] DRD3 [HSA:1814] [KO:K04146] RTN4R [HSA:65078] [KO:K16659] DAOA [HSA:267012] [KO:K24397] HTR2A [HSA:3356] [KO:K04157] AKT1 [HSA:207] [KO:K04456] C4A [HSA:720] [KO:K03989] APOL2 [HSA:23780] [KO:K14480] APOL4 [HSA:80832] [KO:K14480] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | Chlorpromazine hydrochloride [DR:D00789] Fluphenazine decanoate [DR:D00793] Perphenazine [DR:D00503] Prochlorperazine maleate [DR:D00479] Trifluoperazine hydrochloride [DR:D00799] Thioridazine hydrochloride [DR:D00798] Haloperidol decanoate [DR:D01898] Haloperidol lactate [DR:D08035] Lumateperone tosylate [DR:D11170] Molindone hydrochloride [DR:D00796] Ziprasidone hydrochloride [DR:D01939] Ziprasidone mesylate [DR:D02100] Lurasidone hydrochloride [DR:D04820] Thiothixene [DR:D00374] Loxapine [DR:D02340] Loxapine succinate [DR:D00794] Clozapine [DR:D00283] Olanzapine [DR:D00454] Olanzapine pamoate [DR:D06623] Quetiapine fumarate [DR:D00458] Asenapine [DR:D11769] Asenapine maleate [DR:D02995] Olanzapine and samidorphan [DR:D12117] Risperidone [DR:D00426] Aripiprazole [DR:D01164] Aripiprazole lauroxil [DR:D10364] Aripiprazole hydrate [DR:D10516] Paliperidone [DR:D05339] Paliperidone palmitate [DR:D05340] Cariprazine hydrochloride [DR:D09876] Brexpiprazole [DR:D10309] Dexmedetomidine hydrochloride [DR:D01205] |
| Comment | - |
| Other DBs | ICD-11: 6A20 ICD-10: F20 MeSH: D012559 OMIM: 181500 600850 604906 603013 613950 614332 615232 617629 |
| Reference | PMID:16195940 AUTHORS Austin J TITLE Schizophrenia: an update and review. JOURNAL J Genet Couns 14:329-40 (2005) DOI:10.1007/s10897-005-1622-4 PMID:20718829 AUTHORS Cacabelos R, Martinez-Bouza R TITLE Genomics and pharmacogenomics of schizophrenia. JOURNAL CNS Neurosci Ther 17:541-65 (2011) DOI:10.1111/j.1755-5949.2010.00187.x PMID:15274030 (PRODH) AUTHORS Li T, Ma X, Sham PC, Sun X, Hu X, Wang Q, Meng H, Deng W, Liu X, Murray RM, Collier DA TITLE Evidence for association between novel polymorphisms in the PRODH gene and schizophrenia in a Chinese population. JOURNAL Am J Med Genet B Neuropsychiatr Genet 129B:13-5 (2004) DOI:10.1002/ajmg.b.30049 PMID:15197397 (NRG1) AUTHORS Thiselton DL, Webb BT, Neale BM, Ribble RC, O'Neill FA, Walsh D, Riley BP, Kendler KS TITLE No evidence for linkage or association of neuregulin-1 (NRG1) with disease in the Irish study of high-density schizophrenia families (ISHDSF). JOURNAL Mol Psychiatry 9:777-83; image 729 (2004) DOI:10.1038/sj.mp.4001530 PMID:10814723 (DISC1) AUTHORS Millar JK, Wilson-Annan JC, Anderson S, Christie S, Taylor MS, Semple CA, Devon RS, St Clair DM, Muir WJ, Blackwood DH, Porteous DJ TITLE Disruption of two novel genes by a translocation co-segregating with schizophrenia. JOURNAL Hum Mol Genet 9:1415-23 (2000) DOI:10.1093/hmg/9.9.1415 PMID:20385823 (SHANK3) AUTHORS Gauthier J, Champagne N, Lafreniere RG, Xiong L, Spiegelman D, Brustein E, Lapointe M, Peng H, Cote M, Noreau A, Hamdan FF, Addington AM, Rapoport JL, Delisi LE, Krebs MO, Joober R, Fathalli F, Mouaffak F, Haghighi AP, Neri C, Dube MP, Samuels ME, Marineau C, Stone EA, Awadalla P, Barker PA, Carbonetto S, Drapeau P, Rouleau GA TITLE De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia. JOURNAL Proc Natl Acad Sci U S A 107:7863-8 (2010) DOI:10.1073/pnas.0906232107 PMID:18945720 (NRXN1) AUTHORS Rujescu D, Ingason A, Cichon S, Pietilainen OP, Barnes MR, Toulopoulou T, Picchioni M, Vassos E, Ettinger U, Bramon E, Murray R, Ruggeri M, Tosato S, Bonetto C, Steinberg S, Sigurdsson E, Sigmundsson T, Petursson H, Gylfason A, Olason PI, Hardarsson G, Jonsdottir GA, Gustafsson O, Fossdal R, Giegling I, Moller HJ, Hartmann AM, Hoffmann P, Crombie C, Fraser G, Walker N, Lonnqvist J, Suvisaari J, Tuulio-Henriksson A, Djurovic S, Melle I, Andreassen OA, Hansen T, Werge T, Kiemeney LA, Franke B, Veltman J, Buizer-Voskamp JE, Sabatti C, Ophoff RA, Rietschel M, Nothen MM, Stefansson K, Peltonen L, St Clair D, Stefansson H, Collier DA TITLE Disruption of the neurexin 1 gene is associated with schizophrenia. JOURNAL Hum Mol Genet 18:988-96 (2009) DOI:10.1093/hmg/ddn351 PMID:23341099 (SLC1A1) AUTHORS Myles-Worsley M, Tiobech J, Browning SR, Korn J, Goodman S, Gentile K, Melhem N, Byerley W, Faraone SV, Middleton FA TITLE Deletion at the SLC1A1 glutamate transporter gene co-segregates with schizophrenia and bipolar schizoaffective disorder in a 5-generation family. JOURNAL Am J Med Genet B Neuropsychiatr Genet 162B:87-95 (2013) DOI:10.1002/ajmg.b.32125 PMID:28628109 (RBM12) AUTHORS Steinberg S, Gudmundsdottir S, Sveinbjornsson G, Suvisaari J, Paunio T, Torniainen-Holm M, Frigge ML, Jonsdottir GA, Huttenlocher J, Arnarsdottir S, Ingimarsson O, Haraldsson M, Tyrfingsson T, Thorgeirsson TE, Kong A, Norddahl GL, Gudbjartsson DF, Sigurdsson E, Stefansson H, Stefansson K TITLE Truncating mutations in RBM12 are associated with psychosis. JOURNAL Nat Genet 49:1251-1254 (2017) DOI:10.1038/ng.3894 PMID:10679944 (MTHFR) AUTHORS Sibani S, Christensen B, O'Ferrall E, Saadi I, Hiou-Tim F, Rosenblatt DS, Rozen R TITLE Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria. JOURNAL Hum Mutat 15:280-7 (2000) DOI:10.1002/(SICI)1098-1004(200003)15:3<280::AID-HUMU9>3.0.CO;2-I PMID:17160890 (CHI3L1) AUTHORS Zhao X, Tang R, Gao B, Shi Y, Zhou J, Guo S, Zhang J, Wang Y, Tang W, Meng J, Li S, Wang H, Ma G, Lin C, Xiao Y, Feng G, Lin Z, Zhu S, Xing Y, Sang H, St Clair D, He L TITLE Functional variants in the promoter region of Chitinase 3-like 1 (CHI3L1) and susceptibility to schizophrenia. JOURNAL Am J Hum Genet 80:12-8 (2007) DOI:10.1086/510438 PMID:15449241 (SYN2) AUTHORS Chen Q, He G, Qin W, Chen QY, Zhao XZ, Duan SW, Liu XM, Feng GY, Xu YF, St Clair D, Li M, Wang JH, Xing YL, Shi JG, He L TITLE Family-based association study of synapsin II and schizophrenia. JOURNAL Am J Hum Genet 75:873-7 (2004) DOI:10.1086/425588 PMID:1362221 (DRD3) AUTHORS Crocq MA, Mant R, Asherson P, Williams J, Hode Y, Mayerova A, Collier D, Lannfelt L, Sokoloff P, Schwartz JC, et al. TITLE Association between schizophrenia and homozygosity at the dopamine D3 receptor gene. JOURNAL J Med Genet 29:858-60 (1992) DOI:10.1136/jmg.29.12.858 PMID:15532024 (RTN4R) AUTHORS Sinibaldi L, De Luca A, Bellacchio E, Conti E, Pasini A, Paloscia C, Spalletta G, Caltagirone C, Pizzuti A, Dallapiccola B TITLE Mutations of the Nogo-66 receptor (RTN4R) gene in schizophrenia. JOURNAL Hum Mutat 24:534-5 (2004) DOI:10.1002/humu.9292 PMID:12364586 (DAOA) AUTHORS Chumakov I, Blumenfeld M, Guerassimenko O, Cavarec L, Palicio M, Abderrahim H, Bougueleret L, Barry C, Tanaka H, La Rosa P, Puech A, Tahri N, Cohen-Akenine A, Delabrosse S, Lissarrague S, Picard FP, Maurice K, Essioux L, Millasseau P, Grel P, Debailleul V, Simon AM, Caterina D, Dufaure I, Malekzadeh K, Belova M, Luan JJ, Bouillot M, Sambucy JL, Primas G, Saumier M, Boubkiri N, Martin-Saumier S, Nasroune M, Peixoto H, Delaye A, Pinchot V, Bastucci M, Guillou S, Chevillon M, Sainz-Fuertes R, Meguenni S, Aurich-Costa J, Cherif D, Gimalac A, Van Duijn C, Gauvreau D, Ouellette G, Fortier I, Raelson J, Sherbatich T, Riazanskaia N, Rogaev E, Raeymaekers P, Aerssens J, Konings F, Luyten W, Macciardi F, Sham PC, Straub RE, Weinberger DR, Cohen N, Cohen D TITLE Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia. JOURNAL Proc Natl Acad Sci U S A 99:13675-80 (2002) DOI:10.1073/pnas.182412499 PMID:12692777 (HTR2A) AUTHORS Czerski PM, Leszczynska-Rodziewicz A, Dmitrzak-Weglarz M, Kapelski P, Godlewski S, Rybakowski J, Hauser J TITLE Association analysis of serotonin 2A receptor gene T102c polymorphism and schizophrenia. JOURNAL World J Biol Psychiatry 4:69-73 (2003) DOI:10.3109/15622970309167954 PMID:14745448 (AKT1) AUTHORS Emamian ES, Hall D, Birnbaum MJ, Karayiorgou M, Gogos JA TITLE Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. JOURNAL Nat Genet 36:131-7 (2004) DOI:10.1038/ng1296 PMID:26814963 (C4A) AUTHORS Sekar A, Bialas AR, de Rivera H, Davis A, Hammond TR, Kamitaki N, Tooley K, Presumey J, Baum M, Van Doren V, Genovese G, Rose SA, Handsaker RE, Daly MJ, Carroll MC, Stevens B, McCarroll SA TITLE Schizophrenia risk from complex variation of complement component 4. JOURNAL Nature 530:177-83 (2016) DOI:10.1038/nature16549 PMID:11930015 (APOL2 APOL4) AUTHORS Mimmack ML, Ryan M, Baba H, Navarro-Ruiz J, Iritani S, Faull RL, McKenna PJ, Jones PB, Arai H, Starkey M, Emson PC, Bahn S TITLE Gene expression analysis in schizophrenia: reproducible up-regulation of several members of the apolipoprotein L family located in a high-susceptibility locus for schizophrenia on chromosome 22. JOURNAL Proc Natl Acad Sci U S A 99:4680-5 (2002) DOI:10.1073/pnas.032069099 |