KEGG   DISEASE: Schizophrenia
Entry
H01649                      Disease                                
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
Brite
Human diseases [BR:br08402]
 Other diseases
  Mental and behavioural disorders
   H01649  Schizophrenia
Human diseases in ICD-11 classification [BR:br08403]
 06 Mental, behavioural or neurodevelopmental disorders
  Schizophrenia or other primary psychotic disorders
   6A20  Schizophrenia
    H01649  Schizophrenia
Related
pathway
hsa04080  Neuroactive ligand-receptor interaction
hsa04728  Dopaminergic synapse
hsa04724  Glutamatergic synapse
hsa04012  ErbB signaling pathway
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]
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]
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]
Olanzapine and samidorphan [DR:D12117]
Other DBs
ICD-11: 6A20
ICD-10: F20
MeSH: D012559
OMIM: 181500 600850 604906 603013 613950 614332 615232 617629
Reference
  Authors
Austin J
  Title
Schizophrenia: an update and review.
  Journal
J Genet Couns 14:329-40 (2005)
DOI:10.1007/s10897-005-1622-4
Reference
  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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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

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