Schizophrenia

Schizophrenia 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.

Mental and behavioural disorder

MTHFR [HSA:4524] [KO:K00297]
CHI3L1 [HSA:1116] [KO:K17523]
DISC1 [HSA:27185] [KO:K16534]
DISC2 [HSA:27184]
SYN2 [HSA:6854] [KO:K19941]
DRD3 [HSA:1814] [KO:K04146]
RTN4R [HSA:65078] [KO:K16659]
DAOA [HSA:267012]
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]

Chlorpromazine hydrochloride [DR:D00789]
Fluphenazine decanoate [DR:D00793]
Perphenazine [DR:D00503]
Prochlorperazine maleate [DR:D00479]
Thioridazine hydrochloride [DR:D00798]
Haloperidol decanoate [DR:D01898]
Haloperidol lactate [DR:D08035]
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 maleate [DR:D02995]
Risperidone [DR:D00426]
Aripiprazole [DR:D01164]
Aripiprazole lauroxil [DR:D10364]
Cariprazine hydrochloride [DR:D09876]
Brexpiprazole [DR:D10309]
Lumateperone tosylate [DR:D11170]

PMID:16195940

Austin J

Schizophrenia: an update and review.

J Genet Couns 14:329-40 (2005)
DOI:10.1007/s10897-005-1622-4

PMID:20718829 (gene, drug)

Cacabelos R, Martinez-Bouza R

Genomics and pharmacogenomics of schizophrenia.

CNS Neurosci Ther 17:541-65 (2011)
DOI:10.1111/j.1755-5949.2010.00187.x

PMID:26814963

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

Schizophrenia risk from complex variation of complement component 4.

Nature 530:177-83 (2016)
DOI:10.1038/nature16549

PMID:11930015

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

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.

Proc Natl Acad Sci U S A 99:4680-5 (2002)
DOI:10.1073/pnas.032069099

PMID:10814723

Millar JK, Wilson-Annan JC, Anderson S, Christie S, Taylor MS, Semple CA, Devon RS, St Clair DM, Muir WJ, Blackwood DH, Porteous DJ

Disruption of two novel genes by a translocation co-segregating with schizophrenia.

Hum Mol Genet 9:1415-23 (2000)
DOI:10.1093/hmg/9.9.1415

PMID:15532024

Sinibaldi L, De Luca A, Bellacchio E, Conti E, Pasini A, Paloscia C, Spalletta G, Caltagirone C, Pizzuti A, Dallapiccola B

Mutations of the Nogo-66 receptor (RTN4R) gene in schizophrenia.

Hum Mutat 24:534-5 (2004)
DOI:10.1002/humu.9292