[Schizophrenia, genetics and cognition].
Schizophrenia is a complex and heritable disorder. Nevertheless, molecular genetics of schizophrenia remains inconclusive. By developing the concept of endophenotype for the disorder, it is easier to define an association between a phenotype and genetic variants or physiopathological processes. Cognitive disorders could be useful endophenotypes for schizophrenia. For example, the val(158)/met COMT polymorphism has been associated with executive function or working memory. Therefore, several cognitive dysfunctions were proposed as endophenotypes and were investigated in the context of different genetic polymorphisms. Genome-wide association studies and epistatic studies demonstrated the complexity of the mechanisms underlying cognitive disturbance. However, meta-analysis remains inconclusive. Altogether, the study of endophenotypes is an attractive approach to solve the complex mechanisms causing schizophrenia vulnerability. Nevertheless, several limitations exist and include the lack of reproducibility, the discordant results between healthy subjects and patients, the exclusion of the many rare variants.
Pôle universitaire de psychiatrie, hôpital Sainte-Marguerite, 13274 Marseille cedex 09, France. raoul.belzeaux@ap-hm.fr
R
R
Belzeaux
E C
EC
Ibrahim
E
E
Fakra
M
M
Adida
M
M
Cermolacce
J-M
JM
Azorin
D000483:Alleles; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D058068:Endophenotypes; D004843:Epistasis, Genetic / Q000235:genetics; D056344:Executive Function / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008570:Memory, Short-Term / Q000502:physiology; D011110:Polymorphism, Genetic / Q000235:genetics; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D012565:Schizophrenic Psychology
D002394:Catechol O-Methyltransferase