CYP2D6 polymorphism: implications for antipsychotic drug response, schizophrenia and personality traits.
The CYP2D6 gene is highly polymorphic, causing absent (poor metabolizers), decreased, normal or increased enzyme activity (extensive and ultrarapid metabolizers). The genetic polymorphism of the CYP2D6 influences plasma concentration of a wide variety of drugs metabolized in the liver by the cytochrome P450 (CYP) 2D6 enzyme, including antipsychotic drugs used for schizophrenia treatment. Additionally, CYP2D6 is involved in the metabolism of endogenous substrates in the brain, and reported to be located in regions such as the cortex, hippocampus and cerebellum, which are impaired in schizophrenia. Moreover, recently we have found that CYP2D6 poor metabolizers are under-represented in a case-control association study of schizophrenia. Furthermore, null CYP2D6 activity in healthy volunteers is associated with personality characteristics of social cognitive anxiety, which may bear some resemblance to milder forms of psychotic-like symptoms. In keeping with this, CYP2D6 may influence, not only variability to drug response, but also vulnerability to disease in schizophrenia patients.
Extremadura University Hospital and Medical School, Clinical Research Center-CICAB, Servicio Extremeño de Salud, Faculty of Medicine, CICAB Hospital Infanta Cristina, Avda. de Elvas s/n. E-06071, Badajoz, Spain. pdorado@unex.es
Pedro
P
Dorado
Eva M
EM
Peñas-Lledó
Adrián
A
Llerena
D014150:Antipsychotic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D010551:Personality / Q000235:genetics*; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics
D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6