The impact of Cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 genes on suicide attempt and suicide risk-a European multicentre study on treatment-resistant major depressive disorder.
Recently published data have reported associations between cytochrome P450 metabolizer status and suicidality. The aim of our study was to investigate the role of genetic polymorphisms of the cytochrome P450 genes on suicide risk and/or a personal history of suicide attempts. Two hundred forty-three major depressive disorder patients were collected in the context of a European multicentre resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. Suicidality was assessed using the Mini International Neuropsychiatric Interview and the Hamilton Rating Scale for Depression (HAM-D). Treatment response was defined as HAM-D ≤ 17 and remission as HAM-D ≤ 7 after 4 weeks of treatment with antidepressants at adequate dose. Genotyping was performed for all relevant variations of the CYP1A2 gene (*1A, *1F, *1C, *1 J, *1 K), the CYP2C9 gene (*2, *3), the CYP2C19 gene (*2, *17) and the CYP2D6 gene (*3, *4, *5, *6, *9, *19, *XN). No association between both suicide risk and personal history of suicide attempts, and the above mentioned metabolic profiles were found after multiple testing corrections. In conclusion, the investigated cytochrome gene polymorphisms do not seem to be associated with suicide risk and/or a personal history of suicide attempts, though methodological and sample size limitations do not allow definitive conclusions.
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. peter.hoefer@meduniwien.ac.at
Peter
P
Höfer
Alexandra
A
Schosser
Raffaella
R
Calati
Alessandro
A
Serretti
Isabelle
I
Massat
Neslihan Aygun
NA
Kocabas
Anastasios
A
Konstantinidis
Sylvie
S
Linotte
Julien
J
Mendlewicz
Daniel
D
Souery
Joseph
J
Zohar
Alzbeta
A
Juven-Wetzler
Stuart
S
Montgomery
Siegfried
S
Kasper
D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000009:adverse effects; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology*; D005060:Europe; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012737:Sex Factors; D013406:Suicide, Attempted / Q000523:psychology*
D000928:Antidepressive Agents; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D019388:Cytochrome P-450 CYP1A2; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6