Neither Cytochrome P450 Family Genes nor Neuroendocrine Factors could Independently Predict the SSRIs Treatment in the Chinese Han Population

Abstract Objective: This study was intended to explore the relationship between the genetic polymorphisms of the 8 single nucleotide polymorphisms (SNPs) at CYP genes, neuroendocrine factors and the response to selective serotonin reuptake inhibitors (SSRIs) in Chinese Han depressive patients. Method: This was a 6-week randomized controlled trial consisting of 290 Chinese Han depressive patients treated with SSRIs. 8 SNPs of CYP450 genes and 7 neuroendocrine factors were detected. Allele and genotype frequencies were compared between responders and non-responders. The relationships between neuroendocrine factors and treatment response were also analyzed. Results: No significant differences were found in clinical features between 2 groups at the baseline. No statistical correlation was found between either the genotype or allele frequencies of SNPs in CYP1A2, CYP2C19, or CYP2D6 gene and the efficacy of SSRIs. There were strong linkage disequilibria between rs4986894, rs1853205, and rs12767583 of CYP2C19 genes, and rs2472299, rs2472300 of CYP1A2 genes. No associations were found between the above haplotypes and the antidepressant response. No neuroendocrine factor was a significant predictor for a response to SSRI antidepressants independently. The combination of neuroendocrine factors, however, predicted the response by 76.1%. Conclusion: There were no significant associations between the 6 SNPs of CYP gene polymorphisms and SSRI response. Neither cytochrome P450 family genes nor neuroendocrine factors independently predict the patients’ response to the antidepressants separately. A combination of neuroendocrine factors, however, does have the potential to predict the response.

[1]  D. Iosifescu,et al.  Treatments for Depression , 2013 .

[2]  Xueli Sun,et al.  Alterations in hypothalamic–pituitary–adrenal/thyroid (HPA/HPT) axes correlated with the clinical manifestations of depression , 2012, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[3]  J. Cornuz,et al.  Impact of Smoking, Smoking Cessation, and Genetic Polymorphisms on CYP1A2 Activity and Inducibility , 2011, Clinical pharmacology and therapeutics.

[4]  F. Lotrich Gene-environment interactions in geriatric depression. , 2011, The Psychiatric clinics of North America.

[5]  A. Serretti,et al.  Pharmacogenetics of antidepressant response. , 2011, Journal of psychiatry & neuroscience : JPN.

[6]  Yusuke Nakamura,et al.  Genome-wide association study identifies genetic determinants of warfarin responsiveness for Japanese. , 2010, Human molecular genetics.

[7]  A. Zackrisson,et al.  High Frequency of Occurrence of CYP2D6 Gene Duplication/Multiduplication Indicating Ultrarapid Metabolism Among Suicide Cases , 2010, Clinical pharmacology and therapeutics.

[8]  Fernando Rivadeneira,et al.  A genome-wide association study of acenocoumarol maintenance dosage. , 2009, Human molecular genetics.

[9]  E. Binder,et al.  Pharmacogenomics of antidepressant drugs. , 2009, Pharmacology & therapeutics.

[10]  A. Serretti,et al.  Cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 genes are not associated with response and remission in a sample of depressive patients , 2009, International clinical psychopharmacology.

[11]  A. Gunes,et al.  Influence of genetic polymorphisms, smoking, gender and age on CYP1A2 activity in a Turkish population. , 2009, Pharmacogenomics.

[12]  Shufeng Zhou,et al.  A Bioinformatics Approach for the Phenotype Prediction of Nonsynonymous Single Nucleotide Polymorphisms in Human Cytochromes P450 , 2009, Drug Metabolism and Disposition.

[13]  Dennis S. Charney,et al.  Neurobiological mechanisms in major depressive disorder , 2009, Canadian Medical Association Journal.

[14]  A. Sajantila,et al.  Pharmacogenetic variation at CYP2C9, CYP2C19, and CYP2D6 at global and microgeographic scales , 2009, Pharmacogenetics and genomics.

[15]  H. Möller,et al.  Neuroimaging genetics: new perspectives in research on major depression? , 2008, Acta psychiatrica Scandinavica.

[16]  G. Jenkins,et al.  Pharmacokinetic Genes Do Not Influence Response or Tolerance to Citalopram in the STAR*D Sample , 2008, PloS one.

[17]  J Kirchheiner,et al.  The clinical role of genetic polymorphisms in drug-metabolizing enzymes , 2008, The Pharmacogenomics Journal.

[18]  Donna Bergen Neurological Disorders: Public Health Challenges , 2007 .

[19]  M. Sahoo,et al.  Cortisol hypersecretion in unipolar major depression with melancholic and psychotic features: Dopaminergic, noradrenergic and thyroid correlates , 2007, Psychoneuroendocrinology.

[20]  Y. Wing,et al.  Phenotype-genotype Relationship and Clinical Effects of Citalopram in Chinese Patients , 2006, Journal of clinical psychopharmacology.

[21]  J. de Leon,et al.  AmpliChip CYP450 Test: personalized medicine has arrived in psychiatry , 2006, Expert review of molecular diagnostics.

[22]  T. Someya,et al.  Polymorphisms in the 5-Hydroxytryptamine 2A Receptor and CytochromeP4502D6 Genes Synergistically Predict Fluvoxamine-Induced Side Effects in Japanese Depressed Patients , 2006, Neuropsychopharmacology.

[23]  B. Bondy Pharmacogenomics in depression and antidepressants , 2005, Dialogues in clinical neuroscience.

[24]  Lin He,et al.  SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci , 2005, Cell Research.

[25]  M. Daly,et al.  Haploview: analysis and visualization of LD and haplotype maps , 2005, Bioinform..

[26]  Matthias J. Müller,et al.  Impact of polymorphisms of cytochrome-P450 isoenzymes 2C9, 2C19 and 2D6 on plasma concentrations and clinical effects of antidepressants in a naturalistic clinical setting , 2004, European Journal of Clinical Pharmacology.

[27]  J Licinio,et al.  Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response , 2004, Molecular Psychiatry.

[28]  N. Thuerauf,et al.  CYP2D6 Genotype: Impact on Adverse Effects and Nonresponse During Treatment with Antidepressants—a Pilot Study , 2004, Clinical pharmacology and therapeutics.

[29]  K. Otani,et al.  Relationship between clinical effects of fluvoxamine and the steady-state plasma concentrations of fluvoxamine and its major metabolite fluvoxamino acid in Japanese depressed patients , 2003, Psychopharmacology.

[30]  H. Shibuya,et al.  CYP2D6*10 alleles do not determine plasma fluvoxamine concentration/dose ratio in Japanese subjects , 2003, European Journal of Clinical Pharmacology.

[31]  K. Lindpaintner Pharmacogenetics and Pharmacogenomics in Drug Discovery and Development: An Overview , 2003, Clinical chemistry and laboratory medicine.

[32]  P. Sullivan,et al.  Genetic epidemiology of major depression: review and meta-analysis. , 2000, The American journal of psychiatry.

[33]  Alan D. Lopez,et al.  Evidence-Based Health Policy--Lessons from the Global Burden of Disease Study , 1996, Science.

[34]  Tao Li,et al.  A partition-ligation-combination-subdivision EM algorithm for haplotype inference with multiallelic markers: update of the SHEsis (http://analysis.bio-x.cn) , 2009, Cell Research.

[35]  B. Lebowitz,et al.  Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. , 2006, The American journal of psychiatry.

[36]  J. Licinio,et al.  The pharmacogenomics of depression , 2001, The Pharmacogenomics Journal.