Skip to main content
SpringerLink
Log in

Pharmacogenetics of Obsessive-Compulsive Disorder: An Evidence-Update

  • Chapter
  • First Online:
The Neurobiology and Treatment of OCD: Accelerating Progress

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 49))

Abstract

Pharmacogenetics has become increasingly important in the treatment of psychiatric disorders because approximately 50% of individuals who take psychotropic medications do not typically respond to them. Obsessive-compulsive disorder (OCD) is one such chronic and often debilitating mental illness with significant non-response to even the first-line medication, serotonin reuptake inhibitors. Precision medicine utilizing genetic testing panels has received significant attention based on the evidence that the variability of antidepressant response and adverse effects is partly due to the variability in an individual’s genome. Thus, extensive research has investigated the role of genetic factors on antidepressant response in major depressive disorder (MDD) and their utility for guiding antidepressant treatment to significantly improving outcomes in individuals with MDD. However, limited progress remains in the pharmacogenetics of OCD. This chapter will provide an overview of the recent findings in the pharmacogenetics of OCD. Promising results with limited replications have been reported for the cytochrome P450 liver metabolism genes in addition to several serotonergic and glutamatergic system genes, which may play an important role in antidepressant response in the treatment of OCD.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abdolhosseinzadeh S, Sina M, Ahmadiani A, Asadi S, Shams J (2019) Genetic and pharmacogenetic study of glutamate transporter (SLC1A1) in Iranian patients with obsessive-compulsive disorder. J Clin Pharm Ther 44(1):39–48

    Article  CAS  PubMed  Google Scholar 

  • Ahmadipour E, Rashidi FS, Ahmadiani A, Asadi S, Shams J (2018) SLC6A4 polymorphisms rs25533 and I425V: association with obsessive-compulsive disorder and its treatment response in Iranian patients. Personalized Med Psychiatry 11-12:23–29

    Article  Google Scholar 

  • Altar CA, Hornberger J, Shewade A, Cruz V, Garrison J, Mrazek D (2013) Clinical validity of cytochrome P450 metabolism and serotonin gene variants in psychiatric pharmacotherapy. Int Rev Psychiatry 25(5):509–533

    Article  PubMed  Google Scholar 

  • American Psychiatric Association (APA) (2007) Practice guideline for the treatment of patients with obsessive-compulsive disorder. Arlington, VA, USA. http://www.psych.org/psych_pract/treatg/pg/prac_guide.cfm

  • Bernard S, Neville KA, Nguyen AT, Flockhart DA (2006) Interethnic differences in genetic polymorphisms of CYP2D6 in the U.S. population: clinical implications. Oncologist 11(2):126–135

    Article  CAS  PubMed  Google Scholar 

  • Billett EA, Richter MA, King N, Heils A, Lesch KP, Kennedy JL (1997) Obsessive compulsive disorder, response to serotonin reuptake inhibitors and the serotonin transporter gene. Mol Psychiatry 2(5):403–406

    Article  CAS  PubMed  Google Scholar 

  • Brandl EJ, Müller DJ, Richter MA (2012) Pharmacogenetics of obsessive-compulsive disorders. Pharmacogenomics 13(1):71–81

    Article  CAS  PubMed  Google Scholar 

  • Brandl EJ, Tiwari AK, Zhou X, Deluce J, Kennedy JL, Müller DJ, Richter MA (2013) Influence of CYP2D6 and CYP2C19 gene variants on antidepressant response in obsessive-compulsive disorder. Pharmacogenomics J 14(2):176–181

    Article  PubMed  CAS  Google Scholar 

  • Brandl EJ, Tiwari AK, Zhou X, Deluce J, Kennedy JL, Muller DJ, Richter MA (2014) Influence of CYP2D6 and CYP2C19 gene variants on antidepressant response in obsessive-compulsive disorder. Pharm J 14(2):176–181

    CAS  Google Scholar 

  • Brown JT, Schneiderhan M, Eum S, Bishop JR (2017) Serum clomipramine and desmethylclomipramine levels in a CYP2C19 and CYP2D6 intermediate metabolizer. Pharmacogenomics 18(7):601–605

    Article  CAS  PubMed  Google Scholar 

  • Caley CF (2011) Interpreting and applying CYP450 genomic test results to psychotropic medications. J Pharm Pract 24(5):439–446

    Article  PubMed  Google Scholar 

  • Canadian Psychiatric Association (CPA) (2006) Clinical practice guidelines: management of anxiety disorders. Can J Psychiatr 51(2):43S–49S

    Google Scholar 

  • Denys D, Van Nieuwerburge F, Deforce D, Westenberg HG (2007) Prediction of response to paroxetine and venlafaxine by serotonin-related genes in obsessive-compulsive disorder in a randomized, double-blind trial. J Clin Psychiatry 68(5):747–753

    Article  CAS  PubMed  Google Scholar 

  • Desta Z, Zhao X, Shin JG, Flockhart DA (2002) Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin Pharmacokinet 41(12):913–958

    Article  CAS  PubMed  Google Scholar 

  • Di Bella D, Erzegovesi S, Cavallini MC, Bellodi L (2002) Obsessive-compulsive disorder, 5-HTTLPR polymorphism and treatment response. Pharm J 2(3):176–181

    Google Scholar 

  • Dold M, Aigner M, Lanzenberger R, Kasper S (2013) Antipsychotic augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: a meta-analysis of double-blind, randomized, placebo-controlled trials. Int J Neuropsychopharmacol 16(3):557–574

    Article  CAS  PubMed  Google Scholar 

  • Fabbri C, Di Girolamo G, Serretti A (2013) Pharmacogenetics of antidepressant drugs: an update after almost 20 years of research. Am J Med Genet B Neuropsychiatr Genet 162B(6):487–520

    Article  PubMed  CAS  Google Scholar 

  • Fineberg NA, Reghunandanan S, Simpson HB, Phillips KA, Richter MA, Matthews K, Stein DJ, Sareen J, Brown A, Sookman D (2015) Accreditation Task Force of The Canadian Institute for Obsessive Compulsive Disorders. Obsessive-compulsive disorder (OCD): practical strategies for pharmacological and somatic treatment in adults. Psychiatry Res 227(1):114–125

    Article  CAS  PubMed  Google Scholar 

  • Flockhart DA (2007) Drug interactions: cytochrome P450 drug interaction table. Indiana University School of Medicine. http://medicine.iupui.edu/clinpharm/ddis/clinical-table/. Accessed 10 Jan 2014

  • Grados MA, Specht MW, Sung HM, Fortune D (2013) Glutamate drugs and pharmacogenetics of OCD: a pathway-based exploratory approach. Expert Opin Drug Discov 8(12):1515–1527

    Article  CAS  PubMed  Google Scholar 

  • Gvozdic K, Brandl EJ, Taylor DL, Müller DJ (2012) Genetics and personalized medicine in antidepressant treatment. Curr Pharm Des 18(36):5853–5878

    Article  CAS  PubMed  Google Scholar 

  • Hicks JK, Bishop JR, Sangkuhl K, Müller DJ, Li U, Leckband SG, Leeder JS, Graham RL, Chiulli DL, LLerena A, Skaar TC, Scott SA, Stingl JC, Klein TE, Caudle KE, Gaedigk A (2015) Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther 98(2):127–134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hicks JK, Sangkuhl K, Swen JJ, Ellingrod VL, Müller DJ, Shimoda K, Bishop JR, Kharasch ED, Skaar TC, Gaedigk A, Dunnenberger HM, Klein TE, Caudle KE, Stingl JC (2017) Clinical Pharmacogenetics Implementation Consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clin Pharmacol Ther 102(1):37–44

    Article  CAS  PubMed  Google Scholar 

  • Jann MW, Cohen LJ (2000) The influence of ethnicity and antidepressant pharmacogenetics in the treatment of depression. Drug Metabol Drug Interact 16(1):39–67

    Article  CAS  PubMed  Google Scholar 

  • Kariuki-Nyuthe C, Gomez-Mancilla B, Stein DJ (2014) Obsessive-compulsive disorder and the glutamatergic system. Curr Opin Psychiatry 27(1):32–37

    Article  PubMed  Google Scholar 

  • Katzman MA, Bleau P, Blier P, Chokka P, Kjernisted K, Van Ameringen M, Canadian Anxiety Guidelines Initiative Group on behalf of the Anxiety Disorders Association of Canada/Association Canadienne des troubles anxieux and McGill University (2014) Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry 14(Suppl 1):S1

    Article  PubMed  PubMed Central  Google Scholar 

  • Koo MS, Kim EJ, Roh D, Kim CH (2010) Role of dopamine in the pathophysiology and treatment of obsessive-compulsive disorder. Expert Rev Neurother 10(2):275–290

    Article  CAS  PubMed  Google Scholar 

  • Koran LM, Hanna GL, Hollander E, Nestadt G, Simpson HB, American Psychiatric Association (2007) Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry 164(7 Suppl):5–53

    PubMed  Google Scholar 

  • Lazaro-Munoz G, Sabatello M, Huckins L, Peay H, Degenhardt F, Meiser B et al (2019) International society of psychiatric genetics ethics committee: issues facing us. Am J Med Genet B Neuropsychiatr Genet 180(8):543–554

    Article  PubMed  PubMed Central  Google Scholar 

  • Lisoway AJ, Zai G, Tiwari AK, Zai CC, Wigg K, Goncalves V, Zhang D, Freeman N, Müller DJ, Kennedy JL, Richter MA (2018) Pharmacogenetic evaluation of a DISP1 gene variant in antidepressant treatment of obsessive-compulsive disorder. Hum Psychopharmacol 33(4):e2659

    Article  PubMed  CAS  Google Scholar 

  • Marinova Z, Chuang DM, Fineberg N (2017) Glutamate-modulating drugs as a potential therapeutic strategy in obsessive-compulsive disorder. Curr Neuropharmacol 15(7):977–995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McDougle CJ, Epperson CN, Price LH, Gelernter J (1998) Evidence for linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and obsessive compulsive disorder. Mol Psychiatry 3(3):270–273

    Article  CAS  PubMed  Google Scholar 

  • Menzies L, Chamberlain SR, Laird AR, Thelen SM, Sahakian BJ, Bullmore ET (2008) Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited. Neurosci Biobehav Rev 32(3):525–549

    Article  PubMed  Google Scholar 

  • Miguita K, Cordeiro Q, Shavitt RG, Miguel EC, Vallada H (2011) Association study between genetic monoaminergic polymorphisms and OCD response to clomipramine treatment. Arq Neuropsiquiatr 69(2B):283–287

    Article  PubMed  Google Scholar 

  • Milad MR, Rauch SL (2012) Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways. Trends Cogn Sci 16(1):43–51

    Article  PubMed  Google Scholar 

  • Milosavljevic F, Bukvic N, Pavlovic Z, Miljevic C, Pesic V, Molden E, Ingelman-Sundberg M, Leucht S, Jukic MM (2020) Association of CYP2C19 and CYP2D6 poor and intermediate metabolizer status with antidepressant and antipsychotic exposure: a systematic review and meta-analysis. JAMA Psychiatry:e203643. http://doi.org/10.1001/jamapsychiatry.2020.3643

    Google Scholar 

  • Müller DJ, Brandl EJ, Hwang R, Tiwari AK, Sturgess JE, Zai CC, Lieberman JA, Kennedy JL, Richter MA (2012) The AmpliChip® CYP450 test and response to treatment in schizophrenia and obsessive-compulsive disorder: a pilot study and focus on cases with abnormal CYP2D6 drug metabolism. Genet Test Mol Biomarkers 16(8):897–903

    Article  PubMed  CAS  Google Scholar 

  • National Collaborating Centre for Mental Health (UK) (2006) Obsessive-compulsive disorder: core interventions in the treatment of obsessive-compulsive disorder and body dysmorphic disorder. British Psychological Society, Leicester (NICE Clinical Guidelines, No. 31.) https://www.ncbi.nlm.nih.gov/books/NBK56458/

  • Neafsey P, Ginsberg G, Hattis D, Sonawane B (2009) Genetic polymorphism in cytochrome P450 2D6 (CYP2D6): population distribution of CYP2D6 activity. J Toxicol Environ Health B Crit Rev 12(5-6):334–361

    Article  CAS  PubMed  Google Scholar 

  • Pauls DL (2010) The genetics of obsessive-compulsive disorder: a review. Dialogues Clin Neurosci 12(2):149–163

    Article  PubMed  PubMed Central  Google Scholar 

  • Pauls DL, Abramovitch A, Rauch SL, Geller DA (2014) Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective. Nat Rev Neurosci 15(6):410–424

    Article  CAS  PubMed  Google Scholar 

  • Real E, Gratacòs M, Soria V, Escaramís G et al (2009) A brain-derived neurotrophic factor haplotype is associated with therapeutic response in obsessive-compulsive disorder. Biol Psychiatry 66(7):674–680

    Article  CAS  PubMed  Google Scholar 

  • Robbins TW, Vaghi MM, Banca P (2019) Obsessive-compulsive disorder: puzzles and prospects. Neuron 102(1):27–47

    Article  CAS  PubMed  Google Scholar 

  • Qin H, Samuels JF, Wang Y, Zhu Y, Grados MA, Riddle MA, Greenberg BD, Knowles JA, Fyer AJ, McCracken JT, Murphy DL, Rasmussen SA, Cullen BA, Piacentini J, Geller D, Stewart SE, Pauls D, Bienvenu OJ, Goes FS, Maher B, Pulver AE, Valle D, Lange C, Mattheisen M, McLaughlin NC, Liang KY, Nurmi EL, Askland KD, Nestadt G, Shugart YY (2016) Whole-genome association analysis of treatment response in obsessive-compulsive disorder. Mol Psychiatry 21(2):270–276

    Article  CAS  PubMed  Google Scholar 

  • Singh AB, Bousman CA, Ng C, Berk M (2014) Antidepressant pharmacogenetics. Curr Opin Psychiatry 27:43–51

    Article  PubMed  Google Scholar 

  • Sinopoli VM, Burton CL, Kronenberg S, Arnold PD (2017) A review of the role of serotonin system genes in obsessive-compulsive disorder. Neurosci Biobehav Rev 80:372–381

    Article  CAS  PubMed  Google Scholar 

  • Tot S, Erdal ME, Yazici K, Yazici AE, Metin O (2003) T102C and -1438 G/A polymorphisms of the 5-HT2A receptor gene in Turkish patients with obsessive-compulsive disorder. Eur Psychiatry 18(5):249–254

    Article  PubMed  Google Scholar 

  • Van Nieuverburge FC, Denys DA, Westenberg HG, Deforce DL (2009) Response to serotonin reuptake inhibitors in OCD is not influenced by common CYP2D6 polymorphisms. Int J Psychiatry Clin Pract 13(1):345–348

    Google Scholar 

  • Viswanath B, Taj MJRJ, Purushottam M, Kandavel T, Shetty PH, Reddy YC, Jain S (2013) No association between DRD4 gene and SRI treatment response in obsessive-compulsive disorder: need for a novel approach. Asian J Psychiatr 6(4):347–348

    Article  PubMed  Google Scholar 

  • Vulink NC, Westenberg HG, van Nieuwerburgh F, Deforce D, Fluitman SB, Meinardi JS, Denys D (2012) Catechol-O-methyltransferase gene expression is associated with response to citalopram in obsessive-compulsive disorder. Int J Psychiatry Clin Pract 16(4):277–283

    Article  CAS  PubMed  Google Scholar 

  • Wu K, Hanna GL, Rosenberg DR, Arnold PD (2012) The role of glutamate signaling in the pathogenesis and treatment of obsessive-compulsive disorder. Pharmacol Biochem Behav 100(4):726–735

    Article  CAS  PubMed  Google Scholar 

  • Zai G, Brandl EJ, Müller DJ, Richter MA, Kennedy JL (2014) Pharmacogenetics of antidepressant treatment in obsessive-compulsive disorder: an update and implications for clinicians. Pharmacogenomics 15(8):1147–1157

    Article  CAS  PubMed  Google Scholar 

  • Zai G, Barta C, Cath D, Eapen V, Geller D, Grünblatt E (2019) New insights and perspectives on the genetics of obsessive-compulsive disorder. Psychiatr Genet 29(5):142–151

    Article  PubMed  Google Scholar 

  • Zhang L, Liu X, Li T, Yang Y, Hu X, Collier D (2004) Molecular pharmacogenetic studies of drug responses to obsessive-compulsive disorder and six functional genes. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 21(5):479–481

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neurogenetics Section, Molecular Brain Science Department, Campbell Family Mental Health Research Institute, and General Adult Psychiatry and Health Systems Division, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Gwyneth Zai

  2. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Gwyneth Zai

  3. Institute of Medical Science, University of Toronto, Toronto, ON, Canada

    Gwyneth Zai

  4. Behavioural and Clinical Neuroscience Institute, Department of Psychiatry, University of Cambridge, Cambridge, UK

    Gwyneth Zai

Authors
  1. Gwyneth Zai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gwyneth Zai .

Editor information

Editors and Affiliations

  1. Centre for Health Services and Clinical Research, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Hertfordshire, UK

    Naomi A. Fineberg

  2. Department of Psychology and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK

    Trevor W. Robbins

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Zai, G. (2021). Pharmacogenetics of Obsessive-Compulsive Disorder: An Evidence-Update. In: Fineberg, N.A., Robbins, T.W. (eds) The Neurobiology and Treatment of OCD: Accelerating Progress. Current Topics in Behavioral Neurosciences, vol 49. Springer, Cham. https://doi.org/10.1007/7854_2020_205

Download citation

Publish with us

Policies and ethics

Search

Navigation