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COMT val158met moderation of dopaminergic drug effects on cognitive function: a critical review

Abstract

The relationship between dopamine (DA) tone in the prefrontal cortex (PFC) and PFC-dependent cognitive functions (for example, working memory, selective attention, executive function) may be described by an inverted-U-shaped function, in which both excessively high and low DA is associated with impairment. In the PFC, the COMT val158met single nucleotide polymorphism (rs4680) confers differences in catechol-O-methyltransferase (COMT) efficacy and DA tone, and individuals homozygous for the val allele display significantly reduced cortical DA. Many studies have investigated whether val158met genotype moderates the effects of dopaminergic drugs on PFC-dependent cognitive functions. A review of 25 such studies suggests evidence for this pharmacogenetic effect is mixed for stimulants and COMT inhibitors, which have greater effects on D1 receptors, and strong for antipsychotics, which have greater effects on D2 receptors. Overall, COMT val158met genotype represents an enticing target for identifying individuals who are more likely to respond positively to dopaminergic drugs.

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References

  1. Beaulieu JM, Gainetdinov RR . The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev 2011; 63: 182–217.

    Article  CAS  PubMed  Google Scholar 

  2. Usiello A, Baik JH, Rouge-Pont F, Picetti R, Dierich A, LeMeur M et al. Distinct functions of the two isoforms of dopamine D2 receptors. Nature 2000; 408: 199–203.

    Article  CAS  PubMed  Google Scholar 

  3. De Mei C, Ramos M, Iitaka C, Borrelli E . Getting specialized: presynaptic and postsynaptic dopamine D2 receptors. Curr Opin Pharmacol 2009; 9: 53–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lidow MS, Goldman-Rakic PS, Gallager DW, Rakic P . Distribution of dopaminergic receptors in the primate cerebral cortex: quantitative autoradiographic analysis using [3H]raclopride, [3H]spiperone and [3H]SCH23390. Neuroscience 1991; 40: 657–671.

    Article  CAS  PubMed  Google Scholar 

  5. Durstewitz D, Seamans JK . The dual-state theory of prefrontal cortex dopamine function with relevance to catechol-o-methyltransferase genotypes and schizophrenia. Biol Psychiatry 2008; 64: 739–749.

    Article  CAS  PubMed  Google Scholar 

  6. Cropley VL, Fujita M, Innis RB, Nathan PJ . Molecular imaging of the dopaminergic system and its association with human cognitive function. Biol Psychiatry 2006; 59: 898–907.

    Article  CAS  PubMed  Google Scholar 

  7. Haber SN . The place of dopamine in the cortico-basal ganglia circuit. Neuroscience 2014; 282C: 248–257.

    Article  CAS  Google Scholar 

  8. Dreyer JK, Herrik KF, Berg RW, Hounsgaard JD . Influence of phasic and tonic dopamine release on receptor activation. J Neurosci 2010; 30: 14273–14283.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Cools R, D'Esposito M . Inverted-U-shaped dopamine actions on human working memory and cognitive control. Biol Psychiatry 2011; 69: e113–e125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Arnsten AF . Catecholamine regulation of the prefrontal cortex. J Psychopharmacol 1997; 11: 151–162.

    Article  CAS  PubMed  Google Scholar 

  11. Goldman-Rakic PS, Muly EC 3rd, Williams GV . D(1) receptors in prefrontal cells and circuits. Brain Res Brain Res Rev 2000; 31: 295–301.

    Article  CAS  PubMed  Google Scholar 

  12. Zahrt J, Taylor JR, Mathew RG, Arnsten AF . Supranormal stimulation of D1 dopamine receptors in the rodent prefrontal cortex impairs spatial working memory performance. J Neurosci 1997; 17: 8528–8535.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sesack SR, Hawrylak VA, Matus C, Guido MA, Levey AI . Dopamine axon varicosities in the prelimbic division of the rat prefrontal cortex exhibit sparse immunoreactivity for the dopamine transporter. J Neurosci 1998; 18: 2697–2708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Matsumoto M, Weickert CS, Akil M, Lipska BK, Hyde TM, Herman MM et al. Catechol O-methyltransferase mRNA expression in human and rat brain: evidence for a role in cortical neuronal function. Neuroscience 2003; 116: 127–137.

    Article  CAS  PubMed  Google Scholar 

  15. Lachman HM, Papolos DF, Saito T, Yu YM, Szumlanski CL, Weinshilboum RM . Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 1996; 6: 243–250.

    Article  CAS  PubMed  Google Scholar 

  16. Chen J, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S et al. Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. Am J Hum Genet 2004; 75: 807–821.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Slifstein M, Kolachana B, Simpson EH, Tabares P, Cheng B, Duvall M et al. COMT genotype predicts cortical-limbic D1 receptor availability measured with [11C]NNC112 and PET. Mol Psychiatry 2008; 13: 821–827.

    Article  CAS  PubMed  Google Scholar 

  18. Craddock N, Owen MJ, O'Donovan MC . The catechol-O-methyl transferase (COMT) gene as a candidate for psychiatric phenotypes: evidence and lessons. Mol Psychiatry 2006; 11: 446–458.

    Article  CAS  PubMed  Google Scholar 

  19. Lachman HM . Does COMT val158met affect behavioral phenotypes: yes, no, maybe? Neuropsychopharmacology 2008; 33: 3027–3029.

    Article  CAS  PubMed  Google Scholar 

  20. Grace AA . Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience 1991; 41: 1–24.

    Article  CAS  PubMed  Google Scholar 

  21. Arnsten AF . Toward a new understanding of attention-deficit hyperactivity disorder pathophysiology: an important role for prefrontal cortex dysfunction. CNS Drugs 2009; 23: 33–41.

    Article  CAS  PubMed  Google Scholar 

  22. Cheuk DK, Wong V . Meta-analysis of association between a catechol-O-methyltransferase gene polymorphism and attention deficit hyperactivity disorder. Behav Genet 2006; 36: 651–659.

    Article  PubMed  Google Scholar 

  23. Munafo MR, Bowes L, Clark TG, Flint J . Lack of association of the COMT (Val158/108 Met) gene and schizophrenia: a meta-analysis of case-control studies. Mol Psychiatry 2005; 10: 765–770.

    Article  CAS  PubMed  Google Scholar 

  24. Rosa A, Peralta V, Cuesta MJ, Zarzuela A, Serrano F, Martinez-Larrea A et al. New evidence of association between COMT gene and prefrontal neurocognitive function in healthy individuals from sibling pairs discordant for psychosis. Am J Psychiatry 2004; 161: 1110–1112.

    Article  PubMed  Google Scholar 

  25. Malhotra AK, Kestler LJ, Mazzanti C, Bates JA, Goldberg T, Goldman D . A functional polymorphism in the COMT gene and performance on a test of prefrontal cognition. Am J Psychiatry 2002; 159: 652–654.

    Article  PubMed  Google Scholar 

  26. Goldberg TE, Egan MF, Gscheidle T, Coppola R, Weickert T, Kolachana BS et al. Executive subprocesses in working memory: relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia. Arch Gen Psychiatry 2003; 60: 889–896.

    Article  CAS  PubMed  Google Scholar 

  27. Barnett JH, Scoriels L, Munafo MR . Meta-analysis of the cognitive effects of the catechol-O-methyltransferase gene Val158/108Met polymorphism. Biol Psychiatry 2008; 64: 137–144.

    Article  CAS  PubMed  Google Scholar 

  28. Witte AV, Floel A . Effects of COMT polymorphisms on brain function and behavior in health and disease. Brain Res Bull 2012; 88: 418–428.

    Article  CAS  PubMed  Google Scholar 

  29. Robbins TW, Arnsten AF . The neuropsychopharmacology of fronto-executive function: monoaminergic modulation. Annu Rev Neurosci 2009; 32: 267–287.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gelernter J . Genetics of complex traits in psychiatry. Biol Psychiatry 2015; 77: 36–42.

    Article  CAS  PubMed  Google Scholar 

  31. Muller U, von Cramon DY, Pollmann S . D1- versus D2-receptor modulation of visuospatial working memory in humans. J Neurosci 1998; 18: 2720–2728.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Narayanan NS, Land BB, Solder JE, Deisseroth K, DiLeone RJ . Prefrontal D1 dopamine signaling is required for temporal control. Proc Natl Acad Sci USA 2012; 109: 20726–20731.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Chudasama Y, Robbins TW . Dopaminergic modulation of visual attention and working memory in the rodent prefrontal cortex. Neuropsychopharmacology 2004; 29: 1628–1636.

    Article  CAS  PubMed  Google Scholar 

  34. Sawaguchi T, Goldman-Rakic PS . D1 dopamine receptors in prefrontal cortex: involvement in working memory. Science 1991; 251: 947–950.

    Article  CAS  PubMed  Google Scholar 

  35. Dodds CM, Clark L, Dove A, Regenthal R, Baumann F, Bullmore E et al. The dopamine D2 receptor antagonist sulpiride modulates striatal BOLD signal during the manipulation of information in working memory. Psychopharmacology (Berl) 2009; 207: 35–45.

    Article  CAS  Google Scholar 

  36. Mehta MA, Manes FF, Magnolfi G, Sahakian BJ, Robbins TW . Impaired set-shifting and dissociable effects on tests of spatial working memory following the dopamine D2 receptor antagonist sulpiride in human volunteers. Psychopharmacology (Berl) 2004; 176: 331–342.

    Article  CAS  Google Scholar 

  37. la Fougere C, Meisenzahl E, Schmitt G, Stauss J, Frodl T, Tatsch K et al. D2 receptor occupancy during high- and low-dose therapy with the atypical antipsychotic amisulpride: a 123I-iodobenzamide SPECT study. J Nucl Med 2005; 46: 1028–1033.

    CAS  PubMed  Google Scholar 

  38. Bitsios P, Roussos P . Tolcapone, COMT polymorphisms and pharmacogenomic treatment of schizophrenia. Pharmacogenomics 2011; 12: 559–566.

    Article  CAS  PubMed  Google Scholar 

  39. Llerena A, Berecz R, Penas-Lledo E, Suveges A, Farinas H . Pharmacogenetics of clinical response to risperidone. Pharmacogenomics 2013; 14: 177–194.

    Article  CAS  PubMed  Google Scholar 

  40. Diaz-Asper CM, Weinberger DR, Goldberg TE . Catechol-O-methyltransferase polymorphisms and some implications for cognitive therapeutics. NeuroRx 2006; 3: 97–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Berridge CW, Arnsten AF . Psychostimulants and motivated behavior: arousal and cognition. Neurosci Biobehav Rev 2013; 37: 1976–1984.

    Article  CAS  PubMed  Google Scholar 

  42. Gamo NJ, Wang M, Arnsten AF . Methylphenidate and atomoxetine enhance prefrontal function through alpha2-adrenergic and dopamine D1 receptors. J Am Acad Child Adolesc Psychiatry 2010; 49: 1011–1023.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Hakkarainen JJ, Jalkanen AJ, Kaariainen TM, Keski-Rahkonen P, Venalainen T, Hokkanen J et al. Comparison of in vitro cell models in predicting in vivo brain entry of drugs. Int J Pharm 2010; 402: 27–36.

    Article  CAS  PubMed  Google Scholar 

  44. Mattay VS, Goldberg TE, Fera F, Hariri AR, Tessitore A, Egan MF et al. Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc Natl Acad Sci USA 2003; 100: 6186–6191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hamidovic A, Dlugos A, Palmer AA, de Wit H . Catechol-O-methyltransferase val158met genotype modulates sustained attention in both the drug-free state and in response to amphetamine. Psychiatr Genet 2010; 20: 85–92.

    PubMed  PubMed Central  Google Scholar 

  46. Hart AB, de Wit H, Palmer AA . Candidate gene studies of a promising intermediate phenotype: failure to replicate. Neuropsychopharmacology 2013; 38: 802–816.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Wardle MC, Hart AB, Palmer AA, de Wit H . Does COMT genotype influence the effects of d-amphetamine on executive functioning? Genes Brain Behav 2013; 12: 13–20.

    Article  CAS  PubMed  Google Scholar 

  48. Cheon KA, Jun JY, Cho DY . Association of the catechol-O-methyltransferase polymorphism with methylphenidate response in a classroom setting in children with attention-deficit hyperactivity disorder. Int Clin Psychopharmacol 2008; 23: 291–298.

    Article  PubMed  Google Scholar 

  49. Froehlich TE, Epstein JN, Nick TG, Melguizo Castro MS, Stein MA, Brinkman WB et al. Pharmacogenetic predictors of methylphenidate dose-response in attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2011; 50: 1129–39 e2.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Kereszturi E, Tarnok Z, Bognar E, Lakatos K, Farkas L, Gadoros J et al. Catechol-O-methyltransferase Val158Met polymorphism is associated with methylphenidate response in ADHD children. Am J Med Genet B Neuropsychiatr Genet 2008; 147B: 1431–1435.

    Article  CAS  PubMed  Google Scholar 

  51. Park S, Kim JW, Kim BN, Shin MS, Yoo HJ, Cho SC . Catechol-O-methyltransferase Val158-Met polymorphism and a response of hyperactive-impulsive symptoms to methylphenidate: A replication study from South Korea. J Psychopharmacol 2014; 28: 671–676.

    Article  CAS  PubMed  Google Scholar 

  52. McGough JJ, McCracken JT, Loo SK, Manganiello M, Leung MC, Tietjens JR et al. A candidate gene analysis of methylphenidate response in attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2009; 48: 1155–1164.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Sengupta S, Grizenko N, Schmitz N, Schwartz G, Bellingham J, Polotskaia A et al. COMT Val108/158Met polymorphism and the modulation of task-oriented behavior in children with ADHD. Neuropsychopharmacology 2008; 33: 3069–3077.

    Article  CAS  PubMed  Google Scholar 

  54. Salatino-Oliveira A, Genro JP, Zeni C, Polanczyk GV, Chazan R, Guimaraes AP et al. Catechol-O-methyltransferase valine158methionine polymorphism moderates methylphenidate effects on oppositional symptoms in boys with attention-deficit/hyperactivity disorder. Biol Psychiatry 2011; 70: 216–221.

    Article  CAS  PubMed  Google Scholar 

  55. Contini V, Victor MM, Bertuzzi GP, Salgado CA, Picon FA, Grevet EH et al. No significant association between genetic variants in 7 candidate genes and response to methylphenidate treatment in adult patients with ADHD. J Clin Psychopharmacol 2012; 32: 820–823.

    Article  CAS  PubMed  Google Scholar 

  56. McCracken JT, Badashova KK, Posey DJ, Aman MG, Scahill L, Tierney E et al. Positive effects of methylphenidate on hyperactivity are moderated by monoaminergic gene variants in children with autism spectrum disorders. Pharmacogenomics J 2014; 14: 295–302.

    Article  CAS  PubMed  Google Scholar 

  57. Apud JA, Mattay V, Chen J, Kolachana BS, Callicott JH, Rasetti R et al. Tolcapone improves cognition and cortical information processing in normal human subjects. Neuropsychopharmacology 2007; 32: 1011–1020.

    Article  CAS  PubMed  Google Scholar 

  58. Farrell SM, Tunbridge EM, Braeutigam S, Harrison PJ . COMT Val(158)Met genotype determines the direction of cognitive effects produced by catechol-O-methyltransferase inhibition. Biol Psychiatry 2012; 71: 538–544.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Giakoumaki SG, Roussos P, Bitsios P . Improvement of prepulse inhibition and executive function by the COMT inhibitor tolcapone depends on COMT Val158Met polymorphism. Neuropsychopharmacology 2008; 33: 3058–3068.

    Article  CAS  PubMed  Google Scholar 

  60. Ashare RL, Wileyto EP, Ruparel K, Goelz PM, Hopson RD, Valdez JN et al. Effects of tolcapone on working memory and brain activity in abstinent smokers: a proof-of-concept study. Drug Alcohol Depend 2013; 133: 852–856.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Abi-Dargham A, Laruelle M . Mechanisms of action of second generation antipsychotic drugs in schizophrenia: insights from brain imaging studies. Eur Psychiatry 2005; 20: 15–27.

    Article  PubMed  Google Scholar 

  62. Lawler CP, Prioleau C, Lewis MM, Mak C, Jiang D, Schetz JA et al. Interactions of the novel antipsychotic aripiprazole (OPC-14597) with dopamine and serotonin receptor subtypes. Neuropsychopharmacology 1999; 20: 612–627.

    Article  CAS  PubMed  Google Scholar 

  63. Weickert TW, Goldberg TE, Mishara A, Apud JA, Kolachana BS, Egan MF et al. Catechol-O-methyltransferase val108/158met genotype predicts working memory response to antipsychotic medications. Biol Psychiatry 2004; 56: 677–682.

    Article  CAS  PubMed  Google Scholar 

  64. Bertolino A, Caforio G, Blasi G, De Candia M, Latorre V, Petruzzella V et al. Interaction of COMT (Val(108/158)Met) genotype and olanzapine treatment on prefrontal cortical function in patients with schizophrenia. Am J Psychiatry 2004; 161: 1798–1805.

    Article  PubMed  Google Scholar 

  65. Bosia M, Zanoletti A, Spangaro M, Buonocore M, Bechi M, Cocchi F et al. Factors affecting cognitive remediation response in schizophrenia: the role of COMT gene and antipsychotic treatment. Psychiatry Res 2014; 217: 9–14.

    Article  CAS  PubMed  Google Scholar 

  66. Woodward ND, Jayathilake K, Meltzer HY . COMT val108/158met genotype, cognitive function, and cognitive improvement with clozapine in schizophrenia. Schizophr Res 2007; 90: 86–96.

    Article  PubMed  Google Scholar 

  67. Mata I, Arranz MJ, Staddon S, Lopez-Ilundain JM, Tabares-Seisdedos R, Murray RM . The high-activity Val allele of the catechol-O-methyltransferase gene predicts greater cognitive deterioration in patients with psychosis. Psychiatr Genet 2006; 16: 213–216.

    Article  PubMed  Google Scholar 

  68. Rebollo-Mesa I, Picchioni M, Shaikh M, Bramon E, Murray R, Toulopoulou T . COMT (Val(158/108)Met) genotype moderates the impact of antipsychotic medication on verbal IQ in twins with schizophrenia. Psychiatr Genet 2011; 21: 98–105.

    Article  PubMed  Google Scholar 

  69. Arts B, Simons CJ, Drukker M, van Os J . Antipsychotic medications and cognitive functioning in bipolar disorder: moderating effects of COMT Val108/158 Met genotype. BMC psychiatry 2013; 13: 63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Mueller EM, Makeig S, Stemmler G, Hennig J, Wacker J . Dopamine effects on human error processing depend on catechol-O-methyltransferase VAL158MET genotype. J Neurosci 2011; 31: 15818–15825.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Volkow ND, Wang G, Fowler JS, Logan J, Gerasimov M, Maynard L et al. Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain. J Neurosci 2001; 21: RC121.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Ghahremani DG, Lee B, Robertson CL, Tabibnia G, Morgan AT, De Shetler N et al. Striatal dopamine D(2)/D(3) receptors mediate response inhibition and related activity in frontostriatal neural circuitry in humans. J Neurosci 2012; 32: 7316–7324.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Meyer-Lindenberg A, Kohn PD, Kolachana B, Kippenhan S, McInerney-Leo A, Nussbaum R et al. Midbrain dopamine and prefrontal function in humans: interaction and modulation by COMT genotype. Nat Neurosci 2005; 8: 594–596.

    Article  CAS  PubMed  Google Scholar 

  74. Kayser AS, Allen DC, Navarro-Cebrian A, Mitchell JM, Fields HL . Dopamine, corticostriatal connectivity, and intertemporal choice. J Neurosci 2012; 32: 9402–9409.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Apud JA, Weinberger DR . Treatment of cognitive deficits associated with schizophrenia: potential role of catechol-O-methyltransferase inhibitors. CNS Drugs 2007; 21: 535–557.

    Article  CAS  PubMed  Google Scholar 

  76. Abi-Dargham A, Mawlawi O, Lombardo I, Gil R, Martinez D, Huang Y et al. Prefrontal dopamine D1 receptors and working memory in schizophrenia. J Neurosci 2002; 22: 3708–3719.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Okubo Y, Suhara T, Suzuki K, Kobayashi K, Inoue O, Terasaki O et al. Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET. Nature 1997; 385: 634–636.

    Article  CAS  PubMed  Google Scholar 

  78. Floresco SB . Prefrontal dopamine and behavioral flexibility: shifting from an "inverted-U" toward a family of functions. Front Neurosci 2013; 7: 62.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Ryan SG . Regression to the truth: replication of association in pharmacogenetic studies. Pharmacogenomics 2003; 4: 201–207.

    Article  PubMed  Google Scholar 

  80. Bakker PR, van Harten PN, van Os J . Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a meta-analysis of pharmacogenetic interactions. Mol Psychiatry 2008; 13: 544–556.

    Article  CAS  PubMed  Google Scholar 

  81. Nackley AG, Shabalina SA, Tchivileva IE, Satterfield K, Korchynskyi O, Makarov SS et al. Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science 2006; 314: 1930–1933.

    Article  CAS  PubMed  Google Scholar 

  82. Roussos P, Giakoumaki SG, Bitsios P . Tolcapone effects on gating, working memory, and mood interact with the synonymous catechol-O-methyltransferase rs4818c/g polymorphism. Biol Psychiatry 2009; 66: 997–1004.

    Article  CAS  PubMed  Google Scholar 

  83. Zhao QZ, Liu BC, Zhang J, Wang L, Li XW, Wang Y et al. Association between a COMT polymorphism and clinical response to risperidone treatment: a pharmacogenetic study. Psychiatr Genet 2012; 22: 298–299.

    Article  CAS  PubMed  Google Scholar 

  84. Fijal BA, Kinon BJ, Kapur S, Stauffer VL, Conley RR, Jamal HH et al. Candidate-gene association analysis of response to risperidone in African-American and white patients with schizophrenia. Pharmacogenomics J 2009; 9: 311–318.

    Article  CAS  PubMed  Google Scholar 

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Schacht, J. COMT val158met moderation of dopaminergic drug effects on cognitive function: a critical review. Pharmacogenomics J 16, 430–438 (2016). https://doi.org/10.1038/tpj.2016.43

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