Pharmacogenomics approach in psychiatry disorders

authors:

avatar Negar Sarhangi , avatar Farshad Sharifi ORCID , avatar Shekoufeh Nikfar ORCID , avatar Mandana Hasanzad ORCID , *

Koomesh: Vol.24, issue 2; 255-266
published online: July 02, 2022
article type: Research Article
received: June 02, 2021
accepted: February 02, 2022

how to cite: Sarhangi N, Sharifi F, Nikfar S, Hasanzad M. Pharmacogenomics approach in psychiatry disorders. koomesh. 2022;24(2):e152668. 

Abstract

Psychiatric disorders are important health issues in the world, and their management is facing some serious challenges. Drugs that are widely used in the treatment of psychiatric disorders, including antidepressants, antipsychotics, and mood stabilizers, are often associated with many side effects and are adequately effective only in a small proportion of patients. Many factors, including genetic factors, affect the effectiveness of medications prescribed for mental health disorders.  Pharmacogenetics is the study of the association between genetic variations in genes encoding carriers, receptors, and drug-metabolizing enzymes with drug response. Many genes have been identified as affecting the drugs responsible for psychiatric disorders and genetic variation can lead to variations in the efficacy and side effects of drugs. This review article summarizes some psychiatric drugs and related genes, which could have potential functional effects.

References

  • 1.

    Patel V, Chisholm D, Parikh R, Charlson FJ, Degenhardt L, Dua T, et al. Addressing the burden of mental, neurological, and substance use disorders: key messages from Disease Control Priorities. Lancet 2016; 387: 1672-1685.

  • 2.

    Bloom DE, Cafiero E, Jan-Llopis E, Abrahams-Gessel S, Bloom LR, Fathima S, et al. The global economic burden of noncommunicable diseases. Program on the Global Demography of Aging, 2012.

  • 3.

    Cacabelos R, Martinez-Bouza R, Carlos Carril J, Fernandez-Novoa L, Lombardi V, Carrera I, et al. Genomics and pharmacogenomics of brain disorders. Curr Pharm Biotechnol 2012; 13: 674-725.

  • 4.

    Corponi F, Fabbri C, Serretti A. Pharmacogenetics in psychiatry. Adv Pharmacol 2018; 83: 297-331.

  • 5.

    Drozda K, Mller DJ, Bishop JR. Pharmacogenomic testing for neuropsychiatric drugs: current status of drug labeling, guidelines for using genetic information, and test options. Pharmacotherapy 2014; 34: 166-184.

  • 6.

    Kitzmiller JP, Groen DK, Phelps MA, Sadee W. Pharmacogenomic testing: relevance in medical practice: why drugs work in some patients but not in others. Clevel Clin J Med 2011; 78: 243.

  • 7.

    Zhang JP, Lencz T, Malhotra AK. D2 receptor genetic variation and clinical response to antipsychotic drug treatment: a meta-analysis. Am J Psychiatry 2010; 167: 763-772.

  • 8.

    Heils A, Teufel A, Petri S, Stber G, Riederer P, Bengel D, et al. Allelic variation of human serotonin transporter gene expression. J Neurochem 1996; 66: 2621-2624.

  • 9.

    Heinz A, Jones DW, Mazzanti C, Goldman D, Ragan P, Hommer D, et al. A relationship between serotonin transporter genotype and in vivo protein expression and alcohol neurotoxicity. Biol Psychiatry 2000; 47: 643-649.

  • 10.

    Shioe K, Ichimiya T, Suhara T, Takano A, Sudo Y, Yasuno F, et al. No association between genotype of the promoter region of serotonin transporter gene and serotonin transporter binding in human brain measured by PET. Synapse 2003; 48: 184-188.

  • 11.

    van Dyck CH, Malison RT, Staley JK, Jacobsen LK, Seibyl JP, Laruelle M, et al. Central serotonin transporter availability measured with [123I] -CIT SPECT in relation to serotonin transporter genotype. Am J Psychiatry 2004; 161: 525-531.

  • 12.

    David SP, Murthy NV, Rabiner EA, Munaf MR, Johnstone EC, Jacob R, et al. A functional genetic variation of the serotonin (5-HT) transporter affects 5-HT1A receptor binding in humans. J Neurosci 2005; 25: 2586-2590.

  • 13.

    Durham LK, Webb SM, Milos PM, Clary CM, Seymour AB. The serotonin transporter polymorphism, 5HTTLPR, is associated with a faster response time to sertraline in an elderly population with major depressive disorder. Psychopharmacology 2004; 174: 525-529.

  • 14.

    Pollock BG, Ferrell RE, Mulsant BH, Mazumdar S, Miller M, Sweet RA, et al. Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression. Neuropsychopharmacology 2000; 23: 587-590.

  • 15.

    Zanardi R, Serretti A, Rossini D, Franchini L, Cusin C, Lattuada E, et al. Factors affecting fluvoxamine antidepressant activity: influence of pindolol and 5-HTTLPR in delusional and nondelusional depression. Biol Psychiatry 2001; 50: 323-330.

  • 16.

    Smits KM, Smits LJ, Schouten JS, Peeters FP, Prins MH. Does pretreatment testing for serotonin transporter polymorphisms lead to earlier effects of drug treatment in patients with major depression? A decision-analytic model. Clin Ther 2007; 29: 691-702.

  • 17.

    Porcelli S, Fabbri C, Serretti A. Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with antidepressant efficacy. Eur Neuropsychopharmacol 2012; 22: 239-258.

  • 18.

    Taylor MJ, Sen S, Bhagwagar Z. Antidepressant response and the serotonin transporter gene-linked polymorphic region. Biol Psychiatry 2010; 68: 536-543.

  • 19.

    Kim DK, Lim S-W, Lee S, Sohn SE, Kim S, Hahn CG, et al. Serotonin transporter gene polymorphism and antidepressant response. Neuroreport 2000; 11: 215-219.

  • 20.

    Yoshida K, Ito K, Sato K, Takahashi H, Kamata M, Higuchi H, et al. Influence of the serotonin transporter gene-linked polymorphic region on the antidepressant response to fluvoxamine in Japanese depressed patients. Prog Neuropsychopharmacol Biol Psychiatry 2002; 26: 383-386.

  • 21.

    Bousman CA, Sarris J, Won ES, Chang HS, Singh A, Lee HY, et al. Escitalopram efficacy in depression: a cross-ethnicity examination of the serotonin transporter promoter polymorphism. J Clin Psychopharmacol 2014; 34: 645-648.

  • 22.

    Ogilvie AD, Battersby S, Fink G, Harmar A, Goodwin G, Bubb V, et al. Polymorphism in serotonin transporter gene associated with susceptibility to major depression. Lancet 1996; 347: 731-733.

  • 23.

    Ito K, Yoshida K, Sato K, Takahashi H, Kamata M, Higuchi H, et al. A variable number of tandem repeats in the serotonin transporter gene does not affect the antidepressant response to fluvoxamine. Psychiatry Res 2002; 111: 235-239.

  • 24.

    Hu XZ, Rush AJ, Charney D, Wilson AF, Sorant AJ, Papanicolaou GJ, et al. Association between a functional serotonin transporter promoter polymorphism and citalopram treatment in adult outpatients with major depression. Arch Gen Psychiatry 2007; 64: 783-792.

  • 25.

    Mrazek D, Rush A, Biernacka JM, O'Kane D, Cunningham JM, Wieben ED, et al. SLC6A4 variation and citalopram response. Am J Med Genet 2009; 150: 341-351.

  • 26.

    Staeker J, Leucht S, Laika B, Steimer W. Polymorphisms in serotonergic pathways influence the outcome of antidepressant therapy in psychiatric inpatients. Genet Test Mol Biomarkers 2014; 18: 20-31.

  • 27.

    Stanley M, Mann JJ. Increased serotonin-2 binding sites in frontal cortex of suicide victims. Lancet 1983; 321: 214-216.

  • 28.

    Meyer JH, Kapur S, Eisfeld B, Brown GM, Houle S, DaSilva J, et al. The effect of paroxetine on 5-HT2A receptors in depression: an [18F] setoperone PET imaging study. Am J Psychiatry 2001; 158: 78-85.

  • 29.

    Choi MJ, Kang RH, Ham BJ, Jeong HY, Lee MS. Serotonin receptor 2A gene polymorphism (-1438A/G) and short-term treatment response to citalopram. Neuropsychobiology 2005; 52: 155-162.

  • 30.

    Minov C, Baghai TC, Schle C, Zwanzger P, Schwarz MJ, Zill P, et al. Serotonin-2A-receptor and-transporter polymorphisms: lack of association in patients with major depression. Neurosci Lett 2001; 303: 119-122.

  • 31.

    Kato M, Fukuda T, Wakeno M, Fukuda K, Okugawa G, Ikenaga Y, et al. Effects of the serotonin type 2A, 3A and 3B receptor and the serotonin transporter genes on paroxetine and fluvoxamine efficacy and adverse drug reactions in depressed Japanese patients. Neuropsychobiology 2006; 53: 186-195.

  • 32.

    McMahon FJ, Buervenich S, Charney D, Lipsky R, Rush AJ, Wilson AF, et al. Variation in the gene encoding the serotonin 2A receptor is associated with outcome of antidepressant treatment. Am J Hum Genet 2006; 78: 804-814.

  • 33.

    Lesser IM, Castro DB, Gaynes BN, Gonzalez J, Rush AJ, Alpert JE, et al. Ethnicity/race and outcome in the treatment of depression: results from STAR* D. Medical Care 2007; 1043-1051.

  • 34.

    Lucae S, Ising M, Horstmann S, Baune BT, Arolt V, Mller-Myhsok B, et al. HTR2A gene variation is involved in antidepressant treatment response. Eur Neuropsychopharmacol 2010; 20: 65-68.

  • 35.

    Lin JY, Jiang MY, Kan ZM, Chu Y. Influence of 5-HTR2A genetic polymorphisms on the efficacy of antidepressants in the treatment of major depressive disorder: a meta-analysis. J Affect Disord 2014; 168: 430-438.

  • 36.

    Rotondo A, Nielsen DA, Nakhai B, Hulihan-Giblin B, Bolos A, Goldman D. Agonist-promoted down-regulation and functional desensitization in two naturally occurring variants of the human serotonin 1A receptor. Neuropsychopharmacology 1997; 17: 18-26.

  • 37.

    Artigas F, Romero L, de Montigny C, Blier P. Acceleration of the effect of selected antidepressant drugs in major depression by 5-HT1A antagonists. Trends Neurosci 1996; 19: 378-383.

  • 38.

    Prez V, Gilaberte I, Faries D, Alvarez E, Artigas F. Randomised, double-blind, placebo-controlled trial of pindolol in combination with fluoxetine antidepressant treatment. Lancet 1997; 349: 1594-1597.

  • 39.

    Zanardi R, Artigas F, Franchini L, Sforzini L, Gasperini M, Smeraldi E, et al. How long should pindolol be associated with paroxetine to improve the antidepressant response? J Clin Psychopharmacol 1997; 17: 446-450.

  • 40.

    Lemonde S, Turecki G, Bakish D, Du L, Hrdina PD, Bown CD, et al. Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. J Neurosci 2003; 23: 8788-8799.

  • 41.

    Lemonde S, Du L, Bakish D, Hrdina P, Albert PR. Association of the C ( 1019) G 5-HT1A functional promoter polymorphism with antidepressant response. Int J Neuropsychopharmacol 2004; 7: 501-506.

  • 42.

    Yu YW, Tsai SJ, Liou YJ, Hong CJ, Chen TJ. Association study of two serotonin 1A receptor gene polymorphisms and fluoxetine treatment response in Chinese major depressive disorders. Eur Neuropsychopharmacol 2006; 16: 498-503.

  • 43.

    Baune B, Hohoff C, Roehrs T, Deckert J, Arolt V, Domschke K. Serotonin receptor 1A 1019C/G variant: Impact on antidepressant pharmacoresponse in melancholic depression? Neurosci Lett 2008; 436: 111-115.

  • 44.

    Levin GM, Bowles TM, Ehret MJ, Langaee T, Tan JY, Johnson JA, et al. Assessment of human serotonin 1A receptor polymorphisms and SSRI responsiveness. Mol Diagn Ther 2007; 11: 155-160.

  • 45.

    Arias B, Cataln R, Gast C, Gutirrez B, Faans L. Evidence for a combined genetic effect of the 5-HT1A receptor and serotonin transporter genes in the clinical outcome of major depressive patients treated with citalopram. J Psychopharmacol 2005; 19: 166-172.

  • 46.

    Suzuki Y, Sawamura K, Someya T. The effects of a 5-hydroxytryptamine 1A receptor gene polymorphism on the clinical response to fluvoxamine in depressed patients. Pharmacogenomics J 2004; 4: 283-286.

  • 47.

    Garfield LD, Dixon D, Nowotny P, Lotrich FE, Pollock BG, Kristjansson SD, et al. Common selective serotonin reuptake inhibitor side effects in older adults associated with genetic polymorphisms in the serotonin transporter and receptors: data from a randomized controlled trial. Am J Geriatr Psychiatry 2014; 22: 971-979.

  • 48.

    Hashimoto K, Sawa A, Iyo M. Increased levels of glutamate in brains from patients with mood disorders. Biol Psychiatry 2007; 62: 1310-1316.

  • 49.

    Bobula B, Tokarski K, Hess G. Repeated administration of antidepressants decreases field potentials in rat frontal cortex. Neuroscience 2003; 120: 765-769.

  • 50.

    Paddock S, Laje G, Charney D, Rush AJ, Wilson AF, Sorant AJ, et al. Association of GRIK4 with outcome of antidepressant treatment in the STAR* D cohort. Am J Psychiatry 2007; 164: 1181-1188.

  • 51.

    Kawaguchi DM, Glatt SJ. GRIK4 polymorphism and its association with antidepressant response in depressed patients: a meta-analysis. Pharmacogenomics 2014; 15: 1451-1459.

  • 52.

    Perlis RH, Fijal B, Dharia S, Heinloth AN, Houston JP. Failure to replicate genetic associations with antidepressant treatment response in duloxetine-treated patients. Biol Psychiatry 2010; 67: 1110-1113.

  • 53.

    Creese I, Burt DR, Snyder SH. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 1976; 192: 481-483.

  • 54.

    Uchida H, Takeuchi H, Graff-Guerrero A, Suzuki T, Watanabe K, Mamo DC. Dopamine D2 receptor occupancy and clinical effects: a systematic review and pooled analysis. J Clin Psychopharmacol 2011; 31: 497-502.##https://doi.org/10.1097/JCP.0b013e3182214aad.

  • 55.

    Kapur S, Zipursky R, Jones C, Remington G, Houle S. Relationship between dopamine D2 occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. Am J Psychiatry 2000; 157: 514-520.

  • 56.

    Mamo D, Kapur S, Shammi CM, Papatheodorou G, Mann S, Therrien F, et al. A PET study of dopamine D2 and serotonin 5-HT2 receptor occupancy in patients with schizophrenia treated with therapeutic doses of ziprasidone. Am J Psychiatry 2004; 161: 818-825.

  • 57.

    Stone JM, Davis JM, Leucht S, Pilowsky LS. Cortical dopamine D2/D3 receptors are a common site of action for antipsychotic drugs-an original patient data meta-analysis of the SPECT and PET in vivo receptor imaging literature. Schizophr Bull 2009; 35: 789-797.

  • 58.

    Arinami T, Gao M, Hamaguchi H, Toru M. A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia. Hum Mol Genet 1997; 6: 577-582.

  • 59.

    Jnsson E, Nthen M, Grnhage F, Farde L, Nakashima Y, Propping P, et al. Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers. Mol Psychiatry 1999; 4: 290-296.

  • 60.

    Lencz T, Robinson DG, Xu K, Ekholm J, Sevy S, Gunduz-Bruce H, et al. DRD2 promoter region variation as a predictor of sustained response to antipsychotic medication in first-episode schizophrenia patients. Am J Psychiatry 2006; 163: 529-531.

  • 61.

    Wu S, Xing Q, Gao R, Li X, Gu N, Feng G, et al. Response to chlorpromazine treatment may be associated with polymorphisms of the DRD2 gene in Chinese schizophrenic patients. Neurosci Lett 2005; 376: 1-4.##https://doi.org/10.1016/j.neulet.2004.11.014.

  • 62.

    Suzuki A, Kondo T, Mihara K, Yasui-Furukori N, Ishida M, Furukori H, et al. The 141C Ins/Del polymorphism in the dopamine D2 receptor gene promoter region is associated with anxiolytic and antidepressive effects during treatment with dopamine antagonists in schizophrenic patients. Pharmacogenet Genomics 2001; 11: 545-550.

  • 63.

    Yasui-Furukori N, Tsuchimine S, Saito M, Nakagami T, Sugawara N, Fujii A, et al. Comparing the influence of dopamine D2 polymorphisms and plasma drug concentrations on the clinical response to risperidone. J Clin Psychopharmacol 2011; 31: 633-637.

  • 64.

    Misiak B, Frydecka D, Beszlej JA, Samochowiec A, Tybura P, Jablonski M, et al. Effects of antipsychotic treatment on depressive symptoms with respect to genetic polymorphisms related to dopaminergic and serotoninergic neurotransmission in schizophrenia patients. J Clin Psychopharmacol 2016; 36: 518-520.

  • 65.

    Neville MJ, Johnstone EC, Walton RT. Identification and characterization of ANKK1: a novel kinase gene closely linked to DRD2 on chromosome band 11q23. 1. Hum Mutat 2004; 23: 540-545.

  • 66.

    Thompson J, Thomas N, Singleton A, Piggott M, Lloyd S, Perry E, et al. D2 dopamine receptor gene (DRD2) Taq1 A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele. Pharmacogenetics 1997; 7: 479-484.

  • 67.

    Zhang Y, Bertolino A, Fazio L, Blasi G, Rampino A, Romano R, et al. Polymorphisms in human dopamine D2 receptor gene affect gene expression, splicing, and neuronal activity during working memory. Proc Natl Acad Sci 2007; 104: 20552-20557.

  • 68.

    Schfer M, Rujescu D, Giegling I, Guntermann A, Erfurth A, Bondy B, et al. Association of short-term response to haloperidol treatment with a polymorphism in the dopamine D2 receptor gene. Am J Psychiatry 2001; 158: 802-804.

  • 69.

    Suzuki A, Mihara K, Kondo T, Tanaka O, Nagashima U, Otani K, et al. The relationship between dopamine D2 receptor polymorphism at the Taq1 A locus and therapeutic response to nemonapride, a selective dopamine antagonist, in schizophrenic patients. Pharmacogenet Genomics 2000; 10: 335-341.

  • 70.

    Kwon JS, Kim E, Kang DH, Choi JS, Yu KS, Jang IJ, et al. Taq1A polymorphism in the dopamine D2 receptor gene as a predictor of clinical response to aripiprazole. Eur Neuropsychopharmacol 2008; 18: 897-907.

  • 71.

    Shen YC, Chen SF, Chen CH, Lin CC, Chen SJ, Chen YJ, et al. Effects of DRD2/ANKK1 gene variations and clinical factors on aripiprazole efficacy in schizophrenic patients. J Psychiatr Res 2009; 43: 600-606.

  • 72.

    Yamanouchi Y, Iwata N, Suzuki T, Kitajima T, Ikeda M, Ozaki N. Effect of DRD2, 5-HT2A, and COMT genes on antipsychotic response to risperidone. Pharmacogenomics J 2003; 3: 356-361.

  • 73.

    Reynolds GP, Yao Z, Zhang X, Sun J, Zhang Z. Pharmacogenetics of treatment in first-episode schizophrenia: D3 and 5-HT2C receptor polymorphisms separately associate with positive and negative symptom response. Eur Neuropsychopharmacol 2005; 15: 143-151.

  • 74.

    Lane HY, Lee CC, Chang YC, Lu CT, Huang CH, Chang WH. Effects of dopamine D2 receptor Ser311Cys polymorphism and clinical factors on risperidone efficacy for positive and negative symptoms and social function. Int J Neuropsychopharmacol 2004; 7: 461-470.

  • 75.

    Hwang R, Zai C, Tiwari A, Mller D, Arranz M, Morris A, et al. Effect of dopamine D3 receptor gene polymorphisms and clozapine treatment response: exploratory analysis of nine polymorphisms and meta-analysis of the Ser9Gly variant. Pharmacogenomics J 2010; 10: 200-218.

  • 76.

    Calarge CA, Ellingrod VL, Acion L, Miller DD, Moline J, Tansey MJ, et al. Variants of the dopamine D2 receptor and risperidone-induced hyperprolactinemia in children and adolescents. Pharmacogenet Genomics 2009; 19: 373.

  • 77.

    Fukui N, Suzuki Y, Sugai T, Watanabe J, Ono S, Tsuneyama N, et al. Exploring functional polymorphisms in the dopamine receptor D2 gene using prolactin concentration in healthy subjects. Mol Psychiatry 2011; 16: 356-358.

  • 78.

    Sokoloff P, Diaz J, Foll BL, Guillin O, Leriche L, Bezard E, et al. The dopamine D3 receptor: a therapeutic target for the treatment of neuropsychiatric disorders. CNS Neurol Disord Drug Targets 2006; 5: 25-43.

  • 79.

    Vehof J, Burger H, Wilffert B, Al Hadithy A, Alizadeh BZ, Snieder H. Clinical response to antipsychotic drug treatment: association study of polymorphisms in six candidate genes. Eur Neuropsychopharmacol 2012; 22: 625-631.

  • 80.

    Van Tol HH, Wu CM, Guan HC, Ohara K, Bunzow JR, Civelli O, et al. Multiple dopamine D4 receptor variants in the human population. Nature 1992; 358: 149-152.

  • 81.

    Kohn Y, Ebstein R, Heresco-Levy U, Shapira B, Nemanov L, Gritsenko I, et al. Dopamine D4 receptor gene polymorphisms: relation to ethnicity, no association with schizophrenia and response to clozapine in Israeli subjects. Eur Neuropsychopharmacol 1997; 7: 39-43.

  • 82.

    Rao PA, Pickar D, Gejman PV, Ram A, Gershon ES, Gelernter J. Allelic variation in the D4 dopamine receptor (DRD4) gene does not predict response to clozapine. Arch Gen Psychiatry 1994; 51: 912-917.

  • 83.

    Kaiser R, Tremblay P, Schmider J, Henneken M, Dettling M, Mller-Oerlinghausen B, et al. Serotonin transporter polymorphisms: no association with response to antipsychotic treatment, but associations with the schizoparanoid and residual subtypes of schizophrenia. Mol Psychiatry 2001; 6: 179-185.

  • 84.

    Travis MJ, Busatto GF, Pilowsky LS, Mulligan R, Acton PD, Gacinovic S, et al. 5-HT 2A receptor blockade in patients with schizophrenia treated with risperidone or clozapine. Br J Psychiatry 1998; 173: 236-241.

  • 85.

    Arranz M, Munro J, Sham P, Kirov G, Murray R, Collier D, et al. Meta-analysis of studies on genetic variation in 5-HT2A receptors and clozapine response. Schizophr Res 1998; 32: 93-99.

  • 86.

    Sodhi MS, Arranz M, Curtis D, Ball D, Sham P. Association between clozapine response and allelic variation. Neuroreport 1995; 7: 169-172.

  • 87.

    Arranz MJ, Munro J, Birkett J, Bolonna A, Mancama D, Sodhi M, et al. Pharmacogenetic prediction of clozapine response. Lancet 2000; 355: 1615-1616.

  • 88.

    Levitt P, Ebert P, Mirnics K, Nimgaonkar VL, Lewis DA. Making the case for a candidate vulnerability gene in schizophrenia: convergent evidence for regulator of G-protein signaling 4 (RGS4). Biol Psychiatry 2006; 60: 534-537.

  • 89.

    Talkowski ME, Seltman H, Bassett AS, Brzustowicz LM, Chen X, Chowdari KV, et al. Evaluation of a susceptibility gene for schizophrenia: genotype based meta-analysis of RGS4 polymorphisms from thirteen independent samples. Biol Psychiatry 2006; 60: 152-162.

  • 90.

    Campbell DB, Ebert PJ, Skelly T, Stroup TS, Lieberman J, Levitt P, et al. Ethnic stratification of the association of RGS4 variants with antipsychotic treatment response in schizophrenia. Biol Psychiatry 2008; 63: 32-41.

  • 91.

    Lane HY, Liu YC, Huang CL, Chang YC, Wu PL, Huang CH, et al. RGS4 polymorphisms predict clinical manifestations and responses to risperidone treatment in patients with schizophrenia. J Clin Psychopharmacol 2008; 28: 64-68.

  • 92.

    Kaur H, Jajodia A, Grover S, Baghel R, Gupta M, Jain S, et al. Genetic variations of PIP4K2A confer vulnerability to poor antipsychotic response in severely ill schizophrenia patients. PLoS One 2014; 9: e102556.

  • 93.

    Lane HY, Chang YC, Chiu CC, Chen ML, Hsieh MH, Chang WH. Association of risperidone treatment response with a polymorphism in the 5-HT2A receptor gene. Am J Psychiatry 2002; 159: 1593-1595.

  • 94.

    Lane HY, Hsu SK, Liu YC, Chang YC, Huang CH, Chang WH. Dopamine D3 receptor Ser9Gly polymorphism and risperidone response. J Clin Psychopharmacol 2005; 25: 6-11.

  • 95.

    Bertolino A, Caforio G, Blasi G, De Candia M, Latorre V, Petruzzella V, et al. Interaction of COMT Val108/158 Met genotype and olanzapine treatment on prefrontal cortical function in patients with schizophrenia. Am J Psychiatry 2004; 161: 1798-1805.

  • 96.

    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.

  • 97.

    Huang E, Zai CC, Lisoway A, Maciukiewicz M, Felsky D, Tiwari AK, et al. Catechol-O-methyltransferase Val158Met polymorphism and clinical response to antipsychotic treatment in schizophrenia and schizo-affective disorder patients: a meta-analysis. Int J Neuropsychopharmacol 2016; 19.

  • 98.

    Rajagopal VM, Rajkumar AP, Jacob KS, Jacob M. Gene-gene interaction between DRD4 and COMT modulates clinical response to clozapine in treatment-resistant schizophrenia. Pharmacogenet Genomics 2018; 28: 31-35.

  • 99.

    Serretti A, Artioli P. Predicting Response to Lithium in Mood Disorders. Am J Pharmacogenomics 2003; 3: 17-30.

  • 100.

    Harwood A. Lithium and bipolar mood disorder: the inositol-depletion hypothesis revisited. Mol Psychiatry 2005; 10: 117-126.

  • 101.

    Steeir VM, Lvlie R, Osher Y, Belmaker RH, Berle J, Gulbrandsen AK. The polymorphic inositol polyphosphate 1-phosphatase gene as a candidate for pharmacogenetic prediction of lithium-responsive manic-depressive illness. Pharmacogenet Genomics 1998; 8: 259-268.

  • 102.

    Bremer T, Diamond C, McKinney R, Shehktman T, Barrett TB, Herold C, et al. The pharmacogenetics of lithium response depends upon clinical co-morbidity. Mol Diagn Ther 2007; 11: 161-170.

  • 103.

    Benedetti F, Serretti A, Pontiggia A, Bernasconi A, Lorenzi C, Colombo C, et al. Long-term response to lithium salts in bipolar illness is influenced by the glycogen synthase kinase 3- 50 T/C SNP. Neurosci Lett 2005; 376: 51-55.

  • 104.

    Mitjans M AB, Jimenez E, Goikolea JM, Saiz PA, Garcia-Portilla MP ea. Exploring genetic variability at PI, GSK3, HPA, and glutamatergic pathways in lithium response: association with IMPA2, INPP1, and GSK3B genes. J Clin Psychopharmacol 2015; 35: 600-604.

  • 105.

    Hou L, Heilbronner U, Degenhardt F, Adli M, Akiyama K, Akula N, et al. Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study. Lancet 2016; 387: 1085-1093.##.