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Shad, M. Genetic Testing for Antipsychotic Pharmacotherapy. Encyclopedia. Available online: https://encyclopedia.pub/entry/12461 (accessed on 21 December 2024).
Shad M. Genetic Testing for Antipsychotic Pharmacotherapy. Encyclopedia. Available at: https://encyclopedia.pub/entry/12461. Accessed December 21, 2024.
Shad, Mujeeb. "Genetic Testing for Antipsychotic Pharmacotherapy" Encyclopedia, https://encyclopedia.pub/entry/12461 (accessed December 21, 2024).
Shad, M. (2021, July 26). Genetic Testing for Antipsychotic Pharmacotherapy. In Encyclopedia. https://encyclopedia.pub/entry/12461
Shad, Mujeeb. "Genetic Testing for Antipsychotic Pharmacotherapy." Encyclopedia. Web. 26 July, 2021.
Genetic Testing for Antipsychotic Pharmacotherapy
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This entry is adapted from the peer-reviewed paper 10.3390/bs11070097

Genetic testing is increasingly utilized to identify genetic biomarkers for optimizing the efficacy and tolerability of psychotropic drugs, especially antidepressants. However, genetic testing is also being requested to enhance the effectiveness of antipsychotic drugs, which is especially true for the treatment-refractory schizophrenia population, who frequently experience irrational polypharmacy at high dosages with significant adverse effects, generally without much therapeutic benefit.

genetic testing antipsychotic pharmacotherapy schizophrenia

1. Introduction

Genetic testing is increasingly utilized to identify genetic biomarkers for optimizing the efficacy and tolerability of psychotropic drugs, especially antidepressants. Most clinically meaningful findings have been reported using genetic factors affecting the pharmacokinetics (PKs) of antipsychotic drugs, such as genetic polymorphisms in the drug-metabolizing cytochrome-P450 (CYP) enzymes to identify and/or predict effective and tolerable dosages of an antipsychotic drug. Despite these limitations, PG studies investigating PD genetic factors may be helpful to enhance the effectiveness of antipsychotic drugs with more success in the treatment-refractory population.

2. Pharmacogenetic Studies

The data from PG studies are clinically utilized at the individual level to predict and optimize the response to antipsychotic drugs while preventing or minimizing adverse events. A drug’s response or tolerability can be affected by genetic polymorphisms in PK factors, which determine the concentration of a drug at its site(s) of action, and PD factors, which determine a drug’s response or tolerability at its molecular targets. However, these distinctions are rather arbitrary, as changes in a drug’s concentration at the site of action (i.e., PKs) are always associated with changes in a drug’s efficacy and/or tolerability (i.e., PDs) at its site(s) of action.

2.1. Pharmacokinetic (PK) Genetic Biomarkers

Genetic variance in drug-metabolizing enzymes, such as CYP enzymes, represents most of the PK biomarkers. The genetic polymorphisms of CYP enzymes have produced one of the most replicated and clinically relevant findings in patients who develop adverse effects on routinely administered dosages of an antipsychotic drug. As compared to extensive metabolizers, patients that are ultra-rapid metabolizers require higher doses and those who are intermediate metabolizers require lower doses of drugs that are substrates for this enzyme due to altered elimination. If antipsychotic doses are not corrected for this genetic variance, ultra-rapid metabolizers for CYP2D6 may experience decrease or loss in efficacy and poor metabolizers may develop higher levels of antipsychotic drugs resulting in adverse effects, such as extrapyramidal symptoms (EPS) and hyperprolactinemia [1]. These differences may be explained by small sample sizes and a lower frequency of poor metabolizer alleles for CYP2D6 alleles in these ethnic groups as compared to Caucasians.

Deficient activity of CYP enzyme1A2has also been associated with adverse effects due to an increase in plasma levels of antipsychotic drugs that are substrates for this enzyme, such as clozapine and olanzapine [2][3][4]. In contrast, patients with high inducibility of CYP1A2, as observed with smoking in some patients, may end up with subtherapeutic levels of clozapine and olanzapine [5]. One study associated genetic variance in CYP3A4 activity with the efficacy of risperidone, an antipsychotic drug [6], while other studies produced negative results [7][8]. However, polymorphism in a specific transporter, P-glycoprotein (also known as multiple drug resistance-1 (MDR1) or ATP-binding cassette subfamily B member1 gene [9]) has been correlated with efficacy as well as tolerability of risperidone [10] and clozapine [11].

2.2. Pharmacodynamic (PD) Biomarkers

Antipsychotic efficacy across different antipsychotic drugs has been strongly linked with genetic variance in dopamine-2 receptors (DRD2). Polymorphisms of the promotor regions of DRD2, DRD3, and DRD4 have also been linked with antipsychotic efficacy [12][13][14][15][16]. Another biomarker repeatedly associated with antipsychotic efficacy is catechol-o-methyl transferase (COMT), which primarily metabolizes dopamine [17][18][19][20] This finding was also supported by a meta-analysis [21], which showed that patients with met/met homozygosity were more likely to respond to antipsychotic drugs, especially the newer ones.

Another HTR2A genotype, 1438-A/A, has been correlated with antipsychotic response in various ethnic groups. Lack of antipsychotic efficacy and treatment resistance for negative symptoms were found in a French cohort with 5-HT2A−1438-A Another polymorphism in serotonin receptor, HTR1A (i.e.,5-HT1A−1019G), has been associated with lower antipsychotic efficacy in various ethnic groups [22][23][24]. Although multiple other reports have also observed association between specific PD markers and antipsychotic efficacy, these findings are without replication and questionable clinical utility [25][26][27][28][29][30][31][32][33][34].

Some studies have examined the pharmacogenetics of commonly used antipsychotic drugs, such as clozapine, risperidone, and olanzapine. Several studies have examined dopamine receptor polymorphisms to explain clozapine’s unique efficacy and have found replicated genetic variance in DRD1 [35][36], DRD2 [37][38], DRD3 [39][40], and DRD4 [41][42] to be associated with clozapine efficacy. Association between clozapine’s efficacy and genetic variance in the dopamine transporter protein (DAT) has been supported by one study [43] but not the other [15]. Despite several studies producing negative results with polymorphisms in various serotonin targets [44][45][46][47][48][49][50][51][52][53], the overall data support the critical role of the serotonin system in clozapine’s efficacy.

Risperidone is another second-generation antipsychotic drug, which has shown decreased antipsychotic efficacy in patients with DRD2 Ser311 [54] variant associated with the reduced response at DRD2 receptors [55]. Nevertheless, this relationship between COMT variant and antipsychotic efficacy points towards the importance of dopamine levels in antipsychotic response. However, unlike clozapine, no correlation was reported between risperidone response andDRD4variance [56]. Other genetic findings with risperidone have been in single studies and will not be reviewed here [22][13][57][58][59][60][61][62][63][64][65].

variantD3Ser9Gly [66][67], which has also been associated with antipsychotic efficacy of risperidone and clozapine [66][67]. However, this finding was not replicated in Indian patients [68], suggesting ethnic differences in response. However, once again, this olanzapine response was not associated with HRT2A and HRT2C variants in the Indian population [67][68], highlighting the ethnic differences in antipsychotic response. Glutamate metabotropic receptor-3 polymorphism [69] associated with better olanzapine response in only one study, a positive olanzapine’s response with calcium channel variant, calcium voltage-gated channel subunit alpha1 C, rs1006737 was replicated in two studies [70][71].

Although aripiprazole is classified as one of the newer second-generation antipsychotic drugs, it is the first antipsychotic drug with partial agonist activity at D2 receptors and 5HT1A receptors [72]. A couple of studies have documented an association betweenD2TaqI variants and the efficacy of aripiprazole in Korean and Chinese patients [73][74]. In summary, there is inadequate genetic data to compare clinically meaningful differences in genetically mediated antipsychotic response between different antipsychotic drugs, perhaps with the exception of clozapine.

The genetic data for antipsychotic tolerability is not as consistent as those for antipsychotic efficacy, except for weight gain. The margin for controversial results is much higher than those from the efficacy studies, as documented below.

Thus, the poor metabolizers for CYP2D6 have a higher risk for developing EPS due to increased plasma levels of antipsychotic drugs that are CYP2D6 substrates [75][76][77][78][79][80][81][82][83][84][85][86][7][87][2] The results examining relationship between EPS and DRD3 polymorphisms are also controversial; some studies supported the relationship [7][88][89][90][91][92][93][94][95][96][97], but some did not [98][88][89][99][100][101][102], while some strangely reported paradoxical results [103][104][105]. A couple of studies found a direct association between two variants of dopamine metabolizing enzyme, COMT (G158A and A-278G) and risk for TD [106][107]. [108][88][109] and polymorphisms of dopamine-related enzymes, monoamine oxidase A, and monoamine oxidase B [108][110].

Genetic variance in the serotonergic system has also produced inconsistent results; some reports have documented associations between HRT2A polymorphisms and TD [89][105][111][112], and some have not [98][113][114][115]. , one study produced negative results [103]. No clear associations were observed between EPS and genes involved in oxidation and stress, such as manganese superoxide dismutase [116][117][118], nitric oxide synthase [119][120][121], glutathione S-transferase [122], and glutathione peroxidase [123]. Only marginal associations were reported with polymorphism in nicotinamide adenine dinucleotide phosphate (NADPH), dehydrogenase quinone, nitric oxide synthase 3 [124][125], and glutathione S-transferase μ1 [7].

Although there is not much research investigating the role of genetic variance on antipsychotic-induced hyperprolactinemia, any DRD2 polymorphism that increases the risk for EPS will also increase the risk for hyperprolactinemia, as both adverse effects are mediated by D2R blockade. In this context, one study did report 40% higher prolactin levels in patients with DRD2*A1 allele than those without [126]. Interestingly, this increase in prolactin was also observed with clozapine, which is least likely to increase prolactin levels [126].

Although the genetic mechanisms underlying weight gain due to HTR2C polymorphisms are not completely clear, several HRT2C gene haplotypes have been associated with weight gain and metabolic syndrome [127][128][129][130]. Increased negative feedback due to increased levels of leptin observed in patients with haplotype B may explain the resistance against weight gain [131]. Although a meta-analysis revealed a 100% increase in risk for weight gain in patients with HRT2C -759 C allele [132], there were studies that did not find any correlation between the presence of the -759 C allele and weight gain [133][134][135][136][137]. Genetic variance in other serotonin receptors, such as HRT2A 102-T/C, have also been associated with weight gain, obesity, and lipid levels [127][138][139], except one study [140].

Although earlier studies did find an association between weight gain and genetic variance in DRD2 [138][141] or DRD3 [138], one recent study did observe a positive relationship between weight gain and DRD2 variants rs6277 In addition, a functional promoter region variant in DRD2 was implicated in a study of antipsychotic drug-induced weight gain during early psychosis with minimal prior exposure to antipsychotic drugs [142]. Ins/Del in the DRD2 promoter gene demonstrated substantially more weight gain than noncarriers after 6 weeks of treatment with risperidone or olanzapine. Another study reported an association between an increase in body mass index and a DRD4 variable number tandem repeat allele during antipsychotic treatment [143].

Few studies have reported a significant correlation between genetic polymorphism in melanocortin 4 receptors (MC4R) and antipsychotic-induced weight gain [144][145], which is also supported by a genome-wide association study [146] (Table 1). Genetic variance in other adrenergic receptors, such as 5HT1A, have also been associated with changes in body mass index [147]. Leptin appears to play an important role in mediating antipsychotic drug-induced weight gain, as reflected by the association between a leptin gene variant, −2548-A/G, and weight gain, despite the different direction of these results [148][136][149][150][151]. Results with leptin studies were also inconclusive across various ethnic groups, such as Indians [107] and Germans [130].

Table 1. Genetic biomarkers for antipsychotic response and adverse effects.
Antipsychotic Response
Gene Polymorphism Risk Allele Functional Outcome Clinical Outcome Statistical Significance
DRD2 -141C Ins/Del (rs1799732) Del Decreased DRD2 expression Lower antipsychotic response Odds ratio = 0.65
95% confidence interval = 95% CI: 0.43–0.97 [152]
HTR1A C-1019G G Increased HTR1A expression G/G homozygosity with lesser negative symptom improvement [131][22][23][24] p = 0.003
HTR2A T-102-C (rs6313) C Decreased HTR2A expression C/C homozygosity with lower antipsychotic response Odds ratio = 0.61
95% confidence interval = 0.43–8.5 [153]
COMT Val 158Met Val Faster metabolism resulting in lower levels of dopamine Lower antipsychotic response [21] Odds ratio = 1.37;
95% confidence interval = 1.02–1.85)
Weight Gain
HTR2C C-759T (rs3813929) C Lesser expression of HTR2C receptors [154] >7% weight gain over baseline with C allele Odds ratio = 1.64;
95% confidence interval = 0.73–3.69 in chronic subjects [127][128][129][130];
Odds ratio = 5.40
95% confidence interval = 2.08–14.01 during early psychosis [127][128][129][130].
MC4R Rs489693 A Unknown AA homozygotes gained about 3 kg more weight than other genotypes [146] Odds Ratio (95% confidence interval)
Tardive Dyskinesia
CYP2D6 Presence of at least one dysfunctional alleles One of
3, 4, 5, 6, or 10 alleles		 Decreased CYP2D6 enzyme activity Increased risk for tardive dyskinesia 1.83 95% CI: 1.09–3.08) [75][76][77][78][79][80][81][82][83][84][85][86][7][87][2]
HTR2A T102C C Decreased HTR2A expression and binding Presence of tardive dyskinesia 1.64 95% CI: 1.17–2.32 [155]
DRD2 Taq1A (rs1800497) C, A2 Increased DRD2 receptors and binding Presence of tardive dyskinesia 1.30 95% CI: 1.09–1.55 [156]
Agranulocytosis
HLADQB1 G6672C
(rs1133322494)		 G ? autoimmune effect Clozapine discontinuation due to ANC < 500 cells/mm3 Odds ratio = 16.9 [157]

One study reported a correlation between antipsychotic-induced weight gain and polymorphism in insulin-induced gene 2 [158], but a couple of other studies did not [130][159]. Similarly, the association between guanine nucleotide-binding protein subunit beta-3 polymorphism and weight gain in Indians [68] was not replicated in other ethnic groups, such as Koreans [160], Taiwanese [161], and Caucasians [162]. One study failed to find any association between the histamine-1 receptor gene and antipsychotic-induced weight gain [163]. However, associations have been reported between weight gain and/or metabolic syndrome and apolipoprotein E [164], brain-derived neurotrophic factor [138][165], cannabinoid receptor-1 [166],CYP2D6[138][167], multidrug resistance 1 [137], methylenetetrahydrofolate reductase [168][169], peroxisome proliferator-activated receptor-γ [170], synaptosomal-associated protein25[171], and tumor necrosis factor [172][173].

Agranulocytosis is a rare but severe and potentially lethal adverse effect associated with clozapine use. Pharmacogenetic studies have reported strong associations between polymorphisms in the major histocompatibility complex and clozapine-induced agranulocytosis [174][175][176]. Two cohorts from a clozapine study found significantly high odds ratios (16.9) for agranulocytosis in patients with a human leukocyte antigen (HLA)-DQB1, which is a single-nucleotide polymorphism (i.e., 6672G > C) with high specificity and sensitivity rates [157] (Table 1). However, similar to results from the genetic studies investigating antipsychotic-induced TD, involvement of oxidative genes in bone marrow toxicity has also produced inconsistent results, as reflected by a marginal association with NADPH quinone 2

3. Pharmacogenomic (PGx) Studies

These studies have primarily explored the effects of genetically mediated PD differences in a drug’s response and/or adverse effects through a systematic assessment of genes, their products, and individual variation in gene expression and function. This may be the reason why most GWAS studies with antipsychotic drugs are primarily based on post hoc analyses from a large effectiveness trial, CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) [177][178][179][180][181]. Another GWAS found 20 statistically significant polymorphisms at a single locus near the melanocortin 4 receptor (MC4R) gene associated with weight gain in patients undergoing the first trial with antipsychotic drugs, which is consistent with a region previously identified by large-scale GWAS of obesity in the general population [146].

Antipsychotic treatment in a subset of 738 schizophrenia patients from the CATIE study [180] polymorphisms localized within or close to the genes, ETS homologous factor, solute carrier family 26 member 9 (SLC26A9), DRD2, G protein-coupled receptor 137B, carbohydrate sulfotransferase 8, and interleukin1-alpha (IL1A) was associated with improvements in various neurocognitive domain areas. A significant result was also found for the variant rs286913 in the ETS homologous factor related to the effects of ziprasidone on vigilance.

4. Commercially Available Genetic Assays

These assays offer genetic testing for multiple genetic biomarkers (combinatorial assays) for treatment response and/or tolerability identified in other studies to facilitate the selection of effective psychotropic medications. Although there is no specific genetic assay for antipsychotic drugs, combinatorial genotyping of genetic biomarkers is used to optimize the efficacy and tolerability of antipsychotic drugs, especially in the treatment-refractory population. CYP2C19.AmpliChip™is the only FDA-approved genetic test, which is a microarray-based product to assess the activity of CYP2D6 and CYP2C19 and can be helpful in a large number of psychiatric patients as multiple psychotropic drugs are metabolized by these two CYP enzymes. Following are the major resources and genetic assay companies that offer genetic testing for psychotropic drugs.

The GeneSight®(Myriad Health®, South San Francisco, CA, USA) combinatorial assays provide coverage for about 50 PK alleles, including those for CYP2D6, CYP2C19, CYP2C9, CYP2B6, CYP3A4, and CYP1A2, On the basis of information on these genetic biomarkers, an individualized report is created which divides psychotropic medications into a green bin for recommended use, a yellow bin for use with caution, and a red bin use with extreme caution and frequent monitoring.

GeneceptTMassay (Genomind®) also provides testing for PK biomarkers ( CYP2D6, CYP2C19, CYP3A4) and PD markers, (5HT transporter, 5HT2C receptors, DRD2, COMT, CACNA1C, ANK3, and MTHFR). Like the GeneSight report, each patient’s results are provided to the ordering clinician, along with suggested therapeutic options.

Drug-Metabolizing Enzymes and Transporters (DMET™) Plus Solution is one of the largest commercially available genetic assays for about 2000 PK variants across multiple genes. The DMET™ Plus Solution was developed as a platform to identify genetic variance and has not been tested for its efficacy in enhancing clinical outcomes with psychotropic drugs.

References

  1. Crescenti, A.; Mas, S.; Gasso, P.; Parellada, E.; Bernardo, M.; Lafuente, A. Cyp2d6*3, *4, *5 and *6 polymorphisms and antipsychotic-induced extrapyramidal side-effects in patients receiving antipsychotic therapy. Clin. Exp. Pharmacol. Physiol. 2008, 35, 807–811.
  2. Fu, Y.; Fan, C.H.; Deng, H.H.; Hu, S.H.; Lv, D.P.; Li, L.H.; Wang, J.J.; Lu, X.Q. Association of CYP2D6 and CYP1A2 gene polymorphism with tardive dyskinesia in Chinese schizophrenic patients. Acta Pharmacol. Sin. 2006, 27, 328–332.
  3. Basile, V.S.; Ozdemir, V.; Masellis, M.; Walker, M.L.; Meltzer, H.Y.; Lieberman, J.A.; Potkin, S.G.; Alva, G.; Kalow, W.; Macciardi, F.M.; et al. A functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene: Association with tardive dyskinesia in schizophrenia. Mol. Psychiatry 2000, 5, 410–417.
  4. Tiwari, A.K.; Deshpande, S.N.; Lerer, B.; Nimgaonkar, V.L.; Thelma, B.K. Genetic susceptibility to Tardive Dyskinesia in chronic schizophrenia subjects: V. Association of CYP1A2 1545 C>T polymorphism. Pharm. J. 2007, 7, 305–311.
  5. Kroon, L.A. Drug interactions with smoking. Am. J. Health Syst. Pharm. 2007, 64, 1917–1921.
  6. Du, J.; Zhang, A.; Wang, L.; Xuan, J.; Yu, L.; Che, R.; Li, X.; Gu, N.; Lin, Z.; Feng, G.; et al. Relationship between response to risperidone, plasma concentrations of risperidone and CYP3A4 polymorphisms in schizophrenia patients. J. Psychopharmacol. 2010, 24, 1115–1120.
  7. de Leon, J.; Susce, M.T.; Pan, R.M.; Koch, W.H.; Wedlund, P.J. Polymorphic variations in GSTM1, GSTT1, PgP, CYP2D6, CYP3A5, and dopamine D2 and D3 receptors and their association with tardive dyskinesia in severe mental illness. J. Clin. Psychopharmacol. 2005, 25, 448–456.
  8. Tiwari, A.K.; Deshpande, S.N.; Rao, A.R.; Bhatia, T.; Lerer, B.; Nimgaonkar, V.L.; Thelma, B.K. Genetic susceptibility to tardive dyskinesia in chronic schizophrenia subjects: III. Lack of association of CYP3A4 and CYP2D6 gene polymorphisms. Schizophr. Res. 2005, 75, 21–26.
  9. Xing, Q.; Gao, R.; Li, H.; Feng, G.; Xu, M.; Duan, S.; Meng, J.; Zhang, A.; Qin, S.; He, L. Polymorphisms of the ABCB1 gene are associated with the therapeutic response to risperidone in Chinese schizophrenia patients. Pharmacogenomics 2006, 7, 987–993.
  10. Bozina, N.; Kuzman, M.R.; Medved, V.; Jovanovic, N.; Sertic, J.; Hotujac, L. Associations between MDR1 gene polymorphisms and schizophrenia and therapeutic response to olanzapine in female schizophrenic patients. J. Psychiatr. Res. 2008, 42, 89–97.
  11. Lee, S.T.; Ryu, S.; Kim, S.R.; Kim, M.J.; Kim, S.; Kim, J.W.; Lee, S.Y.; Hong, K.S. Association study of 27 annotated genes for clozapine pharmacogenetics: Validation of preexisting studies and identification of a new candidate gene, ABCB1, for treatment response. J. Clin. Psychopharmacol. 2012, 32, 441–448.
  12. Dahmen, N.; Muller, M.J.; Germeyer, S.; Rujescu, D.; Anghelescu, I.; Hiemke, C.; Wetzel, H. Genetic polymorphisms of the dopamine D2 and D3 receptor and neuroleptic drug effects in schizophrenic patients. Schizophr. Res. 2001, 49, 223–225.
  13. Lencz, T.; Robinson, D.G.; Xu, K.; Ekholm, J.; Sevy, S.; Gunduz-Bruce, H.; Woerner, M.G.; Kane, J.M.; Goldman, D.; Malhotra, A.K. 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.
  14. Cohen, B.M.; Ennulat, D.J.; Centorrino, F.; Matthysse, S.; Konieczna, H.; Chu, H.M.; Cherkerzian, S. Polymorphisms of the dopamine D4 receptor and response to antipsychotic drugs. Psychopharmacology 1999, 141, 6–10.
  15. Szekeres, G.; Keri, S.; Juhasz, A.; Rimanoczy, A.; Szendi, I.; Czimmer, C.; Janka, Z. Role of dopamine D3 receptor (DRD3) and dopamine transporter (DAT) polymorphism in cognitive dysfunctions and therapeutic response to atypical antipsychotics in patients with schizophrenia. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2004, 124, 1–5.
  16. Reynolds, G.P.; 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.
  17. Anttila, S.; Illi, A.; Kampman, O.; Mattila, K.M.; Lehtimaki, T.; Leinonen, E. Interaction between NOTCH4 and catechol-O-methyltransferase genotypes in schizophrenia patients with poor response to typical neuroleptics. Pharmacogenetics 2004, 14, 303–307.
  18. Molero, P.; Ortuno, F.; Zalacain, M.; Patino-Garcia, A. Clinical involvement of catechol-O-methyltransferase polymorphisms in schizophrenia spectrum disorders: Influence on the severity of psychotic symptoms and on the response to neuroleptic treatment. Pharm. J. 2007, 7, 418–426.
  19. Weickert, T.W.; Goldberg, T.E.; Mishara, A.; Apud, J.A.; Kolachana, B.S.; Egan, M.F.; Weinberger, D.R. Catechol-O-methyltransferase val108/158met genotype predicts working memory response to antipsychotic medications. Biol. Psychiatry 2004, 56, 677–682.
  20. Woodward, N.D.; Jayathilake, K.; Meltzer, H.Y. COMT val108/158met genotype, cognitive function, and cognitive improvement with clozapine in schizophrenia. Schizophr. Res. 2007, 90, 86–96.
  21. Huang, E.; Zai, C.C.; Lisoway, A.; Maciukiewicz, M.; Felsky, D.; Tiwari, A.K.; Bishop, J.R.; Ikeda, M.; Molero, P.; Ortuno, F.; 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, pyv132.
  22. Wang, L.; Fang, C.; Zhang, A.; Du, J.; Yu, L.; Ma, J.; Feng, G.; Xing, Q.; He, L. The --1019 C/G polymorphism of the 5-HT(1)A receptor gene is associated with negative symptom response to risperidone treatment in schizophrenia patients. J. Psychopharmacol. 2008, 22, 904–909.
  23. Reynolds, G.P.; Arranz, B.; Templeman, L.A.; Fertuzinhos, S.; San, L. Effect of 5-HT1A receptor gene polymorphism on negative and depressive symptom response to antipsychotic treatment of drug-naive psychotic patients. Am. J. Psychiatry 2006, 163, 1826–1829.
  24. Mössner, R.; Schuhmacher, A.; Kühn, K.U.; Cvetanovska, G.; Rujescu, D.; Zill, P.; Quednow, B.B.; Rietschel, M.; Wölwer, W.; Gaebel, W.; et al. Functional serotonin 1A receptor variant influences treatment response to atypical antipsychotics in schizophrenia. Pharm. Genom. 2009, 19, 91–94.
  25. Strous, R.D.; Greenbaum, L.; Kanyas, K.; Merbl, Y.; Horowitz, A.; Karni, O.; Viglin, D.; Olender, T.; Deshpande, S.N.; Lancet, D.; et al. Association of the dopamine receptor interacting protein gene, NEF3, with early response to antipsychotic medication. Int. J. Neuropsychopharmacol. 2007, 10, 321–333.
  26. Krebs, M.O.; Guillin, O.; Bourdell, M.C.; Schwartz, J.C.; Olie, J.P.; Poirier, M.F.; Sokoloff, P. Brain derived neurotrophic factor (BDNF) gene variants association with age at onset and therapeutic response in schizophrenia. Mol. Psychiatry 2000, 5, 558–562.
  27. Zai, G.; Arnold, P.D.; Burroughs, E.; Richter, M.A.; Kennedy, J.L. Tumor necrosis factor-alpha gene is not associated with obsessive-compulsive disorder. Psychiatr. Genet. 2006, 16, 43–45.
  28. Kampman, O.; Anttila, S.; Illi, A.; Saarela, M.; Rontu, R.; Mattila, K.M.; Leinonen, E.; Lehtimaki, T. Neuregulin genotype and medication response in Finnish patients with schizophrenia. Neuroreport 2004, 15, 2517–2520.
  29. Joober, R.; Benkelfat, C.; Lal, S.; Bloom, D.; Labelle, A.; Lalonde, P.; Turecki, G.; Rozen, R.; Rouleau, G.A. Association between the methylenetetrahydrofolate reductase 677C-->T missense mutation and schizophrenia. Mol. Psychiatry 2000, 5, 323–326.
  30. Hamdani, N.; Tabeze, J.P.; Ramoz, N.; Ades, J.; Hamon, M.; Sarfati, Y.; Boni, C.; Gorwood, P. The CNR1 gene as a pharmacogenetic factor for antipsychotics rather than a susceptibility gene for schizophrenia. Eur. Neuropsychopharmacol. 2008, 18, 34–40.
  31. Mancama, D.; Arranz, M.J.; Munro, J.; Osborne, S.; Makoff, A.; Collier, D.; Kerwin, R. Investigation of promoter variants of the histamine 1 and 2 receptors in schizophrenia and clozapine response. Neurosci. Lett. 2002, 333, 207–211.
  32. Zuo, L.; Luo, X.; Kranzler, H.R.; Lu, L.; Rosenheck, R.A.; Cramer, J.; van Kammen, D.P.; Erdos, J.; Charney, D.S.; Krystal, J.; et al. Association study of DTNBP1 with schizophrenia in a US sample. Psychiatr. Genet. 2009, 19, 292–304.
  33. Souza, R.P.; Ismail, P.; Meltzer, H.Y.; Kennedy, J.L. Variants in the oxytocin gene and risk for schizophrenia. Schizophr. Res. 2010, 121, 279–280.
  34. Souza, R.P.; de Luca, V.; Remington, G.; Lieberman, J.A.; Meltzer, H.Y.; Kennedy, J.L.; Wong, A.H. Glial cell line-derived neurotrophic factor receptor alpha 2 (GFRA2) gene is associated with tardive dyskinesia. Psychopharmacology 2010, 210, 347–354.
  35. Potkin, S.G.; Basile, V.S.; Jin, Y.; Masellis, M.; Badri, F.; Keator, D.; Wu, J.C.; Alva, G.; Carreon, D.T.; Bunney, W.E., Jr.; et al. D1 receptor alleles predict PET metabolic correlates of clinical response to clozapine. Mol. Psychiatry 2003, 8, 109–113.
  36. Hwang, R.; Shinkai, T.; De Luca, V.; Ni, X.; Potkin, S.G.; Lieberman, J.A.; Meltzer, H.Y.; Kennedy, J.L. Association study of four dopamine D1 receptor gene polymorphisms and clozapine treatment response. J. Psychopharmacol. 2007, 21, 718–727.
  37. Hwang, R.; Shinkai, T.; De Luca, V.; Müller, D.J.; Ni, X.; Macciardi, F.; Potkin, S.; Lieberman, J.A.; Meltzer, H.Y.; Kennedy, J.L. Association study of 12 polymorphisms spanning the dopamine D(2) receptor gene and clozapine treatment response in two treatment refractory/intolerant populations. Psychopharmacology 2005, 181, 179–187.
  38. Hwang, R.; Shinkai, T.; Deluca, V.; Macciardi, F.; Potkin, S.; Meltzer, H.Y.; Kennedy, J.L. Dopamine D2 receptor gene variants and quantitative measures of positive and negative symptom response following clozapine treatment. Eur. Neuropsychopharmacol. 2006, 16, 248–259.
  39. Shaikh, S.; Collier, D.A.; Sham, P.C.; Ball, D.; Aitchison, K.; Vallada, H.; Smith, I.; Gill, M.; Kerwin, R.W. Allelic association between a Ser-9-Gly polymorphism in the dopamine D3 receptor gene and schizophrenia. Hum. Genet. 1996, 97, 714–719.
  40. Scharfetter, J.; Chaudhry, H.R.; Hornik, K.; Fuchs, K.; Sieghart, W.; Kasper, S.; Aschauer, H.N. Dopamine D3 receptor gene polymorphism and response to clozapine in schizophrenic Pakastani patients. Eur. Neuropsychopharmacol. 1999, 10, 17–20.
  41. Zhao, A.L.; Zhao, J.P.; Zhang, Y.H.; Xue, Z.M.; Chen, J.D.; Chen, X.G. Dopamine D4 receptor gene exon III polymorphism and interindividual variation in response to clozapine. Int. J. Neurosci. 2005, 115, 1539–1547.
  42. Shaikh, S.; Collier, D.; Kerwin, R.W.; Pilowsky, L.S.; Gill, M.; Xu, W.M.; Thornton, A. Dopamine D4 receptor subtypes and response to clozapine. Lancet 1993, 341, 116.
  43. Xu, M.; Xing, Q.; Li, S.; Zheng, Y.; Wu, S.; Gao, R.; Yu, L.; Guo, T.; Yang, Y.; Liu, J.; et al. Pharacogenetic effects of dopamine transporter gene polymorphisms on response to chlorpromazine and clozapine and on extrapyramidal syndrome in schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry 2010, 34, 1026–1032.
  44. Arranz, M.J.; Bolonna, A.A.; Munro, J.; Curtis, C.J.; Collier, D.A.; Kerwin, R.W. The serotonin transporter and clozapine response. Mol. Psychiatry 2000, 5, 124–125.
  45. Nothen, M.M.; Rietschel, M.; Erdmann, J.; Oberlander, H.; Moller, H.J.; Nober, D.; Propping, P. Genetic variation of the 5-HT2A receptor and response to clozapine. Lancet 1995, 346, 908–909.
  46. Rietschel, M.; Naber, D.; Fimmers, R.; Moller, H.J.; Propping, P.; Nothen, M.M. Efficacy and side-effects of clozapine not associated with variation in the 5-HT2C receptor. Neuroreport 1997, 8, 1999–2003.
  47. Malhotra, A.K.; Goldman, D.; Ozaki, N.; Breier, A.; Buchanan, R.; Pickar, D. Lack of association between polymorphisms in the 5-HT2A receptor gene and the antipsychotic response to clozapine. Am. J. Psychiatry 1996, 153, 1092–1094.
  48. Malhotra, A.K.; Goldman, D.; Ozaki, N.; Rooney, W.; Clifton, A.; Buchanan, R.W.; Breier, A.; Pickar, D. Clozapine response and the 5HT2C Cys23Ser polymorphism. Neuroreport 1996, 7, 2100–2102.
  49. Masellis, M.; Basile, V.S.; Meltzer, H.Y.; Lieberman, J.A.; Sevy, S.; Goldman, D.A.; Hamblin, M.W.; Macciardi, F.M.; Kennedy, J.L. Lack of association between the T-->C 267 serotonin 5-HT6 receptor gene (HTR6) polymorphism and prediction of response to clozapine in schizophrenia. Schizophr. Res. 2001, 47, 49–58.
  50. Masellis, M.; Paterson, A.D.; Badri, F.; Lieberman, J.A.; Meltzer, H.Y.; Cavazzoni, P.; Kennedy, J.L. Genetic variation of 5-HT2A receptor and response to clozapine. Lancet 1995, 346, 1108.
  51. Birkett, J.T.; Arranz, M.J.; Munro, J.; Osbourn, S.; Kerwin, R.W.; Collier, D.A. Association analysis of the 5-HT5A gene in depression, psychosis and antipsychotic response. Neuroreport 2000, 11, 2017–2020.
  52. Gutiérrez, B.; Arranz, M.J.; Huezo-Diaz, P.; Dempster, D.; Matthiasson, P.; Travis, M.; Munro, J.; Osborne, S.; Kerwin, R.W. Novel mutations in 5-HT3A and 5-HT3B receptor genes not associated with clozapine response. Schizophr. Res. 2002, 58, 93–97.
  53. Kaiser, R.; Tremblay, P.B.; Schmider, J.; Henneken, M.; Dettling, M.; Müller-Oerlinghausen, B.; Uebelhack, R.; Roots, I.; Brockmöller, J. 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.
  54. Lane, H.Y.; Lee, C.C.; Chang, Y.C.; Lu, C.T.; Huang, C.H.; Chang, W.H. 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.
  55. Itokawa, M.; Arinami, T.; Toru, M. Advanced research on dopamine signaling to develop drugs for the treatment of mental disorders: Ser311Cys polymorphisms of the dopamine D2-receptor gene and schizophrenia. J. Pharmacol. Sci. 2010, 114, 1–5.
  56. Zalsman, G.; Frisch, A.; Lev-Ran, S.; Martin, A.; Michaelovsky, E.; Bensason, D.; Gothelf, D.; Nahshoni, E.; Tyano, S.; Weizman, A. DRD4 exon III polymorphism and response to risperidone in Israeli adolescents with schizophrenia: A pilot pharmacogenetic study. Eur. Neuropsychopharmacol. J. Eur. Coll. Neuropsychopharmacol. 2003, 13, 183–185.
  57. Ikeda, M.; Yamanouchi, Y.; Kinoshita, Y.; Kitajima, T.; Yoshimura, R.; Hashimoto, S.; O’Donovan, M.C.; Nakamura, J.; Ozaki, N.; Iwata, N. Variants of dopamine and serotonin candidate genes as predictors of response to risperidone treatment in first-episode schizophrenia. Pharmacogenomics 2008, 9, 1437–1443.
  58. 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. Pharm. J. 2003, 3, 356–361.
  59. Lane, H.Y.; Hsu, S.K.; Liu, Y.C.; Chang, Y.C.; Huang, C.H.; Chang, W.H. Dopamine D3 receptor Ser9Gly polymorphism and risperidone response. J. Clin. Psychopharmacol. 2005, 25, 6–11.
  60. Liu, B.C.; Zhang, J.; Wang, L.; Li, X.W.; Wang, Y.; Wei, Z.Y.; Ji, J.; Yang, F.P.; Wan, C.L.; Xu, Y.F.; et al. HTR2C promoter polymorphisms are associated with risperidone efficacy in Chinese female patients. Pharmacogenomics 2010, 11, 685–692.
  61. Gu, B.; Wang, L.; Zhang, A.P.; Ma, G.; Zhao, X.Z.; Li, H.F.; Feng, G.Y.; He, L.; Xing, Q.H. Association between a polymorphism of the HTR3A gene and therapeutic response to risperidone treatment in drug-naive Chinese schizophrenia patients. Pharm. Genom. 2008, 18, 721–727.
  62. Lane, H.Y.; Lin, C.C.; Huang, C.H.; Chang, Y.C.; Hsu, S.K.; Chang, W.H. Risperidone response and 5-HT6 receptor gene variance: Genetic association analysis with adjustment for nongenetic confounders. Schizophr. Res. 2004, 67, 63–70.
  63. Wang, L.; Yu, L.; He, G.; Zhang, J.; Zhang, A.P.; Du, J.; Tang, R.Q.; Zhao, X.Z.; Ma, J.; Xuan, J.K.; et al. Response of risperidone treatment may be associated with polymorphisms of HTT gene in Chinese schizophrenia patients. Neurosci. Lett. 2007, 414, 1–4.
  64. Lane, H.Y.; Liu, Y.C.; Huang, C.L.; Chang, Y.C.; Wu, P.L.; Huang, C.H.; Tsai, G.E. RGS4 polymorphisms predict clinical manifestations and responses to risperidone treatment in patients with schizophrenia. J. Clin. Psychopharmacol. 2008, 28, 64–68.
  65. Wei, Z.; Wang, L.; Xuan, J.; Che, R.; Du, J.; Qin, S.; Xing, Y.; Gu, B.; Yang, L.; Li, H.; et al. Association analysis of serotonin receptor 7 gene (HTR7) and risperidone response in Chinese schizophrenia patients. Prog. Neuropsychopharmacol. Biol. Psychiatry 2009, 33, 547–551.
  66. Staddon, S.; Arranz, M.J.; Mancama, D.; Mata, I.; Kerwin, R.W. Clinical applications of pharmacogenetics in psychiatry. Psychopharmacology 2002, 162, 18–23.
  67. Adams, D.H.; Close, S.; Farmen, M.; Downing, A.M.; Breier, A.; Houston, J.P. Dopamine receptor D3 genotype association with greater acute positive symptom remission with olanzapine therapy in predominately caucasian patients with chronic schizophrenia or schizoaffective disorder. Hum. Psychopharmacol. 2008, 23, 267–274.
  68. Thomas, P.; Srivastava, V.; Singh, A.; Mathur, P.; Nimgaonkar, V.L.; Lerer, B.; Thelma, B.K.; Deshpande, S.N. Correlates of response to Olanzapine in a North Indian Schizophrenia sample. Psychiatry Res. 2008, 161, 275–283.
  69. Bishop, J.R.; Ellingrod, V.L.; Moline, J.; Miller, D. Association between the polymorphic GRM3 gene and negative symptom improvement during olanzapine treatment. Schizophr. Res. 2005, 77, 253–260.
  70. Porcelli, S.; Lee, S.J.; Han, C.; Patkar, A.A.; Serretti, A.; Pae, C.U. CACNA1C gene and schizophrenia: A case-control and pharmacogenetic study. Psychiatr. Genet. 2015, 25, 163–167.
  71. Nyegaard, M.; Demontis, D.; Foldager, L.; Hedemand, A.; Flint, T.J.; Sørensen, K.M.; Andersen, P.S.; Nordentoft, M.; Werge, T.; Pedersen, C.B.; et al. CACNA1C (rs1006737) is associated with schizophrenia. Mol. Psychiatry 2010, 15, 119–121.
  72. Natesan, S.; Kapur, S. Antipsychotic therapy over half a century: A tale of discovery from chlorpromazine to aripiprazole. Natl. Med. J. India 2012, 25, 193–195.
  73. Kwon, J.S.; Kim, E.; Kang, D.H.; Choi, J.S.; Yu, K.S.; Jang, I.J.; Shin, S.G. Taq1A polymorphism in the dopamine D2 receptor gene as a predictor of clinical response to aripiprazole. Eur. Neuropsychopharmacol. 2008, 18, 897–907.
  74. Shen, Y.C.; Chen, S.F.; Chen, C.H.; Lin, C.C.; Chen, S.J.; Chen, Y.J.; Luu, S.U. Effects of DRD2/ANKK1 gene variations and clinical factors on aripiprazole efficacy in schizophrenic patients. J. Psychiatr. Res. 2009, 43, 600–606.
  75. Arthur, H.; Dahl, M.L.; Siwers, B.; Sjoqvist, F. Polymorphic drug metabolism in schizophrenic patients with tardive dyskinesia. J. Clin. Psychopharmacol. 1995, 15, 211–216.
  76. Andreassen, O.A.; MacEwan, T.; Gulbrandsen, A.K.; McCreadie, R.G.; Steen, V.M. Non-functional CYP2D6 alleles and risk for neuroleptic-induced movement disorders in schizophrenic patients. Psychopharmacology 1997, 131, 174–179.
  77. Armstrong, M.; Daly, A.K.; Blennerhassett, R.; Ferrier, N.; Idle, J.R. Antipsychotic drug-induced movement disorders in schizophrenics in relation to CYP2D6 genotype. Br. J. Psychiatry 1997, 1702, 3–26.
  78. Kapitany, T.; Meszaros, K.; Lenzinger, E.; Schindler, S.D.; Barnas, C.; Fuchs, K.; Sieghart, W.; Aschauer, H.N.; Kasper, S. Genetic polymorphisms for drug metabolism (CYP2D6) and tardive dyskinesia in schizophrenia. Schizophr. Res. 1998, 32, 101–106.
  79. Scordo, M.G.; Spina, E.; Romeo, P.; Dahl, M.L.; Bertilsson, L.; Johansson, I.; Sjoqvist, F. CYP2D6 genotype and antipsychotic-induced extrapyramidal side effects in schizophrenic patients. Eur. J. Clin. Pharmacol. 2000, 56, 679–683.
  80. Lam, L.C.; Garcia-Barcelo, M.M.; Ungvari, G.S.; Tang, W.K.; Lam, V.K.; Kwong, S.L.; Lau, B.S.; Kwong, P.P.; Waye, M.M.; Chiu, H.F. Cytochrome P450 2D6 genotyping and association with tardive dyskinesia in Chinese schizophrenic patients. Pharmacopsychiatry 2001, 34, 238–241.
  81. Ellingrod, V.L.; Schultz, S.K.; Arndt, S. Abnormal movements and tardive dyskinesia in smokers and nonsmokers with schizophrenia genotyped for cytochrome P450 2D6. Pharmacotherahy 2002, 22, 1416–1419.
  82. Jaanson, P.; Marandi, T.; Kiivet, R.A.; Vasar, V.; Vaan, S.; Svensson, J.O.; Dahl, M.L. Maintenance therapy with zuclopenthixol decanoate: Associations between plasma concentrations, neurological side effects and CYP2D6 genotype. Psychopharmacology 2002, 162, 67–73.
  83. Nikoloff, D.; Shim, J.C.; Fairchild, M.; Patten, N.; Fijal, B.A.; Koch, W.H.; MacPherson, A.; Flockhart, D.; Yoon, Y.R.; Yoon, J.S.; et al. Association between CYP2D6 genotype and tardive dyskinesia in Korean schizophrenics. Pharm. J. 2020, 2, 400–407.
  84. Inada, T.; Senoo, H.; Iijima, Y.; Yamauchi, T.; Yagi, G. Cytochrome P450 II D6 gene polymorphisms and the neuroleptic-induced extrapyramidal symptoms in Japanese schizophrenic patients. Psychiatr. Genet. 2003, 13, 163–168.
  85. Lohmann, P.L.; Bagli, M.; Krauss, H.; Müller, D.J.; Schulze, T.G.; Fangerau, H.; Ludwig, M.; Barkow, K.; Held, T.; Heun, R.; et al. CYP2D6 polymorphism and tardive dyskinesia in schizophrenic patients. Pharmacopsychiatry 2003, 36, 73–78.
  86. Liou, Y.J.; Wang, Y.C.; Bai, Y.M.; Lin, C.C.; Yu, S.C.; Liao, D.L.; Lin, M.W.; Chen, J.Y.; Lai, I.C. Cytochrome P-450 2D6*10 C188T polymorphism is associated with antipsychotic-induced persistent tardive dyskinesia in Chinese schizophrenic patients. Neuropsychobiology 2004, 49, 167–173.
  87. Patsopoulos, N.A.; Ntzani, E.E.; Zintzaras, E.; Ioannidis, J.P. CYP2D6 polymorphisms and the risk of tardive dyskinesia in schizophrenia: A meta-analysis. Pharmacogenet. Genom. 2005, 15, 151–158.
  88. Srivastava, V.; Varma, P.G.; Prasad, S.; Semwal, P.; Nimgaonkar, V.L.; Lerer, B.; Deshpande, S.N.; Bk, T. Genetic susceptibility to tardive dyskinesia among schizophrenia subjects: IV. Role of dopaminergic pathway gene polymorphisms. Pharmacogenet. Genom. 2006, 16, 111–117.
  89. Lattuada, E.; Cavallaro, R.; Serretti, A.; Lorenzi, C.; Smeraldi, E. Tardive dyskinesia and DRD2, DRD3, DRD4, 5-HT2A variants in schizophrenia: An association study with repeated assessment. Int. J. Neuropsychopharmacol. 2004, 7, 489–493.
  90. Gasso, P.; Mas, S.; Bernardo, M.; Alvarez, S.; Parellada, E.; Lafuente, A. A common variant in DRD3 gene is associated with risperidone-induced extrapyramidal symptoms. Pharm. J. 2009, 9, 404–410.
  91. Steen, V.M.; Lovlie, R.; MacEwan, T.; McCreadie, R.G. Dopamine D3-receptor gene variant and susceptibility to tardive dyskinesia in schizophrenic patients. Mol. Psychiatry 1997, 2, 139–145.
  92. Segman, R.; Neeman, T.; Heresco-Levy, U.; Finkel, B.; Karagichev, L.; Schlafman, M.; Dorevitch, A.; Yakir, A.; Lerner, A.; Shelevoy, A.; et al. Genotypic association between the dopamine D3 receptor and tardive dyskinesia in chronic schizophrenia. Mol. Psychiatry 1999, 4, 247–253.
  93. Lerer, B.; Segman, R.H.; Fangerau, H.; Daly, A.K.; Basile, V.S.; Cavallaro, R.; Aschauer, H.N.; McCreadie, R.G.; Ohlraun, S.; Ferrier, N.; et al. Pharmacogenetics of tardive dyskinesia: Combined analysis of 780 patients supports association with dopamine D3 receptor gene Ser9Gly polymorphism. Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol. 2002, 27, 105–119.
  94. Liao, D.L.; Yeh, Y.C.; Chen, H.M.; Chen, H.; Hong, C.J.; Tsai, S.J. Association between the Ser9Gly polymorphism of the dopamine D3 receptor gene and tardive dyskinesia in Chinese schizophrenic patients. Neuropsychobiology 2001, 44, 95–98.
  95. Woo, S.I.; Kim, J.W.; Rha, E.; Han, S.H.; Hahn, K.H.; Park, C.S.; Sohn, J.W. Association of the Ser9Gly polymorphism in the dopamine D3 receptor gene with tardive dyskinesia in Korean schizophrenics. Psychiatry Clin. Neurosci. 2002, 56, 469–474.
  96. Eichhammer, P.; Albus, M.; Borrmann-Hassenbach, M.; Schoeler, A.; Putzhammer, A.; Frick, U.; Klein, H.E.; Rohrmeier, T. Association of dopamine D3-receptor gene variants with neuroleptic induced akathisia in schizophrenic patients: A generalization of Steen’s study on DRD3 and tardive dyskinesia. Am. J. Med. Genet. 2000, 96, 187–191.
  97. Rizos, E.N.; Nikolaos, S.; Katsantoni, E.; Lazou, V.; Sakellaropoulos, K.; Kastania, A.; Kossida, S.; Chatzigeorgiou, K.-S.; Arsenis, G.; Zerva, L.; et al. Association of the dopamine D3 receptor Ser9Gly and of the serotonin 2C receptor gene polymorphisms with tardive dyskinesia in Greeks with chronic schizophrenic disorder. Psychiatr. Genet. 2009, 19, 106–107.
  98. Al Hadithy, A.F.; Wilffert, B.; Stewart, R.E.; Looman, N.M.; Bruggeman, R.; Brouwers, J.R.; Matroos, G.E.; van Os, J.; Hoek, H.W.; van Harten, P.N. Pharmacogenetics of parkinsonism, rigidity, rest tremor, and bradykinesia in African-Caribbean inpatients: Differences in association with dopamine and serotonin receptors. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 2008, 147B, 890–897.
  99. Mihara, K.; Kondo, T.; Higuchi, H.; Takahashi, H.; Yoshida, K.; Shimizu, T.; Kaneko, S. Tardive dystonia and genetic polymorphisms of cytochrome P4502D6 and dopamine D2 and D3 receptors: A preliminary finding. Am. J. Med. Genet. 2002, 114, 693–695.
  100. Liou, Y.J.; Liao, D.L.; Chen, J.Y.; Wang, Y.C.; Lin, C.C.; Bai, Y.M.; Yu, S.C.; Lin, M.W.; Lai, I.C. Association analysis of the dopamine D3 receptor gene ser9gly and brain-derived neurotrophic factor gene val66met polymorphisms with antipsychotic-induced persistent tardive dyskinesia and clinical expression in Chinese schizophrenic patients. Neuromolecular Med. 2004, 5, 243–251.
  101. Rietschel, M.; Krauss, H.; Müller, D.J.; Schulze, T.G.; Knapp, M.; Marwinski, K.; Maroldt, A.O.; Paus, S.; Grünhage, F.; Propping, P.; et al. Dopamine D3 receptor variant and tardive dyskinesia. Eur. Arch. Psychiatry Clin. Neurosci. 2002, 250, 31–35.
  102. Garcia-Barcelo, M.M.; Lam, L.C.; Ungvari, G.S.; Lam, V.K.; Tang, W.K. Dopamine D3 receptor gene and tardive dyskinesia in Chinese schizophrenic patients. J. Neural. Transm. 2001, 108, 671–677.
  103. Zai, C.C.; Tiwari, A.K.; De Luca, V.; Müller, D.J.; Bulgin, N.; Hwang, R.; Zai, G.C.; King, N.; Voineskos, A.N.; Meltzer, H.Y.; et al. Genetic study of BDNF, DRD3, and their interaction in tardive dyskinesia. Eur. Neuropsychopharmacol. J. Eur. Coll. Neuropsychopharmacol. 2009, 19, 317–328.
  104. Chong, S.A.; Tan, E.C.; Tan, C.H.; Mythily Chan, Y.H. Polymorphisms of dopamine receptors and tardive dyskinesia among Chinese patients with schizophrenia. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2003, 116, 51–54.
  105. Wilffert, B.; Al Hadithy, A.F.; Sing, V.J.; Matroos, G.; Hoek, H.W.; van Os, J.; Bruggeman, R.; Brouwers, J.R.; van Harten, P.N. The role of dopamine D3, 5-HT2A and 5-HT2C receptor variants as pharmacogenetic determinants in tardive dyskinesia in African-Caribbean patients under chronic antipsychotic treatment: Curacao extrapyramidal syndromes study IX. J. Psychopharmacol. 2009, 23, 652–659.
  106. Lafuente, A.; Bernardo, M.; Mas, S.; Crescenti, A.; Aparici, M.; Gasso, P.; Deulofeu, R.; Mane, A.; Catalan, R.; Carne, X. Polymorphism of dopamine D2 receptor (TaqIA, TaqIB, and-141C Ins/Del) and dopamine degradation enzyme (COMT G158A, A-278G) genes and extrapyramidal symptoms in patients with schizophrenia and bipolar disorders. Psychiatry Res. 2008, 161, 131–141.
  107. Srivastava, V.; Deshpande, S.N.; Nimgaonkar, V.L.; Lerer, B.; Thelma, B. Genetic correlates of olanzapine-induced weight gain in schizophrenia subjects from north India: Role of metabolic pathway genes. Pharmacogenomics 2008, 9, 1055–1068.
  108. Gassó, P.; Mas, S.; Crescenti, A.; Alvarez, S.; Parramon, G.; Garcia-Rizo, C.; Parellada, E.; Bernardo, M.; Lafuente, A. Lack of association between antipsychotic-induced extrapyramidal symptoms and polymorphisms in dopamine metabolism and transport genes. Psychiatry Res. 2010, 175, 173–175.
  109. Lafuente, A.; Bernardo, M.; Mas, S.; Crescenti, A.; Aparici, M.; Gasso, P.; Catalan, R.; Mateos, J.J.; Lomeña, F.; Parellada, E. Dopamine transporter (DAT) genotype (VNTR) and phenotype in extrapyramidal symptoms induced by antipsychotics. Schizophr. Res. 2007, 90, 115–122.
  110. Matsumoto, C.; Shinkai, T.; Hori, H.; Ohmori, O.; Nakamura, J. Polymorphisms of dopamine degradation enzyme (COMT and MAO) genes and tardive dyskinesia in patients with schizophrenia. Psychiatry Res. 2004, 127, 1–7.
  111. Tan, E.C.; Chong, S.A.; Mahendran, R.; Dong, F.; Tan, C.H. Susceptibility to neuroleptic-induced tardive dyskinesia and the T102C polymorphism in the serotonin type 2A receptor. Biol Psychiatry 2001, 50, 144–147.
  112. Segman, R.H.; Heresco-Levy, U.; Finkel, B.; Goltser, T.; Shalem, R.; Schlafman, M.; Dorevitch, A.; Yakir, A.; Greenberg, D.; Lerner, A.; et al. Association between the serotonin 2A receptor gene and tardive dyskinesia in chronic schizophrenia. Mol. Psychiatry 2001, 6, 225–229.
  113. Herken, H.; Erdal, M.E.; Boke, O.; Savas, H.A. Tardive dyskinesia is not associated with the polymorphisms of 5-HT2A receptor gene, serotonin transporter gene and catechol-o-methyltransferase gene. Eur. Psychiatry 2003, 18, 77–81.
  114. Deshpande, S.N.; Varma, P.G.; Semwal, P.; Rao, A.R.; Bhatia, T.; Nimgaonkar, V.L.; Lerer, B.; Thelma, B.K.I.I. Serotonin receptor gene polymorphisms and their association with tardive dyskinesia among schizophrenia patients from North India. Psychiatr Genet. 2005, 15, 157–158.
  115. Basile, V.S.; Ozdemir, V.; Masellis, M.; Meltzer, H.Y.; Lieberman, J.A.; Potkin, S.G.; Macciardi, F.M.; Petronis, A.; Kennedy, J.L. Lack of association between serotonin-2A receptor gene (HTR2A) polymorphisms and tardive dyskinesia in schizophrenia. Mol. Psychiatry 2001, 6, 230–234.
  116. Zhang, Z.; Zhang, X.; Hou, G.; Sha, W.; Reynolds, G.P. The increased activity of plasma manganese superoxide dismutase in tardive dyskinesia is unrelated to the Ala-9Val polymorphism. J. Psychiatr. Res. 2002, 36, 317–324.
  117. Pae, C.U.; Kim, T.S.; Patkar, A.A.; Kim, J.J.; Lee, C.U.; Lee, S.J.; Jun, T.Y.; Lee, C.; Paik, I.H. Manganese superoxide dismutase (MnSOD: Ala-9Val) gene polymorphism may not be associated with schizophrenia and tardive dyskinesia. Psychiatry Res. 2007, 153, 77–81.
  118. Liu, H.; Wang, C.; Chen, P.H.; Zhang, B.S.; Zheng, Y.L.; Zhang, C.X.; Meng, H.Q.; Wang, Y.; Chen, D.C.; Xiu, M.H.; et al. Association of the manganese superoxide dismutase gene Ala-9Val polymorphism with clinical phenotypes and tardive dyskinesia in schizophrenic patients. Prog. Neuro Psychopharmacol. Biol. Psychiatry 2010, 34, 692–696.
  119. Wang, Y.C.; Liou, Y.J.; Liao, D.L.; Bai, Y.M.; Lin, C.C.; Yu, S.C.; Chen, J.Y. Association analysis of a neural nitric oxide synthase gene polymorphism and antipsychotics-induced tardive dyskinesia in Chinese schizophrenic patients. J. Neural. Transm. 2004, 111, 623–629.
  120. Shinkai, T.; Ohmori, O.; Matsumoto, C.; Hori, H.; Kennedy, J.L.; Nakamura, J. Genetic association analysis of neuronal nitric oxide synthase gene polymorphism with tardive dyskinesia. Neuromolecular. Med. 2004, 5, 163–170.
  121. Liou, Y.J.; Wang, Y.C.; Lin, C.C.; Bai, Y.M.; Lai, I.C.; Liao, D.L.; Chen, J.Y. Association analysis of NAD(P) Hratioquinone oxidoreductase (NQO1) Pro187Ser genetic polymorphism and tardive dyskinesia in patients with schizophrenia in Taiwan. Int. J. Neuropsychopharmacol. 2005, 8, 483–486.
  122. Shinkai, T.; De Luca, V.; Hwang, R.; Matsumoto, C.; Hori, H.; Ohmori, O.; Remington, G.; Meltzer, H.Y.; Lieberman, J.A.; Potkin, S.G.; et al. Association study between a functional glutathione S-transferase (GSTP1) gene polymorphism (Ile105Val) and tardive dyskinesia. Neurosci. Lett. 2005, 388, 116–120.
  123. Shinkai, T.; Müller, D.J.; De Luca, V.; Shaikh, S.; Matsumoto, C.; Hwang, R.; King, N.; Trakalo, J.; Potapova, N.; Zai, G.; et al. Genetic association analysis of the glutathione peroxidase (GPX1) gene polymorphism (Pro197Leu) with tardive dyskinesia. Psychiatry Res. 2006, 141, 123–128.
  124. Liou, Y.J.; Lai, I.C.; Lin, M.W.; Bai, Y.M.; Lin, C.C.; Liao, D.L.; Chen, J.Y.; Lin, C.Y.; Wang, Y.C. Haplotype analysis of endothelial nitric oxide synthase (NOS3) genetic variants and tardive dyskinesia in patients with schizophrenia. Pharm. Genom. 2006, 16, 151–157.
  125. Pae, C.U.; Yu, H.S.; Kim, J.J.; Lee, C.U.; Lee, S.J.; Jun, T.Y.; Lee, C.; Paik, I.H. Quinone oxidoreductase (NQO1) gene polymorphism (609C/T) may be associated with tardive dyskinesia, but not with the development of schizophrenia. Int. J. Neuropsychopharmacol. 2004, 7, 495–500.
  126. Young, R.M.; Lawford, B.R.; Barnes, M.; Burton, S.C.; Ritchie, T.; Ward, W.K.; Noble, E.P. Prolactin levels in antipsychotic treatment of patients with schizophrenia carrying the DRD2*A1 allele. Br. J. Psychiatry 2004, 1851, 47–151.
  127. Gunes, A.; Melkersson, K.I.; Scordo, M.G.; Dahl, M.L. Association between HTR2C and HTR2A polymorphisms and metabolic abnormalities in patients treated with olanzapine or clozapine. J. Clin. Psychopharmacol. 2009, 29, 65–68.
  128. Mulder, H.; Franke, B.; van der-Beek, A.A.; Arends, J.; Wilmink, F.W.; Scheffer, H.; Egberts, A.C. The association between HTR2C gene polymorphisms and the metabolic syndrome in patients with schizophrenia. J. Clin. Psychopharmacol. 2007, 27, 338–343.
  129. Mulder, H.; Cohen, D.; Scheffer, H.; Gispen-de Wied, C.; Arends, J.; Wilmink, F.W.; Franke, B.; Egberts, A.C. HTR2C gene polymorphisms and the metabolic syndrome in patients with schizophrenia: A replication study. J. Clin. Psychopharmacol. 2009, 29, 16–20.
  130. Opgen-Rhein, C.; Brandl, E.J.; Muller, D.J.; Neuhaus, A.H.; Tiwari, A.K.; Sander, T.; Dettling, M. Association of HTR2C, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample. Pharmacogenomics 2010, 11, 773–780.
  131. Reynolds, G.P.; Hill, M.J.; Kirk, S.L. The 5-HT2C receptor and antipsychoticinduced weight gain-mechanisms and genetics. J. Psychopharmacol. 2006, 20, 15–18.
  132. De Luca, V.; Mueller, D.J.; de Bartolomeis, A.; Kennedy, J.L. Association of the HTR2C gene and antipsychotic induced weight gain: A meta-analysis. Int. J. Neuropsychopharmacol. 2007, 10, 697–704.
  133. Tsai, S.J.; Hong, C.J.; Yu, Y.W.; Lin, C.H. −759C/T genetic variation of 5HT2C receptor and clozapine-induced weight gain. Lancet 2002, 360, 1790.
  134. Theisen, F.M.; Hinney, A.; Bromel, T.; Heinzel-Gutenbrunner, M.; Martin, M.; Krieg, J.C.; Remschmidt, H.; Hebebrand, J. Lack of association between the −759C/T polymorphism of the 5-HT2C receptor gene and clozapine-induced weight gain among German schizophrenic individuals. Psychiatr. Genet. 2004, 14, 139–142.
  135. Park, Y.M.; Cho, J.H.; Kang, S.G.; Choi, J.E.; Lee, S.H.; Kim, L.; Lee, H.J. Lack of association between the −759C/T polymorphism of the 5-HT2C receptor gene and olanzapine-induced weight gain among Korean schizophrenic patients. J. Clin. Pharm. Ther. 2008, 33, 55–60.
  136. Yevtushenko, O.O.; Cooper, S.J.; O’Neill, R.; Doherty, J.K.; Woodside, J.V.; Reynolds, G.P. Influence of 5-HT2C receptor and leptin gene polymorphisms, smoking and drug treatment on metabolic disturbances in patients with schizophrenia. Br. J. Psychiatry 2008, 192, 424–428.
  137. Kuzman, M.R.; Medved, V.; Bozina, N.; Hotujac, L.; Sain, I.; Bilusic, H. The influence of 5-HT2C and MDR1 genetic polymorphisms on antipsychotic-induced weight gain in female schizophrenic patients. Psychiatry Res. 2008, 160, 308–315.
  138. Lane, H.Y.; Liu, Y.C.; Huang, C.L.; Chang, Y.C.; Wu, P.L.; Lu, C.T.; Chang, W.H. Risperidone-related weight gain: Genetic and nongenetic predictors. J. Clin. Psychopharmacol. 2006, 26, 128–134.
  139. Al-Janabi, I.; Arranz, M.J.; Blakemore, A.I.; Saiz, P.A.; Susce, M.T.; Glaser, P.E.; Clark, D.; de Leon, J. Association study of serotonergic gene variants with antipsychotic-induced adverse reactions. Psychiatr. Genet. 2009, 19, 305–311.
  140. Hong, C.J.; Lin, C.H.; Yu, Y.W.; Yang, K.H.; Tsai, S.J. Genetic variants of the serotonin system and weight change during clozapine treatment. Pharmacogenetics 2001, 11, 265–268.
  141. Zhang, Z.J.; Yao, Z.J.; Zhang, X.B.; Chen, J.F.; Sun, J.; Yao, H.; Hou, G.; Zhang, X.B. No association of antipsychotic agent-induced weight gain with a DA receptor gene polymorphism and therapeutic response. Acta Pharmacol. Sin. 2003, 24, 235–240.
  142. Lencz, T.; Robinson, D.G.; Napolitano, B.; Sevy, S.; Kane, J.M.; Goldman, D.; Malhotra, A.K. DRD2 promoter region variation predicts antipsychotic-induced weight gain in first episode schizophrenia. Pharmacogenet. Genom. 2010, 20, 569–572.
  143. Popp, J.; Leucht, S.; Heres, S.; Steimer, W. DRD4 48 bp VNTR but not 5-HT2C Cys23Ser receptor polymorphism is related to antipsychotic-induced weight gain. Pharmacogenom. J. 2009, 9, 71–77.
  144. Chowdhury, N.I.; Tiwari, A.K.; Souza, R.P.; Zai, C.C.; Shaikh, S.A.; Chen, S.; Liu, F.; Lieberman, J.A.; Meltzer, H.Y.; Malhotra, A.K.; et al. Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene. Pharm. J. 2013, 13, 272–279.
  145. Czerwensky, F.; Leucht, S.; Steimer, W. MC4R rs489693: A clinical risk factor for second generation antipsychotic-related weight gain? Int. J. Neuropsychopharmacol. 2013, 16, 2103–2109.
  146. Malhotra, A.K.; Correll, C.U.; Chowdhury, N.I.; Müller, D.J.; Gregersen, P.K.; Lee, A.T.; Tiwari, A.K.; Kane, J.M.; Fleischhacker, W.W.; Kahn, R.S.; et al. Association between common variants near the melanocortin 4 receptor gene and severe antipsychotic drug-induced weight gain. Arch. Gen. Psychiatry 2012, 69, 904–912.
  147. Liu, Y.R.; Loh, E.W.; Lan, T.H.; Chen, S.F.; Yu, Y.H.; Chang, Y.H.; Huang, C.J.; Hu, T.M.; Lin, K.M.; Yao, Y.T.; et al. ADRA1A gene is associated with BMI in chronic schizophrenia patients exposed to antipsychotics. Pharm. J. 2010, 10, 30–39.
  148. Templeman, L.A.; Reynolds, G.P.; Arranz, B.; San, L. Polymorphisms of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a first-episode psychosis. Pharmacogenet. Genom. 2005, 15, 195–200.
  149. Calarge, C.A.; Ellingrod, V.L.; Zimmerman, B.; Acion, L.; Sivitz, W.I.; Schlechte, J.A. Leptin gene −2548G/A variants predict risperidone-associated weight gain in children and adolescents. Psychiatr. Genet. 2009, 19, 320–327.
  150. Zhang, X.Y.; Tan, Y.L.; Zhou, D.F.; Haile, C.N.; Cao, L.Y.; Xu, Q.; Shen, Y.; Kosten, T.A.; Kosten, T.R. Association of clozapine-induced weight gain with a polymorphism in the leptin promoter region in patients with chronic schizophrenia in a Chinese population. J. Clin. Psychopharmacol. 2007, 27, 246–251.
  151. Kang, S.G.; Lee, H.J.; Park, Y.M.; Choi, J.E.; Han, C.; Kim, Y.K.; Kim, S.H.; Lee, M.S.; Joe, S.H.; Jung, I.K.; et al. Possible association between the -2548A/G polymorphism of the leptin gene and olanzapine-induced weight gain. Prog. Neuro Psychopharmacol. Biol. Psychiatry 2008, 32, 160–163.
  152. Zhang, J.P.; Lencz, T.; Malhotra, A.K. D2 receptor genetic variation and clinical response to antipsychotic drug treatment: A meta-analysis. Am. J. Psychiatry 2010, 167, 763–772.
  153. Arranz, M.J.; Munro, J.; Sham, P.; Kirov, G.; Murray, R.M.; Collier, D.A.; Kerwin, R.W. Meta-analysis of studies on genetic variation in 5-HT2A receptors and clozapine response. Schizophr. Res. 1998, 32, 93–99.
  154. Buckland, P.R.; Hoogendoorn, B.; Guy, C.A.; Smith, S.K.; Coleman, S.L.; O’Donovan, M.C. Low gene expression conferred by association of an allele of the 5-HT2C receptor gene with antipsychotic-induced weight gain. Am. J. Psychiatry 2005, 162, 613–615.
  155. Lerer, B.; Segman, R.H.; Tan, E.C.; Basile, V.S.; Cavallaro, R.; Aschauer, H.N.; Strous, R.; Chong, S.A.; Heresco-Levy, U.; Verga, M.; et al. Combined analysis of 635 patients confirms an age-related association of the serotonin 2A receptor gene with tardive dyskinesia and specificity for the non-orofacial subtype. Int. J. Neuropsychopharmacol. 2005, 8, 411–425.
  156. Zai, C.C.; De Luca, V.; Hwang, R.W.; Voineskos, A.; Muller, D.J.; Remington, G.; Kennedy, J.L. Meta-analysis of two dopamine D2 receptor gene polymorphisms with tardive dyskinesia in schizophrenia patients. Mol. Psychiatry 2007, 12, 794–795.
  157. Athanasiou, M.C.; Dettling, M.; Cascorbi, I.; Mosyagin, I.; Salisbury, B.A.; Pierz, K.A.; Zou, W.; Whalen, H.; Malhotra, A.K.; Lencz, T.; et al. Candidate gene analysis identifies a polymorphism in HLA-DQB1 associated with clozapine-induced agranulocytosis. J. Clin. Psychiatry 2011, 72, 458–463.
  158. Le Hellard, S.; Theisen, F.M.; Haberhausen, M.; Raeder, M.B.; Fernø, J.; Gebhardt, S.; Hinney, A.; Remschmidt, H.; Krieg, J.C.; Mehler-Wex, C.; et al. Association between the insulin-induced gene 2 (INSIG2) and weight gain in a German sample of antipsychotic-treated schizophrenic patients: Perturbation of SREBP-controlled lipogenesis in drug-related metabolic adverse effects? Mol. Psychiatry 2009, 14, 308–317.
  159. Tiwari, A.K.; Zai, C.C.; Meltzer, H.Y.; Lieberman, J.A.; Muller, D.J.; Kennedy, J.L. Association study of polymorphisms in insulin induced gene 2 (INSIG2) with antipsychotic-induced weight gain in European and African-American schizophrenia patients. Hum. Psychopharmacol. 2010, 25, 253–259.
  160. Park, Y.M.; Chung, Y.C.; Lee, S.H.; Lee, K.J.; Kim, H.; Choi, J.E.; Kang, S.G.; Lee, M.S.; Kim, L.; Lee, H.J. G-protein beta3 Subunit Gene 825C/T Polymorphism Is Not Associated with Olanzapine-Induced Weight Gain in Korean Schizophrenic Patients. Psychiatry Investig. 2009, 6, 39–43.
  161. Tsai, S.J.; Yu, Y.W.; Lin, C.H.; Wang, Y.C.; Chen, J.Y.; Hong, C.J. Association study of adrenergic beta3 receptor (Trp64Arg) and G-protein beta3 subunit gene (C825T) polymorphisms and weight change during clozapine treatment. Neuropsychobiology 2004, 50, 37–40.
  162. Bishop, J.R.; Ellingrod, V.L.; Moline, J.; Miller, D. Pilot study of the G-protein beta3 subunit gene (C825T) polymorphism and clinical response to olanzapine or olanzapine-related weight gain in persons with schizophrenia. Med. Sci. Monit. 2006, 12, 47–50.
  163. Hong, C.J.; Lin, C.H.; Yu, Y.W.; Chang, S.C.; Wang, S.Y.; Tsai, S.J. Genetic variant of the histamine-1 receptor (glu349asp) and body weight change during clozapine treatment. Psychiatr. Genet. 2002, 12, 169–171.
  164. Clark, D.; Skrobot, O.A.; Adebiyi, I.; Susce, M.T.; de Leon, J.; Blakemore, A.F.; Arranz, M.J. Apolipoprotein-E gene variants associated with cardiovascular risk factors in antipsychotic recipients. Eur. Psychiatry 2009, 24, 456–463.
  165. Zhang, X.Y.; Zhou, D.F.; Wu, G.Y.; Cao, L.Y.; Tan, Y.L.; Haile, C.N.; Li, J.; Lu, L.; Kosten, T.A.; Kosten, T.R. BDNF levels and genotype are associated with antipsychotic-induced weight gain in patients with chronic schizophrenia. Neuropsychopharmacology 2008, 33, 2200–2205.
  166. Tiwari, A.K.; Zai, C.C.; Likhodi, O.; Lisker, A.; Singh, D.; Souza, R.P.; Batra, P.; Zaidi, S.H.; Chen, S.; Liu, F.; et al. A common polymorphism in the cannabinoid receptor 1 (CNR1) gene is associated with antipsychotic-induced weight gain in Schizophrenia. Neuropsychopharmacology 2010, 35, 1315–1324.
  167. Ellingrod, V.L.; Miller, D.; Schultz, S.K.; Wehring, H.; Arndt, S. CYP2D6 polymorphisms and atypical antipsychotic weight gain. Psychiatr. Genet. 2002, 12, 55–58.
  168. Ellingrod, V.L.; Miller, D.D.; Taylor, S.F.; Moline, J.; Holman, T.; Kerr, J. Metabolic syndrome and insulin resistance in schizophrenia patients receiving antipsychotics genotyped for the methylenetetrahydrofolate reductase (MTHFR) 677C/T and 1298A/C variants. Schizophr. Res. 2008, 98, 47–54.
  169. van Winkel, R.; Rutten, B.P.; Peerbooms, O.; Peuskens, J.; van Os, J.; De Hert, M. MTHFR and risk of metabolic syndrome in patients with schizophrenia. Schizophr. Res. 2010, 121, 193–198.
  170. Herken, H.; Erdal, M.; Aydin, N.; Sengul, C.; Karadag, F.; Barlas, O.; Akin, F. The association of olanzapine-induced weight gain with peroxisome proliferator-activated receptor-gamma2 Pro12Ala polymorphism in patients with schizophrenia. DNA Cell. Biol. 2009, 28, 515–519.
  171. Muller, D.J.; Klempan, T.A.; De Luca, V.; Sicard, T.; Volavka, J.; Czobor, P.; Sheitman, B.B.; Lindenmayer, J.P.; Citrome, L.; McEvoy, J.P.; et al. The SNAP-25 gene may be associated with clinical response and weight gain in antipsychotic treatment of schizophrenia. Neurosci. Lett. 2005, 379, 81–89.
  172. Basile, V.S.; Masellis, M.; McIntyre, R.S.; Meltzer, H.Y.; Lieberman, J.A.; Kennedy, J.L. Genetic dissection of atypical antipsychotic-induced weight gain: Novel preliminary data on the pharmacogenetic puzzle. J. Clin. Psychiatry 2001, 62, 5–66.
  173. Wang, Y.C.; Bai, Y.M.; Chen, J.Y.; Lin, C.C.; Lai, I.C.; Liou, Y.J. Genetic association between TNF-alpha −308 G>A polymorphism and longitudinal weight change during clozapine treatment. Hum. Psychopharmacol. 2010, 25, 303–309.
  174. Amar, A.; Segman, R.H.; Shtrussberg, S.; Sherman, L.; Safirman, C.; Lerer, B.; Brautbar, C. An association between clozapine-induced agranulocytosis in schizophrenics and HLA-DQB1*0201. Int. J. Neuropsychopharmacol. 1998, 1, 41–44.
  175. Valevski, A.; Klein, T.; Gazit, E.; Meged, S.; Stein, D.; Elizur, A.; Narinsky, E.R.; Kutzuk, D.; Weizman, A. HLA-B38 and clozapine-induced agranulocytosis in Israeli Jewish schizophrenic patients. Eur. J. Immunogenet. 1998, 25, 11–13.
  176. Dettling, M.; Schaub, R.T.; Mueller-Oerlinghausen, B.; Roots, I.; Cascorbi, I. Further evidence of human leukocyte antigen-encoded susceptibility to clozapine-induced agranulocytosis independent of ancestry. Pharmacogenetics 2001, 11, 135–141.
  177. Aberg, K.; Adkins, D.E.; Bukszar, J.; Webb, B.T.; Caroff, S.N.; Miller, D.D.; Sebat, J.; Stroup, S.; Fanous, A.H.; Vladimirov, V.I.; et al. Genomewide association study of movement-related adverse antipsychotic effects. Biol. Psychiatry. 2010, 67, 279–282.
  178. Adkins, D.E.; Aberg, K.; McClay, J.L.; Bukszár, J.; Zhao, Z.; Jia, P.; Stroup, T.S.; Perkins, D.; McEvoy, J.P.; Lieberman, J.A.; et al. Genomewide pharmacogenomic study of metabolic side effects to antipsychotic drugs. Mol. Psychiatry 2011, 16, 321–332.
  179. Alkelai, A.; Greenbaum, L.; Rigbi, A.; Kanyas, K.; Lerer, B. Genome-wide association study of antipsychotic-induced parkinsonism severity among schizophrenia patients. Psychopharmacology 2009, 206, 491–499.
  180. Hermes, E.; Nasrallah, H.; Davis, V.; Meyer, J.; McEvoy, J.; Goff, D.; Davis, S.; Stroup, T.S.; Swartz, M.; Lieberman, J.; et al. The association between weight change and symptom reduction in the CATIE schizophrenia trial. Schizophr. Res. 2011, 128, 166–170.
  181. McClay, J.L.; Adkins, D.E.; Aberg, K.; Bukszar, J.; Khachane, A.N.; Keefe, R.S.; Perkins, D.O.; McEvoy, J.P.; Stroup, T.S.; Vann, R.E.; et al. Genome-wide pharmacogenomic study of neurocognition as an indicator of antipsychotic treatment response in schizophrenia. Neuropsychopharmacology 2011, 36, 616–626.
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