Genetics of second-generation antipsychotic and mood stabilizer-induced weight gain in bipolar disorder: Common and specific effects of key regulators of fat-mass homoeostasis genes

Pharmacogenetics and Genomics

Volumn 25, Issue 7, 2015, Pages 354-362

  Creta, Elia ^a   Fabbri, Chiara ^a   Serretti, Alessandro ^a  

^a UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

Antipsychotics; bipolar disorder; fat mass homoeostasis; gene; mood stabilizers; pharmacogenetics; weight gain

Indexed keywords

ALPHA 2A ADRENERGIC RECEPTOR; CLOZAPINE; FTO PROTEIN; GHRELIN; HISTAMINE H1 RECEPTOR; HTR2C PROTEIN; LEPTIN; LITHIUM; MELANOCORTIN 3 RECEPTOR; MELANOCORTIN 4 RECEPTOR; MTHFR PROTEIN; OLANZAPINE; PMCH PROTEIN; PROTEIN; QUETIAPINE; RISPERIDONE; TBC1D1 PROTEIN; UNCLASSIFIED DRUG; VALPROIC ACID; BENZODIAZEPINE DERIVATIVE; NEUROLEPTIC AGENT; PSYCHOTROPIC AGENT;

ADOLESCENT; AGE; ARTICLE; BIPOLAR DISORDER; BODY WEIGHT; CONTROLLED STUDY; FAT MASS; FEMALE; GENETIC ASSOCIATION; GENETIC IDENTIFICATION; GENETIC PREDISPOSITION; HEREDITY; HIGH RISK PATIENT; HOMEOSTASIS; HUMAN; MAJOR CLINICAL STUDY; MALE; PHENOTYPE; PRESCRIPTION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SEX; SIDE EFFECT; SINGLE NUCLEOTIDE POLYMORPHISM; WEIGHT GAIN; ADIPOSE TISSUE; BODY WEIGHT GAIN; DRUG EFFECTS; GENETICS; GENOME-WIDE ASSOCIATION STUDY; PATHOLOGY;

ADIPOSE TISSUE; ANTIPSYCHOTIC AGENTS; BENZODIAZEPINES; BIPOLAR DISORDER; CLOZAPINE; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HOMEOSTASIS; HUMANS; MALE; POLYMORPHISM, SINGLE NUCLEOTIDE; PSYCHOTROPIC DRUGS; WEIGHT GAIN;

EID: 84931071274     PISSN: 17446872     EISSN: 17446880     Source Type: Journal    
DOI: 10.1097/FPC.0000000000000144     Document Type: Article

References (78)

1. Dickerson FB, Brown CH, Kreyenbuhl JA, Fang L, Goldberg RW, Wohlheiter K, Dixon LB. Obesity among individuals with serious mental illness. Acta Psychiatr Scand 2006; 113:306-313.
2. Lee AK, Bishop JR. Pharmacogenetics of leptin in antipsychotic-associated weight gain and obesity-related complications. Pharmacogenomics 2011; 12:999-1016.
3. Wirshing DA. Schizophrenia and obesity: impact of antipsychotic medications. J Clin Psychiatry 2004; 65 (Suppl 18):13-26.
4. Osborn DP, Levy G, Nazareth I, Petersen I, Islam A, King MB. Relative risk of cardiovascular and cancer mortality in people with severe mental illness from the United Kingdom's General Practice Research Database. Arch Gen Psychiatry 2007; 64:242-249.
5. Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, Weiden PJ. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 1999; 156:1686-1696.
6. Kahn RS, Fleischhacker WW, Boter H, Davidson M, Vergouwe Y, Keet IP, et al. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 2008; 371:1085-1097.
7. Nasrallah HA. Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry 2008; 13:27-35.
8. Crettol S, de Leon J, Hiemke C, Eap CB. Pharmacogenomics in psychiatry: from therapeutic drug monitoring to genomic medicine. Clin Pharmacol Ther 2014; 95:254-257.
9. Gebhardt S, Theisen FM, Haberhausen M, Heinzel-Gutenbrunner M, Wehmeier PM, Krieg JC, et al. Body weight gain induced by atypical antipsychotics: an extension of the monozygotic twin and sib pair study. J Clin Pharm Ther 2010; 35:207-211.
10. Baptista T, Teneud L, Contreras Q, Alastre T, Burguera JL, de Burguera M, et al. Lithium and body weight gain. Pharmacopsychiatry 1995; 28:35-44.
11. Biton V, Mirza W, Montouris G, Vuong A, Hammer AE, Barrett PS. Weight change associated with valproate and lamotrigine monotherapy in patients with epilepsy. Neurology 2001; 56:172-177.
12. Chengappa KN, Chalasani L, Brar JS, Parepally H, Houck P, Levine J. Changes in body weight and body mass index among psychiatric patients receiving lithium, valproate, or topiramate: an open-label, nonrandomized chart review. Clin Ther 2002; 24:1576-1584.
13. Davison KM. The relationships among psychiatric medications, eating behaviors, and weight. Eat Behav 2013; 14:187-191.
14. De Bartolomeis A, Avvisati L, Iasevoli F, Tomasetti C. Intracellular pathways of antipsychotic combined therapies: implication for psychiatric disorders treatment. Eur J Pharmacol 2013; 718:502-523.
15. De Bartolomeis A, Tomasetti C, Cicale M, Yuan PX, Manji HK. Chronic treatment with lithium or valproate modulates the expression of Homer1b/c and its related genes Shank and inositol 1, 4, 5-trisphosphate receptor. Eur Neuropsychopharmacol 2012; 22:527-535.
16. Goodwin G, Fleischhacker W, Arango C, Baumann P, Davidson M, de Hert M, et al. Advantages and disadvantages of combination treatment with antipsychotics ECNP Consensus Meeting, March 2008, Nice. Eur Neuropsychopharmacol 2009; 19:520-532.
17. Tomasetti C, Dell'Aversano C, Iasevoli F, Marmo F, de Bartolomeis A. The acute and chronic effects of combined antipsychotic-mood stabilizing treatment on the expression of cortical and striatal postsynaptic density genes. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35:184-197.
18. Reynolds GP, Kirk SL. Metabolic side effects of antipsychotic drug treatment-pharmacological mechanisms. Pharmacol Ther 2010; 125:169-179.
19. Reynolds GP, Zhang ZJ, Zhang XB. Association of antipsychotic druginduced weight gain with a 5-HT2C receptor gene polymorphism. Lancet 2002; 359:2086-2087.
20. Sicard MN, Zai CC, Tiwari AK, Souza RP, Meltzer HY, Lieberman JA, et al. Polymorphisms of the HTR2C gene and antipsychotic-induced weight gain: an update and meta-analysis. Pharmacogenomics 2010; 11:1561-1571.
21. Bonhaus DW, Weinhardt KK, Taylor M, deSouza A, McNeeley PM, Szczepanski K, et al. RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist. Neuropharmacology 1997; 36:621-629.
22. Humbert-Claude M, Davenas E, Gbahou F, Vincent L, Arrang JM. Involvement of histamine receptors in the atypical antipsychotic profile of clozapine: a reassessment in vitro and in vivo. Psychopharmacology (Berl) 2012; 220:225-241.
23. Vehof J, Risselada AJ, Al Hadithy AF, Burger H, Snieder H, Wilffert B, et al. Association of genetic variants of the histamine H1 and muscarinic M3 receptors with BMI and HbA1c values in patients on antipsychotic medication. Psychopharmacology (Berl) 2011; 216:257-265.
24. Torrealba F, Riveros ME, Contreras M, Valdes JL. Histamine and motivation. Front Syst Neurosci 2012; 6:51.
25. Jassim G, Ferno J, Theisen FM, Haberhausen M, Christoforou A, Havik B, et al. Association study of energy homeostasis genes and antipsychoticinduced weight gain in patients with schizophrenia. Pharmacopsychiatry 2011; 44:15-20.
26. Souza RP, Tiwari AK, Chowdhury NI, Ceddia RB, Lieberman JA, Meltzer HY, et al. Association study between variants of AMP-activated protein kinase catalytic and regulatory subunit genes with antipsychotic-induced weight gain. J Psychiatr Res 2012; 46:462-468.
27. Houston JP, Kohler J, Bishop JR, Ellingrod VL, Ostbye KM, Zhao F, et al. Pharmacogenomic associations with weight gain in olanzapine treatment of patients without schizophrenia. J Clin Psychiatry 2012; 73:1077-1086.
28. Muller DJ, Zai CC, Sicard M, Remington E, Souza RP, Tiwari AK, et al. Systematic analysis of dopamine receptor genes (DRD1-DRD5) in antipsychotic-induced weight gain. Pharmacogenomics J 2012; 12:156-164.
29. Brandl EJ, Frydrychowicz C, Tiwari AK, Lett TA, Kitzrow W, Buttner S, et al. Association study of polymorphisms in leptin and leptin receptor genes with antipsychotic-induced body weight gain. Prog Neuropsychopharmacol Biol Psychiatry 2012; 38:134-141.
30. Chowdhury NI, Tiwari AK, Souza RP, Zai CC, Shaikh SA, Chen S, et al. Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene. Pharmacogenomics J 2013; 13:272-279.
31. Czerwensky F, Leucht S, Steimer W. Association of the common MC4R rs17782313 polymorphism with antipsychotic-related weight gain. J Clin Psychopharmacol 2013; 33:74-79.
32. Malhotra AK, Correll CU, Chowdhury NI, Muller DJ, Gregersen PK, Lee AT, 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.
33. Wu R, Zhao J, Shao P, Ou J, Chang M. Genetic predictors of antipsychoticinduced weight gain: a case-matched multi-gene study. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2011; 36:720-723.
34. Girardet C, Butler AA. Neural melanocortin receptors in obesity and related metabolic disorders. Biochim Biophys Acta 2014; 1842:482-494.
35. Tiwari AK, Brandl EJ, Weber C, Likhodi O, Zai CC, Hahn MK, et al. Association of a functional polymorphism in neuropeptide Y with antipsychotic-induced weight gain in schizophrenia patients. J Clin Psychopharmacol 2013; 33:11-17.
36. Yang Y, Li W, Zhao J, Zhang H, Song X, Xiao B, et al. Association between ghrelin gene (GHRL) polymorphisms and clinical response to atypical antipsychotic drugs in Han Chinese schizophrenia patients. Behav Brain Funct 2012; 8:11.
37. Monteleone P, Milano W, Petrella C, Canestrelli B, Maj M. Endocannabinoid Pro129Thr FAAH functional polymorphism but not 1359G/A CNR1 polymorphism is associated with antipsychotic-induced weight gain. J Clin Psychopharmacol 2010; 30:441-445.
38. Tiwari AK, Zai CC, Likhodi O, Lisker A, Singh D, Souza RP, 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.
39. Reynolds GP, Yevtushenko OO, Gordon S, Arranz B, San L, Cooper SJ. The obesity risk gene FTO influences body mass in chronic schizophrenia but not initial antipsychotic drug-induced weight gain in first-episode patients. Int J Neuropsychopharmacol 2013; 16:1421-1425.
40. Chagnon YC, Bureau A, Gendron D, Bouchard RH, Merette C, Roy MA, Maziade M. Possible association of the pro-melanin-concentrating hormone gene with a greater body mass index as a side effect of the antipsychotic olanzapine. Am J Med Genet B Neuropsychiatr Genet 2007; 144B:1063-1069.
41. Van Winkel R, Rutten BP, 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.
42. Park YM, Chung YC, Lee SH, Lee KJ, Kim H, Byun YC, et al. Weight gain associated with the alpha2a-adrenergic receptor-1291 C/G polymorphism and olanzapine treatment. Am J Med Genet B Neuropsychiatr Genet 2006; 141B:394-397.
43. Sickert L, Muller DJ, Tiwari AK, Shaikh S, Zai C, de Souza R, et al. Association of the alpha 2A adrenergic receptor-1291C/G polymorphism and antipsychotic-induced weight gain in European-Americans. Pharmacogenomics 2009; 10:1169-1176.
44. Kao AC, Muller DJ. Genetics of antipsychotic-induced weight gain: update and current perspectives. Pharmacogenomics 2013; 14:2067-2083.
45. Reynolds GP. Pharmacogenetic aspects of antipsychotic drug-induced weight gain-a critical review. Clin Psychopharmacol Neurosci 2012; 10:71-77.
46. Roerig JL, Steffen KJ, Mitchell JE. Atypical antipsychotic-induced weight gain: insights into mechanisms of action. CNS Drugs 2011; 25:1035-1059.
47. Sachs GS, Thase ME, Otto MW, Bauer M, Miklowitz D, Wisniewski SR, et al. Rationale, design, and methods of the systematic treatment enhancement program for bipolar disorder (STEP-BD). Biol Psychiatry 2003; 53:1028-1042.
48. Hasnain M, Vieweg WV. Weight considerations in psychotropic drug prescribing and switching. Postgrad Med 2013; 125:117-129.
49. Kuo PH, Kao CF, Chen PY, Chen CH, Tsai YS, Lu ML, Huang MC. Polymorphisms of INSIG2, MC4R, and LEP are associated with obesity-and metabolic-related traits in schizophrenic patients. J Clin Psychopharmacol 2011; 31:705-711.
50. Gerken T, Girard CA, Tung YC, Webby CJ, Saudek V, Hewitson KS, et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 2007; 318:1469-1472.
51. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007; 316:889-894.
52. Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J, et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 2007; 3:e115.
53. Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet 2009; 41:18-24.
54. Shing EC, Tiwari AK, Brandl EJ, Zai CC, Lieberman JA, Meltzer HY, et al. Fat mass-and obesity-associated (FTO) gene and antipsychotic-induced weight gain: an association study. Neuropsychobiology 2014; 69:59-63.
55. Song X, Pang L, Feng Y, Fan X, Li X, Zhang W, et al. Fat-mass and obesityassociated gene polymorphisms and weight gain after risperidone treatment in first episode schizophrenia. Behav Brain Funct 2014; 10:35.
56. Tiwari HK, Patki A, Lieberman J, Stroup TS, Allison DB, Leibel RL, Chung WK. Association of allelic variation in genes mediating aspects of energy homeostasis with weight gain during administration of antipsychotic drugs (CATIE Study). Front Genet 2011; 2:56.
57. Gao X, Shin YH, Li M, Wang F, Tong Q, Zhang P. The fat mass and obesity associated gene FTO functions in the brain to regulate postnatal growth in mice. PLoS One 2010; 5:e14005.
58. Cheung MK, Gulati P, O'Rahilly S, Yeo GS. FTO expression is regulated by availability of essential amino acids. Int J Obes (Lond) 2013; 37:744-747.
59. Park SG, Ewalt KL, Kim S. Functional expansion of aminoacyl-tRNA synthetases and their interacting factors: new perspectives on housekeepers. Trends Biochem Sci 2005; 30:569-574.
60. Quevillon S, Robinson JC, Berthonneau E, Siatecka M, Mirande M. Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein. J Mol Biol 1999; 285:183-195.
61. McMurray F, Church CD, Larder R, Nicholson G, Wells S, Teboul L, et al. Adult onset global loss of the fto gene alters body composition and metabolism in the mouse. PLoS Genet 2013; 9:e1003166.
62. Cota D, Proulx K, Smith KA, Kozma SC, Thomas G, Woods SC, Seeley RJ. Hypothalamic mTOR signaling regulates food intake. Science 2006; 312:927-930.
63. Tung YC, Ayuso E, Shan X, Bosch F, O'Rahilly S, Coll AP, Yeo GS. Hypothalamic-specific manipulation of Fto, the ortholog of the human obesity gene FTO, affects food intake in rats. PLoS One 2010; 5:e8771.
64. Kilpelainen TO, Qi L, Brage S, Sharp SJ, Sonestedt E, Demerath E, et al. Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218 166 adults and 19 268 children. PLoS Med 2011; 8: e1001116.
65. Scheid JL, Carr KA, Lin H, Fletcher KD, Sucheston L, Singh PK, et al. FTO polymorphisms moderate the association of food reinforcement with energy intake. Physiol Behav 2014; 132:51-56.
66. Chadt A, Leicht K, Deshmukh A, Jiang LQ, Scherneck S, Bernhardt U, et al. Tbc1d1 mutation in lean mouse strain confers leanness and protects from diet-induced obesity. Nat Genet 2008; 40:1354-1359.
67. Kim JH, Lee JO, Lee SK, Jung JH, You GY, Park SH, et al. Clozapine activates AMP-activated protein kinase (AMPK) in C2C12 myotube cells and stimulates glucose uptake. Life Sci 2010; 87 (1-2):42-48.
68. Albaugh VL, Singareddy R, Mauger D, Lynch CJ. A double blind, placebocontrolled, randomized crossover study of the acute metabolic effects of olanzapine in healthy volunteers. PLoS One 2011; 6:e22662.
69. Meyre D, Farge M, Lecoeur C, Proenca C, Durand E, Allegaert F, et al. R125W coding variant in TBC1D1 confers risk for familial obesity and contributes to linkage on chromosome 4p14 in the French population. Hum Mol Genet 2008; 17:1798-1802.
70. Stone S, Abkevich V, Russell DL, Riley R, Timms K, Tran T, et al. TBC1D1 is a candidate for a severe obesity gene and evidence for a gene/gene interaction in obesity predisposition. Hum Mol Genet 2006; 15:2709-2720.
71. Brandl EJ, Tiwari AK, Lett TA, Shaikh SA, Lieberman JA, Meltzer HY, et al. Exploratory study on association of genetic variation in TBC1D1 with antipsychotic-induced weight gain. Hum Psychopharmacol 2013; 28:183-187.
72. Ellingrod VL, Miller DD, Taylor SF, 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.
73. Risselada AJ, Mulder H, Heerdink ER, Egberts TC. Pharmacogenetic testing to predict antipsychotic-induced weight gain: a systematic review. Pharmacogenomics 2011; 12:1213-1227.
74. Burghardt KJ, Pilsner JR, Bly MJ, Ellingrod VL. DNA methylation in schizophrenia subjects: gender and MTHFR 677C/T genotype differences. Epigenomics 2012; 4:261-268.
75. Berndt SI, Gustafsson S, Magi R, Ganna A, Wheeler E, Feitosa MF, et al. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture. Nat Genet 2013; 45:501-512.
76. Dupuis J, Langenberg C, Prokopenko I, Saxena R, Soranzo N, Jackson AU, et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet 2010; 42:105-116.
77. Knigge A, Kloting N, Schon MR, Dietrich A, Fasshauer M, Gartner D, et al. ADCY5 gene expression in adipose tissue is related to obesity in men and mice. PLoS One 2015; 10:e0120742.
78. Brandl EJ, Tiwari AK, Zai CC, Chowdhury NI, Lieberman JA, Meltzer HY, et al. No evidence for a role of the peroxisome proliferator-activated receptor gamma (PPARG) and adiponectin (ADIPOQ) genes in antipsychoticinduced weight gain. Psychiatry Res 2014; 219:255-260.