Pharmacogenetics of leptin in antipsychotic-associated weight gain and obesity-related complications

Pharmacogenomics

Volumn 12, Issue 7, 2011, Pages 999-1016

  Lee, Amy K ^a   Bishop, Jeffrey R ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

antipsychotic; leptin; leptin receptor; obesity; polymorphism; weight gain

Indexed keywords

AMISULPRIDE; ARIPIPRAZOLE; CLOZAPINE; DOPAMINE 2 RECEPTOR; HALOPERIDOL; HISTAMINE H1 RECEPTOR; NEUROLEPTIC AGENT; OLANZAPINE; QUETIAPINE; RISPERIDONE; SEROTONIN 2C RECEPTOR; SEROTONIN UPTAKE INHIBITOR; ZIPRASIDONE;

ADIPOSE TISSUE; ALLELE; ANTHROPOMETRIC PARAMETERS; AUTOPHOSPHORYLATION; BODY MASS; GENE; GENE STRUCTURE; GENETIC ORGANIZATION; GENETIC VARIABILITY; HERITABILITY; HIP CIRCUMFERENCE; HOMOZYGOSITY; HORMONE ACTION; HORMONE BLOOD LEVEL; HORMONE RELEASE; HUMAN; INSULIN INDUCED GENE 2; LEPTIN GENE; LEPTIN RECEPTOR GENE; MENTAL DISEASE; METABOLIC DISORDER; METABOLIC SYNDROME X; NONHUMAN; OBESITY; PHARMACODYNAMICS; PHARMACOGENETICS; PROTEIN PHOSPHORYLATION; PSYCHOSIS; RECEPTOR AFFINITY; RECEPTOR BLOCKING; REVIEW; RISK FACTOR; SCHIZOAFFECTIVE PSYCHOSIS; SCHIZOPHRENIA; SCHIZOPHRENIFORM DISORDER; SERUM LEPTIN LEVEL; SIDE EFFECT; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; TREATMENT DURATION; TRIACYLGLYCEROL BLOOD LEVEL; WAIST CIRCUMFERENCE; WAIST HIP RATIO; WEIGHT GAIN;

ANTIPSYCHOTIC AGENTS; HUMANS; LEPTIN; OBESITY; POLYMORPHISM, GENETIC; RECEPTOR, SEROTONIN, 5-HT2C; RECEPTORS, DOPAMINE; RECEPTORS, LEPTIN; SCHIZOPHRENIA; WEIGHT GAIN;

EID: 79960752412     PISSN: 14622416     EISSN: 17448042     Source Type: Journal    
DOI: 10.2217/pgs.11.45     Document Type: Review

References (110)

1. Allison DB, Mentore JL, Heo M et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am. J. Psychiatry 156(11), 1686-1696 (1999). (Pubitemid 29517559)
2. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 27(2), 596-601 (2004).
3. Parsons B, Allison DB, Loebel A et al. Weight effects associated with antipsychotics: a comprehensive database analysis. Schizophr. Res. 110(1-3), 103-110 (2009).
4. Arranz MJ, De Leon J. Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research. Mol. Psychiatry 12(8), 707-747 (2007). (Pubitemid 47172693)
5. de Luca V, Mueller DJ, de Bartolomeis A, Kennedy JL. Association of the HTR2C gene and antipsychotic induced weight gain: a meta-analysis. Int. J. Neuropsychopharmacol. 10(5), 697-704 (2007). (Pubitemid 47517523)
6. Sicard MN, Zai CC, Tiwari AK et al. Polymorphisms of the HTR2C gene and antipsychotic-induced weight gain: an update and meta-analysis. Pharmacogenomics 11(11), 1561-1571 (2010).
7. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999-2008. JAMA 303(3), 235-241 (2010).
8. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation 106(25), 3143-3421 (2002).
9. Mottillo S, Filion KB, Genest J et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J. Am. Coll. Cardiol. 56(14), 1113-1132 (2010).
10. Citrome L, Blonde L, Damatarca C. Metabolic issues in patients with severe mental illness. South Med. J. 98(7), 714-720 (2005). (Pubitemid 41061657)
11. Holt RI, Peveler RC. Obesity, serious mental illness and antipsychotic drugs. Diabetes. Obes. Metab. 11(7), 665-679 (2009).
12. Newcomer JW. Metabolic considerations in the use of antipsychotic medications: a review of recent evidence. J. Clin. Psychiatry 68(Suppl. 1), 20-27 (2007).
13. Brown S, Birtwistle J, Roe L, Thompson C. The unhealthy lifestyle of people with schizophrenia. Psychol. Med. 29(3), 697-701 (1999). (Pubitemid 29261358)
14. Jin H, Meyer JM, Mudaliar S, Jeste DV. Impact of atypical antipsychotic therapy on leptin, ghrelin, and adiponectin. Schizophr. Res. 100(1-3), 70-85 (2008).
15. Kinon BJ, Basson BR, Gilmore JA, Tollefson GD. Long-term olanzapine treatment: weight change and weight-related health factors in schizophrenia. J. Clin. Psychiatry 62(2), 92-100 (2001). (Pubitemid 32199865)
16. Gentile S. Contributing factors to weight gain during long-term treatment with second-generation antipsychotics. A systematic appraisal and clinical implications. Obes. Rev. 10(5), 527-542 (2009).
17. Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet 373(9657), 31-41 (2009).
18. Leucht S, Komossa K, Rummel-Kluge C et al. A meta-analysis of head-to-head comparisons of second-generation antipsychotics in the treatment of schizophrenia. Am. J. Psychiatry 166(2), 152-163 (2009).
19. Lieberman JA, Stroup TS, Mcevoy JP et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N. Engl. J. Med. 353(12), 1209-1223 (2005). (Pubitemid 41345943)
20. Gebhardt S, Haberhausen M, Heinzel-Gutenbrunner M et al. Antipsychotic-induced body weight gain: predictors and a systematic categorization of the long-term weight course. J. Psychiatr. Res. 43(6), 620-626 (2009).
21. Aichhorn W, Whitworth AB, Weiss EM, Marksteiner J. Second-generation antipsychotics: is there evidence for sex differences in pharmacokinetic and adverse effect profiles? Drug Saf. 29(7), 587-598 (2006). (Pubitemid 44175029)
22. Basson BR, Kinon BJ, Taylor CC, Szymanski KA, Gilmore JA, Tollefson GD. Factors influencing acute weight change in patients with schizophrenia treated with olanzapine, haloperidol, or risperidone. J. Clin. Psychiatry 62(4), 231-238 (2001). (Pubitemid 32428761)
23. Kinon BJ, Kaiser CJ, Ahmed S, Rotelli MD, Kollack-Walker S. Association between early and rapid weight gain and change in weight over one year of olanzapine therapy in patients with schizophrenia and related disorders. J. Clin. Psychopharmacol. 25(3), 255-258 (2005). (Pubitemid 40685790)
24. Safer DJ. A comparison of risperidone-induced weight gain across the age span. J. Clin. Psychopharmacol. 24(4), 429-436 (2004). (Pubitemid 38944142)
25. Strassnig M, Miewald J, Keshavan M, Ganguli R. Weight gain in newly diagnosed first-episode psychosis patients and healthy comparisons: one-year analysis. Schizophr. Res. 93(1-3), 90-98 (2007).
26. Saddichha S, Ameen S, Akhtar S. Predictors of antipsychotic-induced weight gain in first-episode psychosis: conclusions from a randomized, double-blind, controlled prospective study of olanzapine, risperidone, and haloperidol. J. Clin. Psychopharmacol. 28(1), 27-31 (2008).
27. Ascher-Svanum H, Stensland MD, Kinon BJ, Tollefson GD. Weight gain as a prognostic indicator of therapeutic improvement during acute treatment of schizophrenia with placebo or active antipsychotic. J. Psychopharmacol. 19(Suppl. 6), 110-117 (2005). (Pubitemid 44567865)
28. Theisen FM, Gebhardt S, Haberhausen M et al. Clozapine-induced weight gain: a study in monozygotic twins and same-sex sib pairs. Psychiatr. Genet. 15(4), 285-289 (2005). (Pubitemid 44491467)
29. Wehmeier PM, Gebhardt S, Schmidtke J, Remschmidt H, Hebebrand J, Theisen FM. Clozapine: weight gain in a pair of monozygotic twins concordant for schizophrenia and mild mental retardation. Psychiatry Res. 133(2-3), 273-276 (2005).
30. Zhang XY, Zhou DF, Wu GY et al. BDNF levels and genotype are associated with antipsychotic-induced weight gain in patients with chronic schizophrenia. Neuropsychopharmacology 33(9), 2200-2205 (2008). (Pubitemid 351992089)
31. Lane HY, Liu YC, Huang CL et al. Risperidone-related weight gain: genetic and nongenetic predictors. J. Clin. Psychopharmacol. 26(2), 128-134 (2006).
32. Reynolds GP, Zhang ZJ, Zhang XB. Association of antipsychotic drug-induced weight gain with a 5-HT2C receptor gene polymorphism. Lancet 359(9323), 2086-2087 (2002). (Pubitemid 34680975)
33. Lencz T, Robinson DG, Napolitano B et al. DRD2 promoter region variation predicts antipsychotic-induced weight gain in first episode schizophrenia. Pharmacogenet. Genomics 20(9), 569-572 (2010).
34. Sickert L, Muller DJ, Tiwari AK et al. Association of the a 2A adrenergic receptor-1291C/G polymorphism and antipsychotic-induced weight gain in European-Americans. Pharmacogenomics 10(7), 1169-1176 (2009).
35. Wang YC, Bai YM, Chen JY, Lin CC, Lai IC, Liou YJ. Polymorphism of the adrenergic receptor a 2A-1291C>G genetic variation and clozapine-induced weight gain. J. Neural Transm. 112(11), 1463-1468 (2005).
36. Kroeze WK, Hufeisen SJ, Popadak BA et al. H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacology 28(3), 519-526 (2003).
37. Nasrallah HA. Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol. Psychiatry 13(1), 27-35 (2008). (Pubitemid 350275185)
38. Nonogaki K, Strack AM, Dallman MF, Tecott LH. Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat. Med. 4(10), 1152-1156 (1998). (Pubitemid 28468828)
39. Tecott LH, Sun LM, Akana SF et al. Eating disorder and epilepsy in mice lacking 5-HT2C serotonin receptors. Nature 374(6522), 542-546 (1995).
40. Meltzer HY, Matsubara S, Lee JC. Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values. J. Pharmacol. Exp. Ther. 251(1), 238-246 (1989).
41. Roth BL, Sheffler DJ, Kroeze WK. Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia. Nat. Rev. Drug Discov. 3(4), 353-359 (2004). (Pubitemid 38499762)
42. Blum K, Braverman ER, Holder JM et al. Reward deficiency syndrome: a biogenetic model for the diagnosis and treatment of impulsive, addictive, and compulsive behaviors. J. Psychoactive Drugs 32(Suppl. i-iv), 1-112 (2000). (Pubitemid 32005730)
43. Wang GJ, Volkow ND, Logan J et al. Brain dopamine and obesity. Lancet 357(9253), 354-357 (2001). (Pubitemid 32128542)
44. Elman I, Borsook D, Lukas SE. Food intake and reward mechanisms in patients with schizophrenia: implications for metabolic disturbances and treatment with second-generation antipsychotic agents. Neuropsychopharmacology 31(10), 2091-2120 (2006). (Pubitemid 44413188)
45. Le Foll B, Gallo A, Le Strat Y, Lu L, Gorwood P. Genetics of dopamine receptors and drug addiction: a comprehensive review. Behav. Pharmacol. 20(1), 1-17 (2009).
46. Jorgensen EA, Knigge U, Warberg J, Kjaer A. Histamine and the regulation of body weight. Neuroendocrinology 86(3), 210-214 (2007). (Pubitemid 350073608)
47. Ookuma K, Sakata T, Fukagawa K et al. Neuronal histamine in the hypothalamus suppresses food intake in rats. Brain Res. 628(1-2), 235-242 (1993).
48. Lecklin A, Tuomisto L. The blockade of H1 receptors attenuates the suppression of feeding and diuresis induced by inhibition of histamine catabolism. Pharmacol. Biochem. Behav. 59(3), 753-758 (1998). (Pubitemid 28144220)
49. Han M, Deng C, Burne TH, Newell KA, Huang XF. Short-and long-term effects of antipsychotic drug treatment on weight gain and H1 receptor expression. Psychoneuroendocrinology 33(5), 569-580 (2008).
50. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 372(6505), 425-432 (1994). (Pubitemid 24365442)
51. Isse N, Ogawa Y, Tamura N et al. Structural organization and chromosomal assignment of the human obese gene. J. Biol. Chem. 270(46), 27728-27733 (1995).
52. Sinha MK, Opentanova I, Ohannesian JP et al. Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short-term fasting. J. Clin. Invest. 98(6), 1277-1282 (1996). (Pubitemid 26322051)
53. Licinio J, Mantzoros C, Negrao Ab et al. Human leptin levels are pulsatile and inversely related to pituitary-adrenal function. Nat. Med. 3(5), 575-579 (1997). (Pubitemid 27198660)
54. Sinha MK, Ohannesian JP, Heiman ML et al. Nocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects. J. Clin. Invest. 97(5), 1344-1347 (1996). (Pubitemid 26086355)
55. Baumann H, Morella KK, White DW et al. The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors. Proc. Natl Acad. Sci. USA 93(16), 8374-8378 (1996). (Pubitemid 26269565)
56. Thompson DB, Ravussin E, Bennett PH, Bogardus C. Structure and sequence variation at the human leptin receptor gene in lean and obese Pima Indians. Hum. Mol. Genet. 6(5), 675-679 (1997). (Pubitemid 27199060)
57. Lee GH, Proenca R, Montez JM et al. Abnormal splicing of the leptin receptor in diabetic mice. Nature 379(6566), 632-635 (1996). (Pubitemid 26053452)
58. Morris DL, Rui L. Recent advances in understanding leptin signaling and leptin resistance. Am. J. Physiol. Endocrinol. Metab. 297(6), E1247-1259 (2009).
59. Zhang F, Chen Y, Heiman M, Dimarchi R. Leptin: structure, function and biology. Vitam. Horm. 71, 345-372 (2005). (Pubitemid 43589034)
60. Lammert A, Kiess W, Bottner A, Glasow A, Kratzsch J. Soluble leptin receptor represents the main leptin binding activity in human blood. Biochem. Biophys. Res. Commun. 283(4), 982-988 (2001). (Pubitemid 32924677)
61. Kloek C, Haq AK, Dunn SL, Lavery HJ, Banks AS, Myers MG Jr. Regulation of Jak kinases by intracellular leptin receptor sequences. J. Biol. Chem. 277(44), 41547-41555 (2002). (Pubitemid 35257458)
62. Gong Y, Ishida-Takahashi R, Villanueva EC, Fingar DC, Munzberg H, Myers MG Jr. The long form of the leptin receptor regulates STAT5 and ribosomal protein S6 via alternate mechanisms. J. Biol. Chem. 282(42), 31019-31027 (2007). (Pubitemid 350035238)
63. Vaisse C, Halaas JL, Horvath CM, Darnell JE Jr, Stoffel M, Friedman JM. Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice. Nat. Genet. 14(1), 95-97 (1996). (Pubitemid 26301554)
64. Robertson SA, Leinninger GM, Myers MG Jr. Molecular and neural mediators of leptin action. Physiol. Behav. 94(5), 637-642 (2008). (Pubitemid 351847627)
65. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature 404(6778), 661-671 (2000). (Pubitemid 30205071)
66. Margetic S, Gazzola C, Pegg GG, Hill RA. Leptin: a review of its peripheral actions and interactions. Int. J. Obes. Relat. Metab. Disord. 26(11), 1407-1433 (2002). (Pubitemid 36007818)
67. Sentissi O, Grouselle D, Viala A et al. Ghrelin and leptin levels in schizophrenic patients treated with antipsychotic monotherapy. J. Clin. Psychopharmacol. 29(3), 304-306 (2009).
68. Wang HC, Yang YK, Chen PS, Lee IH, Yeh L, Lu RB. Increased plasma leptin in antipsychotic-naive females with schizophrenia, but not in males. Neuropsychobiology 56(4), 213-215 (2007). (Pubitemid 351567539)
69. Dieudonne MN, Pecquery R, Boumediene A, Leneveu MC, Giudicelli Y. Androgen receptors in human preadipocytes and adipocytes: regional specificities and regulation by sex steroids. Am. J. Physiol. 274(6 Pt 1), C1645-C1652 (1998).
70. Mizutani T, Nishikawa Y, Adachi H et al. Identification of estrogen receptor in human adipose tissue and adipocytes. J. Clin. Endocrinol. Metab. 78(4), 950-954 (1994). (Pubitemid 24118094)
71. O'Brien SN, Welter BH, Mantzke KA, Price M. Identification of progesterone receptor in human subcutaneous adipose tissue. J. Clin. Endocrinol. Metab. 83(2), 509-513 (1998). (Pubitemid 28496531)
72. Elbers JM, Asscheman H, Seidell JC, Frolich M, Meinders AE, Gooren LJ. Reversal of the sex difference in serum leptin levels upon cross-sex hormone administration in transsexuals. J. Clin. Endocrinol. Metab. 82(10), 3267-3270 (1997). (Pubitemid 27419069)
73. Machinal F, Dieudonne MN, Leneveu MC, Pecquery R, Giudicelli Y. In vivo and in vitro ob gene expression and leptin secretion in rat adipocytes: evidence for a regional specific regulation by sex steroid hormones. Endocrinology 140(4), 1567-1574 (1999). (Pubitemid 29149223)
74. Considine RV, Sinha MK, Heiman ML et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N. Engl. J. Med. 334(5), 292-295 (1996). (Pubitemid 26033933)
75. Sentissi O, Epelbaum J, Olie JP, Poirier MF. Leptin and ghrelin levels in patients with schizophrenia during different antipsychotics treatment: a review. Schizophr. Bull. 34(6), 1189-1199 (2008).
76. Ribeiro R, Vasconcelos A, Costa S et al. Overexpressing leptin genetic polymorphism (-2548 G/A) is associated with susceptibility to prostate cancer and risk of advanced disease. Prostate 59(3), 268-274 (2004). (Pubitemid 38509759)
77. Ma D, Feitosa MF, Wilk JB et al. Leptin is associated with blood pressure and hypertension in women from the national heart, lung, and blood institute family heart study. Hypertension 53(3), 473-479 (2009).
78. Hoffstedt J, Eriksson P, Mottagui-Tabar S, Arner P. A polymorphism in the leptin promoter region (-2548 G/A) influences gene expression and adipose tissue secretion of leptin. Horm. Metab. Res. 34(7), 355-359 (2002).
79. Hager J, Clement K, Francke S et al. A polymorphism in the 5́ untranslated region of the human ob gene is associated with low leptin levels. Int. J. Obes. Relat. Metab. Disord. 22(3), 200-205 (1998). (Pubitemid 28112018)
80. Dahlman I, Arner P. Obesity and polymorphisms in genes regulating human adipose tissue. Int. J. Obes. (Lond.) 31(11), 1629-1641 (2007). (Pubitemid 350023156)
81. Rosmond R. Association studies of genetic polymorphisms in central obesity: a critical review. Int. J. Obes. Relat. Metab. Disord. 27(10), 1141-1151 (2003). (Pubitemid 37281662)
82. Stratigopoulos G, Leduc CA, Matsuoka N et al. Functional consequences of the human leptin receptor (LEPR) Q223R transversion. Obesity (Silver Spring) 17(1), 126-135 (2009). (Pubitemid 50324546)
83. Furusawa T, Naka I, Yamauchi Tet al. The Q223R polymorphism in LEPR is associated with obesity in Pacific Islanders. Hum. Genet. 127(3), 287-294 (2010).
84. Quinton ND, Lee AJ, Ross RJ, Eastell R, Blakemore AI. A single nucleotide polymorphism (SNP) in the leptin receptor is associated with BMI, fat mass and leptin levels in postmenopausal Caucasian women. Hum. Genet. 108(3), 233-236 (2001). (Pubitemid 32293670)
85. Yiannakouris N, Yannakoulia M, Melistas L, Chan JL, Klimis-Zacas D, Mantzoros CS. The Q223R polymorphism of the leptin receptor gene is significantly associated with obesity and predicts a small percentage of body weight and body composition variability. J. Clin. Endocrinol. Metab. 86(9), 4434-4439 (2001). (Pubitemid 32848571)
86. Mammes O, Aubert R, Betoulle D et al. LEPR gene polymorphisms: associations with overweight, fat mass and response to diet in women. Eur. J. Clin. Invest. 31(5), 398-404 (2001). (Pubitemid 32476959)
87. Heo M, Leibel RL, Fontaine KR et al. A meta-analytic investigation of linkage and association of common leptin receptor (LEPR) polymorphisms with body mass index and waist circumference. Int. J. Obes. Relat. Metab. Disord. 26(5), 640-646 (2002). (Pubitemid 34499283)
88. Paracchini V, Pedotti P, Taioli E. Genetics of leptin and obesity: a HuGE review. Am. J. Epidemiol. 162(2), 101-114 (2005). (Pubitemid 41373535)
89. Sun Q, Cornelis MC, Kraft P et al. Genome-wide association study identifies polymorphisms in LEPR as determinants of plasma soluble leptin receptor levels. Hum. Mol. Genet. 19(9), 1846-1855 (2010).
90. Zhang ZJ, Yao ZJ, Mou XD et al. Association of-2548G/A functional polymorphism in the promoter region of leptin gene with antipsychotic agent-induced weight gain. Zhonghua Yi Xue Za Zhi 83(24), 2119-2123 (2003).
91. Ruano G, Goethe JW, Caley C et al. Physiogenomic comparison of weight profiles of olanzapine-and risperidone-treated patients. Mol. Psychiatry 12(5), 474-482 (2007). (Pubitemid 46652457)
92. Yevtushenko OO, Cooper SJ, O'Neill R, Doherty JK, Woodside JV, Reynolds GP. Influence of 5-HT2C receptor and leptin gene polymorphisms, smoking and drug treatment on metabolic disturbances in patients with schizophrenia. Br. J. Psychiatry 192(6), 424-428 (2008). (Pubitemid 351809894)
93. Gregoor JG, Van Der Weide J, Mulder H et al. Polymorphisms of the LEP-and LEPR gene and obesity in patients using antipsychotic medication. J. Clin. Psychopharmacol. 29(1), 21-25 (2009).
94. Gregoor JG, Mulder H, Cohen D et al. Combined HTR2C-LEP genotype as a determinant of obesity in patients using antipsychotic medication. J. Clin. Psychopharmacol. 30(6), 702-705 (2010).
95. Opgen-Rhein C, Brandl EJ, Muller DJ et al. Association of HTR2C, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample. Pharmacogenomics 11(6), 773-780 (2010).
96. Fernandez E, Carrizo E, Fernandez V et al. Polymorphisms of the LEP-and LEPR genes, metabolic profile after prolonged clozapine administration and response to the antidiabetic metformin. Schizophr. Res. 121(1-3), 213-217 (2010).
97. Moons T, Claes S, Martens GJ et al. Clock genes and body composition in patients with schizophrenia under treatment with antipsychotic drugs. Schizophr. Res. 125(2-3), 187-193 (2011).
98. Ellingrod Vl, Bishop JR, Moline J, Lin YC, Miller DD. Leptin and leptin receptor gene polymorphisms and increases in body mass index (BMI) from olanzapine treatment in persons with schizophrenia. Psychopharmacol. Bull. 40(1), 57-62 (2007).
99. Srivastava V, Deshpande SN, Nimgaonkar VL, Lerer B, Thelma B. Genetic correlates of olanzapine-induced weight gain in schizophrenia subjects from north India: role of metabolic pathway genes. Pharmacogenomics 9(8), 1055-1068 (2008).
100. Templeman LA, Reynolds GP, 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. Genomics 15(4), 195-200 (2005). (Pubitemid 40569890)
101. Zhang XY, Tan YL, Zhou DF et al. 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. 27(3), 246-251 (2007). (Pubitemid 46763305)
102. Kang SG, Lee HJ, Park YM et al. Possible association between the-2548A/G polymorphism of the leptin gene and olanzapine-induced weight gain. Prog. Neuropsychopharmacol. Biol. Psychiatry 32(1), 160-163 (2008).
103. Perez-Iglesias R, Mata I, Amado JA et al. Effect of FTO, SH2B1, LEP, and LEPR polymorphisms on weight gain associated with antipsychotic treatment. J. Clin. Psychopharmacol. 30(6), 661-666 (2010).
104. Calarge CA, Ellingrod VL, Zimmerman B, Acion L, Sivitz WI, Schlechte JA. Leptin gene-2548G/A variants predict risperidone-associated weight gain in children and adolescents. Psychiatr. Genet. 19(6), 320-327 (2009).
105. Gregoor JG, van der Weide J, Loovers HM, van Megen HJ, Egberts TC, Heerdink ER. Association between LEP and LEPR gene polymorphisms and dyslipidemia in patients using atypical antipsychotic medication. Psychiatr. Genet. 20(6), 311-316 (2010).
106. Kluge M, Schuld A, Schacht A et al. Effects of clozapine and olanzapine on cytokine systems are closely linked to weight gain and drug-induced fever. Psychoneuroendocrinology 34(1), 118-128 (2009).
107. Vehof J, Risselada AJ, Al Hadithy AF 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.) 216(2), 257-265 (2011).
108. Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs 19(Suppl. 1), 1-93 (2005). (Pubitemid 40677047)
109. Thompson A, Lavedan C, Volpi S. Absence of weight gain association with the HTR2C-759C/Tpolymorphism in patients with schizophrenia treated with iloperidone. Psychiatry Res. 175(3), 271-273 (2010).
110. Tartaglia LA. The leptin receptor. J. Biol. Chem. 272(10), 6093-6 (1997). (Pubitemid 27118072)