Sexual dysfunction in male schizophrenia: Influence of antipsychotic drugs, prolactin and polymorphisms of the dopamine D2 receptor genes

Pharmacogenomics

Volumn 12, Issue 8, 2011, Pages 1127-1136

  Zhang, Xiang Rong ^a,b,c   Zhang, Zhi Jun ^a,b   Zhu, Rong Xin ^d   Yuan, Yong Gui ^d   Jenkins, Trisha A ^c   Reynolds, Gavin P ^c,e  

^a MEDICAL SCHOOL OF SOUTHEAST UNIVERSITY   (China)

^b SOUTHEAST UNIVERSITY   (China)

^c QUEEN'S UNIVERSITY BELFAST   (United Kingdom)

^d THE AFFILIATED BRAIN HOSPITAL OF NANJING MEDICAL UNIVERSITY   (China)

^e SHEFFIELD HALLAM UNIVERSITY   (United Kingdom)

Author keywords

antipsychotic; DRD2; eNOS; genetic polymorphism; sexual dysfunction

Indexed keywords

CHLORPROMAZINE; CLOZAPINE; DOPAMINE 2 RECEPTOR; HALOPERIDOL; NEUROLEPTIC AGENT; OLANZAPINE; PROLACTIN; RISPERIDONE;

ADULT; ALLELE; ARTICLE; BLOOD SAMPLING; CONTROLLED STUDY; DISEASE ASSOCIATION; DISEASE SEVERITY; DRD2 GENE; ENOS GENE; ERECTILE DYSFUNCTION; GENE; GENE DELETION; GENE FREQUENCY; GENE INSERTION; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENETIC VARIABILITY; GENOTYPE; HETEROZYGOSITY; HUMAN; MAJOR CLINICAL STUDY; MALE; MALE SEXUAL DYSFUNCTION; MARKER GENE; PROLACTIN BLOOD LEVEL; SCHIZOPHRENIA;

ADULT; ANTIPSYCHOTIC AGENTS; ASIAN CONTINENTAL ANCESTRY GROUP; CHINA; DIAGNOSTIC AND STATISTICAL MANUAL OF MENTAL DISORDERS; DNA; ERECTILE DYSFUNCTION; GENOTYPE; HUMANS; MALE; MIDDLE AGED; NITRIC OXIDE SYNTHASE TYPE III; POLYMORPHISM, GENETIC; POLYMORPHISM, SINGLE NUCLEOTIDE; PROLACTIN; PSYCHIATRIC STATUS RATING SCALES; RECEPTORS, DOPAMINE D2; SCHIZOPHRENIA; SEXUAL DYSFUNCTION, PHYSIOLOGICAL;

EID: 80051736623     PISSN: 14622416     EISSN: 17448042     Source Type: Journal    
DOI: 10.2217/pgs.11.46     Document Type: Article

References (61)

1. Baggaley M. Sexual dysfunction in schizophrenia: focus on recent evidence. Hum. Psychopharmacol. 23(3), 201-209 (2008). (Pubitemid 351577689)
2. Mallis D, Moisidis K, Kirana PS et al. Moderate and severe erectile dysfunction equally affects life satisfaction. J. Sex. Med. 3(3), 442-449 (2006).
3. Olfson M, Uttaro T, Carson WH, Tafesse E. Male sexual dysfunction and quality of life in schizophrenia. J. Clin. Psychiatry 66(3), 331-338 (2005). (Pubitemid 40476756)
4. Perkins DO. Predictors of noncompliance in patients with schizophrenia. J. Clin. Psychiatry 63(12), 1121-1128 (2002). (Pubitemid 36084056)
5. Rosenberg KP, Bleiberg KL, Koscis J, Gross C. A survey of sexual side effects among severely mentally ill patients taking psychotropic medications: impact on compliance. J. Sex. Marital Ther. 29(4), 289-296 (2003). (Pubitemid 36807936)
6. Lambert M, Conus P, Eide P et al. Impact of present and past antipsychotic side effects on attitude toward typical antipsychotic treatment and adherence. Eur. Psychiatry 19(7), 415-422 (2004). (Pubitemid 39422495)
7. Giuliano F, Rampin O. Central neural regulation of penile erection. Neurosci. Biobehav. Rev. 24(5), 517-533 (2000). (Pubitemid 30398513)
8. Heaton JP, Adams MA. Update on central function relevant to sex: remodeling the basis of drug treatments for sex and the brain. Int. J. Impot. Res. 15(Suppl. 5), 25-32 (2003).
9. Cutler AJ. Sexual dysfunction and antipsychotic treatment. Psychoneuroendocrinology 28, 69-82 (2003). (Pubitemid 36015662)
10. Kelly DL, Conley RR. Sexuality and schizophrenia: a review. Schizophr. Bull. 30(4), 767-779 (2004).
11. Knegtering H, van BR, Castelein S et al. Are sexual side effects of prolactin-raising antipsychotics reducible to serum prolactin? Psychoneuroendocrinology 33(6), 711-717 (2008).
12. Eberhard J, Lindstrom E, Holstad M, Levander S. Prolactin level during 5 years of risperidone treatment in patients with psychotic disorders. Acta Psychiatr. Scand. 115(4), 268-276 (2007). (Pubitemid 46425745)
13. Arinami T, Gao M, Hamaguchi H, Toru M. A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia. Hum. Mol. Genet. 6(4), 577-582 (1997). (Pubitemid 27142107)
14. Thompson J, Thomas N, Singleton A et al. D2 dopamine receptor gene (DRD2) Taq1 A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele. Pharmacogenetics 7(6), 479-484 (1997). (Pubitemid 27517576)
15. Pohjalainen T, Rinne JO, Nagren K et al. The A1 allele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers. Mol. Psychiatry 3(3), 256-260 (1998). (Pubitemid 28266335)
16. Young RM, Lawford BR, Barnes M et al. Prolactin levels in antipsychotic treatment of patients with schizophrenia carrying the DRD2*A1 allele. Br. J. Psychiatry 185, 147-151 (2004). (Pubitemid 39061458)
17. Zhang XR, Zhang ZJ, Jenkins TA, Cheng WR, Reynolds GP. The effect of chronic antipsychotic drug administration on nitric oxide synthase activity and gene expression in rat penile tissues. Eur. Neuropsychopharmacol. 20(4), 211-217 (2010).
18. Lee YC, Huang CH, Wang CJ et al. The associations among eNOS G894T gene polymorphism, erectile dysfunction and related risk factors. BJU Int. 100(5), 1116-1120 (2007).
19. Rosas-Vargas H, Coral-Vazquez RM, Tapia R et al. Glu298Asp endothelial nitric oxide synthase polymorphism is a risk factor for erectile dysfunction in the Mexican Mestizo population. J. Androl. 25(5), 728-732 (2004). (Pubitemid 39096306)
20. Nakayama M, Yasue H, Yoshimura M et al. T-786→C mutation in the 5́-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation 99(22), 2864-2870 (1999). (Pubitemid 29258973)
21. Nakayama T, Soma M, Takahashi Y et al. Association analysis of CA repeat polymorphism of the endothelial nitric oxide synthase gene with essential hypertension in Japanese. Clin. Genet. 51(1), 26-30 (1997). (Pubitemid 27116895)
22. Alvarez R, Gonzalez P, Batalla A et al. Association between the NOS3 (-786 T/C) and the ACE (I/D) DNA genotypes and early coronary artery disease. Nitric Oxide 5(4), 343-348 (2001). (Pubitemid 32735386)
23. Andreasen NC, Carpenter WT, Kane JM et al. Remission in schizophrenia: proposed criteria and rationale for consensus. Am. J. Psychiatry 162(3), 441-449 (2005). (Pubitemid 40343909)
24. McGahuey CA, Gelenberg AJ, Laukes CA et al. The Arizona Sexual Experience Scale (ASEX): reliability and validity. J. Sex. Marital Ther. 26(1), 25-40 (2000). (Pubitemid 30046590)
25. Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Pena BM. Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int. J. Impot. Res. 11(6), 319-326 (1999). (Pubitemid 30052683)
26. Byerly MJ, Nakonezny PA, Fisher R, Magouirk B, Rush AJ. An empirical evaluation of the Arizona sexual experience scale and a simple one-item screening test for assessing antipsychotic-related sexual dysfunction in outpatients with schizophrenia and schizoaffective disorder. Schizophr. Res. 81(2-3), 311-316 (2006). (Pubitemid 43107707)
27. Grandy DK, Zhang Y, Civelli O. PCR detection of the TaqA RFLP at the DRD2 locus. Hum. Mol. Genet. 2(12), 2197 (1993). (Pubitemid 24003431)
28. Goldman D, Urbanek M, Guenther D, Robin R, Long JC. Linkage and association of a functional DRD2 variant [Ser311Cys] and DRD2 markers to alcoholism, substance abuse and schizophrenia in Southwestern American Indians. Am. J. Med. Genet. 74(4), 386-394 (1997). (Pubitemid 27349375)
29. Gelernter J, Kranzler H, Cubells JF, Ichinose H, Nagatsu T. DRD2 allele frequencies and linkage disequilibria, including the-141CIns/Del promoter polymorphism, in European-American, African-American, and Japanese subjects. Genomics 51(1), 21-26 (1998).
30. Naber CK, Baumgart D, Altmann C et al. eNOS 894T allele and coronary blood flow at rest and during adenosine-induced hyperemia. Am. J. Physiol. Heart Circ. Physiol. 281(5), 1908-1912 (2001).
31. Marroni AS, Metzger IF, Souza-Costa DC et al. Consistent interethnic differences in the distribution of clinically relevant endothelial nitric oxide synthase genetic polymorphisms. Nitric Oxide 12(3), 177-182 (2005). (Pubitemid 40432137)
32. Ucok A, Incesu C, Aker T, Erkoc S. Sexual dysfunction in patients with schizophrenia on antipsychotic medication. Eur. Psychiatry 22(5), 328-333 (2007). (Pubitemid 47088198)
33. Najman JM, Dunne MP, Boyle FM, Cook MD, Purdie DM. Sexual dysfunction in the Australian population. Aust. Fam. Physician 32(11), 951-954 (2003).
34. Nicolosi A, Glasser DB, Kim SC, Marumo K, Laumann EO. Sexual behaviour and dysfunction and help-seeking patterns in adults aged 40-80 years in the urban population of Asian countries. BJU Int. 95(4), 609-614 (2005). (Pubitemid 40311482)
35. Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: prevalence and predictors. JAMA 281(6), 537-544 (1999). (Pubitemid 29081307)
36. Jonsson EG, Nothen MM, Grunhage F et al. Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers. Mol. Psychiatry 4(3), 290-296 (1999). (Pubitemid 29292183)
37. Wu S, Xing Q, Gao R et al. Response to chlorpromazine treatment may be associated with polymorphisms of the DRD2 gene in Chinese schizophrenic patients. Neurosci. Lett. 376(1), 1-4 (2005). (Pubitemid 40202926)
38. Lencz T, Robinson DG, Xu K et al. DRD2 promoter region variation as a predictor of sustained response to antipsychotic medication in first-episode schizophrenia patients. Am. J. Psychiatry 163(3), 529-531 (2006). (Pubitemid 44469398)
39. Alenius M, Wadelius M, Dahl ML et al. Gene polymorphism influencing treatment response in psychotic patients in a naturalistic setting. J. Psychiatr. Res. 42(11), 884-893 (2008).
40. Ghadirian AM, Chouinard G, Annable L. Sexual dysfunction and plasma prolactin levels in neuroleptic-treated schizophrenic outpatients. J. Nerv. Ment. Dis. 170(8), 463-467 (1982). (Pubitemid 12051650)
41. Nakonezny PA, Byerly MJ, Rush AJ. The relationship between serum prolactin level and sexual functioning among male outpatients with schizophrenia or schizoaffective disorder: a randomized double-blind trial of risperidone vs. quetiapine. J. Sex. Marital Ther. 33(3), 203-216 (2007). (Pubitemid 46535723)
42. Drago F. Prolactin and sexual behavior: a review. Neurosci. Biobehav. Rev. 8(4), 433-439 (1984). (Pubitemid 15155156)
43. Knegtering H, Boks M, Blijd C et al. A randomized open-label comparison of the impact of olanzapine versus risperidone on sexual functioning. J. Sex. Marital Ther. 32(4), 315-326 (2006). (Pubitemid 43995227)
44. Knegtering H, van der Moolen A, Castelein S, Kluiter H, van den Bosch BR. What are the effects of antipsychotics on sexual dysfunctions and endocrine functioning? Psychoneuroendocrinology 28(Suppl. 2), 109-123 (2003). (Pubitemid 36335820)
45. Nakonezny PA, Byerly MJ, Rush AJ. The relationship between serum prolactin level and sexual functioning among male outpatients with schizophrenia or schizoaffective disorder: a randomized double-blind trial of risperidone vs quetiapine. J. Sex. Marital Ther. 33(3), 203-216 (2007). (Pubitemid 46535723)
46. Kleinberg DL, Davis JM, de Coster R, Van Baelen B, Brecher M. Prolactin levels and adverse events in patients treated with risperidone. J. Clin. Psychopharmacol. 19(1), 57-61 (1999). (Pubitemid 29047332)
47. Westheide J, Cvetanovska G, Albrecht C et al. Prolactin, subjective well-being and sexual dysfunction: an open label observational study comparing quetiapine with risperidone. J. Sex. Med. 5(12), 2816-2826 (2008).
48. Corona G, Mannucci E, Fisher AD et al. Effect of hyperprolactinemia in male patients consulting for sexual dysfunction. J. Sex. Med. 4(5), 1485-1493 (2007). (Pubitemid 47337698)
49. Kelly DL, Conley RR. A randomized double-blind 12-week study of quetiapine, risperidone or fluphenazine on sexual functioning in people with schizophrenia. Psychoneuroendocrinology 31(3), 340-346 (2006). (Pubitemid 43261653)
50. Aizenberg D, Modai I, Landa A, Gil-Ad I, Weizman A. Comparison of sexual dysfunction in male schizophrenic patients maintained on treatment with classical antipsychotics versus clozapine. J. Clin. Psychiatry 62(7), 541-544 (2001). (Pubitemid 32703094)
51. Wirshing DA, Pierre JM, Marder SR, Saunders CS, Wirshing WC. Sexual side effects of novel antipsychotic medications. Schizophr. Res. 56(1-2), 25-30 (2002). (Pubitemid 34655464)
52. Dossenbach M, Dyachkova Y, Pirildar S et al. Effects of atypical and typical antipsychotic treatments on sexual function in patients with schizophrenia: 12-month results from the Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study. Eur. Psychiatry 21(4), 251-258 (2006). (Pubitemid 43929245)
53. Strous RD, Kupchik M, Roitman S et al. Comparison between risperidone, olanzapine, and clozapine in the management of chronic schizophrenia: a naturalistic prospective 12-week observational study. Hum. Psychopharmacol. 21(4), 235-243 (2006). (Pubitemid 44043767)
54. Byerly MJ, Nakonezny PA, Bettcher BM et al. Sexual dysfunction associated with second-generation antipsychotics in outpatients with schizophrenia or schizoaffective disorder: an empirical evaluation of olanzapine, risperidone, and quetiapine. Schizophr. Res. 86(1-3), 244-250 (2006). (Pubitemid 44234038)
55. Aizenberg D, Zemishlany Z, Dorfman-Etrog P, Weizman A. Sexual dysfunction in male schizophrenic patients. J. Clin. Psychiatry 56(4), 137-141 (1995).
56. Schotte A, Janssen PF, Gommeren W et al. Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl.) 124(1-2), 57-73 (1996). (Pubitemid 26112775)
57. Brotto LA, Gorzalka BB. Melatonin enhances sexual behavior in the male rat. Physiol. Behav. 68(4), 483-486 (2000). (Pubitemid 30129232)
58. Klint T, Larsson K. Clozapine acts as a 5-HT2 antagonist by attenuating DOI-induced inhibition of male rat sexual behaviour. Psychopharmacology (Berl.) 119(3), 291-294 (1995).
59. Eisenhardt A, Sperling H, Hauck E et al. ACE gene I/D and NOS3 G894T polymorphisms and response to sildenafil in men with erectile dysfunction. Urology 62(1), 152-157 (2003). (Pubitemid 36802105)
60. Gopalakrishnan R, Jacob KS, Kuruvilla A, Vasantharaj B, John JK. Sildenafil in the treatment of antipsychotic-induced erectile dysfunction: a randomized, double-blind, placebo-controlled, flexible-dose, two-way crossover trial. Am. J. Psychiatry 163(3), 494-499 (2006). (Pubitemid 44469393)
61. Benatov R, Reznik I, Zemishlany Z. Sildenafil citrate (Viagra) treatment of sexual dysfunction in a schizophrenic patient. Eur. Psychiatry 14(6), 353-355 (1999).