The MAOA and COMT Gene Polymorphisms in Patients with Schizophrenia Committed Homicide

V.A. Soldatkin, PhD, ScD¹,*; T.P. Shkurat, PhD, ScD²; A.S. Bobkov¹; E.V. Mashkina, PhD²; A.V. Tretyakov³; A.Ya. Perekhov, PhD¹; V.V. Mrykhin, PhD¹; A.I. Kovalev¹; O.A. Bukhanovskaya, PhD¹; M.N. Kryuchkova¹

¹Rostov State Medical University, Rostov-on-Don, Russia; ²Southern Federal University, Rostov-on-Don, Russia;³Psychoneurological dispensary, Novocherkassk, Russia

*Corresponding author: Victor A. Soldatkin, PhD, ScD. Head of Department of Psychiatry and Addiction of Rostov State Medical University; Rostov-on-Don, Russia. E-mail: sva-rostov@mail.ru

Published: December 23, 2014. 

Abstract: 

Numerous studies have indicated that aggression and homicide are more frequent among people with schizophrenia than in the general population. There is considerable evidence that schizophrenia involves a dysbalance between subcortical and cortical dopaminergic systems. The major pathways for catecholamine degradation are oxidative deamination through the action of monoamine oxidase A (MAOA) and by methylation through the action of catechol-O-methyltransferase (COMT).  Activity of both enzymes is encoded by the corresponding genes—MAOA and COMT. The aim of our study was to analyze the association between the COMT-Val158Met and MAOA-uVNTR polymorphisms and the risk of committing homicide by patients with schizophrenia.

Methods: The study included 50 Caucasian male patients with paranoid schizophrenia (PS). All patients were divided into two groups: Group 1 consisted of 26 PS patients who have committed homicide; Group 2 consisted of 24 PS patients who did not have a history of socially violent behavior.  The control group comprised 23 apparently healthy Caucasian men of the same age.  All patients underwent clinical-psychopathological and clinical-anamnestic examinations. Molecular genetic studies were performed in the Shared Research Facility Center "High Technologies" at SFedU. 

Results: Our study revealed no direct correlation between the COMT-Val158Met and MAOA-uVNTR polymorphisms and risk of committing homicide by patients with schizophrenia. At the same time, we detected an association between high-activity gene variants, viz., the MAOA-4R allele and the COMT-158Met/158Met genotype, and the schizoid and unstable premorbid accentuation in patients who had committed murder, whereas the schizoid and unstable accentuation correlated with homicide behavior in patients with schizophrenia.

Conclusion: The obtained findings suggest that genetic variation affects the homicidal behavior indirectly, through the various types of premorbid accentuation and confirm the validity of the well-known concept of "syndrome-person-situation," traced back to the mid-20th century, which explains the commission of serious offenses by patients with schizophrenia.

Keywords: 
schizophrenia, homicide, COMT-Val158Met and MAOA-uVNTR polymorphisms
References: 
  1. Fazel S, Gulati G, Linsell L, Geddes JR, Grann M. Schizophrenia and violence: systematic review and meta-analysis. PLoS Med 2009; 6(8):e1000120.
  2. Soyka M, Graz C, Bottlender R, Dirschedl P, Schoech H. Clinical correlates of later violence and criminal offences in schizophrenia. Schizophr Res 2007; 94(1-3):89-98.
  3. Dmitrieva T B, D Shostakovich B. Aggression and mental health. St. Petersburg. 2002. [Book in Russian].
  4. Fazel S, Grann M. The population impact of severe mental illness on violent crime. Am J Psychiatry.2006; 163(8):1397–403.       
  5. Soldatkin VA, Retyunsky KYu, Bobkov AS, Tretyakov AB. Problem of the repeated homicides committed by patients with schizophrenia (case report). Russ J Psych 2013; 2:20-31. [Article in Russian].
  6. Soyka M. Neurobiology of aggression and violence in schizophrenia Schizophr Bull 2011; 37(5):913-20.
  7. Guillin O, Abi-Dargham A, Laruelle M. Neurobiology of dopamine in schizophrenia. Int Rev Neurobiol 2007; 78:1-39.         
  8. Miczek KA, Meyer-Lindenberg A. Neuroscience of aggression. Springer ( Berlin, Heidelberg); 2014.
  9. Ross CA, Margolis RL, Reading SA, Pletnikov M, Coyle JT. Neurobiology of schizophrenia. Neuron 2006;52(1):139-53.
  10. Šagud M, Mück-Šeler D, Mihaljević-Peleš A, Vuksan-Ćusa B, Živković M, Jakovljević M, et al. Catechol-O-methyl transferase and schizophrenia. Psychiatria Danub 2010; 22(2):270-4.
  11. Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA. Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Science 1993;262(5133):578-80.
  12. Cases O, Seif I, Grimsby J, Gaspar P, Chen K, Pournin S, et al. Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. Science 1995; 268(5218):1763-6.
  13. Sabol SZ, Hu S, Hamer D. A functional polymorphism in the monoamine oxidase A gene promoter. Hum Genet 1998;103(3):273–9
  14. Huang YY, Cate SP, Battistuzzi C, Oquendo MA, Brent D, Mann JJ. An association between a functional polymorphism in the monoamine oxidase a gene promoter, impulsive traits and early abuse experiences. Neuropsychopharmacology 2004; 29(8):1498-505.
  15.  Nishioka SA, Perin EA,  Sampaio AS, Cordeiro Q, Cappi C, Mastrorosa RS, et al. The role of the VNTR functional polymorphism of the promoter region of the MAOA gene on psychiatric disorders. Rev Psiq Clín 2011;38(1):34-42.
  16. Manuck SB, Flory JD, Ferrell RE, Mann JJ, Muldoon MF. A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity. Psychiatry Res 2000;95(1):9-23.
  17. Zammit S, Jones G, Jones SJ, Norton N, Sanders RD, Milham C, et al. Polymorphisms in the MAOA, MAOB, and COMT genes and aggressive behavior in schizophrenia. Am J Med Genet B Neuropsychiatr Genet 2004; 128B(1):19-20.
  18.  Koen L, Kinnear CJ, Corfield VA, Emsley RA, Jordaan E, Keyter N, et al. Violence in male patients with schizophrenia: risk markers in a South African population. Aust N Z J Psychiatry 2004;38(4):254-9.
  19. Strous RD, Nolan KA, Lapidus R, Diaz L, Saito T, Lachman HM. Aggressive behavior in schizophrenia is associated with the low enzyme activity COMT polymorphism: a replication study. Am J Med Genet B Neuropsychiatr Genet 2003; 120B(1):29-34.
  20.  Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, et al. Role of genotype in the cycle of violence in maltreated children. Science 2002; 297(5582):851-4.
  21. Kim-Cohen J, Caspi A, Taylor A, Williams B, Newcombe R, Craig IW, et al. MAOA, maltreatment, and gene-environment interaction predicting children’s mental health: new evidence and a meta-analysis. Mol Psychiatry 2006; 11(10):903-13.
  22. Taylor A, Kim-Cohen J. Meta-analysis of gene-environment interactions in developmental psychopathology. Dev Psychopathol 2007; 19(4):1029-37.
  23. Kieling C, Hutz MH, Genro JP, Polanczyk GV, Anselmi L, Camey S, et al. LA. Gene-environment interaction in externalizing problems among adolescents: evidence from the Pelotas 1993 Birth Cohort Study. J Child Psychol Psychiatry 2013; 54(3):298-304.
  24. Haberstick BC, Lessem JM, Hewitt JK, Smolen A, Hopfer CJ, Halpern CT, et al. MAOA genotype, childhood maltreatment, and their interaction in the etiology of adult antisocial behaviors. Biol Psychiatry 2013; 75(1):25-30.
  25. Lachman HM, Papolos DF, Saito T, Yu YM, Szumlanski CL, Weinshilboum RM. Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 1996; 6(3):243-50.
  26.  Malloy-Diniz LF, Lage GM, Campos SB, de Paula JJ, de Souza Costa D, Romano-Silva MA, et al. Association between the catechol O-methyltransferase (COMT) Val158met polymorphism and different dimensions of impulsivity. PLoS One 2013;8(9):e73509.
  27. Halleland H, Lundervold AJ, Halmøy A, Haavik J, Johansson S. Association between catechol O-methyltransferase (COMT) haplotypes and severity of hyperactivity symptoms in adults. Am J Med Genet B Neuropsychiatr Genet 2009; 150B(3):403-10.
  28.  Liou YJ, Tsai SJ, Hong CJ, Wang YC, Lai IC. Association analysis of a functional catechol-O-methyltransferase gene polymorphism in schizophrenic patients in Taiwan. Neuropsychobiology 2001; 43(1):11-4.
  29.  Zammit S, Jones G, Jones SJ, Norton N, Sanders RD, Milham C, et al.  Polymorphisms in the MAOA, MAOB, and COMT genes and aggressive behavior in schizophrenia. Am J Med Genet B Neuropsychiatr Genet 2004; 128B(1):19-20.
  30. Kim YR, Kim JH, Kim SJ, Lee D, Min SK. Catechol-O-methyltransferase Val158Met polymorphism in relation to aggressive schizophrenia in a Korean population. Eur Neuropsychopharmacol 2008;18(11):820–5
  31.  Gu Y, Yun L, Tian Y, Hu Z. Association between COMT gene and Chinese male schizophrenic patients with violent behavior. Med Sci Monit 2009; 15(9):CR484-9.
  32. Singh JP, Volavka J, Czobor P, Van Dorn RA. A meta-analysis of the Val158Met COMT polymorphism and violent behavior in schizophrenia. PLoS ONE 2012; 7(8): e43423.
  33.  Iofrida C, Palumbo S, Pellegrini S. Molecular genetics and antisocial behavior: Where do we stand? Exp Biol Med (Maywood) 2014; 239(11):1514-23.

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Int J Biomed. 2014; 4(4):213-217. © 2014 International Medical Research and Development Corporation. All rights reserved.