Criminal Behaviour and Mental Health 24: 368–372 (2014) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/cbm.1917
Monoamine oxidase A alleles in violent offenders with antisocial personality disorder: High activity associated with proactive aggression
NATHAN J. KOLLA1, STEPHEN ATTARD2, GAVIN CRAIG3, NIGEL BLACKWOOD3 AND SHEILAGH HODGINS4, 1Department of Psychiatry, University of Toronto, Centre for Addiction and Mental Health, Toronto, Canada; 2St. Andrew’s Healthcare, Northampton, UK; 3Institute of Psychiatry, King’s College London, London, UK; 4Département de Psychiatrie, Université de Montréal: Centre for Addiction and Mental Health, Research Imaging Centre, 250 College Street, Room B26, Toronto, ON, Canada, M5T 1R8 Meta-analysis has confirmed that, among males, carriers of the low-activity variant (L) of the monoamine oxidase A (MAOA) gene who experienced childhood physical abuse (CPA) show elevated rates of aggressive and antisocial behaviour (Byrd and Manuck, 2014). Studies included examined large population samples, and limited outcome variables to conduct disorder diagnoses and measures of aggression that did not distinguish between its proactive and reactive forms. Two studies examined violent convictions: one reported their association with MAOA-L (Reif et al., 2007) and the other with the MAOA high-activity variant (H) (Tikkanen et al., 2010), both among men who had experienced CPA. In another study of offenders, MAOA-L was associated with factor 2 scores on the Psychopathy Checklist: Screening Version (Sadeh et al., 2013). MAOA-H has also been associated with aggression among boys (Beitchman et al., 2004) and adult men (Manuck et al., 2000). The divergence in findings may reflect two distinct mechanisms underlying violence. Evidence suggests that male carriers of the L and H MAOA genes may react to CPA in different ways. Brain imaging studies have shown that MAOA-L in males is associated with hyper-reactivity to affective stimuli, reduced engagement of prefrontal regulatory regions, and disrupted cortico-limbic circuitry regulating emotion processing (Meyer-Lindenberg et al., 2006). Thus, it
Copyright © 2014 John Wiley & Sons, Ltd.
24: 368–372 (2014) DOI: 10.1002/cbm
MAOA-H and proactive aggression in ASPD
has been hypothesized that MAOA-L constitutes vulnerability for reactive aggression, the most common in general population samples, resulting from increased perception of threat (Meyer-Lindenberg et al., 2006). Conversely, callousness or insensitivity has been associated with violent offending and proactive aggression. Callousness moderates the response to CPA (Silva et al., 2012). In a recent study of toddlers, their lower sensitivity to their mothers’ distress was associated with MAOA-H (Pickles et al., 2013). We have conducted exploratory analyses among violent offenders (VOs) and non-offenders (NOs) to estimate associations between MAOA genotype, CPA, reactive and proactive aggression, and factor 1 and 2 Psychopathy Checklist-Revised (PCL-R) (Hare, 2003) scores. Male VOs were recruited through probation services and healthy NOs from the community (Gregory et al., 2012). Official records confirmed criminal histories. All VOs met diagnostic criteria for antisocial personality disorder (First et al., 1997). Trained clinicians rated participants on the PCL-R from file and interview information; participants completed the Reactive-Proactive Aggression Questionnaire (Raine et al., 2006) and interview with one forensic psychiatrist using the Early Trauma Inventory (Bremner et al., 2000). CPA severity was estimated by summing the frequencies of each physical abuse item endorsed, with high CPA defined as scores above the sample median. Genomic DNA was extracted from buccal cells following procedures described by Freeman et al. (2003). The MAOA-VNTR polymorphism was amplified using the primer sequences MAO APT1 (5’ACAGCCTGACCGTGGAGAAG-3’) and MAO APB1 (5’-GAACGGACGCTCCATTCGGA-3’). The polymerase chain reaction and functional classification of alleles as H or L followed Caspi et al. (2002). The associations of MAOA genotype (H or L), CPA (high/low), and the interaction between CPA and MAOA genotype with proactive aggression, reactive aggression, and factor 1 and 2 PCL-R scores were estimated using multiple regression analyses. The association of these variables with group membership (VO or NO) was estimated using logistic regression. Eighteen VOs and 13 NOs completed the Early Trauma Inventory interview and were genotyped. Their characteristics are presented in Table 1. MAOA-H carriers were no more likely than MAOA-L carriers to have experienced CPA. There was no significant genotype by CPA interaction in any of the models, so the interaction term was removed. The model predicting group membership was significant (p = 0.021), suggesting an association with both genotype and CPA. There was a trend towards MAOA-H (β = 1.7, SE = 0.9, p = 0.053) and high CPA (β = 1.5, SE = 0.8, p = 0.085) being independently associated with violent offender status. Models including reactive aggression and PCL-R factor 1 scores were not significant. The model incorporating proactive aggression was significant (p = 0.001), with genotype (MAOA-H; β = 4.4, SE = 1.9, p = 0.021) and CPA (high CPA; β = 6.0, SE = 1.9, p = 0.001). The PCL-R factor 2 score model was also significant (p = 0.033), with CPA as the only independent association (high CPA; β = 4.6, SE = 1.9, p = 0.017).
Copyright © 2014 John Wiley & Sons, Ltd.
24: 368–372 (2014) DOI: 10.1002/cbm
369
370
Kolla et al.
Table 1: Demographic and clinical characteristics
Age (mean ± SD) Ethnicitya Caucasian Black MAOA-H allele High CPA Aggression Reactive aggression (mean ± SD) Proactive aggression (mean ± SD) PCL-R Factor 1 (mean ± SD) Factor 2 (mean ± SD)
Healthy n = 13
Violent offenders n = 18
37.0 ± 7.7
38.3 ± 7.9
7/13 6/13 5/13 3/13
13/18 4/18 14/18 11/18
4.9 ± 2.9
Statistic
df
p-value
t = 0.47
29
0.65 0.45b 0.22b 0.027 0.067b
χ 2 = 4.9
1
8.9 ± 6.0
t = 2.5
29
0.019
2.2 ± 3.1
9.6 ± 6.7
t = 4.2
29
< 0.001
1.1 ± 1.8 2.2 ± 1.6
6.1 ± 3.7 11.9 ± 4.7
t = 4.5 t = 7.2
29 29
< 0.001 < 0.001
SD, standard deviation; df, degrees of freedom; CPA, childhood physical abuse; PCL-R, Psychopathy Checklist-Revised. a Black and Caucasian ethnicities accounted for 96.8% of the sample; b Fisher’s exact test
In the Caspi et al. (2002) birth cohort study, one third of the males carried the MAOA-H variant, 8% experienced severe CPA and 28% probable CPA, and 11% had been convicted of a violent offence. In our sample, 58% carried MAOA-H, 45% had experienced CPA and 58% had a conviction for violence. Fourteen of 18 VOs carried MAOA-H. As in the Caspi cohort, there was no association between genotype and CPA. We detected no interaction of genotype and CPA, which may be because of the small sample. MAOA-H was associated with proactive aggression, as in previous reports showing a relationship between this genetic variant and aggressiveness (Beitchman et al., 2004). Further, CPA was associated with both proactive aggression and lifelong antisocial behaviour. Approximately one third of men in the population carry MAOA-H, yet our results indicate that this genetic variant is associated with predatory aggression. How can this be? MAOA-H may interact with CPA, or other environmental factors, to increase the risk of offending and predatory violence. In order to detect such an interaction, a larger sample of proactively violent offenders would be required. Alternatively, or additionally, carriers of MAOA-H may be emotionally insensitive to negative events such as CPA but learn, through modelling, to engage in proactive aggression. To test this hypothesis, a prospective, genetically-informed investigation of a large cohort would be required. A final possibility is that CPA leads to epigenetic processes that alter the expression of MAOA in a genotype-specific manner.
Copyright © 2014 John Wiley & Sons, Ltd.
24: 368–372 (2014) DOI: 10.1002/cbm
MAOA-H and proactive aggression in ASPD
References Beitchman JH, Mik HM, Ehtesham S, Douglas L, Kennedy JL (2004) MAOA and persistent, pervasive childhood aggression. Molecular Psychiatry 9: 546–547. DOI: 10.1038/sj.mp.4001492 Bremner JD, Vermetten E, Mazure CM (2000) Development and preliminary psychometric properties of an instrument for the measurement of childhood trauma: The early trauma inventory. Depression and Anxiety 12: 1–12. Byrd AL, Manuck SB (2014) MAOA, childhood maltreatment, and antisocial behaviour: meta-analysis of a gene-environment interaction. Biological Psychiatry 75: 9–17. DOI: 10.1016/j.biopsych.2013.05.004 Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R (2002) Role of genotype in the cycle of violence in maltreated children. Science 297: 851–854. DOI: 10.1126/science.1072290297/5582/851 [pii] First MB, Gibbon M, Spitzer RL, Williams JBW, Benjamin LS (1997) Structured Clinical Interview for DSM-IV Axis II Personality Disorders, (SCID-II). Washington, D.C: American Psychiatric Press, Inc. Freeman B, Smith N, Curtis C, Huckett L, Mill J, Craig IW (2003) DNA from buccal swabs recruited by mail: evaluation of storage effects on long-term stability and suitability for multiplex polymerase chain reaction genotyping. Behavior Genetics 33: 67–72. DOI: 0001-8244/03/0100-0067/06 Gregory S, Ffytche D, Simmons A, Kumari V, Howard M, Hodgins S, Blackwood N (2012) The antisocial brain: psychopathy matters. Archives of General Psychiatry 69: 962–972. DOI: 10.1001/archgenpsychiatry.2012.222 Hare R (2003) Hare Psychopathy Checklist-Revised (2nd ed). Toronto: Multi-Health Systems. Manuck SB, Flory JD, Ferrell RE, Mann JJ, Muldoon MF (2000) A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity. Psychiatry Research 95: 9–23. DOI: 0165-1781r00 Meyer-Lindenberg A, Buckholtz JW, Kolachana B, Hariri AR, Pezawas L, Blasi G, Wabnitz A, Honea R, Verchinski B, Callicott JH, Egan M, Mattay V, Weinberger DR (2006) Neural mechanisms of genetic risk for impulsivity and violence in humans. Proceedings of the National Academy of Sciences of the United States of America 103: 6269–6274. DOI: 10.1073/pnas.0511311103 Pickles A, Hill J, Breen G, Quinn J, Abbott K, Jones H, Sharp H (2013) Evidence for interplay between genes and parenting on infant temperament in the first year of life: monoamine oxidase A polymorphism moderates effects of maternal sensitivity on infant anger proneness. The Journal of Child Psychology and Psychiatry 54: 1308–1317. DOI: 10.1111/jcpp.12081 Raine A, Dodge K, Loeber R, Gatzke-Kopp L, Lynam D, Reynolds C, Stouthamer-Loeber M (2006) The reactive-proactive aggression questionnaire: differential correlates of reactive and proactive aggression in adolescent boys. Aggressive Behavior 32: 159–171. DOI: 10.1002/ab.20115 Reif A, Rosler M, Freitag CM, Schneider M, Eujen A, Kissling C, Wenzler D, Jacob CP, Retz-Junginger P, Thome J, Lesch KP, Retz W (2007) Nature and nurture predispose to violent behavior: serotonergic genes and adverse childhood environment. Neuropsychopharmacology 32: 2375–2383. DOI: 10.1038/sj.npp.1301359 Sadeh N, Javdani S, Verona E (2013) Analysis of monoaminergic genes, childhood abuse, and dimensions of psychopathy. Journal of Abnormal Psychology 122: 167–179. DOI: 10.1037/ a0029866 Silva TC, Larm P, Vitaro F, Tremblay RE, Hodgins S (2012) The association between maltreatment in childhood and criminal convictions to age 24: a prospective study of a community sample of males from disadvantaged neighbourhoods. European Child & Adolescent Psychiatry 21: 403–413. DOI: 10.1007/s00787-012-0281-x
Copyright © 2014 John Wiley & Sons, Ltd.
24: 368–372 (2014) DOI: 10.1002/cbm
371
372
Kolla et al.
Tikkanen R, Ducci F, Goldman D, Holi M, Lindberg N, Tiihonen J, Virkkunen M (2010) MAOA alters the effects of heavy drinking and childhood physical abuse on risk for severe impulsive acts of violence among alcoholic violent offenders. Alcoholism: Clinical and Experimental Research 34: 853–860. DOI: 10.1111/j.1530-0277.2010.01157.x 8
Address correspondence to: Nathan J. Kolla, University of Toronto, Department of Psychiatry, Toronto, Canada; Centre for Addiction and Mental Health, Toronto, Canada. Email: [email protected]
Copyright © 2014 John Wiley & Sons, Ltd.
24: 368–372 (2014) DOI: 10.1002/cbm
Monoamine oxidase A alleles in violent offenders with antisocial personality disorder: High activity associated with proactive aggression
NATHAN J. KOLLA1, STEPHEN ATTARD2, GAVIN CRAIG3, NIGEL BLACKWOOD3 AND SHEILAGH HODGINS4, 1Department of Psychiatry, University of Toronto, Centre for Addiction and Mental Health, Toronto, Canada; 2St. Andrew’s Healthcare, Northampton, UK; 3Institute of Psychiatry, King’s College London, London, UK; 4Département de Psychiatrie, Université de Montréal: Centre for Addiction and Mental Health, Research Imaging Centre, 250 College Street, Room B26, Toronto, ON, Canada, M5T 1R8 Meta-analysis has confirmed that, among males, carriers of the low-activity variant (L) of the monoamine oxidase A (MAOA) gene who experienced childhood physical abuse (CPA) show elevated rates of aggressive and antisocial behaviour (Byrd and Manuck, 2014). Studies included examined large population samples, and limited outcome variables to conduct disorder diagnoses and measures of aggression that did not distinguish between its proactive and reactive forms. Two studies examined violent convictions: one reported their association with MAOA-L (Reif et al., 2007) and the other with the MAOA high-activity variant (H) (Tikkanen et al., 2010), both among men who had experienced CPA. In another study of offenders, MAOA-L was associated with factor 2 scores on the Psychopathy Checklist: Screening Version (Sadeh et al., 2013). MAOA-H has also been associated with aggression among boys (Beitchman et al., 2004) and adult men (Manuck et al., 2000). The divergence in findings may reflect two distinct mechanisms underlying violence. Evidence suggests that male carriers of the L and H MAOA genes may react to CPA in different ways. Brain imaging studies have shown that MAOA-L in males is associated with hyper-reactivity to affective stimuli, reduced engagement of prefrontal regulatory regions, and disrupted cortico-limbic circuitry regulating emotion processing (Meyer-Lindenberg et al., 2006). Thus, it
Copyright © 2014 John Wiley & Sons, Ltd.
24: 368–372 (2014) DOI: 10.1002/cbm
MAOA-H and proactive aggression in ASPD
has been hypothesized that MAOA-L constitutes vulnerability for reactive aggression, the most common in general population samples, resulting from increased perception of threat (Meyer-Lindenberg et al., 2006). Conversely, callousness or insensitivity has been associated with violent offending and proactive aggression. Callousness moderates the response to CPA (Silva et al., 2012). In a recent study of toddlers, their lower sensitivity to their mothers’ distress was associated with MAOA-H (Pickles et al., 2013). We have conducted exploratory analyses among violent offenders (VOs) and non-offenders (NOs) to estimate associations between MAOA genotype, CPA, reactive and proactive aggression, and factor 1 and 2 Psychopathy Checklist-Revised (PCL-R) (Hare, 2003) scores. Male VOs were recruited through probation services and healthy NOs from the community (Gregory et al., 2012). Official records confirmed criminal histories. All VOs met diagnostic criteria for antisocial personality disorder (First et al., 1997). Trained clinicians rated participants on the PCL-R from file and interview information; participants completed the Reactive-Proactive Aggression Questionnaire (Raine et al., 2006) and interview with one forensic psychiatrist using the Early Trauma Inventory (Bremner et al., 2000). CPA severity was estimated by summing the frequencies of each physical abuse item endorsed, with high CPA defined as scores above the sample median. Genomic DNA was extracted from buccal cells following procedures described by Freeman et al. (2003). The MAOA-VNTR polymorphism was amplified using the primer sequences MAO APT1 (5’ACAGCCTGACCGTGGAGAAG-3’) and MAO APB1 (5’-GAACGGACGCTCCATTCGGA-3’). The polymerase chain reaction and functional classification of alleles as H or L followed Caspi et al. (2002). The associations of MAOA genotype (H or L), CPA (high/low), and the interaction between CPA and MAOA genotype with proactive aggression, reactive aggression, and factor 1 and 2 PCL-R scores were estimated using multiple regression analyses. The association of these variables with group membership (VO or NO) was estimated using logistic regression. Eighteen VOs and 13 NOs completed the Early Trauma Inventory interview and were genotyped. Their characteristics are presented in Table 1. MAOA-H carriers were no more likely than MAOA-L carriers to have experienced CPA. There was no significant genotype by CPA interaction in any of the models, so the interaction term was removed. The model predicting group membership was significant (p = 0.021), suggesting an association with both genotype and CPA. There was a trend towards MAOA-H (β = 1.7, SE = 0.9, p = 0.053) and high CPA (β = 1.5, SE = 0.8, p = 0.085) being independently associated with violent offender status. Models including reactive aggression and PCL-R factor 1 scores were not significant. The model incorporating proactive aggression was significant (p = 0.001), with genotype (MAOA-H; β = 4.4, SE = 1.9, p = 0.021) and CPA (high CPA; β = 6.0, SE = 1.9, p = 0.001). The PCL-R factor 2 score model was also significant (p = 0.033), with CPA as the only independent association (high CPA; β = 4.6, SE = 1.9, p = 0.017).
Copyright © 2014 John Wiley & Sons, Ltd.
24: 368–372 (2014) DOI: 10.1002/cbm
369
370
Kolla et al.
Table 1: Demographic and clinical characteristics
Age (mean ± SD) Ethnicitya Caucasian Black MAOA-H allele High CPA Aggression Reactive aggression (mean ± SD) Proactive aggression (mean ± SD) PCL-R Factor 1 (mean ± SD) Factor 2 (mean ± SD)
Healthy n = 13
Violent offenders n = 18
37.0 ± 7.7
38.3 ± 7.9
7/13 6/13 5/13 3/13
13/18 4/18 14/18 11/18
4.9 ± 2.9
Statistic
df
p-value
t = 0.47
29
0.65 0.45b 0.22b 0.027 0.067b
χ 2 = 4.9
1
8.9 ± 6.0
t = 2.5
29
0.019
2.2 ± 3.1
9.6 ± 6.7
t = 4.2
29
< 0.001
1.1 ± 1.8 2.2 ± 1.6
6.1 ± 3.7 11.9 ± 4.7
t = 4.5 t = 7.2
29 29
< 0.001 < 0.001
SD, standard deviation; df, degrees of freedom; CPA, childhood physical abuse; PCL-R, Psychopathy Checklist-Revised. a Black and Caucasian ethnicities accounted for 96.8% of the sample; b Fisher’s exact test
In the Caspi et al. (2002) birth cohort study, one third of the males carried the MAOA-H variant, 8% experienced severe CPA and 28% probable CPA, and 11% had been convicted of a violent offence. In our sample, 58% carried MAOA-H, 45% had experienced CPA and 58% had a conviction for violence. Fourteen of 18 VOs carried MAOA-H. As in the Caspi cohort, there was no association between genotype and CPA. We detected no interaction of genotype and CPA, which may be because of the small sample. MAOA-H was associated with proactive aggression, as in previous reports showing a relationship between this genetic variant and aggressiveness (Beitchman et al., 2004). Further, CPA was associated with both proactive aggression and lifelong antisocial behaviour. Approximately one third of men in the population carry MAOA-H, yet our results indicate that this genetic variant is associated with predatory aggression. How can this be? MAOA-H may interact with CPA, or other environmental factors, to increase the risk of offending and predatory violence. In order to detect such an interaction, a larger sample of proactively violent offenders would be required. Alternatively, or additionally, carriers of MAOA-H may be emotionally insensitive to negative events such as CPA but learn, through modelling, to engage in proactive aggression. To test this hypothesis, a prospective, genetically-informed investigation of a large cohort would be required. A final possibility is that CPA leads to epigenetic processes that alter the expression of MAOA in a genotype-specific manner.
Copyright © 2014 John Wiley & Sons, Ltd.
24: 368–372 (2014) DOI: 10.1002/cbm
MAOA-H and proactive aggression in ASPD
References Beitchman JH, Mik HM, Ehtesham S, Douglas L, Kennedy JL (2004) MAOA and persistent, pervasive childhood aggression. Molecular Psychiatry 9: 546–547. DOI: 10.1038/sj.mp.4001492 Bremner JD, Vermetten E, Mazure CM (2000) Development and preliminary psychometric properties of an instrument for the measurement of childhood trauma: The early trauma inventory. Depression and Anxiety 12: 1–12. Byrd AL, Manuck SB (2014) MAOA, childhood maltreatment, and antisocial behaviour: meta-analysis of a gene-environment interaction. Biological Psychiatry 75: 9–17. DOI: 10.1016/j.biopsych.2013.05.004 Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R (2002) Role of genotype in the cycle of violence in maltreated children. Science 297: 851–854. DOI: 10.1126/science.1072290297/5582/851 [pii] First MB, Gibbon M, Spitzer RL, Williams JBW, Benjamin LS (1997) Structured Clinical Interview for DSM-IV Axis II Personality Disorders, (SCID-II). Washington, D.C: American Psychiatric Press, Inc. Freeman B, Smith N, Curtis C, Huckett L, Mill J, Craig IW (2003) DNA from buccal swabs recruited by mail: evaluation of storage effects on long-term stability and suitability for multiplex polymerase chain reaction genotyping. Behavior Genetics 33: 67–72. DOI: 0001-8244/03/0100-0067/06 Gregory S, Ffytche D, Simmons A, Kumari V, Howard M, Hodgins S, Blackwood N (2012) The antisocial brain: psychopathy matters. Archives of General Psychiatry 69: 962–972. DOI: 10.1001/archgenpsychiatry.2012.222 Hare R (2003) Hare Psychopathy Checklist-Revised (2nd ed). Toronto: Multi-Health Systems. Manuck SB, Flory JD, Ferrell RE, Mann JJ, Muldoon MF (2000) A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity. Psychiatry Research 95: 9–23. DOI: 0165-1781r00 Meyer-Lindenberg A, Buckholtz JW, Kolachana B, Hariri AR, Pezawas L, Blasi G, Wabnitz A, Honea R, Verchinski B, Callicott JH, Egan M, Mattay V, Weinberger DR (2006) Neural mechanisms of genetic risk for impulsivity and violence in humans. Proceedings of the National Academy of Sciences of the United States of America 103: 6269–6274. DOI: 10.1073/pnas.0511311103 Pickles A, Hill J, Breen G, Quinn J, Abbott K, Jones H, Sharp H (2013) Evidence for interplay between genes and parenting on infant temperament in the first year of life: monoamine oxidase A polymorphism moderates effects of maternal sensitivity on infant anger proneness. The Journal of Child Psychology and Psychiatry 54: 1308–1317. DOI: 10.1111/jcpp.12081 Raine A, Dodge K, Loeber R, Gatzke-Kopp L, Lynam D, Reynolds C, Stouthamer-Loeber M (2006) The reactive-proactive aggression questionnaire: differential correlates of reactive and proactive aggression in adolescent boys. Aggressive Behavior 32: 159–171. DOI: 10.1002/ab.20115 Reif A, Rosler M, Freitag CM, Schneider M, Eujen A, Kissling C, Wenzler D, Jacob CP, Retz-Junginger P, Thome J, Lesch KP, Retz W (2007) Nature and nurture predispose to violent behavior: serotonergic genes and adverse childhood environment. Neuropsychopharmacology 32: 2375–2383. DOI: 10.1038/sj.npp.1301359 Sadeh N, Javdani S, Verona E (2013) Analysis of monoaminergic genes, childhood abuse, and dimensions of psychopathy. Journal of Abnormal Psychology 122: 167–179. DOI: 10.1037/ a0029866 Silva TC, Larm P, Vitaro F, Tremblay RE, Hodgins S (2012) The association between maltreatment in childhood and criminal convictions to age 24: a prospective study of a community sample of males from disadvantaged neighbourhoods. European Child & Adolescent Psychiatry 21: 403–413. DOI: 10.1007/s00787-012-0281-x
Copyright © 2014 John Wiley & Sons, Ltd.
24: 368–372 (2014) DOI: 10.1002/cbm
371
372
Kolla et al.
Tikkanen R, Ducci F, Goldman D, Holi M, Lindberg N, Tiihonen J, Virkkunen M (2010) MAOA alters the effects of heavy drinking and childhood physical abuse on risk for severe impulsive acts of violence among alcoholic violent offenders. Alcoholism: Clinical and Experimental Research 34: 853–860. DOI: 10.1111/j.1530-0277.2010.01157.x 8
Address correspondence to: Nathan J. Kolla, University of Toronto, Department of Psychiatry, Toronto, Canada; Centre for Addiction and Mental Health, Toronto, Canada. Email: [email protected]
Copyright © 2014 John Wiley & Sons, Ltd.
24: 368–372 (2014) DOI: 10.1002/cbm
