Monoamine Oxidase A (MAOA) and Catechol-O-Methyltransferase (COMT) Gene Polymorphisms Interact with Maternal Parenting in Association with Adolescent Reactive Aggression but not Proactive Aggression: Evidence of Differential Susceptibility

Zhang, Wenxin; Cao, Cong; Wang, Meiping; Ji, Linqin; Cao, Yanmiao

doi:10.1007/s10964-016-0442-1

Cited by 50Neurotransmitter Receptor Influence on BehaviorChild and Adolescent Psychosocial and Emotional DevelopmentBullying, Victimization, and Aggression

Monoamine Oxidase A (MAOA) and Catechol-O-Methyltransferase (COMT) Gene Polymorphisms Interact with Maternal Parenting in Association with Adolescent Reactive Aggression but not Proactive Aggression: Evidence of Differential Susceptibility

Zhang, Wenxin, Cao, Cong, Wang, Meiping, Ji, Linqin, Cao, Yanmiao·2016·Journal of Youth and Adolescence

DOI 10.1007/s10964-016-0442-1

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Abstract

To date, whether and how gene-environment (G × E) interactions operate differently across distinct subtypes of aggression remains untested. More recently, in contrast with the diathesis-stress hypothesis, an alternative hypothesis of differential susceptibility proposes that individuals could be differentially susceptible to environments depending on their genotypes in a "for better and for worse" manner. The current study examined interactions between monoamine oxidase A (MAOA) T941G and catechol-O-methyltransferase (COMT) Val158Met polymorphisms with maternal parenting on two types of aggression: reactive and proactive. Moreover, whether these potential G × E interactions would be consistent with the diathesis-stress versus the differential susceptibility hypothesis was tested. Within the sample of 1399 Chinese Han adolescents (47.2 % girls, M age = 12.32 years, SD = 0.50), MAOA and COMT genes both interacted with positive parenting in their associations with reactive but not proactive aggression. Adolescents with T alleles/TT homozygotes of MAOA gene or Met alleles of COMT gene exhibited more reactive aggression when exposed to low positive parenting, but less reactive aggression when exposed to high positive parenting. These findings provide the first evidence for distinct G × E interaction effects on reactive versus proactive aggression and lend further support for the differential susceptibility hypothesis.

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There was a significant Val158Met x positive parenting interaction on reactive aggression: Met carriers + positive parenting < Val/Val + positive parenting.
“Significant Val158Met x positive parenting on reactive aggression: Met carriers + positive parenting < Val/Val + positive parenting.”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Zhang [54]
There was no significant interaction between Val158Met x parenting on proactive aggression.
“N.S. interaction between Val158Met x parenting on proactive aggression.”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Zhang [54]
There was no significant interaction between T941G x parenting on proactive aggression.
“N.S. interaction between T941G x parenting on proactive aggression.”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Zhang [54]
There was a significant T941G x positive parenting interaction on reactive aggression: T alleles/TT homozygotes + positive parenting < G alleles/GG homozygotes + positive parenting.
“Significant T941G x positive parenting on reactive aggression: T alleles/TT homozygotes + positive parenting < G alleles/GG homozygotes + positive parenting.”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Zhang [54]
In a study on Chinese early adolescents, Val/Val carriers displayed higher reactive aggression compared to Met-allele carriers in the context of higher positive parenting scores, but lower reactive aggression compared to Met-allele carriers with lower positive parenting scores.
“In a study on Chinese early adolescents, Val/Val carriers were reported to display higher reactive aggression compared to Met-allele carriers in the context of higher positive parenting scores, but lower reactive aggression compared to Met-allele carriers with lower positive parenting scores [54].”
From Genetics of child aggression, a systematic review (2024) · cites this paper as [54]

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“[87] 2016 1399 12 M/F Asia RPQ MAOA COMT |β|s ≤ 0.”
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“This approach was based on the dominant genetic model, as recommended by previous studies (e.g., van Ijzendoorn and Bakermans-Kranenburg, 2015; Zhang et al., 2016), and was justified by previous observations in healthy and ADHD subjects showing, for example:”
Method
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“Consistent with previous research [52,53], we collapsed Met/Met with Val/Met genotype groups and dummy-coded the MAOA and COMT genotypes into 1 = G allele or Val/Val genotype and 0 = T allele or presence of Met allele (i.”
Method
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“On the other hand, youth with divorced parents [69] or a negative parenting environment [66] manifested risk from the Met allele.”
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Cao, C., Cao, L., & Chen, J. (2019) · Journal of Youth and Adolescence · doi:10.1007/s10964-019-01004-3 · Cited by 12 · see citing works
Self-citation
The interactive effects of parent-child relationship, sensory processing sensitivity, and the COMT Val158Met polymorphism on preschoolers' prosocial behaviors
Qianwen, L. I. U., & Zhenhong, W. A. N. G. (2023) · Acta Psychologica Sinica · doi:10.3724/sp.j.1041.2023.00711 · Cited by 12 · see citing works
Interactions between the combined genotypes of 5-HTTLPR and BDNF Val66Met polymorphisms and parenting on adolescent depressive symptoms: A three-year longitudinal study
Wang, M., Tian, X., & Zhang, W. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.01.064 · Cited by 9 · see citing works
Self-citation
Association study of Catechol-O-Methyltransferase (COMT) rs4680 Val158Met gene polymorphism and suicide attempt in Mexican adolescents with major depressive disorder
Sanabrais‐Jiménez, M. A., Aguilar-Garcı́a, A., Hernández, S., Sarmiento, E., Ulloa, R. E., Jiménez‐Anguiano, A., & Camarena, B. (2021) · Nordic Journal of Psychiatry · doi:10.1080/08039488.2021.1945682 · Cited by 11 · see citing works
“Interestingly, the Met158 allele have been linked with high levels of aggressiveness which is a personality trait involved in suicidal behavior [38,39].”
Background
COMT and prenatal maternal smoking in associations with conduct problems and crime: the Pelotas 1993 birth cohort study
Salatino‐Oliveira, A., Murray, J., Kieling, C., Genro, J. P., Polanczyk, G. V., Anselmi, L., Wehrmeister, F. C., Barros, F. C., Menezes, A. M. B., Rohde, L. A., et al. (2016) · Scientific Reports · doi:10.1038/srep29900 · Cited by 10 · see citing works
Brain network integration underpins differential susceptibility of adolescent anxiety
Ding, Q., Xu, J., Peng, S., Chen, J., Luo, Y., Li, X., Wu, R., Li, X., & Qin, S. (2023) · Psychological Medicine · doi:10.1017/s0033291723002325 · Cited by 9 · see citing works
Catechol-O-Methyltransferase Gene Val158Met Polymorphism Moderates the Effect of Social Exclusion and Inclusion on Aggression in Men: Findings From a Mixed Experimental Design
Wang, M., Chen, P., Li, H., Kemp, A. H., & Zhang, W. (2021) · Frontiers in Psychology · doi:10.3389/fpsyg.2020.622914 · Cited by 10 · see citing works
Self-citation
Dark Triad traits mediate the interaction between childhood abuse and COMT Val158Met polymorphism on aggression among incarcerated Chinese males
Zhang, J., Leng, J., Yang, C., Cooke, E. M., Gong, P., & Liu, J. (2022) · Current Psychology · doi:10.1007/s12144-022-03092-0 · Cited by 9 · see citing works
“, 2012) and higher reactive aggression (Zhang et al., 2016) after experiencing childhood stressors, such as parental divorce (Nederhof et al.”
BackgroundResultInfluential
The Impact of Adverse Childhood Experiences on the Development of Adolescent Risk-Taking: The Mediating Effect of Self-Control and Moderating Effect of Genetic Variations
Wang, L., Li, J., Liu, Z.-H., Zeng, J., & Dou, K. (2025) · Journal of Youth and Adolescence · doi:10.1007/s10964-025-02136-5 · Cited by 8 · see citing works
“This questionnaire had shown good psychometric properties in Chinese samples (L. Zhang et al., 2016a).”
Unique and interactive associations of proactive and reactive aggression with cortisol secretion
Paré‐Ruel, M., Brendgen, M. R., Ouellet‐Morin, I., LUPIEN, S. J., Vitaro, F., Dionne, G., & Boivin, M. (2021) · Hormones and Behavior · doi:10.1016/j.yhbeh.2021.105100 · Cited by 7 · see citing works
Effects of childhood trauma on aggressive behaviors and hippocampal function: the modulation of COMT haplotypes
Wang, C., Zhu, L., Zheng, W., Peng, H., Wang, J., Cui, Y. J., Liu, B., & Jiang, T. (2023) · Psychoradiology · doi:10.1093/psyrad/kkad013 · Cited by 7 · see citing works
The centrality of cognition and coping styles in driving aggressive responses
Sebalo, I., Ireland, J. L., & Chu, S. (2022) · International Journal of Law and Psychiatry · doi:10.1016/j.ijlp.2022.101842 · Cited by 6 · see citing works
Parenting Practices and Adolescent Effortful Control: MAOA T941G Gene Polymorphism as a Moderator
Zhao, B., Cao, Y., Zhang, L., & Zhang, W. (2020) · Frontiers in Psychology · doi:10.3389/fpsyg.2020.00060 · Cited by 6 · see citing works
Self-citation
Family Socioeconomic Status and Executive Function in Urban Chinese Children: The Effects of Cortisol Reactivity
Wu, M., Wang, Z., Cao, C., & He, Q. (2021) · Journal of Child and Family Studies · doi:10.1007/s10826-021-02056-5 · Cited by 6 · see citing works
“Most of the research on this hypothesis has focused on susceptibility markers such as temperament (e.g., Pitzer et al., 2011) and genetic factors (e.g., Zhang et al., 2016).”
BackgroundSelf-citation
Inhibitory Control Mediates the Associations Between Parenting Practices and Depressive Symptoms in Adolescents: The Moderating Role of Catechol-O-Methyltransferase (COMT) Gene
Cao, Y., Chen, G., Ji, L., & Zhang, W. (2021) · Journal of Youth and Adolescence · doi:10.1007/s10964-021-01466-4 · Cited by 5 · see citing works
“Numerous genetic polymorphisms have been suggested as influencing sensitivity to the environment (e.g., Green et al., 2017; Van Assche et al., 2016; Zhang et al., 2016).”
BackgroundSelf-citation
COMT and DAT1 polymorphisms moderate the indirect effect of parenting behavior on youth ADHD symptoms through neurocognitive functioning
Morgan, J. E., Caplan, B., Tung, I., Noroña, A. N., Baker, B. L., & Lee, S. S. (2017) · Child Neuropsychology · doi:10.1080/09297049.2017.1346067 · Cited by 5 · see citing works
Infanticide and Human Self Domestication
Kimbrough, E. O., Myers, G. M., & Robson, A. J. (2021) · Frontiers in Psychology · doi:10.3389/fpsyg.2021.667334 · Cited by 5 · see citing works
The Val158Met Polymorphism in 8-Year-Old Boys and Girls Moderates the Influence of Parenting Styles on Proactive Aggression: Testing the Sensitivity to the Environment
del Puerto‐Golzarri, N., Azurmendi, A., Muñoz, J. M., Carreras, M. R., & Pascual‐Sagastizábal, E. (2023) · Brain Sciences · doi:10.3390/brainsci13111513 · Cited by 4 · see citing works
“Similar results were reported by Hygen et al. [56] and Tuvblad et al. [57], who observed that individuals homozygous for the Val allele exhibited higher aggression levels in adverse contexts and lower aggression levels in more favorable contexts when compared to those carrying the Met allele.”
Result
Association of genetic variations in the serotonin and dopamine systems with aggressive behavior in the Chinese adolescent population: Single- and multiple-risk genetic variants.
Chang, H.-J., Yan, Q., Tang, L.-N., Huang, J., Ma, Y.-Q., Ye, X.-Z., Wu, C., Wu, L.-G., & Yu, Y.-Z. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.08.052 · Cited by 6 · see citing works
RETN gene polymorphisms interact with alcohol dependence in association with depression
Xu, X., Xu, Z., Zhou, F., Chen, L., Li, H., Niculescu, M., Shen, G., Wu, L., Wang, W., Chen, L., et al. (2023) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.24933 · Cited by 2 · see citing works
COMT Val/Met, stressful life events and externalizing behaviors in youth: A longitudinal study from the ABCD sample
Kant, T., Koyama, E., Zai, C., Sanches, M., Beitchman, J., & Kennedy, J. L. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e21126 · Cited by 2 · see citing works
“However, this was in disagreement with numerous studies reporting that the effects of Val158Met on youth externalizing behaviors may change depending on the presence of different environmental stressors [19,64 – 66].”
Result
The U-shaped relationship between dopaminergic genes and adolescent aggressive behavior: The moderating role of maternal negative parenting
Xiaonan, L. I. N., Yanmiao, C. A. O., ZHANG, W., & Ji, L. (2022) · Acta Psychologica Sinica · doi:10.3724/sp.j.1041.2023.00588 · Cited by 2 · see citing works
“…Zhang et al., 2015）按照 +2 SD将母亲消极教养区分为高组和低组，以探索和阐明表现于+1 SD 之外的显著交互作用。为避免多重共线性，多基因累积分和母亲消极教养均进行标准化处理。为验证结果的可靠性进行系列敏感性分析：（1）对任一单基因重复上述回归模型检验，比较单基因与多基因累积分模型显著性的差异（Cao & Rijlaarsdam, 2022）；（2）使用 MATLAB R2013b 的 regress 和 crossvalind 函数，进行 k fold 交叉验证（Marcot & Hanea, 2021; 张文新等, 2021）；（3）将样本按照…”
InfluentialSelf-citation
Early Childhood Maltreatment and Adolescent Aggressive Behaviors: A Causal Mediation Analysis of Callous-Unemotional Traits
Zhu, D., Li, C., Wang, F., Li, Y., Yuan, M., Li, Y., Cao, L., Wang, S., Wang, G., Su, P., et al. (2026) · Journal of Child and Family Studies · doi:10.1007/s10826-025-03250-5 · Cited by 1 · see citing works
“In one sample of U.S. adolescents, 17.7% reported engaging in fights at school in the past year (Zhang et al., 2016), while rates in lower-income countries were reported to be several times higher (Elgar et al., 2015).”
Influential
Bridging the theory to evidence gap: a systematic review and analysis of individual × environment models of child development
Rankin, P. S. (2019) · The University of Queensland · doi:10.14264/uql.2020.35 · Cited by 1 · see citing works
Dan Olweus and School Bullying Research in China
Zhang, W., & Ji, L. (2025) · doi:10.1002/9781394173556.ch9 · Cited by 1 · see citing works
Self-citation
On the Need for a Biopsychosocial Victimology: A Foundational Model for Focusing Violence Prevention on Women and Children
Posick, C., Lasko, E. N., & Tremblay, R. E. (2018) · Victims & Offenders · doi:10.1080/15564886.2018.1506852
Personality traits of young men with different diplotypes
Vorobyeva, E. V., Ермаков, П. Н., Михайловна, К. Е., Abakumova, I., Fedotova, O., Aralova, M., Latun, W., & Horonko, L. (2019) · Acta Medica International · doi:10.4103/ami.ami_49_18
Biological Factors of Psychological Change
Haller, J. (2020) · Springer eBooks · doi:10.1007/978-3-030-46331-1_10
A Multilocus Approach to Examining Genetic Susceptibility to Stress and Depression Among Young Adults
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Evaluation of the association COMT Val158Met variant and childhood trauma on aggression in Turkish SCZ patients
Aydın, P. Ç., Yıldırım, Y. E., Erol, A., Nursal, A. F., Atar, A. Ö., Oyacı, Y., Ayar, Y., Kişioğlu, S., & Pehlivan, S. (2024) · Nucleosides Nucleotides & Nucleic Acids · doi:10.1080/15257770.2024.2302524
“[11] Based on this information, in this study, we aimed to investigate the association COMT Val158Met variant and childhood trauma on aggression in Turkish SCZ patients.”
Unpacking Violence: Examining Socioeconomic, Psychological, and Genetic Drivers of Gun-Related Homicide and Potential Solutions
Menezes, J. M., & Batra, K. (2025) · Urban Science · doi:10.3390/urbansci9060190
Authoritative parenting style and aggression in adolescents
Biswas, S., & Narad, A. (2025) · Journal of Interdisciplinary Studies in Education · doi:10.32674/98260f69
A systematic review and a meta-analysis of genetic studies linking dopaminergic alleles to aggression: Where are we now?
Palumbo, S., Grassi, G., Mariotti, V., & Pellegrini, S. (2025) · Aggression and Violent Behavior · doi:10.1016/j.avb.2025.102096
Monoamine oxidase inhibitors prevent glucose-dependent energy production and tumorigenesis of bladder cancer
Resta, J. (2022) · doi:10.70675/81126341z7c1bz4fb7z9bedzb20aa5860853
Parental support moderates the interaction of COMT and BDNF genotypes with early life adversity on problem gambling severity index scores among young adults
Mohamed, M. S., Rukh, G., Bendre, M., Vadlin, S., Olofsdotter, S., Åslund, C., Schiöth, H. B., & Nilsson, K. W. (2026) · Psychiatry Research · doi:10.1016/j.psychres.2026.117468

Interacting Effect of Catechol-O-Methyltransferase (COMT) and Monoamine Oxidase A (MAOA) Gene Polymorphisms, and Stressful Life Events on Aggressive Behavior in Chinese Male Adolescents
Wang, M., Li, H., Deater-Deckard, K., & Zhang, W. (2018) · Frontiers in Psychology · doi:10.3389/fpsyg.2018.01079 · Cited by 19 · see citing works
Self-citation
The Val158Met Polymorphism in 8-Year-Old Boys and Girls Moderates the Influence of Parenting Styles on Proactive Aggression: Testing the Sensitivity to the Environment
del Puerto‐Golzarri, N., Azurmendi, A., Muñoz, J. M., Carreras, M. R., & Pascual‐Sagastizábal, E. (2023) · Brain Sciences · doi:10.3390/brainsci13111513 · Cited by 4 · see citing works
Gene-Gene-Environment Interactions of Serotonin Transporter, Monoamine Oxidase A and Childhood Maltreatment Predict Aggressive Behavior in Chinese Adolescents
Zhang, Y., Ming, Q.-S., Yi, J.-Y., Wang, X., Chai, Q.-L., & Yao, S.-Q. (2017) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2017.00017 · Cited by 45 · see citing works
Child exposure to serious life events, COMT, and aggression: Testing differential susceptibility theory.
Hygen, B. W., Belsky, J., Stenseng, F., Lydersen, S., Guzey, I. C., & Wichstrøm, L. (2015) · Developmental Psychology · doi:10.1037/dev0000020 · Cited by 48 · see citing works
The effects of MAOA genotype, childhood trauma, and sex on trait and state‐dependent aggression
Verhoeven, F. E. A., Booij, L., Kruijt, A., Cerit, H., Antypa, N., & van der Does, W. A. J. (2012) · Brain and Behavior · doi:10.1002/brb3.96 · Cited by 64 · see citing works

Authors: Zhang, W., Cao, C., Wang, M., Ji, L., & Cao, Y.
Affiliations: Shandong Normal University (CN)
Corresponding author: Zhang, Wenxin
ORCID: Zhang, Wenxin
Cao, Cong
Wang, Meiping
Ji, Linqin
Cao, Yanmiao
Venue: Journal of Youth and Adolescence
Publisher: Springer Science and Business Media LLC
Published: 2016-03-01
Volume: 45
Issue: 4
Pages: 812-829
ISSN: 0047-2891 (ISSN-L)
1573-6601
DOI: 10.1007/s10964-016-0442-1
OpenAlex: W2288804401
Cited by: 50
References: 56
Citations by year: 2026: 2 · 2025: 5 · 2024: 2 · 2023: 7 · 2022: 7 · 2021: 9 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 3 · 2016: 1
FWCI: 2.43
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Journal of Youth and Adolescence (publishedVersion)
PubMed (publishedVersion)
Funders: National Natural Science Foundation of China (31271105)
Specialized Research Fund for the Doctoral Program of Higher Education (20133704110001)
Natural Science Foundation of Shandong Provicne (ZR2014CQ030)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
Social Sciences › Psychology › Social Psychology › Bullying, Victimization, and Aggression
Keywords: monoamine oxidase A, catechol-O-methyltransferase, COMT Val158Met polymorphism, gene-environment interaction, differential susceptibility hypothesis, maternal care, positive parenting, reactive aggression, proactive aggression, adolescent aggression
MeSH terms: Aggression, Alleles, Catechol O-Methyltransferase, Child, Female, Genotype, Humans, Male, Maternal Behavior, Monoamine Oxidase, Polymorphism, Genetic, Gene-Environment Interaction

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Monoamine Oxidase A (MAOA) and Catechol-O-Methyltransferase (COMT) Gene Polymorphisms Interact with Maternal Parenting in Association with Adolescent Reactive Aggression but not Proactive Aggression: Evidence of Differential Susceptibility

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