MAOA, maltreatment, and gene–environment interaction predicting children’s mental health: new evidence and a meta-analysis
Abstract
Previous research on adults has shown that a functional polymorphism in the promoter region of the monoamine oxidase A (MAOA) gene moderates the impact of childhood maltreatment on risk for developing antisocial behavior. Thus far, attempts to replicate this finding have been mixed. The current study (i) presents new data investigating this finding in a sample of 975 seven-year-old boys, and (ii) evaluates the extant data by conducting a meta-analysis of published findings. We replicated the original finding by showing that the MAOA polymorphism moderates the development of psychopathology after exposure to physical abuse, we extended the finding to childhood closer in time to the maltreatment experience, and we ruled-out the possibility of a spurious finding by accounting for passive and evocative gene-environment correlation. Moreover, meta-analysis demonstrated that across studies, the association between maltreatment and mental health problems is significantly stronger in the group of males with the genotype conferring low vs high MAOA activity. These findings provide the strongest evidence to date suggesting that the MAOA gene influences vulnerability to environmental stress, and that this biological process can be initiated early in life.
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ELA effects are modified by genetics, child sex and/or gender, exposure features (e.g., timing, nature, and intensity), and the presence of other risks or protective factors.
“Some observed modifiers of ELA effects include genetics [25, 87–89], child sex and/or gender [19, 90, 91], exposure features (e.g., timing, nature, and intensity) [21, 25], and the presence of other risks or protective factors [36].”
From Biological embedding of childhood adversity: from physiological mechanisms to clinical implications (2017) · cites this paper as [90]
A genetic variation in the promoter region for the monoamine oxidase A gene (MAOA) increases antisocial behaviours in boys exposed to the stress of child abuse.
“Similarly, a genetic variation in the promoter region for the monoamine oxidase A gene (MAOA) increases antisocial behaviours in boys exposed to the stress of child abuse127.”
From Stress signalling pathways that impair prefrontal cortex structure and function (2009) · cites this paper as [127]
Heterogeneity in adversity exposure in previous samples may explain why gene-by-environment associations have been inconsistently replicated.
“In fact, heterogeneity in adversity exposure in previous samples may explain inconsistent replication of gene-by-environment associations (Kim-Cohen et al., 2006; Munafò et al., 2009).”
From Developmental psychoneuroendocrine and psychoneuroimmune pathways from childhood adversity to disease (2017) · cites this paper as Kim-Cohen et al., 2006
Kim-Cohen et al. (2006) found that the MAO-A polymorphism moderated the development of psychopathology after physical abuse in a sample of 975 seven-year-old boys.
“For example, Kim-Cohen et al. (2006) found that the MAO-A polymorphism moderated the development of psychopathology after experiencing physical abuse in a sample of 975 seven-year-old boys.”
From Human Aggression Across the Lifespan (2011) · cites this paper as Kim-Cohen et al., 2006
Only a few replications of the MAO-A finding have been published.
“So far, there have only been a few replications of this important finding (Foley et al., 2004; Kim-Cohen et al., 2006; Nilsson et al., 2006).”
From Human Aggression Across the Lifespan (2011) · cites this paper as Kim-Cohen et al., 2006
Gene-environment interactions have been found following physical abuse and later antisocial behavior, with a functional polymorphism in the monoamine oxidase A gene that appeared to increase vulnerability to antisocial behaviors among boys who were abused.
“Similarly, gene  environment interactions have been found following physical abuse and later antisocial behavior, with a functional polymorphism in the monoamine oxidase A gene that appeared to increase vulnerability to antisocial behaviors among boys who were abused (Kim-Cohen et al, 2006).”
From Deviations from the expectable environment in early childhood and emerging psychopathology (2015) · cites this paper as Kim-Cohen et al, 2006
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- Authors
- Kim-Cohen, J., Caspi, A., Taylor, A., Williams, B., Newcombe, R., Craig, I. W., & Moffitt, T. E.
- Affiliations
- University of Wisconsin–Madison (US)
- King's College London (GB)
- Venue
- Molecular Psychiatry
- Published
- 2006-06-27
- Volume
- 11
- Issue
- 10
- Pages
- 903-913
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2168826880
- Cited by
- 1,158
- References
- 75
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 13 · 2023: 67 · 2022: 27 · 2021: 31 · 2020: 45 · 2019: 44 · 2018: 36 · 2017: 60 · 2016: 68 · 2015: 71 · 2014: 91 · 2013: 96 · 2012: 93
- FWCI
- 9.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Economic and Social Research Council (L330 25 3002)
- National Institute of Mental Health (MH-49414, MH 45070, R01MH045070)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
- Keywords
- monoamine oxidase A, child abuse, physical abuse, gene-environment interaction, child mental health, antisocial behavior, psychopathology, replication, sex differences, early childhood
- MeSH terms
- Adolescent, Adult, Affective Symptoms, Antisocial Personality Disorder, Child, Child Abuse, Child Behavior, Child Behavior Disorders, Child, Preschool, Environment, Family Relations, Female, Follow-Up Studies, Humans, Male, Middle Aged, Monoamine Oxidase, Polymorphism, Genetic, Promoter Regions, Genetic, Regression Analysis, Violence, Cohort Studies, Crime Victims, Attention Deficit and Disruptive Behavior Disorders, Genetic Predisposition to Disease, Chromosomes, Human, X
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