Identifying mechanisms that underlie links between COMT genotype and aggression in male adolescents with ADHD
Open accessAbstract
BACKGROUND: There is a known strong genetic contribution to aggression in those with ADHD. In a previous investigation of a large population cohort, impaired 'emotional/social cognitive' processing, assessed by questionnaire, was observed to mediate the link between COMT Val158Met and aggression in individuals with ADHD. We set out to replicate and extend this finding in a clinical sample, using task-based and physiological assessments of emotional and cognitive processing. Our aim was to test the hypothesis that directly assessed emotional processing mediates the link between COMT Val158Met and aggression in young people with ADHD. METHODS: Males aged 10-17 years with ADHD were recruited from UK community clinics (n = 194). Research diagnostic interviews (parent and child) were used to assess psychopathology and generate DSM-IV Conduct Disorder symptom scores. Participants completed tasks assessing executive function (response inhibition and set shifting), empathy for fear, sadness and happiness, and fear conditioning [measured using skin conductance responses (SCR) to aversive stimuli]. RESULTS: COMT Val allele carriers showed poorer response inhibition (F = 5.27, p = .02) and set shifting abilities (F = 6.45, p = .01), reduced fear empathy (F = 4.33, p = .04) and reduced autonomic responsiveness (lower SCRs) to the conditioned aversive stimulus (F = 11.74, p = .001). COMT Val158Met did not predict impairments in recognising others' emotions or affective empathy for happiness or sadness. Mediation analysis revealed that impaired fear-related mechanisms indirectly mediated the link between COMT Val158Met and aggression. CONCLUSION: Our findings suggest fear mechanisms as possible targets for psychological interventions to disrupt links between genetic risk and aggressive outcomes in ADHD. Our findings also reveal the potential of hypothesis-driven approaches for identifying neuropsychological mechanisms that mediate genetic risk effects on behaviour and psychopathology.
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Mediation analyses showed that the bias corrected confidence intervals for the path coefficients did not cross zero for both models (0.091-0.613 for fear conditioning; 0.095-0.288 for fear empathy), consistent with a significant indirect effect of COMT genotype on aggression.
“Mediation analyses showed that the bias corrected confidence intervals for the path coefficients did not cross zero for both models (0.091–0.613 for fear conditioning; 0.095–0.288 for fear empathy), consistent with a significant indirect effect of COMT genotype on aggression”
From Genetics of child aggression, a systematic review (2024) · cites this paper as van Goozen [162]
Aggression scores were VV: mean 1.1 SD 1.3, VM: mean 1.1 SD 1.2, MM: mean 1.4 SD 1.7, p = 0.57.
“Table S2: Aggression scores: VV: mean1.1 SD1.3, VM: mean1.1 SD1.2, MM: mean1.4 SD1.7, p = 0.57”
From Genetics of child aggression, a systematic review (2024) · cites this paper as van Goozen [162]
The Results section says Table S2 provides mean scores for the three genotype groups, but our copy does not include those scores. A search for the stated values and p = .57 found only a different, two-group aggression comparison (p = .83), so the quoted Table S2 figures cannot be checked against our copy. (LLM, conf=0.70)
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- Authors
- van Goozen, S. H. M., Langley, K., Northover, C., Hubble, K., Rubia, K., Schepman, K., O'Donovan, M. C., & Thapar, A.
- Affiliations
- School of Psychology Cardiff University Cardiff UK
- Cardiff University (GB)
- King's College London (GB)
- MRC Centre for Neuropsychiatric Genetics and Genomics Cardiff University Cardiff UK
- Corresponding author
- Thapar, Anita
- Venue
- Journal of Child Psychology and Psychiatry
- Publisher
- Wiley
- Published
- 2015-09-23
- Volume
- 57
- Issue
- 4
- Pages
- 472-480
- ISSN
- 0021-9630 (ISSN-L)
- 1469-7610
- PMC
- PMC5102627
- OpenAlex
- W1902218341
- Cited by
- 42
- References
- 36
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 5 · 2020: 6 · 2019: 3 · 2018: 7 · 2017: 8 · 2016: 4
- FWCI
- 5.15
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Child Psychology and Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by)
- Funders
- UK Medical Research Council (G1000632)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- COMT Val158Met, attention deficit hyperactivity disorder, aggression, conduct disorder, fear conditioning, response inhibition, set-shifting, executive function, skin conductance response, mediation, genetic risk, adolescents
- MeSH terms
- Adolescent, Aggression, Catechol O-Methyltransferase, Child, Emotions, Empathy, Fear, Genotype, Humans, Inhibition, Psychological, Male, Executive Function
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