Identifying mechanisms that underlie links between COMT genotype and aggression in male adolescents with ADHD

van Goozen, Stephanie H. M. ORCID: https://orcid.org/0000-0002-5983-4734, Langley, Kate ORCID: https://orcid.org/0000-0002-2033-2657, Northover, Clare, Hubble, Kelly ORCID: https://orcid.org/0000-0002-9280-6268, Rubia, Katya, Schepman, Karen, O'Donovan, Michael C. ORCID: https://orcid.org/0000-0001-7073-2379 and Thapar, Anita ORCID: https://orcid.org/0000-0002-3689-737X 2016. Identifying mechanisms that underlie links between COMT genotype and aggression in male adolescents with ADHD. Journal of Child Psychology and Psychiatry 57 (4) , pp. 472-480. 10.1111/jcpp.12464

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Psychology Medicine Neuroscience and Mental Health Research Institute (NMHRI) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects:	B Philosophy. Psychology. Religion > BF Psychology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	ADHD; aggression; conduct disorder; COMT; genetic; child
Additional Information:	This is an open access article under the terms of the Creative Commons Attribution License.
Publisher:	Wiley
ISSN:	0021-9630
Funders:	MRC
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	10 August 2015
Last Modified:	11 Oct 2023 17:44
URI:	https://orca.cardiff.ac.uk/id/eprint/77076

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