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. 2008 Nov;33(6):499-508.

Serotonin2A receptor binding potential in people with aggressive and violent behaviour

Jeffrey H Meyer  1 , Alan A Wilson, Pablo Rusjan, Michael Clark, Sylvain Houle, Scott Woodside, John Arrowood, Krystle Martin, Michael Colleton
Affiliations

Serotonin2A receptor binding potential in people with aggressive and violent behaviour

Jeffrey H Meyer et al. J Psychiatry Neurosci. 2008 Nov.

Abstract
in English, French

Objective: Indexes of brain serotonin2A (5-HT2A) density have never been investigated in a sample of humans with violent aggressive behaviour unbiased by medication use or current axis I psychiatric disorders. The objective of this study was to investigate prefrontal cortex 5-HT2A binding potential (BPND), an index of 5-HT2A density, in an unbiased sample of people with violent aggressive behaviour.

Methods: We used [18F] setoperone positron emission tomography to measure 5-HT2A BPND in the dorsolateral prefrontal cortex (primarily sampling Brodmann area 9) in 16 participants with violent aggressive behaviour and 16 healthy control participants.

Results: In people with violent aggressive behaviours, the slope of 5-HT2A BPND decline in the dorsolateral prefrontal cortex is 44% less than in healthy control participants (analysis of variance group by age interaction, p = 0.004). Prefrontal cortex 5-HT2A BPND was significantly lower in participants with more severe impulsivity and aggression (multiple linear regression with age and Barratt Impulsivity Scale [BIS] as predictor variables and regional 5-HT2A BPND as dependent variable; effect of BIS, dorsolateral prefrontal cortex: F1,13 = 7.95, p = 0.014).

Conclusion: Lower prefrontal 5-HT2A BPND is related to violent aggression. Lower 5-HT2A BPND occurs at a younger age, when violent behaviour is more frequent, and is more prominent when impulsivity and aggression are more severe.

Objectif: On n'a jamais étudié les indices de la densité de la sérotonine2A (5-HT2A) dans le cerveau d'un échantillon d'êtres humains qui ont un comportement agressif violent sans distorsion attribuable à l'utilisation de médicaments ou à des troubles psychiatriques courants de l'axe I. Cette étude visait à analyser le potentiel de fixation (BPND) de la 5-HT2A dans le cortex préfrontal, indice de la densité de la 5-HT2A, dans un échantillon sans distorsion de personnes qui avaient un comportement agressif violent.

Méthodes: Nous avons utilisé la tomographie par émission de positrons et la [18F] sétopérone pour mesurer le potentiel BPND de la 5-HT2A dans le cortex préfrontal dorsolatéral (principalement dans l'aire de Brodmann 9) chez 16 participants qui avaient un comportement agressif violent et 16 participants témoins en bonne santé.

Résultats: Chez les personnes qui avaient des comportements agressifs violents, la pente de la diminution du potentiel BPND de la 5-HT2A dans le cortex préfrontal dorsolatéral est inférieure de 44 % à celle des participants témoins en bonne santé (analyse des groupes de variance selon l'interaction en fonction de l'âge, p = 0,004). Le potentiel BPND de la 5-HT2A dans le cortex préfrontal était beaucoup moins élevé chez les participants qui avaient une impulsivité et une agression plus sévères (régression linéaire multiple en fonction de l'âge et échelle de l'impulsivité de Barratt [BIS] comme variables prédictives et potentiel BPND régional de la 5-HT2A comme variable dépendante; effet de la BIS, cortex préfrontal dorsolatéral : F1,13 = 7,95, p = 0,014).

Conclusion: On établit un lien entre le potentiel BPND de la 5-HT2A dans le cortex préfrontal moins élevé et l'agressivité violente. Le BPND moins élevé de la 5-HT2A fait son apparition à un âge plus jeune, lorsque le comportement violent est plus fréquent, et il est plus évident lorsque l'impulsivité et l'agression sont plus sévères.

Keywords: aggression; positron emission tomography; receptors, serotonin, 5-HT2A; serotonin; setoperone; suicide.

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Figures

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Fig. 1: Relation between regional cortex serotonin2A (5-HT2A) binding potential [BPND]) and age in participants with violent behaviour compared with nonviolent healthy control participants There was a significant interaction between age and diagnosis for each region (analysis of covariance, interaction between age and diagnosis, dorsolateral prefrontal cortex: F1,28 = 9.86, p = 0.004; orbitofrontal cortex: F1,28 = 13.52, p = 0.001; rostral anterior cingulate cortex: F1,28 = 4.24, p = 0.049; posteromedial temporal cortex: F1,28 = 10.54, p = 0.003).
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Fig. 2: In people with violent behaviour, lower regional cortex serotonin2A (5-HT2A) binding potential [BPND]) is associated with more severe impulsivity. Cortex 5-HT2A BPND scores were strongly associated with Barratt Impulsiveness Scale (BIS) scores such that lower 5-HT2A BPND was associated with more severe impulsivity (analysis of covariance, age and BIS as covariates, regional 5-HT2A BPND as dependent variable, effect of BIS, dorsolateral prefrontal cortex: F1,13 = 7.95, p = 0.014; orbitofrontal cortex: F1,13 = 7.48, p = 0.017; rostral anterior cingulate cortex: F1,13 = 8.34, p = 0.013; posteromedial temporal cortex: F1,13 = 5.43, p = 0.037). For the above figure, age-normalized 5-HT2A BPND values to age 20 are shown. Age-normalized values were calculated by taking the difference between the individual subject age and the age normalized to slope (m) of the age-related decline in 5-HT2A BPND (normalized 5-HT2A BPND = raw 5-HT2A BPND + diff*m).
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