Serotonin2A receptor binding potential in people with aggressive and violent behaviour

Abstract

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.

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

Figures

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).

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).