خصلت خشونت و ویژگی بدون فکر عمل کردن به قشر فرونتال گیرنده 5-HT2A الزام آور در افراد سالم مربوط نمی شوند

Numerous studies indicate that the serotonergic (5-HT) transmitter system is involved in the regulation of impulsive aggression and there is from post-mortem, in vivo imaging and genetic studies evidence that the 5-HT2A receptor may be involved. We investigated 94 healthy individuals (60 men, mean age 47.0±18.7, range 23–86) to determine if trait aggression and trait impulsivity were related to frontal cortex 5-HT2A receptor binding (5-HT2AR) as measured with [18F]-altanserin PET imaging. Trait aggression and trait impulsivity were assessed with the Buss–Perry Aggression Questionnaire (AQ) and the Barratt Impulsiveness Scale 11 (BIS-11). Statistical analyses were conducted using a multiple linear regression model and internal consistency reliability of the AQ and BIS-11 was evaluated by Cronbach's alpha. Contrary to our hypothesis, results revealed no significant associations between 5-HT2AR and the AQ or BIS-11 total scores. Also, there was no significant interaction between gender and frontal cortex 5-HT2AR in predicting trait aggression and trait impulsivity. This is the first study to examine how 5-HT2AR relates to trait aggression and trait impulsivity in a large sample of healthy individuals. Our findings are not supportive of a selective role for 5-HT2AR in mediating the 5-HT related effects on aggression and impulsivity in psychiatrically healthy individuals.

Violence has a substantial impact on our society, accounting for an estimated 1.6 million deaths worldwide annually (Krug et al., 2002). Aggression plays a critical role in the manifestation of violence and criminality, and given the extensive morbidity of this behaviour there is a need for a better understanding of the underlying neurobiological mechanisms. Aggression is most commonly divided into impulsive and premeditated subtypes (Barratt et al., 1999), referring to unplanned or reactive acts of aggression and controlled or proactive acts of aggression, respectively. There is abundant evidence that the 5-HT transmitter system plays a role in the modulation of aggressive behaviour (Siever, 2008), with most studies pointing to an inverse relationship between 5-HT and aggression, in particular impulsive aggression. A meta-analytic review of animal studies using 5-HT reuptake inhibitors (SSRIs), established an inhibitory effect of increased 5-HT levels on aggression (Carrillo et al., 2009). These preclinical findings have to some extent been corroborated in humans, where SSRIs are reported to reduce impulsive aggression in healthy subjects high in aggression scores (Berman et al., 2009) and in personality-disordered individuals with impulsive aggression (Coccaro and Kavoussi, 1997). The neural circuits that regulate impulsive aggression involve the prefrontal cortex, a region of importance for modulating behavioural responses elicited by subcortical structures such as the amygdala (Siever, 2008). Evidence for the involvement of the prefrontal cortex comes from patients with brain lesions in this region, as they display heightened levels of aggression (Anderson et al., 1999 and Grafman et al., 1996). According to prevailing theory, lowered levels of extracellular 5-HT in the prefrontal cortex underlie individual differences in aggression and behavioural disinhibition (Davidson et al., 2000, New et al., 2009 and Siever, 2008). For example, in an acute tryptophan depletion (ATD) study, connectivity within the prefrontal cortex–amygdala circuits was modulated by ATD when processing angry faces (Passamonti et al., 2011). There are several lines of evidence supporting that the serotonin 2A (5-HT2A) receptor is involved in aggression. Numerous studies have convincingly shown that pharmacological compounds that antagonise 5-HT2A/C receptors potently suppress the display of aggressive behaviour in various animal species, including humans (reviewed in; (de Boer and Koolhaas, 2005). Furthermore, specific genetic polymorphisms of the 5-HT2A receptor are associated with aggression (Giegling et al., 2006 and Nomura and Nomura, 2006), although it still remains to be determined if these polymorphisms affect 5-HT2A receptor at protein levels. A post-mortem study has shown that 5-HT2A receptor expression in the prefrontal cortex is positively correlated with lifetime aggression in subjects who committed suicide, but not in subjects who died from non-neurological causes (Oquendo et al., 2006). Finally, two PET-studies have reported that frontal cortex 5-HT2A receptor binding (5-HT2AR) is higher in physically aggressive patients with personality disorders who scored high on a state measure of impulsive aggression (Rosell et al., 2010), and in patients with borderline personality disorder (Soloff et al., 2007) as compared to healthy controls. In the present study we investigated in a large group of healthy individuals whether trait aggression and trait impulsivity are associated with frontal cortex 5-HT2AR as measured with in vivo brain imaging. Based on the findings in previous studies that 5-HT2AR are increased in clinical populations with heightened levels of aggression, we hypothesised that (1) trait aggression and trait impulsivity in healthy subjects are associated with increased frontal cortical 5-HT2AR and that (2) inter-individual variations in regional receptor binding cause variability in behavioural outcomes.

The profile of the group is illustrated in Table 1. Except for testosterone levels there were no statistically significant differences (independent t-test) between men and women. Scale means for both the BPAQ and BIS-11 total score in men and women were slightly lower compared to means reported for general populations in other studies ( Buss and Perry, 1992, Stanford et al., 2009 and Tremblay and Ewart, 2005). Table 1. Descriptives. Descriptive variable Female Male All participants Mean value±S.D. (range in brackets) Mean value±S.D. (range in brackets) Mean value±S.D. (range in brackets) N 34 60 94 Age at AQ/BIS-11 assessment (yrs) 48.6±18.9 (24–84) 46.0±18.6 (23–86) 47.0±18.7 (23–86) Age at day of PET-scan (yrs) 42.4±18.5 (21–80) 39.7±18.2 (20–82) 40.7±18.2 (20–82) Number of years from PET-scan to AQ/BIS-11 assessment 6.2±2.5 (2–10) 6.2±2.4 (2–10) 6.2±2.5 (2–10) BMI (kg/m2) 18.4±2.9 (18.4–29.1) 24.8±2.4 (19.3–29.4) 24.6±2.6 (18.4–29.4) Frontal cortex BPp 1.4±0.4 (0.7–2.0) 1.4±0.4 (0.4–2.1) 1.4±0.4 (0.4–1.4) Testosterone (nmol/L)a 1.0±0.8 (0–3.2) 18.9±7.7 (6.5–38.2) 12.3±10.6 (0–38.2) Neuroticism scoreb 74.3±22.6 (35–118) 66.9±15.3 (33–109) 69.6±18.5 (33–118) AQ total score 52.7±12.9 (29–83) 56.7±11.5 (37–88) 55.3±12.1 (29–88) AQ physical aggression 15.1±4.1 (11–29) 16.5±4.1 (10–27) 16.0±4.1 (10–29) AQ verbal aggression 12.0±3.3 (5–18) 12.9±3.4 (7–22) 12.5±3.4 (5–22) AQ anger 13.4±4.9 (7–25) 13.1±4.4 (7–28) 13.2±4.5 (7–28) AQ hostility 14.4±5.2 (8–25) 15.2±4.5 (9–26) 15.0±4.8 (8–26) BIS-11 total score 58.8±9.0 (38–83) 58.5±7.7 (45–79) 58.6±8.1 (38–83) Attentional impulsiveness 14.2±3.7 (8–22) 13.0±2.3 (9–18) 13.4±2.9 (8–22) Motor impulsiveness 20.7±3.2 (14–30) 21.4±3.3 (15–29) 21.2±3.2 (14–30) Non-planning impulsiveness 23.6±4.5 (16–34) 23.9±4.4 (15–32) 23.8±4.4 (15–34) Education scorec 4.0±1.2 (1–5) 3.7±1.6 (1–5) 3.8±1.4 (1–5) a n=76. b n=93. c n=60.