Lower amygdala fatty acid amide hydrolase in violent offenders with antisocial personality disorder: an [11C]CURB positron emission tomography study

Abstract

Antisocial personality disorder (ASPD) imposes a high societal burden given the repetitive reactive aggression that affected individuals perpetrate. Since the brain endocannabinoid system (ECS) has been implicated in ASPD and aggressive behavior, we utilized [11C]CURB positron emission tomography to investigate fatty acid amide hydrolase (FAAH), an enzyme of the ECS that degrades anandamide, in 16 individuals with ASPD and 16 control participants. We hypothesized that FAAH density would be lower in the amygdala for several reasons. First, decreased FAAH expression is associated with increased cannabinoid receptor 1 stimulation, which may be responsible for amygdala hyper-reactivity in reactive aggression. Second, the amygdala is the seat of the neural circuit mediating reactive aggression. Third, other PET studies of externalizing populations show reduced brain FAAH density. Conversely, we hypothesized that FAAH expression would be greater in the orbitofrontal cortex. Consistent with our hypothesis, we found that amygdala FAAH density was lower in the amygdala of ASPD (p = 0.013). Cerebellar and striatal FAAH expression were inversely related with impulsivity (cerebellum: r = −0.60, p = 0.017; dorsal caudate: r = −0.58, p = 0.023; dorsal putamen: r = −0.55, p = 0.034), while cerebellar FAAH density was also negatively associated with assaultive aggression (r = −0.54, p = 0.035). ASPD presents high levels of disruptive behavior with few, if any, efficacious treatment options. Novel therapeutics that increase FAAH brain levels in a region-specific manner could hold promise for attenuating certain symptom clusters of ASPD, although our results require replication.

Sex vs Gender: An unanswered paradox.

“…The amygdala region is broader in ciswomen with a higher estrogen density than androgen receptors (Halpern, 2013). Furthermore, as we saw, the amygdala mediates empathy (Kolla et al, 2021) and empathy inhibits aggression (Decety & Lamm 2006). Yet, according to Gina Rippon (2019), nobody knows for certain whether having a bigger amygdala [or putamen] makes you more or less aggressive.…”

“…Behaviors related to reproduction are recognizable in both parents in the levels of responses such as sociability, attachment, sentimentality (Stam, Huang, & Van den Stock, 2019), aggression (Zell et al, 2015), in defend or befriend (Hoekzema et al, 2015;Sokolowski & Corbin, 2012;McCarthy et al, 2012;Pearson et al, 2009;Zietsch et al, 2008), instinct (Sweatt et al, 2013), and significantly in empathy (Swain et al, 2007). Others have presented similar claims (see Kolla et al, 2021;Zaidi, 2010;Decety & Lamm 2006).…”

“…This region has also been shown to be sexually dimorphic (Pallayova et al, 2019;Lotze et al, 2019;Reber & Tranel, 2017), and its nuclei have connections to other limbic areas (Crestani et al, 2013;Bonelli & Cummings, 2007). The amygdala mediates empathy (Kolla et al, 2021) and empathy inhibits aggression (Decety & Lamm 2006). In studying neural correlations of empathy in boys with conduct disorder, von Polier et al (2020) emphasized the amygdala's significant role in empathy-related emotional processing, notably, a reduction in amygdala responses in association with low levels of empathy.…”

Higher trait neuroticism is associated with greater fatty acid amide hydrolase binding in borderline and antisocial personality disorders

“…Using [ 11 C]CURB positron emission tomography (PET), we reported that FAAH expression was elevated in the prefrontal cortex (PFC) of BPD and that PFC FAAH density correlated with measures of anger/hostility 23 . Conversely, we also found utilizing [ 11 C]CURB PET that amygdala FAAH expression was lower in the amygdala of ASPD and that impulsive behaviors were negatively associated with FAAH density in other brain regions studied 24 . These findings have enhanced our knowledge about the pathophysiology of BPD and ASPD and their symptom clusters, yet an unanswered question remains how FAAH expression may relate to personality traits such as neuroticism.…”

“…We have previously reported neuroimaging data on a subset of these participants. However, the research questions and analyses for the present investigation were different from those of the previous studies 23 , 24 . BPD participants were primarily female ( n = 18), while all ASPD subjects were male.…”