Elevated fatty acid amide hydrolase in the prefrontal cortex of borderline personality disorder: a [11C]CURB positron emission tomography study

Abstract

Amygdala-prefrontal cortex (PFC) functional impairments have been linked to emotion dysregulation and aggression in borderline personality disorder (BPD). Fatty acid amide hydrolase (FAAH), the major catabolic enzyme for the endocannabinoid anandamide, has been proposed as a key regulator of the amygdala-PFC circuit that subserves emotion regulation. We tested the hypothesis that FAAH levels measured with [11C]CURB positron emission tomography in amygdala and PFC would be elevated in BPD and would relate to hostility and aggression. Twenty BPD patients and 20 healthy controls underwent FAAH genotyping (rs324420) and scanning with [11C]CURB. BPD patients were medication-free and were not experiencing a current major depressive episode. Regional differences in [11C]CURB binding were assessed using multivariate analysis of covariance with PFC and amygdala [11C]CURB binding as dependent variables, diagnosis as a fixed factor, and sex and genotype as covariates. [11C]CURB binding was marginally elevated across the PFC and amygdala in BPD (p = 0.08). In a priori selected PFC, but not amygdala, [11C]CURB binding was significantly higher in BPD (11.0%, p = 0.035 versus 10.6%, p = 0.29). PFC and amygdala [11C]CURB binding was positively correlated with measures of hostility in BPD (r > 0.4; p < 0.04). This study is the first to provide preliminary evidence of elevated PFC FAAH binding in any psychiatric condition. Findings are consistent with the model that lower endocannabinoid tone could perturb PFC circuitry that regulates emotion and aggression. Replication of these findings could encourage testing of FAAH inhibitors as innovative treatments for BPD.

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

“…Here, we suggest that hyperactivity of the amygdala observed in reactively aggressive populations may result from increased CB1 neurotransmission as a result of lower FAAH density. On the contrary, increased OFC activity may stem in part from higher FAAH levels and decreased CB1 activation, consistent with recent findings of another study that found elevated PFC FAAH density in an aggressive population 21 . Application of [ 11 C]CURB PET, a radioligand with high specificity for the FAAH enzyme 13 , could extend functional magnetic resonance imaging findings in reactively aggressive ASPD to contribute plausible neurochemical mechanisms explaining the disorder and pathological core traits.…”

“…We recently reported that there were no significant group differences between amygdala FAAH expression in borderline personality disorder (BPD) and healthy controls 21 . Given some similarities in clinical characteristics between BPD and ASPD, the contrasting effects could suggest at least two interpretations.…”

Sex vs Gender: A Biological Location for Gender, not Sex.

“…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, Arnold, Ball, Blaustein, & De Vries, 2012;Pearson, Lightman, & Evans, 2009;Zietsch et al, 2008), instinct (Sweatt, Nestler, Meaney, & Akbarian, 2013), and significantly in empathy (Swain et al, 2007). Others have presented similar claims (see Kolla et al, 2021;Zaidi, 2010;Decety & Lamm 2006).…”

“…Several studies show the amygdala as crucially involved with enhanced memory of emotional arousal and processing (von Polier et al, 2020;Flasbeck, Enzi, & Brüne, 2019), mediation of reactive and proactive aggression (Kolla et al, 2021;Romero-Martínez et al, 2019;Yang, Joshi, Jahanshad, Thompson, & Baker, 2017).…”

“…The putamen lies in the subcortical region as a part of the basal ganglia (Ghandili & Munakomi, 2020). It plays a role in facilitating movement by history-based motivation to act for reward (Muranishi et al, 2011;Mink, 1996), moderation of physical aggression (Kolla et al, 2021;Li et al, 2020). Putamen size decreases in both sexes during puberty and more markedly in males (Goddings et al, 2014).…”