pubmed.ncbi.nlm.nih.gov

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

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

Nathan J Kolla et al. Neuropsychopharmacology. 2020 Oct.

Erratum in

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.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1. Elevation of prefrontal cortex fatty acid amide hydrolase λk3 in borderline personality disorder.

After controlling for genotype, borderline personality disorder subjects were found to have greater fatty acid amide hydrolase density in the prefrontal cortex compared with healthy controls.

Fig. 2
Fig. 2. Prefrontal cortex fatty acid amide hydrolase λk3 is correlated with hostility (Resentment) controlling for genotype in borderline personality disorder.

That is, borderline personality disorder subjects who had higher scores on the Resentment subscale of the Buss-Durkee Hostility Inventory also had higher fatty acid amide hydrolase expression in the prefrontal cortex.

Fig. 3
Fig. 3. Amygdala fatty acid amide hydrolase λk3 is correlated with hostility (Guilt) controlling for genotype in borderline personality disorder.

Borderline personality disorder participants who scored higher on Guilt subscale scores of the Buss-Durkee Hostility Inventory had greater fatty acid amide hydrolase density in the amygdala.

Similar articles

Cited by

References

    1. Best LM, Williams B, Le Foll B, Mansouri E, Bazinet RP, Lin L, et al. (2020). Lower brain fatty acid amide hydrolase in treatment-seeking patients with alcohol use disorder: a positron emission tomography study with [C-11]CURB. Neuropsychopharmacology. 2020:1–8. - PMC - PubMed
    1. Boileau I, Mansouri E, Williams B, Le Foll B, Rusjan P, Mizrahi R, et al. Fatty acid amide hydrolase binding in brain of cannabis users: imaging with the novel radiotracer [(11)C]CURB. Biol Psychiatry. 2016;80:691–701. doi: 10.1016/j.biopsych.2016.04.012. - DOI - PMC - PubMed
    1. Borgan F, Laurikainen H, Veronese M, Marques TR, Haaparanta-Solin M, Solin O, et al. (2019). In vivo availability of cannabinoid 1 receptor levels in patients with first-episode psychosis. JAMA Psychiatry. 2020;76:1074–84. - PMC - PubMed
    1. Schaefer C, Enning F, Mueller JK, Bumb JM, Rohleder C, Odorfer TM, et al. Fatty acid ethanolamide levels are altered in borderline personality and complex posttraumatic stress disorders. Eur Arch psychiatry Clin Neurosci. 2014;264:459–63. doi: 10.1007/s00406-013-0470-8. - DOI - PubMed
    1. Wong DF, Kuwabara H, Horti AG, Raymont V, Brasic J, Guevara M, et al. Quantification of cerebral cannabinoid receptors subtype 1 (CB1) in healthy subjects and schizophrenia by the novel PET radioligand [11C]OMAR. NeuroImage. 2010;52:1505–13. doi: 10.1016/j.neuroimage.2010.04.034. - DOI - PMC - PubMed

Publication types

MeSH terms

Substances