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

Nathan J Kolla,Isabelle Boileau,R Michael Bagby

doi:10.1038/s41598-022-04789-9

Abstract

Borderline personality disorder (BPD) and antisocial personality disorder (ASPD) are the two most frequently diagnosed and researched DSM-5 personality disorders, and both are characterized by high levels of trait neuroticism. Fatty acid amide hydrolase (FAAH), an enzyme of the endocannabinoid system (ECS), has been linked to regulation of mood through modulation of anandamide, an endocannabinoid. We hypothesized that prefrontal cortex (PFC) FAAH binding would relate to trait neuroticism in personality disorders. Thirty-one individuals with personality disorders (20 with BPD and 11 with ASPD) completed the investigation. All participants completed the revised NEO Personality Inventory, which yields standardized scores (e.g., T scores) for the traits of neuroticism, openness, conscientiousness, agreeableness, and extraversion. All participants were medication free and were not utilizing illicit substances as determined by drug urinalysis. Additionally, none of the participants had a comorbid major depressive episode, bipolar disorder, psychotic disorder, or substance use disorder. Each participant underwent one [11C]CURB PET scan. Consistent with our hypothesis, neuroticism was positively correlated with PFC FAAH binding (r = 0.42, p = 0.021), controlling for genotype. Neuroticism was also positively correlated with dorsal putamen FAAH binding (r = 0.53, p = 0.0024), controlling for genotype. Elevated brain FAAH is an endophenotype for high neuroticism in BPD and ASPD. Novel pharmacological therapeutics that inhibit FAAH could emerge as potential new treatments for BPD and ASPD with high neuroticism.

Highlights

Borderline personality disorder (BPD) and antisocial personality disorder (ASPD) are the two most frequently diagnosed and researched DSM-5 personality disorders, and both are characterized by high levels of trait neuroticism
Using [11C]CURB positron emission tomography (PET), we reported that Fatty acid amide hydrolase (FAAH) expression was elevated in the prefrontal cortex (PFC) of BPD and that PFC FAAH density correlated with measures of anger/hostility[23]
PFC [11C] CURB λk[3] was significantly correlated with neuroticism facets anxiety (r = 0.42, p = 0.023) and self-consciousness (r = 0.37, p = 0.047), controlling for genotype, these results were uncorrected for multiple comparisons

Summary

Introduction

Borderline personality disorder (BPD) and antisocial personality disorder (ASPD) are the two most frequently diagnosed and researched DSM-5 personality disorders, and both are characterized by high levels of trait neuroticism. Neuroticism is one of the Big Five dimensional domains of personality that encompasses individual differences in negative emotional responding to frustration, threat, or loss[1–4] It is operationally defined by items, which, in aggregate, reflect anger, sadness, irritability, self-consciousness, vulnerability, worry, and hostility that correlate well with one another in factor analyses[1–3]. Neuroticism is associated with manifestations of psychological illness, such as mood and anxiety disorders; adverse physical health outcomes; and poorer quality of life[1], comparably less is known about its neurochemical substrate, especially in common mental disorders. This gap in the literature hinders development of new therapeutics that could serve to mitigate the effects of high neuroticism. Enzymatic regulation of AEA by FAAH is able to indirectly control CB1R signaling and ostensibly modulate cognitive processes underlying mood and anxiety s ymptoms[22]

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