Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

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.

SUBMITTER: Kolla NJ

PROVIDER: S-EPMC8782862 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Monoamine Oxidase A in Antisocial Personality Disorder and Borderline Personality Disorder.

Project description:Purpose of reviewVariation in the monoamine oxidase A (MAO-A) gene and MAO-A enzyme levels have been linked to antisocial behavior and aggression in clinical and non-clinical populations. Here, we provide an overview of the genetic, epigenetic, and neuroimaging research that has examined MAO-A structure and function in antisocial personality disorder (ASPD) and borderline personality disorder (BPD).Recent findingsThe low-activity MAO-A variable nucleotide tandem repeat genetic polymorphism has shown a robust association with large samples of violent and seriously violent offenders, many of whom had ASPD. A recent positron emission tomography (PET) study of ASPD similarly revealed low MAO-A density in brain regions thought to contribute to the psychopathology of the condition. By contrast, PET has also demonstrated that brain MAO-A levels are increased in BPD and that they relate to symptoms of low mood and suicidality.SummaryCandidate gene studies have produced the most compelling evidence connecting MAO-A genetic variants to both ASPD and BPD. Still, conflicting results abound in the literature, making it highly unlikely that ASPD or BPD is related to a specific MAO-A genetic variant. Future research should strive to examine how MAO-A genotypes interact with broad-spectrum environmental influences to produce brain endophenotypes that may ultimately become tractable targets for novel treatment strategies.

| S-EPMC5846806 | biostudies-literature

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

Project description: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.

| S-EPMC7814116 | biostudies-literature

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

Project description: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.

| S-EPMC7608329 | biostudies-literature

SERT and BDNF polymorphisms interplay on neuroticism in borderline personality disorder.

Project description:OBJECTIVE:Genetic factors underlying different personality traits are not entirely understood, particularly how genes interact to modulate their effect. We studied 76 patients diagnosed with borderline personality disorder (BPD), characterized by extreme levels of personality traits, especially neuroticism (N), in which we genotyped two polymorphisms, the 5HTTLPR of the Serotonin transporter (SERT) gene, and the Val66Met of the Brain-derived neurotrophic factor (BDNF) gene. RESULTS:We found an association with SERT, where S-allele carriers had significantly higher levels of N than L-homozygous. Furthermore, we found that the protective effect of L-homozygosity is only evident on A-allele carriers of the BDNF Val66Met polymorphism. Genetic constitution in SERT and BDNF seems to be important in neuroticism, the most relevant personality trait on BPD.

| S-EPMC7006183 | biostudies-literature

Overexpression of fatty acid amide hydrolase induces early flowering in Arabidopsis thaliana

Project description:To better understand the molecular basis for the early flowering phenotype of AtFAAH overexpressors, microarray analysis was conducted comparing transcript profiles of wild type to the AtFAAH overexpressors and AtFAAH knockouts.

2012-02-01 | E-MEXP-3486 | biostudies-arrayexpress

Identification of fatty acid amide hydrolase as a metastasis suppressor in breast cancer

Project description:Clinical management of breast cancer (BC) metastasis remains an unmet need as it accounts for 90% of BC-associated mortality. Although the luminal subtype, which represents >70% of BC cases, is generally associated with a favorable outcome, it is susceptible to metastatic relapse as late as 15 years after treatment discontinuation. Seeking therapeutic approaches as well as screening tools to properly identify those patients with a higher risk of recurrence is therefore essential. Here, we report that the lipid-degrading enzyme fatty acid amide hydrolase (FAAH) is a predictor of long-term survival in patients with luminal BC, and that it blocks tumor progression and lung metastasis in cell and mouse models of BC. Together, our findings highlight the potential of FAAH as a biomarker with prognostic value in luminal BC and as a therapeutic target in metastatic disease.

2022-03-09 | GSE197984 | GEO

In smiles we trust? Smiling in the context of antisocial and borderline personality pathology.

Project description:Research suggests that people behave more cooperatively towards those who smile and less cooperatively towards those with personality pathology. Here, we integrated these two lines of research to model the combined effects of smiles and personality pathology on trust. In two experiments, participants read vignettes portraying a person with either borderline personality disorder, antisocial personality disorder, or no personality pathology. These portrayals were paired with a brief video clip that showed a person with either a neutral expression or a smile. Participants then played a Trust game with the "person" presented using each vignette and video clip combination. In Experiment 1, rates of trust were lower in response to the borderline and antisocial personality disorder vignettes compared with the control vignette. Interestingly, the effect of smiles was dependent upon personality. Although participants were more trusting of smiling confederates portrayed as having borderline personality disorder or no pathology, they were less trusting of confederates portrayed as having antisocial personality disorder if they smiled. In Experiment 2, run with a second set of personality vignettes, rates of trust were lower in response to both personality disorder vignettes and higher in response to smiles with no significant interaction. Together, these results suggest that information regarding both the current emotional state as well as the personality traits of a partner are important for creating trust.

| S-EPMC7316324 | biostudies-literature

Cardioprotective effects of fatty acid amide hydrolase inhibitor URB694, in a rodent model of trait anxiety.

Project description:In humans, chronic anxiety represents an independent risk factor for cardiac arrhythmias and sudden death. Here we evaluate in male Wistar rats bred for high (HAB) and low (LAB) anxiety-related behavior, as well as non-selected (NAB) animals, the relationship between trait anxiety and cardiac electrical instability and investigate whether pharmacological augmentation of endocannabinoid anandamide-mediated signaling exerts anxiolytic-like and cardioprotective effects. HAB rats displayed (i) a higher incidence of ventricular tachyarrhythmias induced by isoproterenol, and (ii) a larger spatial dispersion of ventricular refractoriness assessed by means of an epicardial mapping protocol. In HAB rats, acute pharmacological inhibition of the anandamide-degrading enzyme, fatty acid amide hydrolase (FAAH), with URB694 (0.3 mg/kg), (i) decreased anxiety-like behavior in the elevated plus maze, (ii) increased anandamide levels in the heart, (iii) reduced isoproterenol-induced occurrence of ventricular tachyarrhythmias, and (iv) corrected alterations of ventricular refractoriness. The anti-arrhythmic effect of URB694 was prevented by pharmacological blockade of the cannabinoid type 1 (CB1), but not of the CB2, receptor. These findings suggest that URB694 exerts anxiolytic-like and cardioprotective effects in HAB rats, the latter via anandamide-mediated activation of CB1 receptors. Thus, pharmacological inhibition of FAAH might be a viable pharmacological strategy for the treatment of anxiety-related cardiac dysfunction.

| S-EPMC4677398 | biostudies-other

A psychometric investigation of gender differences and common processes across borderline and antisocial personality disorders.

Project description:The comorbidity between borderline personality disorder (BPD) and antisocial personality disorder (ASPD) is well-established, and the 2 disorders share many similarities. However, there are also differences across disorders: most notably, BPD is diagnosed more frequently in women and ASPD in men. We investigated if (a) comorbidity between BPD and ASPD is attributable to 2 discrete disorders or the expression of common underlying processes, and (b) if the model of comorbidity is true across sex. Using a clinical sample of 1,400 drug users in residential substance abuse treatment, we tested 3 competing models to explore whether the comorbidity of ASPD and BPD should be represented by a single common factor, 2 correlated factors, or a bifactor structure involving a general and disorder-specific factors. Next, we tested whether our resulting model was meaningful by examining its relationship with criterion variables previously reported to be associated with BPD and ASPD. The bifactor model provided the best fit and was invariant across sex. Overall, the general factor of the bifactor model significantly accounted for a large percentage of the variance in criterion variables, whereas the BPD and AAB specific factors added little to the models. The association of the general and specific factor with all criterion variables was equal for men and women. Our results suggest common underlying vulnerability accounts for both the comorbidity between BPD and AAB (across sex), and this common vulnerability drives the association with other psychopathology and maladaptive behavior. This in turn has implications for diagnostic classification systems and treatment. (PsycINFO Database Record

| S-EPMC5217473 | biostudies-literature

Sulfonyl fluoride inhibitors of fatty acid amide hydrolase.

Project description:Sulfonyl fluorides are known to inhibit esterases. Early work from our laboratory has identified hexadecyl sulfonylfluoride (AM374) as a potent in vitro and in vivo inhibitor of fatty acid amide hydrolase (FAAH). We now report on later generation sulfonyl fluoride analogs that exhibit potent and selective inhibition of FAAH. Using recombinant rat and human FAAH, we show that 5-(4-hydroxyphenyl)pentanesulfonyl fluoride (AM3506) has similar inhibitory activity for both the rat and the human enzyme, while rapid dilution assays and mass spectrometry analysis suggest that the compound is a covalent modifier for FAAH and inhibits its action in an irreversible manner. Our SAR results are highlighted by molecular docking of key analogs.

| S-EPMC3678964 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data