No abstract

Altered activity of fatty acid amide hydrolase (FAAH), an enzyme of the endocannabinoid system, has been implicated in several neuropsychiatric disorders, including major depressive disorder (MDD). It is speculated that increased brain FAAH expression is correlated with increased depressive symptoms. The aim of this scoping review was to establish the role of FAAH expression in animal models of depression to determine the translational potential of targeting FAAH in clinical studies. A literature search employing multiple databases was performed; all original articles that assessed FAAH expression in animal models of depression were considered. Of the 216 articles that were screened for eligibility, 24 articles met inclusion criteria and were included in this review. Three key findings emerged: (1) FAAH expression is significantly increased in depressive-like phenotypes; (2) genetic knockout or pharmacological inhibition of FAAH effectively reduces depressive-like behavior, with a dose-dependent effect; and (3) differences in FAAH expression in depressive-like phenotypes were largely localized to animal prefrontal cortex, hippocampus and striatum. We conclude, based on the animal literature, that a positive relationship can be established between brain FAAH level and expression of depressive symptoms. In summary, we suggest that FAAH is a tractable target for developing novel pharmacotherapies for MDD.

Studies suggest that abnormalities of the dopaminergic system underlie decision‐making deficits, a hallmark of antisocial personality disorder (ASPD) and psychopathy. The dopamine transporter gene (DAT1) is of particular interest due to a polymorphism that controls dopamine transporter (DAT) activity. However, the association between DAT1 genotypes and decision‐making in ASPD has never been studied. The current study investigated the effect of DAT1 genotype on decision‐making, as measured by the Iowa Gambling Task (IGT), in ASPD and healthy controls. A total of 17 participants with ASPD and 16 healthy control participants without ASPD were sampled. The Hare Psychopathy Checklist‐Revised and the IGT were administered to all participants. All participants provided blood samples for genotyping. Data revealed a novel interaction effect between DAT1 genotype and diagnosis, whereby ASPD participants with low DAT activity genotypes performed significantly worse on the IGT and selected from disadvantageous decks more often, whereas the low DAT activity genotype in the healthy control group was associated with better performance on the IGT, and they selected from disadvantageous decks less often. We demonstrate, for the first time, that low DAT activity genotypes in ASPD with high psychopathic traits contribute to poor decision‐making.