Abstract

RationaleThe endocannabinoid (eCB) system is implicated in several psychiatric disorders. Investigating emotional–motivational dysfunctions as underlying mechanisms, a study in humans revealed that in the C385A polymorphism of the fatty acid amide hydrolase (FAAH), the degrading enzyme of the eCB anandamide (AEA), A carriers, who are characterized by increased signaling of AEA as compared to C/C carriers, exhibited reduced brain reactivity towards unpleasant faces and enhanced reactivity towards reward. However, the association of eCB system with emotional–motivational reactivity is complex and bidirectional due to upcoming compensatory processes.ObjectivesTherefore, we further investigated the relationship of the FAAH polymorphism and emotional–motivational reactivity in humans.MethodsWe assessed the affect-modulated startle, and ratings of valence and arousal in response to higher arousing pleasant, neutral, and unpleasant pictures in 67 FAAH C385A C/C carriers and 45 A carriers.ResultsContrarily to the previous functional MRI study, A carriers compared to C/C carriers exhibited an increased startle potentiation and therefore emotional responsiveness towards unpleasant picture stimuli and reduced startle inhibition indicating reduced emotional reactivity in response to pleasant pictures, while both groups did not differ in ratings of arousal and valence.ConclusionsOur findings emphasize the bidirectionality and thorough examination of the eCB system’s impact on emotional reactivity as a central endophenotype underlying various psychiatric disorders.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-012-2785-y) contains supplementary material, which is available to authorized users.

Highlights

  • The endocannabinoid system is associated with psychiatric disorders which are marked by emotional– motivational dysfunction, e.g., anxiety, addiction, eating disorders, and depression (Davis 2008; Monteleone et al 2009; Parolaro et al 2010; Sipe et al 2002), and it constitutes an important research topic in relation to psychiatric disorders (Lutz 2009)

  • Like the phytocannabinoid Δ9-tetrahydrocannabinol, AEA activates the cannabinoid type 1 (CB1) receptor as the most important binding sites in brain regions involved in regulation of emotions (Mackie 2005)

  • There were no differences between the fatty acid amide hydrolase (FAAH) C385A A variant and C/C variant in sex distribution (χ2(1)0 0.3, p00.264), age, IQ, trait anxiety, impulsivity, empathy, or venturesomeness

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Summary

Introduction

The endocannabinoid (eCB) system is associated with psychiatric disorders which are marked by emotional– motivational dysfunction, e.g., anxiety, addiction, eating disorders, and depression (Davis 2008; Monteleone et al 2009; Parolaro et al 2010; Sipe et al 2002), and it constitutes an important research topic in relation to psychiatric disorders (Lutz 2009). The impact of the eCB system on emotional behavior is very likely due to the central role of the eCB anandamide (AEA). Like the phytocannabinoid Δ9-tetrahydrocannabinol, AEA activates the cannabinoid type 1 (CB1) receptor as the most important binding sites in brain regions involved in regulation of emotions (Mackie 2005). AEA is degraded by the enzyme fatty acid amide hydrolase FAAH should play a key role in AEA-mediated emotional effects

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