Variation in the human cannabinoid receptor CNR1 gene modulates gaze duration for happy faces

Abstract

Background: From an early age, humans look longer at preferred stimuli and also typically look longer at facial expressions of emotion, particularly happy faces. Atypical gaze patterns towards social stimuli are common in autism spectrum conditions (ASC). However, it is unknown whether gaze fixation patterns have any genetic basis. In this study, we tested whether variations in the cannabinoid receptor 1 (CNR1) gene are associated with gaze duration towards happy faces. This gene was selected because CNR1 is a key component of the endocannabinoid system, which is involved in processing reward, and in our previous functional magnetic resonance imaging (fMRI) study, we found that variations in CNR1 modulate the striatal response to happy (but not disgust) faces. The striatum is involved in guiding gaze to rewarding aspects of a visual scene. We aimed to validate and extend this result in another sample using a different technique (gaze tracking).

Methods: A total of 30 volunteers (13 males and 17 females) from the general population observed dynamic emotional expressions on a screen while their eye movements were recorded. They were genotyped for the identical four single-nucleotide polymorphisms (SNPs) in the CNR1 gene tested in our earlier fMRI study.

Results: Two SNPs (rs806377 and rs806380) were associated with differential gaze duration for happy (but not disgust) faces. Importantly, the allelic groups associated with a greater striatal response to happy faces in the fMRI study were associated with longer gaze duration at happy faces.

Conclusions: These results suggest that CNR1 variations modulate the striatal function that underlies the perception of signals of social reward, such as happy faces. This suggests that CNR1 is a key element in the molecular architecture of perception of certain basic emotions. This may have implications for understanding neurodevelopmental conditions marked by atypical eye contact and facial emotion processing, such as ASC.

Figure 1

Schematic structure of the cannabinoid receptor CNR1 gene with all four genotyped single-nucleotide polymorphisms indicated. Top: White boxes indicate untranslated regions, black boxes indicate translated regions and intervening straight line indicates an intronic region. Bottom: The linkage disequilibrium structure of the gene in the Caucasian (CEU) population is shown (using the publicly available HapMap version 3, release R2, database available at http://hapmap.ncbi.nlm.nih.gov/.

Figure 2

Example gaze trail from a single participant and group mean gaze durations for happy faces classified by genotype. (a) Example gaze trail from a single participant on a still frame from a video stimulus showing a happy expression. The black circles represent fixation points and the amount of time (in seconds) spent in each. The dotted lines demarcate each look zone (eyes region and mouth region). (b) Gaze duration for happy faces grouped by genotype for rs806380 (top) and rs806377 (bottom), respectively. Unfilled circles indicate mean gaze duration, and error bars represent ± 1 SEM. From the Mindreading™ set developed by Baron-Cohen et al. [34]