Effect of SSRIs on Ocular Exploration of Face Stimuli
We also found that SSRIs can modulate attentional biases towards faces in a high-risk sample early in treatment, by directly increasing gaze maintenance over the internal features of faces. This suggests that an initial SSRIs' effect in anxious individuals could be to partly correct their dysfunctional pattern of ocular exploration of faces.
Initial attention allocation to salient stimuli is associated with amygdala activation (Vuilleumier, 2005). The present finding is therefore consistent with neuroimaging data showing that short-term repeated SSRI administration to High Ns increased the amygdala signal to facial expression irrespective of emotion type (Di Simplicio et al, 2013). The causal mechanism operating between amygdala activation and eye gaze movements remains unclear. The first neural response could precede attention deployment, guiding the eyes to explore the detected stimuli (Kennedy and Adolphs, 2011), but time spent gazing over the stimuli could equally increase the limbic neural signal (Pessoa and Adolphs, 2010). SSRI-driven modifications could occur at one or both stages of this process.
Notably, in the citalopram-treated group prolonged attention to faces (as measured by the ability to hold the gaze on the face for the entire trial and by the time spent scanning faces) was predictive of better performance in the gender discrimination task and to a more accurate discrimination of positive expressions in a separate facial expressions recognition task. High Ns find happiness recognition particularly difficult compared with non-vulnerable samples (Chan et al, 2007), and the current data suggest that recognition of positive emotional facial expressions improves early with SSRI treatment in this group. Although our data cannot make any causal inference, they suggest that modulation of basic eye-movement and face-exploration parameters by SSRIs are associated with correction of this negative bias in emotion recognition. Further investigations should confirm whether the capacity of different antidepressant agents to shift biases in facial expression recognition in unselected populations (Pringle et al, 2011) is similarly associated with effects on ocular exploration.
By contrast, short-term repeated SSRI administration did not modify the preference for exploring the mouth rather than the eye region seen in High Ns in Study 1. This suggests that antidepressants may produce a non-specific effect on gaze maintenance over faces. In a previous research, 2 weeks of citalopram administration in healthy volunteers increased eye contact compared with placebo in an interaction task with a stranger (Tse and Bond, 2002). Future studies with samples also characterized on social anxiety dimensions, more naturalistic experimental settings, and longer treatment duration could clarify whether the SSRI-mediated increase in face exploration after 1 week would also facilitate with time the reversal of the eye region avoidance when this is present.
Interestingly, citalopram-treated individuals also tended to spacially explore the face area less compared with placebo-treated ones, but this effect appeared prominent for fearful faces of medium intensity. Anxious individuals have been shown to spatially explore larger areas of faces while holding the eye gaze for shorter time duration over the face (Horley et al, 2003). This could reflect a ‘scanning style' of faces that avoids to properly stop over those cues holding potential danger and can impair accurate processing (Armstrong and Olatunji, 2012). This result should be treated with caution given the relatively small sample, with a medium effect size of the comparison. Accordingly, in our sample the spatial extension of eye movements was negatively correlated with gender discrimination accuracy. Hence, the combination of SSRI-induced changes in ocular exploration over fearful expressions and over all faces could lead to a more functional attention deployment toward socially salient stimuli, contributing to the long-term anxiolytic effect of antidepressants. If this were true, antidepressant action would appear to occur via an ‘exposure' mechanism similar to cognitive-behavioral treatments, as we have previously suggested (Di Simplicio et al, 2013).