92 Chapter 5 Testosterone enhances social approach behavior in socially challenging situations where social status may be threatened (Maner et al., 2008; Mazur & Booth, 1998; Terburg & Van Honk, 2013). A recent study showed that pre-treatment rises in testosterone were predictive of better exposure outcomes in terms of larger symptom reduction for individuals with SAD (Hutschemaekers et al., 2020). Moreover, single-dose testosterone administration in individuals with SAD increases automatic approach behavior toward threatening (angry) faces on an AAT (Enter, Spinhoven, et al., 2016) and reduces biased processing (van Peer et al., 2017) and gaze-avoidance toward angry faces (Enter, Terburg, et al., 2016), together suggesting that testosterone can alleviate automatic avoidance behavior in individuals with SAD. Indeed neuroimaging studies have indicated that testosterone administration increases amygdala activation, specifically when one has to approach an angry face and not during threat avoidance (Radke et al., 2015). It does so presumably by enhancing (largely dopaminergic) projections from the amygdala to the ventral striatum, relevant for motivated action (Hermans et al., 2010). Together, these findings suggest that testosterone can stimulate approach behavior in healthy individuals and importantly in highly avoidant individuals with SAD. Translated to clinical application, testosterone administration may be a viable augmentation strategy for exposure therapy for SAD. Indeed, the increased engagement in an exposure session afforded by testosterone may facilitate corrective learning and thereby optimize outcomes (Hutschemaekers et al., 2021). Toward the goal of personalizing treatment, the present study sought to test the hypothesis that testosterone-enhancement of exposure-therapy would be most effective among individuals with SAD who present with high (as opposed to lower) levels of automatic social avoidance tendencies. We tested this hypothesis using data from a clinical trial involving 55 females with SAD who completed a session of exposure therapy and were randomized to receive either a single dose of testosterone (0.5 mg) or placebo prior to this session (Hutschemaekers et al., 2021). To assess the transfer of testosterone effects, the participants engaged in a second exposure session one week later that did not involve testosterone administration. We predicted that social avoidance tendencies as measured at baseline would moderate testosterone augmentation effects, such that those showing stronger social avoidance tendencies at baseline and receive testosterone would profit more compared to those participants that receive placebo. Finally, we tested whether social avoidance tendencies changed over time with (testosterone enhanced) exposure therapy.
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