116 Chapter 6 avoidance for social versus non-social stimuli and this bias did not vary with testosterone enhanced exposure efficacy (no change from pre- to post exposure for both the testosterone and placebo condition). Stronger pre-treatment avoidance tendencies were associated with larger fear reduction under testosterone but not placebo. This effect was present only during the first enhanced session and not in the second non-enhanced session or at the level of symptom severity. These results may suggest that social avoidance tendencies are linked to stronger testosterone enhanced exposure efficacy. Further investigation using multiple enhancement sessions is needed to identify whether social avoidance tendencies can serve as behavioral marker for efficacy of a more extensive testosterone-enhanced exposure therapy. Integration and overarching discussion of the chapters Clinical translation of the challenge hypothesis One specific aim of this dissertation was to test assumptions of the social challenge hypothesis in a clinical context, namely that strong HPG-axis reactivity prior to a social encounter (in this case a speech-exposure), would prepare the individual for successful social approach behavior during the exposure (Wingfield et al., 1990). Accordingly, individuals with high testosterone rises in response to a pre-exposure instruction showed stronger symptom reduction after exposure in chapter 3. Following the predictions of the social challenge hypothesis (Wingfield et al., 1990), we speculate that HPG-axis reactivity to the upcoming social encounter (in our case primed by the exposure instructions) may stimulate in-session approach behavior, that is stronger engagement in the exposure eventually resulting in improved learning. This interpretation was supported by the observation that high pre-exposure testosterone reactivity was related to larger reductions in social anxiety symptoms. However, it did not affect within-session fear levels. The latter may imply that endogenous testosterone reactivity is indeed important for successful exposure by promoting direct (in session) approach behavior rather than affecting fear itself. However, anxiety and approach-avoidance behavior influence each other and our design was not optimized to disentangle anxiolytic from behavioral social-approach effects. A combination of repeated objective and subjective indices for measuring approach behavior and anxiety are needed to shed light on this mechanistic question. This pioneering endogenous testosterone reactivity study (chapter 3) demonstrated that reactivity of the HPG-axis could be a potential biomarker for the efficacy of exposure therapy of SAD. Additionally, these results raised the question whether increases in testosterone, even when administered exogenously, could aid exposure-efficacy.
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