Single dose testosterone administration alleviates gaze avoidance in women with Social Anxiety Disorder
Introduction
Social Anxiety Disorder (SAD) is a common anxiety disorder, characterized by persistent fear and avoidance of social situations (American Psychiatric Association, 2013). SAD has been related to a ubiquitous social hierarchy system, in which individuals with SAD display socially submissive as opposed to socially dominant behavior (Hermans and van Honk, 2006, Maner et al., 2008, Weisman et al., 2011). Typical submissive behavior, such as avoidance of eye contact plays a crucial role in the persistence of this disorder by hindering extinction of fear in social situations (Clark and Wells, 1995, Stein and Stein, 2008). Especially angry facial expressions with direct gaze signal social scrutiny or a potential dominance challenge and elicit avoidance tendencies in highly socially anxious individuals (Öhman, 1986, Roelofs et al., 2010). Indeed, eye-tracking studies investigating gaze behavior in SAD, have demonstrated avoidance of the eye-region of angry faces (Horley et al., 2004, Moukheiber et al., 2012, Moukheiber et al., 2010). Because avoidance behavior is the major maintaining factor in SAD, it is relevant to develop interventions that directly target this behavior (Clark and Wells, 1995, Gamer and Büchel, 2012, Hofmann et al., 2014, Roelofs et al., 2010).
SAD is associated with reduced endogenous testosterone levels (Giltay et al., 2012), and because testosterone is known to reduce social avoidance (Enter et al., 2014, Terburg et al., 2012a), it is striking that so far no studies have tested the direct effects of testosterone administration in SAD. Testosterone has an important role in the regulation of social motivational behavior: It has socially anxiolytic effects, and is associated with social dominance and approach behavior (Bos et al., 2012, Enter et al., 2014, Terburg and van Honk, 2013). Based on recent findings indicating that testosterone administration in healthy females promotes social dominant gaze behavior to angry faces (Terburg et al., 2012a, Terburg et al., 2011), we predicted that testosterone administration would alleviate submissive gaze avoidance to angry faces in individuals with SAD.
We tested this hypothesis in a double-blind and placebo controlled within-subject study. A total of 18 medication-free participants with SAD and 19 healthy control participants received a single dose of 0.5 mg testosterone and a matched placebo in two sessions. In each session, their spontaneous gaze behavior was recorded while they looked at angry, happy, and neutral facial expressions. Gaze avoidance of eye contact was reliably indexed as relative reduction of initial gaze fixations on the eye-region (Becker and Detweiler-Bedell, 2009, Gamer et al., 2010, Gamer and Büchel, 2012, Garner et al., 2006). We predicted that testosterone administration in contrast to placebo would reduce gaze avoidance and increase the number of first fixations to the eyes of angry faces in particular in SAD.
Section snippets
Participants
Characteristics of the participant groups are presented in Table 1 (see also Table S1 and S2). Participants with Social Anxiety Disorder (SAD) were recruited from outpatient anxiety departments of mental health centers, through advertisements on the internet, and in local newspapers. Inclusion criterion was a total score of >60 on the Liebowitz Social Anxiety Scale (LSAS; Liebowitz, 1987, Rytwinski et al., 2009). In addition participants were screened with the Mini International
Percentage first fixations
The percentage first fixations to the eye region for each condition, emotion and group are presented in Table 2. First we conducted a three-way rmANOVA with all emotions in the analysis for the percentage first fixations, with Treatment (placebo, testosterone) and Emotion (angry, happy, neutral) as within-subject factors, and Group (HC, SAD) as between-subjects factor. There was no significant Treatment × Emotion × Group interaction; this counted both when including the SAD (combined) group, F(2,70)
Discussion
This study shows that a single dose testosterone administration can alleviate gaze avoidance, which is one of the core communicative features of social anxiety and Social Anxiety Disorder (SAD) in particular (Weeks et al., 2013). In accordance with previous research, avoidance of eye contact was correlated to severity of social anxiety symptoms. Critically, we showed that administration of testosterone leads to an increase of initial fixations to the eyes of facial stimuli in SAD compared to
Role of the funding source
The funding sources were not involved in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
Conflict of interest
The authors declare no conflicts of interest.
Contributors
Authors DE, KR. and PhS designed the study. Authors DE and AH conducted the study. Authors DE and DT undertook the analysis of the data. Author DE wrote the first draft. All authors contributed to and have approved the final manuscript.
Acknowledgements
This work was supported by research grants from the Netherlands Organization for Scientific Research(NWO) awarded to KR (VIDI grant: #452-07-008—also supporting DE; VICI grant: #453-12-001) and DT (VENI grant: #451-13-004), and by a starting grant from the European Research Council awarded to KR (ERC_StG2012_313749). The testosterone solution and matched placebo were manufactured by the Department of Clinical Pharmacy and Toxicology of the Leiden University Medical Centre, Leiden, The
References (57)
- et al.
Eye tracking of attention in the affective disorders: a meta-analytic review and synthesis
Clin. Psychol. Rev.
(2012) - et al.
Attention processes in the maintenance and treatment of social phobia: hypervigilance, avoidance and self-focused attention
Clin. Psychol. Rev.
(2004) - et al.
Acute effects of steroid hormones and neuropeptides on human social-emotional behavior: a review of single administration studies
Front. Neuroendocrinol.
(2012) - et al.
Dopaminergic and serotonergic activity in neostriatum and nucleus accumbens enhanced by intranasal administration of testosterone
Eur. Neuropsychopharmacol.
(2009) - et al.
The role of testosterone in social interaction
Trends Cogn. Sci.
(2011) - et al.
Alleviating social avoidance: effects of single dose testosterone administration on approach-avoidance action
Horm. Behav.
(2014) - et al.
Neuroimaging in social anxiety disorder: a systematic review of the literature
Prog. Neuropsychopharmacol. Biol. Psychiatry
(2010) - et al.
Oxytocin specifically enhances valence-dependent parasympathetic responses
Psychoneuroendocrinology
(2012) - et al.
Salivary testosterone: associations with depression, anxiety disorders, and antidepressant use in a large cohort study
J. Psychosom. Res.
(2012) - et al.
Testosterone rapidly increases neural reactivity to threat in healthy men: a novel two-step pharmacological challenge paradigm
Biol. Psychiatry
(2014)
Effects of exogenous testosterone on the ventral striatal BOLD response during reward anticipation in healthy women
Neuroimage
Testosterone administration reduces empathetic behavior: a facial mimicry study
Psychoneuroendocrinology
Exogenous testosterone enhances responsiveness to social threat in the neural circuitry of social aggression in humans
Biol. Psychiatry
Reward creates oculomotor salience
Curr. Biol.
Face to face: visual scanpath evidence for abnormal processing of facial expressions in social phobia
Psychiatry Res.
Testosterone and cortisol jointly regulate dominance: evidence for a dual-hormone hypothesis
Horm. Behav.
Gaze behaviour in social blushers
Psychiatry Res.
Gaze avoidance in social phobia: objective measure and correlates
Behav. Res. Ther.
Gaze direction differentially affects avoidance tendencies to happy and angry faces in socially anxious individuals
Behav. Res. Ther.
Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders
Pharmacol. Ther.
Social anxiety disorder
Lancet
The NimStim set of facial expressions: judgments from untrained research participants
Psychiatry Res.
Testosterone shifts the balance between sensitivity for punishment and reward in healthy young women
Psychoneuroendocrinology
Further notes on testosterone as a social hormone
Trends Cogn. Sci.
Pharmacokinetics of three doses of sublingual testosterone in healthy premenopausal women
Psychoneuroendocrinology
Social rank and affiliation in social anxiety disorder
Behav. Res. Ther.
Trait anxiety moderates the association between estradiol and dominance in women
Physiol. Behav.
Social anxiety disorder (social phobia)
Diagnostic and Statistical Manual of Mental Disorders: DSM-V
Cited by (34)
Attentional processes during emotional face perception in social anxiety disorder: A systematic review and meta-analysis of eye-tracking findings
2021, Progress in Neuro-Psychopharmacology and Biological Psychiatry