Elsevier

Psychoneuroendocrinology

Volume 63, January 2016, Pages 26-33
Psychoneuroendocrinology

Single dose testosterone administration alleviates gaze avoidance in women with Social Anxiety Disorder

https://doi.org/10.1016/j.psyneuen.2015.09.008Get rights and content

Highlights

  • We applied single dose testosterone administration in a placebo-controlled design.

  • Avoidance of eye contact in SAD is related to the severity of social anxiety.

  • Testosterone enhanced the initial fixations to the eyes of angry faces in SAD.

  • The findings support and extend social dominance theories of testosterone.

  • The direct effects on a core characteristic of SAD could have clinical implications.

Abstract

Gaze avoidance is one of the most characteristic and persistent social features in people with Social Anxiety Disorder (SAD). It signals social submissiveness and hampers adequate social interactions. Patients with SAD typically show reduced testosterone levels, a hormone that facilitates socially dominant gaze behavior. Therefore we tested as a proof of principle whether single dose testosterone administration can reduce gaze avoidance in SAD. In a double-blind, within-subject design, 18 medication-free female participants with SAD and 19 female healthy control participants received a single dose of 0.5 mg testosterone and a matched placebo, at two separate days. On each day, their spontaneous gaze behavior was recorded using eye-tracking, while they looked at angry, happy, and neutral facial expressions. Testosterone enhanced the percentage of first fixations to the eye-region in participants with SAD compared to healthy controls. In addition, SAD patients’ initial gaze avoidance in the placebo condition was associated with more severe social anxiety symptoms and this relation was no longer present after testosterone administration. These findings indicate that single dose testosterone administration can alleviate gaze avoidance in SAD. They support theories on the dominance enhancing effects of testosterone and extend those by showing that effects are particularly strong in individuals featured by socially submissive behavior. The finding that this core characteristic of SAD can be directly influenced by single dose testosterone administration calls for future inquiry into the clinical utility of testosterone in the treatment of SAD.

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)

  • E.J. Hermans et al.

    Effects of exogenous testosterone on the ventral striatal BOLD response during reward anticipation in healthy women

    Neuroimage

    (2010)
  • E.J. Hermans et al.

    Testosterone administration reduces empathetic behavior: a facial mimicry study

    Psychoneuroendocrinology

    (2006)
  • E.J. Hermans et al.

    Exogenous testosterone enhances responsiveness to social threat in the neural circuitry of social aggression in humans

    Biol. Psychiatry

    (2008)
  • C. Hickey et al.

    Reward creates oculomotor salience

    Curr. Biol.

    (2012)
  • K. Horley et al.

    Face to face: visual scanpath evidence for abnormal processing of facial expressions in social phobia

    Psychiatry Res.

    (2004)
  • P.H. Mehta et al.

    Testosterone and cortisol jointly regulate dominance: evidence for a dual-hormone hypothesis

    Horm. Behav.

    (2010)
  • A. Moukheiber et al.

    Gaze behaviour in social blushers

    Psychiatry Res.

    (2012)
  • A. Moukheiber et al.

    Gaze avoidance in social phobia: objective measure and correlates

    Behav. Res. Ther.

    (2010)
  • K. Roelofs et al.

    Gaze direction differentially affects avoidance tendencies to happy and angry faces in socially anxious individuals

    Behav. Res. Ther.

    (2010)
  • N. Singewald et al.

    Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders

    Pharmacol. Ther.

    (2015)
  • M.B. Stein et al.

    Social anxiety disorder

    Lancet

    (2008)
  • N. Tottenham et al.

    The NimStim set of facial expressions: judgments from untrained research participants

    Psychiatry Res.

    (2009)
  • J. van Honk et al.

    Testosterone shifts the balance between sensitivity for punishment and reward in healthy young women

    Psychoneuroendocrinology

    (2004)
  • J. van Honk et al.

    Further notes on testosterone as a social hormone

    Trends Cogn. Sci.

    (2011)
  • K. van Rooij et al.

    Pharmacokinetics of three doses of sublingual testosterone in healthy premenopausal women

    Psychoneuroendocrinology

    (2012)
  • O. Weisman et al.

    Social rank and affiliation in social anxiety disorder

    Behav. Res. Ther.

    (2011)
  • A. Ziomkiewicz et al.

    Trait anxiety moderates the association between estradiol and dominance in women

    Physiol. Behav.

    (2015)
  • American Psychiatric Association

    Social anxiety disorder (social phobia)

    Diagnostic and Statistical Manual of Mental Disorders: DSM-V

    (2013)
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