Plasma Oxytocin Immunoreactive Products and Response to Trust in Patients With Social Anxiety Disorder

Abstract

Background Generalized Social Anxiety Disorder (GSAD) is characterized by excessive fear and avoidance of several types of social and performance situations. The pathophysiology is not well understood, but research in animals and humans has provided evidence that oxytocin helps regulate normal social affiliative behavior. Previous work in healthy male subjects demonstrated a rise in plasma oxytocin after receiving a high trust signal. To examine the oxytocin system in GSAD, we measured plasma oxytocin in GSAD patients and controls, before and after the social “Trust Game,” a neuroeconomic test examining trust behavior and reaction to trust using real monetary incentives. Methods Thirty-nine subjects with GSAD and 28 healthy controls provided three blood samples for oxytocin measurement before the Trust Game, and one sample after the game. Plasma estradiol was also measured at baseline. The Trust Game protocol version prioritized the sending of a signal of high cooperation and trust to all participants. All analyses controlled for gender and estradiol levels. Results Mean oxytocin levels post-Trust Game (p=0.025), and overall (area under the curve, p=0.011) were lower in GSAD patients compared to controls, after controlling for sex and estradiol. There was no significant change in oxytocin levels after the Game in either group. Conclusions We report low plasma oxytocin levels in patients with generalized social anxiety disorder during a pro-social laboratory task paradigm. Additional research will be important to further examine the relationship between oxytocin and social behavior in GSAD.

Oxytocin Receptor Gene Methylation: Converging Multilevel Evidence for a Role in Social Anxiety

“…OXTR methylation in social anxiety C Ziegler et al Previously, decreased baseline oxytocin plasma levels were observed to be associated with SAD (Hoge et al, 2012), and intranasal application of oxytocin adjunct to psychotherapy significantly improved self-reported speech performance in SAD patients (Guastella et al, 2009). Assuming decreased OXTR methylation resulting in increased OXTR mRNA expression (see Introduction; Dadds et al, 2014;Gregory et al, 2009;Kusui et al, 2001;Mamrut et al, 2013), the present finding of OXTR hypomethylation being associated with SAD as well as with social phobia-related dimensional measures may reflect a compensatory mechanism leading to an upregulation of oxytocin receptor expression against the background of pathologically low oxytocin levels in SAD and social phobia-related phenotypes.…”

“…Furthermore, oxytocin has been suggested as a promising anxiolytic pharmacotherapeutic agent in disorders related to social dysfunctioning (for review see BakermansKranenburg and van Ijzendoorn, 2013;Meyer-Lindenberg et al, 2011). Specifically, in SAD, decreased baseline oxytocin plasma levels have been observed (Hoge et al, 2012), and intranasal application of oxytocin as an adjunct to five weekly exposure therapy sessions significantly improved self-reported speech performance compared with placebo (Guastella et al, 2009). On a brain network level, oxytocin attenuates excessive amygdala activation in response to socially relevant or fear-conditioned emotional stimuli (Domes et al, 2007a;Kirsch et al, 2005;Labuschagne et al, 2010;Petrovic et al, 2008)-a brain activation pattern linked to social avoidance and phobia (Phan et al, 2006).…”

The Role of Oxytocin in Psychiatric Disorders

“…However, within the GSAD sample, higher social anxiety symptom severity adjusted for age and gender was associated with higher oxytocin levels. In another study 93 , patients with GSAD had similar plasma oxytocin levels to a HC group at baseline, but lower oxytocin levels after completing a trust game with a partner.…”

Helping oxytocin deliver: considerations in the development of oxytocin-based therapeutics for brain disorders

“…Regarding the latter, investigators have studied OT levels and their relationship to aspects of autism (Modahl et al, 1998; Al-Ayadhi, 2005), eating disorders (Hoffman et al, 2012; Lawson et al, 2012), post-traumatic stress disorder (Seng et al, 2013), schizophrenia (Goldman et al, 2008; Keri et al, 2009; Rubin et al, 2011), social anxiety disorder (Hoge et al, 2008, 2012) and depression (Scantamburlo et al, 2007; Parker et al, 2010). An important but uninvestigated clinical question is whether a transient or chronic increase of peripheral OT levels via treatment with IN OT (Andari et al, 2010; Gossen et al, 2012) correlates with OT-responsive clinical symptoms or treatment-related symptomatic improvement (e.g., whether OT levels may function as a biomarker).…”