Modulation of Resting-State Amygdala-Frontal Functional Connectivity by Oxytocin in Generalized Social Anxiety Disorder

Abstract

Generalized social anxiety disorder (GSAD) is characterized by aberrant patterns of amygdala-frontal connectivity to social signals of threat and at rest. The neuropeptide oxytocin (OXT) modulates anxiety, stress, and social behaviors. Recent functional neuroimaging studies suggest that these effects are mediated through OXT's effects on amygdala reactivity and/or amygdala-frontal connectivity. The aim of the current study was to examine OXT's effects on amygdala-frontal resting-state functional connectivity (rsFC) in GSAD patients and healthy controls (HCs). In a randomized, double-blind, cross-over design, 18 GSAD and 18 HC participants received intranasal OXT (24 IU or 40.32 μg) or placebo (PBO) before resting-state functional magnetic resonance imaging. In individuals with GSAD, OXT enhanced rsFC of the left and right amygdala with rostral anterior cingulate cortex (ACC)/medial prefrontal cortex (mPFC), and in doing so, reversed (ie, 'normalized') the reduced amygdala-frontal connectivity observed relative to HCs evident on PBO. Higher social anxiety severity in GSAD subjects correlated with lower amygdala-ACC/mPFC connectivity on PBO and higher social anxiety also correlated with greater enhancement in amygdala-frontal connectivity induced by OXT. These findings show that OXT modulates a neural circuit known for social threat processing and emotion regulation, suggesting a neural mechanism by which OXT may have a role in the pathophysiology and treatment of social anxiety disorder.

Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder

“…Previously, decreased amygdala reactivity toward emotional stimuli was found after intranasal OT administration in healthy males (Kirsch et al, 2005), females with borderline personality disorder (BPD) (Bertsch et al, 2013), males with generalized social anxiety disorder (GSAD) (Labuschagne et al, 2010), and male and female PTSD patients (Koch et al, 2015). In addition, OT administration increased resting-state functional connectivity between the amygdala and vmPFC in healthy males (Sripada et al, 2013) and in males with GSAD, normalizing the diminished functional connectivity observed under placebo in GSAD patients (Dodhia et al, 2014). Notably, higher amygdala reactivity in PTSD patients before treatment predicted worse treatment outcome, possibly due to (more) impaired extinction learning and fear regulation (Bryant et al, 2008b).…”

Intranasal Oxytocin Administration Dampens Amygdala Reactivity towards Emotional Faces in Male and Female PTSD Patients

“…In addition, functional MRI (fMRI) studies have shown that OT administration dampened amygdala reactivity toward emotional stimuli in healthy males (Kirsch et al, 2005), males with generalized social anxiety disorder (GSAD; Labuschagne et al, 2010) and females with borderline personality disorder (BPD; Bertsch et al, 2013), although findings for females have been mixed (Domes et al, 2010). Furthermore, OT administration resulted in increased resting-state functional connectivity between the amygdala and vmPFC in healthy males (Sripada et al, 2013) and in patients with GSAD (Dodhia et al, 2014), possibly enhancing top-down control over the fear response.…”

Complex Comorbidity of Substance Use Disorders with Anxiety Disorders: Diagnosis and Treatment

“…Because oxytocin is supposed to have anxiolytic and fear-modulating efects, it becomes a promising treatment option to augment exposure-based therapies for PTSD-SUD comorbidity [73]. Furthermore, with regard to neuroimaging studies, it is postulated that oxytocin might mitigate the dysregulation of corticolimbic brain circuitry, a neurobiological mechanism underlying SUD-AD comorbidity [74]. Current literature indicates that combining oxytocin treatment with psychosocial interventions may improve the treatment outcomes of this comorbidity.…”