title: 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.
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Sonam
authors.initials: S
authors.lastname: Dodhia
authors.affiliation: 1] Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA [2] Mental Health Service, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA.
authors.forename: Avinash
authors.initials: A
authors.lastname: Hosanagar
authors.affiliation: 1] Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA [2] Mental Health Service Line, Jesse Brown VA Medical Center, Chicago, IL, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Fitzgerald
authors.affiliation: School of Psychological Sciences, Monash University, Melbourne, Victoria, Australia.
authors.forename: Izelle
authors.initials: I
authors.lastname: Labuschagne
authors.affiliation: 1] School of Psychological Sciences, Monash University, Melbourne, Victoria, Australia [2] School of Psychology, University of Birmingham, Birmingham, UK.
authors.forename: Amanda G
authors.initials: AG
authors.lastname: Wood
authors.affiliation: 1] School of Psychological Sciences, Monash University, Melbourne, Victoria, Australia [2] Department of Psychiatry, Cambridge University, Cambridge, UK.
authors.forename: Pradeep J
authors.initials: PJ
authors.lastname: Nathan
authors.affiliation: 1] Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA [2] Mental Health Service Line, Jesse Brown VA Medical Center, Chicago, IL, USA [3] Departments of Psychology and Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: K Luan
authors.initials: KL
authors.lastname: Phan
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000679:Amygdala / Q000187:drug effects* / Q000503:physiopathology; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000503:physiopathology; D002491:Central Nervous System Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005625:Frontal Lobe / Q000187:drug effects* / Q000503:physiopathology; D007839:Functional Laterality; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D010121:Oxytocin / Q000008:administration & dosage*; D011569:Psychiatric Status Rating Scales; D012146:Rest; D012938:Social Perception; D055815:Young Adult
chemical_list: D002491:Central Nervous System Agents; D010121:Oxytocin