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

Abstract

Post-traumatic stress disorder (PTSD) is a disabling psychiatric disorder. As a substantial part of PTSD patients responds poorly to currently available psychotherapies, pharmacological interventions boosting treatment response are needed. Because of its anxiolytic and pro-social properties, the neuropeptide oxytocin (OT) has been proposed as promising strategy for treatment augmentation in PTSD. As a first step to investigate the therapeutic potential of OT in PTSD, we conducted a double-blind, placebo-controlled, cross-over functional MRI study examining OT administration effects (40 IU) on amygdala reactivity toward emotional faces in unmedicated male and female police officers with (n = 37, 21 males) and without (n = 40, 20 males) PTSD. Trauma-exposed controls were matched to PTSD patients based on age, sex, years of service and educational level. Under placebo, the expected valence-dependent amygdala reactivity (ie, greater activity toward fearful-angry faces compared with happy-neutral faces) was absent in PTSD patients. OT administration dampened amygdala reactivity toward all emotional faces in male and female PTSD patients, but enhanced amygdala reactivity in healthy male and female traumaexposed controls, independent of sex and stimulus valence. In PTSD patients, greater anxiety prior to scanning and amygdala reactivity during the placebo session were associated with greater reduction of amygdala reactivity after OT administration. Taken together, our results indicate presumably beneficial neurobiological effects of OT administration in male and female PTSD patients. Future studies should investigate OT administration in clinical settings to fully appreciate its therapeutic potential.

Decreased uncinate fasciculus tract integrity in male

“…33 The study consisted of 3 appointments: 1 intake session, during which inclusion and exclusion criteria were assessed, and 2 MRI sessions. The second session took place, on average, 12.77 ± 14.87 days after the first one.…”

“…Hereafter, functional imaging started in both scanning sessions with an emotional face-matching task 34 to elicit robust amygdala activation. 33 The task consisted of 1 visuomotor control condition (scrambled faces; 4 blocks) and 2 emotion conditions: 1 with fearful and angry faces (2 blocks) and 1 with happy and neutral faces (2 blocks; see Appendix 1, Fig. S1, available at jpn.ca for the task design).…”

“…33 These contrast images were fit into a second-level model with group (PTSD v. control) and sex (male v. female) as between-subjects factors, emotion (fearful-angry faces v. happy-neutral faces) as a within-subjects factor and drug order as a covariate. We assessed amygdala and vmPFC activity during emotional face matching for the overall task effect across all participants (see Appendix 1 for fMRI data analysis).…”

Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder

“…The resting-state scan was part of a larger scanning protocol. First, two task-based fMRI scans were conducted: an emotional face-matching task (Koch et al, 2015) and a monetary (Nawijn et al, 2016a) and social (Nawijn et al, 2016b) incentive delay reward task. Hereafter, the resting-state scan was conducted, which began on average 72.51 min (±4.03) after intranasal spray administration, when neuropharmacological OT administration effects on cerebral blood flow (Paloyelis et al, 2014) and elevated OT levels in cerebrospinal fluid (Striepens et al, 2013) are still observed.…”

“…Because of its anxiolytic and prosocial properties, the neuropeptide oxytocin (OT) may be a promising agent for medication-enhanced psychotherapy in PTSD (Koch et al, 2014;Olff et al, 2010). 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).…”