This study aims to investigate the potential beneficial effects of intranasal oxytocin compared to placebo on emotion recognition and acute psychosocial stress in patients with arginine vasopressin deficiency compared to matched healthy controls.
Adult healthy volunteers
Matched for age, sex, BMI, and oestrogen replacement/menopause/hormonal contraceptives to patients.
No medication, except hormonal contraception
Adult patients with a confirmed diagnosis of AVP deficiency based on accepted criteria6
Participation in a trial with investigational drugs within 30 days
Active substance use disorder within the last six months
Consumption of alcoholic beverages >15 drinks/week
Current or previous psychotic disorder (e.g., schizophrenia spectrum disorder)
Crossover
Oxytocin nasal spray
DrugParticipants will be instructed on correctly applying the intranasal study medication and will self-administer a single dose of 24 IU oxytocin under the supervision of unblinded study personnel.
Placebo
Other interventionParticipants will be instructed on correctly applying the intranasal study medication and will self-administer a single dose of placebo (0.9% normal saline) under the supervision of unblinded study personnel.
Effect of oxytocin compared to placebo in patients with AVP deficiency compared to healthy controls on recognition of facial emotions/body expression
Differences between the placebo and oxytocin session will be assessed for each participant in correct recognition of facial emotions \& body expressions assessed with the EmBody (emotion from body expressions) /EmFace (emotion from facial expressions) task of 3 or more score points (score range: 20-80) The EmBody and EmFace subtasks comprise each of 42 stimuli showing body or facial expressions of angry, happy, or neutral affect (14 clips per emotion, half in front view and half in half-profile side view from the left). Stimuli last 1.5 seconds at 24 frames per second and are geometrically and optically standardized to prevent biases induced by ethnic cues (e.g., hair or skin tone) or clothing. Item order is pseudorandom to prevent sequence effects and was determined using the following constraints: the same emotion is shown no more than twice in a row; the same view per emotion is not shown consecutively (i.e., no angry-front, angry-front).
Effect of oxytocin compared to placebo in patients with AVP deficiency compared to healthy controls cortisol in response to acute stress
Differences between the placebo and oxytocin session will be assessed for each participant in cortisol levels in response to acute psychosocial stress induced upon the TSST (Trier Social Stress Test) by 15% or more in the area under the cortisol response curve. Salivary cortisol will be measured (as a measure of unbound cortisol concentrations in plasma) before and upon the TSST. Blood cortisol will also be measured The TSST consists of an unprepared speech and mental arithmetic performed in front of an audience. Previous studies indicated that this stress protocol reliably induces a significant HPA (Hypothalamic-pituitary-adrenal)-axis activation, with 2- to 3-fold increases in free cortisol and subjective responses indicative of moderate stress in healthy individuals.
Emotion recognition
-Percentage of correct classifications per emotion in Facial Emotional Recognition Task (FERT). The FERT assesses the recognition of basic emotions. The task includes 10 neutral faces and 160 faces that express one of four basic emotions with pictures, morphed between 0% (i.e., neutral) and 100% in 10% steps. Stimuli are shown in random order for 500 ms, followed by the rating screen, where participants have to indicate the correct emotion.
Empathy
-Level of direct, indirect, and cognitive empathy for positive and negative emotions in the Multifaceted Empathy Task (MET). MET is a computer-assisted test, which consists of 40 photographs that show people in emotionally charged situations. To measure emotional empathy subjects are asked to rate how much they feel for an individual in each scene and how much they are aroused by each scene on a 1-9-point scale. The 3 aspects are each tested with 20 stimuli with positive valence and 20 with negative valence, resulting in a total of 120 trials.
Subjective emotional response to acute stress
Acute anxiety levels using the STAI-S (State-Trait Anxiety Inventory). This is a questionnaire to determine general anxiety levels. Based on responses to 40 items, with scores ranging from 1 ("almost never") to 4 ("almost always"), a total score is calculated. The STAI has two sub-scales, the State-Anxiety Scale (20 items) and the Trait-Anxiety Scale (20 items). The State-Anxiety Scale evaluates the current state of anxiety, asking how respondents feel "right now," using items that measure subjective feelings of apprehension, tension, nervousness, worry, and activation/arousal of the autonomic nervous system. The Trait-Anxiety Scale evaluates relatively stable aspects of "anxiety proneness," including general states of calmness, confidence, and security. The total scores range from 20 to 80, with higher scores indicating more pronounced anxiety.
Heart rate (bpm)
Heart rate as an indicator for subjective autonomic response to acute stress
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