The Association of Affective Resonance With Empathy Modulated by Negative Symptomatology and Oxytocin

The study design is based on an experimental, double-blinded (participants, instructor), placebo-controlled, proof-of-concept randomized, trial and complies with the CONSORT guidelines. The study was approved by the ethical committee of the Charité - Universitätsmedizin Berlin (EA4/196/19). All study-relevant measures were based on the current Declaration of Helsinki. After eligibility screening, informed consent was obtained at least 24 hours before participants started baseline assessments. Participants were randomly allocated to the experimental condition with admission of oxytocin or to a placebo treatment as the active control condition with MBGT as a positive social context in each condition. Randomization was performed by an independent researcher using a random computer-generated sequence with randomly permuted block sizes. To exclude gender bias, both men and women were included in mixed-gender groups on a balanced basis.

On two dates within one week the application of oxytocin (OXT) nasal spray or placebo took place by trained physicians to test a possible influence of OXT on empathy and other variables in dependence of and the pre-existing expression of a negative symptomatology and a positive social context in form of two psychologically supervised manual-based mindfulness based group sessions (MBGT). Empathy as primary outcome as well as negative symptoms as secondary outcome, and exploratory affect, stress and mindfulness were measured using validated self- and external-rated psychometric questionnaires. Secondary outcomes were conducted merely for exploratory reasons. All outcomes, including venous-blood sampling for OXT plasma levels, were measured before the first session at baseline (T0), after completion of the treatment period of 1-week (T3) and in between after the first session (T1) and before 2nd session (T2). For their time, participants received a financial compensation of 30 Euros after completion of post-intervention assessment.

The patients received either a spray of the synthetic oxytocin (24 I.U. Syntocinon®) or a commercially available nasal spray placebo. P: According to the manufacturer, the nasal sprays for OXT (Syntocinon) and placebo were not distinguishable by appearance, taste, or different rates of ADRs. The choice of dose is based on preliminary studies of optimal effects on aspects of social cognition. Due to an effect latency of 30-80 mins after intranasal administration of OXT on social behavior, the dose was administered 30 min before the 50-min session. The bottles of the nasal sprays were numbered to guarantee blinding of the participants and the treatment team. By applying OXT exclusively before the controlled exercise setting and the refraining from a continuous administration of OXT for one week, reinforcement of negative experiences according to the OXT salience hypothesis outside the created context of the exercises should be avoided. Oxytocin, which is also produced as an endogenous hormone, acts in the human body at Oxytocin receptors in various organ systems. Oxytocin nasal spray (Syntocinon) is used to promote milk let-down in women, who have difficulty breastfeeding and in secondary hypogalactia.

As a positive social context during the placebo-controlled oxytocin application participants attended two supervised MBGT sessions (50 mins each) in groups of 3-6 individuals for a period of one week.

MBGT depicts a novel and innovative treatment program for SSD which was specifically developed within an iterative and participatory research design by our research group MBGT was selected as a positive social context because of explicit feedback from prior studies of participants with schizophrenia spectrum disorders (SSD) that they had felt comfortable during the relevant sessions. Overall, the sessions are taking into account original recommendations for implementing mindfulness in psychosis as well as patient feedback.