The Association of Affective Resonance With Empathy Modulated by Negative Symptomatology and Oxytocin
Condition: Schizophrenia Spectrum Disorders
MeSH terms: Schizophrenia
Study type: Interventional

Summary: 
      In previous studies the neuropeptide oxytocin has been in particular associated with social
      enhancing and anxiety relieving effects.

      The purpose of this study is to investigate the effect of oxytocin on empathy in patients
      with schizophrenia. On a neurobiological level, social effects mediated by oxytocin are based
      on oxytocin's influence on the complexly regulated mesocorticolimbic dopamine system.
      Preliminary studies have already shown that oxytocin increases neuronal connections between
      social reward expectancy networks and networks for socioemotional processes in the brain,
      which on a behavioral level leads to increased social activation, motivation, and also
      improved social perception. Furthermore, an increase in empathy modulated by the amygdala has
      been shown in healthy individuals following oxytocin administration. In particular, primary
      psychotic disorders, such as schizophrenia, are associated with deficits in the domain of
      social cognition, including empathy, with the degree of negative symptoms playing an
      important mediating role. Another study demonstrated a significantly lower expression of
      empathy as well as a significantly lower oxytocin level in patients with schizophrenia
      compared to healthy subjects. According to the hypothesis of social salience, which describes
      an increased importance of certain social stimuli, the effect of oxytocin varies depending on
      specific contexts and individual variables of the perceiving person, such as the degree of
      negative symptoms. Therefore, based on such preliminary findings, the research project will
      explore an effect of oxytocin on empathy within a positively experienced and controlled
      context, especially in patients with schizophrenia regarding their negative symptoms.
    

Detailed description: 
      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.

      Within the sessions, short periods of meditation are used to avoid prolonged periods of
      silence, and basic anchoring techniques and easily comprehensive language were used according
      to recommendations.

      The two sessions of the manual, which were considered most appropriate with regard to a
      positive social setting for individuals with SSD, were tailored to the relevant requirements
      in the context of this study. They focused on two of four core aspects of mindfulness (breath
      and senses in nature) while interacting with other participants, sharing experiences and
      expressing emotions, as well as engaging in activities together and enhancing mutual
      understanding and trust.

      The sessions followed a standardized but adapted procedure described in the manual.

      They started with an introduction to the topic of the session (breathing or senses in
      nature), after which 15 mins of mindfulness exercises were practiced based on the topic.
      Lastly, there were 10 min of sharing experiences, based on the inquiry model as well as 5 min
      for sharing individual aims.

      The first session "Mindfulness of breathing" focused on making participants aware of their
      own breathing within the present moment and introducing the concept of mindfulness. After an
      introduction phase within the group, basic psychoeducation about mindfulness and two
      breathing exercises followed. In form of an inquiry process, participants were able to share
      their experiences and thoughts with the group.

      In the session "Mindfulness of the senses in nature" participants started with a
      self-reflection phase about the meaning of mindfulness in their every-day life, which they
      could share with the group. This was followed by an exercise, activating all senses within
      the present moment and a mindful walk through the nature. After each participant's option to
      share their experiences with the group, the session was finished with a final resumé by each
      participant.

      The sessions were led by a psychotherapist with over ten years of experience in
      mindfulness-based practices together with a psychotherapist in training in cognitive
      behavioral therapy with over three years of experience in mindfulness practice. The sessions
      were implemented outside within a naturalistic setting due to the restrictions of the
      hospital in the context of the Covid-19 pandemic and the resulting ban on conducting
      outpatient groups indoors.

      The manual-based sessions are established procedures in each case, for which no risks have
      been found to have occurred so far on the basis of diverse preliminary work. Adverse effects
      on participants were notexpected. It nonetheless was ensured by regular feedback from the
      participants.
    

Intervention name(s): Oxytocin; Placebo
Intervention type(s): Other; Other
Intervention description(s): Oxytocin nasal spray in a positive social setting.; Placebo nasal spray in a positive social setting.
Intervention MeSH terms: Oxytocin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment