The effectiveness of current treatment options for sociocognitive deficits and negative symptoms (NS) in schizophrenia spectrum disorders (SSD) remains limited. The cause of NS is thought to be an interference between the mesocorticolimbic dopamine system for social reward expectancy and the network for socioemotional processes. Oxytocin (OXT) may enhance functional connectivity between these neuronal networks. Lower plasma OXT levels correlate negatively with NS severity and deficits in social cognition in SSD. It has been shown that intranasal OXT administration improves social cognition in healthy subjects but in SSD results are inconsistent. According to the social salience hypothesis, the effect of OXT varies depending on the social context and individual factors. Also, OXT-mediated effects on psychopathology and NS may depend on genetic variants of OXT receptors (OXTR). In a pilot study, the investigators demonstrated lower NS by OXT administration in a positive social context of mindfulness-based group psychotherapy (MBGT) in SSD. The investigators also demonstrated that symptoms improved after MBGT. A more recent study suggests that, compared to placebo, administering OXT in a positive social context via MBGT leads to significant between-group differences favoring OXT, particularly in NS, affect, and stress. Building on these findings, the present study investigates the stability of these effects, along with psychological and biological markers, in a larger sample of individuals with SSD. The main hypothesis to be tested is that the use of OXT compared to placebo prior to MBGT in patients with SSD will result in a greater reduction in NS with a higher OXT dosage. The research design is based on an experimental, triple-blind, randomized, placebo-controlled trial.

Schizophrenia spectrum disorders (SCZ) are severe mental illnesses with a lifetime prevalence of 1-2%. Three core syndromes characterize SCZ: positive and negative syndromes (NS), as well as a cognitive syndrome. The effectiveness of current treatment options for negative symptoms (NS) and sociocognitive deficits in schizophrenia spectrum disorders (SSD) remains limited.

The cause of NS is thought to be an interference between the mesocorticolimbic dopamine system for social reward expectancy and the network for socioemotional processes. Oxytocin (OXT) may enhance functional connectivity between these neuronal networks. Lower plasma OXT levels correlate negatively with NS severity and deficits in social cognition in SSD. It has been shown that intranasal OXT administration improves social cognition in healthy subjects but in SSD results are inconsistent. According to the social salience hypothesis, the effect of OXT varies depending on the social context and individual factors. Also, OXT-mediated effects on psychopathology and NS may depend on genetic variants of OXT receptors (OXTR). In a pilot study, the investigators demonstrated lower NS by OXT administration in a positive social context of mindfulness-based group psychotherapy (MBGT) in SSD. The investigators also demonstrated that NS and other symptoms improved after MBGT. A more recent study suggests that, compared to placebo, administering OXT in a positive social context via MBGT leads to significant between-group differences favoring OXT, particularly in NS, affect, and stress. Building on these findings, the present study investigates the stability of these effects, along with psychological and biological markers, in a larger sample of individuals with SSD. The main hypothesis to be tested is that the use of OXT compared to placebo prior to MBGT in patients with SSD will result in a greater reduction in NS, i.e. the difference in T0-T8 of the total score on the BNSS (Brief Negative Symptom Scale) after 4 weeks. The BNSS as a validated rater-based instrument designed for clinical trials will be collected by a blinded psychiatrist. MBGT-sessions by experienced psychotherapists take place once a week over four weeks in a group of six patients. They serve as a positive social context for OXT administration. Participants receive either synthetic oxytocin or a placebo 30 minutes before MBGT.

The role of genetic variations (OXTR genes) for the treatment effect on NS will be explored too as well as the effect on various stress markers including cortisol levels and the endocannabinoid system, affect, group cohesion and mindfulness.

The research design is based on an experimental, triple-blind, randomized, placebo-controlled trial.

Inclusion Criteria:

• Declaration of consent
• Psychiatric diagnosis of schizophrenia (ICD-10: F2x.x spectrum) for group of patients
• Mild to moderate positive symptoms (5 ≤ Positive symptoms on individual items using P-PANSS)
• German should either be the native language or spoken at a native level
• No change in systematically recorded psychopharmacological medication in the last 2 weeks before study inclusion

Exclusion Criteria:

• Acute psychotic episode with severe positive symptoms (ICD-10: F2 spectrum, 6 ≥ positive symptoms on individual items using P-PANSS)
• Acute suicidality
• Acute consumption phase of a substance dependence, except nicotine
• No severe physical impairments, neurological diseases and e.g. severe craniocerebral trauma e.g. early childhood brain damage
• Pregnancy and breastfeeding
• Current acute electroconvulsive therapy

If one of the following criteria applies to the participants, we will conduct an individual consultation in advance to determine whether participation in the study is possible:

• Overweight or underweight (body mass index (BMI) < 17.5 or > 30)
• Disease of the endocrine system
• Impaired kidney or liver function
• Metabolic diseases
• Asthma
• Change in blood potassium or sodium levels