"Multimodal Prevention of Psychosis - Investigating Efficacy of N-Acetylcysteine and Psychotherapy in CHR-Patients"

Schizophrenia is a severe mental disorder associated with significant impairments in affective, cognitive and social functioning. Consequently, a special interest in the prevention of schizophrenia and psychotic disorders has emerged. Pharmacological as well as psychological interventions show promising preventive effects. The purpose of this multicentric study is the investigation of possible preventive effects of a treatment combination containing a psychotherapy form and medication (N-Acetylcytein - NAC) in individuals with an enhanced risk for developing schizophrenia. Both treatment forms may reduce the risk in this population due to their specific properties: The psychotherapy can improve social skills, whereas NAC is supposed to develop its protective effects on neuronal level due to its antiinflammatory properties. The investigators will examine the preventive effects by measuring transition rates to psychosis after treatment as well as improvements in social, affective and cognitive functioning.

Psychotic disorders are among the most expensive brain-related disorders in Europe. This is mainly due to their onset early in life and their long-term disabling courses. Current treatments fail to improve most influential factors such as social-cognitive deficits. Prevention is recognized as one of the key strategies to fight these deteriorating outcomes and is expected to significantly reduce both, the societal costs as well as the immense burden for the patients and for their families. Recent meta-analyses indicate promising preventive effects of both pharmacological and cognitive-behavioural interventions. Yet, reported transition rates are still too high. Clinical evidence suggests that disturbances of social functioning predict conversion to psychosis. Neurobiological evidence implicates glutamatergic dysfunction and redox imbalance in the pathophysiology of schizophrenia. The investigators hypothesize that interventions targeting (i) social functioning and (ii) glutamatergic / oxidative pathways already in at-risk states would significantly reduce transition rates. To test these hypotheses, our study is designed as a randomized, placebo-controlled, 18-month trial (six months of intervention plus 12 months of follow-up), involving 200 subjects at-risk for psychosis. Specifically, the investigators will compare the preventive effects of a cognitive-behavioural and social-cognitive intervention to a pharmacological intervention (IPPI) with Acetylcysteine, a drug with a proglutamatergic, neuroprotective and anti-inflammatory profile in a 2x2 factorial design. The results of our planned study are expected to provide new and well tolerated interventions, thus hopefully helping to achieve the major goal of individualized prevention, and, consequently, lower the individual and societal burden of psychosis.