Motivational Intervention for Patients With Schizophrenia

Background: Negative symptoms of schizophrenia, particularly apathy (avolition, asociality, anhedonia), are a major cause of poor functional outcome, and no pharmacological treatment adequately improves them. The Positive Emotions Program for Schizophrenia (PEPS) is a group psychotherapy that targets deficits in anticipating and maintaining positive emotions. It has reduced apathy and anhedonia compared with treatment as usual in a previous randomized trial (Favrod et al., 2019). The neural mechanisms of this effect are unknown. Ventral striatal hypoactivation during reward anticipation, which is associated with apathy, is a candidate response biomarker. Objectives: The primary objective is to test the efficacy of PEPS on apathy compared with treatment as usual (TAU). Secondary objectives are to test whether PEPS changes ventral striatal activation during reward anticipation, whether neural changes are associated with clinical improvement, and whether PEPS affects emotion processing, social decision-making and resting-state networks. Design: This is a single-centre, rater-blinded randomized controlled trial at the Geneva University Hospitals. Eighty-eight outpatients with schizophrenia, schizoaffective disorder or unspecified nonorganic psychosis (aged 18-60, clinically stable, with at least one moderate negative symptom) are randomized 1:1, stratified by sex, to PEPS or TAU. PEPS consists of eight weekly 1-hour group sessions, with about four participants per group. TAU is routine outpatient care, and TAU participants are offered PEPS after completing the study. Thirty healthy controls are also recruited, without randomization or intervention, to provide test-retest benchmarks. All participants undergo clinical assessment and fMRI at baseline and within 2 weeks after the 8-week intervention or waiting period.