Although
antipsychotic drugs are effective for relieving the psychotic symptoms of first-episode
psychosis (
FEP), psychotic relapse is common during the course of the illness. While some FEPs remain remitted even without
medication, antipsychotic discontinuation is regarded as the most common risk factor for the relapse. Considering the actions of
antipsychotic drugs on presynaptic and postsynaptic
dopamine dysregulation, this study evaluated possible mechanisms underlying relapse after
antipsychotic discontinuation. Twenty five FEPs who were clinically stable and 14 matched healthy controls were enrolled. Striatal
dopamine activity was assessed as Kicer value using [18F]
DOPA PET before and 6 weeks after
antipsychotic discontinuation. The D2/3 receptor availability was measured as BPND using [11C]
raclopride PET after
antipsychotic discontinuation. Healthy controls also underwent PET scans according to the corresponding schedule of the patients. Patients were monitored for psychotic relapse during 12 weeks after
antipsychotic discontinuation. 40% of the patients showed psychotic relapse after
antipsychotic discontinuation. The change in Kicer value over time significantly differed between relapsed, non-relapsed patients and healthy controls (Week*Group: F = 4.827, df = 2,253.193, p = 0.009). In relapsed patients, a significant correlation was found between baseline striatal Kicer values and time to relapse after
antipsychotic discontinuation (R2 = 0.518, p = 0.018). BPND were not significantly different between relapsed, non-relapsed patients and healthy controls (F = 1.402, df = 2,32.000, p = 0.261). These results suggest that dysfunctional
dopamine autoregulation might precipitate psychotic relapse after
antipsychotic discontinuation in
FEP. This finding could be used for developing a strategy for the prevention of psychotic relapse related to
antipsychotic discontinuation.