Longitudinal changes in striatocortical connectivity in first-episode psychosis associated with the emergence of treatment resistance

Treatment resistance affects up to one in four individuals with psychosis in the first few years of illness. However, there is limited information about the brain changes associated with treatment resistance, restricting our ability to develop effective prognostic biomarkers or new treatments. Using resting-state functional MRI, we examined striatocortical connectivity in 87 patients who presented a non-affective first-episode of psychosis and 118 healthy controls, with follow-up imaging on more than half of the participants in the next 6 years, totaling 361 images. Crucially, we identified 30 patients who presented treatment-resistant psychosis in this follow-up period. Thus, we examined baseline (at first episode) and longitudinal striatocortical differences within psychosis subgroups (treatment-responsive and treatment-resistant psychosis), and between patients subgroups and healthy controls. Compared to healthy controls, participants with treatment-responsive psychosis presented baseline differences in functional connectivity of ventral striatal systems, without changes over time; whereas patients with treatment-resistant psychosis showed both baseline and longitudinal differences in ventral striatal systems, compared to healthy controls. Treatment-responsive and treatment-resistant psychosis groups differed in longitudinal changes in connectivity between ventral striatal and temporal cortical regions. This is one of the circuits which has been previously related to symptom improvements in patients with first-episode of psychosis. No baseline differences were observed between the two psychosis groups. Overall, treatment-resistant psychosis is characterized by longitudinal changes in striatal systems in early psychosis, which might be used as the basis of future prognostic biomarkers.