Striatal Functional Connectivity In Psychosis Relapse: A Comparison Between Antipsychotic Adherent And Non-Adherent Patients At The Time Of Relapse

ABSTRACT Most individuals with psychotic disorders relapse over their course of illness. Relapse pathophysiology is generally not well captured in studies that do not account for antipsychotic non-adherence, which is common and often unnoticed in schizophrenia. This study was explicitly designed to understand relapse in patients with guaranteed antipsychotic delivery. We compared individuals with psychosis breakthrough on antipsychotic maintenance medication (BAMM, n=23), for whom antipsychotic adherence prior to relapse was confirmed by using long acting injectable antipsychotics, and individuals who at the time of relapse were antipsychotic free (APF, n=27), as they had declared treatment non-adherence. Resting state functional MRI was acquired to conduct a region of interest (ROI) analyses. We generated functional connectivity maps to calculate striatal connectivity index (SCI) values, a prognostic biomarker of treatment response in first episode schizophrenia. Group differences in SCI values (BAMM vs APF) were compared in a linear regression model. We hypothesized that individuals in the BAMM group would have greater aberrant striatal function, thus lower SCI values, than in individuals in the APF group. Furthermore, we conducted exploratory group comparisons at the ROI level. As predicted, the BAMM group had significantly lower SCI values (ß=0.95, standard error=0.378, p=0.013). Group comparisons at the ROI level indicate differences in functional connectivity of dorsal striatum, and greater decoupling in striato-cerebellar connections among the BAMM group. A prognostic biomarker of treatment response in first episode psychosis showed differences by antipsychotic exposure upon relapse, suggesting that relapse during continued antipsychotic treatment may be characterized by aberrant striatal function.