Striatal functional connectivity in psychosis relapse: A hypothesis generating study

Abstract

Most individuals with psychotic disorders relapse over their course of illness, yet the neural processes that may lead to symptom worsening are poorly understood. Importantly, such processes could be potentially affected by antipsychotic adherence status upon relapse (i.e., relapse despite ongoing antipsychotic maintenance vs following antipsychotic discontinuation), reflecting distinct mechanisms. As a first foray into this question, we aim to compare the striatal connectivity index (SCI), a biomarker derived from striatal resting state functional connectivity predictive of treatment response, by adherence status upon relapse. In order to confirm adherence status upon relapse, we compared individuals treated with long-acting injectable antipsychotics upon relapse (i.e., breakthrough psychosis) (n = 23), with individuals who had decided to interrupt antipsychotic treatment and then relapsed (n = 27), as well as healthy controls (n = 26). We acquired for each individual >10 min of resting state fMRI, to generate functional connectivity maps. Region of interest (ROI) analyses were conducted to calculate SCI values for each participant. These values were entered as dependent variable in a linear regression adjusted for sex and age for which adherence status was the independent variable. Individuals in the breakthrough psychosis group had significantly lower SCI values than healthy controls (Cohen's d = 0.99, p < 0.001), and non-adherent individuals upon relapse (Cohen's d = 0.58, p = 0.032), whereas non-adherent individuals had also trend level lower SCI values than healthy controls (Cohen's d = 0.44, p = 0.09). These results suggest the hypothesis that striatal functional connectivity may be aberrant in psychosis relapse, and that this dysfunction may be greater among individuals who developed relapse despite ongoing antipsychotic treatment.