O10.8. STRIATAL CONNECTIVITY IN BREAKTHROUGH PSYCHOSIS ON ANTIPSYCHOTIC MAINTENANCE: PRELIMINARY RESULTS FROM THE BAMM STUDY

Abstract

Background: Although antipsychotic drugs are highly efficacious in preventing psychosis relapse, (1) approximately 15% of treatment adherent patients relapse during the maintenance phase. (2) This phenomenon is known as “breakthrough psychosis on antipsychotic maintenance medication” (BAMM). (3) The biological mechanisms of psychotic relapse in treatment adherent individuals are poorly understood. Recent data from our own and other groups indicate that individuals with poor treatment response demonstrate greater striatal functional connectivity than those who respond to antipsychotic drugs, suggesting that failure to respond to antipsychotic drugs may be mediated through extrastriatal mechanisms. (4-6) The BAMM Study aims to generate data about the role of striatal function in individuals with psychosis who have a history of response to antipsychotics yet fail to maintain such response despite confirmed continuous treatment with long acting injectable (LAI) antipsychotics. Methods: Subjects with a psychotic disorder treated with LAI antipsychotics and history of clinical response to antipsychotic medication and sustained response on LAI's who presented with acute psychosis (BPRS≥4 in >1 psychotic items)(i.e., BAMM) were compared with subjects with a psychotic disorder and history of treatment response to antipsychotics who were treatment non-adherent and acutely psychotic (BPRS≥4 in >1 psychotic items)(i.e. Controls). Drug exposure for the BAMM group was confirmed by serum level and dates of LAI administration. We studied group differences in functional connectivity maps of striatal seeds as in Di Martino et al.(7). Data were preprocessed using the Human Connectome Project pipeline and cleaned with the ICA-FIX procedure, which removed motion artifacts and nuisance variables (white matter and CSF signal), but not global signal. Outputs from this procedure underwent band-pass filtering (0.1-0.01Hz). Time-series for each striatal seed were extracted and correlated with those of voxels in the whole brain. The resulting z-transformed maps for each subject were then used in the group analyses (voxelwise z=2.53, cluster threshold p=0.05). Results: Subjects included in the BAMM group had a defined daily dose of 1.36 (ref=1), had been treated continuously >3 months and received the last LAI a mean of 11.19 days prior to the scan. (Table Presented) The BAMM group had significantly greater striatal functional connectivity than controls in the following regions: left dorsal caudate: postcentral gyrus (peak z=3.47) and precuneus (peak z=4.00); right dorso-rostral putamen: a region spanning orbitofrontal cortex, insula and inferior frontal gyrus (peak z=3.56); left superior ventral striatum: postcentral gyrus (peak z=4.25), supplementary motor cortex (peak z=3.72) and postcentral gyrus (peak z=3.70); and right superior ventral striatum: postcentral gyrus (peak z=3.73). Discussion: The preliminary analyses of the first 22 participants indicate that relapse may have different mechanisms depending on whether or not it occurred despite antipsychotic exposure. These pilot data suggest the hypothesis that non-striatal mechanisms may be involved in the failure to maintain antipsychotic drug response. Longitudinal studies using extrastriatal seeds should be conducted to confirm this hypothesis. This research is relevant to better understand the mechanisms of relapse and treatment resistance.