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Schizophrenia is a heterogeneous disorder that exhibits variable responsiveness to treatment between individuals. Here we conducted a resting-state functional magnetic resonance imaging (rs-fMRI) study to determine whether resistance to first-line antipsychotics is reflected in resting-state connectivity. rs-fMRI data were collected from 15 people who had failed to respond to first-line antipsychotics (clozapine-eligible) and 10 first-line treatment responders (FLR). Image pre-processing and analysis were performed using FMRIB's software library (FSL). Data was decomposed into spatial and temporal components using independent components analysis. Connectivity within each independent component was compared between groups using t-tests and the Bonferroni correction for multiple comparisons. Gender was added as a covariate. Clozapine-eligible individuals exhibited enhanced functional connectivity within the sensorimotor network compared with FLR. Those eligible for clozapine showed additional connectivity with the precuneus compared with FLR. No other comparisons reached statistical significance and no effect of gender was observed. These data reveal differences in functional connectivity between FLR and those eligible for clozapine and suggest that greater connectivity between the SMN and precuneus may be indicative of treatment resistance in people with schizophrenia., (Copyright © 2018. Published by Elsevier B.V.)

Highlights • DWI shows differences between first-line responders and those in need of clozapine. • There was no difference between groups in the mean AD of the corpus callosum. • Lower FA and greater RD in the CC could be a marker of treatment resistance. Abstract Schizophrenia is a heterogeneous disorder exhibiting variable responsiveness to treatment between individuals. Previous work demonstrated that white matter abnormalities may relate to antipsychotic response but no study to date has examined differences between first-line treatment responders (FLR) and clozapine-eligible individuals receiving first-line antipsychotics. The current study aimed to establish whether differences in white matter structure exist between these two cohorts. Diffusion-weighted images were acquired for 15 clozapine-eligible and 10 FLR participants. Measures of fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) were obtained and between-group t -tests interrogating differences in FA were conducted. To investigate the neural basis of a decrease in FA, the significant cluster from FA analysis was masked and used to obtain mean RD and AD measures for that region. Those who were clozapine-eligible had significantly lower FA in the body of the corpus callosum (p < 0.05), associated with a significant increase in mean RD compared with FLR (p < 0.001). No difference in mean AD was observed for this region. These data reveal differences in diffusion measures between FLR and those eligible for clozapine and suggest that lower FA and greater RD in the corpus callosum could exist as a biomarker of treatment resistance in people with schizophrenia. [ABSTRACT FROM AUTHOR]