Aberrant connectivity in the hippocampus, bilateral insula and temporal poles precedes treatment resistance in first-episode psychosis: a prospective resting-state functional magnetic resonance imaging study with connectivity concordance mapping.

Skouras, Stavros; Kleinert, Maria-Lisa; Lee, Edwin H M; Hui, Christy L M; Suen, Yi Nam; Camchong, Jazmin; Chong, Catherine S Y; Chang, Wing Chung; Chan, Sherry K W; Lo, William T L; Lim, Kelvin O; Chen, Eric Y H (2024). Aberrant connectivity in the hippocampus, bilateral insula and temporal poles precedes treatment resistance in first-episode psychosis: a prospective resting-state functional magnetic resonance imaging study with connectivity concordance mapping. Brain Communications, 6(3), fcae094. Oxford University Press 10.1093/braincomms/fcae094

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Functional connectivity resting-state functional magnetic resonance imaging has been proposed to predict antipsychotic treatment response in schizophrenia. However, only a few prospective studies have examined baseline resting-state functional magnetic resonance imaging data in drug-naïve first-episode schizophrenia patients with regard to subsequent treatment response. Data-driven approaches to conceptualize and measure functional connectivity patterns vary broadly, and model-free, voxel-wise, whole-brain analysis techniques are scarce. Here, we apply such a method, called connectivity concordance mapping to resting-state functional magnetic resonance imaging data acquired from an Asian sample (n = 60) with first-episode psychosis, prior to pharmaceutical treatment. Using a longitudinal design, 12 months after the resting-state functional magnetic resonance imaging, we measured and classified patients into two groups based on psychometric testing: treatment responsive and treatment resistant. Next, we compared the two groups' connectivity concordance maps that were derived from the resting-state functional magnetic resonance imaging data at baseline. We have identified consistently higher functional connectivity in the treatment-resistant group in a network including the left hippocampus, bilateral insula and temporal poles. These data-driven novel findings can help researchers to consider new regions of interest and facilitate biomarker development in order to identify treatment-resistant schizophrenia patients early, in advance of treatment and at the time of their first psychotic episode.

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