Resting-state functional connectivity in treatment response and resistance in schizophrenia: A systematic review

Treatment-resistant schizophrenia (TRS) and treatment-responsive schizophrenia may exhibit distinct pathophysiology. Several functional magnetic resonance imaging (fMRI) studies have used resting-state functional connectivity analyses (rs-FC) in TRS patients to identify markers of treatment resistance. However, to date, existing findings have not been systematically evaluated.

A systematic literature search using Embase, MEDLINE, PsycINFO, ProQuest, PUBMED, and Scopus was performed. The query sought fMRI articles investigating rs-FC in treatment response or resistance in patients with schizophrenia. Only studies that examined treatment response, operationalized as the explicit categorization of patients by their response to antipsychotic medication, were considered eligible. Pairwise comparisons between patient groups and controls were extracted from each study.

The search query identified 159 records. Ten studies met inclusion criteria. Five studies examined not TRS (NTRS), and 8 studies examined TRS. Differences in rs-FC analysis methodology precluded direct comparisons between studies. However, disruptions in areas involved in visual and auditory information processing were implicated in both patients with TRS and NTRS. Changes in connectivity with sensorimotor network areas tended to appear in the context of TRS but not NTRS. Moreover, there was some indication that this connectivity could be affected by clozapine.

Functional connectivity may provide clinically meaningful biomarkers of treatment response and resistance in schizophrenia. Studies generally identified similar areas of disruption, though methodological differences largely precluded direct comparison between disruption effects. Implementing data sharing as standard practice will allow future reviews and meta-analyses to identify rs-FC correlates of TRS.