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Prediction of Antipsychotic Response Using a Connectome-Based Neural Signature

A connectome-based functional signature proved to be a promising early predictor of individualized response to antipsychotic treatment in first-episode psychosis. The results in a discovery sample of 49 patients with first-episode psychosis and a validation sample of 24 patients could be an important advance in precision psychiatry.

Participants in the discovery sample underwent multiparadigm functional MRIs (fMRIs) at baseline and were followed clinically for 12 weeks while taking antipsychotic monotherapies. Based on individual-level psychosis scores on the Brief Psychiatric Rating Scale and model generalizability results in the independent validation sample, the investigators found: “The results revealed a paradigm-independent connectomic trait that significantly predicted individualized treatment outcome in both the discovery sample (predicted-versus-observed r = 0.41) and the validation sample (predicted-versus-observed r = 0.47, mean squared error = 0.019). Features that positively predicted psychosis change rates primarily involved connections related to the cerebellar-cortical circuitry, and features that negatively predicted psychosis change rates were chiefly connections within the cortical cognitive systems.”

Editorial: “This study is valuable in introducing a new approach that may advance prediction of response to antipsychotics by combining fMRI data obtained under multiple conditions, although the authors do not show whether the additional task-based measures contributed to increasing accuracy,” editorialists write. “The identification of nodes in the cerebellum and cortex most strongly associated with treatment response may also contribute to circuit-based models of psychosis and pharmacologic treatment mechanisms. Whether the associations between functional connectivity measures at baseline and treatment response are causal remains to be established. For example, because this study included individuals with a range of diagnoses that would be expected to exhibit different responses to antipsychotics, connectivity between specific nodes predictive of response may reflect circuit features of different diagnoses and not circuits responsible for medication effects. The demonstration in future studies that functional connectivity measures change in step with treatment response will be of interest and may strengthen claims of a causal relationship. While some issues remain to be addressed by larger studies, this work lays the groundwork for a promising application of fMRI to an important clinical question in the initial treatment of patients with psychotic disorders.”

Source: American Journal of Psychiatry