Functional neuroimaging in treatment resistant schizophrenia: A systematic review

Despite the availability of several drugs, about 30% of patients with schizophrenia still fail to respond properly to a course of appropriate antipsychotic treatment. Functional neuroimaging studies have shown widespread patterns of altered activation and functional connectivity in treatment-resistant schizophrenia (TRS). The aim of the present study was to examine the available functional magnetic resonance imaging studies investigating TRS and to identify common patterns of altered brain function that could predict the lack of response to antipsychotic treatment in this disorder. Alterations of activation and functional connectivity in fronto-temporal, cortico-striatal, default mode network and salience networks, and of their interplay, were associated with TRS. Our findings support the notion that large-scale network alterations present in schizophrenia lie in a continuum within treatment response with the most severe dysfunction in TRS. Few studies with small sample size and without adequate control group limit the generalizability of current literature. Future controlled longitudinal studies are needed to identify neuroimaging biomarkers of pharmacotherapy response to inform individual treatment selection and facilitate early clinical response.