Frontal lobe fALFF measured from resting-state fMRI at baseline predicts acute treatment response in first episode psychosis

While antipsychotic medications have been utilized for decades, many patients experiencing psychosis do not demonstrate a satisfactory positive symptom response, even in the first episode of illness. Resting state functional magnetic resonance imaging (rs-fMRI) has increasingly been studied as a potential biomarker of antipsychotic treatment response, but studies to date remain limited in terms of sample size and brain regions examined. The present study examined fractional amplitude of low frequency fluctuations (fALFF) derived from rs-fMRI to search the whole brain, in a hypothesis-free manner, for regions that might predict response to 12 weeks of treatments with standard antipsychotic medications (risperidone or aripiprazole). To our knowledge, the present study represents the largest first episode psychosis treatment sample studied with rs-fMRI to date (N=126). At baseline, patients who would later meet strict criteria for clinical response demonstrated significantly greater baseline fALFF in bilateral orbitofrontal cortex compared to non-responders. In a subset of 62 patients who were scanned a second time at the end of treatment, responders and non-responders demonstrated significant increases in fALFF in differing brain regions. Specifically, responders demonstrated significant increases in fALFF, from baseline to follow-up, in bilateral dorsal prefrontal cortex; prefrontal changes were not observed in non-responders or in healthy individuals (n=45) scanned at two time points. Thus, spontaneous activity in orbitofrontal cortex may serve as a prognostic biomarker of antipsychotic treatment, while spontaneous activity in the dorsal prefrontal cortex may serve as a critical target of effective medication.