Frontal lobe fALFF measured from resting-state fMRI as a prognostic biomarker in first-episode psychosis

Clinical response to antipsychotic drug treatment is highly variable, yet prognostic biomarkers are lacking. The goal of the present study was to test whether the fractional amplitude of low-frequency fluctuations (fALFF), as measured from baseline resting-state fMRI data, can serve as a potential biomarker of treatment response to antipsychotics. Patients in the first episode of psychosis (n = 126) were enrolled in two prospective studies employing second-generation antipsychotics (risperidone or aripiprazole). Patients were scanned at the initiation of treatment on a 3T MRI scanner (Study 1, GE Signa HDx, n = 74; Study 2, Siemens Prisma, n = 52). Voxelwise fALFF derived from baseline resting-state fMRI scans served as the primary measure of interest, providing a hypothesis-free (as opposed to region-of-interest) search for regions of the brain that might be predictive of response. At baseline, patients who would later meet strict criteria for clinical response (defined as two consecutive ratings of much or very much improved on the CGI, as well as a rating of ≤3 on psychosis-related items of the BPRS-A) demonstrated significantly greater baseline fALFF in bilateral orbitofrontal cortex compared to non-responders. Thus, spontaneous activity in orbitofrontal cortex may serve as a prognostic biomarker of antipsychotic treatment.