Reduced Amplitude of Low-Frequency Brain Oscillations in the Psychosis Risk Syndrome and Early Illness Schizophrenia.

Low-frequency oscillations (LFOs) of the blood oxygen level-dependent (BOLD) signal are gaining interest as potential biomarkers sensitive to neuropsychiatric pathology. Schizophrenia has been associated with alterations in intrinsic LFOs that covary with cognitive deficits and symptoms. However, the extent to which LFO dysfunction is present before schizophrenia illness onset remains unknown. Resting-state FMRI data were collected from clinical high-risk (CHR; n=45) youth, early illness schizophrenia (ESZ; n=74) patients, and healthy controls (HCs; n=85) aged 12-35 years. Age-adjusted voxelwise fractional amplitude of low-frequency fluctuations (fALFF; 0.01-0.08 Hz) of the BOLD signal was compared among the three groups. Main effects of Group (p<0.005 height threshold, familywise error cluster-level corrected p<0.05) were followed up via Tukey-corrected pairwise comparisons. Significant main effects of Group (p<0.05) revealed decreased fALFF in ESZ and CHR groups relative to HCs, with values in the CHR group falling between those of ESZ and HC groups. These differences were identified primarily in posterior cortex, including temporoparietal regions, extending into occipital and cerebellar lobes. Less LFO activity was related to greater symptom severity in both CHR and ESZ groups in several of these posterior cortical regions. These data support an intermediate phenotype of reduced posterior cortical LFO amplitude in CHR individuals, with resting fALFF values smaller than in HCs but higher than in ESZ patients. Findings indicate that LFO magnitude alterations relate to clinical symptoms and predate psychosis onset but are more pronounced in the early stages of schizophrenia.