Sleep and wake markers of thalamocortical functioning in early-course psychosis and first-degree relatives

Abstract Thalamocortical circuits regulate information flow between sensory inputs and higher-order processing, and their disruption is increasingly implicated in psychotic disorders. However, scalable biomarkers of this circuitry remain limited. We assessed P50 sensory gating, 40 Hz auditory steady-state responses (ASSRs) and sleep spindles in relation to resting-state thalamocortical connectivity in early-course psychosis (EC, n = 19), first-degree relatives (FHR, n = 24), and demographically matched non-psychiatric comparison subjects (NC, n = 28). Compared to NC, EC, and FHR exhibited hyperconnectivity of the thalamus with the primary auditory cortex. Patients showed spindle deficits and impaired sensory gating and ASSRs, while FHR showed abnormal ASSR. In the entire sample, sleep spindles and sensory gating were associated with distinct thalamic connectivity patterns involving sensorimotor and dorsolateral prefrontal cortices, respectively. Our multimodal, circuit-informed approach points to thalamocortical pathways as potential biomarkers of risk and targets for treatment in psychosis. These findings should be interpreted in light of the modest sample sizes and the cross-sectional design, and suggest that wake EEG measures, though scalable, may not fully capture sleep-related thalamic abnormalities.