A novel somato-visual functional connectivity biomarker for affective and non-affective psychosis

People with psychosis are known to exhibit thalamo-cortical hyperconnectivity and cortico-cortical hypoconnectivity with sensory networks, however, it remains unclear if this applies to all sensory networks, whether it impacts affective and non-affective psychosis equally, or whether such differences could form the basis of a viable biomarker. To address the foregoing, we harnessed data from the Human Connectome Early Psychosis Project and computed resting-state functional connectivity (RSFC) matrices for healthy controls and affective/non-affective psychosis patients who were within 5 years of illness onset. Primary visual, secondary visual (“visual2”), auditory, and somatomotor networks were defined via a recent brain network partition. RSFC was determined for 718 regions (358 subcortical) via multiple regression. Both patient groups exhibited cortico-cortical hypoconnectivity and thalamo-cortical hyperconnectivity in somatomotor and visual2 networks. The patient groups were similar on every RSFC comparison. Across patients, a robust psychosis biomarker emerged when thalamo-cortical and cortico-cortical connectivity values were averaged across the somatomotor and visual2 networks, normalized, and subtracted. Four thalamic regions linked to the same two networks disproportionately drove the group difference (p=7e-10, Hedges’ g=1.10). This “somato-visual” biomarker was present in antipsychotic-naive patients and discoverable in a 5 minute scan; it could differentiate psychosis patients from healthy or ADHD controls in two independent data sets. The biomarker did not depend on comorbidities, had moderate test-retest reliability (ICC=.59), and could predict patient status in a held-out sample (sensitivity=.66, specificity=.82, AUC=.83). These results show that- across psychotic disorder diagnoses- an RSFC biomarker can differentiate patients from controls by the early illness stages.