Background and hypothesis: While age at onset in schizophrenia (SCZ) is usually defined by age at onset of psychosis, the illness actually occurs earlier, with a prodrome often starting in childhood or adolescence. We postulated that SCZ with early-adolescence prodromes (SCZ-eaP) presents with social cognition deficits and sensorimotor impairments more similar to autism spectrum disorders (ASD) than SCZ with late-adolescence prodromes (SCZ-laP).
Study design: The movie for the assessment of social cognition and neurological soft signs (NSS) were compared between four groups, ASD, SCZ-eaP (<15 years), SCZ-laP (>15 years), and controls (N = 119), while accounting for age, sex, intelligence quotient, education level, and medication effect. Mediation analyses tested the effect of NSS on social cognition, across groups, and local gyrification indices were used to test whether NSS reflected deviations in early neurodevelopmental trajectories.
Study results: For social cognition and NSS, subjects with ASD were not different from SCZ-eaP, while they differed from SCZ-laP. Age at onset of prodrome correlated with NSS (r = -0.34, P = .018), and social cognition (r = 0.28, P = .048). Neurological soft signs mediated social cognition impairment across diagnoses (β = -1.24, P < 1e-6), and was explained by hypergyrification in the right fusiform gyrus, right frontal pole gyrus, and left postcentral gyrus.
Conclusions: Earlier age of prodrome in SCZ is associated with impaired social cognition, mediated by neurodevelopmentally-related sensorimotor impairments along the ASD-SCZ spectrum. It suggests age of prodrome, rather than the age at psychosis onset, should be considered to define more homogeneous subgroups in SCZ.
Keywords: neuroimaging; neurological soft signs; prodrome; psychosis.
© The Author(s) 2025. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.