Aberrant Brain Topological Properties in Early-Onset and Adult-Onset Schizophrenia: Evidence From First-Episode...

Early-onset schizophrenia (EOS), defined as onset before age 18, is associated with more severe symptoms, higher genetic load, and poorer functional outcomes compared with adult-onset schizophrenia (AOS). Alterations in brain network organization have been widely reported in EOS and may contribute to its distinct clinical profile, although interactive effects of age and disease on connectome topology remain poorly understood.

This study included 45 first-episode drug-naïve patients with EOS, 47 first-episode drug-naïve patients with AOS, and 79 age-matched healthy controls (29 younger, 50 older), with additional exploration in medicated groups (91 EOS and 79 AOS). Resting-state functional magnetic resonance imaging and graph theory analysis were used to compare topological properties of whole-brain networks and subnetworks across groups.

Significant diagnosis × age stratum interactions were identified specifically on clustering coefficients of the somatosensory-motor network (SMN) and auditory network. EOS showed increased normalized clustering coefficients (gamma), whereas AOS exhibited reduced gamma. Crucially, these aberrant patterns in SMN persisted after antipsychotic treatment.

These findings suggest that EOS and AOS may differ in the topological organization of brain networks, particularly within the SMN and auditory network. The persistence of SMN abnormalities after antipsychotic treatment further supports the possibility that EOS has a distinct network-level pathophysiology.

We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure sex balance in the selection of non-human subjects. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group.