LAUSR

OBJECTIVE Thalamic circuit imbalance characterized by increased sensorimotor-thalamic connectivity and decreased prefrontal-thalamic connectivity has been consistently observed in adult-onset schizophrenia (AOS), though it is unclear if this pattern is also a feature of early-onset schizophrenia (EOS). If this is the case, thalamic circuit imbalance can be considered as a core mechanistic defect in schizophrenia, unconfounded by the age of onset. METHOD Totally 116 adolescents with EOS (63 drug-naive EOS) and 55 matched healthy controls (HC) were recruited and underwent resting-state fMRI scans. To define the specific location of the thalamic subregions in thalamocortical circuit, 16 atlas-based thalamic subdivisions were employed in functional connectivity analysis. RESULTS The EOS group showed increased sensorimotor-thalamic connectivity and decreased prefrontal-/cerebello-thalamic connectivity, consistent with AOS. Sensorimotor-thalamic hyperconnectivity was more prominent than prefrontal-thalamic hypoconnectivity, which was circumscribed to the medial prefrontal cortex (mPFC), in EOS. Of note, the EOS group specifically exhibited strengthened thalamic connectivity with the Salience Network (SN). Additionally, the EOS showed a more prominent disruption of the lateral thalamic nuclear connectivity. CONCLUSION Thalamic dysconnectivity observed in the EOS extends the observations from adult patients. Sensorimotor-thalamic hyperconnectivity is critical for the expression of schizophrenia phenotype irrespective of the onset age, raising the possibility of aberrant, but accelerated functional network maturation in EOS. The specific thalamocortical dysconnectivity involving the SN and mPFC may underlie the distinctive features of multi-modal hallucinations and heightened emotional valence of psychotic seen in the EOS.