Imbalance of thalamocortical structural connectivity in adolescents with early-onset schizophrenia

Thalamocortical circuit imbalance, characterized by decreased prefrontal-thalamic connectivity and increased sensorimotor-thalamic connectivity, has been well-documented in adult-onset schizophrenia. We have previously demonstrated functional imbalance of this circuit in adolescents with early-onset schizophrenia (EOS). We now investigate whether this functional imbalance stems from the thalamocortical structural connectivity in EOS, thereby further establishing its relevance to the neurodevelopmental modeling of psychosis.

The study included 212 adolescents (145 EOS patients and 67 healthy controls). To further control the medication effect, the patients were divided into two subgroups (drug-naive vs drug-treated). Fourteen bilateral cortical regions of interest and bilateral thalamus were used as targets and seeds respectively for probabilistic tractography to quantify structural connectivity of the thalamocortical circuit.

Compared to healthy controls, in EOS, structural connectivity of the thalamus with the dorsolateral prefrontal (dlPFC) and parietal cortices was decreased, while connectivity with the sensorimotor cortices was increased. We also observed an unexpected increase in connectivity of the medial prefrontal cortex (mPFC) with thalamus in EOS. The imbalance pattern was replicated in two subgroups regardless of medication status. Further correlation analysis showed that the thalamic hypoconnectivity with the dlPFC and the hyperconnectivity with the mPFC were both related with higher individual symptom burden in patients.

The functional thalamocortical circuit imbalance in adolescents with schizophrenia is underwritten by a similar imbalance in the structural connectivity. A specific thalamocortical structural hyperconnectivity involving the mPFC, previously unobserved in adult-onset patients, may contribute to the distinct clinical manifestations in EOS.