Granger causal connectivity abnormalities based on altered gray matter volume in adolescent-onset schizophrenia and their spatial correspondence with neurotransmitter maps

Abstract Background Previous neuroimaging studies have revealed gray matter volume (GMV) abnormalities in adolescent-onset schizophrenia (AOS). However, the Granger causal connectivity changes associated with these structural abnormalities and their association with neurotransmitter systems remain poorly understood. Methods Structural and resting-state functional magnetic resonance imaging data were obtained from 21 first-episode, drug-naïve patients with AOS and 21 healthy controls (HC). First, voxel-based morphometry (VBM) was used to assess GMV differences between the two groups. Brain regions showing significant GMV differences were selected as seeds for further Granger causality analysis (GCA). Subsequently, the JuSpace toolbox was used to investigate the spatial correlation between changes in Granger causal connectivity and atlas-based neurotransmitter maps. Results Compared to HC, patients with AOS exhibited higher GMV in the right supramarginal gyrus (SMG) and precuneus (PCUN). Regarding the GCA, AOS exhibited increased Granger causal connectivity from the right SMG to the right superior occipital gyrus (SOG) and precentral gyrus (PreCG), whereas Granger causal connectivity from the right PCUN to the right orbital part of the inferior frontal gyrus (ORBinf) was decreased. Furthermore, alterations in Granger causal connectivity based on the right PCUN were spatially associated with the distribution of receptors/transporters for the serotonergic (5-HT1b, SERT), dopaminergic (D1, D2, DAT), GABAergic (GABAa), glutamatergic (mGluR5), endogenous opioid (kappaOp), and cholinergic (VAChT) systems. Conclusion This study revealed neuroanatomical alterations in AOS and whole-brain Granger causal connectivity abnormalities based on structural changes, and identified multiple neurotransmitter systems potentially associated with these functional disruptions. These findings provide valuable insights into the complex neuropathological mechanisms underlying AOS and offer clues for potential therapeutic targets based on neurotransmitter modulation.