Severe Brain Network Hierarchy Disorganization in Treatment-Naïve Deficit vs. Non-Deficit Schizophrenia and Neurotransmitter Associations

Motivation: Schizophrenia subtypes (deficit schizophrenia, DS vs. non-deficit schizophrenia, NDS) exhibit different neurodevelopmental trajectories and treatment responses, with limited antipsychotic efficacy for negative symptoms. Goal(s): To examine whether DS and NDS patients show distinct brain functional hierarchy abnormalities and how they relate to receptor and transporter distributions. Approach: Resting-state fMRI and high-resolution imaging were used to assess functional gradients, clinical correlations, and neurotransmitter spatial associations in 159 participants. Results: DS patients showed greater cortical hierarchy compression and stronger serotonergic associations, while NDS exhibited dopaminergic links. These findings highlight distinct neurochemical pathways influencing symptoms. Impact: This study found that DS showed more severe cortical hierarchy compression linked to serotonergic dysfunction, while NDS was primarily associated with dopaminergic abnormalities, highlighting distinct neurochemical pathways in each subtype.