The interaction between first-episode drug-naïve schizophrenia and age based on gray matter volume and its molecular analysis: a multimodal magnetic resonance imaging study

Objectives Schizophrenia is a neurodevelopmental disorder characterized by progressive and widespread gray matter (GM) atrophy. Studies have shown that normal brain development has an impact on schizophrenia-induced GM alterations. However, the neuropathology and underlying molecular mechanisms of interaction between age and schizophrenia are unclear. Methods This study enrolled 66/84 first-episode drug-naïve patients with early-onset/adult-onset schizophrenia ((EOS)/(AOS)) and matched normal controls (NC) (46 adolescents/73 adults), undergoing T1-weighted high-resolution magnetic resonance imaging. Gray matter volume (GMV) in four groups was detected using 2-way analyses of variance with diagnosis and age as factors. Then, factors-related volume maps and neurotransmitter maps were spatially correlated using JuSpace to determine the relationship to molecular structure. Results Compared to AOS, EOS and adult NC had larger GMV in right middle frontal gyrus. Compared to adolescent NC, EOS and adult NC had smaller GMV in right lingual gyrus, right fusiform gyrus, and right cerebellum_6. Disease-induced GMV reductions were mainly distributed in frontal, parietal, thalamus, visual, motor cortex, and medial temporal lobe structures. Age-induced GMV alterations were mainly distributed in visual and motor cortex. The changed GMV induced by schizophrenia, age, and their interaction was related to dopaminergic and serotonergic receptors. Age is also related to glutamate receptors, and schizophrenia is also associated with GABAaergic and noradrenergic receptors. Conclusions Our results revealed the multimodal neural mechanism of interaction between disease and age. We emphasized age-related GM abnormalities of ventral stream of visual perceptual pathways and high-level cognitive brain in EOS, which may be affected by imbalance of excitatory and inhibitory neurotransmitters.