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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

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Abstract

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.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors would like to express their gratitude to the individuals who participated in this study. We also express our gratitude to the technical staff of the Magnetic Resonance Department of the First Affiliated Hospital of Zhengzhou University, who helped to acquire images of patients, and the staff of the Department of Psychiatry of the First Affiliated Hospital of Zhengzhou University

Funding

This work was supported by the Natural Science Foundation of China (81601467, 81871327), the Medical Science and Technology Research Project of Henan Province (201701011), and the Medical Science and Technology Research Project of Henan province (SBGJ202101013).

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Authors and Affiliations

  1. Department of Magnetic Resonance Imaging, Two Seven District, The First Affiliated Hospital of Zhengzhou University, 1St Construction of E Rd, Zhengzhou, 450052, China

    Jingli Chen, Yarui Wei, Kangkang Xue, Shaoqiang Han, Caihong Wang, Baohong Wen & Jingliang Cheng

  2. Key Laboratory for Functional Magnetic Resonance Imaging and Molecular Imaging of Henan Province, Zhengzhou, China

    Jingli Chen, Yarui Wei, Kangkang Xue, Shaoqiang Han, Caihong Wang & Jingliang Cheng

  3. Engineering Technology Research Center for Detection and Application of Brain Function of Henan Province, Zhengzhou, China

    Jingli Chen, Yarui Wei, Kangkang Xue, Shaoqiang Han, Caihong Wang & Jingliang Cheng

  4. Engineering Research Center of Medical Imaging Intelligent Diagnosis and Treatment of Henan Province, Zhengzhou, China

    Jingli Chen, Yarui Wei, Kangkang Xue, Shaoqiang Han, Caihong Wang & Jingliang Cheng

  5. Key Laboratory of Magnetic Resonance and Brain Function of Henan Province, Zhengzhou, China

    Jingli Chen, Yarui Wei, Kangkang Xue, Shaoqiang Han, Caihong Wang & Jingliang Cheng

  6. Key Laboratory of Brain Function and Cognitive Magnetic Resonance Imaging of Zhengzhou, Zhengzhou, China

    Jingli Chen, Yarui Wei, Kangkang Xue, Shaoqiang Han, Caihong Wang & Jingliang Cheng

  7. Key Laboratory of Imaging Intelligence Research Medicine of Henan Province, Zhengzhou, China

    Jingli Chen, Yarui Wei, Kangkang Xue, Shaoqiang Han, Caihong Wang & Jingliang Cheng

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Chen, J., Wei, Y., Xue, K. et al. 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. Psychopharmacology 240, 813–826 (2023). https://doi.org/10.1007/s00213-023-06323-9

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