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Evaluating Gene Expression and Methylation Profiles of TCF4, MBP, and EGR1 in Peripheral Blood of Drug-Free Patients with Schizophrenia: Correlations with Psychopathology, Intelligence, and Cognitive Impairment

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Abstract

Discovery and validation of new, reliable diagnostic and predictive biomarkers for schizophrenia (SCZ) are an ongoing effort. Here, we assessed the mRNA expression and DNA methylation of the TCF4, MBP, and EGR1 genes in the blood of patients with SCZ and evaluated their relationships to psychopathology and cognitive impairments. Quantitative real-time PCR and quantitative methylation-specific PCR methods were used to assess the expression level and promoter DNA methylation status of these genes in 70 drug-free SCZ patients and 72 healthy controls. The correlation of molecular changes with psychopathology and cognitive performance of participants was evaluated. We observed downregulation of TCF4 and upregulation of MBP mRNA levels in SCZ cases, relative to controls in our study. DNA methylation status at the promoter region of TCF4 demonstrated an altered pattern in SCZ as well. Additionally, TCF4 mRNA levels were inversely correlated with PANSS and Stroop total errors and positively correlated with WAIS total score and working memory, consistent with previous studies by our group. In contrast, MBP mRNA level was significantly positively correlated with PANSS and Stroop total errors and inversely correlated with WAIS total score and working memory. These epigenetic and expression signatures can help to assemble a peripheral biomarker-based diagnostic panel for SCZ.

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Data Availability

All raw data are available upon request from the corresponding authors.

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Acknowledgements

We sincerely thank the staff of the Department of Genomic Psychiatry and Behavioral Genomics (DGPBG) at Roozbeh Hospital, School of Medicine, Tehran University of Medical Science (TUMS).

Funding

This study has been supported by the Tehran University of Medical Sciences under grant No. 32178.

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Authors and Affiliations

  1. Department of Basic Medical Sciences, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai, United Arab Emirates

    Fatemeh Yazarlou

  2. Department of Cellular and Molecular Biology, Faculty of Life Sciences and Biotechnologies, Shahid Beheshti University, Tehran, Iran

    Mobina Tabibian

  3. Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Asaad Azarnezhad

  4. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Habib Sadeghi Rad

  5. Shenzhen Huayuan Biological Science Research Institute, Shenzhen Huayuan Biotechnology Co. Ltd., 601 Building C1, Guangming Science Park, Fenghuang Street, 518000, Shenzhen, Guangdong, People’s Republic of China

    Leonard Lipovich

  6. Center for Molecular Medicine and Genetics, Wayne State University, 540 E. Canfield St., Detroit, MI, 48201, USA

    Leonard Lipovich

  7. Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran

    Golshid Sanati

  8. Department of Medicine, Biomedical Genetics, Boston University School of Medicine, Boston, MA, USA

    Hamid Mostafavi Abdolmaleky

  9. Department of Genomic Psychiatry and Behavioral Genomics (DGPBG), Roozbeh Hospital, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran

    Fatemeh Alizadeh

Authors
  1. Fatemeh Yazarlou
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  2. Mobina Tabibian
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  3. Asaad Azarnezhad
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  4. Habib Sadeghi Rad
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  5. Leonard Lipovich
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  6. Golshid Sanati
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  7. Hamid Mostafavi Abdolmaleky
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  8. Fatemeh Alizadeh
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Contributions

Conceptualization: Fatemeh Alizadeh. Methodology: Fatemeh Alizadeh, Fatemeh Yazarlou, Hamid Mostafavi Abdolmaleky, and Golshid Sanati. Investigation: Fatemeh Alizadeh, Habib Sadeghi Rad, and Mobina. TabibianWriting: Fatemeh Yazarlou, Asaad Azarnezhad, Fatemeh Alizadeh, and Leonard Lipovich. Critical review: Leonard Lipovich, Fatemeh Alizadeh, Fatemeh Yazarlou, and Hamid Mostafavi Abdolmaleky

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Correspondence to Fatemeh Alizadeh.

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Yazarlou, F., Tabibian, M., Azarnezhad, A. et al. Evaluating Gene Expression and Methylation Profiles of TCF4, MBP, and EGR1 in Peripheral Blood of Drug-Free Patients with Schizophrenia: Correlations with Psychopathology, Intelligence, and Cognitive Impairment. J Mol Neurosci 73, 738–750 (2023). https://doi.org/10.1007/s12031-023-02150-x

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