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Can the Imbalance between Neurotrophic and Apoptotic Proteins Be the “Beware the Ides of March” for Unaffected Relatives of Schizophrenia Patients?

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Abstract

Schizophrenia (SZ) is a mental disorder with a strong genetic basis as well as epigenetic aspects. Siblings of patients with SZ can share certain endophenotypes with the patients, suggesting that siblings may be important for distinguishing between trait and state markers. In the current study, we aimed to characterize the balance between pro-BDNF/mature BDNF and its receptors p75NTR/TrkB, which are tPA-BDNF pathways proteins and are thought to play a role in synaptic pruning, as a possible endophenotype of schizophrenia. Forty drug-naïve patients with first-episode psychosis (FEP) matched for age, gender, and level of education, 40 unaffected siblings (UAS) of patients with FEP, and 67 healthy controls (HC) were included in the study. Blood samples were collected from all participants to determine BDNF, pro-BDNF, TrkB and p75NTR, PAI1, tPA, ACTH, and cortisol levels. We showed that levels of proteins of the tPA-BDNF pathway as well as the pro-BDNF/m-BDNF and p75NTR/TrkB ratios could successfully differentiate FEP and their siblings from the HCs by using ROC analysis. Plasma levels of m-BDNF were found to be the lowest in the healthy siblings and highest in the HCs with statistically significant differences between all 3 groups. The plasma level of pro-BDNF in the HC group was similar to the FEP patients, the same in the healthy siblings of the FEP patients. Our data support the hypothesis that imbalance between neurotrophic and apoptotic proteins might occur in SZ and this imbalance could be an endophenotype of the disease.

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Acknowledgements

We are grateful to the University of (University of Health Sciences Turkey) Research Projects Unit, Turkey, because of their financial support for the current research.. In addition, our work has been awarded by the ECNP community at the 2020 ECNP congress.

Funding

Financial support for the current research was provided by the University of (University of Health Sciences Turkey) Research Projects Unit (Date/ Number; 07.03.2019/020).

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Authors and Affiliations

  1. Department of Psychiatry, Bakirkoy Prof Mazhar Osman Training and Research Hospital for Psychiatry, Neurology, and Neurosurgery, 34147, Istanbul, Turkey

    Umit Haluk Yesilkaya, Pelin Ozkara Menekseoglu, Busra Guney Tasdemir & Nesrin Karamustafalioglu

  2. Department of Neuroscience, Medipol University, Istanbul, Turkey

    Umit Haluk Yesilkaya

  3. Department of Psychiatry, Necmettin Erbakan University Meram Medical Faculty, Konya, Turkey

    Sakir Gica

  4. Department of Biochemistry, Dr Sadi Konuk Training and Research Hospital, Istanbul, Turkey

    Zeynep Cirakli

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  1. Umit Haluk Yesilkaya
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  2. Sakir Gica
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  3. Pelin Ozkara Menekseoglu
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  4. Busra Guney Tasdemir
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  5. Zeynep Cirakli
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  6. Nesrin Karamustafalioglu
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Contributions

UHY and SG wrote the manuscript and. BGT and POM collected all the data. ZC analyzed the serum levels of the proteins. NK was responsible for overseeing and coordination of the research. All authors provided feedback and final approval on the manuscript.

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Correspondence to Umit Haluk Yesilkaya.

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Yesilkaya, U.H., Gica, S., Menekseoglu, P.O. et al. Can the Imbalance between Neurotrophic and Apoptotic Proteins Be the “Beware the Ides of March” for Unaffected Relatives of Schizophrenia Patients?. Mol Neurobiol 59, 7413–7422 (2022). https://doi.org/10.1007/s12035-022-03054-4

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