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Effect of BDNF Val66Met polymorphism on hippocampal subfields in multiple sclerosis patients

Molecular Psychiatry volume 27, pages 1010–1019 (2022)Cite this article

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Abstract

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism was shown to strongly affect BDNF function, but its role in modulating gray matter damage in multiple sclerosis (MS) patients is still not clear. Given BDNF relevance on the hippocampus, we aimed to explore BDNF Val66Met polymorphism effect on hippocampal subfield volumes and its role in cognitive functioning in MS patients. Using a 3T scanner, we obtained dual-echo and 3DT1-weighted sequences from 50 MS patients and 15 healthy controls (HC) consecutively enrolled. MS patients also underwent genotype analysis of BDNF, neurological and neuropsychological evaluation. Hippocampal subfields were segmented by using Freesurfer. The BDNF Val66Met polymorphism was found in 22 MS patients (44%). Compared to HC, MS patients had lower volume in: bilateral hippocampus-amygdala transition area (HATA); cornus ammonis (CA)1, granule cell layer of dentate gyrus (GCL-DG), CA4 and CA3 of the left hippocampal head; molecular layer (ML) of the left hippocampal body; presubiculum of right hippocampal body and right fimbria. Compared to BDNF Val66Val, Val66Met MS patients had higher volume in bilateral hippocampal tail; CA1, ML, CA3, CA4, and GCL-DG of left hippocampal head; CA1, ML, and CA3 of the left hippocampal body; left HATA and presubiculum of the right hippocampal head. In MS patients, higher lesion burden was associated with lower volume of presubiculum of right hippocampal body; lower volume of left hippocampal tail was associated with worse visuospatial memory performance; lower volume of left hippocampal head with worse performance in semantic fluency. Our findings suggest the BNDF Val66Met polymorphism may have a protective role in MS patients against both hippocampal atrophy and cognitive impairment. BDNF genotype might be a potential biomarker for predicting cognitive prognosis, and an interesting target to study for neuroprotective strategies.

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Fig. 1: Graphical representation of hippocampal subfields segmentation.

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Data availability

The dataset used and analyzed during the current study is available from the corresponding Author on reasonable request.

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Acknowledgements

We thank Dr. Raffaello Bonacchi from Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute for revising the manuscript.

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Authors and Affiliations

  1. Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Ermelinda De Meo & Massimo Filippi

  2. Vita-Salute San Raffaele University, Milan, Italy

    Ermelinda De Meo & Massimo Filippi

  3. Department NEUROFARBA, Section Neurosciences, University of Florence, Florence, Italy

    Emilio Portaccio, Elio Prestipino, Benedetta Nacmias, Silvia Bagnoli, Benedetta Goretti, Sandro Sorbi & Maria Pia Amato

  4. IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy

    Emilio Portaccio, Benedetta Nacmias, Claudia Niccolai, Sandro Sorbi & Maria Pia Amato

  5. Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

    Lorenzo Razzolini, Luisa Pastò, Angelo Bellinvia & Mattia Fonderico

  6. Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy

    Antonio Giorgio, Maria Laura Stromillo & Nicola De Stefano

  7. Neurology Unit,, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Massimo Filippi

  8. Neurophysiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Massimo Filippi

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  1. Ermelinda De Meo
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Contributions

Ermelinda De Meo contributed to study concept and design, drafting/revising the manuscript, data analysis; Emilio Portaccio contributed to patient recruitment and clinical assessment; Elio Prestipino contributed to patient recruitment, clinical assessment and data analysis; Benedetta Nacmias contributed to genetic analysis; Silvia Bagnoli contributed to genetic analysis; Lorenzo Razzolini contributed to patient recruitment and clinical assessment; Luisa Pastò contributed to patient recruitment and clinical assessment; Claudia Niccolai contributed to neuropsychological assessment; Benedetta Goretti contributed to neuropsychological assessment; Angelo Bellinvia contributed to patient recruitment and clinical assessment; Mattia Fonderico contributed to patient recruitment and clinical assessment; Antonio Giorgio contributed to MRI data analysis; Maria Laura Stromillo contributed to MRI data analysis; Massimo Filippi contributed to study drafting/revising the manuscript; Sandro Sorbi contributed to study drafting/revising the manuscript; Nicola De Stefano contributed to study drafting/revising the manuscript; Maria Pia Amato, MD contributed to study concept and drafting/revising the manuscript.

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Correspondence to Ermelinda De Meo.

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Approval was received from Ethics Committee on human experimentation of the University of Florence, and written informed consent was obtained from all participants prior to study enrollment.

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De Meo, E., Portaccio, E., Prestipino, E. et al. Effect of BDNF Val66Met polymorphism on hippocampal subfields in multiple sclerosis patients. Mol Psychiatry 27, 1010–1019 (2022). https://doi.org/10.1038/s41380-021-01345-1

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