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Psychiatric disorders and SLC6A4 gene variants: possible effects on alcohol dependence and alzheimer’s disease

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Abstract

Serotoninergic system is one of the most important neurotransmission systems investigated in the field of psychiatry. Extensive evidence reveals how alterations of this system, and especially of the SLC6A4 gene, may be associated with psychiatric disorders. In this study we aimed to evaluate the pleiotropic nature of SLC6A4 alterations and their association with the overall risk of brain diseases rather than disorder-specific. SLC6A4 variants, namely 5HTTLPR, STin2, rs2066713, rs25531, rs4251417, rs6354 and rs7224199 were investigated in 4 independent cohorts of subjects with specific psychiatric disorders, including Alcohol dependence disorder (ALC), Alzheimer disease (ALZ), Schizophrenia (SCZ) and Bipolar disorder (BPD). Other variables (biochemical parameters and Psychiatric scales scores) were also tested for association. SLC6A4 polymorphisms are not associated with the risk of developing major psychiatric disorders (SCZ and BPD); however some signals were detected in ALC (HTTLPR pd = 9.25 × 10−03, pr = 7.24 × 10−03; rs2066713 pd = 6.35 × 10−08; rs25531 pd = 2.95 × 10−02; rs4251417 pd = 2.46 × 10−03), and ALZ (rs6354 pr = 1.22 × 10−02; rs7224199 pd = 1.00 × 10−08, pr = 2.65 × 10−02) cohorts. Some associations were also observed on exploratory analyses. Our findings did not reveal any major influence on SCZ and BPD development; On the other hand, some alteration of the SLC6A4 sequence were associated with an increased risk of ALC and ALZ disorders, suggesting common pathways. The results of this study should be carefully interpreted since it suffers of some inherent limitations (e.g. cohort size, slight ethnic heterogeneity). Further analyses may provide better detail on the molecular processes behind SLC6A4 alterations.

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Change history

  • 22 January 2020

    The following authors have double affiliations: <Emphasis Type="Bold">Stefania Boccia, Marco Di Nicola</Emphasis> and they should read

  • 22 January 2020

    The following authors have double affiliations: Stefania Boccia, Marco Di Nicola and they should read

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Acknowledgements

We thank all patients who gave their consent for the analysis of their data.

Funding

None.

Author information

Authors and Affiliations

  1. Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy

    Marco Calabrò & Concetta Crisafulli

  2. Department of Biomedical and NeuroMotor Sciences, University of Bologna, Viale Carlo Pepoli 5, 40123, Bologna, Italy

    Laura Mandelli, Stefano Porcelli & Alessandro Serretti

  3. Laboratory of Biology of Neurodegenerative Disorders, Neuroscience Department, Istituto di Ricerche Farmacologiche Mario Negri IRCSS, Milan, Italy

    Diego Albani

  4. Department of Psychiatry, University of Athens Medical School, Eginition Hospital, Athens, Greece

    Antonis Politis & George N. Papadimitriou

  5. Fondazione Policlinico Universitario “A. Gemelli” - IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy

    Marco Di Nicola, Luigi Janiri & Roberto Colombo

  6. Department of Neuroscience, Imaging and Clinical Sciences, University “G. d’Annunzio” of Chieti, Chieti, Italy

    Giovanni Martinotti

  7. Psychiatry Unit, Department of Medical Sciences, University of Foggia, Foggia, Italy

    Antonello Bellomo

  8. Bipolar Disorders Unit, Institute of Neuroscience, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain

    Eduard Vieta

  9. Unit of Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, Rome, Italy, and Department of Human Sciences and Quality of Life Promotion, San Raffaele University, Rome, Italy

    Stefano Bonassi

  10. Barnet, Enfield and Haringey Mental Health NHS Trust, St.Ann’s Hospital, St.Ann’s Road, London, N15 3 TH, UK

    Alessandra Frustaci

  11. Mental Health Department, ASL Roma 1, Rome, Italy

    Giuseppe Ducci

  12. Dipartimento di Biologia, Università di Pisa, Pisa, Italy

    Stefano Landi

  13. Section of Hygiene, Institute of Public Health, Universita’ Cattolica del Sacro Cuore, Fondazione Policlinico “Agostino Gemelli” IRCCS, Rome, Italy

    Stefania Boccia

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  1. Marco Calabrò
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  2. Laura Mandelli
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  3. Concetta Crisafulli
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  4. Stefano Porcelli
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Contributions

All authors were actively involved in the design of the study, the analytical method of the study, the selection and review of all scientific content. All authors had full editorial control during the writing of the manuscript and finally approved it.

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Correspondence to Alessandro Serretti.

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The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with that can be associated with the subject matter discussed in this manuscript.

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The authors declare that all procedures followed were approved by the national ethical committee. Further, all patients gave their written consent for the analysis of their data.

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Calabrò, M., Mandelli, L., Crisafulli, C. et al. Psychiatric disorders and SLC6A4 gene variants: possible effects on alcohol dependence and alzheimer’s disease. Mol Biol Rep 47, 191–200 (2020). https://doi.org/10.1007/s11033-019-05119-5

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