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

Marco Calabrò, Laura Mandelli, Concetta Crisafulli, Stefano Porcelli, Diego Albani, Antonis Politis, George N. Papadimitriou, Marco Di Nicola, Luigi Janiri, Roberto Colombo, Giovanni Martinotti, Antonello Bellomo, Eduard Vieta, Stefano Bonassi, Alessandra Frustaci, Giuseppe Ducci, Stefano Landi, Stefania Boccia, Alessandro Serretti

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)191-200
Number of pages10
JournalMolecular Biology Reports
Volume47
Issue number1
DOIs
Publication statusE-pub ahead of print - Oct 1 2019

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Keywords

  • Alcohol dependence disorder
  • Alzheimer’s disease
  • Bipolar disorder
  • Genetics
  • Schizophrenia
  • SLC6A4

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Calabrò, M., Mandelli, L., Crisafulli, C., Porcelli, S., Albani, D., Politis, A., Papadimitriou, G. N., Di Nicola, M., Janiri, L., Colombo, R., Martinotti, G., Bellomo, A., Vieta, E., Bonassi, S., Frustaci, A., Ducci, G., Landi, S., Boccia, S., & Serretti, A. (2019). Psychiatric disorders and SLC6A4 gene variants: possible effects on alcohol dependence and alzheimer’s disease. Molecular Biology Reports, 47(1), 191-200. https://doi.org/10.1007/s11033-019-05119-5