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

• Published in: Molecular biology reports Vol. 47; no. 1; pp. 191 - 200
• Main Authors: Calabrò, Marco, Mandelli, Laura, Crisafulli, Concetta, Porcelli, Stefano, Albani, Diego, Politis, Antonis, Papadimitriou, George N., Di Nicola, Marco, Janiri, Luigi, Colombo, Roberto, Martinotti, Giovanni, Bellomo, Antonello, Vieta, Eduard, Bonassi, Stefano, Frustaci, Alessandra, Ducci, Giuseppe, Landi, Stefano, Boccia, Stefania, Serretti, Alessandro
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.01.2020; Springer Nature B.V
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Alcohol; alcohol abuse; Alcoholism - complications; Alcoholism - epidemiology; Alcoholism - genetics; Alzheimer disease; Alzheimer Disease - complications; Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Alzheimer's disease; Animal Anatomy; Animal Biochemistry; Biomedical and Life Sciences; Bipolar disorder; brain; Case-Control Studies; Cohort Studies; Comorbidity; Drug dependence; Gene Frequency; genes; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Greece - epidemiology; Histology; Humans; Italy - epidemiology; Life Sciences; Linkage Disequilibrium; Mental disorders; Mental Disorders - epidemiology; Mental Disorders - genetics; Middle Aged; molecular biology; Morphology; Neurotransmission; Original Article; Polymorphism, Genetic; risk; Schizophrenia; Serotonin; Serotonin Plasma Membrane Transport Proteins - genetics; synaptic transmission; Young Adult; Greece; Italy; Schizophrenia; Genetics; Bipolar disorder; Alzheimer’s disease; Alcohol dependence disorder; SLC6A4
• ISSN: 0301-4851; 1573-4978; 1573-4978
• DOI: 10.1007/s11033-019-05119-5

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 p d  = 9.25 × 10 −03 , p r  = 7.24 × 10 −03 ; rs2066713 p d  = 6.35 × 10 −08 ; rs25531 p d  = 2.95 × 10 −02 ; rs4251417 p d  = 2.46 × 10 −03 ), and ALZ (rs6354 p r  = 1.22 × 10 −02 ; rs7224199 p d  = 1.00 × 10 −08 , p r  = 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.