TY - JOUR
T1 - Psychiatric disorders and SLC6A4 gene variants
T2 - possible effects on alcohol dependence and alzheimer’s disease
AU - Calabrò, Marco
AU - Mandelli, Laura
AU - Crisafulli, Concetta
AU - Porcelli, Stefano
AU - Albani, Diego
AU - Politis, Antonis
AU - Papadimitriou, George N.
AU - Di Nicola, Marco
AU - Janiri, Luigi
AU - Colombo, Roberto
AU - Martinotti, Giovanni
AU - Bellomo, Antonello
AU - Vieta, Eduard
AU - Bonassi, Stefano
AU - Frustaci, Alessandra
AU - Ducci, Giuseppe
AU - Landi, Stefano
AU - Boccia, Stefania
AU - Serretti, Alessandro
N1 - Publisher Copyright:
© 2019, Springer Nature B.V.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
KW - Alcohol dependence disorder
KW - Alzheimer’s disease
KW - Bipolar disorder
KW - Genetics
KW - SLC6A4
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=85074000733&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074000733&partnerID=8YFLogxK
U2 - 10.1007/s11033-019-05119-5
DO - 10.1007/s11033-019-05119-5
M3 - Article
C2 - 31595439
AN - SCOPUS:85074000733
SN - 0301-4851
VL - 47
SP - 191
EP - 200
JO - Molecular Biology Reports
JF - Molecular Biology Reports
IS - 1
ER -