Abstract
Major Depression Disorder (MDD) is a serious mental illness that is one of the most disabling diseases worldwide. In addition, approximately 15% of depression patients are defined treatment-resistant (TRD). Preclinical and genetic studies show that serotonin modulation dysfunction exists in patients with TRD. Some polymorphisms in the promoter region of the serotonin transporter gene (SLC6A4) are likely to be involved in the pathogenesis/treatment of MDD; however, no data are available concerning TRD.Therefore, in order to investigate the possible influence of SLC6A4 polymorphisms on the risk of TRD, we genotyped 310 DSM-IV MDD treatment-resistant patients and 284 healthy volunteers. We analysed the most studied polymorphism 5-HTTLPR (L/S) and a single nucleotide substitution, rs25531 (A/G), in relation to different functional haplotype combinations. However the correct mapping of rs25531 is still debated whether it is within or outside the insertion. Our sequencing analysis showed that rs25531 is immediately outside of the 5-HTTLPR segment.Differences in 5-HTTLPR allele (p=0.04) and in L allele carriers (pALA homozygote haplotype was more represented among the control subjects (p=0.01, OR=0.64 95%CI: 0.45-0.91).In conclusion, this study reports a protective effect of the LALA haplotype on TRD, supporting the hypothesis that lower serotonin transporter transcription alleles are correlated to a common resistant depression mechanism.
| Original language | English |
|---|---|
| Pages (from-to) | 367-370 |
| Number of pages | 4 |
| Journal | Progress in Neuro-Psychopharmacology and Biological Psychiatry |
| Volume | 34 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Aug 2010 |
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Keywords
- 5-HTTLPR
- Rs25531
- SLC6A4
- Treatment-resistant depression
ASJC Scopus subject areas
- Biological Psychiatry
- Pharmacology
Cite this
Serotonin transporter gene polymorphisms and treatment-resistant depression. / Bonvicini, Cristian; Minelli, Alessandra; Scassellati, Catia; Bortolomasi, Marco; Segala, Matilde; Sartori, Riccardo; Giacopuzzi, Mario; Gennarelli, Massimo.
In: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 34, No. 6, 08.2010, p. 367-370.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Serotonin transporter gene polymorphisms and treatment-resistant depression
AU - Bonvicini, Cristian
AU - Minelli, Alessandra
AU - Scassellati, Catia
AU - Bortolomasi, Marco
AU - Segala, Matilde
AU - Sartori, Riccardo
AU - Giacopuzzi, Mario
AU - Gennarelli, Massimo
PY - 2010/8
Y1 - 2010/8
N2 - Major Depression Disorder (MDD) is a serious mental illness that is one of the most disabling diseases worldwide. In addition, approximately 15% of depression patients are defined treatment-resistant (TRD). Preclinical and genetic studies show that serotonin modulation dysfunction exists in patients with TRD. Some polymorphisms in the promoter region of the serotonin transporter gene (SLC6A4) are likely to be involved in the pathogenesis/treatment of MDD; however, no data are available concerning TRD.Therefore, in order to investigate the possible influence of SLC6A4 polymorphisms on the risk of TRD, we genotyped 310 DSM-IV MDD treatment-resistant patients and 284 healthy volunteers. We analysed the most studied polymorphism 5-HTTLPR (L/S) and a single nucleotide substitution, rs25531 (A/G), in relation to different functional haplotype combinations. However the correct mapping of rs25531 is still debated whether it is within or outside the insertion. Our sequencing analysis showed that rs25531 is immediately outside of the 5-HTTLPR segment.Differences in 5-HTTLPR allele (p=0.04) and in L allele carriers (pALA homozygote haplotype was more represented among the control subjects (p=0.01, OR=0.64 95%CI: 0.45-0.91).In conclusion, this study reports a protective effect of the LALA haplotype on TRD, supporting the hypothesis that lower serotonin transporter transcription alleles are correlated to a common resistant depression mechanism.
AB - Major Depression Disorder (MDD) is a serious mental illness that is one of the most disabling diseases worldwide. In addition, approximately 15% of depression patients are defined treatment-resistant (TRD). Preclinical and genetic studies show that serotonin modulation dysfunction exists in patients with TRD. Some polymorphisms in the promoter region of the serotonin transporter gene (SLC6A4) are likely to be involved in the pathogenesis/treatment of MDD; however, no data are available concerning TRD.Therefore, in order to investigate the possible influence of SLC6A4 polymorphisms on the risk of TRD, we genotyped 310 DSM-IV MDD treatment-resistant patients and 284 healthy volunteers. We analysed the most studied polymorphism 5-HTTLPR (L/S) and a single nucleotide substitution, rs25531 (A/G), in relation to different functional haplotype combinations. However the correct mapping of rs25531 is still debated whether it is within or outside the insertion. Our sequencing analysis showed that rs25531 is immediately outside of the 5-HTTLPR segment.Differences in 5-HTTLPR allele (p=0.04) and in L allele carriers (pALA homozygote haplotype was more represented among the control subjects (p=0.01, OR=0.64 95%CI: 0.45-0.91).In conclusion, this study reports a protective effect of the LALA haplotype on TRD, supporting the hypothesis that lower serotonin transporter transcription alleles are correlated to a common resistant depression mechanism.
KW - 5-HTTLPR
KW - Rs25531
KW - SLC6A4
KW - Treatment-resistant depression
UR - http://www.scopus.com/inward/record.url?scp=77955057575&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955057575&partnerID=8YFLogxK
U2 - 10.1016/j.pnpbp.2010.04.020
DO - 10.1016/j.pnpbp.2010.04.020
M3 - Article
AN - SCOPUS:77955057575
VL - 34
SP - 367
EP - 370
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
SN - 0278-5846
IS - 6
ER -