Abstract
It has been suggested that the serotonin or 5-hydroxytriptamine (5-HT) transporter (5-HTT) and its gene-linked polymorphic region (5-HTTLPR) are selective serotonin reuptake inhibitor (SSRI) response modulators in late-life depression (LLD), and particularly in late-life major depressive disorder (MDD). Previous studies differed in design and results. Our study aimed to investigate the solute carrier family 6 (neurotransmitter transporter and serotonin) member 4 (SLC6A4) gene locus, encoding 5-HTT and SSRI treatment response in late-life MDD. For a prospective cohort study, we enrolled 234 patients with late-life MDD to be treated with escitalopram, sertraline, paroxetine or citalopram for 6 months. The SLC6A4 polymorphisms rs4795541 (5-HTTLPR), rs140701 and rs3813034 genotypes spanning the SLC6A4 locus were investigated in blinded fashion. No placebo group was included. We assessed responder or non-responder phenotypes according to a reduction in the 21-item version of the Hamilton Depression Rating Scale (HDRS-21) score of 50%. At follow-up, 30% of the late-life MDD patients were non-responders to SSRI treatment. No time-course of symptoms and responses was made. A poor response was associated with a higher baseline HDRS-21 score. We observed a significant over-representation of the rs4795541-S allele in the responder patients (0.436 versus 0.321; p = 0.023). The single S-allele dose-additive effect had OR = 1.74 (95% CI 1.12-2.69) in the additive regression model. Our findings suggested a possible influence of 5-HTTLPR on the SSRI response in patients with late-life MDD, which is potentially useful in identifying the subgroups of LLD patients whom need a different pharmacological approach.
| Original language | English |
|---|---|
| Pages (from-to) | 623-633 |
| Number of pages | 11 |
| Journal | Journal of Psychopharmacology |
| Volume | 29 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 5 2015 |
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Keywords
- Antidepressant drug resistance
- depression
- depression management
- gene polymorphisms
- geriatrics
- late-life depression
- major depressive disorder
- selective serotonin reuptake inhibitor
- solute carrier family 6
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
- Psychiatry and Mental health
Cite this
Role of the serotonin transporter gene locus in the response to SSRI treatment of major depressive disorder in late life. / Seripa, Davide; Pilotto, Andrea; Paroni, Giulia; Fontana, Andrea; D'Onofrio, Grazia; Gravina, Carolina; Urbano, Maria; Cascavilla, Leandro; Paris, Francesco; Panza, Francesco; Padovani, Alessandro; Pilotto, Alberto.
In: Journal of Psychopharmacology, Vol. 29, No. 5, 05.05.2015, p. 623-633.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of the serotonin transporter gene locus in the response to SSRI treatment of major depressive disorder in late life
AU - Seripa, Davide
AU - Pilotto, Andrea
AU - Paroni, Giulia
AU - Fontana, Andrea
AU - D'Onofrio, Grazia
AU - Gravina, Carolina
AU - Urbano, Maria
AU - Cascavilla, Leandro
AU - Paris, Francesco
AU - Panza, Francesco
AU - Padovani, Alessandro
AU - Pilotto, Alberto
PY - 2015/5/5
Y1 - 2015/5/5
N2 - It has been suggested that the serotonin or 5-hydroxytriptamine (5-HT) transporter (5-HTT) and its gene-linked polymorphic region (5-HTTLPR) are selective serotonin reuptake inhibitor (SSRI) response modulators in late-life depression (LLD), and particularly in late-life major depressive disorder (MDD). Previous studies differed in design and results. Our study aimed to investigate the solute carrier family 6 (neurotransmitter transporter and serotonin) member 4 (SLC6A4) gene locus, encoding 5-HTT and SSRI treatment response in late-life MDD. For a prospective cohort study, we enrolled 234 patients with late-life MDD to be treated with escitalopram, sertraline, paroxetine or citalopram for 6 months. The SLC6A4 polymorphisms rs4795541 (5-HTTLPR), rs140701 and rs3813034 genotypes spanning the SLC6A4 locus were investigated in blinded fashion. No placebo group was included. We assessed responder or non-responder phenotypes according to a reduction in the 21-item version of the Hamilton Depression Rating Scale (HDRS-21) score of 50%. At follow-up, 30% of the late-life MDD patients were non-responders to SSRI treatment. No time-course of symptoms and responses was made. A poor response was associated with a higher baseline HDRS-21 score. We observed a significant over-representation of the rs4795541-S allele in the responder patients (0.436 versus 0.321; p = 0.023). The single S-allele dose-additive effect had OR = 1.74 (95% CI 1.12-2.69) in the additive regression model. Our findings suggested a possible influence of 5-HTTLPR on the SSRI response in patients with late-life MDD, which is potentially useful in identifying the subgroups of LLD patients whom need a different pharmacological approach.
AB - It has been suggested that the serotonin or 5-hydroxytriptamine (5-HT) transporter (5-HTT) and its gene-linked polymorphic region (5-HTTLPR) are selective serotonin reuptake inhibitor (SSRI) response modulators in late-life depression (LLD), and particularly in late-life major depressive disorder (MDD). Previous studies differed in design and results. Our study aimed to investigate the solute carrier family 6 (neurotransmitter transporter and serotonin) member 4 (SLC6A4) gene locus, encoding 5-HTT and SSRI treatment response in late-life MDD. For a prospective cohort study, we enrolled 234 patients with late-life MDD to be treated with escitalopram, sertraline, paroxetine or citalopram for 6 months. The SLC6A4 polymorphisms rs4795541 (5-HTTLPR), rs140701 and rs3813034 genotypes spanning the SLC6A4 locus were investigated in blinded fashion. No placebo group was included. We assessed responder or non-responder phenotypes according to a reduction in the 21-item version of the Hamilton Depression Rating Scale (HDRS-21) score of 50%. At follow-up, 30% of the late-life MDD patients were non-responders to SSRI treatment. No time-course of symptoms and responses was made. A poor response was associated with a higher baseline HDRS-21 score. We observed a significant over-representation of the rs4795541-S allele in the responder patients (0.436 versus 0.321; p = 0.023). The single S-allele dose-additive effect had OR = 1.74 (95% CI 1.12-2.69) in the additive regression model. Our findings suggested a possible influence of 5-HTTLPR on the SSRI response in patients with late-life MDD, which is potentially useful in identifying the subgroups of LLD patients whom need a different pharmacological approach.
KW - Antidepressant drug resistance
KW - depression
KW - depression management
KW - gene polymorphisms
KW - geriatrics
KW - late-life depression
KW - major depressive disorder
KW - selective serotonin reuptake inhibitor
KW - solute carrier family 6
UR - http://www.scopus.com/inward/record.url?scp=84930680760&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930680760&partnerID=8YFLogxK
U2 - 10.1177/0269881115578159
DO - 10.1177/0269881115578159
M3 - Article
C2 - 25827644
AN - SCOPUS:84930680760
VL - 29
SP - 623
EP - 633
JO - Journal of Psychopharmacology
JF - Journal of Psychopharmacology
SN - 0269-8811
IS - 5
ER -