title: Role of the serotonin transporter gene locus in the response to SSRI treatment of major depressive disorder in late life.
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.
authors.affiliation: Department of Medical Sciences, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy dseripa@operapadrepio.it.
authors.forename: Davide
authors.initials: D
authors.lastname: Seripa
authors.affiliation: Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pilotto
authors.affiliation: Department of Medical Sciences, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Paroni
authors.affiliation: Biostatistics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fontana
authors.affiliation: Department of Medical Sciences, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: D'Onofrio
authors.affiliation: Department of Medical Sciences, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gravina
authors.affiliation: Department of Medical Sciences, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Urbano
authors.affiliation: Department of Medical Sciences, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.
authors.forename: Leandro
authors.initials: L
authors.lastname: Cascavilla
authors.affiliation: Department of Medical Sciences, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Paris
authors.affiliation: Department of Medical Sciences, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy Department of Basic Medicine, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Panza
authors.affiliation: Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.affiliation: Department of Medical Sciences, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy Geriatrics Unit, San Antonio Hospital, Padova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pilotto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human
keywords: Antidepressant drug resistance; depression; depression management; gene polymorphisms; geriatrics; late-life depression; major depressive disorder; selective serotonin reuptake inhibitor; solute carrier family 6