Linked Life Data

18288090

Source:http://linkedlifedata.com/resource/pubmed/id/18288090

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2008-10-15
pubmed:abstractText
Recent rodent models of antidepressant response implicate a novel set of genes in mechanisms of antidepressant action. The authors examined variants in four such genes (KCNK2 (TREK1), SLC18A2 (VMAT2), S100A10, and HDAC5) for association with remission in a large effectiveness trial of antidepressant treatments. Subjects were drawn from the Sequenced Treatment Alternatives to Relieve Depression (STAR(*)D) study, a multicenter, prospective, effectiveness trial in major depressive disorder (MDD). Outpatients with nonpsychotic MDD were initially treated with citalopram for up to 14 weeks; those who did not remit with citalopram were sequentially randomized to a series of next-step treatments, each for up to 12 weeks. Single-nucleotide polymorphisms in four genes were examined for association with remission, defined as a clinician-rated Quick Inventory of Depressive Symptomatology (QIDS-C(16)) score < or =5. Of 1554 participants for whom DNA was available, 565 (36%) reached remission with citalopram treatment. No association with any of the four genes was identified. However, among the 751 who entered next-step treatment, variants in KCNK2 were associated with treatment response (Bonferroni-corrected, gene-based empirical p<0.001). In follow-up analyses, KCNK2 was also associated with effects of similar magnitude for third-step treatment among those with unsatisfactory benefit to both citalopram and one next-step pharmacotherapy (n=225). These findings indicate that genetic variation in KCNK2 may identify individuals at risk for treatment resistance. More broadly, they indicate the utility of animal models in identifying genes for pharmacogenetic studies of antidepressant response.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1740-634X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2810-9
pubmed:dateRevised
2011-5-18
pubmed:meshHeading
pubmed-meshheading:18288090-Adolescent, pubmed-meshheading:18288090-Adult, pubmed-meshheading:18288090-Aged, pubmed-meshheading:18288090-Animals, pubmed-meshheading:18288090-Antidepressive Agents, pubmed-meshheading:18288090-Brain Chemistry, pubmed-meshheading:18288090-Citalopram, pubmed-meshheading:18288090-DNA Mutational Analysis, pubmed-meshheading:18288090-Depressive Disorder, pubmed-meshheading:18288090-Drug Resistance, pubmed-meshheading:18288090-Female, pubmed-meshheading:18288090-Gene Expression Regulation, pubmed-meshheading:18288090-Genetic Predisposition to Disease, pubmed-meshheading:18288090-Genotype, pubmed-meshheading:18288090-Humans, pubmed-meshheading:18288090-Male, pubmed-meshheading:18288090-Middle Aged, pubmed-meshheading:18288090-Polymorphism, Single Nucleotide, pubmed-meshheading:18288090-Potassium Channels, Tandem Pore Domain, pubmed-meshheading:18288090-Rodentia, pubmed-meshheading:18288090-Serotonin Uptake Inhibitors, pubmed-meshheading:18288090-Young Adult
pubmed:year
2008
pubmed:articleTitle
Pharmacogenetic analysis of genes implicated in rodent models of antidepressant response: association of TREK1 and treatment resistance in the STAR(*)D study.
pubmed:affiliation
Depression Clinical and Research Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. rperlis@partners.org
pubmed:publicationType
Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Multicenter Study