title: ATP-binding cassette sub-family F member 1 (ABCF1) is identified as a putative therapeutic target of escitalopram in the inflammatory cytokine pathway.
abstract: The inflammatory cytokine pathway may be a potential therapeutic target for major depressive disorder (MDD). Previous reports suggest that antidepressants have anti-inflammatory properties and can cause a reduction in proinflammatory cytokines. Recent evidence suggests this might be mediated at the level of the transcriptome. The current study investigated the transcription of 86 genes in the inflammatory cytokine pathway both at baseline and after eight weeks of escitalopram treatment in MDD patients who were either clinical responders (n=25) or non-responders (n=21), using a subset of samples in the Genome-Based Therapeutic Drugs for Depression project (GENDEP). Changes in expression between baseline and eight weeks of treatment were assessed using two-tailed t-tests. To establish if any significant expression changes related to clinical response, the magnitude of the relative expression change between baseline and eight weeks of treatment was established and binary logistic regressions were used to compare differences between responders and non-responders. ATP-binding cassette sub-family F member 1 (ABCF1), a translational regulator of the inflammatory cytokine pathway showed a significant increase in expression after escitalopram treatment which was significantly greater in responders compared to non-responders, suggesting that ABCF1 may play a role in mediating antidepressant response.
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, King's College London, London, UK. timothy.powell@kcl.ac.uk
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Powell
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Tansey
authors.forename: Gerome
authors.initials: G
authors.lastname: Breen
authors.forename: Anne E
authors.initials: AE
authors.lastname: Farmer
authors.forename: Ian W
authors.initials: IW
authors.lastname: Craig
authors.forename: Rudolf
authors.initials: R
authors.lastname: Uher
authors.forename: Peter
authors.initials: P
authors.lastname: McGuffin
authors.forename: Ursula M
authors.initials: UM
authors.lastname: D'Souza
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Schalkwyk
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use; D015283:Citalopram / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D055815:Young Adult
chemical_list: C115776:ABCF1 protein, human; D018528:ATP-Binding Cassette Transporters; D000928:Antidepressive Agents; D016207:Cytokines; D015283:Citalopram
keywords: Selective serotonin reuptake inhibitor; inflammation; pharmacogenetic; transcription