title: SSRI enhances sensitivity to background outcomes and modulates response rates: A randomized double blind study of instrumental action and depression.
abstract: Serotonin reuptake inhibitors (SSRIs) have immediate effects on synaptic levels of serotonin but their therapeutic effects are often delayed. This delay has been suggested to reflect time required for new learning and therefore that SSRIs might be having effects on the learning process. We examined the effects of elevating serotonin levels, through short-term SSRI administration (escitalopram), on learning about perceptions of instrumental control. A randomised double blind procedure was used to allocate healthy people, categorised as mildly depressed (high BDI⩾10: n=76) or not depressed (low BDI⩽5: n=78) to either a drug (escitalopram, 10mg/7days) or placebo control group. Following treatment, participants were trained with a simple task that involved learning the effectiveness of an instrumental action (key press) and the background context at eliciting an outcome (auditory cue) where there was no programmed contingency. The effects of the drug were (i) to moderate response rates and (ii) to enhance sensitivity to the background or context rate of occurrence of the outcome. These findings suggest that serotonin modulates learning about the long-term rate of outcomes, which supports perception of instrumental control, and that this may provide a clue to the mechanism for supporting the development of the therapeutic effects of the drug.
authors.affiliation: Centre for Social Issues Research, Department of Psychology, University of Limerick, Limerick, Ireland; Health Research Institute, University of Limerick, Limerick, Ireland. Electronic address: rachel.msetfi@ul.ie.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Msetfi
authors.affiliation: Center for Depression, Anxiety and Stress Research, McLean Hospital/Harvard Medical School, Belmont, MA, United States.
authors.forename: Poornima
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Harmer
authors.affiliation: Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom.
authors.forename: Robin A
authors.initials: RA
authors.lastname: Murphy
mesh_terms: D000293:Adolescent; D000328:Adult; D015283:Citalopram / Q000008:administration & dosage / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy* / Q000503:physiopathology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007858:Learning / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011597:Psychomotor Performance / Q000187:drug effects*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Context; Depression; Escitalopram; Learning; Perceived control; Response rate; SSRI; Serotonin