title: Area-specific modulation of neural activation comparing escitalopram and citalopram revealed by pharmaco-fMRI: a randomized cross-over study.
abstract: Area-specific and stimulation-dependent changes of human brain activation by selective serotonin reuptake inhibitors (SSRI) are an important issue for improved understanding of treatment mechanisms, given the frequent prescription of these drugs in depression and anxiety disorders. The aim of this neuroimaging study was to investigate differences in BOLD-signal caused by administration of the SSRIs escitalopram and citalopram using pharmacological functional magnetic resonance imaging (pharmaco-fMRI). Eighteen healthy subjects participated in a placebo-controlled, randomized, double-blind study in cross-over repeated measures design. Each volunteer performed facial emotional discrimination and a sensorimotor control paradigm during three scanning sessions. Citalopram (20 mg/d), escitalopram (10 mg/d) and placebo were administered for 10 days each with a drug-free period of at least 21 days. Significant pharmacological effects on BOLD-signal were found in the amygdala, medial frontal gyrus, parahippocampal, fusiform and middle temporal gyri. Post-hoc t-tests revealed decreased BOLD-signal in the right amygdala and left parahippocampal gyrus in both pharmacological conditions, compared to placebo. Escitalopram, compared to citalopram, induced a decrease of BOLD-signal in the medial frontal gyrus and an increase in the right fusiform and left parahippocampal gyri. Drug effects were concentrated in brain regions with dense serotonergic projections. Both escitalopram and citalopram attenuated BOLD-signal in the amygdala and parahippocampal cortex to emotionally significant stimuli compared to control stimuli. We believe that reduced reactivity in the medial frontal gyrus found for escitalopram compared to citalopram administration might explain the response differences between study drugs as demonstrated in previous clinical trials.
authors.affiliation: MR Center of Excellence, Center for Biomedical Engineering and Physics, Medical University of Vienna, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Windischberger
authors.forename: Rupert
authors.initials: R
authors.lastname: Lanzenberger
authors.forename: Alexander
authors.initials: A
authors.lastname: Holik
authors.forename: Christoph
authors.initials: C
authors.lastname: Spindelegger
authors.forename: Patrycja
authors.initials: P
authors.lastname: Stein
authors.forename: Ulrike
authors.initials: U
authors.lastname: Moser
authors.forename: Florian
authors.initials: F
authors.lastname: Gerstl
authors.forename: Martin
authors.initials: M
authors.lastname: Fink
authors.forename: Ewald
authors.initials: E
authors.lastname: Moser
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
mesh_terms: D000328:Adult; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology*; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000187:drug effects; D015283:Citalopram / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004644:Emotions; D056344:Executive Function / Q000187:drug effects / Q000502:physiology; D005149:Facial Expression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D014796:Visual Perception / Q000187:drug effects / Q000502:physiology; D044465:White People
chemical_list: D015283:Citalopram; D010100:Oxygen; D017367:Selective Serotonin Reuptake Inhibitors