title: Testing the antidepressant properties of the peptide ARA290 in a human neuropsychological model of drug action.
abstract: Studies on the neural effects of Erythropoietin (EPO) indicate that EPO may have antidepressant effects. Due to its hematopoietic effects, EPO may cause serious side-effects with repeated administration if patients are not monitored extensively. ARA290 is an EPO-analog peptide without such hematopoietic side-effects but may have neurotrophic and antidepressant effects. The aim of this study was to investigate the possible antidepressant effects of ARA290 in a neuropsychological model of drug action. Healthy participants (N=36) received ARA290 (2mg) or placebo in a double-blind, randomized, parallel-group design. Neural and cognitive effects were assessed one week after administration. Primary outcome measures were the neural processing of fearful vs happy faces and the behavioral recognition of emotional facial expressions. ARA290-treated individuals displayed lower neural responses to happy faces in the fusiform gyrus. ARA290 tended to lower the recognition of happy and disgust facial expressions. Although ARA290 was not associated with a better memory for positive words, it was associated with faster categorization of positive vs negative words. Finally, ARA290 increased attention towards positive emotional pictures. No effects were observed on mood and affective symptoms. ARA290 may modulate some aspects of emotional processing, however, the direction and the strength of its effects do not unequivocally support an antidepressant-like profile for ARA290. Future studies may investigate the effects of different timing and dose.
authors.affiliation: Institute of Psychology, Leiden University, Wassenaarseweg 52, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands. Electronic address: cerith@fsw.leidenuniv.nl.
authors.forename: Hilâl
authors.initials: H
authors.lastname: Cerit
authors.affiliation: Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands; Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Ilya M
authors.initials: IM
authors.lastname: Veer
authors.affiliation: Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Dahan
authors.affiliation: Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: Niesters
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, UK.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Harmer
authors.affiliation: Psychiatric Centre, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Kamilla W
authors.initials: KW
authors.lastname: Miskowiak
authors.affiliation: Institute of Psychology, Leiden University, Wassenaarseweg 52, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Serge A R B
authors.initials: SA
authors.lastname: Rombouts
authors.affiliation: Institute of Psychology, Leiden University, Wassenaarseweg 52, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands; Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: vanderdoes@fsw.leidenuniv.nl.
authors.forename: Willem
authors.initials: W
authors.lastname: Van der Does
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000098:blood supply / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects; D005149:Facial Expression; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D009842:Oligopeptides; C576178:cibinetide; D010100:Oxygen
keywords: ARA290; Antidepressants; Erythropoietin; Neuropsychological model of drug action