title: Divergent effects of increased serotonergic activity on psychophysiological parameters of human attention.
abstract: Selective serotonin reuptake inhibitors (SSRIs) are frequently combined to the antipsychotic medication of schizophrenia patients, to treat their depressed, cognitive or negative symptoms. No convincing neurochemical theory exists for this combination. The role of serotonin in those psychophysiological parameters of attention that are already found to be disturbed in schizophrenia, e.g. processing negativity (PN), mismatch negativity (MMN) and P300 amplitude, is poorly understood. In the present study the effects of increased serotonergic activity on these psychophysiological parameters is investigated. In a balanced, double-blind, placebo-controlled, cross-over experiment 18 healthy male volunteers received an oral dose of either placebo or of 10 mg escitalopram (a highly specific SSRI) on two separate test days, after which they were tested in an auditory selective attention paradigm and a MMN paradigm. Escitalopram significantly increased PN and MMN compared to placebo, without affecting the P300 amplitude. Furthermore, administration of escitalopram resulted in a small, yet significant, reduction of task performance in the selective attention paradigm compared to placebo, while it did not affect reaction time. Contrary to what was expected, escitalopram enhanced PN and MMN, without affecting the P300 amplitude. The results are discussed in the light of dosage issues and subtypes of serotonergic receptors.
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research, Faculty of Health Sciences, Copenhagen University, University Psychiatric Center Glostrup, Glostrup, Denmark. B.Oranje@cnsr.dk
authors.forename: Bob
authors.initials: B
authors.lastname: Oranje
authors.forename: Kristian
authors.initials: K
authors.lastname: Jensen
authors.forename: Malene
authors.initials: M
authors.lastname: Wienberg
authors.forename: Birte Y
authors.initials: BY
authors.lastname: Glenthøj
mesh_terms: D000161:Acoustic Stimulation; D000328:Adult; D001288:Attention / Q000187:drug effects* / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D015283:Citalopram / Q000097:blood / Q000494:pharmacology; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects; D018913:Event-Related Potentials, P300 / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000187:drug effects; D012701:Serotonin / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000494:pharmacology*
chemical_list: D015283:Citalopram; D006854:Hydrocortisone; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors