The Effects of Increased Central Serotonergic Activity on Information Processing

The Effects of Increased Central Serotonergic Activity on Psychophysiological Parameters of Human Information Processing

It is of great clinical relevance to know if selective serotonin re-uptake inhibitors affect information processing. Our hypothesis was that aspects of information processing would be disturbed whereas others would improve.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Escitalopram; Drug: escitaolpram

Detailed Description

Numerous studies point to an increased serotoninergic activity in schizophrenia. Additionally, patients with schizophrenia often show reduced filtering of sensory information, which is reflected in reduced P50 suppression and reduced prepulse inhibition of the startle refex (PPI). Currently, the reports in literature on the effects of serotonergic agonists on sensory gating in humans are inconclusive. In an initial study performed in our laboratory, however, we found reduced P50 suppression following administration of imipramine (a combined serotonin- and noradrenalin reuptake inhibitor) to healthy volunteers. This result provides evidence for the involvement of either serotonergic, noradrenergic, or a combination of both pathways in sensory gating. In numerous animal studies however, sensory gating is reduced by agonists of 5-HT, which suggests a serotonergic, rather than a noradrenergic, involvement in sensory gating. Therefore, in a follow-up study, the effects of a selective serotonin reuptake inhibitor (escitalopram) will be investigated on sensory gating parameters of healthy volunteers. To further extend the data of our initial study, the subjects will additionally be tested for two more psychophysiological parameters of attention that are usually found to be disturbed in patients with schizophrenia, i.e. mismatch negativity and selective attention. The design will be a double blind, placebo controlled experiment, in which a single dose of escitalopram or placebo will be given to healthy, non-smoking male volunteers on two occasions, separated by at least a week, after which the subjects will be tested in the psychophysiological test battery.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Glostrup, Denmark, DK-2600
    • Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychiatric Center Glostrup

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male subjects
• Good Physical and Mental Health meeting criteria "never mentally ill", which will be evaluated with a medical history checklist, ECG
• Non smokers

Exclusion Criteria:

• Current use of any medication
• Any subject who has received any investigational medication within 30 days prior to the start of this study
• History of neurologic illness
• History of psychiatric illness in first-degree relatives, evaluated with DSM-IV criteria
• History of alcohol and drug abuse. Positive urine screening for amphetamine, cocaine, cannabis, or esctacy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2	Drug: escitaolpram; Either 15 mg of escitalopram or placebo will be administered to healthy volunteers; Other Names: Cipralex
Placebo Comparator: 1	Drug: Escitalopram; Either 10 mg of escitalopram or placebo will be administered to a group of healthy volunteers; Other Names: Cipralex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The PPI (Prepulse Inhibition of the Startle Response) task	Once, 3.5 hrs after intake of capsule
The P50 Suppression task	Once, 3.5 hrs after intake of capsule
The P300 ERP task	Once, 3.5 hrs after intake of capsule
The mismatch negativity (MMN) task	Once, 3.5 hrs after intake of capsule

Collaborators and Investigators

• Sponsor: University of Copenhagen
• Collaborators: Lundbeck Foundation; Glostrup University Hospital, Copenhagen
• Investigators: Study Director: Birte Glenthoj, MD, DMSc., Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychaitric Center Glostrup, Ndr. Ringvej, DK-2600 Glostrup, Denmark

Publications and helpful links

Helpful Links

• Center for Neuropsychiatric Schizophrenia Research (CNSR)

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (Actual): March 1, 2006
• Study Completion (Actual): March 1, 2006

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 21, 2005

Study Record Updates

• Last Update Posted (Estimate): September 19, 2011
• Last Update Submitted That Met QC Criteria: September 16, 2011
• Last Verified: July 1, 2008

More Information

Terms related to this study

• Keywords: PPI; escitalopram; P50 suppression; P300; mismatch negativity
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antiparkinson Agents; Anti-Dyskinesia Agents; Citalopram; Dexetimide
• Other Study ID Numbers: 363037-1