Neurobiological and Neurocognitive Disturbances in First-episode Schizophrenia

Not Applicable

Completed

• Conditions: Schizophrenia
• Interventions: Drug: quetiapine

• Registration Number: NCT00207064
• Lead Sponsor: Birte Glenthoj

Brief Summary

We want to relate disturbances in first-episode schizophrenic patients in serotonin 5-HT2A receptors, brain structure, brain function, and information processing to each other and to psychopathology. Additionally, we want to examine the influence of 5-HT2A receptor blockade on these disturbances. We expect disturbances in the serotonergic system at baseline to correlate with specific structural and functional changes and with disruption in information processing as measured with psychophysiological and neurocognitive methods - and we expect 5-HT2A receptor blockade to reverse some of the functional and cognitive impairments. We do not expect any effect of treatment on brain structure

Detailed Description

Patients and matched healthy controls are examined at baseline and again after the patients have been treated for 6 months with a combined 5-HT2A- and dopamine D2- receptor blocker. We have chosen the atypical antipsychotic compound, quetiapine, for the present study since this drug is characterized by a fast koff/low affinity for the dopamine D2 receptors. The purpose of the study is to examine pathophysiological and neuropsychological mechanisms - not treatment effects. We want to characterize neurobiological and functional endophenotypes or vulnerability indicators and to study their stability over time and their relation to treatment and contemporary psychopathology. To the extent that candidate endophenotypes can be characterized as stable and independent of treatment and contemporary psychopathology they will be analysed together with similar findings from previous (identical)cohorts of schizophrenic patients. Specific disturbances will also be related to candidate genes for schizophrenia.

Study Timeline

• Study Start: 2004-04
• Study First Submitted: 2005-09-10
• Study First Submitted QC: 2005-09-20
• Study First Posted: 2005-09-21
• Primary Completion: 2008-09
• Study Completion: 2008-09
• Status Verified: 2011-09
• Last Update Submitted: 2011-09-16
• Last Update Posted: 2011-09-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

Inclusion Criteria

• First-episode schizophrenia. The controls are matched for age, gender and parental socioeconomic status

Exclusion Criteria

• Previous antipsychotic treatment, mental retardation, organic brain damage, and for the controls a psychiatric diagnosis or first-degree relatives with a psychiatric diagnosis

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
1	quetiapine	-

Primary Outcome Measures

Name	Time	Method
5-HT2A receptor binding and occupancy (PET)	Baseline and after 6 months
Structural MRI	Baseline and after 6 months
Functional MRI	Baseline and after 6 months
Information procession as measured with psychophysiological methods (P300, PPI, P50 gating ect.)	Baseline and after 6 months
An extensive battery of neurocognitive measures	Baseline and after 6 months

Secondary Outcome Measures

Name	Time	Method
PANSS	Baseline and after 6 months

Trial Locations

Locations (3)

Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychiatric Center Glostrup; 🇩🇰 Glostrup, Denmark

Neurobiology Research Unit, Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Danish Research Center for Magnetic Resonance Imaging, Hvidovre Hospital; 🇩🇰 Hvidovre, Denmark