Dopaminergic, Functional, Structural, and Cognitive Disturbances in First-episode Schizophrenia

Not Applicable

Completed

• Conditions: Schizophrenia
• Interventions: Drug: zuclopenthixol; Drug: risperidone

• Registration Number: NCT00206960
• Lead Sponsor: Birte Glenthoj

Brief Summary

We wanted to compare dopamine D2 receptor activity, brain structure, brain function, sensory gating and cognition in neuroleptic-naive schizophrenic patients and matched healthy controls. Additionally, we wanted to examine the effects of 3 months of treatment with either low doses of a typical or an atypical antipsychotic compound on the same functions. The hypotheses were that schizophrenic patients suffered from disturbances in brain function and structure, information processing, and extrastriatal D2 receptor activity, and that these disturbances would be related to each other and to psychopathology. Additionally, we expected the atypical compound to have an effect on some of the disturbances in information processing, and that the atypical compound - in contrast to the typical drug - would show extrastriatal over striatal selectivity.

Detailed Description

31 neuroleptic-naive schizophrenic patients and 25 matched controls were recruited from the greater Copenhagen area. The patients were randomized to treatment with either low doses of the typical antipsychotic compound, zuclopenthixol, or the atypical drug, risperidone. Patients and controls were examined at base-line and patients were re-examined after 3 months of treatment.The study has resulted in two finish Ph.D. theses (Torben Mackeprang and Birgitte Fagerlund).

The data has in part been published in:

Mackeprang T, Tjelle Kristiansen K, Glenthoj B. Prepulse inhibition of the startle response in drug-naïve, first-episode schizophrenic patients before and after 3 months of treatment with a typical or an atypical antipsychotic drug. Biological Psychiatry 2002; 52(9): 863-873.

and

Fagerlund B, Mackeprang T, Gade A, Hemmingsen R, Glenthoj BY. Effects of Low-Dose Risperidone and Low-Dose Zuclopenthixol on Cognitive Functions in First-Episode Drug-Naïve Schizophrenic Patients. CNS Spectr. 2004; 9: 364-74.

and

Glenthoj BY, Mackeprang T, Svarer C, Rasmussen H, Pinborg L, Friberg L, Baaré W, Hemmingsen R, Videbæk C. Frontal dopamine D2/3 receptor binding in drug-naïve first-episode schizophrenic patients correlates with positive psychotic symptoms and gender. Biological Psychiatry 2006; in press. Mar 30; \[Epub ahead of print\]. PMID: 16784819 \[PubMed - as supplied by publisher\].

We are at present conducting a five-year follow-up study of the same cohort of patients and controls and plan a ten-year follow-up as well. The follow-up studies focus on brain structure (MRI), brain function, information processing, and psychopathology. We will correlate changes in structure and function to treatment, but no interventions (pharmacological or otherwise) are planned.

Study Timeline

• Study Start: 1998-01
• Study First Submitted: 2005-09-10
• Study First Submitted QC: 2005-09-13
• Study First Posted: 2005-09-21
• Primary Completion: 2010-09
• Study Completion: 2010-09
• Status Verified: 2011-09
• Last Update Submitted: 2011-09-16
• Last Update Posted: 2011-09-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

• For patients: Clinical diagnosis of schizophrenia.
• The controls were matched to the patients.

Exclusion Criteria

• Patients: Previous antipsychotic treatment, patients who were compulsorily hospitalised or deemed in acute need of medication, mental retardation
• Controls: psychiatric diagnosis, psychiatric diagnosis in first-degree relatives, drug abuse, mental retardation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
1	zuclopenthixol	-
2	risperidone	-

Primary Outcome Measures

Name	Time	Method
All examinations are done at baseline (patients and controls). In the patient group, they are repeated after 3 months of treatment	prospective
PANSS	prospective
SANS	prospective
SAPS	prospective
MRI	prospective
fMRI	prospective
startle response	prospective
PrePulse Inhibition of the startle response (PPI)	prospective
Cognition	prospective

Secondary Outcome Measures

Name	Time	Method
The cognitive test battery comprised tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) as well as paper-and-pencil cognitive tests.	prospective

Trial Locations

Locations (6)

University of Copenhagen, Dept. F, Bispebjerg Hospital; 🇩🇰 Copenhagen NV, Denmark

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

University of Copenhagen, Dept. of Psychiatry E, Bispebjerg Hospital; 🇩🇰 Copenhagen NV, Denmark

Dept. of Nuclear Medicine, University of Copenhagen, Bispebjerg Hospital; 🇩🇰 Copenhagen NV, Denmark

Neurobiology Research Unit, University of Copenhagen, Rigshospitalet; 🇩🇰 Copenhagen, Denmark

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