Neurobiological and Neurocognitive Disturbances in First-episode Schizophrenia

Study Overview
=================
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.

Official Title
-----------------
5-HT2A-receptor Binding: Implications for the Pathophysiology of Schizophrenia and Effects of Treatment With Antipsychotic Drugs

Conditions
-----------------
Schizophrenia

Intervention / Treatment
-----------------
* Drug: quetiapine


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: quetiapine<br>* flexible doses according to the clinical condition<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PANSS |  | Baseline and after 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
first-episode, altanserin, 5-HT2A receptors, MRI, fMRI, PPI, P300, P50 gating, endophenotypes, vulnerability indicators, quetiapine