Pan European Collaboration on Antipsychotic Naïve Schizophrenia II

Study Overview
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Brief Summary
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The study is a prospective 2 year multimodal follow-up study of initially antipsychotic-naïve first-episode psychotic patients involving a standardized intervention with monotherapy with aripiprazole during the first 6 weeks. Patients and matched healthy controls will be examined after 6 weeks, 6 months and 2 years. They will be examined with MR-scannings, neurocognitive tests, EEG, and PET-scannings.

Detailed Description
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The study is a prospective 2 year multimodal follow-up study of initially antipsychotic-naïve first-episode psychotic patients involving a standardized intervention with monotherapy with aripiprazole during the first 6 weeks. Patients and matched healthy controls will be examined at baseline and after 6 weeks, 6 months and 2 years. Levels of glutamate and gamma-aminobutyric acid (GABA) are measured by proton magnetic resonance spectroscopy (1H-MRS) in the anterior cingulate cortex ACC and thalamus. Presynaptic Dopamine level is measured with Positron Emission Tomography Computed Tomography (PET/CT)-scanning using 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (18F-DOPA). Disturbances of the reward system is measured with functional magnetic resonance imaging (fMRI) . Regional cerebral blood flow and activity in the same regions are measured with Pseudo-continuous arterial spin labelling (pCASL). The default mode network, functional and structural connectivity in the associated macro circuits are measured with resting state fMRI, EEG, and diffusion tensor imaging. Structural brain changes (in grey and white matter) are measured with MRI. Cognitive functions are measured with a neuropsychological test battery, and early information processing with event related EEG and electromyography (EMG) (psychophysiological examinations). Further patients psychopathology will be rated.

Official Title
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Pan European Collaboration on Antipsychotic Naïve Schizophrenia II

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Aripiprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients: Fulfilling the diagnostic criteria of schizophrenia or schizoaffective disorder according to ICD-10 (International Classification of Diseases version 10) or DSM-IV/V (Diagnostic and Statistical Manual version 4 /5) Age 18-45 years Never treated with antipsychotic compounds or central nervous system (CNS) stimulants Legally competent Inclusion criteria controls: Matching patients on age (+/- 2 years), sex and parental socioeconomic status Age 18-45 years No psychiatric or physical disease Exclusion Criteria patients: Substance abuse on a daily basis during the last 3 month or patients fulfilling the criteria of ongoing substance abuse due to ICD-10/DSM-IV/V Treatment with antidepressant during the last 30 days Head injury with more than 5 minutes of unconsciousness Patients involuntarily admitted or treated Components of metal implanted by operation Pacemaker Pregnancy Severe physical illness Exclusion criteria controls First degree relatives with psychiatric disease Substance abuse during the last 3 month or positive screening of drugs in urine-sample Head injury with more than 5 minutes of unconsciousness Components of metal implanted by operation Pacemaker Pregnancy Severe physical illness

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: antipsychotic treatment<br>individual doses of aripiprazole for all patients | Drug: Aripiprazole<br>* 6 weeks of individual doses of aripiprazole<br>* Other names: Abilify;|
| No Intervention: no treatment<br>no treatment for all healthy controls | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glutamate level in Anterior Cingulate Cortex (measured with magnetic resonance spectroscopy) | Glutamate level at baseline and change over time as measured with magnetic resonance spectroscopy | Baseline, 6 weeks, 6 months, 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cortical thickness (measured with magnetic resonance and free surfer) | Thickness of grey matter measured with magnetic resonance and free surfer | Baseline, 6 weeks, 6 months & 2 years | 
| Dopamine syntheses capacity in striatum (measured with F-DOPA using Positron emission tomography) | Dopamine measured with F-DOPA using Positron emission tomography | Baseline and 6 weeks follow up | 
| Reward system activation in striatum (measured with functional magnetic resonance imaging) | Reward activity is measured with functional magnetic resonance imaging | Baseline and 6 weeks follow up | 
| Neurocognition (measured with BACS (Brief Assessment of Cognition in Schizophrenia) and CANTAB (Cambridge Neuropsychological Test Automated Battery) | Neurocognition is measured with BACS (Brief Assessment of Cognition in Schizophrenia) and CANTAB (Cambridge Neuropsychological Test Automated Battery) | Baseline, 6 weeks, 6 months & 2 years | 
| Psychopathology (measured with PANSS (Positive and Negative Syndrome Scale) | Psychopathology is measured with PANSS (Positive and Negative Syndrome Scale) | Baseline, 6 weeks, 6 months & 2 years | 
| Prepulse inhibition of the startle reflex and reduced P50 suppression ( measured with event related EEG and EMG) | Disturbances in early information processing in form of impaired sensory filtering as measured with event related EEG and EMG | Baseline, 6 weeks, 6 months & 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ppi, glutamate, dopamine, cognition, cortical thickness, p50