Schizophrenia
Conditions
Keywords
glutamate, dopamine, cognition, cortical thickness, ppi, p50
Brief summary
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
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.
Interventions
DRUGAripiprazole
6 weeks of individual doses of aripiprazole
Sponsors
University of Copenhagen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glutamate level in Anterior Cingulate Cortex (measured with magnetic resonance spectroscopy) | Baseline, 6 weeks, 6 months, 2 years | Glutamate level at baseline and change over time as measured with magnetic resonance spectroscopy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dopamine syntheses capacity in striatum (measured with F-DOPA using Positron emission tomography) | Baseline and 6 weeks follow up | Dopamine measured with F-DOPA using Positron emission tomography |
| Reward system activation in striatum (measured with functional magnetic resonance imaging) | Baseline and 6 weeks follow up | Reward activity is measured with functional magnetic resonance imaging |
| Cortical thickness (measured with magnetic resonance and free surfer) | Baseline, 6 weeks, 6 months & 2 years | Thickness of grey matter measured with magnetic resonance and free surfer |
| Psychopathology (measured with PANSS (Positive and Negative Syndrome Scale) | Baseline, 6 weeks, 6 months & 2 years | Psychopathology is measured with PANSS (Positive and Negative Syndrome Scale) |
| Prepulse inhibition of the startle reflex and reduced P50 suppression ( measured with event related EEG and EMG) | Baseline, 6 weeks, 6 months & 2 years | Disturbances in early information processing in form of impaired sensory filtering as measured with event related EEG and EMG |
| Neurocognition (measured with BACS (Brief Assessment of Cognition in Schizophrenia) and CANTAB (Cambridge Neuropsychological Test Automated Battery) | Baseline, 6 weeks, 6 months & 2 years | Neurocognition is measured with BACS (Brief Assessment of Cognition in Schizophrenia) and CANTAB (Cambridge Neuropsychological Test Automated Battery) |
Countries
Denmark
Outcome results
None listed