The investigators want to relate disturbances in first-episode schizophrenic patients in (dopaminergic) D2 receptors, brain structure, brain function, and information processing to each other and to psychopathology. Additionally, the investigators want to examine the influence of D2 receptor blockade on these disturbances. The investigators expect disturbances in the dopaminergic 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 investigators expect D2 receptor blockade to reverse some of the functional and cognitive impairments.
The study is designed as a 6 week case-control follow-up study of 70 AN FE pt. with SCZ and 70 controls matched with regard to age, gender, and parental socio-economic status. All subjects will be examined with a diagnostic interview (SCAN, Schedule for Clinical Assessment in Neuropsychiatry), medical and family history, and physical examination before inclusion. At baseline all subjects will be examined with single photon emission computed tomography (SPECT), MRI, fMRI, psychophysiology, neurocognition. In addition, they will be screened for drugs, genetic testing, and ECG. Patients will further be examined with clinical validated rating scales to measure psychopathology, subjective well-being, and side-effects. After a period of 6 weeks all assessments are repeated. During that period patients will be treated with amisulpride, while healthy controls will receive no treatment at all. Efficacy of antipsychotic treatment will be evaluated after this initial period of 6 weeks. Based on this evaluation it will be decided to either continue the current (amisulpride) antipsychotic treatment, or to switch to aripiprazole. Efficacy of aripiprazole is evaluated on a monthly basis, if the patient does not respond well enough, than the treatment will be adapted individually. Regardless of treatment, all subjects will be re-assessed in the same test battery as mentioned above, except for SPECT and fMRI, after a period of 6, 12, and 24 months. The developement in specific disturbances and the relationship between these will be analysed.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
136
Individually dosed, according to symptoms, for a period of 6 weeks
Individually dosed, according to symptoms, for a period of 6 weeks
Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychiatric Center Glostrup
Glostrup Municipality, Denmark
Relationship between specific neuropsychiatric measures and improvement on PANSS scores
Time frame: 6 weeks of medical treatment
The relation between D2 binding potential (SPECT) and reward related brain activity (fMRI BOLD response) before and after D2 blockade
Time frame: Baseline, 6 weeks
Time/dose improvement on PPI and other psychophysiological measures of early information processing after D2 blockade
Time frame: Baseline, 2 and 6 weeks, 6,12,24 months
Disturbances in reward related fMRI BOLD response in antipsychotic naive schizophrenic patients
Time frame: Baseline and 6 weeks follow up
Structural changes in grey and white matter before and after D2 blockade
Time frame: 6 weeks, 6, 12 and 24 months,
Cognitive differences at baseline and changes over time after D2 blockade
Time frame: Baseline, 6 weeks, 6,12,24 months
The effect of D2 blockade on reward related fMRI BOLD response
Time frame: 6 weeks of medical treatment
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