Pan European Collaboration on Antipsychotic Naive Schizophrenia (PECANS)

• The relation between D2 binding potential (SPECT) and reward related brain activity (fMRI BOLD response) before and after D2 antagonism [ Time Frame: Baseline, 6 weeks ] [ Designated as safety issue: No ]
• Time/dose improvement on P50 suppression after antipsychotic treatment [ Time Frame: Baseline, 2 and 6 weeks, 6,12,24 months ] [ Designated as safety issue: No ]
• Disturbances in reward related fMRI BOLD response in antipsychotic naive schizophrenic patients [ Time Frame: Baseline and 6 weeks follow up ] [ Designated as safety issue: No ]
• Hippocampal loss and basal ganglia increase after antipsychotic treatment [ Time Frame: 6 weeks, 6, 12 and 24 months, ] [ Designated as safety issue: No ]
• Processing speed improvement over time after antipsychotic treatment [ Time Frame: Baseline, 6 weeks, 6,12,24 months ] [ Designated as safety issue: No ]
• The effect of D2 blockade on reward related fMRI BOLD response [ Time Frame: 6 weeks of medical treatment ] [ Designated as safety issue: No ]

• The relation between D2 binding potentiel (SPECT) and reward related brain avtivity (fMRI BOLD response) before and after D2 antagonism [ Time Frame: Baseline, 6 weeks ] [ Designated as safety issue: No ]
• Time/dose improvement on P50 supression after antipsychotic treatment [ Time Frame: Baseline, 2 and 6 weeks, 6,12,24 months ] [ Designated as safety issue: No ]
• Disturbances in reward related fMRI BOLD response in antipsychotic naive schizophrenic patients [ Time Frame: Baseline ] [ Designated as safety issue: No ]
• Hippocampal loss and basal ganglia increase after antipsychotic treatment [ Time Frame: 6 weeks, 6, 12 and 24 months, ] [ Designated as safety issue: No ]
• Processing speed improvement over time after antipsychotic treatment [ Time Frame: Baseline, 6 weeks, 6,12,24 months ] [ Designated as safety issue: No ]
• The effect of D2 blockade on reward related fMRI BOLD response [ Time Frame: 6 weeks of medical treatment ] [ Designated as safety issue: No ]

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 investigators do not expect any effect of treatment on brain structure.

The study is designed as a 6 week case-control follow-up study of 60 AN FE pt. with SCZ and 60 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.

• Drug: amisulpride
  Individually dosed, according to symptoms, for a period of 6 weeks
  Other Name: Solian
• Drug: aripiprazole
  Individually dosed, according to symptoms, for a period of 6 weeks
  Other Name: abilify

• Active Comparator: first choice treatment
  Treatment with amisulpride
  Intervention: Drug: amisulpride
• Active Comparator: second choice treatment
  treatment with aripiprazole
  Intervention: Drug: aripiprazole

Inclusion Criteria:

For patients: meeting diagnostic criteria for schizophrenia according to ICD 10 or DSM IV antipsychotic naive The controls will be matched to the patients according to gender age and parental socio-economic status.

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Exclusion Criteria:

Patients: mental retardation, other chronic diseases, use of antidepressive medicine during the last month,being pregnant, on going substance abuse

Controls: psychiatric diagnosis, psychiatric diagnosis in first-degree relatives,on going drug abuse, mental retardation -

• Glostrup University Hospital, Copenhagen
• Rigshospitalet, Denmark
• Institute of Psychiatry, London
• UMC Utrecht
• Copenhagen Hospital Corporation