The outline of the current project is to establish a cohort of patients with treatment refractory schizophrenia eligible for clozapine, to identify clinical and biological characteristics of clozapine responding patients. Patients will be offered treatment with clozapine according to national clinical guidelines. Before clozapine is initiated, patients will be offered a thoroughly neurobiological examination, and re-examination will be carried out after 12 weeks of treatment. The primary focus of the examinations will be immunological markers and autoantibodies in the blood and cerebrospinal fluid, permeability of the blood-brain barrier and magnetic resonance imaging of structural, neurochemical and functional brain changes.

Patients will be examined before and after 12 weeks of treatment with clozapine

Examinations at baseline and follow up will be:

• Clinical ratings
• Blood inflammatory markers
• Inflammatory markers in cerebro spinal fluid
• MRI : examination of grey & white matter, glutamate and GABA in Anterior Cingulate cortex and glutamate in thalamus,
• selected cognitive measures

Inclusion Criteria:

• According to ICD-10 fulfill diagnostic criteria for schizophrenia (F20.x), chronical paranoid psychoses (F22), Schizoaffective psychoses (F25) or other non-organic psychoses (F28/F29);
• Age 18-65 years;
• Legally competent;
• Stabil antipsychotic treatment during last month
• Being treatment refractory according to TRIPP-guidelines (Howes et al. 2017) defined as having tried at least two antipsychotic drugs in sufficient dosage (≥600 mg chlorpromazine equivalent) for a sufficient time (≥ 6 weeks) without sufficient symptom improvement (still a moderate level of positive symptoms).
• Recreational use of substances is allowed as long as it does not interfere with compliance
• Fertile females must use safe contraception (spiral or any hormonal contraception).

Exclusion Criteria:

• Involuntarily psychiatric admittance during the study

• Substance abuse that interfere with compliance

• Pregnancy (will be verified by urine-HCG-test in fertile females)

• Toxic or idiosyncratic agranulocytosis in the past

• Reduced bone marrow function according to blood samples

• According to information from patient and available files, noUncontrolled

  • Current uncontrolled epilepsy
  • Current circulatory collapse and / or CNS depression for any cause
  • Current severe kidney, heart or liver disease
  • Current paralytic ileus