psychosis-associated neuroinflammation in schizophrenia

Conditions: Schizophrenia; Psychosis

Summary: previous research has suggested central nervous system inflammatory activity to be critically involved in disease development and progression in schizophrenia, with a complex interplay of inflammatory mechanisms leading to the development of brain abnormalities and medical symptoms related to schizophrenia. however, the mutual interactions of different inflammatory pathways and their relation to disease course have not been sufficiently studied. this study therefore aims to explore the interaction of neuroinflammatory mechanisms in patients with schizophrenia and to assess whether the inflammatory activity in schizophrenia is state-dependent and occurs mainly during psychotic episodes.


Eligibility criteria:
inclusion criteria: * be a man or woman between 18 and 40 years of age, inclusive. * have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in this study. * be medically stable on the basis of physical examination and vital signs performed at screening. * be medically stable on the basis of clinical laboratory tests performed at screening. if the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. * be willing and able to adhere to the prohibitions and restrictions specified in the protocol. schizophrenia subjects: * fulfill dsm-v criteria for the schizophrenia spectrum (dsm-v #295.1-295.6, 295.9, 298.9) * be admitted to hospital for first-episode psychosis or acute relapse of psychosis, as defined by: total score of ≥14 on the positive scale of the "positive and negative syndrome scale" (panss) and at least a score of 5 on 1 item or a score of 4 on 2 "psychotic" panss items p2, p3, p5 or g9 at screening. exclusion criteria: * use of nonsteroidal antiinflammatory drugs, paracetamol, immunosuppressant or immunostimulating drugs within 21 days of screening. * use of systemic corticosteroids within 21 days of screening. * has a history of drug or alcohol dependence according to dsm-v criteria, except nicotine or caffeine, within 6 months before screening. * has history of (co-morbid) somatization or mood disorder according to dsm-v criteria within 6 months before screening. * has a positive test result for drugs of abuse or for alcohol at screening or test day. * female subjects only: is pregnant or breastfeeding * has a history of chronic or acute physical illness associated with abnormal immune changes within the 2 weeks before the study. * leukocytosis (i.e., white blood cell count ≤ 11 x109 /l) on screening and test days. * serology positive for hepatitis b surface antigen (hbsag), hepatitis c antibodies, or hiv antibodies at screening. * has a medical history of any auto-immune disorder or chronic inflammatory disease. * has received electroconvulsive therapy in the last 6 months. * is currently enrolled in a study with an investigational study drug. * worsening or first time occurrence of significant suicidality * has donated blood within 3 months before screening. * has any condition that, in the opinion of the investigator, would compromise the wellbeing of the subject or the study or prevent the subject from meeting or performing study requirements. * low affinity binder of the tspo, as determined by rs6971 polymorphism genotyping at screening * use of benzodiazepines for 3x the half-life prior to pet-scan * presence of irremovable magnetic materials in or on the body * has a medical history of organic brain disease * has a medical history of traumatic brain injury * has a medical history of allergic reaction to any of the substances in the tracer fluid. * unwillingness or inability of subject to undergo pet and/or mri scan (for example due to claustrophobia or lack of cooperation) healthy volunteers: * personal history of psychotic disorder * family history of psychotic or bipolar disorder in first-degree relatives * family history of auto-immune disorder in first-degree relatives schizophrenia patients: - calgary depression scale for schizophrenia (cdss) score \>6 at screening

Keywords: schizophrenia psychosis neuroinflammation microglial activation