Karolinska Schizophrenia Project (KaSP)

Brain Immunoactivation in Drug-Naive Patients with First Episode Schizophrenia

KaSP is a multimodal observational study with the goal of clarifying underlying mechanisms that cause psychotic disorders, such as schizophrenia. Participants with psychotic symptoms are recruited early after first contact with health care, within 4 weeks of starting anti-psychotic medication, and are compared to controls without psychiatric diagnoses on several measures.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia and Disorders with Psychotic Features

Detailed Description

KaSP aims to recruit 120 patients sparsely medicated or drug-naive first episode psychosis (FEP) individuals, along with 80 healthy controls.

Participants undergo the following assessments and measurements:

• Clinical assessment
• Cognitive testing
• Lab results from cerebrospinal fluid, blood, urine, saliva and skin biopsy
• Brain imaging using Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET)
• Pre-Pulse Inhibition (PPI) (a test to evaluate the startle response)
• Measures of arterial stiffness and amount of vascular narrowing

Participants with psychosis are invited back for repeat measurements at 1,5 and 5 years after study enrollment. Controls may be invited back at 1,5 years for repeat of some of the assessments.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Carl M Sellgren, MD, PhD; Phone Number: +46 702127287; Email: carl.sellgren@ki.se
• Study Contact Backup: Name: Lena Lundberg; Phone Number: +46725223907; Email: lena.lundberg.2@ki.se

Study Locations

• Sweden
  • Stockholm, Sweden
    • Recruiting
    • SLSO Psykiatri Stockholm in collaboration w Karolinska Institutet
    • Contact: Carl M Sellgren, MD, PhD; Phone Number: 0046702127287; Email: carl.sellgren@ki.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

FEP are recruited from psychiatry clinics in the greater Stockholm area. HC are recruited by advertisement.

Description

Inclusion Criteria:

For FEP:

• Diagnosis as assessed using DSM-IV of one of the following: schizophrenia, schizophreniform psychosis, psychosis not otherwise specified (NOS), brief psychosis, schizoaffective syndrome, delusional disorder
• First exposure to anti-psychotic medication less than 4 weeks prior to inclusion

Exclusion Criteria:

For FEP:

- Other dominant psychiatric illness deemed to be related to current psychotic symptoms

For HC:

• A history of diagnosis of a major psychiatric disorder, including substance use disorders.
• Family history of psychotic disorders in first degree relatives.

For all:

• Evidence based on medical history, clinical signs, MRI or laboratory tests of clinically significant somatic disorder, or previous disorder with brain engagement (e.g. tumour, neuroinflammatory disease, epilepsy) or significant brain trauma.
• Exposure to an effective radiation dose of 25 mSv during the past year.
• Pregnancy, lactating or breastfeeding (women).
• Meets diagnostic criteria of substance use disorder (excluding nicotine dependence) as assessed using DSM-IV or as determined using repeated positive urine screens during the course of the study.
• Metallic object in the eye, or ferro/electromagnetic implants. History of claustrophobic anxiety during MRI.
• Symptoms of severe bacterial, fungal, or viral infection (including upper respiratory tract infection), with systemic effects as detected by e.g. fever, within 7 days prior to inclusion.
• Treatment with any antihemostatic medication within 2 weeks of lumbar puncture and arterial line placement of either the baseline or 1 year follow-up.
• Blood donation (1 unit or more) within 90 days prior to Screening, plasma donation from 1 week prior to Screening, and platelet donation from 6 weeks prior to inclusion.
• Other unspecified reasons that, in the opinion of the Investigator or the Sponsor, make the participant unsuitable for enrollment. This may include very high symptom severity or signs of aggressiveness and hostility.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
First Episode Psychosis (FEP); Diagnosis of psychotic disorder according to the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV), where anti-psychotic medication was initiated less than four weeks prior to inclusion.
Healthy Control (HC); Age and sex matched individuals

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kynurenic acid (KYNA) in FEP compared to HC	KYNA are measured in CSF and blood samples	Baseline measure
Cytokines in FEP compared to HC	Cytokines are measured in CSF and blood samples	Baseline measure
Microglial activation in FEP compared to HC	Group comparison of binding of the PET ligand [11C]PBR-28	Baseline measure
Dopamine receptors in FEP compared to HC	Group comparison of binding of the PET-ligand [11C]FLB457	Baseline measure
Infectious risk factors in FEP and subsequent relation to clinical outcome	Registry data on previous infections, along with infectious agents measured in CSF and blood. Long term clinical outcome is measured through registry data, by drug-dispensation as well as in-and outpatient care for both somatic and psychiatric disorders.	Registry data in childhood, measurement at baseline, registry data through study completion (with an expected average of 7 years of follow up)

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: Centre for Psychiatry Research, Region Stockholm, Sweden

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2011
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2032

Study Registration Dates

• First Submitted: March 3, 2025
• First Submitted That Met QC Criteria: March 10, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Schizophrenia; Psychosis; Psychotic disorders
• Additional Relevant MeSH Terms: Schizophrenia; Psychotic Disorders; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders
• Other Study ID Numbers: 2010/879-31/1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No