Observational study on early stage psychosis and its mechanisms

Uppsala Psychosis Cohort: a Multimodal Study in Early Stage Psychosis Patients, High Risk Individuals and Healthy Controls

This study looks at people with early stage psychosis and those at risk for it, using brain scans and tests over five years to see how their brains work and what might cause their symptoms.

Quick facts

• Study type: Observational
• Enrollment: 120 (estimated)
• Ages: 18 Years to 40 Years
• Sex: All
• Sponsor: Uppsala University (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Uppsala)
• Trial ID: NCT05763966 on ClinicalTrials.gov

What this trial studies

This observational study focuses on early stage psychosis patients and individuals at high risk for developing psychosis, alongside healthy controls for comparison. It employs advanced imaging techniques, including positron emission tomography (PET) to assess synaptic density, and includes various clinical assessments, cognitive tests, and neurophysiological measures. Participants will undergo repeat assessments over a period of up to five years to investigate the underlying disease mechanisms of psychotic disorders, particularly the synaptic pruning hypothesis.

Who should consider this trial

Good fit: Ideal candidates include individuals diagnosed with schizophrenia or related psychotic disorders within the last three years, as well as those identified as clinically high risk for psychosis.

Not a fit: Patients with other dominant psychiatric illnesses or those on long-term benzodiazepine treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance understanding of psychotic disorders and lead to improved diagnostic and therapeutic strategies.

How similar studies have performed: While the approach of investigating synaptic mechanisms in psychosis is established, the specific methodologies and longitudinal design of this study may provide novel insights.

Eligibility criteria

Inclusion Criteria

For EPP:

* Diagnosis as assessed using DSM-5 of one of the following: schizophrenia, schizophreniform psychosis, psychosis not otherwise specified (NOS), brief psychosis, schizoaffective syndrome, delusional disorder
* Onset of psychotic symptoms together with functional decline no more than 3 years prior to inclusion visit

For CHR-P:

Clinical high risk for psychosis as determined using Structured Interview for Psychosis-risk Syndromes (SIPS).

Exclusion Criteria

For EPP and CHR-P:

* Other dominant psychiatric illness that is deemed to be related to current psychotic symptoms (including bipolar disorder, major depressive disorder, autism)
* Long-term daily treatment (\<2 weeks) with benzodiazepines, such that there is an inability to refrain from treatment during testing procedures.

For HC:

* A history of diagnosis of a major psychiatric disorder, including substance use disorders.
* A family history of psychotic disorders or bipolar disorder in first degree relatives.

For all participants:

* 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).
* Lack of proficiency in Swedish language, or documented intellectual disability that prohibits ability to give informed consent.
* Meets diagnostic criteria of substance use disorder (excluding nicotine dependence) as assessed using DSM-5 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.

Where this trial is running

Uppsala

• Uppsala University Hospital — Uppsala, Sweden (Recruiting)

Study contacts

• Principal investigator: Simon Cervenka, MD, PhD — Uppsala University
• Study coordinator: Simon Cervenka, MD, PhD

Conditions Schizophrenia; Psychosis