Early Psychosis: Investigating Cognition
Glutamate Changes as a New Neurocognitive Marker in Psychosis
University of Nottingham
106 participants
Feb 9, 2026
INTERVENTIONAL
Conditions
Summary
The project aims to explore changes in brain chemistry in individuals who have recently experienced psychosis. Recent research suggests that chemicals in the brain, specifically one called glutamate, may behave differently in people who have experienced psychosis compared to those who have not. It is also known that some individuals with psychosis can find tasks involving memory and attention more challenging. This study aims at understanding how brain chemistry is linked to memory and attention, and if this is different between people who have and have not experienced psychosis. The study will also investigate how a commonly used brain stimulation technique might help people with psychosis and other conditions by altering brain chemistry for a very short period. Non-invasive brain stimulation using very weak electrical stimulation has been used to help improve symptoms in individuals with psychosis and many other conditions, and has been shown to alter brain chemistry for a few hours after stimulation. However, it does not work for everyone. It will be investigated if levels of glutamate can predict whether brain stimulation will help an individual or not. In other words, the study investigates if glutamate can be used as a marker for tailoring treatments. This project also aims to collect personal experiences or challenges that individuals with psychosis face. This information will be gathered through interviews. This will help to understand what specific difficulties individuals have, such as with certain aspects of memory and attention. The interview will also gather opinions and concerns about brain imaging and brain stimulation and current understandings of chemicals in the brain. For example, the study will explore why individuals may not want to take part in brain imaging or brain stimulation.
Eligibility
Inclusion Criteria18
- Eligibility criteria for first episode psychosis group are as follows:
- Aged 18-55 years.
- Ability to understand and willing to give written informed consent.
- Fluent in English to be able to understand all cognitive task instructions and questionnaires.
- Current psychotic disorder of less than 5yrs total duration. Defined as meeting DSM-5 criteria consistent with a diagnosis of schizophrenia, schizoaffective disorder, bipolar affective disorder, or severe depression with psychosis.
- At least 8 weeks of stable treatment.
- Ability to travel to the University of Nottingham for in-person testing.
- Matched healthy control participants will be recruited from a local database of volunteers, from posters and online advertisements.
- Aged 18 - 55 years.
- Ability to understand and willing to give written informed consent.
- English as first language or fluent in English.
- Ability to travel to the University of Nottingham for in-person testing.
- Aged 18+ years.
- Ability to understand and willing to give written informed consent.
- Fluent in English to be able to understand and answer all questions.
- History of psychotic disorder defined as DSM-5 criteria for diagnosis of schizophrenia, schizoaffective disorder, bipolar affective disorder, or severe depression with psychosis. No limit of time since first episode.
- At least 8 weeks of stable treatment.
- Ability to travel to the University of Nottingham for in-person testing.
Exclusion Criteria19
- Clinically significant neurological or comorbid psychiatric disorder in the opinion of the investigator.
- History of clinically significant head injury
- Current harmful use of, or dependence on, psychoactive substances (excluding nicotine) in the opinion of the investigator
- Current use of any medication which may interfere with the study in the opinion of the investigator, i.e. any medication that might affect the neurochemicals of interest
- Contraindications for MR scanning as assessed by SPMIC screening form and trained scanner operator (e.g. claustrophobia, pregnancy, metal implants, etc.)
- Contraindications for transcranial direct current stimulation as assessed by standard screening form (e.g. cardiac pacemaker or other implanted devices, seizures, epilepsy, open head wound, etc.)
- Having taken part within the previous month as a participant in a clinical trial that involved taking a drug or having an invasive procedure.
- Personal or family history of psychosis.
- Clinically significant neurological or psychiatric disorder.
- History of clinically significant head injury.
- Current harmful use of, or dependence on, psychoactive substances (excluding nicotine and caffeine) in the opinion of the investigator.
- Current use of any medication, which may interfere with the study in the opinion of the investigator i.e. any medication that might affect the neurochemicals of interest.
- Contraindications for MR scanning as assessed by SPMIC screening form and trained scanner operator (e.g. claustrophobia, pregnancy etc).
- Contraindications for transcranial direct current stimulation as assessed by standard screening form (e.g. cardiac pacemaker or other implanted devices, seizures, epilepsy, open head wound, etc.)
- Having taken part within the previous month as a participant in a clinical trial that involved taking a drug, being paid an inconvenience allowance, or having an invasive procedure (e.g. venepuncture >50ml, endoscopy).
- Clinically significant neurological or comorbid psychiatric disorder.
- Current harmful use of, or dependence on, psychoactive substances (excluding nicotine) in the opinion of the investigator.
- Having taken part within the previous month as a participant in a clinical trial that involved taking a drug or having an invasive procedure.
- Lived experience where psychosis symptoms have not been directly experienced by the individual (e.g., support or carer role to someone else).
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Interventions
2mA anodal stimulation to be delivered for 20 minutes using a Neuroconn DC stimulator PLUS which will be repeated once after a 20-minute break.
Using a 7T Philips scanner with total scanning session lasting no more than 1 hour.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07196423