Thinking and brain chemistry in early psychosis

Glutamate Changes as a New Neurocognitive Marker in Psychosis

This study will test whether a short session of gentle electrical brain stimulation changes glutamate levels and helps working memory and attention in people who recently experienced psychosis.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 106 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: University of Nottingham (Academic / other)
• Locations: 1 site (Nottingham, Nottinghamshire)
• Trial ID: NCT07196423 on ClinicalTrials.gov

What this trial studies

Researchers will measure glutamate and other brain chemicals using magnetic resonance spectroscopy while participants perform working memory and attention tasks, comparing people with first-episode psychosis to those without. They will apply a brief 'accelerated' session of transcranial direct current stimulation (tDCS) and repeat measurements to see short-term chemical and cognitive changes. The project also gathers views from people with lived experience about cognitive problems and treatments. Participants are adults aged 18–55 with psychosis of less than five years' duration, tested in person at the University of Nottingham.

Who should consider this trial

Good fit: Adults aged 18–55 with a DSM-5 psychotic disorder of less than five years' duration, on stable treatment for at least eight weeks, fluent in English, and able to travel to the University of Nottingham.

Not a fit: People with long-standing psychosis (>5 years), unstable or severe comorbid psychiatric or neurological conditions, current substance dependence, or who cannot undergo MRI or tDCS are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could identify a brain-chemical marker to personalize or improve short-term cognitive treatments for people with early psychosis.

How similar studies have performed: Previous research shows tDCS can transiently alter brain chemistry and sometimes improve cognition, but evidence in psychosis is limited and results have been mixed.

Eligibility criteria

Inclusion Criteria for FEP Group (studies 1a and 1b):

Eligibility criteria for first episode psychosis group are as follows:

1. Aged 18-55 years.
2. Ability to understand and willing to give written informed consent.
3. Fluent in English to be able to understand all cognitive task instructions and questionnaires.
4. 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.
5. At least 8 weeks of stable treatment.
6. Ability to travel to the University of Nottingham for in-person testing.

Exclusion Criteria for FEP Group (Studies 1a and 1b):

1. Clinically significant neurological or comorbid psychiatric disorder in the opinion of the investigator.
2. History of clinically significant head injury
3. Current harmful use of, or dependence on, psychoactive substances (excluding nicotine) in the opinion of the investigator
4. 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
5. Contraindications for MR scanning as assessed by SPMIC screening form and trained scanner operator (e.g. claustrophobia, pregnancy, metal implants, etc.)
6. 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.)
7. Having taken part within the previous month as a participant in a clinical trial that involved taking a drug or having an invasive procedure.

Inclusion Criteria for Healthy Matched Controls (Studies 1a and 1b):

Matched healthy control participants will be recruited from a local database of volunteers, from posters and online advertisements.

Inclusion criteria (matched controls):

1. Aged 18 - 55 years.
2. Ability to understand and willing to give written informed consent.
3. English as first language or fluent in English.
4. Ability to travel to the University of Nottingham for in-person testing.

Exclusion criteria for Health Matched Controls (Studies 1a and 1b):

1. Personal or family history of psychosis.
2. Clinically significant neurological or psychiatric disorder.
3. History of clinically significant head injury.
4. Current harmful use of, or dependence on, psychoactive substances (excluding nicotine and caffeine) in the opinion of the investigator.
5. 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.
6. Contraindications for MR scanning as assessed by SPMIC screening form and trained scanner operator (e.g. claustrophobia, pregnancy etc).
7. 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.)
8. 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).

Inclusion Criteria for participants with lived experiences of psychosis (Study 2):

1. Aged 18+ years.
2. Ability to understand and willing to give written informed consent.
3. Fluent in English to be able to understand and answer all questions.
4. 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.
5. At least 8 weeks of stable treatment.
6. Ability to travel to the University of Nottingham for in-person testing.

Exclusion Criteria for participants with lived experiences of psychosis (Study 2):

1. Clinically significant neurological or comorbid psychiatric disorder.
2. Current harmful use of, or dependence on, psychoactive substances (excluding nicotine) in the opinion of the investigator.
3. Having taken part within the previous month as a participant in a clinical trial that involved taking a drug or having an invasive procedure.
4. Lived experience where psychosis symptoms have not been directly experienced by the individual (e.g., support or carer role to someone else).

Where this trial is running

Nottingham, Nottinghamshire

• University of Nottingham — Nottingham, Nottinghamshire, United Kingdom (Recruiting)

Study contacts

• Principal investigator: Claudia Danielmeier, PhD — University of Nottingham
• Study coordinator: Claudia Danielmeier, PhD

Conditions First Episode Psychosis; Psychosis; psychosis; cognition; glutamate; transcranial direct current stimulation; fMRS; first episode psychosis