About this trial

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 criteria

This trial accepts healthy volunteers

Qualifiers

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.

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

Transcranial direct current stimulation (tDCS)
Device
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.
Magnetic Resonance Imaging
Diagnostic test
Using a 7T Philips scanner with total scanning session lasting no more than 1 hour.

Treatment groups

106 Participants

are divided into 1 treatment group

Group A: Study1a and 1bExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Measures of glutamate and GABA change (quantified using fMRS) during a working memory task

Difference in glutamate and GABA levels between different phases/WM load in a working memory task (Study 1a).

Time frame

Day 1, during fMRS scan, blocks with working memory task vs. blocks with control task.

2

Correlation between glutamate and GABA responses during a WM task and tDCS outcome (accuracy)

Neurometabolite changes during a WM task (as described above, outcome measure 1) will be correlated with changes in accuracy in a WM task after tDCS brain stimulation.

Time frame

within 1 week

3

Correlation between glutamate and GABA responses during a WM task and tDCS outcome (reaction time)

Neurometabolite changes during a WM task (as described above, outcome measure 1) will be correlated with changes in reaction times in a WM task after tDCS brain stimulation.

Time frame

within 1 week

4

Qualitative data analysis: Perceived cognitive impairments in psychosis

Thematic analysis of impact of experiencing cognitive impairments (or perceived improvements) on individuals' lives in semi-structured interviews (Study 2).

Time frame

Study day 2

Secondary outcomes

1

Difference in glutamate levels during working memory task pre- and post-tDCS stimulation

Glutamate concentration in the medial frontal cortex while the participant is engaged in an associative working memory task pre-tDCS stimulation vs. post-tDCS stimulation

Time frame

within 1 week (pre- and post-tDCS fMRS acquisitions; post-tDCS scan will take place immediately after tDCS stimulation)

2

Difference in GABA levels during working memory task pre- and post-tDCS stimulation

GABA concentration in the medial frontal cortex while the participant is engaged in an associative working memory task pre-tDCS stimulation vs. post-tDCS stimulation

Time frame

within 1 week (pre- and post-tDCS fMRS acquisitions; post-tDCS scan will take place immediately after tDCS stimulation)

3

Changes in other neurometabolites (tCR, GSH) during different phases of a working memory task.

Level of neurometabolite concentration (tCR, GSH) in the medial frontal cortex during the associative Working Memeory task as compared to a control condition without working memory load in individuals with psychosis and matched controls.

Time frame

Day 1, during fMRS scan, blocks with working memory task vs. blocks with control task.

4

Correlation of neurometabolite concentration changes (glutamate, GABA) during WM task and psychosis symptom severity (PANSS).

Neurometabolite concentration changes during an associative WM task will be correlated with symptom scores from PANSS.

Time frame

Within 2 months from first fMRS acquisition

Other outcomes

1

Alignment between objective cognitive measures and subjective experiences of cognitive impairments

Qualitative data analysis: the self-reported cognitive strengths and deficits in Study 2 will be compared to the cognitive performance profile (accuracy, RTs, completion times) in working memory, attentional and cognitive control tasks from Study 1. This will be done on an individual case basis.

Time frame

Study day 2

2

Correlation of neurometabolite concentration changes (glutamate, GABA) during WM task (fMRS) and accuracy in a change detection working memory task.

Neurometabolite concentration during the associative working memory task (fMRS, percent change in neurometabolite level between WM task and control condition) will be correlated with accuracy (percentage of correct answers) in a change detection working memory task.

Time frame

Within 2 months of MRS data acquisition.

3

Correlation of neurometabolite concentration changes (glutamate, GABA) during WM task (fMRS) and processing speed (digit-symbol substitution task).

Neurometabolite concentration during the associative working memory task (fMRS, percent change in neurometabolite level between WM task and control condition) will be correlated with number of correctly associated items in the digit-symbol substitution task.

Time frame

Within 2 months of MRS data acquisition.

4

Correlation of neurometabolite concentration changes (glutamate, GABA) during WM task (fMRS) and processing speed (simple and choice RT).

Neurometabolite concentration during the associative working memory task (fMRS, percent change in neurometabolite level between WM task and control condition) will be correlated with reaction times in a simple RT task and the difference in reaction times between a simple and a choice RT task.

Time frame

Within 2 months of MRS data acquisition.

Early Psychosis: Investigating Cognition

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Sponsors and contacts