Glutamate Changes as a New Neurocognitive Marker in Psychosis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 106
- 试验地点
- 2
- 主要终点
- Measures of glutamate and GABA change (quantified using fMRS) during a working memory task
研究概览
简要总结
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.
详细描述
TRIAL / STUDY BACKGROUND INFORMATION AND RATIONALE
Cognitive impairment in psychosis:
Cognitive impairments occur in up to 80% of people living with psychosis. The recent landscape report, commissioned by the Wellcome Trust, highlighted that cognitive impairments are an "area of concern for people with psychosis" (p.36) and, furthermore, that "personalising the intervention approach...is desirable" (p.39). Specific cognitive symptoms are variable across individuals, but they are relevant for the individual as they predict day-to-day functioning and quality of life. Current interventions aiming at cognitive improvements are effective for some, but not all, individuals with psychosis. To increase the amount of viable and effective treatment options, a personalised approach based on improved understanding into the variability in cognitive impairments in psychosis is needed.
This project aims to explore perceptions of cognitive impairment & treatment from those with first-hand experience (Study 2); to explore a potential neurochemical marker (glutamate levels, in particular) for cognitive functioning with a focus on working memory (WM) (Study 1a); and to assess how this marker may predict changes in response to a single 'accelerated' session of non-invasive brain stimulation using transcranial direct current stimulation (tDCS) (Study 1a). Additionally, the study aims to explore the effects of accelerated tDCS on neurochemistry in individuals with first-episode psychosis (FEP; Study 1b). This 'accelerated' approach involves applying two stimulations in proximity during one testing session as recommended by several authors to safely maximise potential stimulation effects. The investigators chose tDCS as intervention method due to its potential for influencing glutamate levels (see below). Through these three interconnected studies using functional magnetic resonance spectroscopy (fMRS), transcranial direct current stimulation (tDCS) and interview approaches, the study aims at better understanding and informing potential future treatment options for cognitive impairment in psychosis.
It is important to note that while this study will use tDCS as part of this project, this is not an interventional study, in the respect that it is not assessing the impact of tDCS directly on symptoms or quality of life. In study 1a, the investigators will explore statistical relationships between changes in neurochemistry during the cognitive task, and changes in task performance during and following tDCS. In study 1b, the study will explore how neurochemistry is temporarily altered following accelerated tDCS in a subset of FEP participants. This will allow to validate previous work in healthy controls showing changes in Glu following tDCS, and to assess relationships between task performance and neurometabolite change. Thus, study 1a aims at establishing a link between neurochemical changes and subsequent responses to tDCS, while study 1b, aims to corroborate that tDCS has indeed influenced neurochemical changes in FEP individuals. Further details in the sections below.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •for FEP Group (studies 1a and 1b):
- •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.
排除标准
- •for FEP Group (Studies 1a and 1b):
- •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.
- •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):
- •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.
- •Exclusion criteria for Health Matched Controls (Studies 1a and 1b):
- •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).
- •Inclusion Criteria for participants with lived experiences of psychosis (Study 2):
- •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 Criteria for participants with lived experiences of psychosis (Study 2):
- •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).
研究组 & 干预措施
Study1a and 1b
Study 1a: Will typically take place over 2-3 sessions (depending on participant's availability) spaced 1-7 days apart on average, and a 2-month follow up (FEP participants only). The first session (which could be split into two) will take approximately 4-5 hours in total consisting of several questionnaires, tasks, and up to 1 hour of MRI scanning. The second session will take approximately 2 hours and involve receiving tDCS stimulation and completing the cognitive task. The 2-month follow up will take up to 2 hours and involve assessing WM performance, symptoms scores (PANSS), CAPE-P15, quality of life and social and occupational functioning.
Study 1b: Will take place on the same day as the second part of study 1a and will involve one additional scan of up to an hour in duration.
干预措施: Transcranial direct current stimulation (tDCS) (Device)
Study1a and 1b
Study 1a: Will typically take place over 2-3 sessions (depending on participant's availability) spaced 1-7 days apart on average, and a 2-month follow up (FEP participants only). The first session (which could be split into two) will take approximately 4-5 hours in total consisting of several questionnaires, tasks, and up to 1 hour of MRI scanning. The second session will take approximately 2 hours and involve receiving tDCS stimulation and completing the cognitive task. The 2-month follow up will take up to 2 hours and involve assessing WM performance, symptoms scores (PANSS), CAPE-P15, quality of life and social and occupational functioning.
Study 1b: Will take place on the same day as the second part of study 1a and will involve one additional scan of up to an hour in duration.
干预措施: Magnetic Resonance Imaging (Diagnostic Test)
结局指标
主要结局
Measures of glutamate and GABA change (quantified using fMRS) during a working memory task
时间窗: Day 1, during fMRS scan, blocks with working memory task vs. blocks with control task.
Difference in glutamate and GABA levels between different phases/WM load in a working memory task (Study 1a).
Correlation between glutamate and GABA responses during a WM task and tDCS outcome (accuracy)
时间窗: within 1 week
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.
Correlation between glutamate and GABA responses during a WM task and tDCS outcome (reaction time)
时间窗: within 1 week
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.
Qualitative data analysis: Perceived cognitive impairments in psychosis
时间窗: Study day 2
Thematic analysis of impact of experiencing cognitive impairments (or perceived improvements) on individuals' lives in semi-structured interviews (Study 2).
Qualitative data analysis: Expectations and concerns around interventions that involve brain scanning and brain stimulation
时间窗: Study day 2
Themes (as outcome of a thematic analysis) that describe FEP participants' interests and expectations for future interventions designed to alleviate the impact of cognitive impairments, particularly regarding any future interventions using non-invasive brain stimulation methods (Study 2). Data will be collected in a semi-structured interview.
次要结局
- Difference in glutamate levels during working memory task pre- and post-tDCS stimulation(within 1 week (pre- and post-tDCS fMRS acquisitions; post-tDCS scan will take place immediately after tDCS stimulation))
- Difference in GABA levels during working memory task pre- and post-tDCS stimulation(within 1 week (pre- and post-tDCS fMRS acquisitions; post-tDCS scan will take place immediately after tDCS stimulation))
- Changes in other neurometabolites (tCR, GSH) during different phases of a working memory task.(Day 1, during fMRS scan, blocks with working memory task vs. blocks with control task.)
- Correlation of neurometabolite concentration changes (glutamate, GABA) during WM task and psychosis symptom severity (PANSS).(Within 2 months from first fMRS acquisition)
- Correlation of neurometabolite concentration changes (glutamate, GABA) during WM task and psychosis symptom severity (SPS).(Within 2 months from first fMRS acquisition)
- Correlation of neurometabolite concentration changes (glutamate, GABA) during WM task and psychosis symptom severity (CAPE-P15).(Within 2 months from first fMRS acquisition)
- Correlation of neurometabolite concentration changes (glutamate, GABA) during WM task and socio-occupational performance (PSP).(Within 2 months from first fMRS acquisition)
- Correlation of neurometabolite concentration changes (glutamate, GABA) during WM task and quality of life (WHOQOL-BREF).(Within 2 months from first fMRS acquisition)
- Correlation of neurometabolite concentration changes (glutamate, GABA) during WM task and experience of disability (WHODAS 2.0)(Within 2 months from first fMRS acquisition)
- Correlation of neurometabolite concentration changes (glutamate, GABA) during WM task and autism spectrum symptoms (AQ-50).(Within 2 months from first fMRS acquisition)
- Correlation of neurometabolite concentration levels (glutamate, GABA) during rest (static MRS) and accuracy in a change detection working memory task.(Within 2 months of MRS data acquisition.)
- Correlation of neurometabolite concentration levels (glutamate, GABA) during rest (static MRS) and performance in the forward/backward number span task.(Within 2 months of MRS data acquisition.)
- Correlation of neurometabolite concentration levels (glutamate, GABA) during rest (static MRS) and performance in the Corsi block test.(Within 2 months of MRS data acquisition.)
- Correlation of neurometabolite concentration levels (glutamate, GABA) during rest (static MRS) and processing speed.(Within 2 months of MRS data acquisition.)
- Correlation of neurometabolite concentration levels (glutamate, GABA) during rest (static MRS) and processing speed (simple and choice reaction time).(Within 2 months of MRS data acquisition.)
- Correlation of neurometabolite concentration levels (glutamate, GABA) during rest (static MRS) and processing speed/attentional shifting (Trail Making Test).(Within 2 months of MRS data acquisition.)
- Correlation of neurometabolite concentration levels (glutamate, GABA) during rest (static MRS) and cognitive control (interference).(Within 2 months of MRS data acquisition.)
- Correlation of neurometabolite concentration levels (glutamate, GABA) during rest (static MRS) and performance monitoring.(Within 2 months of MRS data acquisition.)
- Correlation of neurometabolite concentration levels (glutamate, GABA) during rest (static MRS) and meta-cognitive monitoring.(Within 2 months of MRS data acquisition.)
- Correlation between WM performance and visual imagery scores (VVIQ)(WM performance and VVIQ will be acquired within 10 days.)
- Correlation between WM performance and visual imagery scores (SUIS)(WM performance and SUIS will be acquired within 10 days.)