Early Psychosis: Investigating Cognition

NCT07196423 | Recruiting

• 2 other identifiers: 24048226715/Z/22/Z
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

First Episode Psychosis (FEP); Psychosis

Keywords

psychosis; cognition; glutamate; transcranial direct current stimulation; fMRS; first episode psychosis; GABA; working memory; magnetic resonance spectroscopy

Outcome Measures

Primary Outcomes (5)

• 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).

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

• 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.

  within 1 week

• 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.

  within 1 week

• 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).

  Study day 2

• Qualitative data analysis: Expectations and concerns around interventions that involve brain scanning and brain stimulation

  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.

  Study day 2

Secondary Outcomes (21)

• 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

Other Outcomes (5)

• Alignment between objective cognitive measures and subjective experiences of cognitive impairments

  Study day 2

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

  Within 2 months of MRS data acquisition.

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

  Within 2 months of MRS data acquisition.

Study Arms (1)

Study1a and 1b

EXPERIMENTAL

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.

Device: Transcranial direct current stimulation (tDCS); Diagnostic Test: Magnetic Resonance Imaging

Interventions

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.

Study1a and 1b

Magnetic Resonance Imaging DIAGNOSTIC_TEST

Using a 7T Philips scanner with total scanning session lasting no more than 1 hour.

Study1a and 1b

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• Personal or family history of psychosis.
• Clinically significant neurological or psychiatric disorder.
• History of clinically significant head injury.

Sponsors & Collaborators

• University of Nottingham: lead
• Wellcome Trust: collaborator

Study Sites (1)

University of Nottingham

Nottingham, Nottinghamshire, NG7 2RD, United Kingdom

RECRUITING

Related Publications (27)

• Russo R, Wallace D, Fitzgerald PB, Cooper NR. Perception of comfort during active and sham transcranial direct current stimulation: a double blind study. Brain Stimul. 2013 Nov;6(6):946-51. doi: 10.1016/j.brs.2013.05.009. Epub 2013 Jun 25.

  PMID: 23835166 BACKGROUND

• Hill AT, Fitzgerald PB, Hoy KE. Effects of Anodal Transcranial Direct Current Stimulation on Working Memory: A Systematic Review and Meta-Analysis of Findings From Healthy and Neuropsychiatric Populations. Brain Stimul. 2016 Mar-Apr;9(2):197-208. doi: 10.1016/j.brs.2015.10.006. Epub 2015 Oct 23.

  PMID: 26597929 BACKGROUND

• Yamada Y, Sumiyoshi T. Neurobiological Mechanisms of Transcranial Direct Current Stimulation for Psychiatric Disorders; Neurophysiological, Chemical, and Anatomical Considerations. Front Hum Neurosci. 2021 Feb 4;15:631838. doi: 10.3389/fnhum.2021.631838. eCollection 2021.

  PMID: 33613218 BACKGROUND

• Morey-Nase C, Phillips LJ, Bryce S, Hetrick S, Wright AL, Caruana E, Allott K. Subjective experiences of neurocognitive functioning in young people with major depression. BMC Psychiatry. 2019 Jul 4;19(1):209. doi: 10.1186/s12888-019-2197-1.

  PMID: 31272419 BACKGROUND

• Reinhart RM, Zhu J, Park S, Woodman GF. Medial-Frontal Stimulation Enhances Learning in Schizophrenia by Restoring Prediction Error Signaling. J Neurosci. 2015 Sep 2;35(35):12232-40. doi: 10.1523/JNEUROSCI.1717-15.2015.

  PMID: 26338333 BACKGROUND

• Reinhart RM, Zhu J, Park S, Woodman GF. Synchronizing theta oscillations with direct-current stimulation strengthens adaptive control in the human brain. Proc Natl Acad Sci U S A. 2015 Jul 28;112(30):9448-53. doi: 10.1073/pnas.1504196112. Epub 2015 Jun 29.

  PMID: 26124116 BACKGROUND

• Pilloni G, Charvet LE, Bikson M, Palekar N, Kim MJ. Potential of Transcranial Direct Current Stimulation in Alzheimer's Disease: Optimizing Trials Toward Clinical Use. J Clin Neurol. 2022 Jul;18(4):391-400. doi: 10.3988/jcn.2022.18.4.391.

  PMID: 35796264 BACKGROUND

• Pena-Gomez C, Sala-Lonch R, Junque C, Clemente IC, Vidal D, Bargallo N, Falcon C, Valls-Sole J, Pascual-Leone A, Bartres-Faz D. Modulation of large-scale brain networks by transcranial direct current stimulation evidenced by resting-state functional MRI. Brain Stimul. 2012 Jul;5(3):252-263. doi: 10.1016/j.brs.2011.08.006. Epub 2011 Sep 5.

  PMID: 21962981 BACKGROUND

• Moran EK, Gold JM, Carter CS, MacDonald AW 3rd, Ragland JD, Silverstein SM, Luck SJ, Barch DM. Both unmedicated and medicated individuals with schizophrenia show impairments across a wide array of cognitive and reinforcement learning tasks. Psychol Med. 2022 Apr;52(6):1115-1125. doi: 10.1017/S003329172000286X. Epub 2020 Aug 17.

  PMID: 32799938 BACKGROUND

• Mondino M, Poulet E, Brunelin J. Moving to accelerated protocols of tDCS in schizophrenia: A case report. Brain Stimul. 2021 Jul-Aug;14(4):822-824. doi: 10.1016/j.brs.2021.05.006. Epub 2021 May 19. No abstract available.

  PMID: 34022429 BACKGROUND

• Koolschijn RS, Emir UE, Pantelides AC, Nili H, Behrens TEJ, Barron HC. The Hippocampus and Neocortical Inhibitory Engrams Protect against Memory Interference. Neuron. 2019 Feb 6;101(3):528-541.e6. doi: 10.1016/j.neuron.2018.11.042. Epub 2018 Dec 20.

  PMID: 30581011 BACKGROUND

• Hunter MA, Coffman BA, Gasparovic C, Calhoun VD, Trumbo MC, Clark VP. Baseline effects of transcranial direct current stimulation on glutamatergic neurotransmission and large-scale network connectivity. Brain Res. 2015 Jan 12;1594:92-107. doi: 10.1016/j.brainres.2014.09.066. Epub 2014 Oct 12.

  PMID: 25312829 BACKGROUND

• Heimrath K, Brechmann A, Blobel-Luer R, Stadler J, Budinger E, Zaehle T. Transcranial direct current stimulation (tDCS) over the auditory cortex modulates GABA and glutamate: a 7 T MR-spectroscopy study. Sci Rep. 2020 Nov 18;10(1):20111. doi: 10.1038/s41598-020-77111-0.

  PMID: 33208867 BACKGROUND

• Bystad M, Storo B, Gundersen N, Wiik IL, Nordvang L, Gronli O, Rasmussen ID, Aslaksen PM. Can accelerated transcranial direct current stimulation improve memory functions? An experimental, placebo-controlled study. Heliyon. 2020 Oct 3;6(10):e05132. doi: 10.1016/j.heliyon.2020.e05132. eCollection 2020 Oct.

  PMID: 33033765 BACKGROUND

• Valiengo LDCL, Goerigk S, Gordon PC, Padberg F, Serpa MH, Koebe S, Santos LAD, Lovera RAM, Carvalho JB, van de Bilt M, Lacerda ALT, Elkis H, Gattaz WF, Brunoni AR. Efficacy and Safety of Transcranial Direct Current Stimulation for Treating Negative Symptoms in Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. 2020 Feb 1;77(2):121-129. doi: 10.1001/jamapsychiatry.2019.3199.

  PMID: 31617873 RESULT

• Ullsperger M, Danielmeier C, Jocham G. Neurophysiology of performance monitoring and adaptive behavior. Physiol Rev. 2014 Jan;94(1):35-79. doi: 10.1152/physrev.00041.2012.

  PMID: 24382883 RESULT

• Poreisz C, Boros K, Antal A, Paulus W. Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients. Brain Res Bull. 2007 May 30;72(4-6):208-14. doi: 10.1016/j.brainresbull.2007.01.004. Epub 2007 Jan 24.

  PMID: 17452283 RESULT

• Orlov ND, Tracy DK, Joyce D, Patel S, Rodzinka-Pasko J, Dolan H, Hodsoll J, Collier T, Rothwell J, Shergill SS. Stimulating cognition in schizophrenia: A controlled pilot study of the effects of prefrontal transcranial direct current stimulation upon memory and learning. Brain Stimul. 2017 May-Jun;10(3):560-566. doi: 10.1016/j.brs.2016.12.013. Epub 2016 Dec 28.

  PMID: 28057452 RESULT

• Nakahara T, Tsugawa S, Noda Y, Ueno F, Honda S, Kinjo M, Segawa H, Hondo N, Mori Y, Watanabe H, Nakahara K, Yoshida K, Wada M, Tarumi R, Iwata Y, Plitman E, Moriguchi S, de la Fuente-Sandoval C, Uchida H, Mimura M, Graff-Guerrero A, Nakajima S. Glutamatergic and GABAergic metabolite levels in schizophrenia-spectrum disorders: a meta-analysis of 1H-magnetic resonance spectroscopy studies. Mol Psychiatry. 2022 Jan;27(1):744-757. doi: 10.1038/s41380-021-01297-6. Epub 2021 Sep 28.

  PMID: 34584230 RESULT

• Kirschner H, Klein TA. Beyond a blunted ERN - Biobehavioral correlates of performance monitoring in schizophrenia. Neurosci Biobehav Rev. 2022 Feb;133:104504. doi: 10.1016/j.neubiorev.2021.12.027. Epub 2021 Dec 16.

  PMID: 34922988 RESULT

• Katz B, Au J, Buschkuehl M, Abagis T, Zabel C, Jaeggi SM, Jonides J. Individual Differences and Long-term Consequences of tDCS-augmented Cognitive Training. J Cogn Neurosci. 2017 Sep;29(9):1498-1508. doi: 10.1162/jocn_a_01115. Epub 2017 Mar 2.

  PMID: 28253083 RESULT

• Habtewold TD, Rodijk LH, Liemburg EJ, Sidorenkov G, Boezen HM, Bruggeman R, Alizadeh BZ. A systematic review and narrative synthesis of data-driven studies in schizophrenia symptoms and cognitive deficits. Transl Psychiatry. 2020 Jul 21;10(1):244. doi: 10.1038/s41398-020-00919-x.

  PMID: 32694510 RESULT

• Gold JM. Cognitive deficits as treatment targets in schizophrenia. Schizophr Res. 2004 Dec 15;72(1):21-8. doi: 10.1016/j.schres.2004.09.008.

  PMID: 15531404 RESULT

• Bikson M, Grossman P, Thomas C, Zannou AL, Jiang J, Adnan T, Mourdoukoutas AP, Kronberg G, Truong D, Boggio P, Brunoni AR, Charvet L, Fregni F, Fritsch B, Gillick B, Hamilton RH, Hampstead BM, Jankord R, Kirton A, Knotkova H, Liebetanz D, Liu A, Loo C, Nitsche MA, Reis J, Richardson JD, Rotenberg A, Turkeltaub PE, Woods AJ. Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Brain Stimul. 2016 Sep-Oct;9(5):641-661. doi: 10.1016/j.brs.2016.06.004. Epub 2016 Jun 15.

  PMID: 27372845 RESULT

• Au, J., Karsten, C., Buschkuehl, M., & Jaeggi, S. M. (2017). Optimizing transcranial direct current stimulation protocols to promote long-term learning. Journal of Cognitive Enhancement, 1(1), 65-72.

  RESULT

• Antal A, Alekseichuk I, Bikson M, Brockmoller J, Brunoni AR, Chen R, Cohen LG, Dowthwaite G, Ellrich J, Floel A, Fregni F, George MS, Hamilton R, Haueisen J, Herrmann CS, Hummel FC, Lefaucheur JP, Liebetanz D, Loo CK, McCaig CD, Miniussi C, Miranda PC, Moliadze V, Nitsche MA, Nowak R, Padberg F, Pascual-Leone A, Poppendieck W, Priori A, Rossi S, Rossini PM, Rothwell J, Rueger MA, Ruffini G, Schellhorn K, Siebner HR, Ugawa Y, Wexler A, Ziemann U, Hallett M, Paulus W. Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Clin Neurophysiol. 2017 Sep;128(9):1774-1809. doi: 10.1016/j.clinph.2017.06.001. Epub 2017 Jun 19.

  PMID: 28709880 RESULT

• Wright, A. L., Phillips, L. J., Bryce, S., Morey-Nase, C., & Allott, K. (2019). Subjective experiences of cognitive functioning in early psychosis: a qualitative study. Psychosis, 11(1), 63-74.

  RESULT

Related Links

• Study website

MeSH Terms

Conditions

Psychotic Disorders

Interventions

Transcranial Direct Current Stimulation; Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques; Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Claudia Danielmeier, PhD

  University of Nottingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Claudia Danielmeier, PhD

CONTACT

+44 115 84 66360; claudia.danielmeier@nottingham.ac.uk

Mohammad Z U H Katshu, PhD

CONTACT

+44 1158231287; mohammad.katshu@nottingham.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All participants in Study 1 will receive tDCS non-invasive brain stimulation. Participants in Study 2 will take part in an interview without any intervention.

Study Record Dates

• First Submitted: May 2, 2025
• First Posted: September 29, 2025
• Study Start: February 9, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be shared after publication of the study results. Data shared in OSF and UK Data Service do not have a time limitation.
• Access Criteria: IPD from study 1a and b will be uploaded to OSF. Interview data will be deposited with the UK data service.

Locations

GB (1)