Characterization of High-Level Cognitive Impairments in Patients With Neuropsychiatric Disorders (COGPSY)

Characterization of High-level Cognitive Impairments in Patients With Neuropsychiatric Disorders

Neuropsychiatric disorders are extremely common, severe, and disabling conditions. In the field of psychiatry, they notably include schizophrenia, mood disorders (depressive and bipolar disorders), autism spectrum or neurodevelopmental disorders, obsessive-compulsive disorder, eating disorders, and personality disorders. In the field of neurology, one can cite neurodegenerative diseases (such as Alzheimer's disease, but also frontotemporal dementia or Parkinson's disease, which often represent frequent and challenging differential diagnoses of psychiatric disorders), focal neurological lesions (notably strokes and tumors), or epilepsy.

Cognitive impairments are present in nearly all neuropsychiatric disorders and contribute significantly to disability.

While impairments in working memory and attention, executive functions, and social cognition have been relatively well studied, other cognitive domains remain largely unexplored in these populations. This is particularly the case for various aspects of motivation, metacognition, conscious access, or causal (Bayesian) inference.

Although these domains likely play an important role in prognosis, no consensus currently exists regarding the methods for evaluating these functions.

The main objective of this study is to define a multidimensional, transdiagnostic atlas of high-level cognitive impairments-both specific and shared-across severe psychiatric disorders (notably schizophrenia, depressive disorder, bipolar disorder, autism spectrum or neurodevelopmental disorders, and obsessive-compulsive disorder) and neurological disorders (notably neurodegenerative diseases, focal neurological lesions, and epilepsy), by comparing them to healthy volunteers.

The investigators also aim to investigate the progression of cognitive impairments over time, across different phases of illness (symptom stabilization or exacerbation) or therapeutic intervention, through longitudinal follow-up of patients being monitored within the recruiting center.

Finally, in a more exploratory manner, the investigators aim to investigate the neural correlates of the identified cognitive impairments.

Study Overview

• Status: Recruiting
• Conditions: Depressive Disorder; Schizophrenia; Neurologic Disorders; Bipolar Disorder (BD)
• Intervention / Treatment: Behavioral: Cognitive assessment; Behavioral: Brain MRI (optional); Behavioral: Electroencephalography (optional); Behavioral: Magnetoencephalography (optional)

Detailed Description

This study aims to construct a multidimensional, transdiagnostic atlas of high-level cognitive alterations across a range of severe neuropsychiatric conditions. These include schizophrenia, depressive disorders, bipolar disorder, autism spectrum or neurodevelopmental disorders, and obsessive-compulsive disorder, as well as neurological disorders such as neurodegenerative diseases, focal neurological lesions, and epilepsy. Cognitive performance in these groups will be compared to that of healthy volunteers in order to identify both disorder-specific and shared impairments.

Beyond this primary aim, the study seeks to refine and optimize the cognitive assessment tools used. Tests will be progressively adapted to be more ergonomic, shorter, and better suited for populations with neuropsychiatric conditions. This includes enhancing their intuitiveness, informativeness, and adaptability for digital platforms (e.g., tablet or mobile), while maintaining prior validation and calibration in healthy populations. The adaptation process will be informed by participant feedback and interim analysis.

The study will also examine how cognitive impairments evolve over time and with clinical changes, in participants undergoing psychiatric or neurological follow-up. Repeated cognitive evaluations will be scheduled in relation to clinical evolution, particularly before and after therapeutic interventions used in standard care, such as pharmacological treatment, non-invasive neurostimulation, psychotherapy, or psychoeducation.

In addition, the neural correlates of cognitive impairments will be explored using existing clinical brain imaging when available. Participants without prior imaging may be invited to undergo MRI scans, potentially including additional sequences such as DTI or functional MRI, without contrast administration. Complementary assessments using EEG or MEG may also be conducted, employing classical analyses such as event-related potentials and time-frequency analysis.

In some cases, causal inferences may be drawn by linking specific brain lesions in neurological patients to observed cognitive impairments. Finally, the study will explore whether selected cognitive tests could assist in differential diagnosis between psychiatric and neurological conditions, particularly neurodegenerative disorders.

This is a prospective, multicenter interventional study involving both healthy individuals and patients. It is classified as a minimal-risk, low-burden study and is designed to support the development of a comprehensive, comparative database of high-level cognitive dysfunctions across severe neuropsychiatric disorders.

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jacob DHOTE, Dr; Phone Number: +33 145658177; Email: j.dhote@ghu-paris.fr
• Study Contact Backup: Name: Fabien VINCKIER, Pr; Email: F.VINCKIER@ghu-paris.fr

Study Locations

• France
  • Paris, France
    • Not yet recruiting
    • Hôpital Fondation Adolphe de Rothschild
    • Contact: Pierre BOURDILLON, Dr
  • Paris, France, 75013
    • Recruiting
    • Departement of Adult Psychiatry, GH Pitié Salpétrière
    • Contact: Philippe FOSSATI, Pr; Phone Number: +33 0142162870; Email: philippe.fossati@aphp.fr
  • Paris, France, 75014
    • Recruiting
    • Groupe hospitalo-universitaire Paris Psychiatrie et Neurosciences
    • Contact: Fabien VINCKIER, Pr; Email: F.VINCKIER@ghu-paris.fr
    • Contact: Jacob DHOTE, Dr; Phone Number: 33 + 0145658177; Email: j.dhote@ghu-paris.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

For patients:

• Aged over 18 years
• Diagnosed with a psychiatric disorder according to ICD-10 by a psychiatrist (F10-F98) or diagnosed with a neurological disorder according to ICD-10 by a neurologist (G00-G99)
• Provided written informed consent
• Affiliated with a social security scheme

For healthy volunteers:

• Aged over 18 years
• Provided written informed consent
• Affiliated with a social security scheme

Exclusion Criteria:

For healthy volunteers:

• Current diagnosis of a psychiatric disorder according to ICD-10 (F20-F98) or current prescription of a psychotropic medication, or diagnosis of a neurological disorder according to ICD-10 (G00-G99)
• History of depression (F32)
• Substance use disorder (excluding tobacco)
• Neurological history (e.g., stroke, coma, epilepsy, neuroinflammatory or neurodegenerative disease) or identified cognitive disorder
• Inability to complete cognitive testing (e.g., due to motor or sensory impairment)

For participants undergoing MRI (without contrast agent):

• Presence of MRI contraindications: non-MRI-compatible pacemaker, heart valve, implant, or metallic foreign body
• Pregnancy at the time of MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cognitive assessment; Neuropsychological assessment assessing different cognitive dimensions (e.g., motivation and decision-making, metacognition, access to consciousness, Bayesian inference)

Behavioral: Cognitive assessment; This intervention consists of computerized neuropsychological assessments designed to evaluate high-level cognitive impairments. The tests cover various cognitive dimensions including motivation, metacognition, conscious access, and Bayesian causal inference. These assessments are performed using computers or tablets, aiming to build a multidimensional cognitive atlas comparing patients with severe psychiatric and neurological conditions to healthy volunteers. The tests will be progressively optimized for usability and adapted to the specific difficulties faced by patients. For some participants, additional brain imaging (MRI without contrast, EEG, MEG) may be offered optionally to identify neural correlates of cognitive deficits.; Behavioral: Brain MRI (optional); Brain MRI without contrast perform at one visit to identify neural correlates of cognitive deficits; Behavioral: Electroencephalography (optional); Electroencephalography performed at one visit; Behavioral: Magnetoencephalography (optional); Magnetoencephalography performed at one visit

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Performance scores on validated computerized neuropsychological tasks assessing high-level cognitive domains	Cognitive functions will be assessed using a battery of validated computerized neuropsychological tasks. The specific tasks will be selected and optimized for each target population, based on prior validation in healthy controls. Performance scores (e.g., accuracy, reaction time, decision-making indices) will be compared between patients with severe neuropsychiatric disorders and healthy volunteers.	Baseline, and up to one year after baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optimization of performance scores on validated computerized neuropsychological tasks	A battery of validated computerized neuropsychological tasks will be progressively optimized based on participant feedback and interim analyses. The convergence of performance scores will be evaluated over multiple trials to refine the tests, ensuring suitability for populations with severe neuropsychiatric or neurological disorders.	Baseline, and up to one year after baseline
Change from baseline in performance scores on validated computerized neuropsychological tasks	Changes in cognitive performance scores over time among patients undergoing standard clinical care, including therapeutic interventions. Cognitive evaluations will be repeated before and after major clinical events or treatment changes to assess cognitive stability or improvement	Baseline, and up to one year after baseline
Structural and functional MRI	Structural and functional MRI will be used to generate brain maps measuring gray matter volume (VBM), connectivity (DTI), and regional activation (fMRI). These MRI markers will be related to cognitive performance scores obtained during cognitive testing. Participation in MRI assessments is optional.	At MRI visit, between baseline and study completion (up to 10 years for patients; up to 1 year for healthy volunteers)
Electroencephalography (EEG) event-related potentials (ERP) during cognitive tasks	EEG recordings will be performed during cognitive tasks. Event-related potentials (ERP) will be analyzed to investigate neurophysiological correlates of cognitive performance. These markers will be related to cognitive alterations in patients and compared across groups. Participation in EEG assessments is optional.	At EEG visits, from baseline through study completion (up to 10 years for patients; up to 1 year for healthy volunteers)
EEG time-frequency analyses during cognitive tasks	EEG recordings will be performed during cognitive tasks. Time-frequency analyses will be used to investigate neurophysiological correlates of cognitive performance. These markers will be related to cognitive alterations in patients and compared across groups. Participation in EEG assessments is optional.	At EEG visits, from baseline through study completion (up to 10 years for patients; up to 1 year for healthy volunteers)
Magnetoencephalography (MEG) event-related potentials (ERP) during cognitive tasks	MEG recordings will be performed during cognitive tasks. Event-related potentials (ERP) will be analyzed to investigate neurophysiological correlates of cognitive performance. These ERP markers will be related to cognitive alterations in patients and compared across groups. Participation in MEG assessments is optional.	At MEG visits, from baseline through study completion (up to 10 years for patients; up to 1 year for healthy volunteers)
MEG time-frequency analyses during cognitive tasks	MEG recordings will be performed during cognitive tasks. Time-frequency analyses will be used to investigate neurophysiological correlates of cognitive performance. These markers will be related to cognitive alterations in patients and compared across groups. Participation in MEG assessments is optional.	At MEG visits, from baseline through study completion (up to 10 years for patients; up to 1 year for healthy volunteers)
Predictive capacity of cognitive performance scores for differential diagnosis	Validated cognitive performance tests will be used to evaluate patients longitudinally. The evolution of scores over time will be analyzed to determine the ability of these tests to discriminate between common differential diagnoses, such as frontotemporal dementia and depression. This outcome reflects the predictive capacity of cognitive tests for the final clinical diagnosis.	Baseline, and up to one year after baseline

Collaborators and Investigators

• Sponsor: Centre Hospitalier St Anne
• Collaborators: Institut du Cerveau et de la Moelle (ICM Institute)
• Investigators: Principal Investigator: Pierre BOURDILLON, Dr, Hôpital Fondation Adolphe de Rothschild

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2024
• Primary Completion (Estimated): March 1, 2039
• Study Completion (Estimated): March 1, 2039

Study Registration Dates

• First Submitted: June 13, 2025
• First Submitted That Met QC Criteria: December 16, 2025
• First Posted (Actual): December 19, 2025

Study Record Updates

• Last Update Posted (Actual): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Motivation; Executive function; Metacognition; Social cognition; Cognitive dysfunction; Differential diagnosis; Transdiagnostic approach; High-level cognition; Longitudinal cognitive changes; Cognitive profiling
• Additional Relevant MeSH Terms: Bipolar and Related Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Mood Disorders; Schizophrenia; Cognitive Dysfunction; Depressive Disorder; Bipolar Disorder; Nervous System Diseases; Investigative Techniques; Diagnostic Techniques and Procedures; Diagnosis; Behavioral Disciplines and Activities; Psychological Tests; Diagnostic Techniques, Neurological; Electrodiagnosis; Neuropsychological Tests; Magnetometry; Mental Status and Dementia Tests; Magnetoencephalography
• Other Study ID Numbers: D22-P009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data obtained from medical visits (clinical informations, cognitive data, medical imaging, and EEG/MEG recordings) will be kept, coded and archived for a period of two years after the last publication of the research results or until the final research report is signed. These can be used later for collaborative research (academic and/or industrial partners) in the European Union (EU) and/or abroad exclusively for scientific purposes.
• IPD Sharing Time Frame: The data obtained from medical visits (clinical informations, cognitive data, medical imaging, and EEG/MEG recordings) will be kept, coded and archived for a period of two years after the last publication of the research results or until the final research report is signed.

IPD Sharing Access Criteria

The data can be used for collaborative research (academic and/or industrial partners) in the European Union (EU) and/or abroad exclusively for scientific purposes. Any party must contact the sponsor, who has full property of the data.

In case of requested transfer of the anonymized database resulting from this research abroad (outside the EU), the sponsor will request information regarding data storage and management, to make sure that the other party will be able to ensure a level of security equivalent to French or European Union law.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No