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

Bipolar Disorder (BD), Depressive Disorder, Neurologic Disorders, Schizophrenia

Cognitive dysfunction, Executive function, Metacognition, Motivation, Social cognition, Transdiagnostic approach, High-level cognition, Longitudinal cognitive changes, Cognitive profiling, Differential diagnosis

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.

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.

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