DIALOG: Understanding Disorganisation: A Language-focused Global Initiative in Psychosis

NCT06978465 | Not Yet Recruiting

• 1 other identifier: MP-18-2025-1203
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Disorganized speech, language and communication, also called 'formal thought disorder,' is a key part of severe mental illnesses like psychosis and mood disorders. When someone's communication is disorganized, it makes social interactions difficult, increases stigma and affect educational and employment opportunities. However, we do not know much about why this happens. This project, called DIALOG, aims to understand the brain's role in disorganization by studying everyday language use instead of traditional clinical ratings. The study will look at how our brain creates predictions during interactions and how these processes break down in psychosis. This international project also includes experts with personal experience of mental illness. The study will look at speech, thinking patterns, symptoms, and brain waves. The goal of the study is to see if brain waves are disrupted in psychosis, especially in language-related problems. Speech tasks, like describing pictures, talking about a significant event, and telling a story are administered. These tasks will be audio-recorded for analysis. Non-invasive brain imaging technologies such as Magnetoencephalography (MEG) and Magnetic Resonance Imaging (MRI) are utilized. MRI creates images of the brain's structure, while MEG records magnetic activity from neurons, shown as brain waves. The MRI machine uses a large magnet to create images, and MEG captures small magnetic field changes from brain activity. Participants will also undergo clinical and neurocognitive assessments. The study will combine Large Language Models (LLM) applied to speech recordings with large scale participant data from neuroimaging tools (MRI/MEG). The goal of DIALOG is to pioneer a computationally informed, molecular-to systems-level account of disorganisation, identifying the precise mechanisms that can be targeted with novel treatments. This project aims to gather speech and neuroimaging data from Montreal \[100 healthy volunteers and 50 patients with psychosis\], Groningen \[17 synaptic density PET scans\], Cardiff \[600 participants\] and Marburg \[1600 participants\] with schizophrenia, schizoaffective disorder or mood disorders and user acceptability data at Pavia and Melbourne.

Conditions

Psychosis; Schizophrenia Disorders; Bipolar Affective Disorder; Depressive Disorder

Keywords

disorganization; MEG; language disorder; neural activity; MRI; formal thought disorder; large language models; natural language processing; psycholinguistics

Outcome Measures

Primary Outcomes (3)

• Lexical Predictability measured from speech transcripts

  Lexical probabilities of each word along with surprisal, entropy/perplexity values based on the preceding context will be derived using locally implemented Language Models (Neural Networks) applied to recorded speech data. This is a numerical value derived from model-based estimates of word probability.

  baseline, 1 year

• Effective connectivity within the language network (functional MRI)

  Based on resting functional magnetic resonance imaging, language network dysconnectivity (specifically, the synaptic gain index for regional nodes within the connected network, a ratio without any specific unit) will be estimated. This is a numerical value derived from time series data.

  baseline, 1 year

• Beta-oscillatory power during sentence processing in MEG

  Magnetoencephalography recordings will be analysed along with time stamps from word stimuli to identify a specific frequency band (beta) and its power based on time-frequency transformations.

  baseline

Other Outcomes (3)

• Structural connectivity using diffusion tensor imaging

  baseline

• Functional Connectivity using Magnetoencephalography

  baseline

• Functional Connectivity using resting state functional MRI

  baseline

Study Arms (2)

Patients

For Montreal site as an exemplar: English or French speaking participants, male or female; age 18-65 years. Patients who have been previously diagnosed by their treating physician based on the Diagnostic and Statistical Manual of Mental Disorders 5 Edition (DSM 5) criteria for schizophrenia or schizoaffective disorder. Ethnically and socioeconomically diverse individuals from urban catchments. Women are under-represented in psychosis studies but across sexes disorganisation is equally severe. We aim for \>40% women in our samples via broader inclusion criteria not limited to schizophrenia

Healthy controls

English or French speaking participants, male or female; age 16-65 years. group-matched with the patients for age (within 2 years), and sex matched to patient sample; and have no personal or first-degree family history of Severe Mental Disorders (SMD).

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

From the Greater Montreal Area, participants will be recruited from inpatient/outpatient and community service caseloads held by consultant psychiatrists working at hospital clinics in CIUSSS de l'ouest-de-L'île-de-Montréal. Specifically, involving Douglas Mental Health University Institute: l'Étape Outpatient Clinic, Assertive Community Treatment Clinics, Intensive Psychosocial Rehab Clinic, Aire Ouvert and from Department of Psychiatry clinics at Lakeshore Hospital, St. Mary's Hospital and from the McGill University Health Centre (MUHC). Healthy Control participants will be recruited using research study posters placed on bulletin boards and using online study advertisements.

You may qualify if:

• Healthy Controls group-matched with the patients for age (within 2 years), and sex matched to patient sample; and have no personal or first-degree family history of Severe Mental Disorders (SMD).

You may not qualify if:

• Pregnancy; substance-induced psychosis with no SMD; neurological speech or auditory impairment, contraindication for MRI; Not able to give informed consent (if this is in doubt at the time of referral, we will formally test it). Not be able to speak French or English for clinical interactions; participants who are not proficient will be excluded.

Sponsors & Collaborators

• Douglas Mental Health University Institute: lead

Study Sites (1)

Douglas Mental Health University Institute

Montreal, Quebec, H4H1R3, Canada

Location

MeSH Terms

Conditions

Psychotic Disorders; Schizophrenia; Bipolar Disorder; Depressive Disorder; Language Disorders

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Bipolar and Related Disorders; Mood Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Lena Palaniyappan

  Douglas Mental Health University Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lena Palaniyappan, MD, PhD, FRCPC

CONTACT

5147616131; lena.palaniyappan@mcgill.ca

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 11, 2025
• First Posted: May 18, 2025
• Study Start: May 19, 2025
• Primary Completion (Estimated): April 30, 2030
• Study Completion (Estimated): April 30, 2030
• Last Updated: May 18, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: from year 5
• Access Criteria: Qualified researchers vetted by the data access committee; application with institutional ID, proposal for intended use and a curriculum vitae will be required.

Locations

CA (1)