Understanding Mechanisms of Synaptic Degeneration Underlying Clinical Symptoms in Patients With MDs and NDs.

NCT07234851 | Enrolling By Invitation

• 1 other identifier: IIBSP-NCP-2024-174
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Clinical Study A. Retrospective Neuropathological Study of Synapse dysfunction. This is a cross-sectional study of patients retrospectively collected from existing postmortem collections and from existing collections of iPSC-derived neurons. Postmortem tissue and iPSC-derived neurons from age and sex-matched unaffected volunteers without a MD or ND diagnosis are used as controls.

Conditions

Schizophrenia Disorder; Frontotemporal Dementia, Behavioral Variant; Major Depressive Disorder (MDD); Bipolar Disorder (BD); Alzheimer's Disease

Keywords

synapse; biomarker; induced pluripotent stem cells; mental disorder; neurodegenerative disorder; biofluids; psychiatric symptoms

Outcome Measures

Primary Outcomes (3)

• Synaptic gene dysregulation in schizophrenia and frontotemporal dementia

  A list of genes that are differentially expressed in schizophrenia and frontotemporal dementia compared to controls identified by RNA sequencing a) synaptic fractions isolated from postmortem tissue from the prefrontal cortex of autopsy cases with a clinical diagnosis of schizophrenia or confirmation of frontotemporal lobar degeneration and b) established iPSC clones from patients with a clinical diagnosis of schizophrenia or behavioural variant frontotemporal dementia.

  January 2025 to December 2029

• Molecular pathways related to synapse dysfunction in major depressive disorder, bipolar disorder and schizophrenia

  A list of biological processes that are enriched for proteins that are differentially expressed in major depressive disorder, bipolar disorder and schizophrenia compared to controls identified by proteomic analysis of synaptic fractions isolated from postmortem tissue from the prefrontal cortex of autopsy cases with a clinical diagnosis ofmajor depressive disorder, bipolar disorder or schizophrenia

  January 2025 to December 2029

• Impact of psychiatric and neurodegenerative disorders on synapse density in affected brain regions.

  Density of immunoreactive objects labelled with an antibody to pre and post synapse markers (vGlut1, PSD-95) in the prefrontal cortex, hippocampus and striatum from autopsy cases with a prior diagnosis of major depressive disorder, bipolar disorder, schizophrenia and unaffected controls and brain donors with neuropathological confirmation of Alzheimer's disease or frontotemporal dementia and unaffected controls.

  January 2028 to December 2029

Secondary Outcomes (1)

• Effects of psychotropic drugs on molecular pathways at the synapse related to major depressive disorder, schizophrenia and bipolar disorder

  July 2025 to December 2027

Study Arms (6)

Major depressive disorder

Cases that arrive to autopsy with a previous clinical diagnosis of major depressive disorder

Schizophrenia

Cases that arrive to autopsy with a previous clinical diagnosis of schizophrenia or iPSC clones derived from a patient with a previous clinical diagnosis of schizophrenia

Bipolar disorder

Cases that arrive to autopsy with a previous clinical diagnosis of major depressive disorder

Control

Cases that arrived to autopsy without a prior diagnosis of a neurodegenerative or psychiatric condition or iPSC clones derived from a cognitively unimpaired healthy volunteer

Alzheimer's disease

Cases that arrive to autopsy with neuropathological confirmation of Alzheimer's disease

frontotemporal dementia

Cases that arrive to autopsy with neuropathological confirmation of frontotemporal lobar degeneration

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Resource 1. Frozen samples and paraffin sections from necropsy tissue will be provided by the University of Basque Country, Bilbao. Autopsies are performed in the Basque Institute of Legal Medicine, Bilbao, Spain. Resource 2. Frozen samples and paraffin sections from necropsy tissue are recruited from the neurological tissue bank collection (IDIBAPS, Barcelona). Resource 3. A collection of human induced pluripotent stem cell clones from clinically and genetically well-phenotyped schizophrenia (Natural and Medical Sciences Institute), behavioural variant frontotemporal dementia patients (University of Eastern Finland) and unaffected controls (both sites) that have already been functionally characterised in previous studies.

You may qualify if:

• Age group: Midlife brain donors (age-at-death\>40).
• Sex distribution: % Female in schizophrenia (23%), major depressive disorder and controls (40%), bipolar disorder and controls (55%). These percentages match those typically found in these disorders.
• Antemortem diagnosis of schizophrenia (paranoid-subtype diagnoses only to minimise the impact of potential confounding factors on the results and ensure homogeneity across schizophrenia subjects), major depression or bipolar disorder. Diagnoses are confirrmed antemortem by a psychiatrist using Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria, as recorded in the deceased individuals' medical records.

You may not qualify if:

• For schizophrenia, cases displaying additional neurological or psychiatric conditions, such as histories of substance use disorder will be excluded. Postmortem delay \>24h (to minimise perimortem confounding variables potentially affecting tissue quality.
• Age group: Latelife brain donors (age-at-death\>50).
• Sex distribution: Alzheimer's disease (60%), frontotemporal dementia (65%). These percentages match those typically found in these diseases.
• Neuropathological confirmation of Alzheimer's disease or frontotemporal lobar degeneration (C9orf72 repeat expansion carrier)Alzheimer's disease
• Postmortem delay \>24h (to minimise perimortem confounding variables potentially affecting tissue quality.

Sponsors & Collaborators

• University of Eastern Finland: collaborator
• University of the Basque Country (UPV/EHU): collaborator
• Natural and Medical Sciences Institute (NMI): collaborator
• Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau: lead

Study Sites (1)

Research Institute Sant Pau

Barcelona, 08025, Spain

Location

Biospecimen

Retention: SAMPLES WITH DNA

brain tissue from necropsy, iPSC clones

MeSH Terms

Conditions

Schizophrenia; Pick Disease of the Brain; Depressive Disorder, Major; Bipolar Disorder; Alzheimer Disease; Mental Disorders; Neurodegenerative Diseases

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Frontotemporal Dementia; Frontotemporal Lobar Degeneration; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Depressive Disorder; Mood Disorders; Bipolar and Related Disorders; Tauopathies

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2025
• First Posted: November 19, 2025
• Study Start: February 1, 2025
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): September 30, 2029
• Last Updated: December 11, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Jan2025-Jan2035
• Access Criteria: clinical and research communities

Locations

ES (1)