Translational Investigation of the Glutamatergic and GABAergic System in Schizophrenia

NCT04655235 | Recruiting

• 1 other identifier: 19-201
• Study Type: observational
• Target: 600
• Locations: 1 country
• Sites: 3

Brief Summary

In the last years, the imbalance between excitatory and inhibitory neuronal activity has come to the fore as a possible molecular disease mechanism of schizophrenia . Pharmacological studies have suggested different fMRI and EEG markers of that molecular dysfunction (resting state connectivity changes, auditory mismatch and steady state deficits). However, previous research is inconclusive regarding their genetic basis, their reliability, inter-individual relationship as well as disease specificity. Therefore, in this study we aim at estimating the effect sizes, test-retest-reliability and clinical correlates of the respective markers in a comparative fashion in patients with schizophrenia, their relatives and healthy control subject. To assess their molecular validity, we will assess their relationship with glutamatergic and GABAergic genotypes and cellular disease models. The proof of such a relation would give the opportunity of detecting a glutamatergic and GABAergic imbalance throughout non-invasive imaging. Furthermore, it would help deepening our understanding of the molecular pathophysiology of mental disorders which will be essential for the development of more effective drugs.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (2)

• MMN

  Mismatch negativity amplitude

  1 day to maximum 3 years

• ASSR Power

  40-Hz auditory steady state response spectral power

  1 day to maximum 3 years

Secondary Outcomes (19)

• ASSR Phase Locking

  1 day to maximum 3 years

• Functional connectivity

  1 day to maximum 3 years

• Psychopathology as assessed with the PANSS

  1 day to maximum 3 years

• Psychopathology as assessed with the BPP

  1 day to maximum 3 years

• Psychopathology as assessed with the CGI

  1 day to maximum 3 years

Study Arms (3)

patients with schizophrenia

200 patients with a DSM 5- diagnosis of schizophrenia

Genetic: Genotyping

healthy relatives of patients with schizophrenia

200 healthy relatives of the patients with schizophrenia

Genetic: Genotyping

healthy control subjects

healthy control subjects without relatives with mental disorders

Genetic: Genotyping

Interventions

Genotyping GENETIC

Genotyping of glutamatergic, GABAergic, dopaminergic and other CNS-related genes

healthy control subjects; healthy relatives of patients with schizophrenia; patients with schizophrenia

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The patients will be recruited from the Department of Psychiatry, Psychotherapy and Psychosomatics at Uniklinik RWTH Aachen, Alexianer Krankenhaus and the psychiatric institutions of Katharina Kasper ViaNobis GmbH in Gangelt. The patients will be asked whether their healthy relatives may be contacted in terms of study participation. Additionally, they will be handed the study teams' contact details. Relatives suffering from the same psychiatric disorder as the patients can also be included and will be contacted the same way as the healthy relatives. Healthy controls will be searched via notices in the Uniklinik RWTH Aachen. Furthermore, we will contact former study participants that have given their consent to being contacted for a renewed study participation.

You may qualify if:

• diagnosis of schizophrenia according to DSM-5
• aged 18 to 80
• being mentally and contractually capable to give their consent to study participation

You may not qualify if:

• pregnancy
• structural neurological disease
• a further psychiatric comorbidity that dominates in the clinical appearance
• HEALTHY PARTICIPANTS
• aged 18 to 80
• being mentally and contractually capable to give their consent to study participation
• pregnancy
• structural neurological disease
• psychiatric disorder
• for healthy controls: psychiatric disorders in the family history of first-degree relatives

Sponsors & Collaborators

• RWTH Aachen University: lead

Study Sites (3)

Alexianer Hospital

Aachen, Northrine-Westphalia, 52062, Germany

RECRUITING

ViaNobis - Die Fachklinik

Gangelt, Northrine-Westphalia, 52538, Germany

RECRUITING

University hospital RWTH Aachen

Aachen, 52525, Germany

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

First visit: 10 mL EDTA-blood for genetic analysis and 20 mL blood for serological analysis Second visit: 20 mL EDTA-blood for reprogramming of iPSC

MeSH Terms

Conditions

Schizophrenia

Interventions

Genotype

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Genetic Phenomena

Study Officials

• Arnim Gaebler, M.D.

  Uniklinik RWTH Aachen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Arnim Gaebler, M.D.

CONTACT

+49 241 800; agaebler@ukaachen.de

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Jun.-Prof. Dr. med. Arnim Johannes Gaebler

Study Record Dates

• First Submitted: November 28, 2020
• First Posted: December 7, 2020
• Study Start: October 1, 2021
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): March 1, 2030
• Last Updated: March 14, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3)