Evaluation of the Role of Neurodegeneration in Schizophrenia

NCT05257720 | Completed

• 1 other identifier: 21-667
• Study Type: observational
• Target: 178
• Locations: 1 country
• Sites: 1

Brief Summary

Schizophrenia is a progressive psychiatric disorder with a lifetime prevalence of 1%, its etiology is not fully understood, and it progresses with relapses. There are significant differences between patients in the age of onset, frequency of attacks, response to treatment, and clinical course of the disease. Failure to respond adequately to treatment is defined as resistance to treatment and poses a great challenge in the clinical management of the disease, but the exact cause of treatment resistance has not been clarified yet. Neurodevelopmental hypothesis, neurodegenerative hypothesis, stress-diathesis hypothesis are some of them. In the neurodegenerative hypothesis, it is thought that biochemical changes cause chronic and progressive disorders of the nervous system, and schizophrenia is considered as one of these disorders. S100B, one of the biomarkers released from the central nervous system, is a glycoprotein synthesized by astrocytes; At low concentration, it ensures neuron survival, while at high concentration it causes neuronal cell apoptosis and is associated with neurodegeneration. GFAP on the other hand, can be measured in serum in proportion to the degree of damage by passing into the bloodstream as a result of astrocyte damage. It has been shown that these markers are associated with neurodegenerative diseases, autoimmune diseases and cerebrovascular pathologies and can be measured at a significant level in the blood. As far as is known, neurodegeneration has been found in patients with schizophrenia; however, there are not enough studies in the literature regarding the relationship of this neurodegeneration with treatment response and resistance. In recent years, many biomarker studies related to schizophrenia have been conducted. These studies continue in many different areas such as the early diagnosis of schizophrenia, the treatments to be applied after diagnosis, the response to the treatment given, and the clinical course of the disease, but no biomarker indicating the desired results has yet been found. In this study, measurement of s100B and GFAP serum levels in patients with treatment-resistant schizophrenia, remission schizophrenia and healthy controls, and evaluation of their relationship with response to treatment; Thus, it is aimed to investigate these points that have not been fully elucidated in the pathogenesis of schizophrenia and their use as biomarkers in predicting the response to treatment.

Conditions

Schizophrenia

Keywords

schizophrenia, neurodegeneration, s100b, gfap

Outcome Measures

Primary Outcomes (2)

• serum GFAP levels

  It is planned to measure serum GFAP levels by ELISA method.

  6 months

• serum S100 B protein levels

  It is planned to measure serum S100 B protein levels by ELISA method.

  6 months

Study Arms (3)

Remission

Patient with schizophrenia in remission

Diagnostic Test: GFAP, S100B

treatment resistant

patient with treatment resistant schizophrenia

Diagnostic Test: GFAP, S100B

controls

healthy controls

Diagnostic Test: GFAP, S100B

Interventions

GFAP, S100B DIAGNOSTIC_TEST

It is planned to measure serum GFAP and S100 B protein levels by ELISA method.

Remission; controls; treatment resistant

Eligibility Criteria

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

Study Population

Our research was planned to recruit 60 patients with schizophrenia in remission, 60 patients with treatment-resistant schizophrenia, and 60 healthy volunteers, followed by Mazhar Osman Bakırköy Psychiatry Training and Research Hospital TRSMs and/or inpatient units, according to the inclusion and exclusion criteria. Consent will be obtained from all patients and healthy volunteers participating in the study with an informed consent form that provides information about the purpose of the study.

You may qualify if:

• Being between the ages of 18-65
• Being at least primary school graduate
• Not having mental retardation
• Not having visual and hearing problems that affect communication
• Having a diagnosis of schizophrenia according to DSM-5 criteria
• Absence of comorbid psychiatric disease
• Systemic and/or systemic disease. or neurological (such as hypertension, diabetes mellitus, infection, dementia, epilepsy, Parkinson's disease, cardiovascular, renal, urological, hepatic, pulmonary, genetic, endocrine diseases, nutritional disorders, intoxications, operations, and other organic disorders), S100B and GFAP levels No medical condition known to affect it
• No history of head trauma
• No alcohol and/or substance use disorder
• Body mass index (BMI) \> 18 kg/m2 , BMI \< 25 kg/m2
• Not having been diagnosed with metabolic syndrome
• \. and/or No 2nd degree relatives with schizophrenia and/or a similar psychiatric disorder
• After being informed about the study,
• Being between the ages of 18-65
• Being at least primary school graduate

You may not qualify if:

• Not between the ages of 18-65
• Having a diagnosis of mental retardation
• Having vision and/or hearing problems that affect communication
• Presence of psychiatric illness
• First and/or second degree relatives between schizophrenia and/or another psychiatric disease diagnosis
• Systemic and/or neurological (hypertension, diabetes mellitus, infection, dementia, epilepsy, parkinson's disease, cardiovascular, renal, urological, hepatic, pulmonary, genetic, endocrine diseases, nutritional disorders, intoxications, operations and other organic disorders), presence of medical conditions known to adversely affect S100B and GFAP levels
• Presence of non-psychiatric drug use
• Presence of head trauma
• Presence of alcohol and/or substance use disorder
• Body mass index (BMI) \> 25 kg /m2
• Metabolic syndrome being diagnosed as Having schizophrenia and/or a similar psychiatric disorder in 1st and/or 2nd degree relatives
• After being informed about the study, the patient and/or his guardian or healthy control did not give consent to participate in the study.

Sponsors & Collaborators

• Istanbul Saglik Bilimleri University: lead

Study Sites (1)

T.C. Sağlik Bilimleri Üniversitesi

Istanbul, 34876, Turkey (Türkiye)

Location

Related Publications (11)

• Walker E, Kestler L, Bollini A, Hochman KM. Schizophrenia: etiology and course. Annu Rev Psychol. 2004;55:401-30. doi: 10.1146/annurev.psych.55.090902.141950.

  PMID: 14744221 BACKGROUND

• Khavari B, Cairns MJ. Epigenomic Dysregulation in Schizophrenia: In Search of Disease Etiology and Biomarkers. Cells. 2020 Aug 5;9(8):1837. doi: 10.3390/cells9081837.

  PMID: 32764320 BACKGROUND

• Buoli M, Serati M, Caldiroli A, Cremaschi L, Altamura AC. Neurodevelopmental Versus Neurodegenerative Model of Schizophrenia and Bipolar Disorder: Comparison with Physiological Brain Development and Aging. Psychiatr Danub. 2017 Mar;29(1):24-27. doi: 10.24869/psyd.2017.24.

  PMID: 28291970 BACKGROUND

• Pino O, Guilera G, Gomez-Benito J, Najas-Garcia A, Rufian S, Rojo E. Neurodevelopment or neurodegeneration: review of theories of schizophrenia. Actas Esp Psiquiatr. 2014 Jul-Aug;42(4):185-95. Epub 2014 Jul 1.

  PMID: 25017496 BACKGROUND

• Kochunov P, Hong LE. Neurodevelopmental and neurodegenerative models of schizophrenia: white matter at the center stage. Schizophr Bull. 2014 Jul;40(4):721-8. doi: 10.1093/schbul/sbu070. Epub 2014 May 27.

  PMID: 24870447 BACKGROUND

• Schnieder TP, Dwork AJ. Searching for neuropathology: gliosis in schizophrenia. Biol Psychiatry. 2011 Jan 15;69(2):134-9. doi: 10.1016/j.biopsych.2010.08.027. Epub 2010 Oct 30.

  PMID: 21035789 BACKGROUND

• Takeuchi H, Siu C, Remington G, Fervaha G, Zipursky RB, Foussias G, Agid O. Does relapse contribute to treatment resistance? Antipsychotic response in first- vs. second-episode schizophrenia. Neuropsychopharmacology. 2019 May;44(6):1036-1042. doi: 10.1038/s41386-018-0278-3. Epub 2018 Nov 22.

  PMID: 30514883 BACKGROUND

• Cooper JD, Han SYS, Tomasik J, Ozcan S, Rustogi N, van Beveren NJM, Leweke FM, Bahn S. Multimodel inference for biomarker development: an application to schizophrenia. Transl Psychiatry. 2019 Feb 11;9(1):83. doi: 10.1038/s41398-019-0419-4.

  PMID: 30745560 BACKGROUND

• Pillai A, Schooler NR, Peter D, Looney SW, Goff DC, Kopelowicz A, Lauriello J, Manschreck T, Mendelowitz A, Miller DD, Severe JB, Wilson DR, Ames D, Bustillo J, Kane JM, Buckley PF. Predicting relapse in schizophrenia: Is BDNF a plausible biological marker? Schizophr Res. 2018 Mar;193:263-268. doi: 10.1016/j.schres.2017.06.059. Epub 2017 Jul 19.

  PMID: 28734907 BACKGROUND

• Kim R, Healey KL, Sepulveda-Orengo MT, Reissner KJ. Astroglial correlates of neuropsychiatric disease: From astrocytopathy to astrogliosis. Prog Neuropsychopharmacol Biol Psychiatry. 2018 Dec 20;87(Pt A):126-146. doi: 10.1016/j.pnpbp.2017.10.002. Epub 2017 Oct 6.

  PMID: 28989099 BACKGROUND

• Rodrigues-Amorim D, Rivera-Baltanas T, Del Carmen Vallejo-Curto M, Rodriguez-Jamardo C, de Las Heras E, Barreiro-Villar C, Blanco-Formoso M, Fernandez-Palleiro P, Alvarez-Ariza M, Lopez M, Garcia-Caballero A, Olivares JM, Spuch C. Plasma beta-III tubulin, neurofilament light chain and glial fibrillary acidic protein are associated with neurodegeneration and progression in schizophrenia. Sci Rep. 2020 Aug 31;10(1):14271. doi: 10.1038/s41598-020-71060-4.

  PMID: 32868793 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood sample

MeSH Terms

Conditions

Schizophrenia; Nerve Degeneration

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: January 23, 2022
• First Posted: February 25, 2022
• Study Start: March 28, 2022
• Primary Completion: August 1, 2022
• Study Completion: October 1, 2022
• Last Updated: October 28, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)