CSF levels of synaptosomal-associated protein 25 and synaptotagmin-1 in first-episode psychosis subjects
Post-mortem studies consistently show evidence of reduced synaptic protein levels in patients with schizophrenia. Clinically high-risk subjects show a steeper decrease in grey matter thickness and in vitro modeling using patient-derived cells implicate excessive synaptic pruning during neurodevelopm...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-06-01
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| Series: | IBRO Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S245183012030011X |
| _version_ | 1818450432434896896 |
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| author | Chengai Xu Carl M. Sellgren Helena Fatouros-Bergman Fredrik Piehl Kaj Blennow Henrik Zetterberg Ann Brinkmalm Alexander Frizell Santillo Sofia Lundgren Simon Cervenka Göran Engberg Sophie Erhardt |
| author_facet | Chengai Xu Carl M. Sellgren Helena Fatouros-Bergman Fredrik Piehl Kaj Blennow Henrik Zetterberg Ann Brinkmalm Alexander Frizell Santillo Sofia Lundgren Simon Cervenka Göran Engberg Sophie Erhardt |
| author_sort | Chengai Xu |
| collection | DOAJ |
| description | Post-mortem studies consistently show evidence of reduced synaptic protein levels in patients with schizophrenia. Clinically high-risk subjects show a steeper decrease in grey matter thickness and in vitro modeling using patient-derived cells implicate excessive synaptic pruning during neurodevelopment as a part of the schizophrenia pathophysiology. However, it is unclear to what extent synapse elimination is present during various stages of the disease, which is of clinical importance as in a real-world setting most subjects received their first-episode psychosis (FEP) diagnosis not until their mid-twenties. In the present study, we measured cerebrospinal fluid (CSF) concentrations of the two pre-synaptic proteins synaptosomal-associated protein 25 (SNAP-25) and synaptotagmin-1 (SYT-1), both of which are increased in conditions of ongoing synaptic degeneration, in 44 FEP subjects (mean age 29.9 years) and 21 healthy controls (25.9 years) using immunoprecipitation mass spectrometry. Neither protein was found to differ between healthy controls and patients, and they showed no correlation with symptom ratings, cognitive performance or antipsychotic medication. Additional studies in high-risk subjects in the early prodromal phase will be needed to address if excessive synapse destruction occurs before the development of overt psychotic symptoms. |
| first_indexed | 2024-12-14T20:51:13Z |
| format | Article |
| id | doaj.art-ceda296ab6c44ca8b2a6a72086549797 |
| institution | Directory Open Access Journal |
| issn | 2451-8301 |
| language | English |
| last_indexed | 2024-12-14T20:51:13Z |
| publishDate | 2020-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | IBRO Reports |
| spelling | doaj.art-ceda296ab6c44ca8b2a6a720865497972022-12-21T22:47:48ZengElsevierIBRO Reports2451-83012020-06-018136142CSF levels of synaptosomal-associated protein 25 and synaptotagmin-1 in first-episode psychosis subjectsChengai Xu0Carl M. Sellgren1Helena Fatouros-Bergman2Fredrik Piehl3Kaj Blennow4Henrik Zetterberg5Ann Brinkmalm6Alexander Frizell Santillo7Sofia Lundgren8Simon Cervenka9Göran Engberg10Sophie Erhardt11Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, SwedenDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, SwedenCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm & Stockholm Health Care Services, Stockholm County Council, SwedenNeuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, SwedenDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, SwedenDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; UK Dementia Research Institute at UCL, London, United Kingdom; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United KingdomDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, SwedenCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden; Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, SwedenClinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, SwedenCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm & Stockholm Health Care Services, Stockholm County Council, SwedenDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Corresponding author at: Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 77, Stockholm, Sweden.Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, SwedenPost-mortem studies consistently show evidence of reduced synaptic protein levels in patients with schizophrenia. Clinically high-risk subjects show a steeper decrease in grey matter thickness and in vitro modeling using patient-derived cells implicate excessive synaptic pruning during neurodevelopment as a part of the schizophrenia pathophysiology. However, it is unclear to what extent synapse elimination is present during various stages of the disease, which is of clinical importance as in a real-world setting most subjects received their first-episode psychosis (FEP) diagnosis not until their mid-twenties. In the present study, we measured cerebrospinal fluid (CSF) concentrations of the two pre-synaptic proteins synaptosomal-associated protein 25 (SNAP-25) and synaptotagmin-1 (SYT-1), both of which are increased in conditions of ongoing synaptic degeneration, in 44 FEP subjects (mean age 29.9 years) and 21 healthy controls (25.9 years) using immunoprecipitation mass spectrometry. Neither protein was found to differ between healthy controls and patients, and they showed no correlation with symptom ratings, cognitive performance or antipsychotic medication. Additional studies in high-risk subjects in the early prodromal phase will be needed to address if excessive synapse destruction occurs before the development of overt psychotic symptoms.http://www.sciencedirect.com/science/article/pii/S245183012030011XSchizophreniaSynapse pruningSNAP-25SYT-1 |
| spellingShingle | Chengai Xu Carl M. Sellgren Helena Fatouros-Bergman Fredrik Piehl Kaj Blennow Henrik Zetterberg Ann Brinkmalm Alexander Frizell Santillo Sofia Lundgren Simon Cervenka Göran Engberg Sophie Erhardt CSF levels of synaptosomal-associated protein 25 and synaptotagmin-1 in first-episode psychosis subjects IBRO Reports Schizophrenia Synapse pruning SNAP-25 SYT-1 |
| title | CSF levels of synaptosomal-associated protein 25 and synaptotagmin-1 in first-episode psychosis subjects |
| title_full | CSF levels of synaptosomal-associated protein 25 and synaptotagmin-1 in first-episode psychosis subjects |
| title_fullStr | CSF levels of synaptosomal-associated protein 25 and synaptotagmin-1 in first-episode psychosis subjects |
| title_full_unstemmed | CSF levels of synaptosomal-associated protein 25 and synaptotagmin-1 in first-episode psychosis subjects |
| title_short | CSF levels of synaptosomal-associated protein 25 and synaptotagmin-1 in first-episode psychosis subjects |
| title_sort | csf levels of synaptosomal associated protein 25 and synaptotagmin 1 in first episode psychosis subjects |
| topic | Schizophrenia Synapse pruning SNAP-25 SYT-1 |
| url | http://www.sciencedirect.com/science/article/pii/S245183012030011X |
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