CSF levels of synaptosomal-associated protein 25 and synaptotagmin-1 in first-episode psychosis subjects

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; Karolinska Schizophrenia Project (KaSP) Consortium

doi:10.1016/j.ibror.2020.04.001

CSF levels of synaptosomal-associated protein 25 and synaptotagmin-1 in first-episode psychosis subjects

IBRO Rep. 2020 Apr 13:8:136-142. doi: 10.1016/j.ibror.2020.04.001. eCollection 2020 Jun.

Authors

Chengai Xu¹, Carl M Sellgren¹, Helena Fatouros-Bergman², Fredrik Piehl³, Kaj Blennow^{4

5}, Henrik Zetterberg^{4

5

6

7}, Ann Brinkmalm^{4

5}, Alexander Frizell Santillo^{8

9}, Sofia Lundgren⁹, Simon Cervenka², Göran Engberg¹, Sophie Erhardt¹; Karolinska Schizophrenia Project (KaSP) Consortium

Affiliations

¹ Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
² Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm & Stockholm Health Care Services, Stockholm County Council, Sweden.
³ Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁴ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁵ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁶ UK Dementia Research Institute at UCL, London, United Kingdom.
⁷ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom.
⁸ Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
⁹ Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.

Abstract

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.

Keywords: BACS-SC, Brief Assessment of Cognition in Schizophrenia Symbol Coding; BMI, body mass index; BVMT-R, Brief Visuospatial Memory Test-Revised; CGI, Clinical Global Impression; CPT-IP, Continuous Performance Test-Identical Pairs; DUP, duration of untreated psychosis; FEP, first-episode psychosis; GAF, Global Assessment of Functioning; HC, healthy controls; HVLT-R, Hopkins Verbal Learning Test-Revised; LNS, Letter-Number Span; MSCEIT, Mayer–Salovey– Caruso Emotional Intelligence Test; NAB: MAZES, Neuropsychological Assessment Battery: Mazes; PANSS, the Positive and Negative Syndrome Scale; SNAP-25; SYT-1; Schizophrenia; Synapse pruning; TMT, Trail Making Test; WMS-III, Wechsler Memory Scale-3rd Edition.