Evidence for reduced synaptic protein SNAP-25 in cerebrospinal fluid in major depressive disorder and schizophrenia
Background Decreased cerebrospinal fluid (CSF) levels of synaptic proteins, possibly reflecting impaired synaptic function, have been observed in major depressive disorder (MDD).Objective To investigate the diagnostic utility of the soluble N-ethylmaleimide-sensitive-factor attachment receptor (SNAR...
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BMJ Publishing Group
2025-08-01
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| Series: | BMJ Mental Health |
| Online Access: | https://mentalhealth.bmj.com/content/28/1/e301752.full |
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| author | Patrick Oeckl Petra Steinacker Markus Otto Steffen Halbgebauer MHD Rami Al Shweiki Samir Abu-Rumeileh Naguib Mechawar Carlos Schönfeldt-Lecuona Lorenzo Barba Leonie Werner Alexander Tarabuko Ilyas Al-Ali Christopher R Pryce Nadia Cattane Giulia Poggi Heiko Graf Henning Großkopf Laura Meier Hugh Marston Klaus D Bornemann Bastian Hengerer Karin M Danzer |
| author_facet | Patrick Oeckl Petra Steinacker Markus Otto Steffen Halbgebauer MHD Rami Al Shweiki Samir Abu-Rumeileh Naguib Mechawar Carlos Schönfeldt-Lecuona Lorenzo Barba Leonie Werner Alexander Tarabuko Ilyas Al-Ali Christopher R Pryce Nadia Cattane Giulia Poggi Heiko Graf Henning Großkopf Laura Meier Hugh Marston Klaus D Bornemann Bastian Hengerer Karin M Danzer |
| author_sort | Patrick Oeckl |
| collection | DOAJ |
| description | Background Decreased cerebrospinal fluid (CSF) levels of synaptic proteins, possibly reflecting impaired synaptic function, have been observed in major depressive disorder (MDD).Objective To investigate the diagnostic utility of the soluble N-ethylmaleimide-sensitive-factor attachment receptor (SNARE) complex protein, synaptosomal-associated protein of 25 kDa (SNAP-25), for MDD.Methods Overall, 208 participants with one of MDD, schizophrenia (SCZ) or bipolar disorder (BD), and healthy controls (HCs) were retrospectively enrolled. CSF levels of SNAP-25 were assessed relative to MDD characteristics and the diagnostic potential was analysed. In subgroups of patients, CSF levels of presynaptic neurexin 3 (NRXN3), postsynaptic neurogranin (NRGN) and Alzheimer’s disease biomarkers were measured for comparison.Findings SNAP-25 levels, but not the levels of the other synaptic markers, were significantly decreased in MDD compared with HCs, allowing for discrimination with 68% sensitivity and 67% specificity. SNAP-25 was not associated with MDD severity or antidepressant medication. Compared with HCs, SCZ also displayed decreased SNAP-25 enabling discrimination with 64% sensitivity and 77% specificity. There were strong correlations between levels of synaptic proteins and established Alzheimer pathology markers, with subtle differences in the association pattern between disorders.Discussion Our data suggest that SNAP-25, NRXN3 and NRGN versus beta-amyloid and phosphorylated tau protein 181 (ptau) are regulated differentially across psychiatric disorders and that SNAP-25 has a moderate diagnostic potential for MDD and SCZ. We propose that CSF SNAP-25 level might represent an integrated readout of reduced synaptic function, rather than of synaptic degeneration, in MDD. Further studies are needed to analyse whether this potential can be increased by using multimarker measurements and whether it will be possible to subtype psychiatric disorders according to synaptic involvement in pathophysiology.Clinical implications SNAP-25 and other synaptic proteins in CSF might aid diagnosis and subtyping of MDD and SCZ. The current development of sensitive methods to also determine synaptic proteins in blood samples from patients will advance the validation of the biomarker potential and contribute to understanding of synaptic involvement in the pathophysiology of MDD and SCZ. |
| format | Article |
| id | doaj-art-5078c07d9cb541da92b124a6dd8f8bab |
| institution | Kabale University |
| issn | 2755-9734 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Mental Health |
| spelling | doaj-art-5078c07d9cb541da92b124a6dd8f8bab2025-08-21T10:40:21ZengBMJ Publishing GroupBMJ Mental Health2755-97342025-08-0128110.1136/bmjment-2025-301752Evidence for reduced synaptic protein SNAP-25 in cerebrospinal fluid in major depressive disorder and schizophreniaPatrick Oeckl0Petra Steinacker1Markus Otto2Steffen Halbgebauer3MHD Rami Al Shweiki4Samir Abu-Rumeileh5Naguib Mechawar6Carlos Schönfeldt-Lecuona7Lorenzo Barba8Leonie Werner9Alexander Tarabuko10Ilyas Al-Ali11Christopher R Pryce12Nadia Cattane13Giulia Poggi14Heiko Graf15Henning Großkopf16Laura Meier17Hugh Marston18Klaus D Bornemann19Bastian Hengerer20Karin M Danzer21German Center for Neurodegenerative Diseases (DZNE) Ulm, Ulm, Germany1 Department of Neurology, University Hospital Halle, Halle (Saale), Germany2 Department of Neurology, Ulm University Hospital, Ulm, GermanyNeurology, University of Ulm, Ulm, Germany1 Department of Neurology, Ulm University, Ulm, Baden-Württemberg, Germany1 Department of Neurology, Martin Luther University Halle Wittenberg, Halle (Saale), Germany2Douglas Hospital Research Institute and Brain Bank; McGill University, Montreal, QC, CanadaDepartment of Psychiatry and Psychotherapy III, University Hospital Ulm, Ulm, GermanyDepartment of Neurology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany2 Department of Neurology, Ulm University Hospital, Ulm, Germany1 Department of Neurology, Martin Luther University Halle Wittenberg, Halle (Saale), Germany1 Department of Neurology, Martin Luther University Halle Wittenberg, Halle (Saale), Germany4 University Hospital of Psychiatry, University of Zurich, Zurich, Switzerland5 Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy4 University Hospital of Psychiatry, University of Zurich, Zurich, Switzerland6 Department of Psychiatry and Psychotherapy III, Ulm University Hospital, Ulm, Germany1 Department of Neurology, Martin Luther University Halle Wittenberg, Halle (Saale), Germany2 Department of Neurology, Ulm University Hospital, Ulm, Germany8 CNS Diseases Research, Boehringer Ingelheim Pharma GmbH and Co. KG, Biberach an der Riss, Germany8 CNS Diseases Research, Boehringer Ingelheim Pharma GmbH and Co. KG, Biberach an der Riss, Germany8 CNS Diseases Research, Boehringer Ingelheim Pharma GmbH and Co. KG, Biberach an der Riss, Germany2 Department of Neurology, Ulm University Hospital, Ulm, GermanyBackground Decreased cerebrospinal fluid (CSF) levels of synaptic proteins, possibly reflecting impaired synaptic function, have been observed in major depressive disorder (MDD).Objective To investigate the diagnostic utility of the soluble N-ethylmaleimide-sensitive-factor attachment receptor (SNARE) complex protein, synaptosomal-associated protein of 25 kDa (SNAP-25), for MDD.Methods Overall, 208 participants with one of MDD, schizophrenia (SCZ) or bipolar disorder (BD), and healthy controls (HCs) were retrospectively enrolled. CSF levels of SNAP-25 were assessed relative to MDD characteristics and the diagnostic potential was analysed. In subgroups of patients, CSF levels of presynaptic neurexin 3 (NRXN3), postsynaptic neurogranin (NRGN) and Alzheimer’s disease biomarkers were measured for comparison.Findings SNAP-25 levels, but not the levels of the other synaptic markers, were significantly decreased in MDD compared with HCs, allowing for discrimination with 68% sensitivity and 67% specificity. SNAP-25 was not associated with MDD severity or antidepressant medication. Compared with HCs, SCZ also displayed decreased SNAP-25 enabling discrimination with 64% sensitivity and 77% specificity. There were strong correlations between levels of synaptic proteins and established Alzheimer pathology markers, with subtle differences in the association pattern between disorders.Discussion Our data suggest that SNAP-25, NRXN3 and NRGN versus beta-amyloid and phosphorylated tau protein 181 (ptau) are regulated differentially across psychiatric disorders and that SNAP-25 has a moderate diagnostic potential for MDD and SCZ. We propose that CSF SNAP-25 level might represent an integrated readout of reduced synaptic function, rather than of synaptic degeneration, in MDD. Further studies are needed to analyse whether this potential can be increased by using multimarker measurements and whether it will be possible to subtype psychiatric disorders according to synaptic involvement in pathophysiology.Clinical implications SNAP-25 and other synaptic proteins in CSF might aid diagnosis and subtyping of MDD and SCZ. The current development of sensitive methods to also determine synaptic proteins in blood samples from patients will advance the validation of the biomarker potential and contribute to understanding of synaptic involvement in the pathophysiology of MDD and SCZ.https://mentalhealth.bmj.com/content/28/1/e301752.full |
| spellingShingle | Patrick Oeckl Petra Steinacker Markus Otto Steffen Halbgebauer MHD Rami Al Shweiki Samir Abu-Rumeileh Naguib Mechawar Carlos Schönfeldt-Lecuona Lorenzo Barba Leonie Werner Alexander Tarabuko Ilyas Al-Ali Christopher R Pryce Nadia Cattane Giulia Poggi Heiko Graf Henning Großkopf Laura Meier Hugh Marston Klaus D Bornemann Bastian Hengerer Karin M Danzer Evidence for reduced synaptic protein SNAP-25 in cerebrospinal fluid in major depressive disorder and schizophrenia BMJ Mental Health |
| title | Evidence for reduced synaptic protein SNAP-25 in cerebrospinal fluid in major depressive disorder and schizophrenia |
| title_full | Evidence for reduced synaptic protein SNAP-25 in cerebrospinal fluid in major depressive disorder and schizophrenia |
| title_fullStr | Evidence for reduced synaptic protein SNAP-25 in cerebrospinal fluid in major depressive disorder and schizophrenia |
| title_full_unstemmed | Evidence for reduced synaptic protein SNAP-25 in cerebrospinal fluid in major depressive disorder and schizophrenia |
| title_short | Evidence for reduced synaptic protein SNAP-25 in cerebrospinal fluid in major depressive disorder and schizophrenia |
| title_sort | evidence for reduced synaptic protein snap 25 in cerebrospinal fluid in major depressive disorder and schizophrenia |
| url | https://mentalhealth.bmj.com/content/28/1/e301752.full |
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