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@ARTICLE{Steinacker:280790,
      author       = {Steinacker, Petra and Werner, Leonie and Tarabuko,
                      Alexander and Al-Ali, Ilyas and Mechawar, Naguib and Pryce,
                      Christopher R and Cattane, Nadia and Poggi, Giulia and Al
                      Shweiki, Mhd Rami and Graf, Heiko and Großkopf, Henning and
                      Halbgebauer, Steffen and Oeckl, Patrick and Barba, Lorenzo
                      and Meier, Laura and Abu-Rumeileh, Samir and Marston, Hugh
                      and Bornemann, Klaus D and Hengerer, Bastian and Danzer,
                      Karin M and Schönfeldt-Lecuona, Carlos and Otto, Markus},
      title        = {{E}vidence for reduced synaptic protein {SNAP}-25 in
                      cerebrospinal fluid in major depressive disorder and
                      schizophrenia.},
      journal      = {BMJ mental health},
      volume       = {28},
      number       = {1},
      issn         = {1362-0347},
      address      = {London},
      publisher    = {BMJ Publ. Group},
      reportid     = {DZNE-2025-00974},
      pages        = {e301752},
      year         = {2025},
      abstract     = {Decreased cerebrospinal fluid (CSF) levels of synaptic
                      proteins, possibly reflecting impaired synaptic function,
                      have been observed in major depressive disorder (MDD).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.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.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.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.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.},
      keywords     = {Humans / Synaptosomal-Associated Protein 25: cerebrospinal
                      fluid / Depressive Disorder, Major: cerebrospinal fluid /
                      Depressive Disorder, Major: diagnosis / Schizophrenia:
                      cerebrospinal fluid / Schizophrenia: diagnosis / Male /
                      Female / Adult / Middle Aged / Biomarkers: cerebrospinal
                      fluid / Retrospective Studies / Neurogranin: cerebrospinal
                      fluid / Bipolar Disorder: cerebrospinal fluid / Sensitivity
                      and Specificity / Cross-Sectional Studies (Other) /
                      Depression (Other) / Synaptosomal-Associated Protein 25 (NLM
                      Chemicals) / Biomarkers (NLM Chemicals) / SNAP25 protein,
                      human (NLM Chemicals) / Neurogranin (NLM Chemicals)},
      cin          = {AG Öckl / AG Danzer},
      ddc          = {610},
      cid          = {I:(DE-2719)5000073 / I:(DE-2719)5000072},
      pnm          = {353 - Clinical and Health Care Research (POF4-353) / 352 -
                      Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40840974},
      pmc          = {pmc:PMC12374683},
      doi          = {10.1136/bmjment-2025-301752},
      url          = {https://pub.dzne.de/record/280790},
}