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000280790 1001_ $$00000-0001-6697-6522$$aSteinacker, Petra$$b0
000280790 245__ $$aEvidence for reduced synaptic protein SNAP-25 in cerebrospinal fluid in major depressive disorder and schizophrenia.
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000280790 520__ $$aDecreased 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.
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000280790 650_7 $$2Other$$aCross-Sectional Studies
000280790 650_7 $$2Other$$aDepression
000280790 650_7 $$2NLM Chemicals$$aSynaptosomal-Associated Protein 25
000280790 650_7 $$2NLM Chemicals$$aBiomarkers
000280790 650_7 $$2NLM Chemicals$$aSNAP25 protein, human
000280790 650_7 $$0132654-77-4$$2NLM Chemicals$$aNeurogranin
000280790 650_2 $$2MeSH$$aHumans
000280790 650_2 $$2MeSH$$aSynaptosomal-Associated Protein 25: cerebrospinal fluid
000280790 650_2 $$2MeSH$$aDepressive Disorder, Major: cerebrospinal fluid
000280790 650_2 $$2MeSH$$aDepressive Disorder, Major: diagnosis
000280790 650_2 $$2MeSH$$aSchizophrenia: cerebrospinal fluid
000280790 650_2 $$2MeSH$$aSchizophrenia: diagnosis
000280790 650_2 $$2MeSH$$aMale
000280790 650_2 $$2MeSH$$aFemale
000280790 650_2 $$2MeSH$$aAdult
000280790 650_2 $$2MeSH$$aMiddle Aged
000280790 650_2 $$2MeSH$$aBiomarkers: cerebrospinal fluid
000280790 650_2 $$2MeSH$$aRetrospective Studies
000280790 650_2 $$2MeSH$$aNeurogranin: cerebrospinal fluid
000280790 650_2 $$2MeSH$$aBipolar Disorder: cerebrospinal fluid
000280790 650_2 $$2MeSH$$aSensitivity and Specificity
000280790 7001_ $$aWerner, Leonie$$b1
000280790 7001_ $$aTarabuko, Alexander$$b2
000280790 7001_ $$aAl-Ali, Ilyas$$b3
000280790 7001_ $$aMechawar, Naguib$$b4
000280790 7001_ $$aPryce, Christopher R$$b5
000280790 7001_ $$aCattane, Nadia$$b6
000280790 7001_ $$aPoggi, Giulia$$b7
000280790 7001_ $$aAl Shweiki, Mhd Rami$$b8
000280790 7001_ $$aGraf, Heiko$$b9
000280790 7001_ $$aGroßkopf, Henning$$b10
000280790 7001_ $$0P:(DE-2719)9002026$$aHalbgebauer, Steffen$$b11$$udzne
000280790 7001_ $$0P:(DE-2719)9001560$$aOeckl, Patrick$$b12
000280790 7001_ $$aBarba, Lorenzo$$b13
000280790 7001_ $$0P:(DE-2719)9002179$$aMeier, Laura$$b14$$udzne
000280790 7001_ $$aAbu-Rumeileh, Samir$$b15
000280790 7001_ $$aMarston, Hugh$$b16
000280790 7001_ $$aBornemann, Klaus D$$b17
000280790 7001_ $$aHengerer, Bastian$$b18
000280790 7001_ $$0P:(DE-2719)9001513$$aDanzer, Karin M$$b19$$udzne
000280790 7001_ $$aSchönfeldt-Lecuona, Carlos$$b20
000280790 7001_ $$00000-0003-4273-4267$$aOtto, Markus$$b21
000280790 773__ $$0PERI:(DE-600)3160283-6$$a10.1136/bmjment-2025-301752$$gVol. 28, no. 1, p. e301752 -$$n1$$pe301752$$tBMJ mental health$$v28$$x1362-0347$$y2025
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