Proteomic analysis reveals a biosignature of decreased synaptic protein in cerebrospinal fluid of major depressive disorder.
Transl Psychiatry
; 10(1): 144, 2020 05 12.
Article
em En
| MEDLINE
| ID: mdl-32398672
ABSTRACT
Major depressive disorder (MDD) is a leading cause of morbidity with a lifetime prevalence of 10%. There is increasing evidence suggesting synaptic dysfunction and impaired integrity of certain brain circuits in MDD. Here we investigate the cerebrospinal fluid proteome of psychiatric patients focusing on MDD by deep proteomic profiling approach combined with a further validation step using targeted mass spectrometry. We demonstrate profound CSF proteomic changes during on-going depression episodes in MDD patients (n = 40) in comparison to controls (n = 27), schizophrenia spectrum disorder (n = 13), and bipolar disorder patients (n = 11). The discovery analysis with isobaric tags for relative and absolute quantitation (iTRAQ) reveals changes in proteins associated with synaptic transmission, myelination, and Wnt signaling in CSF of MDD. The multiple reaction monitoring (MRM) validation analysis confirms significantly decreased levels of eight proteins including the membrane synaptic proteins neurexin 3 (NRXN3), contactin-associated protein-like 4 (CNTNAP4), and glutamate ionotropic receptor AMPA type subunit 4 (GRIA4) in the CSF of MDD patients in comparison to the controls. Overall, the study demonstrates proteins that constitute an MDD biosignature for further validation studies and provides insight into the pathophysiology of MDD and other psychiatric disorders.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtorno Bipolar
/
Transtorno Depressivo Maior
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Transl Psychiatry
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Alemanha