Study Report

Reference

Citation	Martins-de-Souza D, 2012 PubMed
Full Info	Martins-de-Souza D, Guest PC, Harris LW, Vanattou-Saifoudine N, Webster MJ, et al. (2012) Identification of proteomic signatures associated with depression and psychotic depression in post-mortem brains from major depression patients. Transl Psychiatry 2: e87.

Study

Hypothesis or Background	Major depressive disorder (MDD) is a leading cause of disability worldwide and results tragically in the loss of almost one million lives in Western societies every year. This is due to poor understanding of the disease pathophysiology and lack of empirical medical tests for accurate diagnosis or for guiding antidepressant treatment strategies
Sample Information	24 MDD patients and 12 matched controls
Method Detail	Here, we have used shotgun proteomics in the analysis of post-mortem dorsolateral prefrontal cortex brain tissue from 24 MDD patients and 12 matched controls. Brain proteomes were pre-fractionated by gel electrophoresis and further analyzed by shotgun data-independent label-free liquid chromatography-mass spectrometry. This led to identification of distinct proteome fingerprints between MDD and control subjects. Some of these differences were validated by Western blot or selected reaction monitoring mass spectrometry.
Method Keywords	gel electrophoresis; shotgun data-independent label-free liquid chromatography-mass spectrometry; Western blot ; selected reaction monitoring mass spectrometry
Result	This included proteins associated with energy metabolism and synaptic function and we also found changes in the histidine triad nucleotide-binding protein 1 (HINT1), which has been implicated recently in regulation of mood and behavior. We also found differential proteome profiles in MDD with (n=11) and without (n=12) psychosis. Interestingly, the psychosis fingerprint showed a marked overlap to changes seen in the brain proteome of schizophrenia patients.
Conclusions	These findings suggest that it may be possible to contribute to the disease understanding by distinguishing different subtypes of MDD based on distinct brain proteomic profiles.

Relationships reported by Martins-de-Souza D, 2012

Component A Approved Name (Name in Paper)	Component A Type	Component B Approved Name (Name in Paper)	Component B Type	Statistical Result	Relationship Description	Result Category (Positive/Negative))
MDD	syndrome	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6 (NADH dehydrogenase Ubiquinone 1 alpha subcomplex subunit 6)	protein	P-value = 0.0025	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 (NADH dehydrogenase Ubiquinone 1-alpha subcomplex subunit 2)	protein	P-value = 0.0349	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Putative cytochrome b-c1 complex subunit Rieske-like protein 1 (Cytochrome b c1 complex subunit)	protein	P-value = 0.0433	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	NADH dehydrogenase [ubiquinone] iron-sulfur protein 5 (NADH dehydrogenase Ubiquinone iron-sulphur protein 5)	protein	P-value = 0.0393	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	ATP synthase subunit g, mitochondrial (ATP synthase subunit g mitochondrial short ATPase)	protein	P-value = 0.037	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	ATP synthase subunit e, mitochondrial (ATP synthase subunit e mitochondrial)	protein	P-value = 0.041	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Fatty acid-binding protein, heart (Fatty acid-binding protein heart)	protein	P-value = 0.0219	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Apolipoprotein E (Apolipoprotein E)	protein	P-value = 0.0279	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Acyl-coenzyme A thioesterase 13 (Acyl coenzyme A thioesterase)	protein	P-value = 0.0445	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Cytochrome c oxidase subunit 4 isoform 1, mitochondrial (Cytochrome c oxidase subunit 4 isoform 1 mitochondrial)	protein	P-value = 0.0311	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Acylphosphatase-2 (Acylphosphatase 2)	protein	P-value = 0.0107	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Cytochrome c oxidase subunit 7A2, mitochondrial (Cytochrome c oxidase polypeptide 7A2 mitochondrial)	protein	P-value = 0.0325	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Cytochrome c oxidase subunit 5B, mitochondrial (Cytochrome c oxidase subunit 5B mitochondrial)	protein	P-value = 0.021	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 (NADH dehydrogenase Ubiquinone 1-alpha subcomplex subunit 13)	protein	P-value = 0.0248	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Cytochrome c (Cytochrome c)	protein	P-value = 0.0311	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Histidine triad nucleotide-binding protein 1 (Histidine triad nucleotide-binding protein 1)	protein	P-value = 0.0038	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Rho-related GTP-binding protein RhoC (Rho-related GTP-binding protein)	protein	P-value = 0.0095	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Peptidyl-prolyl cis-trans isomerase FKBP2 (FK506-binding protein 2)	protein	P-value = 0.0072	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Neuromodulin (Neuromodulin, growth-associated protein 43)	protein	P-value = 0.0302	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Profilin-2 (Profilin 2)	protein	P-value = 0.0032	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Putative tubulin-like protein alpha-4B (Putative tubulin-like protein alpha-4B)	protein	P-value = 0.0238	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Microtubule-associated proteins 1A/1B light chain 3A (Microtubule-associated proteins 1A 1B light chain 3A)	protein	P-value = 0.0455	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Profilin-1 (Profilin-1)	protein	P-value = 0.0259	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Gamma-aminobutyric acid receptor-associated protein-like 2 (Gamma aminobutyric acid receptor-associated protein-like 2)	protein	P-value = 0.0318	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Ribonuclease UK114 (Ribonuclease UK114)	protein	P-value = 0.027	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Fatty acid-binding protein, brain (Fatty acid-binding protein brain)	protein	P-value = 0.0444	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	FXYD domain-containing ion transport regulator 6 (FXYD domain containing ion transport regulator 6)	protein	P-value = 0.0008	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Dihydropyrimidinase-related protein 2 (Dihydropyrimidinase-related protein 2)	protein	P-value = 0.0027	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Dihydropyrimidinase-related protein 3 (Dihydropyrimidinase-related protein 3)	protein	P-value = 0.0124	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Synaptosomal-associated protein 25 (Synaptosomal-associated protein 25)	protein	P-value = 0.007	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Amphiphysin (Amphiphysin)	protein	P-value = 0.0379	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Gamma-synuclein (Gamma synuclein)	protein	P-value = 0.0074	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Alpha-synuclein (Alpha synuclein)	protein	P-value = 0.0382	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Cystatin-B (Cystatin-B)	protein	P-value = 0.0208	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Cystatin-C (Cystatin C)	protein	P-value = 0.0284	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	CDGSH iron-sulfur domain-containing protein 1 (CDGSH iron sulfur domain-containing protein 1)	protein	P-value = 0.014	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Single-stranded DNA-binding protein, mitochondrial (ss DNA-binding protein mitochondrial short Mt SSB)	protein	P-value = 0.0397	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	DNA-binding protein SATB2 (DNA-binding protein SATB2)	protein	P-value = 0.0314	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive
MDD	syndrome	Histone H4 (Histone H4)	protein	P-value = 0.0265	Differentially expressed proteins in all post mortem brains from MDD patients compared with controls	Positive