Disease biomarkers in cerebrospinal fluid of patients with first-onset psychosis.
BACKGROUND
Psychosis is a severe mental condition that is characterized by a loss of contact with reality and is typically associated with hallucinations and delusional beliefs. There are numerous psychiatric conditions that present with psychotic symptoms, most importantly schizophrenia, bipolar affective disorder, and some forms of severe depression referred to as psychotic depression. The pathological mechanisms resulting in psychotic symptoms are not understood, nor is it understood whether the various psychotic illnesses are the result of similar biochemical disturbances. The identification of biological markers (so-called biomarkers) of psychosis is a fundamental step towards a better understanding of the pathogenesis of psychosis and holds the potential for more objective testing methods.


RESULTS
Surface-enhanced laser desorption ionization mass spectrometry was employed to profile proteins and peptides in a total of 179 cerebrospinal fluid samples (58 schizophrenia patients, 16 patients with depression, five patients with obsessive-compulsive disorder, ten patients with Alzheimer disease, and 90 controls). Our results show a highly significant differential distribution of samples from healthy volunteers away from drug-naïve patients with first-onset paranoid schizophrenia. The key alterations were the up-regulation of a 40-amino acid VGF-derived peptide, the down-regulation of transthyretin at approximately 4 kDa, and a peptide cluster at approximately 6,800-7,300 Da (which is likely to be influenced by the doubly charged ions of the transthyretin protein cluster). These schizophrenia-specific protein/peptide changes were replicated in an independent sample set. Both experiments achieved a specificity of 95% and a sensitivity of 80% or 88% in the initial study and in a subsequent validation study, respectively.


CONCLUSIONS
Our results suggest that the application of modern proteomics techniques, particularly mass spectrometric approaches, holds the potential to advance the understanding of the biochemical basis of psychiatric disorders and may in turn allow for the development of diagnostics and improved therapeutics. Further studies are required to validate the clinical effectiveness and disease specificity of the identified biomarkers.
Huang
Jeffrey T-J
JT
Institute of Biotechnology, University of Cambridge, Cambridge, United Kingdom.
Leweke
F Markus
FM
Oxley
David
D
Wang
Lan
L
Harris
Nathan
N
Koethe
Dagmar
D
Gerth
Christoph W
CW
Nolden
Brit M
BM
Gross
Sonja
S
Schreiber
Daniela
D
Reed
Benjamin
B
Bahn
Sabine
S
D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001921:Brain / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D009414:Nerve Growth Factors / Q000134:cerebrospinal fluid / Q000378:metabolism; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D011228:Prealbumin / Q000134:cerebrospinal fluid / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism; D011618:Psychotic Disorders / Q000134:cerebrospinal fluid*; D012559:Schizophrenia / Q000097:blood / Q000378:metabolism; D012563:Schizophrenia, Paranoid / Q000134:cerebrospinal fluid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D015415:Biomarkers; D009414:Nerve Growth Factors; D010446:Peptide Fragments; D011228:Prealbumin; C510637:VGF protein, human