CSF metabolic and proteomic profiles in patients prodromal for psychosis.
BACKGROUND
The initial prodromal state of psychosis (IPS) is defined as an early disease stage prior to the onset of overt psychosis characterized by sub-threshold or more unspecific psychiatric symptoms. Little is known regarding the biochemical changes during this period.


RESULTS
We investigated the metabolic/proteomic profiles of cerebrospinal fluid (CSF) of first-onset drug naïve paranoid schizophrenia patients (n = 54) and individuals presenting with initial prodromal symptoms (n = 24), alongside healthy volunteers (n = 70) using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy and surface enhanced laser desorption ionization (SELDI) mass spectrometry, respectively. Partial least square discriminant analysis (PLS-DA) showed that 36%/29% of IPS patients displayed proteomic/metabolic profiles characteristic of first-onset, drug naïve schizophrenia, i.e., changes in levels of glucose and lactate as well as changes in a VGF-derived peptide (VGF23-62) and transthyretin protein concentrations. However, only 29% (n = 7) of the investigated IPS patients (who to date have been followed up for up to three years) have so far received a diagnosis of schizophrenia. The presence of biochemical alterations in the IPS group did not correlate with the risk to develop schizophrenia.


CONCLUSIONS
Our results imply that schizophrenia-related biochemical disease processes can be traced in CSF of prodromal patients. However, the biochemical disturbances identified in IPS patients, at least when measured at a single time point, may not be sufficient to predict clinical outcome.
Huang
Jeffrey T-J
JT
Institute of Biotechnology, University of Cambridge, Cambridge, United Kingdom.
Leweke
F Markus
FM
Tsang
Tsz M
TM
Koethe
Dagmar
D
Kranaster
Laura
L
Gerth
Christoph W
CW
Gross
Sonja
S
Schreiber
Daniela
D
Ruhrmann
Stephan
S
Schultze-Lutter
Frauke
F
Klosterkötter
Joachim
J
Holmes
Elaine
E
Bahn
Sabine
S
D000328:Adult; D005260:Female; D005947:Glucose / Q000134:cerebrospinal fluid; D006801:Humans; D019344:Lactic Acid / Q000134:cerebrospinal fluid; D008297:Male; D055442:Metabolome / Q000502:physiology*; D009479:Neuropeptides / Q000134:cerebrospinal fluid; D019906:Nuclear Magnetic Resonance, Biomolecular; D011228:Prealbumin / Q000134:cerebrospinal fluid; D011237:Predictive Value of Tests; D020543:Proteome / Q000502:physiology*; D040901:Proteomics; D012563:Schizophrenia, Paranoid / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000503:physiopathology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D055815:Young Adult
D009479:Neuropeptides; D011228:Prealbumin; D020543:Proteome; C522413:VGF peptide; D019344:Lactic Acid; D005947:Glucose
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