CSF metabolic and proteomic profiles in patients prodromal for psychosis

TY - JOUR

T1 - CSF metabolic and proteomic profiles in patients prodromal for psychosis

AU - Huang, Jeffrey T.

AU - Leweke, F. Markus

AU - Tsang, Tsz M.

AU - Koethe, Dagmar

AU - Kranaster, Laura

AU - Gerth, Christoph W.

AU - Gross, Sonja

AU - Schreiber, Daniela

AU - Ruhrmann, Stephan

AU - Schutlze-Lutter, Frauke

AU - Klosterkötter, Joachim

AU - Holmes, Elaine

AU - Bahn, Sabine

N1 - Funding: This research was supported by the Stanley Medical Research Institute (SMRI) and the Koeln Fortune Program. Further thanks to The Henry Smith Charity and the BBSRC for financial support. S.B. holds a NARSAD Essel Independent Investigator Fellowship.

PY - 2007/8/22

Y1 - 2007/8/22

N2 - 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. Methodology/Principal Findings: We investigated the metabolic/proteomic profiles of cerebrospinal fluid (CSF) of first onset drug naïve paranoid schizophrenía patients (n=54) and individuals presenting with initial prodromal symptoms (n=24), alongside healthy volunteers (n=70) using proton nuclear magnetic resonance (1H-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/Significance: 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.

AB - 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. Methodology/Principal Findings: We investigated the metabolic/proteomic profiles of cerebrospinal fluid (CSF) of first onset drug naïve paranoid schizophrenía patients (n=54) and individuals presenting with initial prodromal symptoms (n=24), alongside healthy volunteers (n=70) using proton nuclear magnetic resonance (1H-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/Significance: 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.

U2 - 10.1371/journal.pone.0000756

DO - 10.1371/journal.pone.0000756

M3 - Article

C2 - 17712404

AN - SCOPUS:39749171224

SN - 1932-6203

VL - 2

SP - 1

EP - 7

JO - PLoS ONE

JF - PLoS ONE

IS - 8

M1 - e756

ER -