Ohrmann P, Siegmund A, Suslow T, Spitzberg K, Kersting A, Arolt V et al. Evidence for glutamatergic neuronal dysfunction in the prefrontal cortex in chronic but not in first-episode patients with schizophrenia: a proton magnetic resonance spectroscopy study. Schizophr Res 73: 153-157
University of Muenster, Department of Psychiatry, Albert-Schweitzer-Str. 11, Germany. Schizophrenia Research
(Impact Factor: 3.92).
04/2005; 73(2-3):153-7. DOI: 10.1016/j.schres.2004.08.021
Based upon pharmacological challenge and postmortem studies, schizophrenia has been hypothesized to be caused by decreased glutamatergic neurotransmission. We investigated the glutamatergic neuronal metabolism of the dorsolateral prefrontal cortex with localized 1H magnetic resonance spectroscopy in 18 first-episode patients, 21 chronic patients with schizophrenia, and 21 age-matched controls. Chronic patients had significantly lower levels of glutamate/glutamine (Glx) and N-acetylaspartate (NAA) compared to healthy controls and first-episode patients. Reduced metabolite levels were not correlated with duration of illness or medication. Our results indicate glutamatergic dysfunction in chronic schizophrenia that could be evidence of a progressive brain disorder.
Available from: Kate Merritt
- "Several studies have investigated associations between regional glutamatergic metabolite levels and the severity of positive psychotic symptoms (Table 1), and most found no association between regional Glx, glutamate or glutamine levels and positive symptom severity, in either high genetic or clinical risk populations (36, 37), first-episode psychosis (18, 19, 37–40) or chronic schizophrenia (26–28, 30, 41–46). "
[Show abstract] [Hide abstract]
ABSTRACT: The glutamate hypothesis of schizophrenia, proposed over two decades ago, originated following the observation that administration of drugs that block NMDA glutamate receptors, such as ketamine, could induce schizophrenia-like symptoms. Since then, this hypothesis has been extended to describe how glutamate abnormalities may disturb brain function and underpin psychotic symptoms and cognitive impairments. The glutamatergic system is now a major focus for the development of new compounds in schizophrenia. Relationships between regional brain glutamate function and symptom severity can be investigated using proton magnetic resonance spectroscopy (1H-MRS) to estimate levels of glutamatergic metabolites in vivo. Here we briefly review the 1H-MRS studies that have explored relationships between glutamatergic metabolites, symptoms, and cognitive function in clinical samples. While some of these studies suggest that more severe symptoms may be associated with elevated glutamatergic function in the anterior cingulate, studies in larger patient samples selected on the basis of symptom severity are required.
Frontiers in Psychiatry 11/2013; 4:151. DOI:10.3389/fpsyt.2013.00151
Available from: Lun Yang
- "Glutamate was reduced in the hippocampus and had a trend of decrease in the cortex in our study (Table 1 & Figure 2). The change of glutamate in the brain of schizophrenia patients has been the subject of discussion since 1980 but no consensus has so far been achieved –. Animal models offer valuable evidence in this field. Acute injection of MK-801 in rats has been shown to cause an elevation of glutamate in certain brain regions , . "
[Show abstract] [Hide abstract]
ABSTRACT: Although a number of proteins and genes relevant to schizophrenia have been identified in recent years, few are known about the exact metabolic pathway involved in this disease. Our previous proteomic study has revealed the energy metabolism abnormality in subchronic MK-801 treated rat, a well-established animal model for schizophrenia. This prompted us to further investigate metabolite levels in the same rat model to better delineate the metabolism dysfunctions and provide insights into the pathology of schizophrenia.
Metabolomics, a high-throughput investigatory strategy developed in recent years, can offer comprehensive metabolite-level insights that complement protein and genetic findings. In this study, we employed a nondestructive metabolomic approach (1H-MAS-NMR) to investigate the metabolic traits in cortex and hippocampus of MK-801 treated rats. Multivariate statistics and ingenuity pathways analyses (IPA) were applied in data processing. The result was further integrated with our previous proteomic findings by IPA analysis to obtain a systematic view on our observations.
Clear distinctions between the MK-801 treated group and the control group in both cortex and hippocampus were found by OPLS-DA models (with R(2)X = 0.441, Q(2)Y = 0.413 and R(2)X = 0.698, Q(2)Y = 0.677, respectively). The change of a series of metabolites accounted for the separation, such as glutamate, glutamine, citrate and succinate. Most of these metabolites fell in a pathway characterized by down-regulated glutamate synthesis and disturbed Krebs cycle. IPA analysis further confirmed the involvement of energy metabolism abnormality induced by MK-801 treatment.
Our metabolomics findings reveal systematic changes in pathways of glutamate metabolism and Krebs cycle in the MK-801 treated rats' cortex and hippocampus, which confirmed and improved our previous proteomic observation and served as a valuable reference to the etiology research of schizophrenia.
PLoS ONE 04/2013; 8(4):e60598. DOI:10.1371/journal.pone.0060598 · 3.23 Impact Factor
Available from: Alice Egerton
- "The glutamate plus GABA / Cr signal was elevated , and a subsequent follow-up study revealed that these elevations were decreased following neuroleptic treatment . More recently, studies in chronic, medicated, patients report decreases in glutamate and glutamine, or Glx, in the anterior cingulate cortex  , dorsolateral prefrontal cortex  , and mesial prefrontal cortex . These decreases in chronic medicated patients contrast with the increases in 1H-MRS measures of medial prefrontal glutamatergic transmission reported in early psychosis    and following NMDAR antagonist administration . "
[Show abstract] [Hide abstract]
ABSTRACT: Over the last 50 years, evidence for central involvement of glutamatergic neurotransmission in the pathophysiology of schizophrenia has accumulated. Recent advances in neuroimaging technology now allow several components of glutamatergic neurotransmission to be assessed in the living human brain. Positron emission tomography (PET) or single photon emission tomography (SPET) in combination with select radiotracers allows visualization of glutamatergic receptors in vivo, and magnetic resonance (MR) - based techniques allow mapping of the effects of glutamatergic agents on regional brain activation, and the measurement of regional glutamate concentrations. These imaging studies have provided evidence for regional glutamatergic abnormalities in psychosis, and are beginning to describe both the evolution of these abnormalities over the course of the illness and their response to therapeutic intervention. In parallel, advances in small animal imaging and the development of animal models have provided a platform to explore the neuropathological consequences of glutamatergic abnormality, and the potential antipsychotic efficacy of novel compounds. The molecular diversity of the glutamatergic system has driven the design of several compounds targeting aspects of glutamatergic transmission, and clinical trials have yielded encouraging results. Here, we review the contribution of imaging studies to date in understanding glutamatergic abnormalities in psychosis, and discuss the potential of new glutamatergic compounds for treatment of the disorder.
Current pharmaceutical biotechnology 01/2012; 13(8):1500-12. DOI:10.2174/138920112800784961 · 2.51 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.