The relation between peripheral and central glutamate and glutamine in healthy male volunteers.

OBJECTIVE: High-field strength proton magnetic resonance spectroscopy ((1)H-MRS) and peripheral blood analyses reported in the literature reveal glutamate (Glu) and glutamine (Gln) abnormalities in schizophrenia. Given the relative ease and feasibility of using peripheral measures, the present study investigates the relation between peripheral and brain Glu and Gln levels. METHODS: We recruited healthy volunteers (n = 17, mean age 21.9 [standard deviation 2.9, range 18-29] yr) between May and December 2005. All participants underwent 3 Tesla (1)H-MRS analysis with segmentation (grey matter, white matter, cerebrospinal fluid) at the Nuclear Magnetic Resonance Centre at the University of Alberta Hospital to quantify medial prefrontal cortical (mPFC) Glu and Glx (i.e., combination of Glu and Gln). Within 1 week of (1)H-MRS analysis, we collected plasma from the same participants for Glu and Gln quantification, using high-performance liquid chromatography at the Neurochemical Research Unit at the University of Alberta. RESULTS: There was no correlation between plasma Glu and either medial prefrontal cortical Glu or Glx (R(1,15) = 0.019, p = 0.944 and R(1,15) = 0.081, p = 0.757, respectively). Similarly, there was no correlation between plasma Gln and either mPFC Glu or Glx (R(1,15) = 0.029, p = 0.911 and R(1,15) = 0.025, p = 0.925, respectively). CONCLUSION: Our findings support the use of (1)H-MRS, instead of peripheral blood analysis, for investigating glutamatergic dysfunction in the brain.

Determination of d-serine and related neuroactive amino acids in human plasma by high-performance liquid chromatography with fluorimetric detection.

A simple and versatile methodology using high-performance liquid chromatography (HPLC) with fluorimetric detection was developed to simultaneously determine d-serine along with other metabolically related neuroactive amino acids in the glutamatergic system: L-serine, L-glutamate, L-glutamine, and glycine. On-column sensitivity was in the lower picomole range. Of two chiral thiol reagents investigated, amino acid derivatives of o-phthaldialdehyde (OPA) in combination with N-isobutyryl-L-cysteine were found to have consistently higher responses than their corresponding N-tert-butyloxycarbonyl-L-cysteine derivatives. This methodology was applied to the quantitative detection of amino acids in human plasma and lays the foundation for further investigations of the role of neuroactive amino acids in the pathophysiology and treatment of neurological and psychiatric disorders.

Neuroactive steroids in schizophrenia.

Schizophrenia is a psychiatric disorder with a complicated pathophysiology, involving many biochemical abnormalities in the brain. Because neuroactive steroids (NASs) modulate neurotransmitter systems that are implicated in the pathology of schizophrenia, recent research has focused on examining the role that NASs play in the illness. Although research in this area is relatively new, it appears that NASs may potentially be implicated in the pathophysiology of the illness. This paper reviews the current understanding of NASs, the research literature on NASs in schizophrenia and in animal models of the illness (including the effects of antipsychotic medication on NASs) and on the potential antipsychotic role of NASs themselves and, finally, discusses future directions for this area of schizophrenia research.