MR spectroscopy: its potential role for drug development for the treatment of psychiatric diseases

Abstract

Magnetic resonance spectroscopy (MRS) is likely in the near future to play a key role in the process of drug discovery and evaluation. As the pharmaceutical industry seeks biochemical markers of drug delivery, efficacy and toxicity, this non-invasive technique offers numerous ways to study adults and children repeatedly and without ionizing radiation. In this article, we survey an array of the information that MRS offers about neurochemistry in general and psychiatric disorders and their treatment in particular. We also present growing evidence of glial abnormalities in neuropsychiatric disorders and discuss what MRS is contributing to that line of investigation. The third major direction of this article is the discussion of where MRS techniques are headed and how those new techniques can contribute to studies of mechanisms of psychiatric disease and drug discovery.

Correlations of ADHD symptoms with neurometabolites measured by 1H magnetic resonance spectroscopy

“…NAA is a neurometabolite present exclusively in neurons and is considered to be a biomarker of neural viability and metabolic health, a sensitive indicator of neuronal damage (61), and mitochondrial source of energy (62). NAA changes as manifestations of brain neuroplasticity are discussed (63).…”

“…Cholinecontaining compounds present inside the tCho (total choline) peak, phosphocholine and glycerophosphocholine, are involved in the metabolism of membrane lipids, namely phosphatidylcho- line and sphingomyelin. Thus the peak of choline is considered to be an indicator of membrane metabolism and provides the information about the increased membrane degradation or synthesis (61). In the right frontal lobe, higher choline resonances have been found in children with ADHD compared to healthy subjects (53).…”

Tissue‐specific toxicological effects of cadmium in green mussels (Perna viridis): Nuclear magnetic resonance‐based metabolomics study

“…In this study, the altered levels of glutamate and glutamine imply that, when the mussels were exposed to Cd, free metallic ions could enter the central nervous system, causing disturbed glutamate-glutamine metabolism, leading to neurotoxicity. Lactate is related to the reduced use of metabolites in the citric acid cycle and to an increase in anaerobic cell energy metabolism, in which it results from conditions under which the activation of glycolysis exceeds that of oxidative phosphorylation (extreme exercise) or from muscle activity when energy demand exceeds energy supply [50]. The elevation of NAD in adductor muscle was concomitant with that in the digestive gland tissues from the same experimental mussels with high-dose Cd exposure.…”

Magnetic resonance assays of haloperidol in human serum albumin

“…19 F MR has been already used in clinical studies of mapping fluorine drugs in human brain (Lyoo and Renshaw, 2002). The result of work in this area is the fact that accumulation of agents in the brain can be much slower than in plasma (Mason and Krystal, 2006). In addition, drug level in brain can exceed drug level in plasma (Strauss and Dager, 2001).…”