CYP2D6 gene test in psychiatric patients and healthy volunteers.

BACKGROUND: Antipsychotic drug therapy meets difficulties in predicting response in psychiatric patients. The medical treatment of these patients may be improved significantly by systematic phamacogenetic diagnosis identifying the drug metabolic capacities of each patient. Genetic polymorphisms in the coding sequence for the drug metabolizing cytochrome P450 enzyme CYP2D6 represent a pharmacogenetic target. METHODS: A cohort (n = 225) representing psychiatric patients seen during an 18-month trial period was included in the project after the subjects accepted a blood sample being taken to analyse their CYP2D6 allelic composition. To investigate any putative difference in allele frequencies among the psychiatric patients compared to earlier publications on allele frequencies in Caucasian populations, another cohort (n = 122) of local healthy volunteers was likewise included. RESULTS: Allelic frequencies in the psychiatric patients and healthy volunteers were indistinguishable. Alleles *1 and *2 encoding for normal enzyme activity and alleles *3, *4, *5, *6, *13/*16 representing non-active forms were found as well as alleles *9, *10, *41 encoding for enzymes with decreased activity. Furthermore, examples of the previously described duplications of *1 and *2, which result in enhanced enzyme activity, were also identified. CONCLUSION: A systematic CYP2D6 gene test of hospitalized psychiatric patients revealed the identification of pharmacogenetically relevant alleles affecting capacity to metabolize antipsychotics. The frequencies of phenotypes in affected patients were 8.4 % intermediate metabolizers (IMs), 8.4 % poor metabolizers (PMs) and 3.1 % ultrafast metabolizers (UMs), whereas 52.4 % were extensive metabolizers (EMs) and 27.6 % heterozygous EMs.

1H NMR spectroscopic investigations of tissue metabolite biomarker response to Cu II exposure in terrestrial invertebrates: identification of free histidine as a novel biomarker of exposure to copper in earthworms.

High resolution 1H NMR spectroscopy of biofluids, cells and tissue extracts allows rapid, non destructive analysis for a wide range of metabolites and organic compounds with minimal sample pre treatment. We have applied high resolution 1H NMR spectroscopy to investigate the biochemical effects of Cu II in two earthworm species Eisenia andrei n =78 and Lumbricus rubellus n =45 exposed under laboratory and semi field conditions respectively. The most marked metabolic response was the elevation of endogenous whole body free histidine in animals which positively correlated with increasing copper exposure and total copper burden in the semi field experiment. Histidine forms thermodynamically stable copper complexes under a wide range of physico chemical conditions and we proposed that the elevation of free histidine in response to copper challenge provides an energetically low cost detoxification mechanism. Histidine elevation may also provide a novel molecular biomarker of Cu II exposure in environmental situations.