Catechol-O-methyltransferase (COMT) polymorphisms modulate working memory in individuals with schizophrenia and healthy controls

Objective: Cognitive impairment is a core feature of schizophrenia, related to dopaminergic dysfunction in the prefrontal cortex (PFC). It is hypothesized that functional single nucleotide polymorphism (SNP) rs4680 of the catechol-O-methyltransferase (COMT) gene could mediate the relationship between cognition and dopamine activity in the PFC. Other COMT SNPs could also play a role. Methods: We evaluated the role of three COMT SNPs (rs737865, rs165599, and rs4680) in schizophrenia and their impact on three working memory tasks. For genetic association analyses, 212 individuals with schizophrenia and 257 healthy controls (HCs) were selected. The Visual Working Memory (VWM) Task, Keep Track Task, and Letter Memory Task were administered to 133 schizophrenics and 93 HCs. Results: We found a significant association of rs737865, with the GG genotype exerting a protective effect and the GA haplotype (rs4680/rs165599) exerting a risk effect for schizophrenia. COMT rs4680 AA carriers and rs737865 AA carriers scored lowest on the Keep Track Task. When the genotype*group interaction effect was evaluated, rs165599 exerted opposite effects for VWM and Keep Track task performance in patients and controls, with AA carriers scoring lowest on both tests among controls, but highest among patients. Conclusion: These data support the hypothesis that COMT polymorphisms may be associated with schizophrenia and modulate cognition in patients and controls.

Research Progress on Abused Drugs Metabolic in vivo / 法医学杂志

Under the catalysis of a variety of metabolic enzymes in vivo, such as UDP-glucuronyl transferases, cytochrome P450, carboxylesterase, sulfotransferase, butyrylcholinesterase, catechol-O-methyl transferase and 6-morphine dehydrogenase, the drugs perform glucuronidation, hydrolysis, oxidation, sulfonation and other reactions, then translate into active or inactive metabolites, which are excreted through urination, bile or the other pathways at last. Different drugs own their different metabolic pathways. This paper introduces the studies about the metabolism of drugs in human and animal in recent years, such as morphine-like drugs, amphetamine, ketamine, cannabis and cocaine, and reviews the research progress about the sites of metabolism, metabolic enzymes, metabolites and physiological activity of those drugs metabolic in vivo.

Changes in hypothalamic catechol-0-methyl-transferase during sexual differentiation of the brain

1. An assay using [14 C-methyl]-S-adenosyl-L-methionine was used to measure catecholamine-O-methyl-transferase (COMT) activity in the hypothalamus of newborn male and female rats from day 1 to day 12 and in adult animals after day 60. 2. There was no difference in COMT activity between sexes until day 8, when it became significantly higher in females. 3. Administration of 200 microng testosterone propionate to female rats at birth reduced the hypothalamic COMT level of the adult to that observed for male littermates. The response was dose-dependent in the range 50 to 200 microng. The hypothalamic contnet of COMT after puberty of male rats castrated ar birth was comparable to that of post-pubertal females. 4. These results show that COMT, one of the enzymes involved in the control of brain biogenic amines, is also affected by the process of sexual differentiation of the brain