Monoamine Oxidase in Neuropsychiatry and Behavior

Abstract

Monoamine oxidase (MAO) catalyzes the oxidative deamination of a number of biogenic amines, including the key neurotransmitters serotonin (5-HT), norepinephrine (NE), and dopamine (DA) and the neuromodulator phenylethylamine (PEA). Two forms of MAO, designated "MAO A" and "MAO B," have been identified on the basis of biochemical properties and, subsequently, by cloning the relevant genes. Of the two, MAO A exhibits a higher affinity for 5-HT and NE and for the inhibitor clorgyline (Johnston 1968), whereas MAO B has a higher affinity for PEA, benzylamine, and the inhibitor deprenyl (Knoll and Magyar 1972). DA is a substrate for both MAO A and MAO B. Although most tissues express both isoenzymes, human placenta and fibroblasts express predominantly MAO A, and platelets and lymphocytes express only MAO B (for review, see Shih et al. 1999).The ability of the MAOs to catabolize neurotransmitters has made these enzymes attractive candidates in the study of neurological diseases and psychiatric and behavioral traits. Indeed, even before the genes for MAO A and B were cloned, the role of MAO B in psychiatric disorders was widely studied. Platelets, which are easily obtained and lack MAO A expression, were the cell type of choice for much of this work. Low platelet MAO B activity has been associated with bipolar disorder, suicidal behavior, and alcoholism (Devor et al. 1993), as well as with sensation seeking and poor impulse control (Oreland 1993;Holschneider and Shih 1998). However, much of this biochemical work may need to be revisited, given the recent finding that smoking inhibits both MAO A activity and MAO B activity (Fowler et al. 1996a(Fowler et al. , 1996b. For instance, after correcting for the effect of smoking, Simpson et al. (1999) determined that MAO

Malignancy-associated X chromosome allelic losses in foregut endocrine neoplasms: further evidence from lung tumors

“…MAOA gene product preferentially catalyzes the oxidative deamination of biogenic amines such as 5-hydroxytryptamine, norepinephrine and epinephrine. 24 To our knowledge, no data on cancerassociated allelic losses involving the microsatellite MAOA, as well as DXS56 at Xq13.2-Xq13.3, have been reported in the literature so far.…”

A high-density single-nucleotide polymorphism screen of 23 candidate genes in attention deficit hyperactivity disorder: suggesting multiple susceptibility genes among Chinese Han population

“…30 Dysregulation of monoamine pathways has long been implicated as one of the mechanisms involved in the etiology of ADHD. Several groups [31][32][33][34][35][36] have set out to test whether MAOA confers risk for ADHD, however, definite conclusion has not yet been received.…”

Mutations in human monoamine-related neurotransmitter pathway genes

“…Selective MAO-A deficiency observed in males from a Dutch family revealed relatively mild symptoms associated with impulsive aggression (for more details on the different phenotypes of these patients see Brunner et al [1993]; Lenders et al [1996]; and ). Furthermore, MAOA deficient knockout mice manifested a distinct behavioral disturbances, including enhanced aggression in males, and aggression was normalized by restoring MAOA expression [Cases et al, 1995;Shih and Thompson, 1999]. In the Dutch family, MAO-A deficiency was diagnosed based on urinary metabolites like elevated NMET and tyramine, low 5HIAA, VMA and HVA, as well as mutation analysis of the MAOA gene.…”