Association between a functional polymorphism in the monoamine oxidase A gene promoter and major depressive disorder

Abstract

Various polymorphisms of the X-chromosomal monoamine oxidase A (MAO-A) gene were investigated for association with affective disorders. However, none of the studied variants could consistently be associated with either major depressive or bipolar affective disorder. Recently, a positive association between panic disorder and a novel functional repeat polymorphism in the MAO-A gene promoter, with the longer alleles being more active, was reported. Since monoaminergic neurotransmission is supposed to play an important role in affective disorders, we investigated a potential association of this polymorphism with major depressive illness in a sample of 146 unrelated patients of German descent and a control group of 101 individuals with a negative life history for affective disorders. Similarly to the recent findings in panic disorder, we observed a significantly increased frequency of genotypes containing only long alleles in female patients with recurrent major depression in comparison with age- and sex-matched controls. Thus, our data suggest that an excess of high-activity MAO-A gene promoter alleles resulting in an elevated MAO-A activity is a risk factor for major depressive disorder in females. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:801-803, 2000.

Maternal Recurrent Mood Disorders and High-Functioning Autism

“…One form of this polymorphism was associated with relatively higher social and language ability in boys. This same MAOA polymorphism also has been implicated as playing a role in the etiology of recurrent major depression in women (Schulze et al, 2000). This could explain why effects in the current study were specific to mothers and not to fathers.…”

Impulsivity, aggression, and serotonin: a molecular psychobiological perspective

“…The transcriptional efficiency of the three-repeat allele was two-fold lower than those with longer repeats and enzyme activity is correlated with repeat length (Denney, Koch, & Craig, 1999). Preliminary evidence indicates that length variation of the MAOA-LPR confers vulnerability to antisocial behavior in alcohol-dependent males (Samochowiec et al, 1999) is linked to impulsivity, hostility and lifetime aggression history as well as CNS serotonergic function in a community sample of men (Manuck, Flory, Ferrell, Mann, & Muldoon, 2000), may be associated with aggression-related behavior in rhesus monkeys (Bennett, Lesch, & Higley, unpublished results), and appears to be a risk factor for panic disorder and unipolar depression in female patients (Deckert et al, 1999;Schulze et al, 2000) but not for other psychiatric disorders (Furlong, Rubinsztein, Walsh, Paykel, & Rubinsztein, 1999;Syagailo et al, manuscript submitted).…”

MAOA Variants and Genetic Susceptibility to Major Psychiatric Disorders

“…Monoamine oxidase A (MAOA) is a key enzyme that degrades many monoaminergic neurotransmitters in the brain and has drawn much attention in investigations of severe psychiatric disorders like SCZ, BPD, and MDD [14,15]. Previous genetic analyses in small samples implied that MAOA variants may confer susceptibility to SCZ [16], BPD [17], MDD [18,19], attention deficit hyperactivity disorder [20], and panic disorder [21], but negative results have also been observed [22][23][24][25]. Genetic association studies on MAOA gene have primarily focused on the following common variants: a promoter variable number tandem repeat (uVNTR) polymorphism [19,22], a VNTR in the intron 1 (VNTR) [26,27], a dinucleotide repeat in intron 2 (MAOA-CA) [26,28], and some exonic single nucleotide polymorphisms (SNPs, rs1799835 and rs1370770) [19,26,29].…”