Association of the MAOA promoter uVNTR polymorphism with suicide attempts in patients with major depressive disorder.

backgroundThe MAOA uVNTR polymorphism has been documented to affect the MAOA gene at the transcriptional level and is associated with aggressive impulsive behaviors, depression associated with suicide (depressed suicide), and major depressive disorder (MDD). We hypothesized that the uVNTR polymorphism confers vulnerability to MDD, suicide or both. The aim of this study was to explore the association between the MAOA uVNTR and depressed suicide, using multiple controls.

methodsFour different groups were included: 432 community controls, 385 patients with MDD who had not attempted suicide, 96 community subjects without mental disorders who had attempted suicide, and 109 patients with MDD who had attempted suicide. The MAOA uVNTR polymorphism was genotyped by a PCR technique. The symptom profiles and personal characteristics in each group were also compared.

resultsThe MAOA 4R allele was more frequent in males with MDD than in male community controls (χ2 = 4.182, p = 0.041). Logistic regression analysis showed that, among the depressed subjects, those younger in age, more neurotic or who smoked had an increased risk of suicide (β = -0.04, p = 0.002; β = 0.15, p = 0.017; β = 0.79, p = 0.031, respectively). Moreover, among those who had attempted suicide, those younger in age, with more paternal overprotection, and more somatic symptoms were more likely to be in the MDD group than in the community group (β = -0.11, p < 0.001; β = 0.15, p = 0.026; β = 1.11, p < 0.001). Structural equation modeling (SEM) showed that nongenetic factors, such as age, paternal overprotection, and somatic symptoms, were associated with MDD, whereas depressed suicide were associated with severity of depression, personality traits, age, marital status, and inversely associated with anxiety symptoms. However, depression did not affect suicidal behavior in the community group.

conclusionThe MAOA 4R allele is associated with enhanced vulnerability to suicide in depressed males, but not in community subjects. The MAOA 4R allele affects vulnerability to suicide through the mediating factor of depressive symptoms. Further large-scale studies are needed to verify the psychopathology of the relationships among MAOA uVNTR polymorphism, symptom profiles, and suicidal behavior.