Monoamine oxidase A (MAOA) activity is altered in mood disorders and lower activity associated with aggressive behavior. The gene has a functional polymorphism with a variable number tandem repeat (VNTR) in the upstream regulatory region (MAOA-uVNTR). In this study, we examined possible associations between the MAOA-uVNTR polymorphism and mood disorders, suicidal behavior, aggression/impulsivity, and effects of reported childhood abuse. In total, 663 unrelated subjects with a psychiatric disorder and 104 healthy volunteers were genotyped for the 30 base pair functional VNTR. A novel repeat variation was identified. No statistically significant associations were found between this functional MAOA-uVNTR polymorphism and mood disorders or suicide attempts. However, the lower expression allele was associated with a history of abuse before 15 years of age in male subjects and with higher impulsivity in males but not females. Our results suggest that the lower expression of the MAOA-uVNTR polymorphism is related to a history of early abuse and may sensitize males, but not females, to the effects of early abuse experiences on impulsive traits in adulthood. The polymorphism may be a marker for impulsivity that in turn may contribute to the risk for abuse. This trait could then be further aggravated by abuse.

Dysfunction of the serotonin (5-HT1A) receptor (5-HTR1A) has been implicated in mood disorders, anxiety disorders, psychosis and the action of antidepressants. A common C(-1018)G [C(-1019)G] functional polymorphism in the promoter region of the human 5-HT1A receptor gene has been reported, which may be useful in identifying psychopathology associated with altered function of the human 5-HT1A receptor. We studied the relationship of this polymorphism to psychopathology and 5-HT1A binding in prefrontal cortex. The 5-HT1A receptor genotype for the C(-1019)G polymorphism was typed in 696 unrelated psychiatric subjects, 107 unrelated healthy volunteers, and in post-mortem brain samples from 241 cases. 5-HT1A receptor binding was assayed in post-mortem prefrontal cortex using [3H]8-OH-DPAT, and specific binding determined by 1 microM 5-HT. An association of genotype distribution and allele frequency of the 5-HTR1A C(-1019)G locus was observed in schizophrenia (chi2=9.51, d.f.=2, p=0.009; chi2=9.52, d.f.=1, p=0.002; Armitage's trend test: chi2=9.07, d.f.=1, p=0.003), in substance use disorder (chi2=8.41, d.f.=2, p=0.015; chi2=8.35, d.f.=1, p=0.004; Armitage's trend test: chi2=6.27, d.f.=1, p=0.0012), and in panic attack (chi2=6.31, d.f.=2, p=0.043; chi2=6.14, d.f.=1, p=0.013; Armitage's trend test: chi2=6.27, d.f.=1, p=0.012). An association of the 5-HTR1A C(-1019)G locus with schizophrenia, substance use disorder, and panic attack was suggested by our results. In post-mortem brain samples, 5-HT1A receptor binding in prefrontal cortex and suicide were not associated with genotype. The relationship does not appear to be explained by binding differences, although we cannot rule out altered receptor affinity and transduction.