Risk factors for the neurohumoral alterations underlying personality disturbances

Numerous studies have shown that MAO-B activity in platelets correlates with specific personality characteristics such as sensation seeking and impulsiveness. Low levels of platelet MAO as well as the personality traits associated with these low levels have been associated with type 2 alcoholism, recurrent criminality and antisocial violent behavior. Platelet MAO has a high degree of heritability and regulation of MAOB gene expression seems to explain most of the inter-individual differences in activity. The transcription factor family AP-2 is an important regulatory factor for neural gene expression and neural development, especially in midbrain structures, including the monoaminergic nuclei. In man, the gene encoding AP-2beta contains a polymorphic region in the second intron, consisting of a variable number of tandem repeats [CAAA](4-5). The long AP-2beta allele has previously been associated with specific personality traits as well as with binge-eating disorder characterized by an impulsive temperament. We have shown that males and females homozygous for the long AP-2beta allele display significantly lower platelet MAO activity compared to subjects with one or two short alleles. Thus, we find it likely that the personality disturbances previously linked to low platelet MAO activity could be associated with the presence of two long alleles of the AP-2beta gene. We suggest that the molecular mechanisms underlying the association between platelet MAO and vulnerability, e.g. substance abuse, may involve specific transcription factors that regulate the expression of midbrain monoamine structures as well as that of platelet MAO.