Mild learning difficulties and offending behaviour--is there a link with monoamine oxidase A deficiency?

ABSTRACT

We have attempted to replicate the findings of Brunner et al., who described a large Dutch kindred where several males were of borderline intelligence and showed characteristically aggressive and sometimes dangerous or extremely antisocial behaviour. The genetic defect for this syndrome was assigned to the p11-p21 region of the X chromosome following linkage analysis in a single kindred. Subsequent sequencing of a candidate gene, monoamine oxidase A (MAO-A), at the position of maximum linkage revealed a causative mutation in the coding region of the MAO-A gene in position 936. In addition to identifying both the phenotype and the associated mutation found by Brunner et al., we also wished to test the hypothesis that mutations elsewhere in the MAO-A gene could cause the low intelligence quotient/personality disorder phenotype associated with low urinary catecholamine degradation products. Fifty-four male subjects similar in clinical characteristics to the affected males in the Dutch kindred were identified within secure mental health facilities in England and Wales. All were assessed using the antisocial personality disorder section of the SCID-II interview instrument, and information about their offending behaviour and family history was obtained from the medical notes. A blood and early-morning urine sample was obtained from each patient. Analysis of urinary excretion patterns of biogenic amines and their metabolites, represented as ratios of normetanefrine to vanillylmandelic acid, revealed two possible cases of MAO-A deficiency, which were found to be negative after resampling.