Disrupted dopaminergic neurotransmission in 22q11 deletion syndrome

22q11 Deletion syndrome (22q11DS) is associated with chromosome 22q11 microdeletions and high rates of psychiatric disorders. Susceptibility for these disorders could be explained by haploinsufficiency of the catechol-O-methyltransferase gene, which encodes an enzyme involved in dopamine (DA) breakdown. It is unknown how dopaminergic neurotransmission is affected in people with 22q11DS. To date, there have been no controlled studies investigating dopaminergic neurotransmission in people with 22q11DS. We report the results of a challenge study in high-functioning adults with 22q11DS and age- and gender-matched controls using neuro-endocrine and peripheral dopaminergic markers. At baseline, 22q11DS subjects compared to controls had higher urine DA levels and lower plasma levels of the predominant DA metabolite homovanillic acid (HVA). Following DA depletion, 22q11DS subjects showed lower urine and plasma HVA levels and a lower prolactin response than controls. The ratio of DA/HVA, a rough index of DA turnover, was significantly higher in the 22q11DS subjects at baseline and after DA depletion. Our results suggest that adults with 22q11DS have disrupted dopaminergic neurotransmission, which might explain their susceptibility for psychiatric disorders.