22q11.2 deletion syndrome as a natural model for COMT haploinsufficiency-related dopaminergic dysfunction in ADHD

Abstract

In the current issue of IJNP Gothelf and co-workers report an important study which sheds light on the association between chromosome 22q11.2 deletion syndrome (22q11.2 DS; velocardiofacial syndrome, VCFS), dopaminergic transmission, and psychiatric disorders. 22q11.2 DS occurs in at least 1/5000 live births and thus is the most common chromosomal deletion syndrome in humans (Botto et al., 2003). The deletion in the long arm of chromosome 22, usually comprises up to 3 Mb, and is transmitted dominantly, although most patients suffer from de-novo mutations. The clinical phenotype ranges from immune deficiency with thymal aplasia, congenital heart abnormalities, velopharyngeal insufficiency with hypernasal speech, slight dysmorphy with characteristic facies, to severe syndromal developmental abnormalities with mental retardation (Shprintzen, 2000). Most interestingly for the field of neuropsychiatry, 22q11.2 DS is associated with an increased rate of variety of psychiatric disorders. In childhood and adolescence, 22q11.2 DS is associated with attention deficit hyperactivity disorder (ADHD; Antshel et al., 2005; Niklasson et al., 2002), affecting up to 55% of the patients (Gothelf et al., 2004). Another, less frequent comorbidity in adolescence seems to be obsessive–compulsive disorder (OCD; Gothelf et al., 2006). Finally, there is an increased prevalence for comorbidity with schizophrenic and bipolar affective psychoses in adulthood (Murphy, 2005).