Dopamine metabolism in adults with 22q11 deletion syndrome, with and without schizophrenia – relationship with COMT Val 108/158 Met polymorphism, gender and symptomatology

22q11 Deletion syndrome (22q11DS) is a major risk factor for schizophrenia. In addition, both conditions are associated with alterations of the dopaminergic system. The catechol- O-methyltransferase (COMT) gene, located within the deleted region, encodes for the enzyme COMT that is important for degradation of catecholamines, including dopamine (DA). COMT activity is sexually dimorphic and its gene contains a functional polymorphism, Val 108/158 Met; the Met allele is associated with lower enzyme activity. We report the first controlled catecholamine study in 22q11DS-related schizophrenia. Twelve adults with 22q11DS with schizophrenia (SCZ+) and 22 adults with 22q11DS without schizophrenia (SCZ-) were genotyped for the COMT Val 108/158 Met genotype. We assessed dopaminergic markers in urine and plasma. We also correlated these markers with scores on the Positive and Negative Symptom Scale (PANSS). Contrary to our expectations, we found SCZ+ subjects to be more often Val hemizygous and SCZ- subjects more often Met hemizygous. Significant COMT cross gender interactions were found on dopaminergic markers. In SCZ+ subjects there was a negative correlation between prolactin levels and scores on the general psychopathology subscale of the PANSS scores. These findings suggest intriguing, but complex, interactions of the COMT Val 108/158 Met polymorphism, gender and additional factors on DA metabolism, and its relationship with schizophrenia.