Striatal dopamine transporter binding in adults with 22q11.2 copy number variants: a SPECT study

Abstract Copy number variants at the 22q11.2 chromosomal locus, hemizygous 22q11.2 deletions or duplications, are associated with a broad spectrum of neuropsychiatric and other medical conditions. Individuals with a 22q11.2 deletion are at increased risk for developing early-onset Parkinson’s disease. The catechol-O-methyltransferase gene at 22q11.2 is involved in dopamine metabolism. While previous studies have examined several aspects of dopamine function in individuals with 22q11.2 copy number variants, striatal dopamine transporter availability, a regulator of synaptic dopamine, has not yet been systematically investigated. Therefore, dopamine transporter availability was quantified in nine adults with a 22q11.2 deletion, nine with a 22q11.2 duplication, and eight controls using a brain-dedicated single-photon emission computed tomography (SPECT) system. Specific striatal binding ratios were calculated with the occipital lobe as reference region. Permutation analysis of covariance controlling for age and sex showed significantly higher striatal dopamine transporter availability in adults with 22q11.2 deletions compared with those with duplications (p = 0.026, η2p= 0.30). No significant differences were observed between adults with 22q11.2 copy number variants and controls. These findings suggest distinct nigrostriatal dopaminergic profiles associated with 22q11.2 copy number variant status, which may play a role in shaping frequently occurring neurological and psychiatric phenotypes in these individuals.