Cargando…

Lower [(18)F]fallypride binding to dopamine D(2/3) receptors in frontal brain areas in adults with 22q11.2 deletion syndrome: a positron emission tomography study

BACKGROUND: The 22q11.2 deletion syndrome (22q11DS) is caused by a deletion on chromosome 22 locus q11.2. This copy number variant results in haplo-insufficiency of the catechol-O-methyltransferase (COMT) gene, and is associated with a significant increase in the risk for developing cognitive impair...

Descripción completa

Detalles Bibliográficos
Autores principales: van Duin, Esther D. A., Ceccarini, Jenny, Booij, Jan, Kasanova, Zuzana, Vingerhoets, Claudia, van Huijstee, Jytte, Heinzel, Alexander, Mohammadkhani-Shali, Siamak, Winz, Oliver, Mottaghy, Felix, Myin-Germeys, Inez, van Amelsvoort, Thérèse
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cambridge University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168654/
https://www.ncbi.nlm.nih.gov/pubmed/30935427
http://dx.doi.org/10.1017/S003329171900062X
Descripción
Sumario:BACKGROUND: The 22q11.2 deletion syndrome (22q11DS) is caused by a deletion on chromosome 22 locus q11.2. This copy number variant results in haplo-insufficiency of the catechol-O-methyltransferase (COMT) gene, and is associated with a significant increase in the risk for developing cognitive impairments and psychosis. The COMT gene encodes an enzyme that primarily modulates clearance of dopamine (DA) from the synaptic cleft, especially in the prefrontal cortical areas. Consequently, extracellular DA levels may be increased in prefrontal brain areas in 22q11DS, which may underlie the well-documented susceptibility for cognitive impairments and psychosis in affected individuals. This study aims to examine DA D(2/3) receptor binding in frontal brain regions in adults with 22q11DS, as a proxy of frontal DA levels. METHODS: The study was performed in 14 non-psychotic, relatively high functioning adults with 22q11DS and 16 age- and gender-matched healthy controls (HCs), who underwent DA D(2/3) receptor [(18)F]fallypride PET imaging. Frontal binding potential (BP(ND)) was used as the main outcome measure. RESULTS: BP(ND) was significantly lower in adults with 22q11DS compared with HCs in the prefrontal cortex and the anterior cingulate gyrus. After Bonferroni correction significance remained for the anterior cingulate gyrus. There were no between-group differences in BP(ND) in the orbitofrontal cortex and anterior cingulate cortex. CONCLUSIONS: This study is the first to demonstrate lower frontal D(2/3) receptor binding in adults with 22q11DS. It suggests that a 22q11.2 deletion affects frontal dopaminergic neurotransmission.