n-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2-3-dimethoxybenzamide and DiGeorge-Syndrome

Individuals with 22q11.2 deletion syndrome (22q11DS) are at increased risk of developing psychosis and cognitive impairments, which may be related to dopaminergic and glutamatergic abnormalities. Therefore, in this exploratory study, we examined the association between dopaminergic and glutamatergic functioning in 22q11DS. Additionally, the associations between glutamatergic functioning and brain volumes in 22q11DS and healthy controls (HC), as well as those between dopaminergic and cognitive functioning in 22q11DS, were also examined.. In this cross-sectional, multimodal imaging study, glutamate, glutamine, and their combined concentration (Glx) were assessed in the anterior cingulate cortex (ACC) and striatum in 17 22q11DS patients and 20 HC using 7T proton magnetic resonance spectroscopy. Ten 22q11DS patients also underwent. No significant associations were found between ACC or striatal (1) glutamate, glutamine, or Glx concentrations and (2) D. Although our results did not reach statistical significance, our findings suggest an association between glutamatergic functioning and brain volume in HC but not in 22q11DS. Additionally, D

Topics: Benzamides; Cognition; Cross-Sectional Studies; DiGeorge Syndrome; Dopamine; Glutamic Acid; Glutamine; Humans; Positron-Emission Tomography; Proton Magnetic Resonance Spectroscopy

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 D2/3 receptor binding in frontal brain regions in adults with 22q11DS, as a proxy of frontal DA levels.. 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 D2/3 receptor [18F]fallypride PET imaging. Frontal binding potential (BPND) was used as the main outcome measure.. BPND 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 BPND in the orbitofrontal cortex and anterior cingulate cortex.. This study is the first to demonstrate lower frontal D2/3 receptor binding in adults with 22q11DS. It suggests that a 22q11.2 deletion affects frontal dopaminergic neurotransmission.

Topics: Adult; Benzamides; Brain Mapping; Catechol O-Methyltransferase; DiGeorge Syndrome; Female; Humans; Male; Middle Aged; Positron-Emission Tomography; Prefrontal Cortex; Psychotic Disorders; Receptors, Dopamine D2; Young Adult

22q11.2 deletion syndrome (22q11DS) is a genetic disorder caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk for developing psychosis. The catechol-O-methyltransferase (COMT) gene is located in the deleted region and involved in dopamine (DA) breakdown. Impaired reinforcement learning (RL) is a recurrent feature in psychosis and thought to be related to abnormal striatal DA function. This study aims to examine RL and the potential association with striatal DA-ergic neuromodulation in 22q11DS. Twelve non-psychotic adults with 22q11DS and 16 healthy controls (HC) were included. A dopamine D

Topics: Adult; Benzamides; Brain Mapping; Catechol O-Methyltransferase; Corpus Striatum; DiGeorge Syndrome; Dopamine; Dopamine D2 Receptor Antagonists; Female; Fluorodeoxyglucose F18; Humans; Intelligence Tests; Learning Disabilities; Magnetic Resonance Imaging; Male; Methionine; Middle Aged; Mutation; Positron-Emission Tomography; Reinforcement, Psychology; Task Performance and Analysis; Valine