The Relationships between Dopaminergic, Glutamatergic, and Cognitive Functioning in 22q11.2 Deletion Syndrome: A Cross-Sectional, Multimodal (1)H-MRS and (18)F-Fallypride PET Study

Background: 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. Methods: 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 (18)F-fallypride positron emission tomography to measure dopamine D(2/3) receptor (D(2/3)R) availability in the ACC and striatum. Cognitive performance was assessed with the Cambridge Neuropsychological Test Automated Battery. Results: No significant associations were found between ACC or striatal (1) glutamate, glutamine, or Glx concentrations and (2) D(2/3)R availability. In HC but not in 22q11DS patients, we found a significant relationship between ACC volume and ACC glutamate, glutamine, and Glx concentration. In addition, some aspects of cognitive functioning were significantly associated with D(2/3)R availability in 22q11DS. However, none of the associations remained significant after Bonferroni correction. Conclusions: 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(2/3)R availability seems to be related to cognitive functioning in 22q11DS. Studies in larger samples are needed to further elucidate our findings.