The relationship between glutamate, dopamine, and cortical gray matter: A simultaneous PET-MR study

Abstract

Prefrontal cortex has been shown to regulate striatal dopaminergic function via glutamatergic mechanisms in preclinical studies. Concurrent disruption of these systems is also often seen in neuropsychiatric disease. The simultaneous measurement of striatal dopamine signaling, cortical gray matter, and glutamate levels is therefore of major interest, but has not been previously reported. In the current study, twenty-eight healthy subjects underwent 2 simultaneous [11C]-( + )-PHNO PET-MRI scans, once after placebo and once after amphetamine in a double-blind randomized cross-over design, to measure striatal dopamine release, striatal dopamine receptor (D2/3R) availability, anterior cingulate glutamate+glutamine (Glx) levels, and cortical gray matter volumes at the same time. Voxel-based morphometry was used to investigate associations between neurochemical measures and gray matter volumes. Whole striatum D2/3R availability was positively associated with prefrontal cortex gray matter volume (pFWE corrected = 0.048). This relationship was mainly driven by associative receptor availability (pFWE corrected = 0.023). In addition, an interaction effect was observed between sensorimotor striatum D2/3R availability and anterior cingulate Glx, such that in individuals with greater anterior cingulate Glx concentrations, D2/3R availability was negatively associated with right frontal cortex gray matter volumes, while a positive D2/3R-gray matter association was observed in individuals with lower anterior cingulate Glx levels (pFWE corrected = 0.047). These results are consistent with the hypothesis that the prefrontal cortex is involved in regulation of striatal dopamine function. Furthermore, the observed associations raise the possibility that this regulation may be modulated by anterior cingulate glutamate concentrations.

The relationship between striatal dopamine and anterior cingulate glutamate in first episode psychosis changes with antipsychotic treatment

“…Striatal dopamine synthesis capacity (Ki cer ) can be measured in-vivo using positron emission tomography, and cortical glutamate can be measured using proton magnetic resonance spectroscopy (MRS). Effects on separate components of the dopamine and glutamate systems have been examined in few in-vivo studies [ 16 ] but not together in the same population. One study showed a decrease in Ki cer with sub-chronic haloperidol in 9 people with schizophrenia free of antipsychotic medication [ 17 ], whilst another found no difference in whole striatal Ki cer in 17 people with first episode psychosis, initially not taking antipsychotic medication, who were then treated naturalistically with second generation antipsychotics [ 18 ].…”