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Purpose: Aging is a major societal concern due to age-related functional losses. Synapses are crucial components of neural circuits, and synaptic density could be a sensitive biomarker to evaluate brain function. [11C]UCB-J is a positron emission tomography (PET) ligand targeting synaptic vesicle glycoprotein 2A (SV2A), which can be used to evaluate brain synaptic density in vivo. Methods: We evaluated age-related changes in gray matter synaptic density, volume, and blood flow using [11C]UCB-J PET and magnetic resonance imaging (MRI) in a wide age range of 80 cognitive normal subjects (21–83 years old). Partial volume correction was applied to the PET data. Results: Significant age-related decreases were found in 13, two, and nine brain regions for volume, synaptic density, and blood flow, respectively. The prefrontal cortex showed the largest volume decline (4.9% reduction per decade: RPD), while the synaptic density loss was largest in the caudate (3.6% RPD) and medial occipital cortex (3.4% RPD). The reductions in caudate are consistent with previous SV2A PET studies and likely reflect that caudate is the site of nerve terminals for multiple major tracts that undergo substantial age-related neurodegeneration. There was a non-significant negative relationship between volume and synaptic density reductions in 16 gray matter regions. Conclusion: MRI and [11]C-UCB-J PET showed age-related decreases of gray matter volume, synaptic density, and blood flow; however, the regional patterns of the reductions in volume and SV2A binding were different. Those patterns suggest that MR-based measures of GM volume may not be directly representative of synaptic density. [ABSTRACT FROM AUTHOR]

Background: Metabotropic glutamate receptor 5 (mGlu5) dysregulation has been implicated in the pathophysiology of trauma-related psychopathology, and there are direct interactions between the endocannabinoid and glutamatergic systems. However, relationships between cannabis use (CU) and mGlu5 have not been directly investigated in trauma-related psychopathology., Methods: Using positron emission tomography (PET) with [18F]FPEB, we examined relationships between CU status and mGlu5 availability in vivo in a cross-diagnostic sample of individuals with trauma-related psychopathology(N = 55). Specifically, we tested whether mGlu5 availability in frontolimbic regions of interest (ROIs; dlPFC, OFC, vmPFC, amygdala, hippocampus) differed as a function of CU status., Results: Past year CU (n = 22) was associated with 18.97-19.12% higher mGlu5 availability in frontal and 14.24-16.55% higher in limbic ROIs relative to participants with no recent CU. Similarly, past month/monthly CU (n = 16) was associated with higher mGlu5 availability in frontal (18.05-20.62%) and limbic (15.53-16.83%) ROIs. mGlu5 availability in the OFC and amygdala was negatively associated with depressive symptoms in the past year CU group. In both CU groups, exploratory analyses showed negative correlations between mGlu5 availability and sadness across all ROIs, and with perceptions of worthlessness, and past failures (r's = -.46-.66, p's = .006-.033) in the vmPFC. Participants with CU reported lower mean depressive symptoms (p's = .019-.031) relative to those without CU., Conclusions: These findings have substantial implications for our understanding of interactions between CU and glutamatergic neurotransmission in trauma-related psychopathology, underscoring the need for treatment development efforts to consider the effects of CU in this population., (© The Author(s) 2024. Published by Oxford University Press on behalf of CINP.)