Abstract
P237
Introduction: Synaptic phenotypes in living patients with psychiatric disorders are poorly characterized. Excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is a fundamental component for neurotransmission. We recently developed a positron emission tomography (PET) tracer for AMPAR, [11C]K-2, the first technology to visualize AMPARs in living human brain.
Methods: One hundred forty-nine patients with psychiatric disorders (schizophrenia, n=42; bipolar disorder, n=37; depression, n=35; and autism spectrum disorder, n=35) and 70 healthy participants underwent a PET scan with [11C]K-2 for measurement of AMPAR density. Brain regions with correlation between AMPAR density and symptomatology scores of each disease and those that showed differences in AMPAR density between patients and healthy participants were identified by using a voxel-wise analysis.
Results: Specific brain regions that showed correlation between AMPAR density and symptomatology scores were detected in each of four disorders. We also found brain areas with significant differences in AMPAR density between patients with each psychiatric disorder and healthy participants. Some of these areas were observed across diseases, indicating that these are commonly affected areas throughout psychiatric disorders.
Conclusions: Schizophrenia, bipolar disorder, depression, and autism spectrum disorder are uniquely characterized by AMPAR distribution patterns. Moreover, the presence of the commonly affected regions in comparison to healthy controls suggests that these disorders may share the biological characteristic in terms of AMPAR. Our approach to psychiatric disorders using [11C]K-2 can elucidate the biological mechanisms across diseases and pave the way to develop novel diagnostics and therapeutics based on the synapse physiology.
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