{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T09:02:10Z","timestamp":1794214930920,"version":"4.8.0"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neural Circuits"],"abstract":"<jats:p>An accurate diagnostic method using biological indicators is critically needed for bipolar disorder (BD) and major depressive disorder (MDD). The excitatory glutamate \u03b1-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is a crucial regulator of synaptic function, and its dysregulation may play a central role in the pathophysiology of psychiatric disorders. Our recently developed positron emission tomography (PET) tracer, [<jats:sup>11<\/jats:sup>C]K-2, enables the quantitative visualization of AMPAR distribution and is considered useful for characterizing synaptic phenotypes in patients with psychiatric disorders. This study aimed to develop a machine learning-based method to differentiate bipolar disorder from major depressive disorder using AMPAR density. Sixteen patients with BD and 27 patients with MDD, all in depressive episodes, underwent PET scans with [<jats:sup>11<\/jats:sup>C]K-2 and structural magnetic resonance imaging. AMPAR density was estimated using the standardized uptake value ratio from 30 to 50 min after tracer injection, normalized to whole brain radioactivity. A partial least squares model was trained to predict diagnoses based on AMPAR density, and its performance was evaluated using a leave-one-pair-out cross-validation. Significant differences in AMPAR density were observed in the parietal lobe, cerebellum, and frontal lobe, notably the dorsolateral prefrontal cortex between patients with BD and patients with MDD during a depressive episode. The model achieved an area under the curve of 0.80, sensitivity of 75.0%, and specificity of 77.8%. These findings suggest that AMPAR density measured with [<jats:sup>11<\/jats:sup>C]K-2 can effectively distinguish BD from MDD and may aid diagnosis, especially in patients with ambiguous symptoms or incomplete clinical presentation.<\/jats:p>","DOI":"10.3389\/fncir.2025.1624179","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T06:16:09Z","timestamp":1754288169000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Differentiation between bipolar disorder and major depressive disorder based on AMPA receptor 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