Differentiation between bipolar disorder and major depressive disorder based on AMPA receptor distribution

An accurate diagnostic method using biological indicators is critically needed for bipolar disorder (BD) and major depressive disorder (MDD). The excitatory glutamate α-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, [<sup>11</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 [<sup>11</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 [<sup>11</sup>C]K-2 can effectively distinguish BD from MDD and may aid diagnosis, especially in patients with ambiguous symptoms or incomplete clinical presentation.

Authors

Institutions

Publication Details

Journal
Frontiers in Neural Circuits
Published
2025-08-04
DOI
https://doi.org/10.3389/fncir.2025.1624179
Primary Topic
Bipolar Disorder and Treatment
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Differentiation between bipolar disorder and major depressive disorder based on AMPA receptor distribution

Teruki Koizumi, Ryo Mitoma, Akira Suda, Takuya Takahashi et al.
Frontiers in Neural Circuits
Bipolar Disorder and Treatment
article

Differentiation between bipolar disorder and major depressive disorder based on AMPA receptor distribution

Teruki Koizumi, Ryo Mitoma, Akira Suda, Takuya Takahashi, Yuuki Takada, Hiroki Abe, Akitoyo Hishimoto, Hiroyuki Uchida, Waki Nakajima, Hidehiko Okazawa, Hirotaka Kosaka, Osamu Togao, Kie Takahashi, Mai Hatano, Yoji Hirano, Junichi Chikazoe, Tetsu Arisawa, Sakiko Tsugawa, Nobuhiro Nagai, Shunya Kurokawa, Shinichiro Nakajima, Taisuke Yatomi, Hideaki Tani, Shingo Baba, Shunsuke Tamura, Takeshi Asami, Yohei Ohtani, Tsuyoshi Eiro, Yuhei Kikuchi, Kotaro Nakano, Yuichi Kimura, Masaru Mimura, Akane Sano, Tomoyuki Miyazaki
article en

Abstract

An accurate diagnostic method using biological indicators is critically needed for bipolar disorder (BD) and major depressive disorder (MDD). The excitatory glutamate α-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, [<sup>11</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 [<sup>11</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 [<sup>11</sup>C]K-2 can effectively distinguish BD from MDD and may aid diagnosis, especially in patients with ambiguous symptoms or incomplete clinical presentation.

Frontiers in Neural CircuitsVol. 19
University of Fukui (JP), Hiroshima University (JP), University of Miyazaki (JP), Kyushu University (JP), Keio University (JP), Kobe University (JP), The University of Tokyo (JP), Yokohama City University (JP), Kindai University (JP)
Japan Research Foundation for Clinical Pharmacology, Japan Agency for Medical Research and Development, Keio University, Ministry of Education, Culture, Sports, Science and Technology, SENSHIN Medical Research Foundation, Japan Society for the Promotion of Science
Good health and well-being
Openalex Percentile: Top 77%
Bipolar Disorder and Treatment
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.