{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:51:19Z","timestamp":1788544279507,"version":"build-2803163510"},"reference-count":71,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T00:00:00Z","timestamp":1730160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council (NSTC)","award":["109-2320-B-038-057-MY3"],"award-info":[{"award-number":["109-2320-B-038-057-MY3"]}]},{"name":"National Science and Technology Council (NSTC)","award":["110-2321-B-006-004"],"award-info":[{"award-number":["110-2321-B-006-004"]}]},{"name":"National Science and Technology Council (NSTC)","award":["110-2811-B-039-507"],"award-info":[{"award-number":["110-2811-B-039-507"]}]},{"name":"National Science and Technology Council (NSTC)","award":["110-2320-B-039-048-MY2"],"award-info":[{"award-number":["110-2320-B-039-048-MY2"]}]},{"name":"National Science and Technology Council (NSTC)","award":["110-2320-B-039-047-MY3"],"award-info":[{"award-number":["110-2320-B-039-047-MY3"]}]},{"name":"National Science and Technology Council (NSTC)","award":["110-2813-C-039-327-B"],"award-info":[{"award-number":["110-2813-C-039-327-B"]}]},{"name":"National Science and Technology Council (NSTC)","award":["110-2314-B-039-029-MY3"],"award-info":[{"award-number":["110-2314-B-039-029-MY3"]}]},{"name":"National Science and Technology Council (NSTC)","award":["111-2321-B-006-008"],"award-info":[{"award-number":["111-2321-B-006-008"]}]},{"name":"National Science and Technology Council (NSTC)","award":["111-2314-B-039-041-MY3"],"award-info":[{"award-number":["111-2314-B-039-041-MY3"]}]},{"name":"National Science and Technology Council (NSTC)","award":["113-2314-B-039-046"],"award-info":[{"award-number":["113-2314-B-039-046"]}]},{"name":"National Science and Technology Council (NSTC)","award":["113-2320-B-281-001"],"award-info":[{"award-number":["113-2320-B-281-001"]}]},{"name":"National Science and Technology Council (NSTC)","award":["113-2923-B-039-001-MY3"],"award-info":[{"award-number":["113-2923-B-039-001-MY3"]}]},{"name":"National Science and Technology Council (NSTC)","award":["110-13"],"award-info":[{"award-number":["110-13"]}]},{"name":"National Science and Technology Council (NSTC)","award":["111-52"],"award-info":[{"award-number":["111-52"]}]},{"name":"National Science and Technology Council (NSTC)","award":["112-24"],"award-info":[{"award-number":["112-24"]}]},{"name":"National Science and Technology Council (NSTC)","award":["112-47"],"award-info":[{"award-number":["112-47"]}]},{"name":"National Science and Technology Council (NSTC)","award":["113-24"],"award-info":[{"award-number":["113-24"]}]},{"name":"National Science and Technology Council (NSTC)","award":["113-38"],"award-info":[{"award-number":["113-38"]}]},{"name":"National Science and Technology Council (NSTC)","award":["113-40"],"award-info":[{"award-number":["113-40"]}]},{"name":"National Science and Technology Council (NSTC)","award":["CMRC-CMA-2"],"award-info":[{"award-number":["CMRC-CMA-2"]}]},{"name":"National Science and Technology Council (NSTC)","award":["110-AWARD-02"],"award-info":[{"award-number":["110-AWARD-02"]}]},{"name":"National Science and Technology Council (NSTC)","award":["110-N-17"],"award-info":[{"award-number":["110-N-17"]}]},{"name":"National Science and Technology Council (NSTC)","award":["111-SR-73"],"award-info":[{"award-number":["111-SR-73"]}]},{"name":"National Science and Technology Council (NSTC)","award":["DMR-110-124"],"award-info":[{"award-number":["DMR-110-124"]}]},{"name":"National Science and Technology Council (NSTC)","award":["111-245"],"award-info":[{"award-number":["111-245"]}]},{"name":"National Science and Technology Council (NSTC)","award":["112-097"],"award-info":[{"award-number":["112-097"]}]},{"name":"National Science and Technology Council (NSTC)","award":["112-086"],"award-info":[{"award-number":["112-086"]}]},{"name":"National Science and Technology Council (NSTC)","award":["112-109"],"award-info":[{"award-number":["112-109"]}]},{"name":"National Science and Technology Council (NSTC)","award":["112-232"],"award-info":[{"award-number":["112-232"]}]},{"name":"National Science and Technology Council (NSTC)","award":["113-210"],"award-info":[{"award-number":["113-210"]}]},{"name":"National Science and Technology Council (NSTC)","award":["DMR-HHC-109-11"],"award-info":[{"award-number":["DMR-HHC-109-11"]}]},{"name":"National Science and Technology Council (NSTC)","award":["HHC-109-12"],"award-info":[{"award-number":["HHC-109-12"]}]},{"name":"National Science and Technology Council (NSTC)","award":["HHC-110-10"],"award-info":[{"award-number":["HHC-110-10"]}]},{"name":"National Science and Technology Council (NSTC)","award":["HHC-111-8"],"award-info":[{"award-number":["HHC-111-8"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["109-2320-B-038-057-MY3"],"award-info":[{"award-number":["109-2320-B-038-057-MY3"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["110-2321-B-006-004"],"award-info":[{"award-number":["110-2321-B-006-004"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["110-2811-B-039-507"],"award-info":[{"award-number":["110-2811-B-039-507"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["110-2320-B-039-048-MY2"],"award-info":[{"award-number":["110-2320-B-039-048-MY2"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["110-2320-B-039-047-MY3"],"award-info":[{"award-number":["110-2320-B-039-047-MY3"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["110-2813-C-039-327-B"],"award-info":[{"award-number":["110-2813-C-039-327-B"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["110-2314-B-039-029-MY3"],"award-info":[{"award-number":["110-2314-B-039-029-MY3"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["111-2321-B-006-008"],"award-info":[{"award-number":["111-2321-B-006-008"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["111-2314-B-039-041-MY3"],"award-info":[{"award-number":["111-2314-B-039-041-MY3"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["113-2314-B-039-046"],"award-info":[{"award-number":["113-2314-B-039-046"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["113-2320-B-281-001"],"award-info":[{"award-number":["113-2320-B-281-001"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["113-2923-B-039-001-MY3"],"award-info":[{"award-number":["113-2923-B-039-001-MY3"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["110-13"],"award-info":[{"award-number":["110-13"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["111-52"],"award-info":[{"award-number":["111-52"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["112-24"],"award-info":[{"award-number":["112-24"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["112-47"],"award-info":[{"award-number":["112-47"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["113-24"],"award-info":[{"award-number":["113-24"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["113-38"],"award-info":[{"award-number":["113-38"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["113-40"],"award-info":[{"award-number":["113-40"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["CMRC-CMA-2"],"award-info":[{"award-number":["CMRC-CMA-2"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["110-AWARD-02"],"award-info":[{"award-number":["110-AWARD-02"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["110-N-17"],"award-info":[{"award-number":["110-N-17"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["111-SR-73"],"award-info":[{"award-number":["111-SR-73"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["DMR-110-124"],"award-info":[{"award-number":["DMR-110-124"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["111-245"],"award-info":[{"award-number":["111-245"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["112-097"],"award-info":[{"award-number":["112-097"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["112-086"],"award-info":[{"award-number":["112-086"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["112-109"],"award-info":[{"award-number":["112-109"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["112-232"],"award-info":[{"award-number":["112-232"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["113-210"],"award-info":[{"award-number":["113-210"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["DMR-HHC-109-11"],"award-info":[{"award-number":["DMR-HHC-109-11"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["HHC-109-12"],"award-info":[{"award-number":["HHC-109-12"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["HHC-110-10"],"award-info":[{"award-number":["HHC-110-10"]}]},{"name":"An-Nan Hospital, China Medical University, Tainan, Taiwan","award":["HHC-111-8"],"award-info":[{"award-number":["HHC-111-8"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["109-2320-B-038-057-MY3"],"award-info":[{"award-number":["109-2320-B-038-057-MY3"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["110-2321-B-006-004"],"award-info":[{"award-number":["110-2321-B-006-004"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["110-2811-B-039-507"],"award-info":[{"award-number":["110-2811-B-039-507"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["110-2320-B-039-048-MY2"],"award-info":[{"award-number":["110-2320-B-039-048-MY2"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["110-2320-B-039-047-MY3"],"award-info":[{"award-number":["110-2320-B-039-047-MY3"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["110-2813-C-039-327-B"],"award-info":[{"award-number":["110-2813-C-039-327-B"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["110-2314-B-039-029-MY3"],"award-info":[{"award-number":["110-2314-B-039-029-MY3"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["111-2321-B-006-008"],"award-info":[{"award-number":["111-2321-B-006-008"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["111-2314-B-039-041-MY3"],"award-info":[{"award-number":["111-2314-B-039-041-MY3"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["113-2314-B-039-046"],"award-info":[{"award-number":["113-2314-B-039-046"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["113-2320-B-281-001"],"award-info":[{"award-number":["113-2320-B-281-001"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["113-2923-B-039-001-MY3"],"award-info":[{"award-number":["113-2923-B-039-001-MY3"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["110-13"],"award-info":[{"award-number":["110-13"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["111-52"],"award-info":[{"award-number":["111-52"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["112-24"],"award-info":[{"award-number":["112-24"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["112-47"],"award-info":[{"award-number":["112-47"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["113-24"],"award-info":[{"award-number":["113-24"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["113-38"],"award-info":[{"award-number":["113-38"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["113-40"],"award-info":[{"award-number":["113-40"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["CMRC-CMA-2"],"award-info":[{"award-number":["CMRC-CMA-2"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["110-AWARD-02"],"award-info":[{"award-number":["110-AWARD-02"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["110-N-17"],"award-info":[{"award-number":["110-N-17"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["111-SR-73"],"award-info":[{"award-number":["111-SR-73"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["DMR-110-124"],"award-info":[{"award-number":["DMR-110-124"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["111-245"],"award-info":[{"award-number":["111-245"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["112-097"],"award-info":[{"award-number":["112-097"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["112-086"],"award-info":[{"award-number":["112-086"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["112-109"],"award-info":[{"award-number":["112-109"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["112-232"],"award-info":[{"award-number":["112-232"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["113-210"],"award-info":[{"award-number":["113-210"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["DMR-HHC-109-11"],"award-info":[{"award-number":["DMR-HHC-109-11"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["HHC-109-12"],"award-info":[{"award-number":["HHC-109-12"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["HHC-110-10"],"award-info":[{"award-number":["HHC-110-10"]}]},{"name":"Ministry of Education (MOE), Taiwan","award":["HHC-111-8"],"award-info":[{"award-number":["HHC-111-8"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["109-2320-B-038-057-MY3"],"award-info":[{"award-number":["109-2320-B-038-057-MY3"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["110-2321-B-006-004"],"award-info":[{"award-number":["110-2321-B-006-004"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["110-2811-B-039-507"],"award-info":[{"award-number":["110-2811-B-039-507"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["110-2320-B-039-048-MY2"],"award-info":[{"award-number":["110-2320-B-039-048-MY2"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["110-2320-B-039-047-MY3"],"award-info":[{"award-number":["110-2320-B-039-047-MY3"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["110-2813-C-039-327-B"],"award-info":[{"award-number":["110-2813-C-039-327-B"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["110-2314-B-039-029-MY3"],"award-info":[{"award-number":["110-2314-B-039-029-MY3"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["111-2321-B-006-008"],"award-info":[{"award-number":["111-2321-B-006-008"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["111-2314-B-039-041-MY3"],"award-info":[{"award-number":["111-2314-B-039-041-MY3"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["113-2314-B-039-046"],"award-info":[{"award-number":["113-2314-B-039-046"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["113-2320-B-281-001"],"award-info":[{"award-number":["113-2320-B-281-001"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["113-2923-B-039-001-MY3"],"award-info":[{"award-number":["113-2923-B-039-001-MY3"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["110-13"],"award-info":[{"award-number":["110-13"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["111-52"],"award-info":[{"award-number":["111-52"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["112-24"],"award-info":[{"award-number":["112-24"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["112-47"],"award-info":[{"award-number":["112-47"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["113-24"],"award-info":[{"award-number":["113-24"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["113-38"],"award-info":[{"award-number":["113-38"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["113-40"],"award-info":[{"award-number":["113-40"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["CMRC-CMA-2"],"award-info":[{"award-number":["CMRC-CMA-2"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["110-AWARD-02"],"award-info":[{"award-number":["110-AWARD-02"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["110-N-17"],"award-info":[{"award-number":["110-N-17"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["111-SR-73"],"award-info":[{"award-number":["111-SR-73"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["DMR-110-124"],"award-info":[{"award-number":["DMR-110-124"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["111-245"],"award-info":[{"award-number":["111-245"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["112-097"],"award-info":[{"award-number":["112-097"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["112-086"],"award-info":[{"award-number":["112-086"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["112-109"],"award-info":[{"award-number":["112-109"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["112-232"],"award-info":[{"award-number":["112-232"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["113-210"],"award-info":[{"award-number":["113-210"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["DMR-HHC-109-11"],"award-info":[{"award-number":["DMR-HHC-109-11"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["HHC-109-12"],"award-info":[{"award-number":["HHC-109-12"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["HHC-110-10"],"award-info":[{"award-number":["HHC-110-10"]}]},{"name":"China Medical University, Taichung, Taiwan","award":["HHC-111-8"],"award-info":[{"award-number":["HHC-111-8"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["109-2320-B-038-057-MY3"],"award-info":[{"award-number":["109-2320-B-038-057-MY3"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["110-2321-B-006-004"],"award-info":[{"award-number":["110-2321-B-006-004"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["110-2811-B-039-507"],"award-info":[{"award-number":["110-2811-B-039-507"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["110-2320-B-039-048-MY2"],"award-info":[{"award-number":["110-2320-B-039-048-MY2"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["110-2320-B-039-047-MY3"],"award-info":[{"award-number":["110-2320-B-039-047-MY3"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["110-2813-C-039-327-B"],"award-info":[{"award-number":["110-2813-C-039-327-B"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["110-2314-B-039-029-MY3"],"award-info":[{"award-number":["110-2314-B-039-029-MY3"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["111-2321-B-006-008"],"award-info":[{"award-number":["111-2321-B-006-008"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["111-2314-B-039-041-MY3"],"award-info":[{"award-number":["111-2314-B-039-041-MY3"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["113-2314-B-039-046"],"award-info":[{"award-number":["113-2314-B-039-046"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["113-2320-B-281-001"],"award-info":[{"award-number":["113-2320-B-281-001"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["113-2923-B-039-001-MY3"],"award-info":[{"award-number":["113-2923-B-039-001-MY3"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["110-13"],"award-info":[{"award-number":["110-13"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["111-52"],"award-info":[{"award-number":["111-52"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["112-24"],"award-info":[{"award-number":["112-24"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["112-47"],"award-info":[{"award-number":["112-47"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["113-24"],"award-info":[{"award-number":["113-24"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["113-38"],"award-info":[{"award-number":["113-38"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["113-40"],"award-info":[{"award-number":["113-40"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["CMRC-CMA-2"],"award-info":[{"award-number":["CMRC-CMA-2"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["110-AWARD-02"],"award-info":[{"award-number":["110-AWARD-02"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["110-N-17"],"award-info":[{"award-number":["110-N-17"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["111-SR-73"],"award-info":[{"award-number":["111-SR-73"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["DMR-110-124"],"award-info":[{"award-number":["DMR-110-124"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["111-245"],"award-info":[{"award-number":["111-245"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["112-097"],"award-info":[{"award-number":["112-097"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["112-086"],"award-info":[{"award-number":["112-086"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["112-109"],"award-info":[{"award-number":["112-109"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["112-232"],"award-info":[{"award-number":["112-232"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["113-210"],"award-info":[{"award-number":["113-210"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["DMR-HHC-109-11"],"award-info":[{"award-number":["DMR-HHC-109-11"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["HHC-109-12"],"award-info":[{"award-number":["HHC-109-12"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["HHC-110-10"],"award-info":[{"award-number":["HHC-110-10"]}]},{"name":"China Medical University Hospital, Taichung, Taiwan","award":["HHC-111-8"],"award-info":[{"award-number":["HHC-111-8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Objective: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have demonstrated protective effects in major depressive disorder (MDD) patients receiving antidepressant treatment. However, there have been a few double-blind randomized controlled trials focused on n-3 PUFAs as monotherapy in MDD, and the outcomes have been mixed. This study aimed to assess the clinical effects of n-3 PUFAs monotherapy in patients with MDD. Methods: A total of 60 patients with MDD participated in this 12-week double-blind randomized controlled trial. They were randomized to either the n-3 PUFAs group (n = 30; 3.2 g of eicosapentaenoic acid, EPA and docosahexaenoic acid, DHA per day) or the placebo group (n = 30; 3.2 g of soybean oil per day). The severity of depression was evaluated using the Hamilton Rating Scale for Depression (HRSD). Results: The n-3 PUFAs group had a significantly lower HRSD score compared with the placebo group at week 4 (p = 0.004), week 6 (p = 0.006), week 8 (p = 0.004), and week 12 (p = 0.01). The n-3 PUFAs group showed slightly higher rates for both remission (26.7% vs. 10%, p = 0.095) and response (23.3% vs. 6.7%, p = 0.145) compared with the placebo group at week 12, but these differences did not reach statistical significance. Conclusions: These findings suggested that monotherapy of n-3 PUFAs could improve depression and potentially serve as an alternative option for MDD patients.<\/jats:p>","DOI":"10.3390\/nu16213688","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T10:45:35Z","timestamp":1730198735000},"page":"3688","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The Efficacy of Omega-3 Fatty Acids as the Monotherapy for Depression: A Randomized, Double-Blind, Placebo-Controlled Pilot Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0772-2742","authenticated-orcid":false,"given":"Suet-Kei","family":"Wu","sequence":"first","affiliation":[{"name":"Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung 404, Taiwan"},{"name":"Graduate Institute of Nutrition, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3964-9339","authenticated-orcid":false,"given":"Kai-Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9048-6363","authenticated-orcid":false,"given":"Wen-Chun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nursing, National Tainan Junior College of Nursing, Tainan 700, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6716-4830","authenticated-orcid":false,"given":"Ikbal Andrian","family":"Malau","sequence":"additional","affiliation":[{"name":"Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung 404, Taiwan"},{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0129-7980","authenticated-orcid":false,"given":"Halliru","family":"Zailani","sequence":"additional","affiliation":[{"name":"Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung 404, Taiwan"},{"name":"Graduate Institute of Nutrition, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Ho","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2914-5513","authenticated-orcid":false,"given":"Shih-Yi","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5582-0928","authenticated-orcid":false,"given":"Jane Pei-Chen","family":"Chang","sequence":"additional","affiliation":[{"name":"Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung 404, Taiwan"},{"name":"College of Medicine, China Medical University, Taichung 404, Taiwan"},{"name":"Child and Adolescent Psychiatry Division, Department of Psychiatry, China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8549-1432","authenticated-orcid":false,"given":"Wei-Che","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Cathay General Hospital, Taipei 106, Taiwan"},{"name":"School of Medicine, Fu Jen Catholic University, Taipei 242, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4501-2502","authenticated-orcid":false,"given":"Kuan-Pin","family":"Su","sequence":"additional","affiliation":[{"name":"Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung 404, Taiwan"},{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan"},{"name":"College of Medicine, China Medical University, Taichung 404, Taiwan"},{"name":"An-Nan Hospital, China Medical University, Tainan 709, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16065","DOI":"10.1038\/nrdp.2016.65","article-title":"Major depressive disorder","volume":"2","author":"Otte","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","first-page":"1517","article-title":"Depression Is the Leading Cause of Disability Around the World","volume":"317","author":"Friedrich","year":"2017","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Keshavarz, K., Hedayati, A., Rezaei, M., Goudarzi, Z., Moghimi, E., Rezaee, M., and Lotfi, F. (2022). Economic burden of major depressive disorder: A case study in Southern Iran. BMC Psychiatry, 22.","DOI":"10.1186\/s12888-022-04220-7"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1176\/appi.ajp.163.1.28","article-title":"Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: Implications for clinical practice","volume":"163","author":"Trivedi","year":"2006","journal-title":"Am. J. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1176\/ps.2009.60.11.1439","article-title":"What did STAR*D teach us? Results from a large-scale, practical, clinical trial for patients with depression","volume":"60","author":"Gaynes","year":"2009","journal-title":"Psychiatr. Serv."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e2116674","DOI":"10.1001\/jamanetworkopen.2021.16674","article-title":"Benefits of Electroconvulsive Therapy for Patients with Major Depressive Disorder","volume":"4","author":"Gaynes","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Alvarez-Mon, M.A., Ortega, M.A., Garc\u00eda-Montero, C., Fraile-Martinez, O., Monserrat, J., Lahera, G., Mora, F., Rodriguez-Quiroga, A., Fernandez-Rojo, S., and Quintero, J. (2021). Exploring the Role of Nutraceuticals in Major Depressive Disorder (MDD): Rationale, State of the Art and Future Prospects. Pharmaceuticals, 14.","DOI":"10.3390\/ph14080821"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.bbi.2019.03.012","article-title":"Omega-3 polyunsaturated fatty acids in cardiovascular diseases comorbid major depressive disorder\u2014Results from a randomized controlled trial","volume":"85","author":"Chang","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Iqbal, A.Z., Wu, S.K., Zailani, H., Chiu, W.C., Liu, W.C., Su, K.P., and Lee, S.D. (2023). Effects of Omega-3 Polyunsaturated Fatty Acids Intake on Vasomotor Symptoms, Sleep Quality and Depression in Postmenopausal Women: A Systematic Review. Nutrients, 15.","DOI":"10.20944\/preprints202309.0073.v1"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1111\/j.1476-5381.2009.00189.x","article-title":"Long-chain n-3 polyunsaturated fatty acids: New insights into mechanisms relating to inflammation and coronary heart disease","volume":"158","author":"Mavrommatis","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1505s","DOI":"10.1093\/ajcn\/83.6.1505S","article-title":"n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases","volume":"83","author":"Calder","year":"2006","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6773","DOI":"10.1038\/s41380-021-01160-8","article-title":"Omega-3 polyunsaturated fatty acids protect against inflammation through production of LOX and CYP450 lipid mediators: Relevance for major depression and for human hippocampal neurogenesis","volume":"26","author":"Borsini","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wang, Y., Dong, L., Pan, D., Xu, D., Lu, Y., Yin, S., Wang, S., Xia, H., Liao, W., and Sun, G. (2022). Effect of High Ratio of n-6\/n-3 PUFAs on Depression: A Meta-Analysis of Prospective Studies. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.889576"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1159\/000502652","article-title":"International Society for Nutritional Psychiatry Research Practice Guidelines for Omega-3 Fatty Acids in the Treatment of Major Depressive Disorder","volume":"88","author":"Guu","year":"2019","journal-title":"Psychother. Psychosom."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Sch\u00f6nenberger, K.A., Sch\u00fcpfer, A.C., Gloy, V.L., Hasler, P., Stanga, Z., Kaegi-Braun, N., and Reber, E. (2021). Effect of Anti-Inflammatory Diets on Pain in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis. Nutrients, 13.","DOI":"10.3390\/nu13124221"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.plefa.2006.07.010","article-title":"Role of omega-3 fatty acids in brain development and function: Potential implications for the pathogenesis and prevention of psychopathology","volume":"75","author":"McNamara","year":"2006","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.plefa.2009.05.017","article-title":"Evaluation of docosahexaenoic acid deficiency as a preventable risk factor for recurrent affective disorders: Current status, future directions, and dietary recommendations","volume":"81","author":"McNamara","year":"2009","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_18","first-page":"151","article-title":"Mind-body interface: The role of n-3 fatty acids in psychoneuroimmunology, somatic presentation, and medical illness comorbidity of depression","volume":"17","author":"Su","year":"2008","journal-title":"Asia Pac. J. Clin. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.biopsych.2010.03.018","article-title":"A meta-analytic review of polyunsaturated fatty acid compositions in patients with depression","volume":"68","author":"Lin","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1093\/aje\/kwu050","article-title":"Longitudinal Associations Between Fish Consumption and Depression in Young Adults","volume":"179","author":"Smith","year":"2014","journal-title":"Am. J. Epidemiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1002\/da.23257","article-title":"Low omega-3 polyunsaturated fatty acids predict reduced response to standard antidepressants in patients with major depressive disorder","volume":"39","author":"Cussotto","year":"2022","journal-title":"Depress. Anxiety"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.4088\/JCP.10m05966blu","article-title":"The efficacy of omega-3 supplementation for major depression: A randomized controlled trial","volume":"72","author":"Turecki","year":"2011","journal-title":"J. Clin. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1517\/13543784.2013.836487","article-title":"Omega-3 polyunsaturated fatty acids for major depressive disorder","volume":"22","author":"Su","year":"2013","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1159\/000198167","article-title":"Biological mechanism of antidepressant effect of omega-3 fatty acids: How does fish oil act as a \u2018mind-body interface\u2019?","volume":"17","author":"Su","year":"2009","journal-title":"Neuro-Signals"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e1476","DOI":"10.4088\/JCP.15l10011","article-title":"Personalized medicine with Omega-3 fatty acids for depression in children and pregnant women and depression associated with inflammation","volume":"76","author":"Su","year":"2015","journal-title":"J. Clin. Psychiatry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.4088\/JCP.v68n0712","article-title":"A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids","volume":"68","author":"Lin","year":"2007","journal-title":"J. Clin. Psychiatry"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Pruneti, C., and Guidotti, S. (2023). Need for Multidimensional and Multidisciplinary Management of Depressed Preadolescents and Adolescents: A Review of Randomized Controlled Trials on Oral Supplementations (Omega-3, Fish Oil, Vitamin D3). Nutrients, 15.","DOI":"10.3390\/nu15102306"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.jpsychires.2018.09.016","article-title":"Influence of adjuvant omega-3-polyunsaturated fatty acids on depression, sleep, and emotion regulation among outpatients with major depressive disorders\u2014Results from a double-blind, randomized and placebo-controlled clinical trial","volume":"107","author":"Jahangard","year":"2018","journal-title":"J. Psychiatr. Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Chaves, R.d.C.S., Aguiar, O.B., Moreno, A.B., Brunoni, A.R., Molina, M.d.C.B., Viana, M.C., Benso\u00f1or, I., Griep, R.H., and da Fonseca, M.d.J.M. (2022). Consumption of Omega-3 and Maintenance and Incidence of Depressive Episodes: The ELSA-Brasil Study. Nutrients, 14.","DOI":"10.3390\/nu14153227"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1038\/npp.2017.160","article-title":"Omega-3 Polyunsaturated Fatty Acids in Youths with Attention Deficit Hyperactivity Disorder: A Systematic Review and Meta-Analysis of Clinical Trials and Biological Studies","volume":"43","author":"Chang","year":"2018","journal-title":"Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1097\/01.jcp.0000246214.49271.f1","article-title":"n-3 polyunsaturated fatty acids decrease anxiety feelings in a population of substance abusers","volume":"26","author":"Branchey","year":"2006","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e1301","DOI":"10.4088\/JCP.15r09925","article-title":"Omega-3 and Omega-6 Polyunsaturated Fatty Acids in Bipolar Disorder: A Review of Biomarker and Treatment Studies","volume":"77","author":"Saunders","year":"2016","journal-title":"J. Clin. Psychiatry"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"129","DOI":"10.9758\/cpn.2015.13.2.129","article-title":"Omega-3 Polyunsaturated Fatty Acids in Prevention of Mood and Anxiety Disorders","volume":"13","author":"Su","year":"2015","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1038\/mp.2012.111","article-title":"Are omega-3 fatty acids antidepressants or just mood-improving agents? The effect depends upon diagnosis, supplement preparation, and severity of depression","volume":"17","author":"Lin","year":"2012","journal-title":"Mol. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.plefa.2018.01.001","article-title":"Safety and tolerability of prescription omega-3 fatty acids: A systematic review and meta-analysis of randomized controlled trials","volume":"129","author":"Chang","year":"2018","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1080\/00048670701827275","article-title":"Comparison of therapeutic effects of omega-3 fatty acid eicosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder","volume":"42","author":"Jazayeri","year":"2008","journal-title":"Aust. N. Z. J. Psychiatry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1177\/1060028016656017","article-title":"Effect of Omega-3 Fatty Acids on Depressive Symptoms in HIV-Positive Individuals: A Randomized, Placebo-Controlled Clinical Trial","volume":"50","author":"Ravi","year":"2016","journal-title":"Ann. Pharmacother."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"644","DOI":"10.4088\/JCP.v69n0418","article-title":"Omega-3 fatty acids for major depressive disorder during pregnancy: Results from a randomized, double-blind, placebo-controlled trial","volume":"69","author":"Su","year":"2008","journal-title":"J. Clin. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.jad.2010.04.008","article-title":"Eicosapentaenoic acid as an add-on to antidepressant medication for co-morbid major depression in patients with diabetes mellitus: A randomized, double-blind placebo-controlled study","volume":"126","author":"Bot","year":"2010","journal-title":"J. Affect. Disord."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Shinto, L., Marracci, G., Mohr, D.C., Bumgarner, L., Murchison, C., Senders, A., and Bourdette, D. (2016). Omega-3 Fatty Acids for Depression in Multiple Sclerosis: A Randomized Pilot Study. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147195"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"17m11596","DOI":"10.4088\/JCP.17m11596","article-title":"A Double-Blind Placebo-Controlled Trial of Omega-3 Fatty Acids as a Monotherapy for Adolescent Depression","volume":"79","author":"Gabbay","year":"2018","journal-title":"J. Clin. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"54","DOI":"10.4088\/JCP.14m08986","article-title":"A double-blind, randomized controlled clinical trial comparing eicosapentaenoic acid versus docosahexaenoic acid for depression","volume":"76","author":"Mischoulon","year":"2015","journal-title":"J. Clin. Psychiatry"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Luo, X.D., Feng, J.S., Yang, Z., Huang, Q.T., Lin, J.D., Yang, B., Su, K.P., and Pan, J.Y. (2020). High-dose omega-3 polyunsaturated fatty acid supplementation might be more superior than low-dose for major depressive disorder in early therapy period: A network meta-analysis. BMC Psychiatry, 20.","DOI":"10.1186\/s12888-020-02656-3"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/s41398-019-0515-5","article-title":"Efficacy of omega-3 PUFAs in depression: A meta-analysis","volume":"9","author":"Liao","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"ref_45","unstructured":"American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders: DSM-IV, American Psychiatric Association."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1177\/1742395312467658","article-title":"The Hamilton Rating Scale for Depression: The making of a \u201cgold standard\u201d and the unmaking of a chronic illness, 1960\u20131980","volume":"9","author":"Worboys","year":"2013","journal-title":"Chronic Illn."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0924-977X(03)00032-4","article-title":"Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial","volume":"13","author":"Su","year":"2003","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0924-977X(02)00130-X","article-title":"Polyunsaturated fatty acid deficit in patients with bipolar mania","volume":"13","author":"Chiu","year":"2003","journal-title":"Eur. Neuropsychopharmacol. J. Eur. Coll. Neuropsychopharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1176\/appi.ajp.159.3.477","article-title":"Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder","volume":"159","author":"Nemets","year":"2002","journal-title":"Am. J. Psychiatry"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Wolters, M., von der Haar, A., Baalmann, A.K., Wellbrock, M., Heise, T.L., and Rach, S. (2021). Effects of n-3 Polyunsaturated Fatty Acid Supplementation in the Prevention and Treatment of Depressive Disorders-A Systematic Review and Meta-Analysis. Nutrients, 13.","DOI":"10.3390\/nu13041070"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Yang, R., Wang, L., Jin, K., Cao, S., Wu, C., Guo, J., Chen, J., Tang, H., and Tang, M. (2022). Omega-3 Polyunsaturated Fatty Acids Supplementation Alleviate Anxiety Rather Than Depressive Symptoms Among First-Diagnosed, Drug-Na\u00efve Major Depressive Disorder Patients: A Randomized Clinical Trial. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.876152"},{"key":"ref_52","first-page":"Cd004692","article-title":"Omega-3 fatty acids for depression in adults","volume":"11","author":"Appleton","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1007\/s11096-023-01643-4","article-title":"Clinical pharmacy services in mental health in Europe: A commentary paper of the European Society of Clinical Pharmacy Special Interest Group on Mental Health","volume":"45","author":"Stuhec","year":"2023","journal-title":"Int. J. Clin. Pharm."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1007\/s00394-019-02090-6","article-title":"EPA and DHA as markers of nutraceutical treatment response in major depressive disorder","volume":"59","author":"Cribb","year":"2020","journal-title":"Eur. J. Nutr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41537-022-00214-2","article-title":"Reduced erythrocyte membrane polyunsaturated fatty acid levels indicate diminished treatment response in patients with multi- versus first-episode schizophrenia","volume":"8","author":"Li","year":"2022","journal-title":"Schizophrenia"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"21m14074","DOI":"10.4088\/JCP.21m14074","article-title":"Omega-3 Fatty Acids for Major Depressive Disorder with High Inflammation: A Randomized Dose-Finding Clinical Trial","volume":"83","author":"Mischoulon","year":"2022","journal-title":"J. Clin. Psychiatry"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1038\/s41386-022-01527-7","article-title":"Clinical response to EPA supplementation in patients with major depressive disorder is associated with higher plasma concentrations of pro-resolving lipid mediators","volume":"48","author":"Liu","year":"2023","journal-title":"Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1159\/000501158","article-title":"Clinical Efficacy and Biological Regulations of \u03c9-3 PUFA-Derived Endocannabinoids in Major Depressive Disorder","volume":"88","author":"Yang","year":"2019","journal-title":"Psychother. Psychosom."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1467s","DOI":"10.1093\/ajcn\/83.6.1467S","article-title":"Distribution, interconversion, and dose response of n-3 fatty acids in humans","volume":"83","author":"Arterburn","year":"2006","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1051\/rnd:2005047","article-title":"Conversion of alpha-linolenic acid to longer-chain polyunsaturated fatty acids in human adults","volume":"45","author":"Burdge","year":"2005","journal-title":"Reprod. Nutr. Dev."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Sparkes, C., Sinclair, A.J., Gibson, R.A., Else, P.L., and Meyer, B.J. (2020). High Variability in Erythrocyte, Plasma and Whole Blood EPA and DHA Levels in Response to Supplementation. Nutrients, 12.","DOI":"10.3390\/nu12041017"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1160\/TH14-12-1003","article-title":"Moderate oral supplementation with docosahexaenoic acid improves platelet function and oxidative stress in type 2 diabetic patients","volume":"114","author":"Colas","year":"2015","journal-title":"Thromb. Haemost."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"102219","DOI":"10.1016\/j.plefa.2020.102219","article-title":"Dose- and time-dependent increase in circulating anti-inflammatory and pro-resolving lipid mediators following eicosapentaenoic acid supplementation in patients with major depressive disorder and chronic inflammation","volume":"164","author":"So","year":"2021","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.1096\/fj.09-133421","article-title":"Increasing intakes of the long-chain \u03c9-3 docosahexaenoic acid: Effects on platelet functions and redox status in healthy men","volume":"23","author":"Guillot","year":"2009","journal-title":"FASEB J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.plefa.2018.03.004","article-title":"Omega-6 fatty acids and inflammation","volume":"132","author":"Innes","year":"2018","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Glencross, B.D., Bachis, E., Betancor, M.B., Calder, P., Liland, N., Newton, R., and Ruyter, B. (2024). Omega-3 Futures in Aquaculture: Exploring the Supply and Demands for Long-Chain Omega-3 Essential Fatty Acids by Aquaculture Species. Rev. Fish. Sci. Aquac., 1\u201350.","DOI":"10.1080\/23308249.2024.2388563"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e707","DOI":"10.1002\/iid3.707","article-title":"n-3 polyunsaturated fatty acids improve depression-like behavior by inhibiting hippocampal neuroinflammation in mice via reducing TLR4 expression","volume":"10","author":"Hu","year":"2022","journal-title":"Immunity Inflamm. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"137","DOI":"10.4162\/nrp.2021.15.2.137","article-title":"Role of n-3 long-chain polyunsaturated fatty acids in human nutrition and health: Review of recent studies and recommendations","volume":"15","year":"2021","journal-title":"Nutr. Res. Pract."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.imr.2015.07.003","article-title":"Omega-3 fatty acids and the treatment of depression: A review of scientific evidence","volume":"4","author":"Wani","year":"2015","journal-title":"Integr. Med. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.clnu.2017.03.027","article-title":"Fish oil LC-PUFAs do not affect blood coagulation parameters and bleeding manifestations: Analysis of 8 clinical studies with selected patient groups on omega-3-enriched medical nutrition","volume":"37","author":"Jeansen","year":"2018","journal-title":"Clin. Nutr."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s12933-017-0523-9","article-title":"Treatment with high-dose n-3 PUFAs has no effect on platelet function, coagulation, metabolic status or inflammation in patients with atherosclerosis and type 2 diabetes","volume":"16","author":"Poreba","year":"2017","journal-title":"Cardiovasc. Diabetol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/21\/3688\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:23:20Z","timestamp":1760113400000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/21\/3688"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,29]]},"references-count":71,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["nu16213688"],"URL":"https:\/\/doi.org\/10.3390\/nu16213688","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,29]]}}}