Biological assessments for severity of and therapeutic response to depressive mixed state

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07504
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: University of the Ryukyus
• Principal Investigator: Kondo Tsuyoshi 琉球大学, 医学(系)研究科(研究院), 教授 (40215455)
• Co-Investigator(Kenkyū-buntansha): 座間味 優 琉球大学, 医学(系)研究科(研究院), 助教 (60896570)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 大うつ病性エピソード / 抑うつ性混合状態 / DMX-12 / 自閉スペクトラム症 / 炎症性サイトカイン / 神経栄養因子

Outline of Final Research Achievements

First, the effects of comorbid autism spectrum disorder (ASD) on the prevalece and severity of depressive mixed state (DMX) were investigated. Depressed patients with ASD showed more disruptive emotion/behavior symptoms than those without ASD. Mulptople regression analysis also revealed that ASD was a significant contributing factor to DMX. These suggest that careful monitoring of and adequate behavioral/pharmacologival treatments for DMX are requisite during major depressive episode in ASD patients.
Second, serum biomarkers associated with neuroinflammation and neuroprotection were monitored during DMX episode. DMX-positive patients showed higher levels of brain-derived neurotrophic factor (BDNF) than DMX-negative patients. Logistic regression analysis also revealed that BDNF was a significant contributing factor to the severity of DMX. These suggest that BDNF increases as a compensatory mechanism to counteract severe depression, which might result in expression as the DMX phenotype.

Free Research Field

精神神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究成果の学術的および社会的意義については、まず一つに、自閉スペクトラムの特性を有する大うつ病エピソードにおいて、潜在する抑うつ性混合状態の存在を見極め、適切な行動管理や薬物療法を行う必要性を臨床上明確に示した点にあり、自閉特性のある若年のうつ病患者への安易な抗うつ薬導入に警鐘を鳴らすものである。
また、これまで生物学的病態が不明であった抑うつ性混合状態において、予想と異なり神経栄養因子が逆説的に上昇することを示し、うつ病の重症化に拮抗する形で代償的にBDNFが増加し、表現型として抑うつ性混合状態を生じうる、といった一種の神経再生の過程であるとの新たな仮説を提供した研究としても意義深い。