The development of the neural circuits based treatment and prevention of major depression in patients having a history of childhood maltreatment.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03603
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Hiroshima University
• Principal Investigator: Yasumasa Okamoto 広島大学, 医系科学研究科(医), 教授 (70314763)
• Co-Investigator(Kenkyū-buntansha): 岡田 剛 広島大学, 医系科学研究科(医), 准教授 (10457286) ; 淵上 学 広島大学, 医系科学研究科(医), 講師 (40403571)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: うつ病 / 幼少期ストレス / fMRI / うつ病モデルラット / 神経回路

Outline of Final Research Achievements

In human studies, depression patients showed a negative correlation between childhood abuse and trauma and resting brain activity in the left dorsolateral prefrontal cortex. In addition, we found that the more the experience of being punished in childhood, the lower the functional connection between the left and right globus pallidum in adulthood.
In animal studies, we found that childhood stress decreased excitatory neurons in the ventral pallidum and increased vulnerability to depression in adulthood. In addition, environmental enrichment, which has been reported to restore stress reactivity due to childhood maltreatment, reduced vulnerability to depression without the recovery of the decreased excitatory neurons in the ventral pallidum.

Free Research Field

精神神経医科学

Academic Significance and Societal Importance of the Research Achievements

ヒト臨床研究では、うつ病の中でも幼少期の不遇な体験を経た群に特有の異常な脳活動パターンを抽出した。また、淡蒼球と関連した脳機能的結合の機能的意義をヒトfMRI研究で明らかにした。
モデル動物研究では、幼少期ストレス後のうつ病モデルラットの腹側淡蒼球において興奮性神経細胞の減少という神経回路の構造異常を見出し、成長後のうつ病発症脆弱性をもたらすことを明らかにした。更に、この脆弱性の形成と回復には異なる機序が存在することを示した。