| Project/Area Number |
17K16389
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Psychiatric science
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
Furuse Kengo 札幌医科大学, 医学部, 研究員 (60608214)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | うつ病 / 難治性うつ病 / BDNF / 抗うつ薬 / 抗精神病薬 / Brain-derived exosome / 側坐核 / 扁桃体 / バイオマーカー |
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| Outline of Final Research Achievements |
We have conducted comparative analysis of pathophysiology of depression with high therapeutic response and refractory depression that is difficult to diagnose and treat, focusing on BDNF dynamic change in blood / depression related brain regions. The antidepressants sertraline and escitalopram attenuated the depressive behavior in the depression model rat which was induced by chronic adolescent corticosterone administration. On the other hand, in the refractory depression model rat induced by combining adolescent corticosterone administration and embryonic alcohol exposure, escitalopram but not sertraline indicated an antidepressant effect. In addition, in the depression model rat, the recovery of BDNF decline in blood and hippocampus was related to the antidepressive effect of antidepressants, and recoveries of decreased BDNF in blood and nucleus accumbens were related to the antidepressant action in the refractory depression model rat.
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| Academic Significance and Societal Importance of the Research Achievements |
実臨床において，うつ病の診断基準を満たしたとしても，その中には多彩な類型が含まれており生物学的背景を異にするものが混在していると考えられる。例えば，双極性うつ病，パーソナリティ障害やアルコール依存，胎生期あるいは幼少期の劣悪な環境を背景としたもの，高齢者の変性疾患に類似したものなどである。本課題では，うつ病の中核群について単一的に原因を求めるものではなく，うつ病症状を一種の動態，振舞いとして捉え直し，“神経活動に基づくBDNF発現の脳内局在”からうつ病の多様性を探究することを目指し，うつ病モデルと，臨床知見に基づく難治性のうつ病モデルを作成して病態の比較解析を実施する。
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