Elucidation of Genetic Specificity between Anxiety Disorders and Major Depressive Disorder using Intermediate Phenotypes

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07497
• 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: Gifu University
• Principal Investigator: Shioiri Toshiki 岐阜大学, 大学院医学系研究科, 教授 (40235487)
• Co-Investigator(Kenkyū-buntansha): 大井 一高 岐阜大学, 医学部附属病院, 准教授 (70629203)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 中間表現型 / 不安症 / パニック症 / うつ病 / ゲノム / 遺伝的共通性 / 遺伝的疾患特異性 / ポリジェニックリスクスコア

Outline of Final Research Achievements

Anxiety disorders and major depressive disorder are complex psychiatric disorders with a multifactorial genetic inheritance and a heritability rate of 30-50%, exhibiting clinical and genetic heterogeneity. We investigated the genetic commonalities and specificities between these disorders utilizing intermediate phenotypes such as personality traits, cognitive functions, and sleep. It demonstrated genetic commonalities between these disorders as well as their association with adjustment disorder, suicidal attempts, neuroticism, cognitive functions, and ages of first sexual intercourse and first childbirth. In contrast, in children, genetic risks for anxiety were associated with sleep disturbances and nightmares, while depression was associated with difficulties in falling asleep, nocturnal awakenings, and hypersomnia. Furthermore, by integrating various polygenic risk scores through machine learning, we showed improvements in distinguishing anxiety disorder.

Free Research Field

精神医学

Academic Significance and Societal Importance of the Research Achievements

不安症とうつ病間の遺伝的共通性や、神経症などの中間表現型との遺伝的共通性の検討はこれまでに行われてきたが、不安症とうつ病間の遺伝的疾患特異性を検討した研究は存在しなかった。本研究では、神経症などの中間表現型以外にも、不安症とうつ病間で遺伝的共通性を呈する中間表現型がいくつか存在することを示した。一方で、幼少時の悪夢や入眠困難、中途覚醒などの中間表現型は、不安症とうつ病間で遺伝的疾患特異性が存在することを明らかにした。また、生殖関連行動が早いことが不安症において双方向性の因果関係を有することを示し、これは不安症の発症年齢が広範囲に渡ることに起因し、発症前後ともに介入が可能であることを示唆している