探究年齡及飲食品質對於 時型與重鬱症之間關係的影響

Abstract

研究背景 重鬱症（Major Depressive Disorder, MDD）是一種常見的心理健康問題，會嚴重影響社會心理功能並降低生活品質，其盛行率在世界各地存在較高程度的異質性。重鬱症的危險因素包括個人因素、生活方式因素和環境因素，包含了年齡、不好的睡眠特徵和不健康的飲食習慣等。其中時型（chronotype）代表了個體睡眠時間和日常活動時間的偏好，並可通過晨型-夜型問卷（MEQ）定義為早晨型、中間型和夜晚型。 先前的孟德爾隨機化（Mendelian randomization, MR）研究提供了早晨型時型會顯著降低重鬱症風險的因果關係證據。然而過去的研究表明，隨著年齡的增加個體的時型可能會發生變化，並且早晨型的生活型態可能與健康的飲食品質有關。值得注意的是，時型和重鬱症之間存在一些共同影響的因子，例如年齡及生活型態，因此，年齡和飲食品質可能會影響觀察到的時型與重鬱症之間的相關性。 綜上所述，本研究目的在檢測遺傳基因代理的早晨型時型與年齡以及飲食品質之間的交互作用，是否會影響晨型與降低重鬱症風險之間的因果關係。 研究方法與材料 本研究納入來自英國生物資料庫（UK Biobank）的103,378名參與者，透過自我報告的問題獲得個體的時型與重鬱症狀態，並且藉由24小時飲食回顧記錄來計算AHEI-2010（Alternative Healthy Eating Index-2010）的分數以評估個體的飲食品質。本研究使用了來自英國生物資料庫和23andMe資料庫的晨型全基因組關聯研究（GWAS）獲得的遺傳變異作為工具變量，進行了孟德爾隨機化分析。不僅如此，為了探討年齡和飲食品質分別對晨型時型與重鬱症之間關係的影響，本研究進行了分層的孟德爾隨機化分析。 研究結果 本研究通過單一樣本孟德爾隨機化分析，發現晨型時型可能顯著降低重鬱症的發生風險（OR = 0.831，p值 < 0.00001）。在不同年齡和AHEI-2010分數組別的分層孟德爾隨機化分析結果中，效應估計值幾乎一致：三組年齡組別的OR值分別為0.832、0.817以及0.841；三種飲食品質連續變項的三分位數組別的OR值皆大約為0.8。不僅如此，異質性檢驗結果也表明不同年齡和飲食品質分數組別間的效應估計值無顯著差異，因此本研究表明時型與年齡組別或遺傳變異與飲食品質組別之間對時型與重鬱症的因果關係並未有明顯的交互作用存在。 結論 本研究結果表明，年齡和早晨型時型之間，或飲食品質和早晨型時型之間都沒有顯著的交互作用。本研究也顯示了早晨型時型與重鬱症之間因果關係的穩固性。然而，未來的研究應考慮更廣泛的年齡範圍以及個人的飲食習慣和行為，以進一步了解年齡和飲食對此因果關係的潛在影響。

Background Major depressive disorder (MDD) is a common mental health problem that severely impairs social and psychological functioning and reduces the quality of life. Its prevalence varies around the world. The risk factors for depression include personal factors, lifestyle factors, and environmental factors, such as aging, poor sleeping behaviors, and unhealthy diet. Chronotype refers as a preference for individual’s sleep and activities time in our 24 hours daily, and it can be defined as morning, intermediate, or evening type through the morningness-eveningness questionnaire (MEQ). Previous Mendelian randomization (MR) studies have provided evidence of a causal relationship between the morning chronotype and a reduced risk of depression. However, previous study has indicated that individual's chronotype may change with age, as well as morning chronotype may be associated with a higher diet quality. Notably, there are some common influencing factors between chronotype and depression, such as age and lifestyle. Therefore, age and dietary quality may affect the relationship between chronotype and depression. In summary, this study aims to examine the interaction between genetically proxied morning chronotype and age or diet quality, on the causal relationship between morning chronotype and reduced MDD risk. Methods and Materials This study included 103,378 participants from the UK Biobank. Chronotype (exposure) and the depression status (outcome) were both obtained through self-reported questions, and dietary quality was assessed by the Alternative Healthy Eating Index-2010 (AHEI-2010) score calculated from the 24-hour dietary recall records. Additionally, this study used genetic variants from a morning chronotype genome-wide association study, which used the UK Biobank data as the instrumental variables to conduct the MR analyses. To investigate the potential effect modification of age and diet quality on the relationship between morning chronotype and depression, stratified MR analyses were performed. Results This study found through one-sample MR analysis that the morning chronotype people may have the lower risk of depression (OR = 0.831, p value < 0.00001). In the stratified MR analyses by age and AHEI-2010 score, the effect estimates were almost consistent: the odds ratio for the three age groups were 0.832, 0.817, and 0.841, respectively; the odds ratio for tertiles of the three diet quality continuous variables were all around 0.8. Furthermore, heterogeneity tests indicated no significant differences in effect estimates between different age and diet quality score subgroups. Therefore, this study suggests that the interaction between genetic variants and age or diet quality on the causal relationship between chronotype and depression risk are not significant. Conclusion Our results suggested no significant interaction between age and chronotype, nor between diet quality and chronotype. This study also indicated the robustness of the causal relationship between chronotype and depression. However, future studies should consider a broader age range and individuals' dietary habits to further clarify the potential influence of age and diet on this causal relationship.