Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Department of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience, Vrije Universiteit Medical Center and GGZ inGeest, Amsterdam, The Netherlands.
Transl Psychiatry. 2021 Feb 4;11(1):96. doi: 10.1038/s41398-021-01236-7.
Studies considering the causal role of body mass index (BMI) for the predisposition of major depressive disorder (MDD) based on a Mendelian Randomization (MR) approach have shown contradictory results. These inconsistent findings may be attributable to the heterogeneity of MDD; in fact, several studies have documented associations between BMI and mainly the atypical subtype of MDD. Using a MR approach, we investigated the potential causal role of obesity in both the atypical subtype and its five specific symptoms assessed according to the Statistical Manual of Mental Disorders (DSM), in two large European cohorts, CoLaus|PsyCoLaus (n = 3350, 1461 cases and 1889 controls) and NESDA|NTR (n = 4139, 1182 cases and 2957 controls). We first tested general obesity measured by BMI and then the body fat distribution measured by waist-to-hip ratio (WHR). Results suggested that BMI is potentially causally related to the symptom increase in appetite, for which inverse variance weighted, simple median and weighted median MR regression estimated slopes were 0.68 (SE = 0.23, p = 0.004), 0.77 (SE = 0.37, p = 0.036), and 1.11 (SE = 0.39, p = 0.004). No causal effect of BMI or WHR was found on the risk of the atypical subtype or for any of the other atypical symptoms. Our findings show that higher obesity is likely causal for the specific symptom of increase in appetite in depressed participants and reiterate the need to study depression at the granular level of its symptoms to further elucidate potential causal relationships and gain additional insight into its biological underpinnings.
基于孟德尔随机化（MR）方法，研究肥胖指数（BMI）与重度抑郁症（MDD）易感性之间的因果关系，结果显示相互矛盾。这些不一致的发现可能归因于 MDD 的异质性；事实上，有几项研究记录了 BMI 与 MDD 主要非典型亚型之间的关联。我们使用 MR 方法，在两个大型欧洲队列 CoLaus|PsyCoLaus（n=3350，1461 例病例和 1889 例对照）和 NESDA|NTR（n=4139，1182 例病例和 2957 例对照）中，研究了肥胖在非典型亚型及其根据《精神障碍诊断与统计手册》（DSM）评估的五个特定症状中的潜在因果作用。我们首先测试了 BMI 衡量的一般肥胖程度，然后测试了腰围-臀围比（WHR）衡量的身体脂肪分布。结果表明，BMI 与食欲增加症状有潜在的因果关系，反向方差加权、简单中位数和加权中位数 MR 回归估计斜率分别为 0.68（SE=0.23，p=0.004）、0.77（SE=0.37，p=0.036）和 1.11（SE=0.39，p=0.004）。BMI 或 WHR 对非典型亚型或任何其他非典型症状的风险均无因果影响。我们的研究结果表明，较高的肥胖程度可能是导致抑郁患者食欲增加的特定症状的原因，并重申需要在症状的颗粒水平上研究抑郁症，以进一步阐明潜在的因果关系，并深入了解其生物学基础。
