TY - JOUR
T1 - Assessing the Evidence for Causal Associations Between Body Mass Index, C-Reactive Protein, Depression, and Reported Trauma Using Mendelian Randomization
AU - Palmos, Alish B.
AU - Hübel, Christopher
AU - Lim, Kai Xiang
AU - Hunjan, Avina K.
AU - Coleman, Jonathan R.I.
AU - Breen, Gerome
N1 - Funding Information:
This work was supported by funding from Lundbeckfonden (Grant No. R276-2018-4581 [to CH]). This paper represents independent research partly funded by the National Institute for Health Research Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors. GB has received consultancy fees from Compass Pathways Ltd and Otsuka Ltd. All other authors report no biomedical financial interests or potential conflicts of interest.
Publisher Copyright:
© 2022 The Authors
PY - 2023/1/17
Y1 - 2023/1/17
N2 - Background: Traumatic experiences are described as the strongest predictors of major depressive disorder (MDD), with inflammation potentially mediating the association between trauma and symptom onset. However, several studies indicate that body mass index (BMI) exerts a large confounding effect on both inflammation and MDD. Methods: First, we sought to replicate previously reported associations between these traits in a large subset of the UK Biobank, using regression models with C-reactive protein (CRP) and MDD and as the outcome variables in 113,481 and 30,137 individuals, respectively. Second, we ran bidirectional Mendelian randomization analyses between these traits to establish a potential causal framework between BMI, MDD, reported childhood trauma, and inflammation. Results: Our phenotypic analyses revealed no association between CRP and MDD but did suggest a strong effect of BMI and reported trauma on both CRP (BMI: β = 0.43, 95% CI = 0.43–0.43, p ≤ .001; childhood trauma: β = 0.02, 95% CI = 0.00–0.03, p = .006) and MDD (BMI: odds ratio [OR] = 1.16, 95% CI = 1.14–1.19, p ≤ .001; childhood trauma: OR = 1.99, 95% CI = 1.88–2.11, p ≤ .001). Our Mendelian randomization analyses confirmed a lack of causal relationship between CRP and MDD but showed evidence consistent with a strong causal influence of higher BMI on increased CRP (β = 0.37, 95% CI = 0.36–0.39, p ≤ .001) and a bidirectional influence between reported trauma and MDD (OR trauma-MDD = 1.75, 95% CI = 1.49–2.07, p ≤ .001; OR MDD-trauma = 1.22, 95% CI = 1.18–1.27, p ≤ .001). Conclusions: Our findings highlight the importance of controlling for both BMI and trauma when studying MDD in the context of inflammation. They also suggest that the experience of traumatic events can increase the risk for MDD and that MDD can increase the experience of traumatic events.
AB - Background: Traumatic experiences are described as the strongest predictors of major depressive disorder (MDD), with inflammation potentially mediating the association between trauma and symptom onset. However, several studies indicate that body mass index (BMI) exerts a large confounding effect on both inflammation and MDD. Methods: First, we sought to replicate previously reported associations between these traits in a large subset of the UK Biobank, using regression models with C-reactive protein (CRP) and MDD and as the outcome variables in 113,481 and 30,137 individuals, respectively. Second, we ran bidirectional Mendelian randomization analyses between these traits to establish a potential causal framework between BMI, MDD, reported childhood trauma, and inflammation. Results: Our phenotypic analyses revealed no association between CRP and MDD but did suggest a strong effect of BMI and reported trauma on both CRP (BMI: β = 0.43, 95% CI = 0.43–0.43, p ≤ .001; childhood trauma: β = 0.02, 95% CI = 0.00–0.03, p = .006) and MDD (BMI: odds ratio [OR] = 1.16, 95% CI = 1.14–1.19, p ≤ .001; childhood trauma: OR = 1.99, 95% CI = 1.88–2.11, p ≤ .001). Our Mendelian randomization analyses confirmed a lack of causal relationship between CRP and MDD but showed evidence consistent with a strong causal influence of higher BMI on increased CRP (β = 0.37, 95% CI = 0.36–0.39, p ≤ .001) and a bidirectional influence between reported trauma and MDD (OR trauma-MDD = 1.75, 95% CI = 1.49–2.07, p ≤ .001; OR MDD-trauma = 1.22, 95% CI = 1.18–1.27, p ≤ .001). Conclusions: Our findings highlight the importance of controlling for both BMI and trauma when studying MDD in the context of inflammation. They also suggest that the experience of traumatic events can increase the risk for MDD and that MDD can increase the experience of traumatic events.
KW - Body mass index
KW - Causation
KW - Depression
KW - Genetics
KW - Inflammation
KW - Mendelian randomization
KW - Trauma
UR - http://www.scopus.com/inward/record.url?scp=85148561869&partnerID=8YFLogxK
U2 - 10.1016/j.bpsgos.2022.01.003
DO - 10.1016/j.bpsgos.2022.01.003
M3 - Article
AN - SCOPUS:85148561869
SN - 2667-1743
VL - 3
SP - 110
EP - 118
JO - Biological Psychiatry Global Open Science
JF - Biological Psychiatry Global Open Science
IS - 1
ER -