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Causal Association Between Obesity, Circulating Glutamine Levels, and Depression: A Mendelian Randomization Study
Ruixin He1,2, Ruizhi Zheng1,2, Jie Zheng1,2
1Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
The Journal of Clinical Endocrinology and Metabolism
|December 13, 2022
Summary
Higher body mass index (BMI) is linked to lower glutamine levels, and both obesity and reduced glutamine causally contribute to depression. This study clarifies the causal links between obesity, glutamine, and depressive symptoms.
Area of Science:
- Metabolic Psychiatry
- Nutritional Neuroscience
- Genetic Epidemiology
Background:
- Obesity and glutamatergic dysfunction are potential depression risk factors.
- Glutamine metabolism is disturbed in obesity, but causal links remain unclear.
Purpose of the Study:
- To explore causalities between glutamine levels, depressive symptoms, major depressive disorder (MDD), and body mass index (BMI).
- Utilize bidirectional Mendelian randomization (MR) to investigate these relationships.
Main Methods:
- Conducted 2-sample bidirectional MR analyses.
- Performed univariable MR, multivariable MR (MVMR), and linkage disequilibrium score regression (LDSR).
Main Results:
- Genetic downregulation of glutamine causally linked to MDD, anhedonia, tiredness, and depressed mood.
- Elevated BMI causally linked to lower glutamine levels and more severe depressive symptoms.
- BMI causally related to depressed mood independently of glutamine; tiredness causally linked to elevated BMI.
Conclusions:
- Higher BMI causally associated with lower glutamine levels.
- Obesity and glutamine downregulation are causally linked to depression.
- Findings support a causal pathway from obesity to depression via glutamine metabolism.
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