Teasing Out Causality in Obesity and Depression

The Melancholy of Departure, painting by Giorgio de Chirico / WikiArtCausality in the relationship between obesity and depression is mighty hard to discern in a rigorous way. For clinicians, it seems obvious that obesity creates a risk for depression. Likewise, the observation that depression in some patients can lead to obesity is easy to find. But understanding that causal relationship is a challenge. Mere association is not enough.

So a new study using Mendelian randomization offers some very welcome insight. This study suggests that obesity, measured by BMI, has a causal relationship with lower glutamine levels and that both obesity and low glutamine levels have a causal relationship with depression.

The Link to Glutamine

Ruixin He and colleagues explain that they were able to tap large data sources to help them better detect the causal nature of these relationships. For example, they note that the depression-related data from 449,019 subjects in their analysis is nearly four times as much as was assembled for prior analyses. The authors say that to their knowledge,  “this study is the first to dissect the associations between glutaminergic metabolism, obesity, and depression.”

The link to glutamine is important because these data support a conclusion that the causal relationship between obesity and depression is dependent upon glutamine levels. The researchers conclude by saying:

Our findings are clinically relevant because they provide insight into how obesity may affect psychiatry and suggest that weight control and therapy targeting glutamatergic dysfunction may be potential treatment of depression, which provides novel perspective for design of clinical trials.”

Stronger Insight

This research adds to the insight from three other Mendelian randomization studies of causality in the relationship of obesity and depression – all published last year. Those studies served to document the causal relationships between obesity, metabolic dysregulation, and depression.

Taken together, this body of research offers important clues that will lead to better options for care in these closely related conditions.

Click here for the new study by He et al, here, here, and here for the other recent Mendelian randomization studies of this question. For further perspective, click here.

The Melancholy of Departure, painting by Giorgio de Chirico / WikiArt

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December 23, 2022

One Response to “Teasing Out Causality in Obesity and Depression”

  1. December 24, 2022 at 9:56 am, John DiTraglia said:

    Benjamin Plackett in his perspective says, “The science is not so clear because there are so many contradicting studies,” he says. “But our systematic review showed that calorie-restricted diets can decrease people’s depression score.”
    That might be because in the early days of dieting there is weight loss that is encouraging. But hunger is also very stressful.
    Is there a way to measure and increase self esteem?