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Researchers discover a possible link between BMI and depression

7 August 2017

Having a higher body mass index (BMI) may increase the risk of developing depression, a new study from researchers at the MRC IEU has found. The study also investigated schizophrenia and bipolar disorder, but found no causal link to BMI.

Researchers found that a higher BMI leads to an increased risk of developing depression. However, the findings were not statistically robust due to constraints on available genetic data. Future studies with access to genetic data collected from more individuals may be able to confirm or refute this potential causal link between BMI and depression.

Psychiatric disorders such as depression, bipolar and schizophrenia are the leading cause of years lived with disability, a measure of the disease burden on a population. Previous evidence from observational studies has suggested that obesity, measured by BMI, may be linked to psychiatric disorders. However, such correlations may be explained by reverse causality, where psychiatric conditions can increase weight gain (eg, due to side effects of anti-psychotic medication), or by bias due to common causes of obesity and psychiatric diseases (ie, confounding).

The researchers used two-sample Mendelian Randomization (MR), which exploits the strengths of genetic data, to determine if there was a causal link between BMI and risk of depression, bipolar disorder and schizophrenia. The two-sample design allowed researchers to use publicly available data from large consortia of genetic studies, helping to improve statistical power and avoiding non-conservative bias which may occur when only one sample is used.

Three two sample MR methods were utilised in the study, each with different assumptions. The link between BMI and depression remained present throughout all methodologies which may indicate a causal link rather than violations of a specific assumption. However, the overall statistical evidence was weak meaning it is uncertain whether this causal link exists.  

The sample size of genetic data from individuals with schizophrenia was much larger than that for individuals with bipolar disorder or depression, but nevertheless there was no indication of an effect of BMI on schizophrenia risk. Therefore, the lack of strong statistical evidence in this case is more likely due to absence of a meaningful causal effect of BMI on schizophrenia rather than lack of statistical power.

Fernando Hartwig, lead author on the paper says "Investigating the causal relationships between BMI and psychiatric disorders in non-experimental epidemiological studies is greatly complicated by factors such as side effects of anti-psychotic medication on weight gain, and bias due to latent, pre-clinical disease that may affect BMI. Therefore, alternatives that are likely to be less affected by such biases, such as exploiting the strengths of genetic data through Mendelian randomization, are required. 

“The two-sample design that we employed allowed us to use data from much larger sample sizes than previous Mendelian randomization studies on this topic, and for a greater number of genetic variants, which improved statistical power and allowed us to employ a range of methods that make different assumptions. Higher BMI was consistently related to higher risk of developing depression across those methods, which is compatible with a causal effect. However, the results were not statistically robust. Recently, larger genetic studies on depression were published, so now it is possible to use these data to confirm or refute this possible causal link."

For more information on the methods of the study you can find the paper here: https://www.ncbi.nlm.nih.gov/m/pubmed/27601421/

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