The origins of depression are currently being studied and it seems like inflammation and weight might be the cause of depression.
Inflammation and weight addressed as the origins of depression
Major depressive disorder (MDD), commonly known as depression, is a significant global health concern. Antidepressant medication and psychotherapy are the usual courses of treatment, but in some cases, the depression may not respond to treatment, known as treatment-resistant depression (TRD).
A recent study in BMC Medicine explores the connection between inflammation and body mass index (BMI) and the development of TRD.
Depression is a leading contributor to chronic disability, with MDD ranking third or higher on the list of causes of disability.
According to News Medical, about 7% of cases of major depressive disorder are diagnosed as treatment-resistant depression. To effectively manage these patients, it’s important to understand why they are not responding to standard treatment.
Research has shown that individuals with a high body mass index (BMI) may be at greater risk for MDD, potentially due to decreased physical health impacting their mood.
In fact, this association between BMI and subsequent depression has been observed in over 25% of cases. The greater the BMI, the more likely a person were to develop MDD later.
The link between obesity and depression may be partially explained by negative social reactions towards those who are overweight. Major depressive disorder typically affects adults and not children or adolescents.
Even if there are no negative metabolic effects, obesity is still linked to a higher risk of depression, which supports the idea that social factors play a role. Effective weight management can lead to a decrease in symptoms of depression.
Research is being conducted to investigate the presence of inflammation in obesity. CRP, a liver protein that is synthesized during inflammation, is being studied to determine its role in disease progression.
Although there is controversy regarding its role as a driver of disease, it is widely accepted as a biomarker of disease progression in autoimmune and infectious diseases.
Analyzing the association between CRP and TRD
To study the association between CRP and TRD, the Mendelian randomization (MR) approach was used. This is a research method in epidemiology that involves testing the associations of genetic variables, usually single nucleotide polymorphisms (SNPs), that predict an exposure of interest (such as CRP in this study) with the outcome of interest (TRD).
To accurately identify causal associations, it is important to avoid the influence of other factors that could affect the CRP value, like smoking, BMI, or autoimmune disease.
However, pleiotropic errors can still occur where the SNP affects the outcome but not through the exposure being studied. To prevent this, researchers conduct multivariable MR (MVMR) studies that consider a larger set of genetically predicted exposures. MVMR studies have found that increasing BMI is associated with an increase in CRP levels.
Investigations and study results
Using MR, researchers investigated the relationship between inflammation, body mass index (BMI), and depression.
Observational correlations revealed that treatment-resistant depression (TRD) was associated with higher levels of both C-reactive protein (CRP) and BMI compared to individuals with major depressive disorder (MDD) or those who were healthy.
While the CRP levels were not consistently indicative of active inflammation, individuals with MDD or TRD had higher levels than the control group. Additionally, females make up a higher percentage of individuals in both the MDD and TRD cohorts.
According to the study, inflammation can make depression more severe, and this is partly due to its connection with higher BMI values. It was also found that BMI can contribute to treatment-resistant depression (TRD) even without the presence of inflammation.
This suggests that social factors may also play a role in the risk for depression, regardless of the metabolic or inflammatory effects caused by a high BMI.
