The first study to investigate the links between depression and inflammation in patients with obesity undergoing bariatric surgery has shown that the association between depression and poor weight loss following surgery is driven by the inflammation.
The study team, led by researchers from the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) at King's College London, noted that depression and obesity were "highly co-morbid disorders" that often occur together in a "vicious cycle". Both are rapidly increasing in prevalence globally and are leading causes of disability and mortality.
Previous research had suggested that release of inflammatory proteins as part of the immune response might be "a shared disease mechanism" driving both conditions, yet there were few longitudinal studies.
In addition, the researchers noted that the only effective, long-term weight loss intervention for obesity is bariatric surgery, through which patients can lose up to 60% to 70% of their excess weight, but that the pre-surgical prevalence of depression was very high — at 45% — in bariatric surgery candidates.
"Urgent Need" to Identify Risk Factors for Poor Outcomes
Moreover, although the rapid weight loss induced by bariatric surgery is typically associated with a dramatic improvement in depressive symptoms, a preoperative depression diagnosis may increase the risk for poor weight loss following bariatric surgery. Therefore, the team said, there was "an urgent medical need to identify whether depression is a risk factor for poor clinical outcomes after bariatric surgery".
Given the apparent links with inflammation, they set out to investigate the differences in inflammatory proteins between obese patients with and without depression before and after bariatric surgery, and the possible effect of these on surgery outcomes.
Subjects were 85 obese (BMI >35) participants from King's College Hospital already enrolled in an ongoing study of bariatric surgery and depression, of whom 41 had symptoms of depression that reached the threshold of clinical diagnosis. Participants' levels of serum high-sensitivity C-reactive protein (CRP) and inflammatory cytokines, such as interleukin-4 (IL-4), IL-6, and IL-10 were measured before and after bariatric surgery in both blood and adipose tissue.
Before surgery, participants with depression had significantly higher serum levels of CRP and IL-6, as well as a higher IL-6/10 ratio, after controlling for confounders. Six months after surgery, patients with pre-existing depression still had significantly higher levels of inflammatory markers despite similar weight loss to controls.
Inflammation the Driver of Poor Weight Loss
Analysis showed "a strong relationship between depression and inflammation" in obese patients both before and after surgery, and indicated that it was increased inflammation, rather than depression, that was driving poor weight loss after bariatric surgery.
Hierarchical regression showed higher baseline hsCRP levels predicted poorer weight loss (β = −0.28, p = 0.01) but had no effect on depression severity at follow-up (β = −0.02, p = 0.9). Instead, more severe baseline depressive
symptoms and childhood emotional abuse predicted greater depression severity after surgery (β = 0.81, p < 0.001; and β = 0.31, p = 0.001, respectively).
The team said that overall, bariatric surgery led to weight loss in all patients in line with expectations. Of the patients who had depression before surgery and completed the 6-month follow-up, most also experienced a reduction in their depressive symptoms, so that only 10 (34.5%) still had clinical depression after the surgery.
"Increased inflammation, rather than depression diagnosis, may be responsible for the high variability in weight loss and depression outcomes among bariatric patients," they concluded.
Study Has "Important Clinical Implications"
The research was funded by the National Institute for Health and Care Research (NIHR) and published in the journal Psychological Medicine. First author Dr Anna McLaughlin, a postdoctoral research associate at IoPPN, said: "Our study is the first to show that inflammation levels in the blood, rather than depression, play a significant role in weight loss outcomes after bariatric surgery. Additionally, our research aligns with previous findings, emphasising that patients with childhood trauma may benefit from more psychological support after surgery."
Lead author Valeria Mondelli, clinical professor of psychoneuroimmunology at IoPPN, said: "Our study has important clinical implications as it identifies specific targets for future personalised interventions, which could improve physical and mental health outcomes after bariatric surgery."
If increased inflammation predicts lower weight-loss after bariatric surgery, this suggests that approaches to lower inflammation could enable better outcomes after surgery, she said.
According to the Department of Health and Social Care, obesity costs the NHS around £6 billion a year, and this figure is predicted to rise to over £9.6 billion each year by 2050.
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