Depression and obesity are highly comorbid disorders, which are both characterised by chronic, low-grade inflammation. Chronic inflammation increases the risk for adverse health outcomes in patients with depression and obesity, but it is unclear whether excess weight or depressive symptoms are the driving factor contributing to increased inflammation. Research shows that the atypical depression subtype is associated with weight gain and metabolic abnormalities, and it has been hypothesised that atypical depressive symptoms may increase inflammation and exacerbate comorbid depression and obesity. Further highlighting the bidirectional relationship between depression and obesity, studies of obese patients with depression undergoing bariatric surgery have found that the rapid weight loss induced by surgery is associated with a dramatic improvement in depressive symptoms. However, other studies of bariatric patients have suggested that a pre-operative depression diagnosis is a contraindication for successful weight loss after bariatric surgery. Given the putative role of inflammation in the vicious cycle between depression and obesity, it is possible that inflammation may influence weight loss and changes in depression symptoms following bariatric surgery.
My PhD thesis investigated the role of inflammation in association with depression, excess weight, obesity and bariatric surgery in four separate stages. Inflammatory markers included high-sensitivity C-Reactive Protein (hsCRP) and cytokines, such as interleukin-6 (IL-6) and interleukin-2 (IL-2), measured in blood samples. Anti-inflammatory markers included cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10) measured in blood samples, and the stress hormone cortisol measured in saliva samples. Firstly, I investigated hsCRP and cortisol levels in a cross-sectional study of overweight and normal weight individuals, with and without depression. Secondly, I investigated hsCRP levels, cytokines and cortisol levels in association with depression in bariatric surgery candidates prior to surgery. Thirdly, I investigated changes in weight loss, depressive symptoms and hsCRP levels in bariatric patients 6 months after surgery. Fourthly, I identified baseline predictors of clinical outcomes (weight loss and depression) after bariatric surgery, by combining pre-operative and post-operative data from bariatric patients.
In the cross-sectional study of depression and excess weight, overweight patients with depression had significantly higher hsCRP levels compared with overweight controls (p=0.042), normal weight depressed patients (p<0.001) and normal weight controls (p<0.001). Overweight patients with depression were at a significantly increased risk of having clinically elevated hsCRP levels ≥3 mg/L (odds ratio: 2.44, p<0.001), relative to all other groups (all p>0.1). No differences in cortisol levels were observed among groups.
In the study of bariatric candidates prior to surgery, candidates with depression had significantly higher hsCRP, IL-6, IL-6/IL-10 ratio, lower IL-4, abnormal IL-2 levels and lower cortisol levels compared with control bariatric candidates (all p<0.05). Atypical depression symptoms were associated with lower cortisol levels (p=0.02), but were not associated with higher hsCRP, IL-6, IL-6/IL-10 ratio, or lower IL-4 levels (all p>0.05).
In the follow-up study of bariatric patients 6 months after surgery, 19 patients (65.5%) with depression at baseline no longer met the clinical criteria for depression at follow-up. There were no differences in rates of weight loss or hsCRP levels at follow-up between patients with a pre-operative diagnosis of depression and control patients (both p>0.1). Patients with atypical depression showed a trend for the greatest improvement in depressive symptoms at follow-up, compared with non-atypical patients with depression (p=0.08).
Longitudinal analyses of bariatric patients showed that higher hsCRP levels prior to surgery predicted attenuated weight loss 6 months after bariatric surgery (β = -0.3, p=0.006). However, higher inflammation and attenuated weight loss were not associated with depression outcomes after surgery. Rather, higher depression severity prior to surgery and childhood emotional abuse were found to predict higher depression severity 6 months after bariatric surgery (β = 0.81, p<0.001 and β = 0.31, p=0.001, respectively). Interestingly, higher atypical symptoms prior to surgery predicted a greater improvement in depression symptoms after bariatric surgery (β = -0.36, p=0.008).
In conclusion, my findings provided evidence that depression significantly contributes to higher levels of peripheral inflammation, beyond the effects of excess weight and obesity. Moreover, my results suggested that higher inflammation is one of the driving factors predicting attenuated weight loss following bariatric surgery, rather than depression. My findings also raised the possibility that atypical depression is not associated with increased inflammation, but bariatric patients with atypical depression may be most likely to experience the greatest psychological benefit after bariatric surgery. Further research is needed to confirm these findings and investigate whether anti-inflammatory treatments may help to improve clinical outcomes after bariatric surgery and break the vicious cycle between depression and obesity.