2026 ECNP Congress

PS04-4102

Atypical symptoms associated with metabolic, but not inflammatory, biomarkers in bariatric surgery patients with depression

Melisa Kose — A.P. McLaughlin, N. Mariani, R. Milton, L. Giulia, Z. Zajowska, V. Mondelli · King's College London, Psychological Medicine, London, United Kingdom

2026 ECNP Congress

Introduction

Obesity and depression are highly prevalent conditions significantly impacting global health; in England alone, 25% of adults are reported to have obesity and 20% depression. With this high and growing incidence, the high comorbidity between the disorders is unsurprising, contributing to a vicious cycle between the two conditions [1], [2]. In parallel, there has been a growing interest in the role of immune and metabolic abnormalities within and on this comorbidity [3], [4]. While traditional models have focused on more typical symptoms of depression, recent research highlights the relevance of understanding atypical symptoms (e.g., hypersomnia, lethargy, weight gain, and increased appetite) [5].

Aims

For this study, we worked with patients living with obesity, with or without comorbid depression, who were scheduled to undergo bariatric weight-loss surgery. We aimed to investigate 1) changes in typical and atypical depression symptoms before and 3-years after bariatric surgery and 2) which metabolic and inflammatory biomarkers are associated with these changes.

Methods

We investigated 37 participants from the bariatric surgery and depression (BARDEP) study for whom both baseline pre-surgery (age=46.7±11.6; BMI=48.5±6.6kg/m2) and 3-year post-surgery (age=49.7±11.3; BMI=36.59±6.98kg/m2) data were obtained. All participants had obesity (BMI ≥30kg/m2), with (n=15) and without (n=22) comorbid baseline depression. Symptoms were measured using the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS) and divided into three clusters: HAM-D-17, Atypical-8, and total 25-item-combined scores. Blood samples were collected at Baseline, and at 3-year follow-up to measure peripheral inflammation in serum. Weight-loss percentage (WLP) and changes in BMI were calculated. Group differences (t-tests/Wilcoxon), Spearman’s correlations, and regression analyses were computed.

Results

In the MDD group, total SIGHADS scores were significantly reduced post-surgery [t(13)=1.974, p=0.035, one-tailed], seemingly driven by distinct improvement in atypical symptoms of depression [t(13)=1.939, p=0.037, one-tailed] while HAM-D (or typical) scores did not change. Nevertheless, participants in the MDD group remained significantly more likely to report worse depressive symptoms than controls in all three domains at 3-years post-surgery. In contrast, the control group saw significant worsening in typical [t(21)=2.383, p=0.013], atypical [t(21)=2.996, p=0.003], and total scores [t(21)=3.172, p=0.002], though remained below the relevant clinical thresholds for all domains. Both MDD and control groups saw significant reductions in weight [t(14)=5.083, p<0.001 and t(21)=14.34, p<0.001 respectively], BMI score [t(14)=9.449, p<0.001; t(21)=14.37, p<0.001], and trunk muscle mass [t(12)=4.993, p<0.001; t(18)=6.385, p<0.001] by 3 years after bariatric surgery. In MDD, only IL-6 (Z=-3.059; p=0.002), and TNF-α (Z=-3.059; p=0.002) were significantly decreased by 3-years; however, these changes were not correlated with the changes (Δ) seen in atypical symptoms. Improvement in atypical symptoms were correlated with WLP [r(13)=-0.589, p=0.021], Δ-weight [r(13)=0.697,p=0.004], Δ-BMI [r(13)=0.556, p=0.031], and Δ-fat mass [r(9)=0.700, p=0.016]. Baseline weight domains did not, however, predict the improvement in atypical symptoms by 3-year follow-up.

Conclusions

Our data suggests a unique relationship between atypical symptoms and metabolic (i.e., WLP, BMI, fat/muscle), but not inflammatory, biomarkers. Our findings suggest weight-loss interventions may be particularly beneficial in the long-term for those individuals with atypical depression.

References

  1. ​Carey, M., Small, H., Yoong, S. L., Boyes, A., Bisquera, A., & Sanson-Fisher, R. (2014). Prevalence of comorbid depression and obesity in general practice: a cross-sectional survey. British Journal of General Practice, 64(620), e122–e127.
  2. ​Keaver, L., Xu, B., Jaccard, A., & Webber, L. (2020). Morbid obesity in the UK: A modelling projection study to 2035. Scandinavian Journal of Public Health, 48(4), 422–427.
  3. ​McLaughlin, A., Lambert, E. R., Milton, R., Mariani, N., Kose, M., Nikkheslat, N., Patsalos, O., Ferraro, L., Chamseddine, G., Panagiotopoulos, S., Chang, A., Ramar, S., Rubino, F., & Mondelli, V. (2023). Peripheral inflammation associated with depression and reduced weight loss: a longitudinal study of bariatric patients. Psychological Medicine.
  4. ​Milaneschi, Y., Simmons, W. K., van Rossum, E. F. C., & Penninx, B. W. (2019). Depression and obesity: evidence of shared biological mechanisms. Molecular Psychiatry, 24(1), 18–33.
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