Psychopathological features, peripheral neuroendocrine biomarkers and clinical chemistry correlates in bariatric surgery candidates

Background: Obesity is a heterogeneous group with multifactorial pathogenesis (genetic, environmental, behavioral, psychological) and high morbidity/mortality; Bariatric Surgery (BS) is an option for severe obesity (BMI>35 or 30-34.9 with comorbidities). Severe obesity derived from a complex interplay between neuroendocrine, immune-inflammatory, and metabolic pathways, potentially influenced by a wide range of psychopathological features. BS candidates have high rates of lifetime psychiatric disorders, suggesting specific neural and peripheral alterations. In these subjects, evaluating psychopathological features such as mood and trauma-and-loss symptoms together with peripheral biomarkers is crucial, considering their potential role in influencing brain-periphery axes as well as eating behavior and pre/post-operative management. Aims: Exploratory survey on preoperative psychopathological and clinical biochemical data in BS candidates. The aim is to examine relationships between biochemical parameters (including inflammatory indices) and psychiatric features along a dimensional approach, including subthreshold symptoms, to characterize heterogeneity and identify clinical-biochemical profiles for personalized care. Methods: Participants were recruited at the University-Hospital of Pisa (AOUP) during pre-surgical evaluations, including psychiatric assessment. Inclusion criteria: age 18-70, assessment ability, informed consent. Data were collected from routine biochemical and psychiatric assessments and specific biochemical tests conducted on pre-operative biological samples. Psychopathological assessment encompassed a clinical interview and self-report psychometric questionnaires (MOODS-SR, TALS-SR), investigating depressive/manic symptoms, trauma/loss symptoms, alterations in circadian rhythms and vegetative functions. Biochemical assessment included plasma levels of cortisol, glucose, HbA1c, insulin, lipids, uric acid, homocysteine, CRP, ESR, blood cell counts, with NLR, MLR, PLR calculation. Bivariate (Spearman’s correlations) and multivariate (PCA) analyses were performed (using GraphPad Prism and JMP software). Results: a total of 45 patients with mean BMI=42 were finally recruited. Descriptive analyses showed generally low morning cortisol levels; approx. 50% of the sample with altered glicemic pattern; a subset with dyslipidemia; half with elevated inflammatory indices. High prevalence of depressive and trauma-related symptoms was found. Spearman’s correlations revealed interesting findings between metabolic indices and neuroendocrine/nutritional factors and psychopathological features. Several of them were then corroborated by PCA, which revealed two dominant components: PC1 (19% variance) links psychopathological and hematological factors (particularly PLT and PLR, with a negative correlation with Cortisol), suggesting blunted HPA axis in subjects with depressive/post-traumatic symptoms. PC2 (17.6% variance) reflects inflammatory and metabolic markers, with limited psychopathological influence, suggesting a different pattern along the heterogeneity of the sample. Conclusions: These exploratory insights suggest widespread subthreshold depressive symptoms, PTSD features, circadian, sleep, and appetite disturbances in BS candidates (or, at in least, in subgroups), related to lower HPA activity, elevated glucose, and inflammation (particularly represented by ESR and platelet activity). Future longitudinal studies with larger samples and specific analyses are needed to clarify these findings and clinical implications.