Inflammation, metabolic dysregulation, and depression profiles related to anhedonia and atypical, energy-related symptoms

• Anhedonia is associated with inflammation and metabolic dysregulation. • These associations were only partly explained by health and lifestyle variables. • The magnitude of the association with inflammation and metabolic dysregulation appears to be smaller for anhedonia than for atypical, energy-related symptoms. • When AES and anhedonia are modelled together, the associations between biomarkers and anhedonia disappeared or reversed in direction, highlighting the complex interplay between anhedonia and AES. Depression manifests heterogenous bio-clinical profiles. Anhedonia has been previously linked to inflammation. Other research has associated inflammation and metabolic dysregulations with atypical, energy-related depressive symptoms (AES). In the present study, we examined the associations of inflammation and metabolic dysregulations with anhedonia and compared these associations with those of inflammation and metabolic dysregulations with AES, and with a negative control symptom profile, previously shown unrelated to inflammation and metabolic dysregulation. Data was from 2,981 persons of the Netherlands Study of Depression and Anxiety (NESDA). Inflammatory markers included C-reactive protein (CRP), Interleukin-6 (IL-6), Tumor Necrosis Factor alpha (TNF-α), and glycoprotein acetyls. Metabolic markers were body mass index (BMI), waist circumference, triglycerides, high-density-lipoprotein cholesterol (HDL cholesterol), glucose and leptin. Anhedonia, AES and negative control symptom profiles were based on sum scores from different items from the Inventory of Depressive Symptomatology Self-Report (IDS-SR). The results were internally replicated in NESDA’s 6-year follow-up (N = 2,256). Anhedonia was positively associated with IL-6, glycoprotein acetyls, BMI, waist circumference, triglycerides, glucose, and leptin (β ranging from 0.063 to 0.122) and negatively associated with HDL cholesterol (β = -0.063). Associations were only partially explained by major lifestyle and health-related factors and confirmed at 6-year follow-up ( r = 0.939 correlation between estimates at baseline and follow-up). AES showed highly consistent associations with the markers, with relatively larger effects as compared to anhedonia, while the negative control symptoms were linked only to higher glycoprotein acetyls. Our results indicate consistent associations between several markers of inflammation and metabolic dysregulation with anhedonia and AES. Full characterization of depression profiles and their complex interrelations should be leveraged in future clinical research to select specific subgroup of depressed patients and develop more targeted treatment approaches.