Inflammatory and metabolic disturbances are associated with more severe trajectories of late-life depression.

Late-life depression is a highly prevalent mental health condition with devastating consequences even from its earliest stages. Alterations in physiological functions, such as inflammatory and metabolic, have been described in patients with depression. However, little is known on the association between depression symptom course and metabolic and inflammation dysregulation. This study aimed to depict the course of depression symptoms while ageing, taking into consideration inter-individual heterogeneity. Moreover, it intended to study the associations between inflammatory and metabolic risk profiles and symptom trajectories. To do so, data from 13,203 adults aged 50-90 years (52.75% women; mean age at baseline = 65.07, SD = 10.00) were used. Blood sample and blood pressure measures were taken from 1536 participants (56.58% women; mean age at baseline = 61.73 years, sd = 7.64). Depression symptoms were assessed every two years across a 10-year follow-up. Trajectories were identified by means of latent class mixed modelling. Inflammation and metabolic risk profile scores were obtained from plasma and diagnostic-based indicators in the follow-up, using a robust latent-factor approach. Multigroup modelling was used to study the associations between the profiles and symptom trajectories. As a result, three heterogeneous trajectories of symptoms were identified (low-symptom, moderate-symptom and high-symptom trajectory). Participants depicting a high-symptom trajectory showed the greatest inflammation profile score and high metabolic risk. Moderate-symptom trajectory was also related to high inflammation and metabolic risk. To sum up, at-risk trajectories of symptoms were associated with high inflammation and risk of metabolic diseases. This study provides valuable evidence to advance personalised medicine and mental health precision, considering person-specific profiles and physiological concomitants.