Fig. 1.

Hypothesized interplay of biological factors in unipolar depression. In this diagram, the interconnectedness of various pathways that are involved in unipolar depression is graphically presented. Negative feedback loops are highlighted with red arrows, while positive feedback is indicated by green arrows. Stress triggers a hormonal cascade, starting with elevated CRH (Corticotropin-Releasing Hormone), which leads to increased ACTH (Adrenocorticotropic Hormone) production, ultimately resulting in the release of Cortisol. High Cortisol levels reduce HRV (Heart Rate Variability) and facilitate the release of inflammatory markers like IL-6 and CRP. In depressed individuals, reduced AAT-1 levels hinder the proper reduction of inflammatory interleukins. Changes in the expression of neurotrophic factors, such as BDNF and IGF-1, have been associated with abnormal neural plasticity. Growth hormone (GH) stimulates the liver to produce IGF-1. IGF-1 also plays a role in insulin homeostasis. Low IGF-1 levels are associated with depression which lead to increased blood sugar levels as well as HbA1c levels