Depression

A group of mood disorders characterized by persistent sadness, loss of interest, and disturbances in sleep, appetite, and cognition. Note that all symptoms are connected to cortisol, depending on how the HPA-axis is working.

HPA-axis patterns in different depression types:

• Melancholic Depression (high cortisol) - Classic stress-driven depression. The HPA-axis is overactive, with high CRH and ACTH output and elevated cortisol throughout the day. This leads to early morning awakening, anxiety, loss of appetite, and weight loss. Common in acute or early-stage major depression.
• Atypical Depression (low cortisol) - Often follows long-term stress or trauma. The HPA-axis becomes blunted or burnt out, producing too little cortisol. Symptoms include fatigue, hypersomnia, increased appetite, and emotional numbness. This form overlaps with adrenal fatigue and chronic stress syndromes, often linked to nutrient depletion or poor adrenal recovery.
• Panic or Anxiety-Reactive Depression - Characterized by surges of cortisol during panic or fear states. The HPA-axis over-responds to small triggers, creating cyclical spikes of cortisol and adrenaline. Symptoms include heart palpitations, insomnia, and ruminating thoughts. Over time, this can shift toward exhaustion (low cortisol).
• Seasonal / Circadian Depression - Involves disrupted cortisol rhythm rather than high or low levels. The daily peak occurs too early or too late, impairing sleep and energy regulation. Light exposure, melatonin timing, and regular sleep help restore rhythm.
• Dysthymia (Persistent Low-Grade Depression) - A mild but chronic depressive state often linked to low or flattened cortisol curve. The HPA-axis shows poor responsiveness and reduced variability, associated with chronic inflammation, suboptimal adrenal output, and nutrient-related stress vulnerability.

Metabolic & dietary context: Ketones and low-carbohydrate metabolism calm the HPA-axis by stabilizing glucose and reducing cortisol demand, improving symptoms. However, prolonged fasting for ketone production can worsen stress signaling and lead to anorexic behavior — dietary balance is essential.