Chronic Stress and Depression: How HPA Axis Dysfunction Damages the Hippocampus

How does chronic stress cause depression?

Chronic stress disrupts the brain’s stress response system (HPA axis), causing cortisol dysregulation and inflammation that damages the hippocampus - the brain’s memory and mood center. This creates a cascade of brain changes that lead to depression. Key mechanisms:

• Cortisol dysregulation - stress hormones become imbalanced
• Hippocampus damage - brain’s memory and mood center gets damaged
• Neuroinflammation - brain inflammation contributes to depression
• Cascade effect - stress creates multiple brain changes that maintain depression

A 2025 review published in the International Journal of Molecular Sciences examines how prolonged HPA axis activation creates a cascade of neurobiological changes that damage the hippocampus and contribute to both the development and maintenance of depression.

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Inflamed Depression: How Inflammation Drives Depression and Anti-Inflammatory Treatments

Is depression an inflammatory disease?

Yes. Inflammation plays a key role in depression pathophysiology, especially for approximately one-third of patients who don’t respond to traditional antidepressants, with inflammatory processes contributing to altered neurotransmitter metabolism, disrupted neuroplasticity, and treatment resistance. A comprehensive 2024 review published in Pharmacological Research reveals that inflammation is not just a consequence of depression but actively drives depressive symptoms through multiple neurobiological pathways, offering new treatment approaches beyond conventional monoamine-targeting antidepressants.

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What Really Works for PANS or PANDAS? A Review of 698 Cases

Dr. Kumar’s Take:

This large community-based survey gives us one of the clearest pictures yet of what works, and what doesn’t, for treating PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) or PANDAS (Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus). The key insight? Aggressive early treatment of infections and inflammation works better than just psych meds. Long courses of broad-spectrum antibiotics, IVIG in immune-deficient patients, and even common NSAIDs like ibuprofen made a measurable impact. SSRIs and psych meds were hit-or-miss, often poorly tolerated. If your child is struggling with sudden-onset OCD or tics, make sure infections and inflammation are fully addressed. Don’t stop at psychiatric meds alone.

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