The Science of Stress Resilience (Nestler & Russo, 2024)

Описание: This micro-lesson explores Eric Nestler & Russo's 2024 publication "Neurobiological basis of stress resilience" (Full Text: https://pmc.ncbi.nlm.nih.gov/articles....

I. Stress & Resilience
Resilience: Ability to maintain normal function under severe stress.
Implicated in stress responses and mental health disorders.
Focus of clinical and preclinical research, particularly in the past 15 years.
Resilience is not passive; it's an active process.
Involves specific neural adaptaptations that protect brain cells from stress damage.

II. What Rodent Models Reveal About Resilience
Resilience: Active adaptations, not just absence of harm, drive resilience to chronic stress.
Distinct molecular, cellular, and circuit‑level mechanisms emerge only in resilient individuals.
Growing human validation: Many rodent‑identified pathways are now confirmed in humans.

III. Key Biological Systems Involved
Molecular & transcriptional changes that promote protective gene expression.
Circuit‑level adaptations in limbic regions known to have high expression of stress receptors.
(A) Hippocampus (especially the ventral hippocampus)
(B) Prefrontal Cortex (PFC).
(C) Nucleus accumbens (NAc).
(D) Amygdala.
These brain regions have high expression (amount) of stress hormone receptors.
This makes them sensitive and responsive to stess.
They're also known to have high neural plasticity (neurogenesis and neuroplasticity).
(E) Blood‑brain barrier & immune interactions also help maintain balance under stress.

IV. The Two Janus Faces of Stress
Stress operates on a Goldilocks, Inverted U-Shaped Curve.
Too Little Stress: Not enough motivation to function.
Too Much Stress: Fight/Flight/Freeze/Fawn (equally nonfunctioning).
Eustress ("Good Stress"):
Manageable.
Controllable, Predictable, Acute (Short), Tolerable.
Distress ("Bad Stress"):
Unmanageable.
Uncontrollable, Unpredictable, Repeated, Prolonged, Chronic, Extreme, Developmental.

V. Stress & Neural Plasticity
Neural Plasticity: Brain's ability to adapt structurally and functionally to change.
(A) Neurogenesis: Cell Proliferation, Re-generation (New Brain Cell Birth).
Neurogenesis is associated with (humans) and causes (rodents) depression reversal.
(B) Neuroplasticity: Changes in number and strenght of connections between brain cells.
Neuroplasticity is implicated in learning, memory; brain wiring and rewiring.
Eustress ("Good Stress"): Enhances neural plasticity (and mood).
Distress ("Bad Stress"): Halts neurogenesis; causes cell death.

VI. Implications for Treating Stress‑Related Disorders
New therapeutic direction: Introdue natural resilience mechanisms (vs. only reversing damage).
Potential applications for depression, PTSD, anxiety disorders, and stress susceptibility.
Paradigm shift: Psychiatry is moving toward pro‑resilience interventions.
E.g., Psychoplatogens, Psychedelics that target Neural Plasticity (Ketamine, Psilocybin, etc).

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