3i - DEPRESSION IN PNEI FRAMEWORK

Question 1

Core concept

Answer 1

• Traditional models focus narrowly on monoamine deficiency (ex: serotonin)
• Article proposes integrated PNEI model: depression arises from interactions among nervous, endocrine, immune & psychological systems
• Depression viewed as chronic, systemic disorder of inflammation & neuroendocrine imbalance, not just
  chemical imbalance in brain

Question 2

Major systems involved in PNEI depression model

Answer 2

Table

Question 3

Key pathophysiological mechanisms:
- HPA axis dysregulation
- neuroinflammation
- epigenetics & early life stress

Answer 3

HPA Axis Dysregulation
- Chronic stress leads to overactivation of CRF → ACTH → cortisol
- High cortisol disrupts circadian rhythms, impairs memory, reduces hippocampal volume & weakens immune response

Neuroinflammation
Immune cells release cytokines that:
- Cross the blood-brain barrier
- Impair serotonin production via the kynurenine pathway
- Activate microglia → neuronal damage

Epigenetics & Early Life Stress
- Early adverse life events modify gene expression through methylation/acetylation.
- These changes predispose individuals to altered stress responses and mood disorders later in life

Question 4

Clinical & diagnostic implications

Answer 4

Table

Question 5

Therapeutic strategies: beyond antidepressants :
- integrated pharmaco
- lifestyle & psychological interventions

Answer 5

Integrated Pharmacological
- Antidepressants may help but often don’t address inflammation or HPA dysfunction.
- Future approaches: anti-inflammatory agents, glutamate modulators, omega-3 fatty acids.

Lifestyle & Psychosocial Interventions
- Mindfulness-based cognitive therapy (MBCT): Reduces relapse risk, modulates stress reactivity.
- Exercise: Elevates BDNF, lowers cortisol, reduces inflammation.
- Nutrition: Mediterranean diet improves gut microbiota, reduces depression scores.
- Psychotherapy: Essential for addressing trauma and cognitive distortion patterns