Psychoneuroimmunology

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PNI Basics - Brain-Body Banter

  • Psychoneuroimmunology (PNI): Study of interactions between nervous system, endocrine system, & immune system.
  • Bidirectional Communication: Brain influences immune function; immune responses affect brain & behavior.
  • Key Mediators:
    • Cytokines: Immune signaling molecules (e.g., IL-1, IL-6, TNF-α). Act on brain, induce sickness behavior.
    • Neurotransmitters: (e.g., Serotonin, Dopamine, Norepinephrine) modulate immune cells.
    • Hormones: (e.g., Cortisol via HPA axis) regulate immune responses.
  • Stress & Immunity: Chronic stress often leads to immunosuppression or dysregulation, ↑ vulnerability to illness.

Sickness Behavior: A coordinated set of behavioral changes (lethargy, anhedonia, social withdrawal) induced by pro-inflammatory cytokines (e.g., IL-1β, TNF-α) acting on the brain, representing an adaptive response to conserve energy and fight infection. This is a common link between inflammation and psychiatric symptoms like depression.

  • Clinical Relevance: PNI helps understand inflammatory basis of depression, anxiety, schizophrenia, and neurodegenerative disorders.

Messengers & Pathways - Immune Chatter

  • Key Players:
    • Cytokines: Immune messengers.
      • Pro-inflammatory: $IL-1\beta$, $IL-6$, $TNF-\alpha$ (📌 "Hot T-bone stEAk"). Cause sickness behavior.
      • Anti-inflammatory: $IL-10$, $TGF-\beta$.
    • HPA Axis: Bidirectional. Stress alters immunity via cortisol. Chronic stress → dysregulation, pro-inflammatory state.
    • Vagus Nerve: "Inflammatory reflex." Afferent (sensory), efferent ($ACh$ ↓ $TNF-\alpha$).
    • Microglia: Brain's resident immune cells; activated by peripheral signals.
  • Pathways:
    • Humoral: Cytokines via blood (BBB, CVOs).
    • Neural: Vagus nerve signals to brain.

Gut-Brain Axis: Microbiota, Immune, and Neural Pathways

⭐ IL-1, IL-6, and TNF-alpha are key pro-inflammatory cytokines implicated in depression by inducing sickness behavior and affecting neurotransmitter systems.

Stress & Sickness - Pressure Cooker Effects

  • Psychoneuroimmunology (PNI): Study of interactions between CNS, endocrine, and immune systems.
  • Stress Response Systems:
    • Sympathetic-Adrenal-Medullary (SAM) Axis: Rapid; releases adrenaline/noradrenaline. ↑HR, ↑BP.
    • Hypothalamic-Pituitary-Adrenal (HPA) Axis: Slower; releases cortisol.
  • Acute Stress: Can be immune-enhancing (e.g., ↑NK cell activity, ↑inflammation initially).
  • Chronic Stress: Generally immune-suppressive & dysregulating.
    • Prolonged cortisol → ↓lymphocyte function, ↓antibody production, impaired cytokine balance.
    • Shifts from Th1 (cell-mediated) to Th2 (humoral) immunity.
  • Sickness Behavior: Adaptive response to infection (fever, lethargy, anhedonia, ↓appetite).
    • Mediated by pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) acting on the brain.
    • Chronic stress can mimic or exacerbate sickness behavior.

Stress Response: HPA, SAM, and Immune System

⭐ Chronic stress-induced HPA axis dysregulation (e.g., blunted cortisol awakening response) is linked to increased vulnerability to infections and autoimmune conditions. It can also worsen psychiatric symptoms in disorders like depression and anxiety by promoting neuroinflammation and altering neurotransmitter systems.

PNI in Mental Illness - Mind's Immune Mix-up

  • Depression:
    • ↑ Pro-inflammatory cytokines: IL-1β, IL-6, TNF-α, impacting mood.
    • Microglial activation contributes to neuroinflammation.
    • Kynurenine pathway dysregulation: ↑ kynurenine (neurotoxic), ↓ serotonin.
    • HPA axis hyperactivity.
  • Schizophrenia:
    • Maternal Immune Activation (MIA) during gestation is a key risk factor.
    • ↑ Cytokines (IL-6, TNF-α), C-Reactive Protein (CRP).
    • Microglial priming and dysfunction.
  • Anxiety Disorders (GAD, PTSD):
    • ↑ Inflammatory markers (IL-6, TNF-α, CRP).
    • Gut-brain axis dysregulation; altered gut microbiota.
  • Bipolar Disorder:
    • State-dependent inflammation: ↑ pro-inflammatory cytokines during mood episodes.
    • Oxidative stress.
  • Therapeutic Hints:
    • Adjunctive anti-inflammatory agents (e.g., celecoxib), probiotics. Factors influencing mood, behavior, and brain activity

⭐ Elevated C-Reactive Protein (CRP), an inflammatory marker, is linked to increased risk and severity of depression, and predicts poorer antidepressant response.

High‑Yield Points - ⚡ Biggest Takeaways

  • Pro-inflammatory cytokines (IL-1, IL-6, TNF-α) are linked to depression, anxiety, and schizophrenia.
  • HPA axis dysregulation connects stress, immunity, and mental illness.
  • Activated microglia drive neuroinflammation in psychiatric disorders.
  • The gut-brain axis influences mental health via immune pathways and microbiome.
  • Chronic stress triggers immune dysregulation in psychiatric conditions.
  • Cytokine-induced sickness behavior mimics depressive symptoms.
  • Targeting inflammation is an emerging psychiatric treatment strategy.

Practice Questions: Psychoneuroimmunology

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Which of the following produces neuropsychiatric symptoms?

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Flashcards: Psychoneuroimmunology

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Which hormone levels are increased in mania?_____

TAP TO REVEAL ANSWER

Which hormone levels are increased in mania?_____

Dopamine and NE

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