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The immune system and
anxiety disorders
David Christmas
Cambridge and Peterborough NHS Trust
Agenda
• Introduction to the immune system
– The immune system and the CNS
• How the immune system can influence
psycholog...
Immune system in brief
How does peripheral immune
activity influence the CNS?
A. Active transport of
cytokines across
BBB
B. Activation of vagus
...
How the immune system
influences psychological
symptoms
Immune alterations
Neuropsychiatric effects
Activated
microglia
Di...
How the immune system
influences psychological
symptoms
Immune alterations
Neuropsychiatric effects
Activate
microglia
Dir...
• Physiological levels helpful
– IL-1β – maintains plasticity and LTP
– TNF-α – Upregulates AMPA and improves
synaptic str...
Cytokine effects on
hippocampusSynapticstrength/LTP
Increasing IL-1, TNF, IL-6
Adapted from Khairova 2009
Correlates with ...
How the immune system
influences psychological
symptoms
Immune alterations
Neuropsychiatric effects
Activated
microglia
Di...
Aetiology of IFN-Induced Depression:
Trp Metabolism
Diet
5HT
Aromatic
amino acid
decarboxylase
Tryptophan
Tryptophan
hydro...
Aetiology of IFN-Induced Depression:
Tryp/5-HT Depletion?
Bonaccorso et al. J Clin Psychopharm. 2002
Capuron et al. Mol Ps...
Change in tryptophan correlates
with increasing depression
• Increase in K/Trp ratio (IDO): p = 0.017
• Assoc with depress...
How the immune system
influences psychological
symptoms
Immune alterations
Neuropsychiatric effects
Activated
microglia
Di...
HPA axis
• Pro-inflammatory cytokines
– Activate HPA axis
– May downregulate Glucocorticoid receptors
centrally – causes i...
How the immune system
influences psychological
symptoms
Immune alterations
Neuropsychiatric effects
Activated
microglia
Di...
Activated Microglia
• Produce increased:
– IL-1b, IL-6, TNF-a, MCP-1 (more
macrophages)
– Cause damage through reactive ox...
Stress and Immune function
Anxiety and immune function –
Psychological Stress
Carpenter et al Neuropsychopharmacology 2010
Anxiety and immune system
Immune stressor
Wright Brain Behaviour Immunity 2005
Anxiety and immune response
correlate during challenge
TNF
Reichenberg Archives of General Psychiatry 2001
Anxiety varies with immune
markers in general population
Pitsavos Atherosclerosis 2006
Immune changes and PTSD
Gill Perspectives in Psych Care 2009
Immune and HPA changes in
PTSD
• Increased proinflammatory cytokines
– IL-1b, TNFa, IL-6, CRP
– Increased IL-6 response ti...
IL-1β reduced in OCD
IL-1βPg/ml
Brambilla Biological Psychiatry 1997
Denys Psychoneuroendicrinology 2006
Summary
• Brain has constituent immune cells
– Have many homeostatic functions in addition
to traditional pathogen removal...
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The immune system and anxiety disorders

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Presentation from the International Congress of the Royal College of Psychiatrists 24-27 June 2014, London

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Transcript of "The immune system and anxiety disorders"

  1. 1. The immune system and anxiety disorders David Christmas Cambridge and Peterborough NHS Trust
  2. 2. Agenda • Introduction to the immune system – The immune system and the CNS • How the immune system can influence psychological symptoms • Anxiety and immune changes – Stress and immune function – Anxiety disorders and immune function
  3. 3. Immune system in brief
  4. 4. How does peripheral immune activity influence the CNS? A. Active transport of cytokines across BBB B. Activation of vagus nerve C. Passage of cytokines through porous areas of BBB D. Direct migration of circulating immune cells E. All of the above A ctive transportofcy... A ctivation ofvagus n... Passage ofcytokines... D irectm igration ofci... A llofthe above 0% 0% 0%0%0%
  5. 5. How the immune system influences psychological symptoms Immune alterations Neuropsychiatric effects Activated microglia Direct neuronal/ monoaminergic effects Altered tryptophan metabolism Altered HPA axis functioning
  6. 6. How the immune system influences psychological symptoms Immune alterations Neuropsychiatric effects Activate microglia Direct neuronal/ monoaminergic effects Altered tryptophan metabolism Altered HPA axis functioning
  7. 7. • Physiological levels helpful – IL-1β – maintains plasticity and LTP – TNF-α – Upregulates AMPA and improves synaptic strength • High pathological levels – IL-1β – inhibits LTP – TNF-α – impaired LTP – IL-6 – inhibits LTP and glutamate release
  8. 8. Cytokine effects on hippocampusSynapticstrength/LTP Increasing IL-1, TNF, IL-6 Adapted from Khairova 2009 Correlates with “depression”
  9. 9. How the immune system influences psychological symptoms Immune alterations Neuropsychiatric effects Activated microglia Direct neuronal/ monoaminergic effects Altered tryptophan metabolism Altered HPA axis functioning
  10. 10. Aetiology of IFN-Induced Depression: Trp Metabolism Diet 5HT Aromatic amino acid decarboxylase Tryptophan Tryptophan hydroxylase 5-HTP 5-HT Tryptophan Metabolic Pathway
  11. 11. Aetiology of IFN-Induced Depression: Tryp/5-HT Depletion? Bonaccorso et al. J Clin Psychopharm. 2002 Capuron et al. Mol Psych. 2002 Indoleamine dioxygenase Diet 5HT  Aromatic amino acid decarboxylase Tryptophan Tryptophan hydroxylase 5-HTP 5-HT L-Kynurenine IFNs Tryptophan Metabolic Pathway
  12. 12. Change in tryptophan correlates with increasing depression • Increase in K/Trp ratio (IDO): p = 0.017 • Assoc with depression: R2 =0.340, p = 0.001 IDO vs Mood -15 -10 -5 0 5 10 15 20 25 30 35 -20 -15 -10 -5 0 5 10 15 20 Change BDI ChangeIDO Christmas in preparation
  13. 13. How the immune system influences psychological symptoms Immune alterations Neuropsychiatric effects Activated microglia Direct neuronal/ monoaminergic effects Altered tryptophan metabolism Altered HPA axis functioning
  14. 14. HPA axis • Pro-inflammatory cytokines – Activate HPA axis – May downregulate Glucocorticoid receptors centrally – causes increased cortisol release • Glucocorticoids normally anti-inflammatory • But during prolonged stress are pro- inflammatory in CNS – increased IL-1b and TNFa
  15. 15. How the immune system influences psychological symptoms Immune alterations Neuropsychiatric effects Activated microglia Direct neuronal/ monoaminergic effects Altered tryptophan metabolism Altered HPA axis functioning
  16. 16. Activated Microglia • Produce increased: – IL-1b, IL-6, TNF-a, MCP-1 (more macrophages) – Cause damage through reactive oxygen species – Increased IDO expression • Some mice models lacking Hoxb8 – Display OCD-like grooming behaviour
  17. 17. Stress and Immune function
  18. 18. Anxiety and immune function – Psychological Stress Carpenter et al Neuropsychopharmacology 2010
  19. 19. Anxiety and immune system Immune stressor Wright Brain Behaviour Immunity 2005
  20. 20. Anxiety and immune response correlate during challenge TNF Reichenberg Archives of General Psychiatry 2001
  21. 21. Anxiety varies with immune markers in general population Pitsavos Atherosclerosis 2006
  22. 22. Immune changes and PTSD Gill Perspectives in Psych Care 2009
  23. 23. Immune and HPA changes in PTSD • Increased proinflammatory cytokines – IL-1b, TNFa, IL-6, CRP – Increased IL-6 response time of trauma may predict PTSD at 6 months • HPA dysfunction – Reduced CSF CRF – Increased circulating cortisol – Increased response/sensitivity to Dex
  24. 24. IL-1β reduced in OCD IL-1βPg/ml Brambilla Biological Psychiatry 1997 Denys Psychoneuroendicrinology 2006
  25. 25. Summary • Brain has constituent immune cells – Have many homeostatic functions in addition to traditional pathogen removal • Cross-talk between CNS and peripheral immune systems • Psychological stressors induce immune responses and vice versa • Much work is needed to delineate role of immune system in anxiety disorders
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