2. Brain-derived neurotrophic factor plasma levels in patients suffering from post-traumatic stress disorder Liliana Dell'Osso a, Claudia Carmassi a,, Alessandro Del Debbio a, Mario Catena Dell'Osso a, Carolina Bianchi a, Eleonora da Pozzo a, Nicola Origlia b, Luciano Domenici b,c, Gabriele Massimetti a, Donatella Marazziti a, Armando Piccinni a Presented by: Justin P. Smith

3. PTSD Exposure Combat or military exposure Child sexual or physical abuse Terrorist attacks Sexual or physical assault Serious accidents, such as a car wreck. Natural disasters, such as a fire, tornado, hurricane, flood, or earthquake

4. How PTSD Develops How intense the trauma was or how long it lasted If you lost someone you were close to or were hurt How close you were to the event How strong your reaction was How much you felt in control of events How much help and support you got after the event

5. Reliving the event (also called re-experiencing symptoms)- memory recall Avoiding situations that remind you of the event- avoiding stimulation, context Feeling numb- blunted affect Feeling keyed up (also called hyperarousal)- over active amygdala? Common Symptoms

6. BDNF- Brain Derived Neurotrophic Factor Protein, from BDNF-gene Promotes cell survival & regulates proliferation and differentiation of neurons Stress down regulates BDNF mRNA Upregulated during learning Necessary for LTP

7. BDNF cont Role in: growth, development, maintenance and function of neuronal systems Modulates synaptic plasticity and neurotransmitter release & intracellular signal-transduction

8. BDNF & TrkB TrkB- protein-tyrosine kinase receptor Together help with LTP (long lasting synaptic plasticity) Role in learning and memory Role in pathogenesis of mood and anxiety disorders

9. BDNF and TrkB TrkB- intracellular kinase-activating receptor

10. BDNF & TrkB in Rats after PSS Predator Scent Stress – place rat on soiled litter for 10 min. (controls on unsoiled litter) 7 Days later....... Found in CA1 (of hippocampus): – Down-regulated BDNF mRNA – Upregulated TrkB Fits-less BDNF - need more receptors!

11. Western Blot- Protein RT-PCR

13. Hippocampus

14. Rat Hippocampus

15. CA1

16. Role of Hippocampus Long term memory and spatial navigation

17. THIS IS STRESSFUL!

18. Predisposed to Stress Rats given corticosterone in drinking water had a decrease in NMDA (NR2B), AMPA subunits, GluR2/3 & BDNF Also looked at fear extinction learning: ok to be in this place now….

19. Receptors NMDA-Ionotropic

20. Benarroch, E. E. Neurology 2008;70:964-968 Figure 112">

21. Oral Corticosterone cont.

22. Oral Corticosterone

23. Take Away Predisposed stress can decrease fear extinction… Make it harder to learn that “its” O-K.

25. 1 st study looking at BDNF w/ PTSD PTSD patients would be expected to have lower BDNF levels Hippocampus, Amygdala and Cingulate (limbic system) involved fMRI of PTSD show decreased hippocampal volume + correlation blood-brain BDNF levels

26. Methods 18 PTSD, 18 Controls How long did PTSDers have PTSD? Blood collected 8-9am (following fast) ELISA

27. 22% (8%)

28. PTSD vs. Control

29. # of traumas

30. +/- 1 year from trauma

31. Discussion BDNF lower in PTSD Limits – Small sample size – BDNF in blood not brain Possible role of BDNF in PTSD Predator vs. Prey attitude among individuals exposed to the same stress

33. Thank You