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

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

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

• 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

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

BDNF cont

• Role in: growth, development, maintenance and function of neuronal systems

• Modulates synaptic plasticity and neurotransmitter release & intracellular signal-transduction

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

BDNF and TrkB

• TrkB- intracellular kinase-activating receptor

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!

Western Blot- Protein

RT-PCR

Hippocampus

Rat Hippocampus

CA1

Role of Hippocampus

• Long term memory and spatial navigation

THIS IS STRESSFUL!

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….

Receptors NMDA-Ionotropic

Benarroch, E. E. Neurology 2008;70:964-968

Figure 112">

Oral Corticosterone cont.

Oral Corticosterone

Take Away

• Predisposed stress can decrease fear extinction…

• Make it harder to learn that “its” O-K.

1st 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

Methods

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

22% (8%)

PTSD vs. Control

# of traumas

+/- 1 year from trauma

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

Thank You