The Onset of Depression due to Epigenetic Methylation of the Brain-derived Neurotrophic factor gene

1. THE ONSET OF DEPRESSION DUE TO EPIGENETIC METHYLATION
OF THE BRAIN-DERIVED NEUROTROPHIC FACTOR GENE
Background Mechanisms Review of Literature
Acknowledgements & Future ResearchSignificance
Major Depressive Disorder (MDD)
• Most commonly diagnosed psychiatric
disorder and affects 150 million people
worldwide (World Health Organization)
• 6.7% of Americans over the age of 18
develop depression
Brain-Derived Neurotrophic Factor (BDNF)
• Provides instruction of protein BDNF in
brain and spinal cord
• Promotes survival of neurons through
maturation and instructs neurogenesis
• Active at synapses by synaptogenesis
• Expression of BDNF is altered through
epigenetic mechanisms
DNA Methylation
• Epigenetic mechanism that silences gene
• Transfer of a methyl group onto the
cytosine at a CpG site
• Forms a 5-methylcytosine
• Intervenes prior to translation by
destructing mRNA
DNA Methylation of BDNF
• Expression of BDNF can be altered
by DNA methylation
• Methylation of BDNF silences
production and haults neurogenesis
• Decrease in the survival of neurons
causes depressed behaviors due to
miscommunication in brain
• Antidepressants can reverse
depressed behaviors by activating
the BDNF gene through acetylation
• I would like to thank my my family, friends, and teachers Mrs.
Salomone, Mr. Keith, and Mrs. Greenwald for giving me
guidance and support with all of my work this year.
• This summer I will shadowing my mentor, Dr. Kathryn
Humphreys, in her lab at Stanford University, in a study called
BABIES
• BABIES will be the first study to use MRI to examine neural,
endocrinological, and behavioral characteristics of infants of
depressed and non-depressed mothers
Transcription
Censor
molecules
intervene &
destroy mRNA
Prevents
translation
of BDNF
• BDNF promoter methylation and suicidal
behavior in depressive patients
• Kang et al. studied DNA methylation
patterns of the BDNF promoter in patients
with MDD
• Higher BDNF methylation was associated
with previous suicidal attempts and
suicidal ideation during treatment (p<.05)
Differences in brain derived neurotrophic
factor protein levels of depressed
individuals who died through suicide
• Hayley et al. studied BDNF changes in the
brain to analyze the differences in
depressed behaviors depending on
gender and brain region
• Significantly lower BDNF levels in suicide
patients (p<.05)
• Hippocampus and frontal cortex showed
significantly decreased patterns of BDNF
(p<.05)
•
• Higher BDNF promoter methylation in the brain may be a
biological marker of suicidal behavior
• Therefore, MDD patients with higher BDNF methylation are at a
greater risk for committing suicide
• Since BDNF plays an important role in neuronal plasticity,
decreased BDNF levels can cause improper maintenance of
neurons, which could result in an inability of the brain to adapt
to stress and challenges
• Difficulties in adapting to situations may lead to a higher risk
for suicidal behaviors.
Byram Hills High School • Authentic Science Research • Devon Wolfe
Decreased
expression
of BDNF
Increased
depressed
behaviors
BDNF Gene Silencing(http://web.stanford.edu/group/hopes/cgi-bin/hopes_test/gene-silencing/)
Duman, R.S., Malberg, J., Nakagawa, S., Dʹ′Sa, C. (2014). Neuronal plasticity and survival in mood disorders. Biological Psychiatry. 48, 732–739.
Dwivedi, Y., Rizavi, H.S., Conley, R.R., Roberts, R.C., Tamminga, C.A., Pandey, G.N. (2003). Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine
kinase B in postmortem brain of suicide subjects. Archives of General Psychiatry. 60, 804–815.
Dang, H.J., Kim, J.M., Lee, J.Y., Kim, S.Y., Bae, K.Y., Yoon, J.S. (2013). BDNF promoter methylation and suicidal behavior in depressive patients. 42, 203-222
Hayley, S., Du, L., Litteljohn, D., Palkovits, M., Faludi, G., Merali, Z., Poulter, M.O., Anisman, H. (2015). Gender and brain regions specific differences in brain derived neurotrophic
factor protein levels of depressed individuals who died through suicide.600, 12-6