THE ONSET OF DEPRESSION DUE TO EPIGENETIC METHYLATION OF THE BRAIN-DERIVED NEUROTROPHIC FACTOR GENEBackground Mechanisms Review of Literature

Acknowledgements & Future Research

Significance

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 translatio

n 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., D′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, 203-222Hayley, 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