What is BDNF and Why it's Important for Mental Health?

     The Brain Derived Neurotrophic Factor (BDNF) is a gene that maps a protein with the same name; it is prevalent in the human body and brain. Neurotrophins are a cluster of ‘growth factor’ proteins that signal cells to survive, mature and proliferate. They are involved in the survival, development, and proper function of brain neurons. Neurons are information messengers that transmit signals and communicate with different parts of the brain and nervous system to help humans think, move, act, and feel.

     Animal studies have consistently revealed that chronic stress reduces BDNF expression in the brain. This can literally decrease brain volumes in parts of the brain such as the hippocampus, which are heavily involved in emotional regulation as well the pre-frontal cortex which regulates cognition. Chronic stress can lead to depression, and clinical studies indicate that those with untreated depression continue to show decreased blood levels of BDNF.

 

How is brain volume decreased during major depression?

     When the body’s stress systems are consistently activated due imminent stressors, excitatory neurons and systems that communicate to keep us vigilant, are overexcited- this is called excitotoxicity. The BDNF system is responsible for successfully maintaining these systems and the signals they transmit to different parts of the brain. The BDNF system also helps in the growth of new cells and neurons.  A lack of BDNF sustains the neurotoxic effects that chronic stress has on all neurotransmitter systems including serotonin, dopamine and noradrenaline which regulate mood.

 

Activity-dependent BDNF hypothesis of depression

Activity-dependent BDNF hypothesis of depression. Increased neuronal activity, induced by an enriched environment (e.g., physical exercise, mental stimulation with learning exercise and sensory input, and social interactions) and/or medication up-regulates BDNF expression in the hippocampus and cortex. This, in turn, increases neuronal activity and this positive feedback loop can maintain an active mind state. In contrast, any disruption in BDNF expression, caused by epigenetic regulation processes, stress, and/or reduced neuronal activity, would lead to decreases in neuronal activity and activity-driven BDNF expression. This vicious cycle of decreased neuronal activity and reduced BDNF expression may cause depression.

Sakata K. Brain-Derived Neurotrophic Factor for Depression Therapeutics. Austin J Pharmacol Ther. 2014;2(1): 1006. ISSN: 2373-6208.

Can I be born with a deficient BDNF system?

     While there is no such thing as completely non-functional BDNF, there Is such thing as deficient function in BDNF, and this can be determined by genetics. There is a certain location on the BDNF gene that affects BDNF activity and expression this is known as BDNF rs6265 C--T. The genetic variant met (T) allele or variant decreases expression of “pro-BDNF” the precursor of BDNF by which BDNF is formed.

     This T allele has been associated with reduced resilience to stressful life events, worsened memory and increase anxiety due to less BDNF, which in turns worsens synaptic connections between neurons and decreases the general rate of cell regeneration (BDNF). Around 30% of the population is heterozygous BDNF rs6265 CT for this gene single nucleotide polymorphism (SNP), which reduces function moderately, and around 3% of the population is homozygous BDNF rs6265 TT which reduces BDNF function significantly.

 

What can be done to improve and maintain the expression of BDNF?

  • Exercise: Exercise helps promote the existence of metabolic factors that increase the genetic transcription of BDNF. Studies show that increases in BDNF were sustained several weeks after consistent moderate exercise
  • Intermittent fasting or ketogenic diet, ketones are burned to produce b-hydroxybutyrate a metabolic factor which also aids in the transcription of BDNF
  • Supplements such as omega 3 fatty acids that support brain health
  • Antioxidant foods such as curcumin, coffee, blueberries, green tea

Medications to increase the expression of BDNF

  • Antidepressants (SNRIs, SSRIs). Studies have indicated that the majority of SSRI and SNRIS increase neurotrophic factors in the brains and plasma BDNF levels, as BDNF crosses the blood brain barrier with ease, blood levels of BDNF can be an appropriate marker for BDNF function
  • Psychedelics (medically micro dosed Ketamine, Psilocybin) These medications treat ‘treatment resistant depression’ by promoting the release of BDNF, restoring neurotransmitter systems

 

by Sandra Hanna Bsc. Pharm

 

 

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