Understanding the role of stress hormones in depression, anxiety and epigenetics
Ongoing stress, depression and anxiety disorders affect the delicate balance of hormones and the receptor sites (altered sensitivity). We have receptor sites for hormones which play an integral role in sending messages to say if there is enough of a hormone letting the body know whether to produce more (much like a feedback system). There are a number of stress related hormones including CRH (corticotropin releasing hormone), glucocorticoid hormone, vasopressin, oxytocin and estrogen. Neuroendocrine is a term for the brain/hormone system which is the regulator of these hormones.
The nitty gritty on hormone receptors and a little on gene polymorphisms
The glucocorticoid hormones are produced in the adrenal cortex and are also known as steroid hormones. These hormones suppress the immune system, reduce inflammation and affect metabolic behaviour. So you can see there is an interplay between the brain via the hypothalamic pituitary axis (HPA axis), the immune system and the endocrine system (hormone system). Under stress the brain tells the adrenals to produce glucocorticoids.
Acute stress resulting in a temporary inhibition of CRH which in turn leads to an increase of ACTH (adrenocorticotrophin hormone) becomes a problem in chronic ongoing stress as the ACTH becomes elevated in turn affecting sleep, appetite and mood.
CRH is a key player in the stress response. It regulates the nervous system and hormones affecting our psychological wellbeing and is known in research to malfunction in mood disorders such as depression and anxiety. CRH dysfunction is particularly relevant in anxiety disorders. This is due to the effect on GABA (Gamma-amino butyric acid) mediated by activation of Corticotropin Releasing Hormone -Receptor 1 CRH-R1 (CRH receptors in the amygdala).
During depression the glucocorticoid receptors (GR) reduce in the hippocampus, pituitary and frontal cortex of the brain, and in immune cells.
Let’s talk about Brain Derived Neurotrophic Factor (BDNF)
Neural plasticity and neurogenesis are of primary importance in terms of adaptation and healthy brain function. Neurotrophic factors greatly affect plasticity and neurogenesis and the main types of neurotrophic factors are neurotrophins, ciliary neurotrophic factor and glial cell-derived neurotrophic factor. Nerve growth factor, brain-derived neurotrophic factor and neurotropins 3 and 4 are well known neurotrophins. When the signalling of these neurotrophins are disturbed depression, anxiety and other neurodegenerative disorders occur.
BDNF increases plasticity, neurogenesis, production of neurotransmitters and acts as a synapse modulator. We love BDNF and we want more of it! BDNF gene expression has been observed to be reduced in various neurodegenerative and psychological disorders. BDNF is also reduced by stress which contributes to the aetiology of depression. BDNF actually exerts antidepressant activity in the brain. There are genetic polymorphisms or gene variants that affect the function of BDNF in turn increasing the risk of depression. This polymorphism affects Met-BDNF. Generalised anxiety disorder, obsessive compulsive disorder and panic disorder have also received some attention in research connecting low BDNF to these disorders.
There a multitude of enzymes (proteins that exert a function) that regulate various catecholamines (neurotransmitters such as dopamine) which have been implicated in the aetiology of depression and anxiety. Some include tyrosine hydroxylase (TH), dopamine-B-hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT), catechol-o-methyltransferase (COMT), monoamine oxidaseses (MAO), GAD and GABA transaminase. These enzymes all have multiple types and roles in metabolism and different people have different gene variants which can upregulate or downregulate the function of these enzymes.
What is pharmacogenomics?
Latest science allows us to individualise prescriptions of antidepressant and antipsychotic drugs, predict drug effect and risk of side effects by looking at individual biochemistry and genetic polymorphisms through simple DNA testing. Make an appointment with us today to request gene testing for pharmacogenomic profiling to integrate with your psychiatrist, psychologist and or GP. Herbal medicines are also available with high level evidence and comparable effect of medication with fewer side effects. We work alongside your medical team to integrate your treatment to optimise outcomes for you and personalise your care. After all one size does not fit all.
Our take home message today is that genes are likened to the loaded gun and may not mean anything, it is the environment that pulls the trigger. Empower yourself and learn how to optimise your environment for best function of genes and how to increase BDNF to improve mood and reduce anxiety. The best thing about epigenetics is that our genes are not in control of us, we can influence how they behave by making small diet and lifestyle adjustments and ensuring the best possible environment to live in.
Written by your Australia wide naturopath servicing Sydney, Brisbane, Adelaide, Melbourne, Darwin, Perth, Glen Innes and the New England area, Inverell, Armidale, Emmaville, Uralla, Surry Hills or where ever you are travelling from with online skype or phone consults available.
If you enjoyed this article check out our earlier piece on the holistic understanding of depression
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Swati Sahoo, Brijesh S. 2019, Pharmacogenomic assessment of herbal drugs in affective disorders, Biomedicine and pharmacotherapy, vol. 109, pp.1148-1162.
Disclaimer: Information provided here is educational and general information only and not a substitute for personal health advice. Please consult with your health care professional if anything you have read here concerns or interests you.