Monday Article #66: Light therapy treatment in mood disorders
Depression is categorised as a mental disorder according to the 5th edition of the diagnostic and statistical manual of mental disorders (DSM-5), and it exists in different forms such as seasonal affective depression (SAD) and postpartum depression. There are many approaches to treating depression, ranging from biological and psychological treatments. Such treatments include the use of antidepressants and psychotherapy, both which are as effective as one another (Tuunainen et al., 2004).
In this article, light therapy will be addressed as a form of treatment for depression. This is a type of phototherapy that is used to treat SAD through exposing oneself to light. Light therapy aligns the brain’s circadian rhythm (our biological clock), regulates serotonin circulation in the brain (which affects mood), enhances our attentiveness and contributes to keeping a consistent sleep pattern, all of which improves symptoms of depression (Watt, 2021).
Before moving onto the molecular interactions involved in light therapy, it is important to understand the underlying mechanisms of mood disorders. Cortisol level is regulated by the hypothalamus-pituitary-adrenal (HPA) axis through this negative feedback loop: Upon activation of the HPA axis, the secretion of adrenocorticotropic hormone (ACTH) is followed by the secretion of corticotropin-releasing hormones (CRH). Both hormones trigger the release of cortisol, which inhibits CRH and ACTH via the glucocorticoid receptor (GR). Hyperactivity of the HPA axis would contribute to mood disorders. As cortisol is associated with more depressive symptoms, it is suggested that in a pathological case, GR functioning declines, reducing the negative feedback loop, thus a higher cortisol level (Bais et al., 2021).
Another possible mechanism is associated with the disruption to the suprachiasmatic nucleus (SCN) functioning. The SCN is located in the hypothalamus and plays an important role in regulating the circadian rhythm. Because of this, light might be an indirect benefit to depressive symptoms. The SCN receives light from the retinohypothalamic tract which receives light projection from the retina and intrinsically photosensitive retinal ganglion cells. Due to the fact that SCN controls the HPA axis, light therapy could reset the HPA axis and return cortisol levels to its normal range (Bais et al., 2021).
Although investigation into neuronal recovery provides little to no evidence regarding the underlying mechanism, it does provide promising treatments for the future. Recent findings focusing on cellular mechanisms show that energy released by the light is capable of increasing cellular metabolites and signalling molecules. As shown in Figure 1., there are several possible pathways in which light triggers the electron transport chain (Prindeze et al., 2012).
Figure 1. An illustration of light therapy on the mitochondrial electron transport chain (Prindeze et al., 2012).
The chromosphere believed to be receiving photostimulation is the mitochondrial respiratory chain enzyme cytochrome c oxidase. In response to light therapy, concentration of reactive oxygen species (ROS) has increased significantly. ROS plays a role in converting harmful superoxide and peroxide found in the body into oxygen and water respectfully. Similarly, production of ATP increased alongside ROS. Calcium ion flow has been investigated to be associated with the ROS signalling pathways, though it is dependent on the dose of light. Releasing of calcium ions has correlation to the concentration of hydrogen peroxide (H2O2), whereby an increased concentration of calcium ions is caused by the addition of H2O2 (Prindeze et al., 2012) .
Out of various repetitive studies, red light at the wavelength of 630-690nm have produced the most productive response and is used in the majority of light studies (Prindeze et al., 2012). Scientists are discovering alternative therapeutics to treat mood disorders, and one of which is light therapy. Though with many individual differences in patience, this results in inconsistency throughout various studies. The underlying cellular mechanism of light therapy is not well known and has yet to be unravelled.
Bais, B., Hoogendijk, W.J.G. and Lambregtse-van den Berg, M.P. (2021) ‘Light therapy for mood disorders’, The Human Hypothalamus: Neuropsychiatric Disorders, pp. 49–61. doi:10.1016/b978-0-12-819973-2.00004-6.
Prindeze, N.J., Moffatt, L.T. and Shupp, J.W. (2012) ‘Mechanisms of action for light therapy: A review of molecular interactions’, Experimental Biology and Medicine, 237(11), pp. 1241–1248. doi:10.1258/ebm.2012.012180.
Tuunainen, A., Kripke, D.F. and Endo, T. (2004) ‘Light therapy for non-seasonal depression’, Cochrane Database of Systematic Reviews [Preprint]. doi:10.1002/14651858.cd004050.pub2.
Watt, A. (2021) How does light therapy help treat depression?, Healthline. Available at: https://www.healthline.com/health/depression/light-therapy (Accessed: 27 June 2023).
This article was prepared by Fatini Khadrishah