Flights are terrible because airplanes use filtered air which stimulates my inner germaphobe, but even after the plane lands jet lag is waiting for me. The symptoms of jet lag include decreased alertness, insomnia, poor performance and impaired cognitive skills (Cho, Ennaceur, Cole, & Suh, 2000). Jet lag occurs when your inner clock and external time desynchronize. The duration of jet lag varies depending on the individual and the difference between the time zones; it takes approximately 1 day for each hour of time zone change for your body to adjust (Arendt, 2018). Healthcare professionals, such as nurses and doctors, are great examples of shift workers because hospitals are open 24/7 and, therefore, require staff at all hours.
Research has shown that the hypothalamus and the adrenal gland acts as an overseer to re-synchronize the circadian rhythm (Welsh, Yoo, Liu, Takahashi, Kay, 2004). Mice with removed adrenal glands experience a faster rate of re-entrainment, which is how long it takes for the symptoms of jet lag to dissipate; in other words, the adrenal glands prevent your circadian rhythm from changing too suddenly (Welsh, Yoo, Liu, Takahashi, Kay, 2004). The hormone used to regulate the circadian rhythm is adrenal corticosterone; and blocking it secretion has been shown to the increase the rate of re-entrainment (Kiessling, Eichele, Oster, 2010).
Taking in consideration the symptoms of jet lag, and the role of adrenal corticosterone in jet lag. Would it be ethical to provide healthcare professionals, who shift work, hormone therapy in order to inhibit corticosterone synthesis and alleviate the symptoms of jet lag?
Kiessling, S., Eichele, G., & Oster, H. (2010). Adrenal glucocorticoids have a key role in circadian resynchronization in a mouse model of jet lag. The Journal of clinical investigation, 120(7), 2600–2609. doi:10.1172/JCI41192
Cho, K., Ennaceur, A., Cole, J. C., & Suh, C. K. (2000). Chronic jet lag produces cognitive deficits. The Journal of neuroscience : the official journal of the Society for Neuroscience, 20(6), RC66. doi:10.1523/JNEUROSCI.20-06-j0005.2000
Welsh DK, Yoo SH, Liu AC, Takahashi JS, Kay SA. Bioluminescence imaging of individual fibroblasts reveals persistent, independently phased circa- dian rhythms of clock gene expression. Curr Biol. 2004;14(24):2289–2295.
Arendt J. (2018). Approaches to the Pharmacological Management of Jet Lag. Drugs, 78(14), 1419–1431. doi:10.1007/s40265-018-0973-8
As someone who worked in the emergency department, I too often felt the miserable effects of having to switch between morning and nightly shifts. While the inclusion of hormone therapies to inhibit corticosterone and its effects on blunting the rate of re-entrainment is tempting, I felt it was important to consider that corticosterone is not specific to re-entrainment, and that medications altering corticosterone action could potentially produce other effects.
ReplyDeleteAccording to Mitra & Sapolsky, the basal amygdala, which is responsible for feelings of aggression and fear, has a high concentration of glucocorticoid receptors, and is particularly responsive towards inducing anxiety (2008). Additionally, this study demonstrated plasticity of amygdaloid neurons, showing dendrite hypertrophy that was a particularly sensitive response to elevations in corticosterone. With regard to the treatment method you've presented, I am curious to if inhibition of corticosterone (ie: via a competitive inhibitor) may instead produce a calming, anti-anxiety effect as well, a potentially beneficial effect in some circumstances. However, other studies such as Venkova et al. also demonstrate changes in colonic motility when manipulating corticosterone levels, a potentially negative side effect when considering potential comorbidities that may arise in interested patients with existing GI-related disorders (2010). When prescribing or developing a medication targeting the effects of corticosterone, I think it is important to consider the widespread effects across all systems and investigate methods to localize the desired effect in order to avoid undesired patient outcomes.
References:
Mitra, R. & Sapolsky, R.M. (2008). Acute corticosterone treatment is sufficient to induce anxiety and amygdaloid dendritic hypertrophy. Proc. Natl. Acad. Sci. U.S.A., 105(14), 5573-5578, doi: 10.1073/pnas.0705615105
Venkova. K., Johnson, A.C., Myers, B., Meerveld, B.G.V. (2010). Exposure of the amygdala to elevated levels of corticosterone alters colonic motility in response to acute psychological stress. Neuropharmacology, 58(7), 1161-1167, https://doi.org/10.1016/j.neuropharm.2010.02.012