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Review
. 2023 Jan 17:13:1099276.
doi: 10.3389/fphys.2022.1099276. eCollection 2022.

Women's mood at high altitude. sexual dimorphism in hypoxic stress modulation by the tryptophan-melatonin axis

D E Alcantara-Zapata  1 , N Lucero  2 , N De Gregorio  3 , P Astudillo Cornejo  4 , C Ibarra Villanueva  4 , M J Baltodano-Calle  1 , G F Gonzales  1   5 , C Behn  3   6
Affiliations
Review

Women's mood at high altitude. sexual dimorphism in hypoxic stress modulation by the tryptophan-melatonin axis

D E Alcantara-Zapata et al. Front Physiol. .

Abstract

Sexual (and gender)-dimorphism in tolerance to hypobaric hypoxia increasingly matters for a differential surveillance of human activities at high altitude (HA). At low altitudes, the prevalence of anxiety and depression in women has already been found to double when compared with men; it could be expected to even increase on exposure to HA. In purposefully caring for the health of women at HA, the present work explores the potential involvement of the tryptophan (Trp)-melatonin axis in mood changes on exposure to hypobaric hypoxia. The present work highlights some already known anxiogenic effects of HA exposure. Hypoxia and insomnia reduce serotonin (5-HT) availability; the latter defect being expressed as failure of brown adipose tissue (BAT) activation and mood disorders. Rapid eye movement (REM) sleep organization and synapsis restoration that are additionally affected by hypoxia impair memory consolidation. Affective complaints may thus surge, evolving into anxiety and depression. Sex-related differences in neural network organization and hormonal changes during the menstrual cycle, and certainly also during the life cycle, underscore the possibility of 5-HT-related mood alterations, particularly in women on HA exposure. The mean brain rate of 5-HT synthesis at sea level is already 1.5-fold higher in males than in females. sexual dimorphism also evidences the overexpression effects of SERT, a 5-HT transporter protein. Gonadal and thyroid hormones, as influenced by HA exposure, further modulate 5-HT availability and its effects in women. Besides caring for adequate oxygenation and maintenance of one's body core temperature, special precautions concerning women sojourning at HA should include close observations of hormonal cycles and, perhaps, also trials with targeted antidepressants.

Keywords: REM sleep; high altitude; serotonin; thermogenesis; tryptophan; women’s mood.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Stress and hypoxia mediated increase of the tryptophan derived metabolic kynurenine 128 pathway in detriment of 5-HT generation. Indoleamine 2,3-dioxygenase (IDO), being upregulated 129 by stress, enhances toxic kynurenine signaling. By reducing tryptophan hidroxylase (TPH) activities, 130 hypoxia concomitantly diminishes 5-HT availability.
FIGURE 2
FIGURE 2
Hypothetical sex-related mental disorder on exposure to high altitude (HA). Stress and hypoxia decrease the availability of 5-HT at HA; brain synthesis of the latter already being lower in women than in men. Moreover, estrogen (E)-mediated support of 5-HT is blocked by stress. The lack of 5-HT diminishes brown adipose tissue (BAT)–dependent heat generation. Metabolic energy already being reduced by hypoxia, and possibly also by goiter, which may consequently generate a tradeoff in order to prioritize the energy requirements of thermoregulation, possibly at the expense of synapse repair. Memory consolidation thereby being interfered could allow mood changes to surge; the latter, in turn, additionally enhancing stress and insomnia. A vicious circle may thus be installed, potentially triggering the generation of mental disorders. Line thickness indicates the magnitude of effects.
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References

    1. Altemus M., Sarvaiya N., Neill Epperson C. (2014). Sex differences in anxiety and depression clinical perspectives. Front. Neuroendocrinol. 35, 320–330. 10.1016/j.yfrne.2014.05.004 - DOI - PMC - PubMed
    1. Aquino Lemos V., Antunes H. K. M., Santos R. V. T., Lira F. S., Tufik S., Mello M. T. (2012). High altitude exposure impairs sleep patterns, mood, and cognitive functions. Psychophysiology 49, 1298–1306. 10.1111/j.1469-8986.2012.01411.x - DOI - PubMed
    1. Baglioni C., Nanovska S., Regen W., Spiegelhalder K., Feige B., Nissen C., et al. (2016). Sleep and mental disorders: A meta-analysis of polysomnographic research. Psychol. Bull. 142, 969–990. 10.1037/bul0000053 - DOI - PMC - PubMed
    1. Baker F. C., Lee K. A. (2018). Menstrual cycle effects on sleep. Sleep. Med. Clin. 13, 283–294. 10.1016/j.jsmc.2018.04.002 - DOI - PubMed
    1. Bauer M., Heinz A., Whybrow P. (2002). Thyroid hormones, serotonin and mood: Of synergy and significance in the adult brain. Mol. Psychiatry 7, 140–156. 10.1038/sj.mp.4000963 - DOI - PubMed

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