Introduction
Some contributions recently published on Frontiers in Psychiatry highlighted that dysregulation in daily rhythms could be related to higher risk of bipolar disorders (1, 2). On the other hand, dysregulation of sleep-wake rhythms and light pollution were found associated with prostate cancer (3). Indeed, it has been hypothesized the dysregulation of rhythmicity of melatonin and cortisol, the true markers of hormonal cycles, can affect the natural fluctuations of sex hormones, whose alteration could be the determinant of the increasing cancer risk (4, 5). An alteration in the concentrations of progesterone-derived hormones in blood has been identified during the luteal phase of the menstrual cycle in mood disorders with a concentration gradient that rises from healthy women, to women with stabilized depressive disorder and women with stabilized bipolar disorder, the latter with higher progesterone derived hormones level (6). Numerous steroids including those derived from progesterone have a specific effect and are synthesized in the Central Nervous System (neurosteroids) (7), in fact today they represent a horizon for research on the therapy of mood disorders (8–10). It was therefore hypothesized that progesterone could have an endogenous stabilizing role in contrast with the mood stimulating role of androgens, estrogens, and progestogens sulfates (8). It was argued that the alteration of circadian rhythms typical of bipolar disorders could have a link with the well-known rhythm's alterations of sex hormones (6, 8). It is also well-known that steroid and neurosteroid hormones have an active role in neuroplasticity, and that this aspect is strongly compromised in chronic mood disorders (11).
Subsections Relevant for the Subject
Thymosin Beta-4 is a small protein involved in cell motiliy and tumorigenesis (12, 13). Thymosin beta-4 blood levels were found to be altered in both depressive and bipolar disorders. As such, the candidate role of Thymosin beta-4 as biomarker would deserve further investigation (14). It is known that thymosin beta 4 can affect the hypothalamus pituitary and medullary axis of the adrenal gland, with consequences on sex hormones (14). Thymosin beta 4 has in fact had been hypothesized to be a specific positive regulator of estrogen and negative regulator of progesterone derived hormones (15, 16). Furthermore, in a disorder such as toxoplasmosis, suspected to be associated with bipolar disorder (17–19), the vesicles produced by toxoplasma in neurological locations have been found to contain large amounts of thymosin beta4 (20).
Discussion
All these indications suggest a possible link between timosine beta4, dysregulation of circadian rhythms, neurosteroid hormones and consequent high risk of mood and bipolar disorders. There is a need for future studies that focus on such evidence and hypotheses.
Publisher's Note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Statements
Author contributions
All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.
Conflict of interest
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.
References
1.
CartaMGOualiUPerraABen Cheikh AhmedABoeLAissaAet al. Living with bipolar disorder in the time of Covid-19: biorhythms during the severe lockdown in Cagliari, Italy, and the moderate lockdown in Tunis, Tunisia. Front Psychiatry. (2021) 12:634765. 10.3389/fpsyt.2021.634765
2.
SteardoLJrde FilippisRCarboneEASegura-GarciaCVerkhratskyADe FazioP. Sleep disturbance in bipolar disorder: neuroglia and circadian rhythms. Front Psychiatry. (2019) 10:501. 10.3389/fpsyt.2019.00501
3.
KimKYLeeEKimYJKimJ. The association between artificial light at night and prostate cancer in Gwangju City and South Jeolla Province of South Korea. Chronobiol Int. (2017) 34:203–11. 10.1080/07420528.2016.1259241
4.
CartaMGPretiAAkiskalHS. Coping with the New Era: noise and light pollution, hyperactivity and steroid hormones. Towards an evolutionary view of bipolar disorders. Clin Pract Epidemiol Ment Health. (2018) 14:33–6. 10.2174/1745017901814010033
5.
CartaMGColomFErfurthAFornaroMGrunzeHHantoucheEet al. In Memory of Hagop Akiskal. Clin Pract Epidemiol Mental Health. (2021) 17:48–51. 10.2174/1745017902117010048
6.
HardoyMCSerraMCartaMGContuPPisuMGBiggioG. Increased neuroactive steroid concentrations in women with bipolar disorder or major depressive disorder. J Clin Psychopharmacol. (2006) 26:379–84. 10.1097/01.jcp.0000229483.52955.ec
7.
EndresDPerlovERieringANMaierVStichODerschRet al. Steroid-responsive chronic schizophreniform syndrome in the context of mildly increased antithyroid peroxidase antibodies. Front Psychiatry. (2017) 8:64. 10.3389/fpsyt.2017.00064
8.
CartaMGBhatKMPretiA. GABAergic neuroactive steroids: a new frontier in bipolar disorders?Behav Brain Funct. (2012) 8:61. 10.1186/1744-9081-8-61
9.
Apter-LevyYZagoory-SharonOFeldmanR. Chronic depression alters mothers' DHEA and DEHA-to-cortisol ratio: implications for maternal behavior and child outcomes. Front Psychiatry. (2020) 11:728. 10.3389/fpsyt.2020.00728
10.
CornettEMRandoLLabbéAMPerkinsWKayeAMKayeADet al. Brexanolone to treat postpartum depression in adult women. Psychopharmacol Bull. (2021) 51:115–30.
11.
LosenkovISMulderNJVLevchukLAVyalovaNMLoonenAJMBoskerFJ. Association between BDNF gene variant Rs6265 and the severity of depression in antidepressant treatment-free depressed patients. Front Psychiatry. (2020). 11:38. 10.3389/fpsyt.2020.00038
12.
TheunissenWFanniDNemolatoSDi FeliceECabrasTGerosaCet al. Thymosin beta 4 and thymosin beta 10 expression in hepatocellular carcinoma. Eur J Histochem. (2014) 58:2242. 10.4081/ejh.2014.2242
13.
NemolatoSVan EykenPCabrasTCauFFanariMULocciAet al. Expression pattern of thymosin beta 4 in the adult human liver. Eur J Histochem. (2011) 55:e25. 10.4081/ejh.2011.e25
14.
KimHRheeSJLeeHHanDLeeTYKimMet al. Identification of altered protein expression in major depressive disorderand bipolar disorder patients using liquid chromatography-tandem massspectrometry. Psychiatry Res. (2021) 299:113850. 10.1016/j.psychres.2021.113850
15.
SuhBYNaylorPHGoldsteinALRebarRW. Modulation of thymosin beta 4 by estrogen. Am J Obstet Gynecol. (1985) 151:544–9.
16.
SalhabMPapillierPPerreauCGuyader-JolyCDupontJMermillodPet al. Thymosins β-4 and β-10 are expressed in bovine ovarian follicles and upregulated in cumulus cells during meiotic maturation. Reprod Fertil Dev. (2010) 22:1206–21. 10.1071/RD10015
17.
FryeMACoombesBJMcElroySLJones-BrandoLBondDJVeldicMet al. Association of Cytomegalovirus and Toxoplasma gondii antibody titers with bipolar disorder. JAMA Psychiatry. (2019) 76:1285–93. 10.1001/jamapsychiatry.2019.2499
18.
Alvarado-EsquivelCEstrada-MartínezSPérez-AlamosAR. A case-control seroprevalence study on the association between Toxoplasma gondii infection and bipolar disorder. Front Psychiatry. (2019) 10:766. 10.3389/fpsyt.2019.00766
19.
HusseinEAMKhalifaHRamadanGKHassaanSHShaabanIFarragHMM. Seroprevalence of Toxoplasma gondii among patients with schizophrenia and bipolar disorder in Upper Egypt: a comparative study with a control group. Ann Parasitol. (2020) 66:183–92. 10.17420/ap6602.253
20.
PopeSMLässerC. Toxoplasma gondii infection of fibroblasts causes the production of exosome-like vesicles containing a unique array of mRNA and miRNA transcripts compared to serum starvation. J Extracell Vesicles. (2013) 2. 10.3402/jev.v2i0.22484
Summary
Keywords
bipolar disorder, thymosin beta-4, neurosteroids, social rhythm, biorhythm
Citation
Carta MG, Fanni D, Orrù G and Faa G (2021) Commentary: Sleep Disturbance in Bipolar Disorder: Neuroglia and Circadian Rhythms. Front. Psychiatry 12:730360. doi: 10.3389/fpsyt.2021.730360
Received
25 June 2021
Accepted
10 August 2021
Published
30 September 2021
Volume
12 - 2021
Edited by
Sairam Parthasarathy, University of Arizona, United States
Reviewed by
Camilla Gesi, ASST Fatebenefratelli Sacco, Italy
Updates
Copyright
© 2021 Carta, Fanni, Orrù and Faa.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Mauro Giovanni Carta mgcarta@tiscali.it
This article was submitted to Sleep Disorders, a section of the journal Frontiers in Psychiatry
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.