The Mediation Effect of Peripheral Biomarkers of Calcium Metabolism and Chronotypes in Bipolar Disorder Psychopathology
Abstract
:1. Introduction
- (1)
- identifying the association between calcium imbalance and a specific chronotype in a cohort of BD patients;
- (2)
- testing the mediation role of high PTH levels between a specific chronotype and illness severity in BD patients.
2. Material and Method
2.1. Procedures and Measures
2.2. Statistical Analysis
3. Results
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Głąbska, D.; Kołota, A.; Lachowicz, K.; Skolmowska, D.; Stachoń, M.; Guzek, D. Vitamin D Supplementation and Mental Health in Multiple Sclerosis Patients: A Systematic Review. Nutrients 2021, 13, 4207. [Google Scholar] [CrossRef]
- Choukri, M.A.; Conner, T.S.; Haszard, J.J.; Harper, M.J.; Houghton, L.A. Effect of vitamin D supplementation on depressive symptoms and psychological wellbeing in healthy adult women: A double-blind randomised controlled clinical trial. J. Nutr. Sci. 2018, 7, e23. [Google Scholar] [CrossRef]
- Bertone-Johnson, E.R.; Powers, S.I.; Spangler, L.; Brunner, R.L.; Michael, Y.L.; Larson, J.C.; Millen, A.E.; Bueche, M.N.; Salmoirago-Blotcher, E.; Liu, S.; et al. Vitamin D intake from foods and supplements and depressive symptoms in a diverse population of older women. Am. J. Clin. Nutr. 2011, 94, 1104–1112. [Google Scholar] [CrossRef]
- Kjærgaard, M.; Joakimsen, R.; Jorde, R. Low serum 25-hydroxyvitamin D levels are associated with depression in an adult Norwegian population. Psychiatry Res. 2011, 190, 221–225. [Google Scholar] [CrossRef]
- Ganji, V.; Milone, C.; Cody, M.M.; McCarty, F.; Wang, Y.T. Serum vitamin D concentrations are related to depression in young adult US population: The Third National Health and Nutrition Examination Survey. Int. Arch. Med. 2010, 3, 29. [Google Scholar] [CrossRef]
- Polak, M.; Houghton, L.; Reeder, A.; Harper, M.; Conner, T. Serum 25-Hydroxyvitamin D Concentrations and Depressive Symptoms among Young Adult Men and Women. Nutrients 2014, 6, 4720–4730. [Google Scholar] [CrossRef]
- Pike, J.W.; Meyer, M.B.; Lee, S.-M.; Onal, M.; Benkusky, N.A. The vitamin D receptor: Contemporary genomic approaches reveal new basic and translational insights. J. Clin. Investig. 2017, 127, 1146–1154. [Google Scholar] [CrossRef]
- Eyles, D.W.; Smith, S.; Kinobe, R.; Hewison, M.; McGrath, J.J. Distribution of the Vitamin D receptor and 1α-hydroxylase in human brain. J. Chem. Neuroanat. 2005, 29, 21–30. [Google Scholar] [CrossRef]
- Berk, M.; Post, R.; Ratheesh, A.; Gliddon, E.; Singh, A.; Vieta, E.; Carvalho, A.F.; Ashton, M.M.; Berk, L.; Cotton, S.M.; et al. Staging in bipolar disorder: From theoretical framework to clinical utility. World Psychiatry 2017, 16, 236–244. [Google Scholar] [CrossRef]
- Kumar, R.; Rathi, H.; Haq, A.; Wimalawansa, S.J.; Sharma, A. Putative roles of vitamin D in modulating immune response and immunopathology associated with COVID-19. Virus Res. 2021, 292, 198235. [Google Scholar] [CrossRef]
- Berk, M.; Sanders, K.M.; Pasco, J.A.; Jacka, F.N.; Williams, L.J.; Hayles, A.L.; Dodd, S. Vitamin D deficiency may play a role in depression. Med. Hypotheses 2007, 69, 1316–1319. [Google Scholar] [CrossRef]
- Frey, B.N.; Andreazza, A.C.; Houenou, J.; Jamain, S.; Goldstein, B.I.; Frye, M.A.; Leboyer, M.; Berk, M.; Malhi, G.S.; Lopez-Jaramillo, C.; et al. Biomarkers in bipolar disorder: A positional paper from the International Society for Bipolar Disorders Biomarkers Task Force. Aust. New Zeal. J. Psychiatry 2013, 47, 321–332. [Google Scholar] [CrossRef]
- Herzog, E.D.; Hermanstyne, T.; Smyllie, N.J.; Hastings, M.H. Regulating the Suprachiasmatic Nucleus (SCN) Circadian Clockwork: Interplay between Cell-Autonomous and Circuit-Level Mechanisms. Cold Spring Harb. Perspect. Biol. 2017, 9, a027706. [Google Scholar] [CrossRef]
- Cavieres-Lepe, J.; Ewer, J. Reciprocal Relationship Between Calcium Signaling and Circadian Clocks: Implications for Calcium Homeostasis, Clock Function, and Therapeutics. Front. Mol. Neurosci. 2021, 14, 666673. [Google Scholar] [CrossRef]
- Buhr, E.D.; Yoo, S.H.; Takahashi, J.S. Temperature as a Universal Resetting Cue for mammalian circadian oscillators. Science 2010, 330, 379–385. [Google Scholar] [CrossRef]
- Bernard, S.; Gonze, D.; Čajavec, B.; Herzel, H.; Kramer, A. Synchronization-Induced Rhythmicity of Circadian Oscillators in the Suprachiasmatic Nucleus. PLoS Comput. Biol. 2007, 3, e68. [Google Scholar] [CrossRef]
- Shaheen, M.; Cheema, Y.; Shahbaz, A.U.; Bhattacharya, S.K.; Weber, K.T. Intracellular calcium overloading and oxidative stress in cardiomyocyte necrosis via a mitochondriocentric signal-transducer-effector pathway. Exp. Clin. Cardiol. 2011, 16, 109–115. [Google Scholar]
- Brown, S.J.; Ruppe, M.D.; Tabatabai, L.S. The Parathyroid Gland and Heart Disease. Methodist Debakey Cardiovasc. J. 2017, 13, 49. [Google Scholar] [CrossRef]
- Steardo, L.; Luciano, M.; Sampogna, G.; Carbone, E.A.; Caivano, V.; Di Cerbo, A.; Giallonardo, V.; Palummo, C.; Vece, A.; Del Vecchio, V.; et al. Clinical Severity and Calcium Metabolism in Patients with Bipolar Disorder. Brain Sci. 2020, 10, 417. [Google Scholar] [CrossRef]
- Yan, L.; Smale, L.; Nunez, A.A. Circadian and photic modulation of daily rhythms in diurnal mammals. Eur. J. Neurosci. 2020, 51, 551–566. [Google Scholar] [CrossRef]
- O’Neill, J.S.; Maywood, E.S.; Hastings, M.H. Cellular Mechanisms of Circadian Pacemaking: Beyond Transcriptional Loops. Handb. Exp. Pharmacol. 2013, 217, 67–103. [Google Scholar] [CrossRef]
- Fagiani, F.; Di Marino, D.; Romagnoli, A.; Travelli, C.; Voltan, D.; Di Cesare Mannelli, L.; Racchi, M.; Govoni, S.; Lanni, C. Molecular regulations of circadian rhythm and implications for physiology and diseases. Signal Transduct. Target. Ther. 2022, 7, 41. [Google Scholar] [CrossRef] [PubMed]
- Vitale, J.A.; Roveda, E.; Montaruli, A.; Galasso, L.; Weydahl, A.; Caumo, A.; Carandente, F. Chronotype influences activity circadian rhythm and sleep: Differences in sleep quality between weekdays and weekend. Chronobiol. Int. 2015, 32, 405–415. [Google Scholar] [CrossRef]
- Díaz-Morales, J.F.; Escribano, C.; Jankowski, K.S. Chronotype and time-of-day effects on mood during school day. Chronobiol. Int. 2015, 32, 37–42. [Google Scholar] [CrossRef] [PubMed]
- Melo, M.C.A.; Abreu, R.L.C.; Linhares Neto, V.B.; de Bruin, P.F.C.; de Bruin, V.M.S. Chronotype and circadian rhythm in bipolar disorder: A systematic review. Sleep Med. Rev. 2017, 34, 46–58. [Google Scholar] [CrossRef]
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed.; American Psychiatric Association: Washington, DC, USA, 2013. [Google Scholar]
- Hamilton, M. A rating scale for depression. J. Neurol. Neurosurg. Psychiatry 1960, 23, 56–62. [Google Scholar] [CrossRef]
- Maier, W.; Buller, R.; Philipp, M.; Heuser, I. The Hamilton Anxiety Scale: Reliability, validity and sensitivity to change in anxiety and depressive disorders. J. Affect. Disord. 1988, 14, 61–68. [Google Scholar] [CrossRef]
- Young, R.C.; Biggs, J.T.; Ziegler, V.E.; Meyer, D.A. A rating scale for mania: Reliability, validity and sensitivity. Br. J. Psychiatry 1978, 133, 429–435. [Google Scholar] [CrossRef]
- Rose, D.; Gelaye, B.; Sanchez, S.; Castañeda, B.; Sanchez, E.; Yanez, N.D.; Williams, M.A. Morningness/eveningness chronotype, poor sleep quality, and daytime sleepiness in relation to common mental disorders among Peruvian college students. Psychol. Health Med. 2015, 20, 345–352. [Google Scholar] [CrossRef]
- Jamovi Project. Jamovi, Version 0.9; [Computer Software]. 2018. Available online: http://www.jamovi.org (accessed on 6 July 2022).
- Edery, I. Circadian rhythms. Temperatures to communicate by. Science 2010, 330, 329–330. [Google Scholar] [CrossRef] [PubMed]
- Müller, M.J.; Cabanel, N.; Olschinski, C.; Jochim, D.; Kundermann, B. Chronotypes in patients with nonseasonal depressive disorder: Distribution, stability and association with clinical variables. Chronobiol. Int. 2015, 32, 1343–1351. [Google Scholar] [CrossRef]
- Romo-Nava, F.; Blom, T.J.; Cuellar-Barboza, A.B.; Winham, S.J.; Colby, C.L.; Nunez, N.A.; Biernacka, J.M.; Frye, M.A.; McElroy, S.L. Evening chronotype as a discrete clinical subphenotype in bipolar disorder. J. Affect. Disord. 2020, 266, 556–562. [Google Scholar] [CrossRef]
- Melo, M.C.; Garcia, R.F.; de Araújo, C.F.; Luz, J.H.; de Bruin, P.F.; d Bruin, V.M. Chronotype in bipolar disorder: An 18-month prospective study. Braz. J. Psychiatry 2020, 42, 68–71. [Google Scholar] [CrossRef] [PubMed]
- Tonetti, L.; Natale, V. Discrimination between extreme chronotypes using the full and reduced version of the Morningness-Eveningness Questionnaire. Chronobiol. Int. 2019, 36, 181–187. [Google Scholar] [CrossRef]
- Oliveira, T.; Marinho, V.; Carvalho, V.; Magalhães, F.; Rocha, K.; Ayres, C.; Teixeira, S.; Nunes, M.; Bastos, V.H.; Pinto, G.R. Genetic polymorphisms associated with circadian rhythm dysregulation provide new perspectives on bipolar disorder. Bipolar Disord. 2018, 20, 515–522. [Google Scholar] [CrossRef]
- Jankowski, K.S.; Dmitrzak-Weglarz, M. ARNTL, CLOCK and PER3 polymorphisms—Links with chronotype and affective dimensions. Chronobiol. Int. 2017, 34, 1105–1113. [Google Scholar] [CrossRef]
- Norman, P.; Spack Daniel, E.; Shumer, N.J.N. Circadian Misalignment and Health. Physiol. Behav. 2017, 176, 139–148. [Google Scholar] [CrossRef]
- Montaruli, A.; Castelli, L.; Mulè, A.; Scurati, R.; Esposito, F.; Galasso, L.; Roveda, E. Biological Rhythm and Chronotype: New Perspectives in Health. Biomolecules 2021, 11, 487. [Google Scholar] [CrossRef] [PubMed]
- Everitt, H.; Baldwin, D.S.; Stuart, B.; Lipinska, G.; Mayers, A.; Malizia, A.L.; Manson, C.C.; Wilson, S. Antidepressants for insomnia in adults. Cochrane Database Syst. Rev. 2018, 2018, CD010753. [Google Scholar] [CrossRef]
- Jodele. Sleep disturbances in Schizophrenia and Psychosis. Physiol. Behav. 2016, 176, 100–106. [Google Scholar] [CrossRef]
- Gao, Q.; Sheng, J.; Qin, S.; Zhang, L. Chronotypes and affective disorders: A clock for mood? Brain Sci. Adv. 2019, 5, 145–160. [Google Scholar] [CrossRef]
- Mokros, L.; Nowakowska-Domagała, K.; Witusik, A.; Pietras, T. Evening chronotype as a bipolar feature among patients with major depressive disorder: The results of a pilot factor analysis. Braz. J. Psychiatry 2022, 44, 35–40. [Google Scholar] [CrossRef] [PubMed]
- Bothwell, M.Y.; Gillette, M.U. Circadian redox rhythms in the regulation of neuronal excitability. Free Radic. Biol. Med. 2018, 119, 45–55. [Google Scholar] [CrossRef]
- Egstrand, S.; Nordholm, A.; Morevati, M.; Mace, M.L.; Hassan, A.; Naveh-Many, T.; Rukov, J.L.; Gravesen, E.; Olgaard, K.; Lewin, E. A molecular circadian clock operates in the parathyroid gland and is disturbed in chronic kidney disease associated bone and mineral disorder. Kidney Int. 2020, 98, 1461–1475. [Google Scholar] [CrossRef]
- Hassan, A.; Khalaily, N.; Kilav-Levin, R.; Nechama, M.; Volovelsky, O.; Silver, J.; Naveh-Many, T. Molecular Mechanisms of Parathyroid Disorders in Chronic Kidney Disease. Metabolites 2022, 12, 111. [Google Scholar] [CrossRef] [PubMed]
- Richter, H.G.; Torres-Farfàn, C.; Rojas-Garcìa, P.P.; Campino, C.; Torrealba, F.; Seròn-Ferré, M. The Circadian Timing System: Making Sense of day/night gene expression. Biol. Res. 2004, 37, 11–28. [Google Scholar] [CrossRef] [PubMed]
- Shimba, S.; Ishii, N.; Ohta, Y.; Ohno, T.; Watabe, Y.; Hayashi, M.; Wada, T.; Aoyagi, T.; Tezuka, M. Brain and muscle Arnt-like protein-1 (BMAL1), a component of the molecular clock, regulates adipogenesis. Proc. Natl. Acad. Sci. USA 2005, 102, 12071–12076. [Google Scholar] [CrossRef] [PubMed]
- Panda, S. Circadian physiology of metabolism. Science 2016, 354, 1008–1015. [Google Scholar] [CrossRef] [PubMed]
- Fuleihan, G.E.-H.; Klerman, E.B.; Brown, E.N.; Choe, Y.; Brown, E.M.; Czeisler, C.A. The Parathyroid Hormone Circadian Rhythm Is Truly Endogenous—A General Clinical Research Center Study 1. J. Clin. Endocrinol. Metab. 1997, 82, 281–286. [Google Scholar] [CrossRef]
- Xie, Y.; Tang, Q.; Chen, G.; Xie, M.; Yu, S.; Zhao, J.; Chen, L. New Insights Into the Circadian Rhythm and Its Related Diseases. Front. Physiol. 2019, 10, 682. [Google Scholar] [CrossRef]
- Centeno, P.P.; Herberger, A.; Mun, H.-C.; Tu, C.; Nemeth, E.F.; Chang, W.; Conigrave, A.D.; Ward, D.T. Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. Nat. Commun. 2019, 10, 4693. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Olauson, H.; Lindberg, K.; Amin, R.; Sato, T.; Jia, T.; Goetz, R.; Mohammadi, M.; Andersson, G.; Lanske, B.; Larsson, T.E. Parathyroid-Specific Deletion of Klotho Unravels a Novel Calcineurin-Dependent FGF23 Signaling Pathway That Regulates PTH Secretion. PLoS Genet. 2013, 9, e1003975. [Google Scholar] [CrossRef] [PubMed]
- Rejnmark, L.; Lauridsen, A.; Vestergaard, P.; Heickendorff, L.; Andreasen, F.; Mosekilde, L. Diurnal rhythm of plasma 1,25-dihydroxyvitamin D and vitamin D-binding protein in postmenopausal women: Relationship to plasma parathyroid hormone and calcium and phosphate metabolism. Eur. J. Endocrinol. 2002, 146, 635–642. [Google Scholar] [CrossRef] [PubMed]
- Anjum, I.; Jaffery, S.S.; Fayyaz, M.; Samoo, Z.; Anjum, S. The Role of Vitamin D in Brain Health: A Mini Literature Review. Cureus 2018, 10, e2960. [Google Scholar] [CrossRef]
- Menon, V.; Kar, S.K.; Suthar, N.; Nebhinani, N. Vitamin D and Depression: A Critical Appraisal of the Evidence and Future Directions. Indian J. Psychol. Med. 2020, 42, 11–21. [Google Scholar] [CrossRef]
- Vergun, O.; Keelan, J.; Khodorov, B.I.; Duchen, M.R. Glutamate-induced mitochondrial depolarisation and perturbation of calcium homeostasis in cultured rat hippocampal neurones. J. Physiol. 1999, 519, 451–466. [Google Scholar] [CrossRef]
- Lattanzi, D.; Di Palma, M.; Cuppini, R.; Ambrogini, P. GABAergic Input Affects Intracellular Calcium Levels in Developing Granule Cells of Adult Rat Hippocampus. Int. J. Mol. Sci. 2020, 21, 1715. [Google Scholar] [CrossRef]
- Sabir, M.S.; Haussler, M.R.; Mallick, S.; Kaneko, I.; Lucas, D.A.; Haussler, C.A.; Whitfield, G.K.; Jurutka, P.W. Optimal vitamin D spurs serotonin: 1,25-dihydroxyvitamin D represses serotonin reuptake transport (SERT) and degradation (MAO-A) gene expression in cultured rat serotonergic neuronal cell lines. Genes Nutr. 2018, 13, 19. [Google Scholar] [CrossRef]
- Roffe-Vazquez, D.N.; Huerta-Delgado, A.S.; Castillo, E.C.; Villarreal-Calderón, J.R.; Gonzalez-Gil, A.M.; Enriquez, C.; Garcia-Rivas, G.; Elizondo-Montemayor, L. Correlation of Vitamin D with Inflammatory Cytokines, Atherosclerotic Parameters, and Lifestyle Factors in the Setting of Heart Failure: A 12-Month Follow-Up Study. Int. J. Mol. Sci. 2019, 20, 5811. [Google Scholar] [CrossRef]
- Wimalawansa, S.J. Vitamin D Deficiency: Effects on Oxidative Stress, Epigenetics, Gene Regulation, and Aging. Biology 2019, 8, 30. [Google Scholar] [CrossRef]
- Faye, P.A.; Poumeaud, F.; Miressi, F.; Lia, A.S.; Demiot, C.; Magy, L.; Favreau, F.; Sturtz, F.G. Focus on 1,25-Dihydroxyvitamin D3 in the Peripheral Nervous System. Front. Neurosci. 2019, 13, 348. [Google Scholar] [CrossRef] [PubMed]
- Gezen-Ak, D.; Dursun, E.; Yilmazer, S. The Effects of Vitamin D Receptor Silencing on the Expression of LVSCC-A1C and LVSCC-A1D and the Release of NGF in Cortical Neurons. PLoS ONE 2011, 6, e17553. [Google Scholar] [CrossRef] [PubMed]
- Groves, N.J.; McGrath, J.J.; Burne, T.H.J. Vitamin D as a Neurosteroid Affecting the Developing and Adult Brain. Annu. Rev. Nutr. 2014, 34, 117–141. [Google Scholar] [CrossRef] [PubMed]
- Ceolin, G.; Mano, G.P.R.; Hames, N.S.; Antunes, L.D.C.; Brietzke, E.; Rieger, D.K.; Moreira, J.D. Vitamin D, Depressive Symptoms, and COVID-19 Pandemic. Front. Neurosci. 2021, 15, 879. [Google Scholar] [CrossRef]
- Nanou, E.; Catterall, W.A. Calcium Channels, Synaptic Plasticity, and Neuropsychiatric Disease. Neuron 2018, 98, 466–481. [Google Scholar] [CrossRef] [Green Version]
Demographic Variables | MEQ-E (n = 32) | MEQ-I (n = 41) | MEQ-M (n =27) | p |
---|---|---|---|---|
Marital status, yes N (%) | 12 (37.5) | 22 (53.7) | 12 (44.4) | 0.638 |
Females, yes N (%) | 17 (53.1) | 15 (36.6) | 18 (66.7) | 0.058 |
Diploma, yes N (%) | 24 (75.0) | 32 (78.0) | 21 (77.8) | 0.951 |
Employed, yes N (%) | 19 (59.4) | 29 (70.7) | 14 (51.9) | 0.084 |
Family Psychiatric History, yes N (%) | 25 (78.1) | 25 (61.0) | 18 (66.7) | 0.276 |
Bipolar type 1, yes N (%) | 30 (93.8) | 15 (36.6) | 10 (37.0) | <0.001 |
Age, M (SD) | 46.8 (15.5) | 46.3 (11.4) | 46.3 (15.9) | 0.978 |
Psychopathological Features Comparison among the Different Chronotypes | ||||||
---|---|---|---|---|---|---|
MEQ-E | MEQ-I | MEQ-M | χ2 | df | p | |
Antidepressant switch, N (%) | 19 (65.5%) | 4 (13.8%) | 6 (20.7%) | 22.316 | 2 | <0.001 |
Aggressive behavior, N (%) | 24 (42.1%) | 21 (36.8%) | 12 (21.1%) | 6.526 | 2 | 0.038 |
Mixed features, N (%) | 30 (62.5%) | 10 (20.8%) | 8 (16.7%) | 38.926 | 2 | <0.001 |
Anxious features, N (%) | 30 (62.5%) | 19 (30.2%) | 14 (22.2%) | 19.301 | 2 | <0.001 |
Psychotic symptoms, N (%) | 30 (68.2%) | 9 (20.5%) | 5 (11.4%) | 47.348 | 2 | <0.001 |
History of Suicide, N (%) | 21 (65.6%) | 5 (15.6%) | 6 (18.8%) | 25.204 | 2 | <0.001 |
MEQ-E+ | MEQ-E- | χ2 | df | p | ||
Antidepressant switch, N (%) | 19 (65.5%) | 10 (34.5%) | 21.087 | 1 | <0.001 | |
Aggressive behavior, N (%) | 24 (42.1%) | 33 (57.9%) | 6.221 | 1 | 0.017 | |
Mixed features, N (%) | 30 (62.5%) | 18 (37.5%) | 38.788 | 1 | <0.001 | |
Anxious features, N (%) | 30 (47.6%) | 33 (52.4%) | 19.089 | 1 | <0.001 | |
Psychotic symptoms, N (%) | 30 (68.2%) | 14 (31.8%) | 47.270 | 1 | <0.001 | |
History of Suicide, N (%) | 21 (65.6%) | 11 (34.4%) | 24.452 | 1 | <0.001 |
MEQ-E | MEQ-I | MEQ-M | χ2 | df | p | ε² | |
---|---|---|---|---|---|---|---|
Number of total episodes, M (SD) | 17.7 (12.8) | 7.9 (6.1) | 5.9 (3.7) | 23.337 | 2 | <0.001 | 0.23573 |
Number of depressive episodes, M (SD) | 9.0 (6.6) | 4.1 (3.2) | 3.1 (1.9) | 20.309 | 2 | <0.001 | 0.20724 |
Number of manic episodes, M (SD) | 4.6 (3.2) | 3.3 (2.5) | 2.4 (1.5) | 5.168 | 2 | 0.075 | 0.09570 |
Number of hypomanic episodes, M (SD) | 4.8 (4.6) | 2.6 (1.6) | 2.2 (1.0) | 6.183 | 2 | 0.045 | 0.06648 |
Age at first psychiatric contact, M (SD) | 29.8 (8.5) | 29.6 (9.5) | 30.6 (12.7) | 0.242 | 2 | 0.886 | 0.00244 |
Age at illness onset, M (SD) | 27.1 (7.9) | 26.6 (9.1) | 28.7 (12.9) | 0.669 | 2 | 0.716 | 0.00676 |
HAM-D, M (SD) | 46.4 (11.2) | 27.1 (11.8) | 23.9 (11.6) | 43.330 | 2 | <0.001 * | 0.4377 |
HAM-A, M (SD) | 21.1 (8.3) | 7.9 (9.5) | 8.5 (9.6) | 28.648 | 2 | <0.001 * | 0.2894 |
YMRS, M (SD) | 29.1 (6.4) | 18.7 (8.7) | 21.3 (9.9) | 22.293 | 2 | <0.001 * | 0.2252 |
Calcium levels, M (SD) | 9.5 (0.5) | 9.4 (±0.4) | 9.5 (0.4) | 1.706 | 2 | 0.426 * | 0.0172 |
PTH levels, M (SD) | 62.2 (12.6) | 40.8 (17.6) | 38.5 (21.7) | 27.114 | 2 | <0.001 * | 0.2739 |
Vitamin D levels, M (SD) | 33.3 (11.2) | 44.2 (47.6) | 38.9 (10.9) | 6.069 | 2 | 0.048 * | 0.0613 |
Dwass-Steel-Critchlow-Fligner Pairwise Comparisons for Psychopathological Scale | |||||||
Chronotype | HAMD Total Score | HAMA Total Score | YMRS Total Score | ||||
w | p | w | p | w | p | ||
MEQ-E | MEQ-I | −8.112 | <0.001 | −6.946 | <0.001 | −6.61 | <0.001 |
MEQ-E | MEQ-M | −8.034 | <0.001 | −5.900 | <0.001 | −4.34 | 0.006 |
MEQ-I | MEQ-M | −0.532 | 0.925 | 0.834 | 0.826 | 1.43 | 0.571 |
Dwass-Steel-Critchlow-Fligner Pairwise Comparisons for Biological Variable | |||||||
Chronotype | Ca++ Levels | PTH Levels | Vitamin D Levels | ||||
w | p | w | p | w | p | ||
MEQ-E | MEQ-I | −1.510 | 0.534 | −6.71 | <0.001 | 2.43 | 0.198 |
MEQ-E | MEQ-M | −0.716 | 0.868 | −5.87 | <0.001 | 3.35 | 0.047 |
MEQ-I | MEQ-M | 1.531 | 0.525 | −1.38 | 0.591 | 1.30 | 0.627 |
Mediation Analyses | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
a. Mediation YMRS | ||||||||||
95% Confidence Interval | ||||||||||
Effect | Label | Estimate | SE | Lower | Upper | Z | p | % Mediation | ||
Indirect | a × b | −1.08 | 1.09 | −3.2 | 1.13 | −0.997 | 0.319 | 11.6 | ||
Direct | c | −8.24 | 1.66 | −11.45 | −4.79 | −4.955 | <0.001 | 88.4 | ||
Total | c + a × b | −9.33 | 1.56 | −12.45 | −6.34 | −5.968 | <0.001 | 100 | ||
Path Estimates | ||||||||||
95% Confidence Interval | ||||||||||
Label | Estimate | SE | Lower | Upper | Z | p | ||||
MEQ-E | → | PTH | a | −22.3409 | 3.1036 | −28.4843 | −16.339 | −7.2 | <0.001 | |
PTH | → | YMRS | b | 0.0485 | 0.0482 | −0.0466 | 0.14 | 1 | 0.315 | |
MEQ-E | → | YMRS | c | −8.2447 | 1.6639 | −11.4546 | −4.789 | −4.96 | <0.001 | |
b. Mediation HAM-D. | ||||||||||
95% Confidence Interval | ||||||||||
Effect | Label | Estimate | SE | Lower | Upper | Z | p | % Mediation | ||
Indirect | a × b | −5.15 | 1.75 | −9.03 | −2.24 | −2.94 | 0.003 | 25.5 | ||
Direct | c | −15.05 | 2.86 | −20.51 | −8.95 | −5.26 | <0.001 | 74.5 | ||
Total | c + a × b | −20.2 | 2.39 | −24.77 | −15.4 | −8.45 | <0.001 | 100 | ||
Path Estimates | ||||||||||
95% Confidence Interval | ||||||||||
Label | Estimate | SE | Lower | Upper | Z | p | ||||
MEQ-E | → | PTH | a | −22.341 | 3.0735 | −27.964 | −15.984 | −7.27 | <0.001 | |
PTH | → | HAM-D | b | 0.231 | 0.0656 | 0.108 | 0.371 | 3.51 | <0.001 | |
MEQ-E | → | HAM-D | c | −15.046 | 2.8577 | −20.508 | −8.946 | −5.26 | <0.001 | |
c. Mediation HAM-A. | ||||||||||
95% Confidence Interval | ||||||||||
Effect | Label | Estimate | SE | Lower | Upper | Z | p | % Mediation | ||
Indirect | a × b | −3.16 | 1.24 | −5.89 | −1.14 | −2.56 | 0.01 | 27.5 | ||
Direct | c | −8.32 | 2.05 | −12.13 | −4.18 | −4.07 | <0.001 | 72.5 | ||
Total | c + a × b | −11.48 | 1.72 | −14.85 | −8.15 | −6.66 | <0.001 | 100 | ||
Path Estimates | ||||||||||
95% Confidence Interval | ||||||||||
Label | Estimate | SE | Lower | Upper | Z | p | ||||
MEQ-E | → | PTH | a | −22.341 | 3.3179 | −28.6972 | −15.307 | −6.73 | <0.001 | |
PTH | → | HAM-A | b | 0.142 | 0.0477 | 0.0518 | 0.243 | 2.97 | 0.003 | |
MEQ-E | → | HAM-A | c | −8.318 | 2.0458 | −12.1337 | −4.181 | −4.07 | <0.001 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
de Filippis, R.; D’Angelo, M.; Carbone, E.A.; De Fazio, P.; Steardo, L., Jr. The Mediation Effect of Peripheral Biomarkers of Calcium Metabolism and Chronotypes in Bipolar Disorder Psychopathology. Metabolites 2022, 12, 827. https://doi.org/10.3390/metabo12090827
de Filippis R, D’Angelo M, Carbone EA, De Fazio P, Steardo L Jr. The Mediation Effect of Peripheral Biomarkers of Calcium Metabolism and Chronotypes in Bipolar Disorder Psychopathology. Metabolites. 2022; 12(9):827. https://doi.org/10.3390/metabo12090827
Chicago/Turabian Stylede Filippis, Renato, Martina D’Angelo, Elvira Anna Carbone, Pasquale De Fazio, and Luca Steardo, Jr. 2022. "The Mediation Effect of Peripheral Biomarkers of Calcium Metabolism and Chronotypes in Bipolar Disorder Psychopathology" Metabolites 12, no. 9: 827. https://doi.org/10.3390/metabo12090827
APA Stylede Filippis, R., D’Angelo, M., Carbone, E. A., De Fazio, P., & Steardo, L., Jr. (2022). The Mediation Effect of Peripheral Biomarkers of Calcium Metabolism and Chronotypes in Bipolar Disorder Psychopathology. Metabolites, 12(9), 827. https://doi.org/10.3390/metabo12090827