Article Review: Neuroendocrine Interplay: How Hormones Shape Human Psychology and Mental Disorders
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This article examines the critical link between hormones and psychological states, essential for understanding mental health and behavior. It notes that aggressive behavior in psychiatric patients may stem from hormonal imbalances and surveys prevalent mental disorders worldwide—including anxiety disorders (excessive fear), depression (persistent low mood), bipolar disorder (extreme mood swings), PTSD (post-trauma effects), and schizophrenia (disrupted cognition and behavior), alongside eating and behavioral disorders. Affecting millions globally, these conditions highlight the need to explore their biological and psychological underpinnings.
Hormones, defined as chemical messengers from endocrine glands, regulate bodily functions via the bloodstream. Beyond simple signaling, they intricately modulate growth, metabolism, homeostasis, mood, and emotions. Key hormones influencing mental health include: serotonin (mood and anxiety regulation), cortisol (stress response), dopamine (reward and motivation), oxytocin (social bonding), melatonin (sleep cycles), and ghrelin/leptin (appetite control). Imbalances in these systems can trigger mental health disorders.
The article underscores that deciphering hormone-psychology interactions is vital for advancing mental health treatments and improving well-being.
1. Volavka J (ed): (2002) Neurobiology of Violence. 2nd edition.American Psychiatric Association Publishing, Washington, DC, .
2. Roh JW; Park HJ and Kang UG:(2007) Hormones and psychiatric Disorders. Clin Psychopharmacol Neurosci 5: 3-13, ..
3. Institute of Health Metrics and Evaluation. Global Health Data Exchange (GHDx). (Accessed 14 May 2022).
4. Charlson, F.; van Ommeren, M.; Flaxman, A.; Cornett, J.;Whiteford, H.; & Saxena, S.(2018) New WHO prevalence estimates of mental disorders in conflict settings: a systematic review and meta-analysis. Lancet. ;384,240–248.
5. Laursen TM; Nordentoft M; Mortensen PB.(2014) Excess early mortality in schizophrenia. Annual Review of Clinical Psychology;10,425-438.
6. Tortora GJ; Derrickson BH. (2017) Principles of anatomy and physiology. 15th ed. Hoboken, NJ: Wiley; .
7. Guyton AC; Hall JE. (2021) Guyton and Hall textbook of medical physiology. 14th ed. Philadelphia, PA: Elsevier; .
8. Layunta E; Latorre E; Grasa L; Arruebo MP; Buey B; Alcalde AI; Mesonero JE. (2022) Intestinal serotonergic system is modulated by Toll-like receptor 8. J Physiol Biochem. Aug;78(3):688-701.
9. Raghupathi R; Duffield MD; Zelkas L; Meedeniya A; Brookes SJ;Sia TC; Wattchow DA; Spencer NJ; Keating DJ.(2013) Identification of unique release kinetics of serotonin from guinea-pig and human enterochromaffin cells. J Physiol. Dec 01;581(23):5858-75.
10. Masand PS; Gupta S. (1988) Selective serotonin-reuptake inhibitors: an update. Harv Rev Psychiatry. Jul-Aug;7(2):68-84.
11. Micheli L; Ceccarelli M; D’Andrea G; Tirone F.(2018) Depression and adult neurogenesis: Positive effects of the antidepressant fluoxetine and of physical exercise. Brain Res Bull. Oct;143:181-183.
12. Strawn JR; Geracioti L; Rajdev N; Clemenza K; Levine A.(2018) Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: an evidence-based treatment review. Expert Opin Pharmacother. Jul;19(10):1057-1070.
13. Berger M; Gray JA; Roth BL.(2008) The expanded biology of serotonin. Annu Rev Med.;60:355-66.
14. Waraich P; Goldner E.M; Somers J.M; Hsu L.(2004) Prevalence and incidence studies of mood disorders: A systematic review of the literature. Can. J. Psychiatry. ;49:124–138. Doi:10.1177/070674370404900208.
15. Cleare A; Pariante C.M.; Young A.H.; Anderson I.M.; Christmas D.; Cowen P.J.; Dickens C.; Ferrier I.N.; Geddes J.; Gilbody S.; et al.(2015) Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2008 British Association for Psychopharmacology guidelines. J.Psychopharmacol.;28:458–525. Doi: 10.1177/0268881115581083.
16. Scotton WJ; Hill LJ; Williams AC; Barnes NM.(2018) Serotonin Syndrome: Pathophysiology, Clinical Features, Management, and Potential Future Directions. Int J Tryptophan Res. ;12:1178646818873825.
17. Ramamoorthy S; Cidlowski JA.(2016) Corticosteroids: Mechanisms of Action in Health and Disease. Rheum Dis Clin North Am. Feb;42(1):15-31, vii.
18. Kadmiel M; Cidlowski JA. (2013) Glucocorticoid receptor signaling in health and disease. Trends Pharmacol Sci. Sep;34(8):518-30.
19. Slaney T. R.; Mabrouk O. S.; Porter-Stransky K. A.; Aragona B. J.; Kennedy R. T. (2013) Chemical gradients within brain extracellular space measured using low flow push-pull perfusion sampling in vivo. ACS Chemical Neuroscience. ;4(2):321–328.
20. Calabresi P.; Picconi B.; Tozzi A.; Di Filippo M.(2007) Dopamine-mediated regulation of corticostriatal synaptic plasticity. Trends in Neurosciences. ;30(5):211–218.
21. An J. H.; Oh B.-K.; Choi J. W.(2013) Detection of tyrosine hydroxylase in dopaminergic neuron cell using gold nanoparticles-based barcode DNA. Journal of Biomedical Nanotechnology.;8(4):638–643.
22. Tolleson C.; Claassen D.(2012) The function of tyrosine hydroxylase in the normal and Parkinsonian brain. CNS and Neurological Disorders—Drug Targets. ;11(4):381–386.
23. Müller T. (2015) Catechol-o-methyltransferase inhibitors in Parkinson’s disease. Drugs. ;75:157–174.
24. Schmitt K. C.; Rothman R. B.; Reith M. E. (2013) Nonclassical pharmacology of the dopamine transporter: atypical inhibitors, allosteric modulators, and partial substrates. Journal of Pharmacology and Experimental Therapeutics. ;346(1):2–10.
25. Chen S.; Zhang X. J.; Xie W. J.; Qiu H. Y.; Liu H.; Le W. D.(2015) A new VMAT-2 inhibitor NBI-641448 in the treatment of huntington disease. CNS Neuroscience & Therapeutics.;21(8):662–671.
26. Wise, R. A. (2004). Dopamine, learning and motivation. Nature Reviews Neuroscience, 5(6), 483-484.
27. Schultz, W. (2015). Neuronal reward and decision signals: from theories to data.
28. Berridge, K. C. (2007). The debate over dopamine’s role in reward: the case for incentive salience. Psychopharmacology, 181(3), 381-431.
29. Montague, P. R.; Dayan, P.; & Sejnowski, T. J. (1996). A framework for mesencephalic dopamine systems based on predictive Hebbian learning. Journal of Neuroscience, 16(5), 1936-1947.
30. Gray’s Anatomy:(2015) The Anatomical Basis of Clinical Practice (41 ed.). Elsevier Health Sciences. . p. 358. ISBN 878-0-7020-6851-5.
31. Audunsdottir K; Quintana DS (2022). “Oxytocin’s dynamic role across the lifespan”. Aging Brain. 2: 100028. doi:10.1016/j.nbas.2021.100028. ISSN 2588-8588. PMC 8887153. PMID 36808876. S2CID 246314607.
32. Leng G; Leng RI (November 2021). “Oxytocin: A citation network analysis of 10 000 papers”. Journal of Neuroendocrinology. 33 (11) 52.Francis DD; Young LJ; Meaney MJ; Insel TR (May 2002). “Naturally occurring differences in maternal care are associated with the expression of oxytocin and vasopressin (V1a) receptors: gender differences”. Journal of Neuroendocrinology. 14 (5): 348–53.
33. Rogers K (7 July 2023). “Oxytocin”. Encyclopædia Britannica.
34. Uvnas-Moberg K; Ekstrom-Bergstrom A; Berg M; Buckley S; Pajalic Z; Hadjigeorgiou E; Kotlowska A; Lengler L; Kielbratowska B; Leon-Larios F; Magistretti CM; Downe S; Lindstrom B; Dencker A:(2019) Maternal plasma levels of oxytocin during physiological childbirth - a systematic review with implications for uterine contractions and central actions of oxytocin. BMC Pregnancy Childbirth. Aug 9;19(1):285.
35. Chiras DD (2012). Human Biology (7th ed.). Sudbury, MA: Jones & Bartlett Learning. p. 262.
36. Arrowsmith S; Wray S:(2014) Oxytocin: its mechanism of action and receptor signalling in the myometrium. J Neuroendocrinol.Jun;26(6):356-68. doi: 10.1111/jne.12154.
37. Caicedo Mera JC; Cárdenas Molano MA; García López CC; Acevedo Triana C; Martínez Cotrina J.(2021) Discussions and perspectives regarding oxytocin as a biomarker in human investigations. Heliyon. 2021;7:e08288. doi: 10.1016/j.heliyon..e08288.
38. Carmassi C; Marazziti D; Mucci F; et al.(2021) Decreased Plasma Oxytocin Levels in Patients With PTSD. Front Psychol;12:612338. doi: 10.3388/fpsyg.612338 .
39. Ferreira AC; Osório FL. (2022) Peripheral oxytocin concentrations in psychiatric disorders - A systematic review and methanalysis:Further evidence. Prog Neuropsychopharmacol Biol Psychiatry. ;117:110561. doi: 10.1016/j.pnpbp.110561.
40. Cataldo I; Azhari A; Lepri B; Esposito G.(2018) Oxytocin receptors (OXTR) and early parental care: An interaction that modulates psychiatric disorders. Res Dev Disabil;82:27–38.
41. Quintana DS; Lischke A; Grace S; Scheele D; Ma Y; Becker B. (2021)Advances in the field of intranasal oxytocin research: lessons learned and future directions for clinical research. Mol Psychiatry;26:80–91.
42. “Role of endorphins discovered”. PBS Online: A Science Odyssey:(2008) People and Discoveries. public Broadcasting System.January 1, 1998. Archived from the original on 2019-05-14.Retrieved 2008-10-15
43. Stefano GB; Ptáček R; Kuželová H; Kream RM (2012).“Endogenous morphine: up-to-date review 2011” (PDF). FoliaBiol. (Praha). C. 58 p. 2: 49–56. PMID:22578954. Archived from the original (PDF) on 2018-03-28.
44. Alonso J.; Mortier P.; Auerbach R.P.; Bruffaerts R.; Vilagut G.;Cuijpers P.; Demyttenaere K.; Ebert D.D.; Ennis E.; Gutiérrez-García R.A.; et al.(2018) Severe role impairment associated with mental disorders: Results of the WHO World Mental Health Surveys International College Student Project. Depress. Anxiety;35:802–814.
45. Panerai A.E.; Vecchiet J.; Panzeri P.; Meroni P.; Scarone S.;Pizzigallo E.; Giamberardino M.A.; Sacerdote P.(2002) Peripheral blood mononuclear cell beta-endorphin concentration is decreased in chronic fatigue syndrome and fibromyalgia but not in depression: Preliminary report. Clin. J. Pain;18:270–273.
46. Mathieu-Kia A.M.; Fan L.Q.; Kreek M.J.; Simon E.J.; Hiller J.M.(2001) Mu-, delta- and kappa-opioid receptor populations are differentially altered in distinct areas of postmortem brains of Alzheimer’s disease patients. Brain Res;893:121–134.
47. Markus RP; Fernandes PA; Kinker GS; Cruz-Machado SdS;Marçola M. (2018) Immune-pineal axis – acute inflammatory responses coordinate melatonin synthesis by pinealocytes and phagocytes. Br J Pharmacol:175:3239–50.
48. Simonneaux V; Ribelayga C.(2003) Generation of the melatonin endocrine message in mammals: a review of the complex regulation of melatonin synthesis by norepinephrine, peptides, and other pineal transmitters. Pharmacol Rev. 55:325–95.
49. Hidalgo MPL; Caumo W; Dantas G; Franco DG; Torres IL;da S; Pezzi J, et al.(2011) 6-Sulfatoxymelatonin as a predictor of clinical outcome in depressive patients. Hum Psychopharmacol Clin Exp.26:252–7.
50. Jury Freitas J; Bertuol Xavier N; Comiran Tonon A; Carissimi A; Timm Pizutti L; Vieira Ilgenfritz CA; et al. (2019) 6-Sulfatoxymelatonin predicts treatment response to fluoxetine in major depressive disorder. Ther Adv Psychopharmacol.9:2045125319881927.
51. Otsuka T; Kawai M,; Togo Y; Goda R; Kawase T; Matsuo H; et al. (2014) Photoperiodic responses of depression-like behavior, the brain serotonergic system, and peripheral metabolism in laboratory mice. Psychoneuroendocrinology.40:37–47.
52. Stefanovic B; Spasojevic N; Jovanovic P; Dronjak S.(2019) Melatonin treatment affects changes in adrenal gene expression of catecholamine biosynthesizing enzymes and norepinephrine transporter in the rat model of chronic-stress-induced depression. Can J Physiol Pharmacol.97:685–90.
53. Vega-Rivera NM; Ortiz-López L; Granados-Juárez A; Estrada-Camarena EM; Ramírez-Rodríguez GB.(2020) Melatonin reverses the depression-associated behaviour and regulates microglia, fractalkine expression and neurogenesis in adult mice exposed to chronic mild stress. Neuroscience. 440:316–36.
54. Crescenzo FD; Lennox A; Gibson JC; Cordey JH; Stockton S; Cowen PJ; et al. (2017) Melatonin as a treatment for mood disorders: a systematic review. Acta Psychiatr Scand.136:549–58.
55. Auger RR; Burgess HJ; Emens JS; Deriy LV; Thomas SM;Sharkey KM. (2015) . An Update for 2015: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med.11:1199–236.
56. Sletten TL; Magee M; Murray JM; Gordon CJ; Lovato N; Kennaway DJ; et al.(2018) Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: a double-blind, randomised clinical trial. PLoS Med.15:e1002587.
57. Ferracioli-Oda E; Qawasmi A; Bloch MH. (2013) Meta-analysis: melatonin for the treatment of primary sleep disorders. PLoS ONE. 8:e63773.
58. Inui A; Asakawa A; Bowers CY;et al .(2004) “Ghrelin,appetite, and gastric motility: the emerging role of the stomach as an endocrine organ”.
59. Cummings DE; Weigle DS; Frayo RS; Breen PA; Ma MK; Dellinger EP; Purnell JQ (2002). “Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery”.
60. Kojima M; Hosoda H; Date Y; Nakazato M; Matsuo H; Kangawa K (1999). “Ghrelin is a growth-hormone-releasing acylated peptide from stomach”.
61. Liira J; Verbeek JH; Costa G; Driscoll TR; Sallinen M; Isotalo LK; et al.(2014) Pharmacological interventions for sleepiness and sleep disturbances caused by shift work. Cochrane Database Syst Rev.8:CD009776.
62. Atcha Z; Chen WS; Ong AB; Wong FK; Neo A; Browne ER; Witherington J; Pemberton DJ (2009). “Cognitive enhancing effects of ghrelin receptor agonists”.
63. Schellekens H; Finger BC; Dinan TG; Cryan JF.(2012) Ghrelin signalling and obesity: at the interface of stress, mood and food reward. Pharmacol Ther;135:316–326.
64. Matsuo K; Nakano M; Nakashima M; Watanuki T; Egashira K; Matsubara T; Watanabe Y.(2012) Neural correlates of plasma acylated ghrelin level in individuals with major depressive disorder. Brain es;1473:185–192.
65. Ozsoy S; Besirli A; Abdulrezzak U; Basturk M.(2014) Serum ghrelin and leptin levels in patients with depression and the effects of treatment. Psychiatry Investig;11:167–172.
66. Castañeda TR; Tong J; Datta R; Culler M; Tschöp MH (2010). “Ghrelin in the regulation of body weight and metabolism”.
67. Diano S; Farr SA; Benoit SC; McNay EC; da Silva I; Horvath B; Gaskin FS; Nonaka N; Jaeger LB; Banks WA; Morley JE; Pinto S; Sherwin RS; Xu L; Yamada KA; Sleeman MW; Tschöp MH; Horvath TL (2006). “Ghrelin controls hippocampal spine synapse density and memory performance”.
68. Mundey K; Benloucif S; Harsanyi K; Dubocovich ML; Zee PC. (2005) Phase-dependent treatment of delayed sleep phase syndrome with melatonin. Sleep.28:1271–8.
69. Kluge M; Schussler P; Schmid D; Uhr M; Kleyer S; Yassouridis A; Steiger A.(2009) Ghrelin plasma levels are not altered in major depression. Neuropsychobiology;59:199–204.
70. Ribeiro R; Vasconcelos A; Costa S; Pinto D; Morais A; Oliveira J; Lobo F; Lopes C; Medeiros R (2004). “Overexpressing leptin genetic polymorphism (-2548 G/A) is associated with susceptibility to prostate cancer and risk of advanced disease”. Prostate.
71. Otsuka R; Yatsuya H; Tamakoshi K; Matsushita K; Wada K; Toyoshima H (2006). “psychological stress and serum leptin concentrations in Japanese men”. Obesity (Silver Spring).
72. Nakashima K; Akiyoshi J; Hatano K; Hanada H; Tanaka Y; Tsuru J; Matsushita H; Kodama K; Isogawa K.(2008) Ghrelin gene polymorphism is associated with depression, but not panic disorder. Psychiatr Genet;18:257.
73. Lutter M; Sakata I; Osborne-Lawrence S; Rovinsky SA; Anderson JG; Jung S; Birnbaum S; Yanagisawa M; Elmquist JK; Nestler EJ; et al.(2008) The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress. Nat Neurosci;11:752–753.
74. Häfner S; Baumert J; Emeny RT; Lacruz ME; Thorand B; Herder C; Koenig W; Rupprecht R; Ladwig KH. (2012) Sleep disturbances and depressed mood: a harmful combination associated with increased leptin levels in women with normal weight. Biol Psychol.;89:163–169.
75. Kristenssson E; Sundqvist M; Astin M; Kjerling M; Mattsson H; Dornonville de la Cour C; Håkanson R; Lindström E.(2006) Acute psychological stress raises plasma ghrelin in the rat. Regul Pept;134:114–117.
76. Chuang JC; Zigman JM.(2010) Ghrelin’s Roles in Stress, Mood, and Anxiety Regulation. Int J Pept;2010:460549.
77. Irizarry L (2014). “Thyroid Hormone Toxicity”. Medscape. WedMD LLC.
78. Samuels MH.(2014) Psychiatric and cognitive manifestations of hypothyroidism. Curr Opin Endocrinol Diabetes Obes;21:377–383.
79. Lutter M; Sakata I; Osborne-Lawrence S; Rovinsky SA; Anderson JG; Jung S; Birnbaum S; Yanagisawa M; Elmquist JK; Nestler EJ; et al.(2008) The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress. Nat Neurosci;11:752–753.
80. Esel E; Ozsoy S; Tutus A; Sofuoglu S; Kartalci S; Bayram F; Kokbudak Z; Kula M. (2005) Effects of antidepressant treatment and of gender on serum leptin levels in patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry;29:565–570.
81. Dictionary of Chemistry Terms (in Arabic, English, and French) (1st edition), Damascus: Arabic Language Academy in Damascus, (2014).
82. Samuels MH.(2014) Psychiatric and cognitive manifestations of hypothyroidism. Curr Opin Endocrinol Diabetes Obes;21:377–383.
83. Asher R. Br Med J.(1949) Myxoedematous madness;2:555–562.
84. Mason GA; Bondy SC; Nemeroff CB; Walker CH; Prange AJ Jr. (1987) Psychoneuroendocrinology.The effects of thyroid state on beta-adrenergic and serotonergic receptors in rat brain.;12:261–270.
85. Baker ME (2013). “What are the physiological estrogens?”. Steroids.
