Leptin and Adiponectin in Patients with Depression: Clinical and Biochemical Interrelations

Background: leptin and adiponectin, having neurotrophic and immunomodulatory properties, are considered as potential links between metabolic disorders and mood disorders. However, data on their levels in depression remain contradictory. The aim was to study the relationship of leptin and adiponectin levels with the clinical characteristics of recurrent and bipolar depression. Patients, Participants and Methods: in a cross-sectional study conducted on the basis of the St. Petersburg State Medical Institution P.P. Kashchenko Hospital. St. Petersburg, 50 patients with a depressive episode (DE) with mood disorders and 35 participants without mental disorders participated. The Montgomery-Asberg scale was used to assess depression. Serum levels of leptin and adiponectin were determined by enzyme immunoassay. Results: patients with mood disorders with current DE did not differ from healthy controls in terms of leptin level, but had significantly lower level of adiponectin. In direct comparison, patients with current DE with bipolar and recurrent depression did not differ in hormone levels. Women with current DE had higher levels of leptin and adiponectin compared to men. In the healthy control group, there were no significant differences between men and women in hormone levels. Leptin levels in patients and healthy controls were positively associated with body mass index. Hormone levels were not associated with the age of onset of the disorder, the severity of depression, the duration of the disease and the current DE. Conclusions: a decrease of adiponectin level was revealed in patients with current DE in mood disorders, while the level of leptin remained unchanged. The observed effects were independent of the nosology and clinical characteristics of depression, but were modulated by the patient's gender. It is necessary to take into account gender characteristics when studying the relationship between mood disorders and metabolic disorders.

1. Malhi GS, Mann JJ. Depression. Lancet. 2018;392(10161):2299–2312. doi: 10.1016/S0140-6736(18)31948-2

2. Vancampfort D, Vansteelandt K, Correll CU, Mitchell AJ, De Herdt A, Sienaert P, Probst M, De Hert M. Metabolic syndrome and metabolic abnormalities in bipolar disorder: a meta-analysis of prevalence rates and moderators. Am J Psychiatry. 2013;170(3):265–274. doi: 10.1176/appi.ajp.2012.12050620

3. Platzer M, Fellendorf FT, Bengesser SA, Birner A, Dalkner N, Hamm C, Hartleb R, Queissner R, Pilz R, Rieger A, Maget A, Mangge H, Zelzer S, Reininghaus B, Kapfhammer HP, Reininghaus EZ. Adiponectin is decreased in bipolar depression. World J Biol Psychiatry. 2019;20(10):813–820. doi: 10.1080/15622975.2018.1500033

4. Bond DJ, Andreazza AC, Hughes J, Dhanoa T, Torres IJ, Kozicky JM, Young LT, Lam RW, Yatham LN. A longitudinal study of the relationships between mood symptoms, body mass index, and serum adipokines in bipolar disorder. J Clin Psychiatry. 2017;78(4):441–448. doi: 10.4088/JCP.15m10189

5. Lassale C, Batty GD, Baghdadli A, Jacka F, Sánchez-Villegas A, Kivimäki M, Akbaraly T. Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies. Mol Psychiatry. 2019;24(7):965–986. doi: 10.1038/s41380-018-0237-8

6. Fu X, Wang Y, Zhao F, Cui R, Xie W, Liu Q, Yang W. Shared biological mechanisms of depression and obesity: focus on adipokines and lipokines. Aging (Albany NY). 2023;15(12):5917–5950, doi: 10.18632/aging.204847

7. Aguilar-Valles A, Inoue W, Rummel C, Luheshi GN. Obesity, adipokines and neuroinfiammation. Neuropharmacology. 2015;96:124–134. doi: 10.1016/j.neuropharm.2014.12.023

8. Ercan SN, Sanlier N. The Role of Adipokines and Gene Polymorphisms in the Development of Obesity-Induced Depression. Curr Obes Rep. 2025;14(1):62. doi: 10.1007/s13679-025-00652-w

9. Park HK, Ahima RS. Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism. Metabolism. 2015 Jan;64(1):24–34. doi: 10.1016/j.metabol.2014.08.004

10. Obradovic M, Sudar-Milovanovic E, Soskic S, Essack M, Arya S, Stewart AJ, Gojobori T, Isenovic ER. Leptin and obesity: role and clinical implication. Front Endocrinol (Lausanne). 2021;12:585887. doi: 10.3389/fendo.2021.585887

11. Li Y, Onodera T, Scherer PE. Adiponectin. Trends Endocrinol Metab. 2024;35(7):674–675. doi: 10.1016/j.tem.2024.05.004

12. Parida S, Siddharth S, Sharma D. Adiponectin, obesity, and cancer: clash of the bigwigs in health and disease. Int J Mol Sci. 2019;20(10):2519. doi: 10.3390/ijms20102519

13. Shariq AS, Brietzke E, Rosenblat JD, Barendra V, Pan Z, McIntyre RS. Targeting cytokines in reduction of depressive symptoms: a comprehensive review. Prog Neuropsychopharmacol Biol Psychiatry. 2018;83:86–91. doi: 10.1016/j.pnpbp.2018.01.003

14. Cao B, Chen Y, Brietzke E, Cha D, Shaukat A, Pan Z, Park C, Subramaniapillai M, Zuckerman H, Grant K, Mansur RB, McIntyre RS. Leptin and adiponectin levels in major depressive disorder: a systematic review and meta-analysis. J Affect Disord. 2018;238:101–110, doi: 10.1016/j.jad.2018.05.008

15. Garza JC, Guo M, Zhang W, Lu XY. Leptin increases adult hippocampal neurogenesis in vivo and in vitro. J Biol Chem. 2008;283(26):18238–47. doi: 10.1074/jbc.M800053200

16. Song J, Kang SM, Kim E, Kim CH, Song HT, Lee JE. Adiponectin receptor-mediated signaling ameliorates cerebral cell damage and regulates the neurogenesis of neural stem cells at high glucose concentrations: an in vivo and in vitro study. Cell Death Dis. 2015;6:e1844. doi: 10.1038/cddis.2015.220

17. Misiak B, Stramecki F, Kasznia J, Lis M, Stańczykiewicz B. Adiponectin levels in patients with bipolar disorder: a systematic review and meta-analysis. Psychoneuroendocrinology. 2019;104:74–79. doi: 10.1016/j.psyneuen.2019.02.019

18. Ge T, Fan J, Yang W, Cui R, Li B. Leptin in depression: a potential therapeutic target. Cell Death Dis. 2018;9(11):1096. doi: 10.1038/s41419-018-1129-1

19. Zhang Y, Munshi S, Burrows K, Kuplicki R, FigueroaHall LK, Aupperle RL, Khalsa SS, Teague TK, Taki Y, Paulus MP, Savitz J, Zheng H. Leptin's inverse association with brain morphology and depressive symptoms: a discovery and confirmatory study across 2 independent samples. Biol Psychiatry Cogn Neurosci Neuroimaging. 2024;9(7):714–725. doi: 10.1016/j.bpsc.2024.04.005

20. Zhang D, Guo M, Zhang W, Lu XY. Adiponectin stimulates proliferation of adult hippocampal neural stem/progenitor cells through activation of p38MAPK/GSK-3β/β-catenin signaling cascade. J Biol Chem. 2011;286(52):44913–20, doi: 10.1074/jbc.M111.310052

21. Liu J, Guo M, Zhang D, Cheng SY, Liu M, Ding J, Scherer PE, Liu F, Lu XY. Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity. Proc Natl Acad Sci U S A. 2012;109(30):12248–53. doi: 10.1073/pnas.1202835109

22. Carvalho AF, Rocha DQ, McIntyre RS, Mesquita LM, Köhler CA, Hyphantis TN, Sales PM, Machado-Vieira R, Berk M. Adipokines as emerging depression biomarkers: a systematic review and meta-analysis. J Psychiatr Res. 2014;59:28–37. doi: 10.1016/j.jpsychires.2014.08.002

23. Fernandes BS, Dash S, Jacka F, Dodd S, Carvalho AF, Köhler CA, Steiner J, da Graça Cantarelli M, Nardin P, Gonçalves CA, Berk M. Leptin in bipolar disorder: a systematic review and meta-analysis. Eur Psychiatry. 2016;35:1–7. doi: 10.1016/j.eurpsy.2016.02.003

24. Farr OM, Tsoukas MA, Mantzoros CS. Leptin and the brain: influences on brain development, cognitive functioning and psychiatric disorders. Metabolism. 2015;64(1):114–30, doi: 10.1016/j.metabol.2014.07.004

25. Montgomery SA, Åsberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382–389. doi: 10.1192/bjp.134.4.382

26. Hung YJ, Hsieh CH, Chen YJ, Pei D, Kuo SW, Shen DC, Sheu WH, Chen YC. Insulin sensitivity, proinfiammatory markers and adiponectin in young males with different subtypes of depressive disorder. Clin Endocrinol (Oxf). 2007;67(5):784–9. doi: 10.1111/j.1365-2265.2007.02963.x

27. Huang KL, Chen MH, Hsu JW, Tsai SJ, Bai YM. Using classification and regression tree modeling to investigate appetite hormones and proinfiammatory cytokines as biomarkers to differentiate bipolar I depression from major depressive disorder. CNS Spectr. 2021:1–7. doi: 10.1017/S109285292100016X

28. Su SC, Sun MT, Wen MJ, Lin CJ, Chen YC, Hung YJ. Brain-derived neurotrophic factor, adiponectin, and proinfjmmatory markers in various subtypes of depression in young men. Int J Psychiatry Med. 2011;42(3):211–26. doi: 10.2190/PM.42.3.a

29. Cordas G, Gazal M, Schuch EM, Spessato BC, Branco J, Jansen K, Oses JP, Quevedo LA, Souza LD, Pinheiro RT, Portela LV, da Silva RA, Lara DR, Kaster MP, Ghisleni G. Leptin in depressive episodes: is there a difference between unipolar and bipolar depression? Neuroendocrinology. 2015;101(1):82–6. doi: 10.1159/000371803

30. Ma Z, Gingerich RL, Santiago JV, Klein S, Smith CH, Landt M. Radioimmunoassay of leptin in human plasma. Clin Chem. 1996;42:942–6. PMID: 8665687

31. Esel E, Ozsoy S, Tutus A, Sofuoglu S, Kartalci S, Bayram F, Kokbudak Z, Kula M. Effects of antidepressant treatment and of gender on serum leptin levels in patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29(4):565–70, doi: 10.1016/j.pnpbp.2005.01.009

32. Milano W, Ambrosio P, Carizzone F, De Biasio V, Di Munzio W, Foia MG, Capasso A. Depression and obesity: analysis of common biomarkers. Diseases. 2020;8(2):23. doi: 10.3390/diseases8020023

33. Morris AA, Ahmed Y, Stoyanova N, Hooper WC, De Staerke C, Gibbons G, Quyyumi A, Vaccarino V. The association between depression and leptin is mediated by adiposity. Psychosom Med. 2012;74(5):483–8. doi: 10.1097/PSY.0b013e31824f5de0

34. Khanna D, Khanna S, Khanna P, Kahar P, Patel BM. Obesity: a chronic low-grade infiammation and its markers. Cureus. 2022;14(2):e22711. doi: 10.7759/cureus.22711

35. Ragguett RM, Hanh M, Messina G, ChieffiS, Monda M, De Luca V. Association between antipsychotic treatment and leptin levels across multiple psychiatric populations: an updated meta-analysis. Hum Psychopharmacol. 2017;32(6). doi: 10.1002/hup.2631