Evaluation of Morning and Evening Serum Melatonin Levels in Generalized Anxiety Disorder

Öz

Objective: Melatonin is a key regulator of circadian rhythm and has been suggested to be associated with psychiatric disorders. Evidence regarding the relationship between melatonin and generalized anxiety disorder (GAD) remains limited and methodologically heterogeneous. This study aimed to compare morning and evening serum melatonin levels in patients with GAD and healthy controls. Materials and Methods: This cross-sectional, observational case–control study included 35 patients diagnosed with GAD according to DSM-5-TR criteria and 50 healthy individuals. Venous blood samples were collected at 10:00 AM and 10:00 PM from different participant groups. Serum melatonin levels were measured using the ELISA method. Between-group comparisons were performed using the Welch-corrected independent samples t-test. Results: No significant difference was observed between groups in morning melatonin levels (p=0.183). Evening measurements also showed no statistically significant difference between groups (p=0.053). A significant morning–evening difference was observed in the control group (p=0.01), whereas no significant difference was found in the GAD group (p=0.71). A statistically significant difference in Δ values was observed between the groups (p=0.03). Conclusion: Absolute serum melatonin levels in patients with generalized anxiety disorder (GAD) were not found to differ from those of healthy individuals. However, the absence of the physiological evening increase observed in the control group may indicate a potential alteration in circadian melatonin organization in the GAD group. This finding should be confirmed by further studies involving repeated within-subject measurements and multi-time-point sampling.

Anahtar Kelimeler

• Generalized anxiety disorder
• melatonin
• circadian rhythm
• serum melatonin level
• case-control study

Yaygın Anksiyete Bozukluğunda Sabah ve Akşam Serum Melatonin Düzeylerinin Değerlendirilmesi

Öz

Amaç: Melatonin, sirkadiyen ritmin temel düzenleyicilerinden biri olup psikiyatrik bozukluklarla ilişkili olabileceği düşünülmektedir. Yaygın Anksiyete Bozukluğu (YAB) ile melatonin arasındaki ilişkiye dair bulgular sınırlı ve yöntemsel olarak heterojendir. Bu çalışmada, YAB hastaları ile sağlıklı kontrollerde sabah ve akşam serum melatonin düzeylerinin karşılaştırılması amaçlandı. Gereç ve Yöntem: Bu kesitsel, gözlemsel hasta–kontrol çalışmasına DSM-5-TR tanı kriterlerine göre YAB tanısı alan 35 hasta ve 50 sağlıklı birey dahil edildi. Venöz kan örnekleri sabah saat 10:00 ve akşam saat 22:00’de farklı katılımcı gruplarından elde edildi. Serum melatonin düzeyleri ELISA yöntemi ile ölçüldü. Gruplar arası karşılaştırmalarda Welch düzeltmeli bağımsız örneklem t-testi kullanıldı. Bulgular: Sabah melatonin düzeyleri açısından gruplar arasında anlamlı fark saptanmadı (p=0,183). Akşam ölçümlerinde gruplar arasında fark istatistiksel olarak anlamlı değildi (p=0,053). Kontrol grubunda sabah–akşam farkı anlamlı iken (p=0,01), YAB grubunda anlamlı bulunmadı (p=0,71). Gruplar arasında Δ değerleri açısından istatistiksel olarak anlamlı fark saptandı (p=0,03). Sonuç: YAB hastalarında mutlak serum melatonin düzeyleri sağlıklı bireylerden farklı bulunmamıştır. Bununla birlikte kontrol grubunda gözlenen fizyolojik akşam artışının YAB grubunda belirgin olmaması, sirkadiyen melatonin organizasyonunda olası bir farklılığa işaret edebilir. Bu bulgunun birey içi tekrarlı ölçümler ve çok zamanlı örnekleme içeren ileri çalışmalarla doğrulanması gerekmektedir.

Anahtar Kelimeler

• Yaygın anksiyete bozukluğu
• melatonin
• sirkadiyen ritim
• serum melatonin düzeyi
• hasta-kontrol çalışması

Kaynakça

1. 1. Hattori A, Suzuki N. Receptor-mediated and receptor-independent actions of melatonin in vertebrates. Zool Sci 2024;41(1):105-16. DOI: https://doi.org/10.2108/zs230057
2. 2. Sharo H, Amann Y, Woźniak S. The negative effect on human health due to disruption of circadian rhythm in modern times. Med J Cell Biol 2024; 12 (1): 21-5. DOI: 10.2478/acb-2024-0002
3. 3. Asefy Z, et al. Melatonin hormone as a therapeutic weapon against neurodegenerative diseases. Cell Mol Biol 2021;67(3):99-105. DOI: http://dx.doi.org/10.14715/cmb/2021.67.3.13
4. 4. Ikram M, et al. Melatonin as a Potential Regulator of Oxidative Stress, and Neuroinflammation: Mechanisms and Implications for the Management of Brain Injury-Induced Neurodegeneration. J Inflamm Res 2021;14:6251-64. DOI: 10.2147/JIR.S334423.
5. 5. Hickie IB, Crouse JJ. Sleep and circadian rhythm disturbances: plausible pathways to major mental disorders?. World Psychiatry 2024; 23:150-1. DOI: 10.1002/wps.21154
6. 6. Geoffroy P, Maruani J. Chronobiology of Mood Disorders: The Role of the Biological Clock in Depression and Bipolar Disorder. Biol Psychiatry 2025; 98:830-41. DOI: https://doi.org/10.1016/j.biopsych.2025.05.005.
7. 7. Bitzer-Quintero OK, et al. Psycho-Neuro-Endocrine-Immunology: A Role for Melatonin in This New Paradigm. Molecules 2022;27(15):4888. DOI: https://doi.org/10.3390/molecules27154888
8. 8. Won E, Na K-S, Kim Y-K. Associations between Melatonin, Neuroinflammation, and Brain Alterations in Depression. Int J Mol Sci 2022; 23(1):305. DOI: 10.3390/ijms23010305

9. 9. Tonon AC, et al. Melatonin and Depression: A Translational Perspective From Animal Models to Clinical Studies. Front. Psychiatry 2021;12:638981. DOI: 10.3389/fpsyt.2021.638981
10. 10. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Text Revision (DSM-5-TR). Washington (DC): American Psychiatric Association; 2022. DOI: https://doi.org/10.1176/appi.books.9780890425787
11. 11. Tafet GE, Nemeroff CB. The links between stress and depression: Psychoneuroendocrinological perspectives. J Neuropsychiatry Clin Neurosci 2016;28(2):77-88. DOI: 10.1176/appi.neuropsych.15030053
12. 12. Zanoaga MD, et al. Brainwide Mendelian Randomization Study of Anxiety Disorders and Symptoms. Biol Psychiatry 2024:15;95(8):810-17. DOI: 10.1016/j.biopsych.2023.11.006
13. 13. Peng J, et al. Temporal network of experience sampling methodology identifies sleep disturbance as a central symptom in generalized anxiety disorder. BMC Psychiatry 2024;24(241):2-11. DOI: 10.1186/s12888-024-05698-z
14. 14. Amini SN, et al. Beyond cognition and sleep: Stop the domino effect. J Exp Clin Med 2023;40(1): 132-149. DOI: 10.52142/omujecm.40.1.28
15. 15. Cox RC, et al. Diurnal variation in anxiety and activity is influenced by chronotype and probable anxiety-related disorder status. Psychiatry Res 2024;338(116006): 1-10. DOI: 10.1016/j.psychres.2024.116006
16. 16. Zisapel N, Tarrasch R, Laudon M. The relationship between melatonin and cortisol rhythms: clinical implications of melatonin therapy. Drug Dev Res 2025;65:119-25. DOI: https://doi.org/10.1002/ddr.20014
17. 17. Cardinali DP, Brown GM, Pandi-Perumal SR. Melatonin's Benefits and Risks as a Therapy for Sleep Disturbances in the Elderly: Current Insights. Nat Sci Sleep 2022;14(14):1843-55. DOI: 10.2147/NSS.S380465
18. 18. Lyman KM, McClung CA. Keeping time: investigating the relationship between circadian rhythm and mood disorders via precise circadian measurement techniques. Research Directions: Depression 2025;2(e6):1–8. DOI: 10.1017/dep.2025.10002
19. 19. Harsanyi S, Kupcova I, Csobonyeiova M, Klein M. Salivary hormones in depression: the future in diagnosis and treatment. Ann Gen Psychiatry 2025; 24(9): 1-11. DOI: https://doi.org/10.1186/s12991-025-00548-y
20. 20. Axelsson J, Balter LJ. Associations between chronotype and psychiatric symptoms across the adult lifespan. Transl Psychiatry 2025;15(522):1-9. DOI: https://doi.org/10.1038/s41398-025-03782-w