The Role of Resolvin D1 in Indicating Chronic Inflammation and Axonal Damage in Bipolar Disorder: A Comparative Study of Manic and Depressive Episodes

Overview

Journal Noro Psikiyatr Ars

Date 2025 Mar 6

PMID 40046207

Authors

Burcu Kok Kendirlioglu

Ozge Yuksel Oksuz

Tevfik Kalelioglu

Sule Sozen

Pelin Unalan Ozpercin

Refik Cihnioglu

Nesrin Karamustafalioglu

Affiliations

Soon will be listed here.

Abstract

Introduction: Bipolar disorder (BD) is a chronic disorder associated with significant psychiatric morbidity and disability. Recent research has linked inflammatory processes to the pathology of BD. Resolvin D1 (RvD1), an anti-inflammatory molecule derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has been shown to inhibit apoptosis and neuroinflammation, and promote neurogenesis. This study aims to determine changes in serum RvD1 levels between acute episode and euthymic periods in patients with BD and their association with inflammatory and metabolic syndrome (MetS) parameters.

Methods: This prospective clinical study was conducted with patients diagnosed with BD-I according to SCID-5. Patients whose serum RvD1 levels were assessed during manic and depressive episodes in the previous study were invited to return to the study after at least 8 weeks, when they had reached the euthymic period. Blood samples for RvD1, C-reactive protein (CRP), and hemogram tests were collected during both acute episodes and remission periods.

Results: The study included 32 patients in manic episodes, 27 in depressive episodes, and 41 healthy controls, with no significant age difference among the groups. RvD1 levels decreased significantly from manic episodes to complete remission period (p=0.017, z=-2.391) during follow-up. The decrease from depression to remission was not statistically significant. Serum RvD1 levels in patients with depressive episodes in remission remained high in the control group (p=0.581, z=-0.553). During the follow-up period, white blood cell (p=0.009, z=-2.606) and neutrophil (p=0.007, z=-2.693) in mania period and CRP values in depression period (p=0.004, z=-2.880) were found to have decreased statistically.

Conclusions: The study indicates that serum RvD1 levels are elevated during manic and depressive episodes in BD patients compared to healthy controls and decrease significantly during the remission period in patients with manic episode. We propose the potential utility of RvD1 as a diagnostic marker for identifying manic and depressive states. We can assume that there is an inflammatory process in BD in which RvD1 also plays a role. Further research is needed to explore the therapeutic potential of targeting RvD1 pathways in BD treatment.

References

Deyama S, Ishikawa Y, Yoshikawa K, Shimoda K, Ide S, Satoh M . Resolvin D1 and D2 Reverse Lipopolysaccharide-Induced Depression-Like Behaviors Through the mTORC1 Signaling Pathway. Int J Neuropsychopharmacol. 2017; 20(7):575-584. PMC: 5492780. DOI: 10.1093/ijnp/pyx023. View

McNamara R, Jandacek R, Tso P, Blom T, Welge J, Strawn J . First-episode bipolar disorder is associated with erythrocyte membrane docosahexaenoic acid deficits: Dissociation from clinical response to lithium or quetiapine. Psychiatry Res. 2015; 230(2):447-53. PMC: 4655201. DOI: 10.1016/j.psychres.2015.09.035. View

Drew P, Chavis J . Female sex steroids: effects upon microglial cell activation. J Neuroimmunol. 2000; 111(1-2):77-85. DOI: 10.1016/s0165-5728(00)00386-6. View

Ishikawa Y, Deyama S, Shimoda K, Yoshikawa K, Ide S, Satoh M . Rapid and sustained antidepressant effects of resolvin D1 and D2 in a chronic unpredictable stress model. Behav Brain Res. 2017; 332:233-236. DOI: 10.1016/j.bbr.2017.06.010. View

Ho C, Ismail N, Koh J, Gunaseelan S, Low Y, Ng Y . Localisation of Formyl-Peptide Receptor 2 in the Rat Central Nervous System and Its Role in Axonal and Dendritic Outgrowth. Neurochem Res. 2018; 43(8):1587-1598. PMC: 6061218. DOI: 10.1007/s11064-018-2573-0. View

Young A, Juruena M . The Neurobiology of Bipolar Disorder. Curr Top Behav Neurosci. 2021; 48:1-20. DOI: 10.1007/7854_2020_179. View

McElroy S, Keck Jr P . Obesity in bipolar disorder: an overview. Curr Psychiatry Rep. 2012; 14(6):650-8. DOI: 10.1007/s11920-012-0313-8. View

Meinhard N, Kessing L, Vinberg M . The role of estrogen in bipolar disorder, a review. Nord J Psychiatry. 2013; 68(2):81-7. DOI: 10.3109/08039488.2013.775341. View

Furuyashiki T, Akiyama S, Kitaoka S . Roles of multiple lipid mediators in stress and depression. Int Immunol. 2019; 31(9):579-587. DOI: 10.1093/intimm/dxz023. View

10.

Das U . Polyunsaturated fatty acids and their metabolites in the pathobiology of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2012; 42:122-34. DOI: 10.1016/j.pnpbp.2012.06.010. View

11.

Kurosawa K, Terao T, Kanehisa M, Shiotsuki I, Ishii N, Takenaka R . Naturally absorbed polyunsaturated fatty acids, lithium, and suicide-related behaviors: A case-controlled study. J Affect Disord. 2018; 241:200-205. DOI: 10.1016/j.jad.2018.08.006. View

12.

Khan M, He L . The role of polyunsaturated fatty acids and GPR40 receptor in brain. Neuropharmacology. 2015; 113(Pt B):639-651. DOI: 10.1016/j.neuropharm.2015.05.013. View

13.

Leao F, Waltrick A, Verri Jr W, Cunha J, Zanoveli J . Resolvin D5 disrupts anxious- and depressive-like behaviors in a type 1 diabetes mellitus animal model. Naunyn Schmiedebergs Arch Pharmacol. 2022; 395(10):1269-1282. DOI: 10.1007/s00210-022-02274-8. View

14.

Hotamisligil G . Inflammation and metabolic disorders. Nature. 2006; 444(7121):860-7. DOI: 10.1038/nature05485. View

15.

Pomponi M, Pomponi M . Alzheimer's disease prevention & acetyl salicylic acid: a believable story. Indian J Med Res. 2014; 139(1):1-3. PMC: 3994724. View

16.

Laan M, Qvarfordt I, Riise G, Andersson B, Larsson S, Linden A . Increased levels of interleukin-16 in the airways of tobacco smokers: relationship with peripheral blood T lymphocytes. Thorax. 1999; 54(10):911-6. PMC: 1745375. DOI: 10.1136/thx.54.10.911. View

17.

Babic D, Maslov B, Martinac M, Nikolic K, Uzun S, Kozumplik O . Bipolar disorder and metabolic syndrome: comorbidity or side effects of treatment of bipolar disorder. Psychiatr Danub. 2010; 22(1):75-8. View

18.

Zhang Y, Wang J, Ye Y, Zou Y, Chen W, Wang Z . Peripheral cytokine levels across psychiatric disorders: A systematic review and network meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2023; 125:110740. DOI: 10.1016/j.pnpbp.2023.110740. View

19.

Li C, Birmaher B, Rooks B, Gill M, Hower H, Axelson D . High Prevalence of Metabolic Syndrome Among Adolescents and Young Adults With Bipolar Disorder. J Clin Psychiatry. 2019; 80(4). PMC: 6802953. DOI: 10.4088/JCP.18m12422. View

20.

Rasgon N, Bauer M, Glenn T, Elman S, Whybrow P . Menstrual cycle related mood changes in women with bipolar disorder. Bipolar Disord. 2003; 5(1):48-52. DOI: 10.1034/j.1399-5618.2003.00010.x. View