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

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.

Keywords: Axonal degeneration; bipolar disorder; metabolic syndrome; neuroinflammation; resolvin D1.

Figure 1

Part A: There was a statistically significant difference in the first measurement of RvD1 values between the three groups (p <0.001, z=15.719, df=2). RvD1 levels in the control group were significantly lower than those in the mania and depression groups (after Bonferroni correction adjusted p=0.001, z=27.731; p=0.008, z=23.843, respectively). This difference remained significant between the mania and control groups even after adjustment for age, sex, body mass index, and smoking status (p=0.003, F=6.263, df=2). There was no statistically significant difference between the RvD1 measurements in the mania and depression groups (p=1, z=3.888). The values in the table are plotted on a logarithmic scale. Part B: When compared with the control group, a statistically significant difference was found between the groups in terms of the second RvD1 measurements (p=0.033, z=6.812, df=2). The serum RvD1 levels in the control group were significantly lower than those in the post-depression group (after Bonferroni correction adjusted p=0.044, z=17.521). This difference remained significant between the post-depression and control groups even after adjustment for age, sex, body mass index, and smoking status (p=0.021, F=4.049, df=2). There was no statistically significant difference between the patients in the post-mania and post-depression periods (p=1.000, z=-4.751) and the post-mania and control groups (p=0.186, z=12.770). The values in the table are plotted on a logarithmic scale. Part C: There was a significant difference between the first measurement of the acute episode and the second measurement of RvD1 when they reached the remission period in the mania group (p=0.017, z=-2.391, n=32). There was no significant difference between the first and second RvD1 measurements in the depression group (p=0.581, z=-0.553, n=27). The values in the table are plotted on a logarithmic scale.