Table 4.
Studies of state related changes in inflammatory markers in persons with mood disorders.
| Author, Year | Sample | Number of Inflammatory and Related Markers | State-Related Findings | Type I Error Management |
|---|---|---|---|---|
| Tsai SY et al., 2001 | 31 inpatients with mania (mean YMRS 34) and during subsequent remission (mean YMRS 4) and 31 healthy controls | 2: sIL-2R, sIL-6R | Higher sIL-2R in mania than remission. YMRS scores correlated with sIL-2R levels. | No single primary hypothesis or control for multiple comparisons. |
| Liu H-C et al., 2004 | 52 persons with mania (mean YMRS 35) followed to remission (mean YMRS 5) and matched healthy controls (expanded Su KP et al., 2002 sample). | 7: IL-1RA, sCD4, sCD8, IFN-γ, IL-2, IL-4, IL-10 | Not statistically assessed although values of IL-1RA and IL-4 decreased by at least 25%. | Hypothesized pattern of cell-mediated immunity impairment with mania. No single primary hypothesis or control for multiple comparisons. |
| O'Brien SM et al., 2006 | 21 persons with bipolar disorder (12 with mania and 9 with depression) and 21 controls | 5: IL-6, sIL-6R, IL-8, IL-10, TNF-α | Higher TNF-α with mania than depression. IL-8 greater with depression than mania. | No primary hypothesis or control for multiple comparisons. |
| Dickerson F et al., 2007 | 122 outpatients with bipolar disorder in various mood states and 165 controls | 1: CRP | CRP associated with YMRS score (mania) and YMRS threshold of > 6. | No primary hypothesis or control for multiple comparisons across continuoius and dichotomized psychopathology measures. |
| Ortiz-Dominguez A et al., 2007 | 20 patients with bipolar 1 (10 with mania and mean YMRS of 30 and 10 with depression and mean HDRS of 23) and 33 controls | 5: TNF-α, IL-1β, IL-2, IL-4, IL-6 | Higher IL-4 with mania compared to depression, higher IL-1β and IL-6 with depression compared to mania. | No primary hypothesis or control for multiple comparisons |
| Cunha AB et al., 2008 | 80 patients with bipolar disorder (30 with mania and mean YMRS of 35, 30 with euthymia, and 20 with depression and mean HDRS of 23) and 32 controls | 1: CRP | Higher hsCRP with mania compared to depression or euthymia. | N/A |
| De Berardis D et al. 2008 | 90 patients with bipolar I disorder (30 with mania and mean YMRS of 32, 30 euthymic, 30 with depression and mean HDRS of 25) and 30 controls | 1: CRP | CRP levels higher with mania and depression compared to euthymia. CRP correlated with YMRS in mania and HDRS in depression. | No correction for two hypotheses (CRP and total cholesterol). |
| Brietzke E et al., 2009 | 61 patients with bipolar disorder (23 with mania and mean YMRS 33, 14 euthymic, and 24 with depression and mean HDRS 20) and 25 controls | 6: TNF-α, IL-2, IL-4, IL-6, IL-10, IFN-γ | Elevated IL-2, IL-4, and IL-6 with mania vs. controls. Elevated Il-6 with depression vs. controls. Manic symptoms correlated with IL-6 and IL-2, depressive symptoms correlated with IL-2. | Bonferroni correction for multiple comparisons. |
| Hope S et al., 2011 | 112 patients with bipolar disorder (58 depressed, 26 euthymic, 17 “elevated” with mean YMRS only 7.8), 153 with schizophrenia, and 239 controls | 6: sTNF-R1, IL-1RA, IL-6, hsCRP, OPG, vWf | Lower OPG and IL-6 with depression relative to euthymia. Lower sTNF-R1 and IL-1Ra with depression relative to mania. | No primary hypothesis or control for multiple comparisons. |
| Fontoura PC et al., 2012 | 28 patients with bipolar disorder (9 with mania, 10 with euthymia, and 9 with depression) and 12 controls | 1 inflammatory (several others for nitric oxide signaling and antioxidant activity) | CRP elevated in mania compared with all other groups. Superoxide dismutase activity higher with mania. | Bonferroni correction for multiple comparisons. |
| Tsai SY et al., 2012 | 33 patients with bipolar I and mania (YMRS>26), some followed to partial or full remission, and 33 controls | 3: hsCRP, IL-1RA, sTNF-R1 | hsCRP higher for those in full remission than partial remission, but not mania. IL-1Ra higher with mania (marginally) and partial remission than full remission. | No primary hypothesis or control for multiple comparisons. |
| Barbosa IG et al., 2014 | 46 patients with bipolar disorder (23 with mania and mean YMRS of 26, and 23 with euthymia and mean YMRS of 1) and 23 controls. | 2: IL-33, sST2 | None identified. | No primary hypothesis or control for multiple comparisons. |
| Bai YM et al. 2014 | 130 patients with bipolar disorder (I or II, various states) and 130 normal subjects | 6: sIL-6R, sIL-2R, CRP, sTNF-R1, sP-selectin, MCP-1 | Lower sTNF-R1 with bipolar II vs. bipolar I disorder and depression vs. manic/hypomanic/euthymic. | No primary hypothesis or control for multiple comparisons. |
The following studies were identified from systematic review of PubMed using search terms for major depression or bipolar disorder and inflammation (limit=human) and review of references from selected articles. Studies not designed to assess the impact of specific mood states in a mood disorder (e.g. no comparison to normal mood state in those with mood disorder) are not included. In the case of duplicate publications of the same sample, the most recent sample was selected. Those studies focused on changes in response to a particular treatment (e.g. lithium, sertraline) were also excluded.
Abbreviations: CRP=C-reactive protein, HDRS=Hamilton Depression Rating Scale, hsCRP=highly sensitive CRP, IFN-γ=interferon gamma, IL=interleukin, IL-1RA=interleukin-1 receptor antagonist, MCP-1=monocyte chemotactic protein-1, OPG= osteoprotegerin, sCD4=soluble CD4, sCD8=soluble CD8, sIL-2R=soluble interleukin-2 receptors, sIL-6R=soluble interleukin-6 receptors, sP-selectin=soluble P-selectin receptor, sST2=soluble receptor ST2, sTNF-R1=soluble tumor necrosis factor receptor 1, TNF-α=tumor necrosis factor alpha, vWF=von Willebrand factor, YMRS=Young Mania Rating Scale