TABLE 3.
Potential circulating cytokine biomarkers of stress and mood disorders
| Marker | Disorder | Changes | Clinical symptoms | References |
|---|---|---|---|---|
| IL‐1β (interleukin‐1) | BD | ↑ | Positive correlation with depressive symptoms (IDS‐30 score) | a Rao et al. (2010) and Vares et al., (2020) |
| — | Euthymic phase | Vares et al., (2020) | ||
| ↓ | Manic Phase | Ortiz‐Domínguez et al., (2007) | ||
| MDD | ↑ | Positive correlation with severity of the symptoms (HAM‐D) | Osimo et al., (2020) and Das et al. (2021) | |
| PTSD | ↑/— | Waheed et al. (2018) | ||
| ↑ |
Negative correlation with HIPP volume Inflammation load (high IL‐1β and IL‐6) correlates with symptom severity (re‐experiencing, arousal, CAPS and MADRS scores) |
Zimmerman et al. (2012) | ||
| IL‐4 (interleukin‐4) | BD | ↑/↓ |
Contradictions on manic phase Increase in euthymic phase |
Kim et al., (2007), Ortiz‐Domínguez et al., (2007), and Brietzke, Kauer‐Sant’Anna, et al., (2009) |
| MDD | ↓ | Decreases in suicide patients | Osimo et al., (2020) and Yuan et al., (2019) | |
| PTSD | ↑ | N/A | Guo et al., (2012) | |
| — | Yuan et al., (2019) | |||
| IL‐6 (interleukin‐6) | BD | ↑ | Manic and depressive phase, correlates with irritability and aggressivity in manic phase | Kim et al., (2007) and Brietzke, Kauer‐Sant’Anna, et al., (2009) |
| ↑ | Acute and remission phases | Pantović‐Stefanović et al., (2018) | ||
| MDD | ↑ | No association with depressive symptoms | Köhler et al., (2017) and Osimo et al., (2020) | |
| Mahajan et al., (2018) | ||||
| Associated with symptom severity (HAM‐D) | Carboni et al., (2019) | |||
| PTSD | ↑ | Brahmajothi and Abou‐Donia (2020) | ||
| ↑ | Anhedonia and avoidance correlation with PFC activation in patients with high levels, correlation with self‐reported resilience | Mehta et al., (2020) | ||
| TNF‐α (tumor necrosis factor alpha) | BD |
↑ — |
Manic phase | Kim et al., (2007), Goldsmith et al. (2016), and Brietzke, Stertz, et al. (2009) |
| — | Euthymic and depressive phase | Goldsmith et al. (2016) and Vares et al., (2020) | ||
| ↓ | Acute and remission phases | Pantović‐Stefanović et al., (2018) | ||
| MDD | ↑ | Köhler et al., (2017) and Osimo et al., (2020) | ||
| Correlation with symptoms severity (HAM‐D) | Das et al. (2021) | |||
| PTSD | ↑ | Correlation with self‐reported resilience | O'Donovan, Chao et al. (2015), Imai et al., (2019), and Brahmajothi and Abou‐Donia (2020) | |
| CRP (C‐reactive protein) | BD | ↑ | Manic phase | Evers et al. (2019) |
| — | No changes in all phases | Balukova et al. (2016) | ||
| MDD | ↑ |
Correlation with depression symptom severity (BDI‐II). Correlates with reduced functional connectivity of AMY and PFC (in comorbid PTSD or anxiety only) |
Powers et al. (2019) and Mehta et al., (2018) | |
| Significant association: baseline CRP and treatment (venlafaxine) response (HAM‐D), ♂ | Carboni et al., (2019) | |||
| PTSD | ↑ |
Negatively correlates with mPFC activation Positively correlates with dissociation symptoms, correlates with PTSD symptoms (CAPS) |
Mehta et al., (2020) and Powers et al. (2019) | |
| Michopoulos et al. (2015) | ||||
| Positive correlation with disease severity (re‐experiencing and arousal) | Farr et al., (2015) |
Abbreviations: BDI‐II, Beck Depression Inventory‐II; CAPS, Clinician‐Administered PTSD Scale;HAM‐D, Hamilton depression rating scale; HC, healthy controls; IDS‐30, Inventory of Depressive Symptoms; MADRS, Montgomery–Asberg Depression Rating Scale.
All markers measured in the blood, with the exception of one measurement from frontal cortex (post‐mortem tissue) (Rao et al., 2010).