Table 2. List of representative chemokines that have been linked to mental disorders.

Chemokines	Key cellular characters and pathophysiological function	Mental disorders	Evidence supporting the potential link between chemokines and mental disorder
CCL: chemokine (C-C motif) ligand; CXCL: chemokine (C-X-C motif) ligand; MDD: major depressive disorder.
CXC superfamily
CXCL1	Chemokine (C-X-C motif) ligand 1 (CXCL1) is a small peptide that acts as a chemoattractant for immune cells, especially neutrophils to the site of injury or infection and plays an important role in regulation of immune and inflammatory responses. CXCL1 is also involved in the processes of wound healing and tumorigenesis. CXCL1 contributes to the release of prostaglandins and thus causes increased sensitivity to pain and drives nociceptive sensitization.	Depressive symptoms Depression	Rats treated with CXCL1 showed a decrease in burrowing behavior and open-field activity.[81] Repeated social defeat in mice caused an increase in the CXCL1 levels in the brain. This suggests higher leukocyte recruitment in the brain vasculature.[82]
CXCL2	Chemokine (C-X-C motif) ligand 2 (CXCL2) is also called macrophage inflammatory protein 2-α (MIP2-α) and serves as a neutrophil chemoattractant. CXCL2 is involved in immune responses including wound healing, cancer metastasis, and angiogenesis.	Depression	Repeated social defeat in mice also caused an increase in the CXCL2 levels in the brain.[82]
CXCL4	Chemokine (C-X-C motif) ligand 4 (CXCL4) is also known as Platelet factor 4 (PF4), and plays a major role in neutralization of heparin-like molecules on the endothelial surface of blood vessels, thereby inhibiting local antithrombin activity and promoting coagulation. CXCL4 is a chemoattractant for neutrophils and fibroblasts and is involved with inflammation and wound repair.	Depression	Increased levels of CXCL4 were seen in depressed patients.[83]
CXCL7	Chemokine (C-X-C motif) ligand 7 (CXCL7) is released in large amounts from platelets following their activation. CXCL7 may function as an immediate-early mediator of neutrophil recruitment released from platelets at sites of inflammation.	Depression	Increased levels of CXCL7 were also seen in depressed patients.[83]
CXCL8	Chemokine (C-X-C motif) ligand 8 (CXCL8) is the most potent human neutrophil-attracting chemokine and plays crucial roles in the response to infection and tissue injury. CXCL8 is also known as Interleukin 8 (IL-8), which is produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells, and endothelial cells. CXCL8 plays a key role in neutrophil recruitment and degranulation and its secretion serves as a key parameter in localized inflammation.	Depression	Levels of CXCL8 in blood samples for depressed patients were higher than the average for control subjects but this was after controlling for only healthy patients. This suggests that inflammatory changes of underlying physical disease could mask the changes in chemokine levels in depressed patients.[83]
CXCL10	Chemokine (C-X-C motif) ligand 10 (CXCL10), also known as Interferon gamma-induced protein 10 (IP-10), is a circulating inflammatory marker. CXCL10 is a biomarker for the development of heart failure and left ventricular dysfunction.	MDD with suicidal ideation	Significantly higher blood levels of CXCL10 were seen in patients with MDD with suicidal ideation as compared to MDD alone.[84]
CXCL12	Chemokine (C-X-C motif) ligand 12 (CXCL12) is also known as stromal cell-derived factor 1 (SDF-1). CXCL12 is strongly chemotactic for lymphocytes and is involved with cell migration that contributes to inflammation, including neuroinflammation by attracting leukocytes across the blood brain barrier. Excessive production and accumulation of CXCL12 are cytotoxic.	Stress	Increased level of CXCL12 in the hippocampus and prefrontal cortex suggests the excessive activation of microglial cells.[85]
CC superfamily
CCL2	Chemokine (C-C motif) ligand 2 (CCL2) is also called as monocyte chemoattractant protein-1 (MCP-1), which attracts monocytes in the circulatory system helping them to enter the encompassing injured and inflamed tissues where they transform into tissue macrophages. CCL2 is involved in the neuro-inflammatory processes in various neurodegenerative diseases.	MDD Stress Bipolar disorder	This specific chemokine is a type of inflammatory chemokine which is implicated in chemotactic migration of peripheral monocytes to the brain.[86] Increased levels of CCL2 are seen in patients with bipolar disorder.[87]
CCL3	Chemokine (C-C motif) ligand 3 (CCL3) is also known as macrophage inflammatory protein 1α (MIP-1α). CCL3 is involved in acute inflammatory state in recruitment and activation of polymorphonuclear leukocytes.	Depression	Depressed patients had a higher level of CCL3 which also acts as a macrophage inflammatory protein-1ɑ when compared to healthy control.[83,88,89]
CCL4	Chemokine (C-C motif) ligands 4 (CCL4) is also known as macrophage inflammatory protein 1β (MIP-1β) and is produced during inflammation and tissue damage to attract immune cells such as leukocytes to migrate into peripheral tissues.	Depression	Plasma levels of CCL4 were shown to be decreased in depressed patients.[83,90,91]
CCL11	Chemokine (C-C motif) ligand 11 (CCL11) is also known as eosinophil chemotactic protein and eotaxin-1. CCL11 selectively recruits eosinophils by inducing their chemotaxis, and is implicated in allergic responses as well as neurogenesis and mental disorders.	Depression	Increased levels of CCL11 are seen in patients with bipolar disorder as well as depression.[83]
CCL22	Chemokine (C-C motif) ligand 22 (CCL22) plays a role in trafficking of the activated T lymphocytes to inflammatory sites.	MDD	MDD patients who responded to anti-depressive therapy had increased levels of CCL22. This is a macrophage-derived chemokine which suggests that chemotaxis and infiltration of monocytes, and the recruitment of T-helper 2 cells (Th2) and T-regulatory cells through the blood brain barrier is a potential pathway for the role of chemokines in MDD.[68]