Inflamed moods: A review of the interactions between inflammation and mood disorders

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 53; pp. 23 - 34
• Main Authors: Rosenblat, Joshua D., Cha, Danielle S., Mansur, Rodrigo B., McIntyre, Roger S.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 04.08.2014; Elsevier
• Subjects: Adult and adolescent clinical studies; Animals; Biogenic Monoamines - metabolism; Biological and medical sciences; Bipolar disorder; Bipolar disorders; Cytokines; Cytokines - metabolism; Depression; Humans; Inflammation; Inflammation - complications; Inflammation - metabolism; Major depressive disorder; Medical sciences; Mood disorder; Mood disorders; Mood Disorders - complications; Mood Disorders - metabolism; Neuropharmacology; Non-steroidal anti-inflammatory drug (NSAID); Pharmacology. Drug treatments; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; CRP; BD; SSRIs; NSAID; ACTH; Bipolar disorder; Non-steroidal anti-inflammatory drug (NSAID); IBD; MDD; SLE; LPS; Major depressive disorder; ASA; IFN; IDO; CSF; PAMPs; COX-1 and COX-2; MAOIs; TDO; WHO; AA; Mood disorder; PGE2; Cytokines; TCAs; cPLA2; Inflammation; O-3 PUFA; RA; 5-HIAA; HPA; CRH; Drug; Interaction; Cytokine; Depression; Review; Non steroidal antiinflammatory agent; Mood
• ISSN: 0278-5846; 1878-4216; 1878-4216
• DOI: 10.1016/j.pnpbp.2014.01.013

Mood disorders have been recognized by the World Health Organization (WHO) as the leading cause of disability worldwide. Notwithstanding the established efficacy of conventional mood agents, many treated individuals continue to remain treatment refractory and/or exhibit clinically significant residual symptoms, cognitive dysfunction, and psychosocial impairment. Therefore, a priority research and clinical agenda is to identify pathophysiological mechanisms subserving mood disorders to improve therapeutic efficacy. During the past decade, inflammation has been revisited as an important etiologic factor of mood disorders. Therefore, the purpose of this synthetic review is threefold: 1) to review the evidence for an association between inflammation and mood disorders, 2) to discuss potential pathophysiologic mechanisms that may explain this association and 3) to present novel therapeutic options currently being investigated that target the inflammatory–mood pathway. Accumulating evidence implicates inflammation as a critical mediator in the pathophysiology of mood disorders. Indeed, elevated levels of pro-inflammatory cytokines have been repeatedly demonstrated in both major depressive disorder (MDD) and bipolar disorder (BD) patients. Further, the induction of a pro-inflammatory state in healthy or medically ill subjects induces ‘sickness behavior’ resembling depressive symptomatology. Potential mechanisms involved include, but are not limited to, direct effects of pro-inflammatory cytokines on monoamine levels, dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, pathologic microglial cell activation, impaired neuroplasticity and structural and functional brain changes. Anti-inflammatory agents, such as acetyl-salicylic acid (ASA), celecoxib, anti-TNF-α agents, minocycline, curcumin and omega-3 fatty acids, are being investigated for use in mood disorders. Current evidence shows improved outcomes in mood disorder patients when anti-inflammatory agents are used as an adjunct to conventional therapy; however, further research is needed to establish the therapeutic benefit and appropriate dosage. •Inflammation and mood disorders have a bidirectional interaction.•Cytokines, monoamines, the HPA axis and microglial cells are key players involved.•Anti-inflammatory agents show promise for use in the treatment of mood disorders.