Generic placeholder image

Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Inflammatory Biomarkers for Mood Disorders - A Brief Narrative Review

Author(s): Hui H. Chang and Po S. Chen*

Volume 26 , Issue 2 , 2020

Page: [236 - 243] Pages: 8

DOI: 10.2174/1381612826666200115100726

Price: $65


Background: The nervous system and the immune system interact consistently in the brain and peripheries. Inflammation in the brain not only alters the metabolism of neurotransmitters, but also causes network dysfunction, structural changes, and the development of mood symptomology in patients with mood disorders. In addition, the dysregulation of the neuroimmune axis in mood disorders drives multiple-system comorbidities. Furthermore, patients with low-grade inflammation are more likely to exhibit treatment resistance with both pharmacotherapy and non-pharmacotherapy.

Objective: The aim of this review was to examine the available data regarding not only evidence of inflammation in the pathophysiology of mood disorders and their comorbid conditions, but also potential inflammatory biomarkers of mood disorders.

Methods: Studies of the use of adjunct anti-inflammatory medications in mood disorders, and inflammatory biomarkers that may guide treatment outcomes in mood disorders, were summarized.

Results: Studies have demonstrated that certain adjunct anti-inflammatory medications might help to improve mood symptoms and reduce comorbidities, and the baseline levels of inflammatory biomarkers, such as peripheral C-reactive protein (CRP), could be used to stratify the treatment outcome. All results suggested that the identification of peripheral and brain inflammatory biomarkers for the diagnosis, outcome prediction, staging, and stratification of interventions of mood disorders has emerged as an important area of translational research in psychiatry.

Conclusion: Inflammatory biomarkers could guide interventions and enhance treatment response in patients with mood disorders. The main challenge is that substantial complexities might hamper the attainment of this goal.

Keywords: Inflammation, mood disorders, biomarker, C-reactive protein, pharmacotherapy, anti-inflammatory medications.

McEwen BS. Brain on stress: how the social environment gets under the skin. Proc Natl Acad Sci USA 2012; 109(Suppl. 2): 17180-5.
[] [PMID: 23045648]
Miller AH, Raison CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol 2016; 16(1): 22-34.
[] [PMID: 26711676]
Irwin MR, Cole SW. Reciprocal regulation of the neural and innate immune systems. Nat Rev Immunol 2011; 11(9): 625-32.
[] [PMID: 21818124]
Powell ND, Sloan EK, Bailey MT, et al. Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via β-adrenergic induction of myelopoiesis. Proc Natl Acad Sci USA 2013; 110(41): 16574-9.
[] [PMID: 24062448]
Leboyer M, Soreca I, Scott J, et al. Can bipolar disorder be viewed as a multi-system inflammatory disease? J Affect Disord 2012; 141(1): 1-10.
[] [PMID: 22497876]
Danese A, Moffitt TE, Pariante CM, Ambler A, Poulton R, Caspi A. Elevated inflammation levels in depressed adults with a history of childhood maltreatment. Arch Gen Psychiatry 2008; 65(4): 409-15.
[] [PMID: 18391129]
Liukkonen T, Silvennoinen-Kassinen S, Jokelainen J, et al. The association between C-reactive protein levels and depression: results from the northern Finland 1966 birth cohort study. Biol Psychiatry 2006; 60(8): 825-30.
[] [PMID: 16616729]
Müller N, Krause D, Barth R, et al. Childhood adversity and current stress are related to pro- and anti-inflammatory cytokines in major depression. J Affect Disord 2019; 253: 270-6.
[] [PMID: 31063941]
Nelson BW, Wright DB, Allen NB, Laurent HK. Maternal stress and social support prospectively predict infant inflammation. Brain Behav Immun 2019. In press
[] [PMID: 31077776]
Hodes GE, Kana V, Menard C, Merad M, Russo SJ. Neuroimmune mechanisms of depression. Nat Neurosci 2015; 18(10): 1386-93.
[] [PMID: 26404713]
Cole SW, Levine ME, Arevalo JM, Ma J, Weir DR, Crimmins EM. Loneliness, eudaimonia, and the human conserved transcriptional response to adversity. Psychoneuroendocrinology 2015; 62: 11-7.
[] [PMID: 26246388]
Fredrickson BL, Grewen KM, Coffey KA, et al. A functional genomic perspective on human well-being. Proc Natl Acad Sci USA 2013; 110(33): 13684-9.
[] [PMID: 23898182]
Wohleb ES, Franklin T, Iwata M, Duman RS. Integrating neuroimmune systems in the neurobiology of depression. Nat Rev Neurosci 2016; 17(8): 497-511.
[] [PMID: 27277867]
Maes M, Carvalho AF. The compensatory immune-regulatory reflex system (CIRS) in depression and bipolar disorder. Mol Neurobiol 2018; 55(12): 8885-903.
[] [PMID: 29611101]
Köhler CA, Freitas TH, Stubbs B, et al. Peripheral alterations in cytokine and chemokine levels after antidepressant drug treatment for major depressive disorder: systematic review and meta-analysis. Mol Neurobiol 2018; 55(5): 4195-206.
[PMID: 28612257]
Goldsmith DR, Rapaport MH, Miller BJ. A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Mol Psychiatry 2016; 21(12): 1696-709.
[] [PMID: 26903267]
Wohleb ES, McKim DB, Sheridan JF, Godbout JP. Monocyte trafficking to the brain with stress and inflammation: a novel axis of immune-to-brain communication that influences mood and behavior. Front Neurosci 2015; 8: 447.
[] [PMID: 25653581]
Kraus C, Kadriu B, Lanzenberger R, Zarate CA Jr, Kasper S. Prognosis and improved outcomes in major depression: a review. Transl Psychiatry 2019; 9(1): 127.
[] [PMID: 30944309]
Setiawan E, Attwells S, Wilson AA, et al. Association of translocator protein total distribution volume with duration of untreated major depressive disorder: a cross-sectional study. Lancet Psychiatry 2018; 5(4): 339-47.
[] [PMID: 29496589]
Scaini G, Barichello T, Fries GR, et al. TSPO upregulation in bipolar disorder and concomitant downregulation of mitophagic proteins and NLRP3 inflammasome activation. Neuropsychopharmacology 2019; 44(7): 1291-9.
[] [PMID: 30575805]
Opel N, Cearns M, Clark S, et al. Large-scale evidence for an association between low-grade peripheral inflammation and brain structural alterations in major depression in the BiDirect study. J Psychiatry Neurosci 2019; 44(6): 423-31.
[] [PMID: 31304733]
Shahab S, Mulsant BH, Levesque ML, et al. Brain structure, cognition, and brain age in schizophrenia, bipolar disorder, and healthy controls. Neuropsychopharmacology 2019; 44(5): 898-906.
[] [PMID: 30635616]
Schwarz E, Doan NT, Pergola G, et al. IMAGEMEND Consortium. Karolinska Schizophrenia Project (KaSP) Consortium. Reproducible grey matter patterns index a multivariate, global alteration of brain structure in schizophrenia and bipolar disorder. Transl Psychiatry 2019; 9(1): 12.
[] [PMID: 30664633]
Felger JC, Li Z, Haroon E, et al. Inflammation is associated with decreased functional connectivity within corticostriatal reward circuitry in depression. Mol Psychiatry 2016; 21(10): 1358-65.
[] [PMID: 26552591]
Mehta ND, Haroon E, Xu X, Woolwine BJ, Li Z, Felger JC. Inflammation negatively correlates with amygdala-ventromedial prefrontal functional connectivity in association with anxiety in patients with depression: preliminary results. Brain Behav Immun 2018; 73: 725-30.
[] [PMID: 30076980]
Yin L, Xu X, Chen G, et al. Inflammation and decreased functional connectivity in a widely-distributed network in depression: centralized effects in the ventral medial prefrontal cortex. Brain Behav Immun 2019; 80: 657-66.
[] [PMID: 31078690]
Tu PC, Li CT, Lin WC, Chen MH, Su TP, Bai YM. Structural and functional correlates of serum soluble IL-6 receptor level in patients with bipolar disorder. J Affect Disord 2017; 219: 172-7.
[] [PMID: 28558364]
Tsai SY, Gildengers AG, Hsu JL, Chung KH, Chen PH, Huang YJ. Inflammation associated with volume reduction in the gray matter and hippocampus of older patients with bipolar disorder. J Affect Disord 2019; 244: 60-6.
[] [PMID: 30317016]
Kim YK, Jung HG, Myint AM, Kim H, Park SH. Imbalance between pro-inflammatory and anti-inflammatory cytokines in bipolar disorder. J Affect Disord 2007; 104(1-3): 91-5.
[] [PMID: 17434599]
Iwata M, Ota KT, Duman RS. The inflammasome: pathways linking psychological stress, depression, and systemic illnesses. Brain Behav Immun 2013; 31: 105-14.
[] [PMID: 23261775]
Nerurkar L, Siebert S, McInnes IB, Cavanagh J. Rheumatoid arthritis and depression: an inflammatory perspective. Lancet Psychiatry 2019; 6(2): 164-73.
[] [PMID: 30366684]
Khandaker GM, Zuber V, Rees JMB, et al. Shared mechanisms between coronary heart disease and depression: findings from a large UK general population-based cohort. Mol Psychiatry 2019. (Online ahead of print).
[] [PMID: 30886334]
Bialek K, Czarny P, Strycharz J, Sliwinski T. Major depressive disorders accompanying autoimmune diseases - response to treatment. Prog Neuropsychopharmacol Biol Psychiatry 2019; 95, 109678
[] [PMID: 31238086]
Forty L, Ulanova A, Jones L, et al. Comorbid medical illness in bipolar disorder. Br J Psychiatry 2014; 205(6): 465-72.
[] [PMID: 25359927]
Kapczinski F, Dal-Pizzol F, Teixeira AL, et al. Peripheral biomarkers and illness activity in bipolar disorder. J Psychiatr Res 2011; 45(2): 156-61.
[] [PMID: 20541770]
Nordestgaard BG, Zacho J. Lipids, atherosclerosis and CVD risk: is CRP an innocent bystander? Nutr Metab Cardiovasc Dis 2009; 19(8): 521-4.
[] [PMID: 19695857]
Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003; 107(3): 499-511.
[] [PMID: 12551878]
Wei W, Yang S, Qiu Y, et al. CRP gene polymorphism contributes genetic susceptibility to dyslipidemia in Han Chinese population. Mol Biol Rep 2014; 41(4): 2335-43.
[] [PMID: 24474658]
da Silva J, Gonçalves-Pereira M, Xavier M, Mukaetova-Ladinska EB. Affective disorders and risk of developing dementia: systematic review. Br J Psychiatry 2013; 202(3): 177-86.
[] [PMID: 23457181]
Krogh J, Benros ME, Jørgensen MB, Vesterager L, Elfving B, Nordentoft M. The association between depressive symptoms, cognitive function, and inflammation in major depression. Brain Behav Immun 2014; 35: 70-6.
[] [PMID: 24016864]
Steffens DC, McQuoid DR, Potter GG. Amnestic mild cognitive impairment and incident dementia and Alzheimer’s disease in geriatric depression. Int Psychogeriatr 2014; 26(12): 2029-36.
[] [PMID: 25032667]
Wu KY, Chang CM, Liang HY, et al. Increased risk of developing dementia in patients with bipolar disorder: a nested matched case-control study. Bipolar Disord 2013; 15(7): 787-94.
[] [PMID: 23992521]
Leonard BE. Inflammation, depression and dementia: are they connected? Neurochem Res 2007; 32(10): 1749-56.
[] [PMID: 17705097]
Hung Chi M, Hua Chang H, Tzeng NS, et al. The prevalence of metabolic syndrome in drug-naïve bipolar II disorder patients before and after twelve week pharmacological intervention. J Affect Disord 2013; 146(1): 79-83.
[] [PMID: 23017540]
Oxenkrug GF. Metabolic syndrome, age-associated neuroendocrine disorders, and dysregulation of tryptophan-kynurenine metabolism. Ann N Y Acad Sci 2010; 1199: 1-14.
[] [PMID: 20633104]
Chang HH, Lee IH, Gean PW, et al. Treatment response and cognitive impairment in major depression: association with C-reactive protein. Brain Behav Immun 2012; 26(1): 90-5.
[] [PMID: 21839826]
Tsai SY, Chung KH, Huang SH, Chen PH, Lee HC, Kuo CJ. Persistent inflammation and its relationship to leptin and insulin in phases of bipolar disorder from acute depression to full remission. Bipolar Disord 2014; 16(8): 800-8.
[] [PMID: 25130211]
Sharma AN, Bauer IE, Sanches M, et al. Common biological mechanisms between bipolar disorder and type 2 diabetes: focus on inflammation. Prog Neuropsychopharmacol Biol Psychiatry 2014; 54: 289-98.
[] [PMID: 24969830]
Goldstein BI, Kemp DE, Soczynska JK, McIntyre RS. Inflammation and the phenomenology, pathophysiology, comorbidity, and treatment of bipolar disorder: a systematic review of the literature. J Clin Psychiatry 2009; 70(8): 1078-90.
[] [PMID: 19497250]
Vogelzangs N, Duivis HE, Beekman AT, et al. Association of depressive disorders, depression characteristics and antidepressant medication with inflammation. Transl Psychiatry 2012; 2, e79
[] [PMID: 22832816]
Ayorech Z, Tracy DK, Baumeister D, Giaroli G. Taking the fuel out of the fire: evidence for the use of anti-inflammatory agents in the treatment of bipolar disorders. J Affect Disord 2015; 174: 467-78.
[] [PMID: 25553408]
Herman FJ, Simkovic S, Pasinetti GM. Neuroimmune nexus of depression and dementia: shared mechanisms and therapeutic targets. Br J Pharmacol 2019; 176(18): 3558-84.
[] [PMID: 30632147]
Fond G, Hamdani N, Kapczinski F, et al. Effectiveness and tolerance of anti-inflammatory drugs’ add-on therapy in major mental disorders: a systematic qualitative review. Acta Psychiatr Scand 2014; 129(3): 163-79.
[] [PMID: 24215721]
Köhler-Forsberg ON, Lydholm C, Hjorthøj C, Nordentoft M, Mors O, Benros ME. Efficacy of anti-inflammatory treatment on major depressive disorder or depressive symptoms: meta-analysis of clinical trials. Acta Psychiatr Scand 2019; 139(5): 404-19.
[] [PMID: 30834514]
Kim SW, Kang HJ, Jhon M, et al. Statins and inflammation: new therapeutic opportunities in psychiatry. Front Psychiatry 2019; 10: 103.
[] [PMID: 30890971]
Akhondzadeh S, Jafari S, Raisi F, et al. Clinical trial of adjunctive celecoxib treatment in patients with major depression: a double blind and placebo controlled trial. Depress Anxiety 2009; 26(7): 607-11.
[] [PMID: 19496103]
Müller N, Schwarz MJ, Dehning S, et al. The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry 2006; 11(7): 680-4.
[] [PMID: 16491133]
Sarris J, Mischoulon D, Schweitzer I. Omega-3 for bipolar disorder: meta-analyses of use in mania and bipolar depression. J Clin Psychiatry 2012; 73(1): 81-6.
[] [PMID: 21903025]
Layé S, Nadjar A, Joffre C, Bazinet RP. Anti-Inflammatory effects of omega-3 fatty acids in the brain: physiological mechanisms and relevance to pharmacology. Pharmacol Rev 2018; 70(1): 12-38.
[] [PMID: 29217656]
Liao Y, Xie B, Zhang H, et al. Efficacy of omega-3 PUFAs in depression: a meta-analysis. Transl Psychiatry 2019; 9(1): 190.
[] [PMID: 31383846]
Berk M, Copolov DL, Dean O, et al. N-acetyl cysteine for depressive symptoms in bipolar disorder-a double-blind randomized placebo-controlled trial. Biol Psychiatry 2008; 64(6): 468-75.
[] [PMID: 18534556]
Magalhães PV, Dean OM, Bush AI, et al. N-acetyl cysteine add-on treatment for bipolar II disorder: a subgroup analysis of a randomized placebo-controlled trial. J Affect Disord 2011; 129(1-3): 317-20.
[] [PMID: 20800897]
Hewlings SJ, Kalman DS. Curcumin: a review of it’s effects on human health. Foods 2017; 6(10): 92.
[] [PMID: 29065496]
Ng QX, Koh SSH, Chan HW, Ho CYX. Clinical use of curcumin in depression: a meta-analysis. J Am Med Dir Assoc 2017; 18(6): 503-8.
[] [PMID: 28236605]
Fusar-Poli L, Vozza L, Gabbiadini A, et al. Curcumin for depression: a meta-analysis. Crit Rev Food Sci Nutr 2019; 1-11. In press
[] [PMID: 31423805]
Rosenblat JD. Targeting the immune system in the treatment of bipolar disorder. Psychopharmacology (Berl) 2019; 236(10): 2909-21.
[] [PMID: 30756134]
Kubera M, Holan V, Mathison R, Maes M. The effect of repeated amitriptyline and desipramine administration on cytokine release in C57BL/6 mice. Psychoneuroendocrinology 2000; 25(8): 785-97.
[] [PMID: 10996474]
Maes M, Song C, Lin A-H, et al. Negative immunoregulatory effects of antidepressants: inhibition of interferon-γ and stimulation of interleukin-10 secretion. Neuropsychopharmacology 1999; 20(4): 370-9.
[] [PMID: 10088138]
Inserra A, Mastronardi CA, Rogers G, Licinio J, Wong M-L. Neuroimmunomodulation in major depressive disorder: focus on caspase 1, inducible nitric oxide synthase, and interferon-gamma. Mol Neurobiol 2019; 56(6): 4288-305.
[] [PMID: 30306457]
Chen MH, Li CT, Lin WC, et al. Rapid inflammation modulation and antidepressant efficacy of a low-dose ketamine infusion in treatment-resistant depression: a randomized, double-blind control study. Psychiatry Res 2018; 269: 207-11.
[] [PMID: 30153598]
Cui W, Ning Y, Hong W, Wang J, Liu Z, Li MD. Crosstalk between inflammation and glutamate system in depression: signaling pathway and molecular biomarkers for ketamine’s antidepressant effect. Mol Neurobiol 2019; 56(5): 3484-500.
[] [PMID: 30140973]
Wang L, Wang R, Liu L, Qiao D, Baldwin DS, Hou R. Effects of SSRIs on peripheral inflammatory markers in patients with major depressive disorder: a systematic review and meta-analysis. Brain Behav Immun 2019; 79: 24-38.
[] [PMID: 30797959]
Ximenes JC, de Oliveira Gonçalves D, Siqueira RM, et al. Valproic acid: an anticonvulsant drug with potent antinociceptive and anti-inflammatory properties. Naunyn Schmiedebergs Arch Pharmacol 2013; 386(7): 575-87.
[] [PMID: 23584602]
Watkins CC, Sawa A, Pomper MG. Glia and immune cell signaling in bipolar disorder: insights from neuropharmacology and molecular imaging to clinical application. Transl Psychiatry 2014; 4, e350
[] [PMID: 24448212]
Beurel E, Jope RS. Inflammation and lithium: clues to mechanisms contributing to suicide-linked traits. Transl Psychiatry 2014; 4, e488
[] [PMID: 25514751]
Koukopoulos A, Serra G, Koukopoulos AE, Reginaldi D, Serra G. The sustained mood-stabilizing effect of memantine in the management of treatment resistant bipolar disorders: findings from a 12-month naturalistic trial. J Affect Disord 2012; 136(1-2): 163-6.
[] [PMID: 22030128]
Niculescu AB, Levey D, Le-Niculescu H, Niculescu E, Kurian SM, Salomon D. Psychiatric blood biomarkers: avoiding jumping to premature negative or positive conclusions. Mol Psychiatry 2015; 20(3): 286-8.
[] [PMID: 25582618]
Brunoni AR, Supasitthumrong T, Teixeira AL, et al. Differences in the immune-inflammatory profiles of unipolar and bipolar depression. J Affect Disord 2020; 262: 8-15.
[] [PMID: 31693974]
Osimo EF, Baxter LJ, Lewis G, Jones PB, Khandaker GM. Prevalence of low-grade inflammation in depression: a systematic review and meta-analysis of CRP levels. Psychol Med 2019; 49(12): 1958-70.
[] [PMID: 31258105]
Glaus J, von Känel R, Lasserre AM, et al. Mood disorders and circulating levels of inflammatory markers in a longitudinal population-based study. Psychol Med 2018; 48(6): 961-73.
[] [PMID: 28929992]
Wysokiński A, Margulska A, Strzelecki D, Kłoszewska I. Levels of C-reactive protein (CRP) in patients with schizophrenia, unipolar depression and bipolar disorder. Nord J Psychiatry 2015; 69(5): 346-53.
[] [PMID: 25495587]
Bai YM, Su TP, Tsai SJ, et al. Comparison of inflammatory cytokine levels among type I/type II and manic/hypomanic/euthymic/ depressive states of bipolar disorder. J Affect Disord 2014; 166: 187-92.
[] [PMID: 25012430]
Dargél AA, Godin O, Kapczinski F, Kupfer DJ, Leboyer M. C-reactive protein alterations in bipolar disorder: a meta-analysis. J Clin Psychiatry 2015; 76(2): 142-50.
[] [PMID: 25742201]
Halder I, Marsland AL, Cheong J, Muldoon MF, Ferrell RE, Manuck SB. Polymorphisms in the CRP gene moderate an association between depressive symptoms and circulating levels of C-reactive protein. Brain Behav Immun 2010; 24(1): 160-7.
[] [PMID: 19796676]
Fernandes BS, Steiner J, Molendijk ML, et al. C-reactive protein concentrations across the mood spectrum in bipolar disorder: a systematic review and meta-analysis. Lancet Psychiatry 2016; 3(12): 1147-56.
[] [PMID: 27838212]
Dickerson F, Stallings C, Origoni A, Boronow J, Yolken R. Elevated serum levels of C-reactive protein are associated with mania symptoms in outpatients with bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry 2007; 31(4): 952-5.
[] [PMID: 17391822]
Becking K, Boschloo L, Vogelzangs N, et al. The association between immune activation and manic symptoms in patients with a depressive disorder. Transl Psychiatry 2013; 3, e314
[] [PMID: 24150223]
Hamer M, Batty GD, Marmot MG, Singh-Manoux A, Kivimäki M. Anti-depressant medication use and C-reactive protein: results from two population-based studies. Brain Behav Immun 2011; 25(1): 168-73.
[] [PMID: 20863880]
Fond G, Brunel L, Boyer L. C-reactive protein as a differential biomarker of bipolar II depression versus major depressive disorder. World J Biol Psychiatry 2017; 18(1): 71-2.
[] [PMID: 27586819]
Siwek M, Sowa-Kućma M, Styczeń K, et al. Associations of serum cytokine receptor levels with melancholia, staging of illness, depressive and manic phases, and severity of depression in bipolar disorder. Mol Neurobiol 2017; 54(8): 5883-93.
[] [PMID: 27660275]
Angst J, Azorin JM, Bowden CL, et al. Prevalence and characteristics of undiagnosed bipolar disorders in patients with a major depressive episode: the BRIDGE study. Arch Gen Psychiatry 2011; 68(8): 791-8.
[] [PMID: 21810644]
Berk M, Williams LJ, Jacka FN, et al. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med 2013; 11: 200.
[] [PMID: 24228900]
Siwek M, Szewczyk B, Dudek D, et al. Zinc as a marker of affective disorders. Pharmacol Rep 2013; 65(6): 1512-8.
[] [PMID: 24552999]
Sowa-Kućma M, Styczeń K, Siwek M, et al. Are there differences in lipid peroxidation and immune biomarkers between major depression and bipolar disorder: effects of melancholia, atypical depression, severity of illness, episode number, suicidal ideation and prior suicide attempts. Prog Neuropsychopharmacol Biol Psychiatry 2018; 81: 372-83.
[] [PMID: 28867391]
Siwek M, Sowa-Kućma M, Styczeń K, et al. Decreased serum zinc concentration during depressive episode in patients with bipolar disorder. J Affect Disord 2016; 190: 272-7.
[] [PMID: 26540081]
Cope EC, Levenson CW. Role of zinc in the development and treatment of mood disorders. Curr Opin Clin Nutr Metab Care 2010; 13(6): 685-9.
[] [PMID: 20689416]
Al-Hakeim H, Al-Fadhel S, Al-Dujaili AH, Maes M. In major depression, increased serum dynorphin and kappa opioid receptor levels are positively associated with mu opioid receptor levels and immune activation and are attenuated by nicotine dependence. Preprints 2019; 2019, 040176
Modabbernia A, Taslimi S, Brietzke E, Ashrafi M. Cytokine alterations in bipolar disorder: a meta-analysis of 30 studies. Biol Psychiatry 2013; 74(1): 15-25.
[] [PMID: 23419545]
Nowak G, Szewczyk B, Wieronska JM, et al. Antidepressant-like effects of acute and chronic treatment with zinc in forced swim test and olfactory bulbectomy model in rats. Brain Res Bull 2003; 61(2): 159-64.
[] [PMID: 12832002]
Nowak G, Siwek M, Dudek D, Zieba A, Pilc A. Effect of zinc supplementation on antidepressant therapy in unipolar depression: a preliminary placebo-controlled study. Pol J Pharmacol 2003; 55(6): 1143-7.
[PMID: 14730113]
Styczeń K, Sowa-Kućma M, Dudek D, et al. Zinc and copper concentration do not differentiate bipolar disorder from major depressive disorder. Psychiatr Pol 2018; 52(3): 449-57.
[] [PMID: 30218561]
Soto M, Herzog C, Pacheco JA, et al. Gut microbiota modulate neurobehavior through changes in brain insulin sensitivity and metabolism. Mol Psychiatry 2018; 23(12): 2287-301.
[] [PMID: 29910467]
Ait-Belgnaoui A, Durand H, Cartier C, et al. Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats. Psychoneuroendocrinology 2012; 37(11): 1885-95.
[] [PMID: 22541937]
Rogers GB, Keating DJ, Young RL, Wong ML, Licinio J, Wesselingh S. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Mol Psychiatry 2016; 21(6): 738-48.
[] [PMID: 27090305]
Sampson TR, Debelius JW, Thron T, et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell 2016; 167(6): 1469-1480. e12.
[] [PMID: 27912057]
Pesonen A-K, Eriksson JG, Heinonen K, et al. Cognitive ability and decline after early life stress exposure. Neurobiol Aging 2013; 34(6): 1674-9.
[] [PMID: 23337341]
Hedges DW, Woon FL. Early-life stress and cognitive outcome. Psychopharmacology (Berl) 2011; 214(1): 121-30.
[] [PMID: 21107538]
Hu S, Li A, Huang T, et al. Gut microbiota changes in patients with bipolar depression. Adv Sci (Weinh) 2019; 6(14), 1900752
[] [PMID: 31380217]
Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuroendocrinol Lett 2008; 29(1): 117-24.
[PMID: 18283240]
Gareau MG, Silva MA, Perdue MH. Pathophysiological mechanisms of stress-induced intestinal damage. Curr Mol Med 2008; 8(4): 274-81.
[] [PMID: 18537635]
Jiang H, Ling Z, Zhang Y, et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun 2015; 48: 186-94.
[] [PMID: 25882912]
Black CN, Bot M, Scheffer PG, Cuijpers P, Penninx BWJH. Is depression associated with increased oxidative stress? A systematic review and meta-analysis. Psychoneuroendocrinology 2015; 51: 164-75.
[] [PMID: 25462890]
Slyepchenko A, Maes M, Jacka FN, et al. Gut microbiota, bacterial translocation, and interactions with diet: pathophysiological links between major depressive disorder and non-communicable medical comorbidities. Psychother Psychosom 2017; 86(1): 31-46.
[] [PMID: 27884012]
Maes M, Moraes JB, Congio A, et al. Development of a novel staging model for affective disorders using partial least squares bootstrapping: effects of lipid-associated antioxidant defenses and neuro-oxidative stress. Mol Neurobiol 2019; 56(9): 6626-44.
[] [PMID: 30911933]
Allen J, Romay-Tallon R, Brymer KJ, Caruncho HJ, Kalynchuk LE. Mitochondria and mood: mitochondrial dysfunction as a key player in the manifestation of depression. Front Neurosci 2018; 12: 386.
[] [PMID: 29928190]
Andreazza AC, Duong A, Young LT. Bipolar disorder as a mitochondrial disease. Biol Psychiatry 2018; 83(9): 720-1.
[] [PMID: 29050637]
O’Brien SM, Scully P, Fitzgerald P, Scott LV, Dinan TG. Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy. J Psychiatr Res 2007; 41(3-4): 326-31.
[] [PMID: 16870211]
Harley J, Luty S, Carter J, Mulder R, Joyce P. Elevated C-reactive protein in depression: a predictor of good long-term outcome with antidepressants and poor outcome with psychotherapy. J Psychopharmacol (Oxford) 2010; 24(4): 625-6.
[] [PMID: 19282426]
Syed SA, Beurel E, Loewenstein DA, et al. Defective inflammatory pathways in never-treated depressed patients are associated with poor treatment response. Neuron 2018; 99(5): 914-24. e3.
Strawbridge R, Hodsoll J, Powell TR, et al. Inflammatory profiles of severe treatment-resistant depression. J Affect Disord 2019; 246: 42-51.
[] [PMID: 30578945]
Vogelzangs N, Beekman AT, van Reedt Dortland AK, et al. Inflammatory and metabolic dysregulation and the 2-year course of depressive disorders in antidepressant users. Neuropsychopharmacology 2014; 39(7): 1624-34.
[] [PMID: 24442097]
Chamberlain SR, Cavanagh J, de Boer P, et al. Treatment-resistant depression and peripheral C-reactive protein. Br J Psychiatry 2019; 214(1): 11-9.
[] [PMID: 29764522]
Carboni L, McCarthy DJ, Delafont B, et al. Biomarkers for response in major depression: comparing paroxetine and venlafaxine from two randomised placebo-controlled clinical studies. Transl Psychiatry 2019; 9(1): 182.
[] [PMID: 31375659]
Fried EI, von Stockert S, Haslbeck JMB, Lamers F, Schoevers RA, Penninx BWJH. Using network analysis to examine links between individual depressive symptoms, inflammatory markers, and covariates. Psychol Med 2019. In press
[] [PMID: 31615595]
Carlier A, Berkhof JG, Rozing M, et al. Inflammation and remission in older patients with depression treated with electroconvulsive therapy; findings from the MODECT study✰. J Affect Disord 2019; 256: 509-16.
[] [PMID: 31279250]
Uher R, Tansey KE, Dew T, et al. An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline. Am J Psychiatry 2014; 171(12): 1278-86.
[] [PMID: 25017001]
Rapaport MH, Nierenberg AA, Schettler PJ, et al. Inflammation as a predictive biomarker for response to omega-3 fatty acids in major depressive disorder: a proof-of-concept study. Mol Psychiatry 2016; 21(1): 71-9.
[] [PMID: 25802980]
Raison CL, Rutherford RE, Woolwine BJ, et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry 2013; 70(1): 31-41.
[] [PMID: 22945416]
McIntyre RS, Subramaniapillai M, Lee Y, et al. Efficacy of adjunctive infliximab vs placebo in the treatment of adults with bipolar I/II depression: a randomized clinical trial. JAMA Psychiatry 2019.
[] [PMID: 31066887]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy