Advertisement

The Role of Inflammation in the Pathophysiology of Depression and Suicidal Behavior

Implications for Treatment
  • Gianluca Serafini
    Correspondence
    Corresponding author.
    Affiliations
    Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health DINOGMI, Section of Psychiatry, University of Genoa, Genoa, Italy

    IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, Genoa 16132, Italy
    Search for articles by this author
  • Alessandra Costanza
    Affiliations
    Department of Psychiatry, Faculty of Medicine, University of Geneva (UNIGE), Geneva, Switzerland, Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), Lugano, Switzerland

    Department of Psychiatry, Faculty of Biomedical Sciences, University of Italian Switzerland (USI), Lugano, Switzerland
    Search for articles by this author
  • Andrea Aguglia
    Affiliations
    Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health DINOGMI, Section of Psychiatry, University of Genoa, Genoa, Italy

    IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, Genoa 16132, Italy
    Search for articles by this author
  • Andrea Amerio
    Affiliations
    Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health DINOGMI, Section of Psychiatry, University of Genoa, Genoa, Italy

    IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, Genoa 16132, Italy
    Search for articles by this author
  • Alice Trabucco
    Affiliations
    Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health DINOGMI, Section of Psychiatry, University of Genoa, Genoa, Italy
    Search for articles by this author
  • Andrea Escelsior
    Affiliations
    Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health DINOGMI, Section of Psychiatry, University of Genoa, Genoa, Italy

    IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, Genoa 16132, Italy
    Search for articles by this author
  • Leo Sher
    Affiliations
    James J. Peters VA Medical Center, Bronx, NY, USA

    Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Department of Psychiatry, New York, NY, USA
    Search for articles by this author
  • Mario Amore
    Affiliations
    Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health DINOGMI, Section of Psychiatry, University of Genoa, Genoa, Italy

    IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, Genoa 16132, Italy
    Search for articles by this author

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.

      Subscribe:

      Subscribe to Medical Clinics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Alejos M.
        • Vázquez-Bourgon J.
        • Santurtún M.
        • et al.
        Do patients diagnosed with a neurological disease present increased risk of suicide?.
        Neurologia (Engl Ed). 2020; (S0213-4853:30129-8)
        • Kessler R.C.
        • Berglund P.
        • Demler O.
        The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R).
        JAMA. 2003; 289: 3095-3105
        • Menon V.
        • Vijayakumar L.
        Interventions for attempted suicide.
        Curr Opin Psychiatry. 2022; 35: 317-323
        • Messaoud A.
        • Mensi R.
        • Douki W.
        • et al.
        Reduced peripheral availability of tryptophan and increased activation of the kynurenine pathway and cortisol correlate with major depression and suicide.
        World J Biol Psychiatry. 2019; 20: 703-711
        • Liu Q.
        • He H.
        • Yang J.
        • et al.
        Changes in the global burden of depression from 1990 to 2017: findings from the global burden of disease study.
        J Psychiatr Res. 2020; 126: 134-140
        • Hasler G.
        Pathophysiology of depression: do we have any solid evidence of interest to clinicians?.
        World Psychiatry. 2010; 9: 155-161
        • Koo P.C.
        • Berger C.
        • Kronenberg G.
        • et al.
        Combined cognitive, psychomotor and electrophysiological biomarkers in major depressive disorder.
        Eur Arch Psychiatry Clin Neurosci. 2019; 269: 823-832
        • Perna G.
        • Alciati A.
        • Daccò S.
        • et al.
        Personalized psychiatry and depression: the role of sociodemographic and clinical variables.
        Psychiatry Investig. 2020; 17: 193-206
        • Koolschijn P.C.M.
        • van Haren N.E.
        • Lensvelt-Mulders G.J.
        • et al.
        Brain volume abnormalities in major depressive disorder: A meta-analysis of magnetic resonance imaging studies.
        Hum Brain Mapp. 2009; 30: 3719-3735
        • Menke A.
        Precision pharmacotherapy: psychiatry’s future direction in preventing, diagnosing, and treating mental disorders.
        Pharmacogenomics Pers Med. 2018; 11: 211-222
        • Costanza A.
        • Amerio A.
        • Aguglia A.
        • et al.
        When sick brain and hopelessness meet: some aspects of suicidality in the neurological patient.
        CNS Neurol Disord Drug Targets. 2020; 19: 257-263
        • Costanza A.
        • D'Orta I.
        • Perroud N.
        • et al.
        Neurobiology of suicide: do biomarkers exist?.
        Int J Legal Med. 2014; 128: 73-82
        • Lutz P.E.
        • Mechawar N.
        • Turecki G.
        Neuropathology of suicide: recent findings and future directions.
        Mol Psychiatr. 2017; 22: 395-1412
        • Hawton K.l.
        • Casañas I.
        • Comabella C.
        • et al.
        Risk factors for suicide in individuals with depression: a systematic review.
        J Affect Disord. 2013; 147: 17-28
        • Moitra M.
        • Santomauro D.
        • Degenhardt L.
        • et al.
        Estimating the risk of suicide associated with mental disorders: A systematic review and meta-regression analysis.
        J Psychiatr Res. 2021; 137: 242-249
        • Ribeiro J.D.
        • Huang X.
        • Fox K.R.
        • et al.
        Depression and hopelessness as risk factors for suicide ideation, attempts and death: meta-analysis of longitudinal studies.
        Br J Psychiatry. 2018; 212: 279-286
        • Réus G.Z.
        • Titus S.E.
        • Abelaira H.M.
        Neurochemical correlation between major depressivedisorder and neurodegenerative diseases.
        Life sciences. 2016; 158: 121-129
        • Pandey G.N.
        • Rizavi H.S.
        • Zhang H.
        • et al.
        Abnormal protein and mRNA expression of inflammatory cytokines in the prefrontal cortex of depressed individuals who died by suicide.
        J Psychiatry Neurosci. 2018; 43: 376-385
        • Costanza A.
        • Amerio A.
        • Aguglia A.
        • et al.
        Hyper/neuroinflammation in COVID-19 and suicide etiopathogenesis: hypothesis for a nefarious collision?.
        Neurosci Biobehav Rev. 2022; 136: 104606
        • Courtet P.
        • Giner L.
        • Seneque M.
        • et al.
        Neuroinflammation in suicide: Toward a comprehensive model.
        World J Biol Psychiatry. 2016; 17: 564-586
        • Crawford B.
        • Craig Z.
        • Mansell G.
        • et al.
        DNA methylation and inflammation marker profiles associated with a history of depression.
        Hum Mol Genet. 2009; 27: 2840-2850
        • Jackson N.A.
        • Jabbi M.,M.
        Integrating biobehavioral information to predict mood disordersuiciderisk.
        Brain Behav Immun Health. 2022; 24: 100495
        • Serafini G.
        • Parisi V.M.
        • Aguglia A.
        • et al.
        A specific inflammatory profile underlying suicide risk? Systematic review of the main literature findings.
        Int J Environ Res Public Health. 2020; 17: 2393
        • Serafini G.
        • Pompili M.
        • Seretti E.M.
        • et al.
        The role of inflammatory cytokines in suicidal behavior: a systematic review.
        Eur Neuropsychopharmacol. 2013; 23: 1672-1686
        • Bergmans R.S.
        • Kelly K.M.
        • Mezuk B.
        Inflammation as a unique marker of suicide ideation distinct from depression syndrome among U.S. adults.
        J Affect Disord. 2019; 245: 1052-1060
        • Bouças A.P.
        • Rheinheimer J.
        • Lagopoulos J.
        Why severe COVID-19 patients are at greater risk of developing depression: a molecular perspective.
        Neuroscientist. 2020; 28: 11-19
        • Brundin L.
        • Sellgren C.M.
        • Lim C.K.
        • et al.
        An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation.
        Transl Psychiatry. 2016; 6: e865
        • Kayser M.S.
        • Dalmau J.
        The emerging link between autoimmune disorders and neuropsychiatric disease.
        J Neuropsychiatry Clin Neurosci. 2011; 23: 90-97
        • Raison C.L.
        • Borisov A.S.
        • Broadwell S.D.
        • et al.
        Depression during pegylated interferon-alpha plus ribavirin therapy: prevalence and prediction.
        J Clin Psychiatry. 2005; 66: 41-48
        • Jabbi M.
        • Arasappan D.
        • Eickhoff S.B.
        • et al.
        Neuro-transcriptomic signatures for mood disorder morbidity and suicide mortality.
        J Psychiatr Res. 2020; 127: 62-74
        • Pantazatos S.P.
        • Huang Y.Y.
        • Rosoklija G.B.
        • et al.
        Whole-transcriptome brain expression and exon-usage profiling in major depression and suicide: evidence for altered glial, endothelial and ATPase activity.
        Mol Psychiatr. 2017; 22: 760-773
        • Barnes J.
        • Mondelli V.
        • Pariante C.M.
        Genetic contributions of inflammation to depression.
        Neuropsychopharmacology. 2017; 42: 81-98
        • Bufalino C.
        • Hepgul N.
        • Aguglia E.
        • et al.
        The role of immune genes in the association between depression and inflammation: a review of recent clinical studies.
        Brain Behav Immun. 2013; 31: 31-47
        • Dantzer R.
        • O'Connor J.C.
        • Freund G.G.
        • et al.
        From inflammation to sickness and depression: when the immune system subjugates the brain.
        Nat Rev Neurosci. 2008; 9: 46-56
        • Miller A.H.
        • Maletic V.
        • Raison C.L.
        Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression.
        Biol Psychiatry. 2009; 65: 732-741
        • Crawford B.
        • Craig Z.
        • Mansell G.
        • et al.
        DNA methylation and inflammation marker profiles associated with a history of depression.
        Hum Mol Genet. 2009; 27: 2840-2845
        • Karlovic D.
        • Serretti A.
        • Vrkic N.
        • et al.
        Serum concentrations of CRP, IL-6, TNF-alpha and cortisol in major depressive disorder with melancholic or atypical features.
        Psychiatry Res. 2012; 198: 74-80
        • Köhler C.A.
        • Freitas T.H.
        • Maes M.
        • et al.
        Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies.
        Acta Psychiatr Scand. 2017; 135: 373-387
        • Maes M.
        • Yirmyia R.
        • Noraberg J.
        • et al.
        The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression.
        Metab Brain Dis. 2009; 24: 27-53
        • Hepgul N.
        • Cattaneo A.
        • Zunszain P.A.
        • et al.
        Depression pathogenesis and treatment: what can we learn from blood mRNA expression?.
        BMC Med. 2013; 11: 28
        • Maes M.
        • Stevens W.
        • Peeters D.
        • et al.
        A study on the blunted natural killer cell activity in severely depressed patients.
        Life Sci. 1992; 50: 505-513
        • Myint A.M.
        • Leonard B.E.
        • Steinbusch H.W.
        • et al.
        Th1, Th2, and Th3 cytokine alterations in major depression.
        J Affect Disord. 2005; 88: 167-173
        • Huang T.L.
        • Lee C.T.
        T-helper 1/T-helper 2 cytokine imbalance and clinical phenotypes of acute-phase major depression.
        Psychiatry Clin Neurosci. 2007; 61: 415-420
        • Cheng Y.
        • Desse S.
        • Martinez A.
        • et al.
        TNFa disrupts blood brain barrier integrity to maintain prolonged depressive-like behavior in mice.
        Brain Behav Immun. 2018; 69: 556-56
        • Nadeem A.
        • Ahmad S.F.
        • Al-Harbi N.O.
        • et al.
        IL-17A causes depression-like symptoms via NF-κB and p38MAPK signaling pathways in mice: Implications for psoriasis associated depression.
        Cytokine. 2017; 97: 14-24
        • Griffiths C.E.M.
        • Fava M.
        • Miller A.H.
        • et al.
        Impact of ixekizumab treatment on depressive symptoms and systemic inflammation in patients with moderate-to-severe psoriasis: an integrated analysis of three phase 3 clinical studies.
        Psychother Psychosom. 2017; 86: 260-267
        • Lee H.Y.
        • Kim Y.K.
        Transforming growth factor-beta1 and major depressive disorder with and without attempted suicide: preliminary study.
        Psychiatry Res. 2010; 178: 92-96
        • Syed S.A.
        • Beurel E.
        • Loewenstein D.A.
        • et al.
        Defective inflammatory pathways in never-treated depressed patients are associated with poor treatment response.
        Neuron. 2018; 99: 914-924.e3
        • Lamers F.
        • Milaneschi Y.
        • de Jonge P.
        • et al.
        Metabolic and inflammatory markers: associations with individual depressive-symptoms.
        Psychol Med. 2018; 48: 1102-1110
        • Li Z.
        • Qi D.
        • Chen J.
        • et al.
        Venlafaxine inhibits the upregulation of plasma tumor necrosis factor-alpha (TNFα) in the Chinese patients with major depressive disorder: a prospective longitudinal study.
        Psychoneuroendocrinology. 2013; 38: 107-114
        • Réus G.Z.
        • Titus S.E.
        • Abelaira H.M.
        • et al.
        Neurochemical correlation between major depressive disorder and neurodegenerative diseases.
        Life Sci. 2016; 158: 121-129
        • Rothermundt M.
        • Arolt V.
        • Fenker J.
        • et al.
        Different immune patterns in melancholic and non-melancholic major depression.
        Eur Arch Psychiatry Clin Neurosci. 2001; 251: 90-97
        • Dunjic-Kostic B.
        • Ivkovic M.
        • Radonjic N.V.
        • et al.
        Melancholic and atypical major depression–connection between cytokines, psychopathology and treatment.
        Prog Neuropsychopharmacol Biol Psychiatry. 2013; 43: 1-6
        • Black C.
        • Miller B.J.
        Meta-analysis of cytokines and chemokines in suicidality: distinguishing suicidal versus nonsuicidal patients.
        Biol Psychiatry. 2015; 78: 28-37
        • Kowalczyk P.
        • Sulejczak D.
        • Kleczkowska P.
        • et al.
        Mitochondrial oxidativestress-a causative factor and therapeutic target in many diseases.
        Int J Mol Sci. 2021; 22: 13384
        • Lushchak V.I.
        • Duszenko M.
        • Gospodaryov D.V.
        • et al.
        Oxidativestress and energy metabolism in the brain: midlife as a turning point.
        Antioxidants (Basel). 2021; 10: 1715
        • Ng F.
        • Berk M.
        • Dean O.
        • et al.
        Oxidative stress in psychiatric disorders: evidence base and therapeutic implications.
        Int J Neuropsychopharmacol. 2008 Sep; 11: 851-876
        • Bansal Y.
        • Kuhad A.
        Mitochondrial dysfunction in depression.
        Curr Neuropharmacol. 2016; 14: 610-618
        • Szebeni A.
        • Szebeni K.
        • DiPeri T.P.
        • et al.
        Elevated DNA Oxidation and DNA Repair Enzyme Expression in Brain White Matter in Major Depressive Disorder.
        Int J Neuropsychopharmacol. 2017; 20: 363-373
        • Bal N.
        • Acar S.T.
        • Yazici A.
        • et al.
        Altered levels of malondialdehyde and Vitamin E in major depressive disorder and generalized anxiety disorder.
        Dusunen Adam J Psychiatry Neurol Sci. 2012; 25: 206
        • Maes M.
        • De Vos N.
        • Pioli R.
        • et al.
        Lower serum vitamin E concentrations in major depression. Another marker of lowered antioxidant defenses in that illness.
        J Affect Disord. 2000; 58: 241-246
        • Maes M.
        • Mihaylova I.
        • Kubera M.
        • et al.
        Lower whole blood glutathione peroxidase (GPX) activity in depression, but not in myalgic encephalomyelitis/chronic fatigue syndrome: another pathway that may be associated with coronary artery disease and neuroprogression in depression.
        Neuroendocrinol Lett. 2011; 32: 133-140
        • Rybka J.
        • Kedziora-Kornatowska K.
        • Banaś-Lezańska P.
        • et al.
        Interplay between the pro-oxidant and antioxidant systems and proinflammatory cytokine levels, in relation to iron metabolism and the erythron in depression.
        Free Radic Biol Med. 2013; 63: 187-194
        • Jiménez-Fernández S.
        • Gurpegui M.
        • Garrote-Rojas D.
        • et al.
        Oxidativestress parameters and antioxidants in adults with unipolar or bipolar depression versus healthy controls: Systematic review and meta-analysis.
        J Affect Disord. 2022; 314: 211-221
        • Kong Y.
        • Liu C.
        • Zhang C.
        • et al.
        Association between serum uric acid levels and suicide attempts in adolescents and young adults with major depressive disorder: a retrospective study.
        Neuropsychiatr Dis Treat. 2022; 18: 1469-1477
        • Lindqvist D.
        • Dhabhar F.S.
        • James S.J.
        • et al.
        Oxidative stress, inflammation and treatment response in major depression.
        Psychoneuroendocrinology. 2017; 76: 197-205
        • Li Y.
        • Song W.
        • Tong Y.
        • et al.
        Isoliquiritin ameliorates depression by suppressing NLRP3-mediated pyroptosis via miRNA-27a/SYK/NF-κB axis.
        J Neuroinflam. 2021; 18: 1-23
        • López-López A.L.
        • Jaime H.B.
        • Escobar Villanueva M.D.C.
        • et al.
        Chronic unpredictable mild stress generates oxidative stress and systemic inflammation in rats.
        Physiol Behav. 2016; 161: 15-23
        • Wigner P.
        • Synowiec E.
        • Czarny P.
        • et al.
        Effects of venlafaxine on the expression level and methylation status of genes involved in oxidative stress in rats exposed to a chronic mild stress.
        J Cell Mol Med. 2020; 24: 5675
        • Celikbilek A.
        • Yesim Gocmen A.
        • Tanik N.
        • et al.
        Serum lipid peroxidation markers are correlated with those in brain samples in different stress models.
        Acta Neuropsychiatr. 2014; 26: 51-57
        • Danese A.
        • Pariante C.M.
        • Caspi A.
        • et al.
        Childhood maltreatment predicts adult inflammation in a life-course study.
        Proc Natl Acad Sci U S A. 2007; 104: 1319
        • Belvederi Murri M.
        • Pariante C.
        • Mondelli V.
        • et al.
        HPA axis and aging in depression: systematic review and meta-analysis.
        Psychoneuroendocrinology. 2014; 41: 46-62
        • Du X.
        • Pang T.Y.
        Is Dysregulation of the HPA-axis a core pathophysiology mediating co-morbid depression in neurodegenerative diseases?.
        Front Psychiatry. 2015; 6: 32
        • Schatzberg A.F.
        • Rothschild A.J.
        • Langlais P.J.
        • et al.
        A corticosteroid/dopamine hypothesis for psychotic depression and related states.
        J Psychiatr Res. 1985; 19: 57-64
        • Bielajew C.
        • Konkle A.
        • Merali Z.
        The effects of chronic mild stress on male Sprague–Dawley and Long Evans rats: I. Biochemical and physiological analyses.
        Behav Brain Res. 2002; 136: 583-592
        • Davenport M.D.
        • Tiefenbacher S.
        • Lutz C.K.
        • et al.
        Analysis of endogenous cortisol concentrations in the hair of rhesus macaques.
        Gen Comp Endocrinol. 2006; 147: 255-261
        • De Andrade J.
        • Céspedes I.
        • Abrão R.
        • et al.
        Chronic unpredictable mild stress alters an anxiety-related defensive response, Fos immunoreactivity and hippocampal adult neurogenesis.
        Behav Brain Res. 2013; 250: 81-90
        • Qin D.
        • Rizak J.
        • Chu X.
        • et al.
        A spontaneous depressive pattern in adult female rhesus macaques.
        Sci Rep. 2015; 5: 11267
        • Zoubovsky S.P.
        • Hoseus S.
        • Tumukuntala S.
        • et al.
        Chronic psychosocial stress during pregnancy affects maternal behavior and neuroendocrine function and modulates hypothalamic CRH and nuclear steroid receptor expression.
        Transl Psychiatry. 2020; 10: 6
        • Feng X.
        • Wang L.
        • Yang S.
        • et al.
        Maternal separation produces lasting changes in cortisol and behavior in rhesus monkeys.
        Proc Natl Acad Sci U S A. 2011; 108: 14312-14317
        • Holsboer F.
        The corticosteroid receptor hypothesis of depression.
        Neuropsychopharmacology. 2000; 23: 477-501
        • Raison C.L.
        • Miller A.H.
        When not enough is too much: the role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders.
        Am J Psychiatry. 2003; 160: 1554-1565
        • Genis-Mendoza A.D.
        • Dionisio-García D.M.
        • Gonzalez-Castro T.B.
        • et al.
        Increased levels of cortisol in individuals with suicide attempt and its relation with the number of suicide attempts and depression.
        Front Psychiatry. 2022; 13: 912021
        • Dhabhar F.S.
        Enhancing versus suppressive effects of stress on immune function: implications for immunoprotection and immunopathology.
        Neuroimmunomodulation. 2009; 16: 300-317
        • Alcocer-Gómez E.
        • de Miguel M.
        • Casas-Barquero N.
        • et al.
        NLRP3 inflammasome is activated in mononuclear blood cells from patients with major depressive disorder.
        Brain Behav Immun. 2014; 36: 111-117
        • Paugh S.W.
        • Bonten E.J.
        • Evans W.E.
        Inflammasome-mediated glucocorticoid resistance: the receptor rheostat.
        Mol Cell. Oncol. 2015; 3: e106594
        • Hestad K.
        • Alexander J.
        • Rootwelt H.
        • et al.
        The role of tryptophan dysmetabolism and quinolinic acid in depressive and neurodegenerative diseases.
        Biomolecules. 2022; 12: 998
        • Correia A.S.
        • Vale N.
        Tryptophan metabolism in depression: a narrative review with a focus on serotonin and kynurenine pathways.
        Int J Mol Sci. 2022; 23: 8493
        • Moreno F.A.
        • Parkinson D.
        • Palmer C.
        • et al.
        CSF neurochemicals during tryptophan depletion in individuals with remitted depression and healthy controls.
        Eur Neuropsychopharmacol. 2010; 20: 18-24
        • Capuron L.
        • Gumnick J.F.
        • Musselman D.L.
        • et al.
        Neurobehavioral effects of interferon-alpha in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions.
        Neuropsychopharmacology. 2002; 26: 643-652
        • Kohl C.
        • Walch T.
        • Huber R.
        • et al.
        Measurement of tryptophan, kynurenine and neopterin in women with and without postpartum blues.
        J Affect Disord. 2005; 86: 135-142
        • Swardfager W.
        • Herrmann N.
        • Dowlati Y.
        • et al.
        Indoleamine 2,3-dioxygenase activation and depressive symptoms in patients with coronary artery disease.
        Psychoneuroendocrinology. 2009; 34: 1560-1566
        • Serafini G.
        • Adavastro G.
        • Canepa G.
        • et al.
        Abnormalities in kynurenine pathway metabolism in treatment-resistant depression and suicidality: a systematic review.
        CNS Neurol Disord Drug Targets. 2017; 16: 440-445
        • Raison C.L.
        • Dantzer R.
        • Kelley K.W.
        • et al.
        CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-alpha: relationship to CNS immune responses and depression.
        Mol Psychiatry. 2010; 15: 393-403
        • O'Connor J.C.
        • André C.
        • Wang Y.
        • et al.
        Interferon-gamma and tumor necrosis factor-alpha mediate the upregulation of indoleamine 2,3-dioxygenase and the induction of depressive-like behavior in mice in response to bacillus Calmette-Guerin.
        J Neurosci. 2009; 29: 4200-4209
        • O'Connor J.C.
        • Lawson M.A.
        • André C.
        • et al.
        Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice.
        Mol Psychiatry. 2009; 14: 511-522
        • O'Connor J.C.
        • André C.
        • Wang Y.
        • et al.
        Interferon-gamma and tumor necrosis factor-alpha mediate the upregulation of indoleamine 2,3-dioxygenase and the induction of depressive-like behavior in mice in response to bacillus Calmette-Guerin.
        J Neurosci. 2009; 29: 4200-4209
        • Lugo-Huitron R.
        • Blanco-Ayala T.
        • Ugalde-Muniz P.
        • et al.
        On the antioxidant properties of kynurenic acid: free radical scavenging activity and inhibition of oxidative stress.
        Neurotoxicol Teratol. 2011; 33: 538-547
        • Maddison D.C.
        • Giorgini F.
        The kynurenine pathway and neurodegenerative disease.
        Semin Cell Dev Biol. 2015; 40: 134-141
        • Steiner J.
        • Walter M.
        • Gos T.
        • et al.
        Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: evidence for an immune-modulated glutamatergic neurotransmission?.
        J Neuroinflammation. 2011; 8: 94
        • Meier T.B.
        • Drevets W.C.
        • Wurfel B.E.
        • et al.
        Relationship between neurotoxic kynurenine metabolites and reductions in right medial prefrontal cortical thickness in major depressive disorder.
        Brain Behav Immun. 2016; 53: 39-48
      1. Melatonin in mood disorders.
        World J Biol Psychiatry. 2006; 7: 138-151
        • Savitz J.
        • Drevets W.C.
        • Smith C.M.
        • et al.
        Putative neuroprotective and neurotoxic kynurenine pathway metabolites are associated with hippocampal and amygdalar volumes in subjects with major depressive disorder.
        Neuropsychopharmacology. 2015; 40: 463-471
        • Tanaka M.
        • Bohár Z.
        • Martos D.
        • et al.
        Antidepressant-like effects of kynurenic acid in a modified forced swim test.
        Pharmacol Rep. 2020; 72: 449-455
        • Jovanovic F.
        • Sudhakar A.
        • Knezevic N.N.
        The Kynurenine pathway and polycystic ovary syndrome: inflammation as a common denominator.
        Int J Tryptophan Res. 2022; 15 (11786469221099214)
        • Liu J.
        • Clough S.J.
        • Dubocovich M.L.
        Role of the MT1 and MT2 melatonin receptors in mediating depressive- and anxiety-like behaviors in C3H/HeN mice.
        Genes Brain Behav. 2017; 16: 546-553
        • Demirkan A.
        • Lahti J.
        • Direk N.
        • et al.
        Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies.
        Psychol Med. 2016; 46: 1613-1623
        • Valdes-Tovar M.
        • Estrada-Reyes R.
        • Solis-Chagoyan H.
        • et al.
        Circadian modulation of neuroplasticity by melatonin: a target in the treatment of depression.
        Br J Pharmacol. 2018; 175: 3200-3208
      2. Srinivasan V, Smits M, Spence W, Lowe AD, Kayumov L, Pandi-Perumal SR, Parry B, Cardinali DP.

        • Soumier A.
        • Banasr M.
        • Lortet S.
        • et al.
        Mechanisms contributing to the phase-dependent regulation of neurogenesis by the novel antidepressant, agomelatine, in the adult rat hippocampus.
        Neuropsychopharmacology. 2009; 34: 2390-2403
        • Lee M.Y.
        • Kuan Y.H.
        • Chen H.Y.
        • et al.
        Intravenous administration of melatonin reduces the intracerebral cellular inflammatory response following transient focal cerebral ischemia in rats.
        J Pineal Res. 2007; 42: 297-309
        • Silva S.O.
        • Rodrigues M.R.
        • Ximenes V.F.
        • et al.
        Neutrophils as a specific target for melatonin and kynuramines: Effects on cytokine release.
        J Neuroimmunol. 2004; 156: 146-152
        • Anderson G.
        Linking the biological underpinnings of depression: role of mitochondria interactions with melatonin, inflammation, sirtuins, tryptophan catabolites, DNA repair and oxidative and nitrosative stress, with consequences for classification and cognition.
        Prog Neuropsychopharmacol Biol Psychiatry. 2018; 80: 255-266
        • Dominguez-Alonso A.
        • Ramirez-Rodriguez G.
        • Benitez-King G.
        Melatonin increases dendritogenesis in the hilus of hippocampal organotypic cultures.
        J Pineal Res. 2012; 52: 427-436
        • Won E.
        • Na K.S.
        • Kim Y.K.
        Associations between melatonin, neuroinflammation, and brain alterations in depression.
        Int J Mol Sci. 2021; 23: 305
        • Müller N.
        Immunology of major depression.
        Neuroimmunomodulation. 2014; 21: 123-130
        • Dvorakova M.
        • Zvolský P.
        • Herzog P.
        • et al.
        Endogenous psychoses and T and B lymphocytes.
        Leipzig, Germany. 1980; 107: 221-228
        • Dantzer R.
        Cytokine, sickness behavior, and depression.
        Immunol Allergy Clin N Am. 2009; 29: 247-264
        • Smith R.S.
        The macrophage theory of depression.
        Med Hypotheses. 1991; 35: 298-306
        • Kronfol Z.
        • Silva Jr., J.
        • Greden J.
        • et al.
        Impaired lymphocyte function in depressive illness.
        Life Sci. 1983; 33: 241-247
        • Schleifer S.J.
        • Keller S.E.
        • Meyerson A.T.
        • et al.
        Lymphocyte function in major depressive disorder.
        Arch Gen Psychiatry. 1984; 41: 484-486
        • Wu M.K.
        • Huang T.L.
        • Huang K.W.
        • et al.
        Association between toll-like receptor 4 expression and symptoms of major depressive disorder.
        Neuropsychiatr Dis Treat. 2015; 11: 1853-1857
        • Grosse L.
        • Carvalho L.A.
        • Birkenhager T.K.
        • et al.
        Circulating cytotoxic T cells and natural killer cells as potential predictors for antidepressant response in melancholic depression. Restoration of T regulatory cell populations after antidepressant therapy.
        Psychopharmacology (Berl.). 2016; 233: 1679-1688
        • Irwin M.
        • Gillin J.C.
        Impaired natural killer cell activity among depressed patients.
        Psychiatry Res. 1987; 20: 181-182
        • Darko D.F.
        • Lucas A.H.
        • Gillin J.C.
        • et al.
        Cellular immunity and the hypothalamic-pituitary axis in major affective disorder: a preliminary study.
        Psychiatry Res. 1988; 25: 1-9
        • Schiweck C.
        • Valles-Colomer M.
        • Arolt V.
        • et al.
        Depression and suicidality: a link to premature T helper cell aging and increased Th17 cells.
        Brain Behav Immun. 2020; https://doi.org/10.1016/j.bbi.2020.02.005
        • Tondo L.
        • Burrai C.
        • Scamonatti L.
        • et al.
        Comparison between clinician-rated and self-reported depressive symptoms in Italian psychiatric patients.
        Neuropsychobiology. 1988; 19: 1-5
        • Rock R.B.
        • Gekker G.
        • Hu S.
        • et al.
        Role of microglia in central nervous system infections.
        Clin Microbiol Rev. 2004; 17: 942-964
        • Cotter D.
        • Mackay D.
        • Landau S.
        • et al.
        Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder.
        Arch Gen Psychiatry. 2001; 58: 545-555
        • Ongür D.
        • Drevets W.C.
        • Price J.L.
        Glial reduction in the subgenual prefrontal cortex in mood disorders.
        Proc Natl Acad Sci U S A. 1998; 95: 13290-13295
        • Owen D.R.
        • Narayan N.
        • Wells L.
        • et al.
        Pro-inflammatory activation of primary microglia and macrophages increases 18 kDa translocator protein expression in rodents but not humans.
        J Cereb Blood Flow Metab. 2017; 37: 2679-2690
        • Enache D.
        • Pariante C.M.
        • Mondelli V.
        Markers of central inflammation in major depressive disorder: a systematic review and meta-analysis of studies examining cerebrospinal fluid, positron emission tomography and post-mortem brain tissue.
        Brain Behav Immun. 2019; 81: 24
        • Luczynski P.
        • Whelan S.O.
        • O'Sullivan C.
        • et al.
        Adult microbiota-deficient mice have distinct dendritic morphological changes: differential effects in the amygdala and hippocampus.
        Eur J Neurosci. 2016; 44: 2654-2666
        • Jiang H.
        • Ling Z.
        • Zhang Y.
        • et al.
        Altered fecal microbiota composition in patients with major depressive disorder.
        Brain Behav Immun. 2015; 48: 186-194
        • Zheng P.
        • Zeng B.
        • Zhou C.
        • et al.
        Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism.
        Mol Psychiatry. 2016; 21: 786-796
        • Zheng X.
        • Cheng Y.
        • Chen Y.
        • et al.
        Ferulicacid improves depressive-like behavior in prenatally-stressed offspring rats via anti-inflammatory activity and HPA axis.
        Int J Mol Sci. 2019; 20: 493
        • Spiller R.
        • Garsed K.
        Infection, inflammation, and the irritable bowel syndrome.
        Dig Liver Dis. 2009; 41: 844-849
        • Kelly J.R.
        • Borre Y.
        • O' Brien C.
        • et al.
        Transferring the blues: depression-associated gut microbiota induces neurobehavioural changes in the rat.
        J Psychiatr Res. 2016; 82: 109-118
        • Desbonnet L.
        • Garrett L.
        • Clarke G.
        • et al.
        Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression.
        Neuroscience. 2010; 170: 1179-1188
        • Westfall S.
        • Pasinetti G.M.
        The gut microbiota links dietary polyphenols with management of psychiatric mood disorders.
        Front Neurosci. 2019; 13: 1196
        • Cai T.
        • Zheng S.P.
        • Shi X.
        • et al.
        Therapeutic effect of fecal microbiota transplantation on chronic unpredictable mild stress-induced depression.
        Front Cell Infect Microbiol. 2022; 12: 900652
        • Guo Y.
        • Xie J.P.
        • Deng K.
        • et al.
        Prophylactic Effects of Bifidobacterium adolescentis on Anxiety and Depression-Like Phenotypes After Chronic Stress: A Role of the Gut Microbiota-Inflammation Axis.
        Front Behav Neurosci. 2019 Jun 18; 13: 126
        • Skonieczna-żydecka K.
        • Grochans E.
        • Maciejewska D.
        • et al.
        Faecal short chain fatty acids profile is changed in Polish depressive women.
        Nutrients. 2018; 10: 1939
        • Webster M.J.
        Infections, inflammation, and psychiatric illness: review of postmortem evidence.
        Curr Top Behav Neurosci. 2022; (https://doi.org/10.1007/7854_2022_362. Epub ahead of print. PMID: 35505055.)
        • Horwath E.
        Psychiatric and neuropsychiatric manifestations of HIV infection.
        J Int Assoc Physicians AIDS Care (Chic). 2002; 1: S1-S15
        • Kirch D.G.
        Infection and autoimmunity as etiologic factors in schizophrenia: a review and reappraisal.
        Schizophr Bull. 1993; 19: 355-370
        • Llach C.D.
        • Vieta E.
        Mind long COVID: Psychiatric sequelae of SARS-CoV-2 infection.
        Eur Neuropsychopharmacol. 2021; 49: 119-121
        • Lyketsos C.G.
        • Federman E.B.
        Psychiatric disorders and HIV infection: impact on one another.
        Epidemiol Rev. 1995; 17: 152-164
        • Schwemmle M.
        Borna disease virus infection in psychiatric patients: are we on the right track?.
        Lancet Infect Dis. 2001; 1: 46-52
        • Okusaga O.
        • Yolken R.H.
        • Langenberg P.
        • et al.
        Association of seropositivity for influenza and coronaviruses with history of mood disorders and suicide attempts.
        J Affect Disord. 2011; 130: 220-225
        • Yirmiya R.
        • Rimmerman N.
        • Reshef R.
        Depression as a microglial disease.
        Trends Neurosci. 2015; 38: 637-658
        • Rakofsky J.J.
        • Dunlop B.W.
        Nothing to sneeze at: upper respiratory infections and mood disorders.
        Curr Psychiatry. 2019; 18: 29-34
        • Zhang R.
        • Jiang T.
        • Li N.
        • et al.
        [The negative psychology for the public in Zhejiang province during the epidemic of human H7N9 avian influenza.
        Zhonghua Yu Fang Yi Xue Za Zhi. 2015; 49: 1073-1079
        • Lee S.H.
        • Shin H.S.
        • Park H.Y.
        • et al.
        Depression as a mediator of chronic fatigue and post-traumatic stress symptoms in Middle East respiratory syndrome survivors.
        Psychiatry Investig. 2019; 16: 59-64
        • Glaser R.
        • Robles T.F.
        • Sheridan J.
        • et al.
        Mild depressive symptoms are associated with amplified and prolonged inflammatory responses after influenza virus vaccination in older adults.
        Arch Gen Psychiatry. 2003; 60: 1009-1014
        • Ismael F.
        • Bizario J.C.S.
        • Battagin T.
        • et al.
        Post-infection depressive, anxiety and post-traumatic stress symptoms: a prospective cohort study in patients with mild COVID-19.
        Prog Neuropsychopharmacol Biol Psychiatry. 2021; 111: 110341
        • Adams T.B.
        • Wharton C.M.
        • Quilter L.
        • et al.
        The association between mental health and acute infectious illness among a national sample of 18- to 24-year-old college students.
        J Am Coll Health. 2008; 56: 657-663
        • Andersson N.W.
        • Goodwin R.D.
        • Okkels N.
        • et al.
        Depression and the risk of severe infections: prospective analyses on a nationwide representative sample.
        Int J Epidemiol. 2016; 45: 131-139
        • Janssen H.L.
        • Brouwer J.T.
        • van der Mast R.C.
        • et al.
        Suicide associated with alfa-interferon therapy for chronic viral hepatitis.
        J Hepatol. 1994; 21: 241-243
        • Courtet P.
        • Jaussent I.
        • Genty C.
        • et al.
        Increased CRP levels may be a trait marker of suicidal attempt.
        Eur Neuropsychopharmacol. 2015; 25: 1824-1831
        • Ganança L.
        • Oquendo M.A.
        • Tyrka A.R.
        • et al.
        The role of cytokines in the pathophysiology of suicidal behavior.
        Psychoneuroendocrinology. 2016; 63: 296-310
        • Vasupanrajit A.
        • Jirakran K.
        • Tunvirachaisakul C.
        • et al.
        Suicide attempts are associated with activated immune-inflammatory, nitro-oxidative, and neurotoxic pathways: a systematic review and meta-analysis.
        J Affect Disord. 2021; 295: 80-92
        • Saiz P.A.
        • Garcia-Portilla P.
        • Paredes B.
        • et al.
        Association study of the interleukin-1 gene complex and tumor necrosis factor alpha gene with suicide attempts.
        Psychiatr Genet. 2008; 18: 147-150
        • Sowa-Kucma M.
        • Styczen 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: 372-383
        • Kim Y.K.
        • Hong J.P.
        • Hwang J.A.
        • et al.
        TNF-alpha -308G>A polymorphism is associated with suicide attempts in major depressive disorder.
        J Affect Disord. 2013; 150: 668-672
        • Janelidze S.
        • Ventorp F.
        • Erhardt S.
        • et al.
        Altered chemokine levels in the cerebrospinal fluid and plasma of suicide attempters.
        Psychoneuroendocrinology. 2013; 38: 853-862
        • Asberg M.
        Neurotransmitters and suicidal behavior. The evidence from cerebrospinal fluid studies.
        Ann N Y Acad Sci. 1997; 836: 158-181
        • Hernández-Díaz Y.
        • Genis-Mendoza A.D.
        • González-Castro T.B.
        • et al.
        Association and genetic expression between genes involved in HPA axis and suicide behavior: a systematic review.
        Genes (Basel). 2021; 12: 1608
        • Sandyk R.
        Awerbuch GI Nocturnal melatonin secretion in suicidal patients with multiple sclerosis.
        Int J Neurosci. 1993; 71: 173-182
        • Stanley M.
        • Brown G.M.
        Melatonin levels are reduced in the pineal glands of suicide victims.
        Psychopharmacol Bull. 1988; 24: 484
        • Steenbergen L.
        • Sellaro R.
        • van Hemert S.
        • et al.
        A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood.
        Brain Behav Immun. 2015; 48: 258-264
        • Miranda O.
        • Fan P.
        • Qi X.
        • et al.
        DeepBiomarker: identifying important lab tests from electronic medical records for the prediction of suicide-related events among PTSD patients.
        J Pers Med. 2022 Mar 24; 12: 524
        • Lindqvist D.
        • Janelidze S.
        • Hagell P.
        • et al.
        Interleukin-6 is elevated in the cerebrospinal fluid of suicide attempters and related to symptom severity.
        Biol Psychiatry. 2009; 66: 287-292
        • Isung J.
        • Aeinehband S.
        • Mobarrez F.
        • et al.
        Low vascular endothelial growth factor and interleukin-8 in cerebrospinal fluid of suicide attempters.
        Transl Psychiatry. 2012; 2: e196
        • Isung J.
        • Mobarrez F.
        • Nordström P.
        • et al.
        Low plasma vascular endothelial growth factor (VEGF) associated with completed suicide.
        World J Biol Psychiatry. 2012; 13: 468-473
        • Noroozi R.
        • Omrani M.D.
        • Ayatollahi S.A.
        • et al.
        Interleukin (IL)-8 polymorphisms contribute in suicide behavior.
        Cytokine. 2018; 111: 28-32
        • Janelidze S.
        • Mattei D.
        • Westrin A.
        • et al.
        Cytokine levels in the blood may distinguish suicide attempters from depressed patients.
        Brain Behav Immun. 2011; 25: 335-339
        • Nässberger L.
        • Träskman-Bendz L.
        Increased soluble interleukin-2 receptor concentrations in suicide attempters.
        Acta Psychiatr Scand. 1993; 88: 48-52
        • Conejero I.
        • Jaussent I.
        • Cazals A.
        • et al.
        Association between baseline pro-inflammatory cytokines and brain activation during social exclusion in patients with vulnerability to suicide and depressive disorder.
        Psychoneuroendocrinology. 2019; 99: 236-242
        • Bay-Richter C.
        • Linderholm K.R.
        • Lim C.K.
        • et al.
        A role for inflammatory metabolites as modulators of the glutamate N-methyl-D-aspartate receptor in depression and suicidality.
        Brain Behav Immun. 2015; 43: 110-117
        • Sublette M.E.
        • Galfalvy H.C.
        • Fuchs D.
        • et al.
        Plasma kynurenine levels are elevated in suicide attempters with major depressive disorder.
        Brain Behav Immun. 2011; 25: 1272-1278
        • Knowles E.E.M.
        • Curran J.E.
        • Göring H.H.H.
        • et al.
        Family-based analyses reveal novel genetic overlap between cytokine interleukin-8 and risk for suicide attempt.
        Brain Behav Immun. 2019; 80: 292-299
        • Melhem N.M.
        • Munroe S.
        • Marsland A.
        • et al.
        Blunted HPA axis activity prior to suicide attempt and increased inflammation in attempters.
        Psychoneuroendocrinology. 2017; 77: 284-294
        • Vasupanrajit A.
        • Jirakran K.
        • Tunvirachaisakul C.
        • et al.
        Inflammation and nitro-oxidativestress in current suicidal attempts and current suicidalideation: a systematic review and meta-analysis.
        Mol Psychiatry. 2022; 27: 1350-1361
        • Keaton S.A.
        • Madaj Z.B.
        • Heilman P.
        • et al.
        An inflammatory profile linked to increased suicide risk.
        J Affect Disord. 2019; 247: 57-65
        • Grudet C.
        • Malm J.
        • Westrin A.
        • et al.
        Suicidal patients are deficient in vitamin D, associated with a pro-inflammatory status in the blood.
        Psychoneuroendocrinology. 2014; 50: 210-219
        • Ohlsson L.
        • Gustafsson A.
        • Lavant E.
        • et al.
        Leaky gut biomarkers in depression and suicidal behavior.
        Acta Psychiatr Scand. 2019; 139: 185-193
        • O’Donovan A.
        • Rush G.
        • Hoatam G.
        • et al.
        Suicidal ideation is associated with elevated inflammation in patients with major depressive disorder.
        Depress Anxiety. 2013; 30: 307-314
        • Kim Y.K.
        • Hong J.P.
        • Hwang J.A.
        • et al.
        TNF-alpha -308G>A polymorphism is associated with suicide attempts in major depressive disorder.
        J Affect Disord. 2013; 150: 668-672
        • Coryell W.
        • Wilcox H.
        • Evans S.J.
        • et al.
        Aggression, impulsivity and inflammatory markers as risk factors for suicidal behavior.
        J Psychiatr Res. 2018; 106: 38-42
        • Kim Y.K.
        • Lee S.W.
        • Kim S.H.
        • et al.
        Differences in cytokines between non-suicidal patients and suicidal patients in major depression.
        Prog Neuropsychopharmacol Biol Psychiatry. 2008; 32: 356-361
        • Gabbay V.
        • Klein R.G.
        • Alonso C.M.
        • et al.
        Immune system dysregulation in adolescent major depressive disorder.
        J Affect Disord. 2009; 115: 177-182
        • Mendlovic S.
        • Mozes E.
        • Eilat E.
        • et al.
        Immune activation in non-treated suicidal major depression.
        Immunol Lett. 1999; 67: 105-108
        • Grassi-Oliveira R.
        • Brieztke E.
        • Teixeira A.
        • et al.
        Peripheral chemokine levels in women with recurrent major depression with suicidal ideation.
        Br J Psychiatry. 2012; 34: 71-75
        • Wang Q.
        • Roy B.
        • Turecki G.
        • et al.
        Role of complex epi-genetic switching in tumor necrosis factor-alpha upregulation in the prefrontal cortexof suicide subjects.
        Am J Psychiatry. 2018; 175: 262-274
        • Schiavone S.
        • Neri M.
        • Mhillaj E.
        • et al.
        The NADPH oxidase NOX2 as a novel biomarker for suicidality: evidence from human post mortem brain samples.
        Transl Psychiatry. 2016; 6: e813
        • Tonelli L.H.
        • Stiller J.
        • Rujescu D.
        • et al.
        Elevated cytokine expression in the orbitofrontal cortex of victims of suicide.
        Acta Psychiatr Scand. 2008; 117: 198-206
        • Pandey G.N.
        • Rizavi H.S.
        • Ren X.
        • et al.
        Region-specific alterations in glucocorticoid receptor expression in the postmortem brain of teenage suicide victims.
        Psychoneuroendocrinology. 2013; 38: 2628-2639
        • Gonçalves de Andrade E.
        • González Ibáñez F.
        • Tremblay M.È.
        Microglia as a hub for suicide neuropathology: future investigation and prevention targets.
        Front Cell Neurosci. 2022; 16: 839396
        • Torres-Platas S.G.
        • Cruceanu C.
        • Chen G.G.
        • et al.
        Evidence for increased microglial priming and macrophage recruitment in the dorsal anterior cingulate white matter of depressed suicides.
        Brain Behav Immun. 2014; 42: 50-59
        • Janelidze S.
        • Ventorp F.
        • Erhardt S.
        • et al.
        Altered chemokine levels in the cerebrospinal fluid and plasma of suicide attempters.
        Psychoneuroendocrinology. 2013; 38: 853-862
        • Hennings J.M.
        • Ising M.
        • Uhr M.
        • et al.
        Effects of weariness of life, suicide ideations and suicide attempt on HPA axis regulation in depression.
        Psychoneuroendocrinology. 2021; 131: 105286
        • Chandley M.J.
        • Szebeni A.
        • Szebeni K.
        • et al.
        Markers of elevated oxidativestress in oligodendrocytes captured from the brainstem and occipital cortex in major depressive disorder and suicide.
        Prog Neuropsychopharmacol Biol Psychiatry. 2022; 117: 110559
        • Vargas H.O.
        • Nunes S.O.
        • Pizzo de Castro M.
        • et al.
        Oxidative stress and lowered total antioxidant status are associated with a history of suicide attempts.
        J Affect Disord. 2013; 150: 923-930
        • Köhler-Forsberg O.
        • N Lydholm C.
        • Hjorthøj C.
        • Nordentoft M.
        • et al.
        Efficacy of anti-inflammatory treatment on major depressive disorder or depressive symptoms: meta-analysis of clinical trials.
        Acta Psychiatr Scand. 2019; 139: 404-419
        • Beurel E.
        • Toups M.
        • Nemeroff C.B.
        The Bidirectional Relationship of Depression and Inflammation: Double Trouble.
        Neuron. 2020; 107: 234-256
        • Eyre H.A.
        • Air T.
        • Proctor S.
        • et al.
        A critical review of the efficacy of non-steroidal anti-inflammatory drugs in depression.
        Prog Neuropsychopharmacol Biol Psychiatry. 2015; 57: 11
        • Lehrer S.
        • Rheinstein P.H.
        Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce suicidal ideation and depression.
        Discov Med. 2019; 28: 205-212
        • Eren I.
        • Naziroǧlu M.
        • Demirdaş A.
        • et al.
        Venlafaxine modulates depression-induced oxidative stress in brain and medulla of rat.
        Neurochem Res. 2007; 32: 497-505
        • Wigner P.
        • Synowiec E.
        • Czarny P.
        • et al.
        Effects of venlafaxine on the expression level and methylation status of genes involved in oxidative stress in rats exposed to a chronic mild stress.
        J Cell Mol Med. 2020; 24: 5675
        • Bakhtiari-Dovvombaygi H.
        • Izadi S.
        • Zare Moghaddam M.
        • et al.
        Beneficial effects of vitamin D on anxiety and depression-like behaviors induced by unpredictablechronic mild stress by suppression of brain oxidative stressand neuroinflammation in rats.
        Naunyn Schmiedebergs Arch Pharmacol. 2021; 394: 655-667
        • Steenkamp L.R.
        • Hough C.M.
        • Reus V.I.
        • et al.
        Severity of anxiety- but not depression- is associated with oxidative stress in Major Depressive Disorder.
        J Affect Disord. 2017; 219: 193-200
        • Ising M.
        • Horstmann S.
        • Kloiber S.
        • et al.
        Combined dexamethasone/corticotropin releasing hormone test predicts treatment response in major depression - a potential biomarker?.
        Biol Psychiatry. 2007; 62: 47-54
        • Berardelli I.
        • Serafini G.
        • Cortese N.
        • et al.
        The involvement of hypothalamus-pituitary-adrenal (HPA) axis in suicide risk.
        Brain Sci. 2020 Sep 21; 10: 653
        • Pompili M.
        • Serafini G.
        • Innamorati M.
        • et al.
        The hypothalamic-pituitary-adrenal axis and serotonin abnormalities: a selective overview for the implications of suicide prevention.
        Eur Arch Psychiatry Clin Neurosci. 2010; 260: 583-600
        • Chaki S.
        Vasopressin V1B Receptor Antagonists as Potential Antidepressants.
        Int J Neuropsychopharmacol. 2021; 24: 450-463
        • Iijima M.
        • Yoshimizu T.
        • Shimazaki T.
        • et al.
        Antidepressant and anxiolytic profiles of newly synthesized arginine vasopressin V1Breceptor antagonists: TASP0233278 and TASP0390325.
        Br J Pharmacol. 2014; 171: 3511-3525
        • Ge J.-F.
        • Peng L.
        • Cheng J.-Q.
        • et al.
        Antidepressant-like effect of resveratrol: Involvement of antioxidant effect and peripheral regulation on HPA axis.
        Pharmacol Biochem Behav. 2013; 114–115: 64-69
        • Yang X.-H.
        • Song S.-Q.
        • Xu Y.
        Resveratrol ameliorates chronic unpredictable mild stress-induced depression-like behavior: Involvement of the HPA axis, inflammatory markers, BDNF, and Wnt/β-catenin pathway in rats.
        Neuropsychiatr Dis Treat. 2017; 13: 2727-2736
        • Zheng P.
        • Zeng B.
        • Zhou C.
        • et al.
        Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism.
        Mol Psychiatry. 2016; 21: 786-796
        • Majidi J.
        • Kosari-Nasab M.
        • Salari A.-A.
        Developmental minocycline treatment reverses the effects of neonatal immune activation on anxiety- and depression-like behaviors, hippocampal inflammation, and HPA axis activity in adult mice.
        Brain Res Bull. 2016; 120: 1-13
        • Ke Q.
        • Li R.
        • Cai L.
        • et al.
        Ro41-5253, a selective antagonist of retinoic acid receptor α, ameliorates chronic unpredictable mild stress-induced depressive-like behaviors in rats: Involvement of regulating HPA axis and improving hippocampal neuronal deficits.
        Brain Res Bull. 2019; 146: 302-309
        • Howland R.H.
        Mifepristone as a therapeutic agent in psychiatry.
        J Psychosoc Nurs Ment Health Serv. 2013; 51: 11-14
        • Huang T.L.
        • Lee C.T.
        T-helper 1/T-helper 2 cytokine imbalance and clinical phenotypes of acute-phase major depression.
        Psychiatry Clin Neurosci. 2007 Aug; 61: 415-420
        • Isingrini E.
        • Desmidt T.
        • Belzung C.
        • et al.
        Endothelial dysfunction: a potential therapeutic target for geriatric depression and brain amyloid deposition in Alzheimer's disease?.
        Curr Opin Investig Drugs. 2009; 10 (2007): 46-55
        • Hughes T.D.
        • Güner O.F.
        • Iradukunda E.C.
        • et al.
        The Kynurenine Pathway and Kynurenine 3-Monooxygenase Inhibitors.
        Molecules. 2022; 27: 273
        • Guo Y.
        • Liu Y.
        • Wu W.
        • et al.
        Indoleamine 2,3-dioxygenase (Ido) inhibitors and their nanomedicines for cancer immunotherapy.
        Biomaterials. 2021; 276: 121018
        • Feng Y.
        • Bowden B.F.
        • Kapoor V.
        Ianthellamide A, a selective kynurenine-3-hydroxylase inhibitor from the Australian marine sponge Ianthella quadrangulata.
        Bioorg Med Chem Lett. 2012; 22: 3398-3401
        • Kim H.T.
        • Na B.K.
        • Chung J.
        • et al.
        Structural Basis for Inhibitor-Induced Hydrogen Peroxide Production by Kynurenine 3-Monooxygenase.
        Cell Chem. Biol. 2018; 25: 426-438
        • Röver S.
        • Cesura A.M.
        • Huguenin P.
        • et al.
        Synthesis and biochemical evaluation of N-(4-phenylthiazol-2- yl)benzenesulfonamides as high-affinity inhibitors of kynurenine 3-hydroxylase.
        J Med Chem. 1997; 40: 4378-4385
        • Detanico B.C.
        • Piato A.L.
        • Freitas J.J.
        • et al.
        Antidepressant-like effects of melatonin in the mouse chronic mild stress model.
        Eur J Pharmacol. 2009; 607: 121-125
        • Mantovani M.
        • Pertile R.
        • Calixto J.B.
        • et al.
        Melatonin exerts an antidepressant-like effect in the tail suspension test in mice: Evidence for involvement of N-methyl-D-aspartate receptors and the L-arginine-nitric oxide pathway.
        Neurosci Lett. 2003; 343: 1-4
        • Raghavendra V.
        • Kaur G.
        • Kulkarni S.K.
        Anti-depressant action of melatonin in chronic forced swimming-induced behavioral despair in mice, role of peripheral benzodiazepine receptor modulation.
        Eur Neuropsychopharmacol. 2000; 10: 473-481
        • Norman T.R.
        • Olver J.S.
        Agomelatine for depression: expanding the horizons?.
        Expert Opin Pharmacother. 2019; 20: 647-656
        • Wang X.Q.
        • Wang D.Q.
        • Bao Y.P.
        • et al.
        Preliminary Study on Changes of Sleep EEG power and plasmamelatonin in male patients with majordepressivedisorder after 8 weeks treatment.
        Front Psychiatry. 2021; 12: 736318
        • Garzon C.
        • Guerrero J.M.
        • Aramburu O.
        • et al.
        Effect of melatonin administration on sleep, behavioral disorders and hypnotic drug discontinuation in the elderly: A randomized, double-blind, placebo-controlled study.
        Aging Clin Exp Res. 2009; 21: 38-42
        • Madsen M.T.
        • Isbrand A.
        • Andersen U.O.
        • et al.
        The effect of melatonin on depressive symptoms, anxiety, circadian and sleep disturbances in patients after acute coronary syndrome (MEDACIS): Study protocol for a randomized controlled trial.
        Trials. 2017; 18: 81
        • Høier N.K.
        • Madsen T.
        • Spira A.P.
        • et al.
        Associations between treatment with melatonin and suicidal behavior: a nationwide cohort study.
        J Clin Sleep Med. 2022; 18: 2451-2458
        • Raison C.L.
        • Rutherford R.E.
        • Woolwine B.J.
        • 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: 31-41
        • Tyring S.
        • Bagel J.
        • Lynde C.
        • et al.
        Patient-reported outcomes in moderate-to-severe plaque psoriasis with scalp involvement: results from a randomized, double-blind, placebo-controlled study of etanercept.
        J Eur Acad Dermatol Venereol. 2013; 27: 125-128
        • Langley R.G.
        • Feldman S.R.
        • Han C.
        • et al.
        Ustekinumab significantly improves symptoms of anxiety, depression, and skin-related quality of life in patients with moderate-to-severe psoriasis: Results from a randomized, double-blind, placebo-controlled phase III trial.
        J Am Acad Dermatol. 2010; 63: 457-465
        • Sun Y.
        • Wang D.
        • Salvadore G.
        • et al.
        The effects of interleukin-6 neutralizing antibodies on symptoms of depressed mood and anhedonia in patients with rheumatoid arthritis and multicentric Castleman’s disease.
        Brain Behav Immun. 2017; 66: 156-164
        • McIntyre R.S.
        • 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; 76: 783-790
        • Shayowitz M.
        • Bressler M.
        • Ricardo A.P.
        • et al.
        Infliximab-induced depression and suicidal behavior in adolescent with crohn's disease: case report and review of literature.
        Pediatr Qual Saf. 2019; 4: e229
        • Lebwohl M.G.
        • Papp K.A.
        • Marangell L.B.
        • et al.
        Psychiatric adverse events during treatment with brodalumab: analysis of psoriasis clinical trials.
        J Am Acad Dermatol. 2018; 78: 81-89.e5
        • Dinan K.
        • Dinan T.
        Antibiotics and mental health: The good, the bad and the ugly.
        J Intern Med. 2022; (https://doi.org/10.1111/joim.13543. Epub ahead of print. PMID: 35819136.)
        • Kacal M.J.
        Is minocycline effective for treating depression?.
        J Am Acad Physician Assist. 2022; 35: 13-14
        • Kutkat O.
        • Moatasim Y.
        • Al-Karmalawy A.A.
        • et al.
        Robust antiviral activity of commonly prescribed antidepressants against emerging coronaviruses: in vitro and in silico drug repurposing studies.
        Sci Rep. 2022; 12: 12920
        • Costanza A.
        • Placenti V.
        • Amerio A.
        • et al.
        Chloroquine/hydroxychloroquine use and suicide risk: hypotheses for confluent etiopathogenetic mechanisms?.
        Behav Sci (Basel). 2021 Nov 7; 11: 154
        • Hamm B.S.
        • Rosenthal L.J.
        Psychiatric aspects of chloroquine and hydroxychloroquine treatment in the wake of coronavirus disease-2019: psychopharmacological interactions and neuropsychiatric sequelae.
        Psychosomatics. 2020; 61: 597-606
        • Steenbergen L.
        • Sellaro R.
        • van Hemert S.
        • et al.
        A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood.
        Brain Behav Immun. 2015; 48 (258–26)
        • Slykerman R.F.
        • Hood F.
        • Wickens K.
        • et al.
        Effect of Lactobacillus rhamnosus HN001 in pregnancy on postpartum symptoms of depression and anxiety: a randomised double-blind placebo-controlled trial.
        EBioMedicine. 2017; 24: 159-165
        • Akkasheh G.
        • Kashani-Poor Z.
        • Tajabadi-Ebrahimi M.
        • et al.
        Clinical and metabolic response to probiotic administration in patients with major depressive disorder: a randomized, double-blind, placebo-controlled trial.
        Nutrition. 2016; 32: 315-320
        • Kazemi A.
        • Noorbala A.A.
        • Azam K.
        • et al.
        Effect of probiotic and prebiotic vs placebo on psychological outcomes in patients with major depressive disorder: a randomized clinical trial.
        Clin Nutr. 2019; 38: 522-528
        • Shah A.M.
        • Yang W.
        • Mohamed H.
        • et al.
        Microbes: a hidden treasure of polyunsaturated fatty acids.
        Front Nutr. 2022 Mar 17; 9: 827837
        • Goldberg S.B.
        • Pace B.T.
        • Nicholas C.R.
        • et al.
        The experimental effects of psilocybin on symptoms of anxiety and depression: a meta-analysis.
        Psychiatry Res. 2020; 284: 112749
        • Strumila R.
        • Nobile B.
        • Korsakova L.
        • et al.
        Psilocybin, a Naturally Occurring Indoleamine Compound, Could Be Useful to Prevent Suicidal Behaviors.
        Pharmaceuticals (Basel). 2021; 14: 1213
        • Wang L.
        • Wang R.
        • Liu L.
        • et al.
        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
        • O'Donnell C.
        • Demler T.L.
        • Trigoboff E.
        Selective Serotonin Reuptake Inhibitors (SSRIs) and Their Effect on Patient Aggression in Adult Patients in a State Psychiatric Facility: A Retrospective Analysis.
        Innov Clin Neurosci. 2022; 19: 33-38
        • Murrough J.W.
        • Iosifescu D.V.
        • Chang L.C.
        • et al.
        Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial.
        Am J Psychiatry. 2013; 170: 1134-1142
        • Yang Y.
        • Song Y.
        • Zhang X.
        • et al.
        Ketamine relieves depression-like behaviors induced by chronic postsurgical pain in rats through anti-inflammatory, anti-oxidant effects and regulating BDNF expression.
        Psychopharmacology. 2020; 237: 1657-1669
        • Chen S.
        • Sang N.
        Histone deacetylase inhibitors: the epigenetic therapeutics that repress hypoxia-inducible factors.
        J Biomed Biotechnol. 2010; 2011: 197946
        • Peng X.
        • Huang M.
        • Zhao W.
        • et al.
        RAGE mediates airway inflammation via the HDAC1 pathway in a toluene diisocyanate-induced murine asthma model.
        BMC Pulm Med. 2022; 22: 61
        • Emanuele E.
        The histone deacetylase inhibitor FK228 may have therapeutic usefulness to prevent suicidal behaviour via upregulation of the guanosine triphosphatase Rap-1.
        Med Hypotheses. 2007; 68: 451-452
        • Li S.H.
        • Achilles M.R.
        • Werner-Seidler A.
        • et al.
        Appropriate use and operationalization of adherence to digital cognitive behavioral therapy for depression and anxiety in youth: systematic review.
        JMIR Ment Health. 2022; 9: e37640
        • Núñez D.
        • Gaete J.
        • Meza D.
        • et al.
        Testing the effectiveness of a blended intervention to reduce suicidalideation among school adolescents in chile: a protocol for a cluster randomized controlled trial.
        Int J Environ Res Public Health. 2022; 19: 3947
        • Shields G.S.
        • Spahr C.M.
        • Slavich G.M.
        Psychosocial Interventions and immune system function: a systematic review and meta-analysis of randomized clinical trials.
        JAMA Psychiatry. 2020; 77: 1031-1043
        • Goldsmith D.R.
        • Rapaport M.H.
        • Miller B.J.
        A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression.
        Mol Psychiatry. 2016; 21: 1696-1709