{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:45:47Z","timestamp":1791359147009,"version":"4.3.1"},"reference-count":115,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T00:00:00Z","timestamp":1712966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Seasonal rhythms affect the immune system. Evidence supports the involvement of immuno-inflammatory mechanisms in bipolar disorder (BD), with the neutrophil to lymphocyte ratio (NLR), and the systemic immune-inflammatory index (SII; platelets \u00d7 neutrophils\/lymphocytes) consistently reported to be higher in patients with BD than in HC, but seasonal rhythms of innate and adaptive immunity have never been studied. We retrospectively studied NLR and SII in 824 participants divided into three groups: 321 consecutively admitted inpatients affected by a major depressive episode in course of BD, and 255 consecutively admitted inpatients affected by obsessive\u2013compulsive disorder (OCD; positive psychiatric control), and 248 healthy controls (HC). Patients with BD showed markedly higher markers of systemic inflammation in autumn and winter, but not in spring and summer, in respect to both HC and patients with OCD, thus suggesting a specific effect of season on inflammatory markers in BD, independent of a shared hospital setting and drug treatment. Given that systemic inflammation is emerging as a new marker and as target for treatment in depressive disorders, we suggest that seasonal rhythms should be considered for tailoring antidepressant immuno-modulatory treatments in a precision medicine approach.<\/jats:p>","DOI":"10.3390\/ijms25084310","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T10:24:26Z","timestamp":1713176666000},"page":"4310","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Higher Seasonal Variation of Systemic Inflammation in Bipolar Disorder"],"prefix":"10.3390","volume":"25","author":[{"given":"Sara","family":"Dallaspezia","sequence":"first","affiliation":[{"name":"Division of Neuroscience, IRCCS Ospedale San Raffaele, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7050-1375","authenticated-orcid":false,"given":"Vincenzo","family":"Cardaci","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Vita-Salute San Raffaele, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario Gennaro","family":"Mazza","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, IRCCS Ospedale San Raffaele, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"De Lorenzo","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Rovere Querini","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Vita-Salute San Raffaele, 20132 Milano, Italy"},{"name":"Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Colombo","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Vita-Salute San Raffaele, 20132 Milano, Italy"},{"name":"Mood Disorders Unit, IRCCS Ospedale San Raffaele, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Benedetti","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, IRCCS Ospedale San Raffaele, 20132 Milano, Italy"},{"name":"Universit\u00e0 Vita-Salute San Raffaele, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.2147\/CLEP.S372341","article-title":"Seasonal effects on hospitalizations due to mood and psychotic disorders: A nationwide 31-year register study","volume":"14","author":"Svirskis","year":"2022","journal-title":"Clin. Epidemiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1016\/S0140-6736(02)11737-5","article-title":"Effect of sunlight and season on serotonin turnover in the brain","volume":"360","author":"Lambert","year":"2002","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1001\/archpsyc.65.9.1072","article-title":"Seasonal variation in human brain serotonin transporter binding","volume":"65","author":"Willeit","year":"2008","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1038\/sj.npp.1301560","article-title":"Enhanced serotonin transporter function during depression in seasonal affective disorder","volume":"33","author":"Willeit","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1093\/brain\/aww043","article-title":"Seasonal difference in brain serotonin transporter binding predicts symptom severity in patients with seasonal affective disorder","volume":"139","author":"Andersen","year":"2016","journal-title":"Brain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3389\/fpsyt.2020.00071","article-title":"Neuroinflammation in bipolar depression","volume":"11","author":"Benedetti","year":"2020","journal-title":"Front. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.euroneuro.2021.11.003","article-title":"Selective association of cytokine levels and kynurenine\/tryptophan ratio with alterations in white matter microstructure in bipolar but not in unipolar depression","volume":"55","author":"Comai","year":"2022","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.bbi.2016.05.007","article-title":"A dynamic course of T cell defects in individuals at risk for mood disorders","volume":"58","author":"Snijders","year":"2016","journal-title":"Brain. Behav. Immun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.biopsych.2011.10.025","article-title":"Depression and inflammation: An intricate relationship","volume":"71","author":"Dantzer","year":"2012","journal-title":"Biol. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.neubiorev.2011.12.005","article-title":"Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression","volume":"36","author":"Leonard","year":"2012","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.biopsych.2013.09.037","article-title":"Autoimmunity, inflammation, and psychosis: A search for peripheral markers","volume":"75","author":"Bergink","year":"2014","journal-title":"Biol. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s11920-014-0541-1","article-title":"Bipolar disorder: Role of immune-inflammatory cytokines, oxidative and nitrosative stress and tryptophan catabolites","volume":"17","author":"Anderson","year":"2015","journal-title":"Curr. Psychiatry Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.it.2005.11.006","article-title":"Cytokines sing the blues: Inflammation and the pathogenesis of depression","volume":"27","author":"Raison","year":"2006","journal-title":"Trends Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.euroneuro.2023.01.003","article-title":"New biomarkers in mood disorders: Insights from immunopsychiatry and neuroimaging","volume":"69","author":"Benedetti","year":"2023","journal-title":"Eur. Neuropsychopharmacol. J. Eur. Coll. Neuropsychopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"22209","DOI":"10.1038\/s41598-023-49146-6","article-title":"Circulating cytotoxic immune cell composition, activation status and toxins expression associate with white matter microstructure in bipolar disorder","volume":"13","author":"Aggio","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jad.2016.05.047","article-title":"Inflammatory cytokines influence measures of white matter integrity in Bipolar Disorder","volume":"202","author":"Benedetti","year":"2016","journal-title":"J. Affect. Disord."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.jad.2014.11.010","article-title":"Disruption of white matter integrity marks poor antidepressant response in bipolar disorder","volume":"174","author":"Bollettini","year":"2015","journal-title":"J. Affect. Disord."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.jad.2014.12.030","article-title":"Cognitive performances associate with measures of white matter integrity in bipolar disorder","volume":"174","author":"Poletti","year":"2015","journal-title":"J. Affect. Disord."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.euroneuro.2020.11.009","article-title":"Higher baseline interleukin-1\u03b2 and TNF-\u03b1 hamper antidepressant response in major depressive disorder","volume":"42","author":"Benedetti","year":"2021","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1177\/02698811231190859","article-title":"Hippocampal and parahippocampal volume and function predict antidepressant response in patients with major depression: A multimodal neuroimaging study","volume":"37","author":"Paolini","year":"2023","journal-title":"J. Psychopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.euroneuro.2023.07.010","article-title":"Neutrophil to lymphocyte ratio and antidepressant treatment response in patients with major depressive disorder: Effect of sex and hippocampal volume","volume":"76","author":"Paolini","year":"2023","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.bbi.2024.02.019","article-title":"Low-dose interleukin 2 antidepressant potentiation in unipolar and bipolar depression: Safety, efficacy, and immunological biomarkers","volume":"118","author":"Poletti","year":"2024","journal-title":"Brain Behav. Immun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1001\/2013.jamapsychiatry.4","article-title":"A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: The role of baseline inflammatory biomarkers","volume":"70","author":"Raison","year":"2013","journal-title":"JAMA Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"G\u0119dek, A., Szular, Z., Antosik, A.Z., Mierzejewski, P., and Dominiak, M. (2023). Celecoxib for Mood Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J. Clin. Med., 12.","DOI":"10.3390\/jcm12103497"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/s41386-020-00948-6","article-title":"Augmentation therapy with minocycline in treatment-resistant depression patients with low-grade peripheral inflammation: Results from a double-blind randomised clinical trial","volume":"46","author":"Nettis","year":"2021","journal-title":"Neuropsychopharmacology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e2230367","DOI":"10.1001\/jamanetworkopen.2022.30367","article-title":"Effect of minocycline on depressive symptoms in patients with treatment-resistant depression: A randomized clinical trial","volume":"5","author":"Clemens","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"100561","DOI":"10.1016\/j.bbih.2022.100561","article-title":"Sex differences in a double-blind randomized clinical trial with minocycline in treatment-resistant depressed patients: CRP and IL-6 as sex-specific predictors of treatment response","volume":"26","author":"Lombardo","year":"2022","journal-title":"Brain Behav. Immun. -Health"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1097\/YIC.0000000000000403","article-title":"Antidepressant psychopharmacology: Is inflammation a future target?","volume":"37","author":"Benedetti","year":"2022","journal-title":"Int. Clin. Psychopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/nri.2015.5","article-title":"The role of inflammation in depression: From evolutionary imperative to modern treatment target","volume":"16","author":"Miller","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"17351","DOI":"10.4088\/JCP.11m07396","article-title":"Relationship of prior antidepressant exposure to long-term prospective outcome in bipolar I disorder outpatients","volume":"73","author":"Post","year":"2012","journal-title":"J. Clin. Psychiatry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1097\/YIC.0b013e3283409419","article-title":"Differential clinical characteristics, medication usage, and treatment response of bipolar disorder in the US versus The Netherlands and Germany","volume":"26","author":"Post","year":"2011","journal-title":"Int. Clin. Psychopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1001\/jama.2023.18588","article-title":"Diagnosis and treatment of bipolar disorder: A review","volume":"330","author":"Nierenberg","year":"2023","journal-title":"JAMA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/0006-3223(95)00295-2","article-title":"Lifetime rates of suicide attempts among subjects with bipolar and unipolar disorders relative to subjects with other Axis I disorders","volume":"39","author":"Chen","year":"1996","journal-title":"Biol. Psychiatry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"506","DOI":"10.4088\/JCP.v64n0503","article-title":"Factors Associated with Suicide Attempts in 648 Patients with Bipolar Disorder in the Stanley Foundation Bipolar Network","volume":"64","author":"Leverich","year":"2003","journal-title":"J. Clin. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1001\/archpsyc.58.9.844","article-title":"Excess mortality in bipolar and unipolar disorder in Sweden","volume":"58","author":"Osby","year":"2001","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1749-6632.1986.tb27909.x","article-title":"Suicide and bipolar disorders","volume":"487","author":"Jamison","year":"1986","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jpsychires.2006.10.013","article-title":"Immunological aspects in the neurobiology of suicide: Elevated microglial density in schizophrenia and depression is associated with suicide","volume":"42","author":"Steiner","year":"2008","journal-title":"J. Psychiatr. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.bbi.2023.02.021","article-title":"Suicide in bipolar disorder patients is associated with hippocampal microglia activation and reduction of lymphocytes-activation gene 3 (LAG3) microglial checkpoint expression","volume":"110","author":"Naggan","year":"2023","journal-title":"Brain Behav. Immun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e163","DOI":"10.1017\/S2045796020000748","article-title":"Seasonality of suicide: A multi-country multi-community observational study","volume":"29","author":"Yu","year":"2020","journal-title":"Epidemiol. Psychiatr. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1038\/s41380-021-01381-x","article-title":"A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials","volume":"27","author":"Sforzini","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jphotobiol.2009.11.014","article-title":"Photoimmunomodulation and melatonin","volume":"98","author":"Haldar","year":"2010","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2671","DOI":"10.4049\/jimmunol.153.6.2671","article-title":"Activation of human monocytes by the pineal hormone melatonin","volume":"153","author":"Morrey","year":"1994","journal-title":"J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/jpi.12075","article-title":"The role of melatonin in the cells of the innate immunity: A review","volume":"55","author":"Calvo","year":"2013","journal-title":"J. Pineal Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"102255","DOI":"10.1016\/j.isci.2021.102255","article-title":"Seasonal and daytime variation in multiple immune parameters in humans: Evidence from 329,261 participants of the UK Biobank cohort","volume":"24","author":"Wyse","year":"2021","journal-title":"iScience"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jad.2015.06.003","article-title":"Enhanced inflammatory and T-helper-1 type responses but suppressed lymphocyte proliferation in patients with seasonal affective disorder and treated by light therapy","volume":"185","author":"Song","year":"2015","journal-title":"J. Affect. Disord."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/acps.12424","article-title":"Light therapy and serotonin transporter binding in the anterior cingulate and prefrontal cortex","volume":"132","author":"Harrison","year":"2015","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Liu, B., and Taioli, E. (2015). Seasonal variations of complete blood count and inflammatory biomarkers in the US population-analysis of NHANES data. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0142382"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"108","DOI":"10.2215\/CJN.03880411","article-title":"Seasonal variations in mortality, clinical, and laboratory parameters in hemodialysis patients: A 5-year cohort study","volume":"7","author":"Usvyat","year":"2012","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1001\/jamapsychiatry.2017.1567","article-title":"Inflammation in the neurocircuitry of obsessive-compulsive disorder","volume":"74","author":"Attwells","year":"2017","journal-title":"JAMA Psychiatry"},{"key":"ref_50","unstructured":"Meyer, J. (2021). The Neurobiology and Treatment of OCD: Accelerating Progress, Springer."},{"key":"ref_51","first-page":"193","article-title":"Seasonal variations in obsessive-compulsive disorder: Analysis of prospective-clinical data","volume":"58","author":"Tufan","year":"2021","journal-title":"Arch. Neuropsychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"160","DOI":"10.4103\/0972-6748.151701","article-title":"Seasonal obsessive-compulsive disorder","volume":"23","author":"Sinha","year":"2014","journal-title":"Ind. Psychiatry J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.neubiorev.2016.03.011","article-title":"Systematic review of environmental risk factors for obsessive-compulsive disorder: A proposed roadmap from association to causation","volume":"65","author":"Brander","year":"2016","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.jad.2019.11.040","article-title":"Exploring circannual rhythms and chronotype effect in patients with Obsessive-Compulsive Tic Disorder (OCTD): A pilot study","volume":"262","author":"Vitale","year":"2020","journal-title":"J. Affect. Disord."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1001\/archpsyc.1993.01820170095015","article-title":"Seasonal effects on platelet 5-HT content in patients with OCD and controls","volume":"50","author":"Brewerton","year":"1993","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1176\/ajp.148.12.1727","article-title":"Seasonal variation in obsessive-compulsive disorder: Preliminary experience with light treatment","volume":"148","author":"Yoney","year":"1991","journal-title":"Am. J. Psychiatry"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e986","DOI":"10.4088\/JCP.16m11310","article-title":"Higher Baseline Proinflammatory Cytokines Mark Poor Antidepressant Response in Bipolar Disorder","volume":"78","author":"Benedetti","year":"2017","journal-title":"J. Clin. Psychiatry"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.3389\/fpsyt.2020.590095","article-title":"Pro-inflammatory cytokines predict brain metabolites concentrations in the anterior cingulate cortex of patients with bipolar disorder","volume":"11","author":"Poletti","year":"2020","journal-title":"Front. Psychiatry"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jpsychires.2021.05.071","article-title":"Circulating inflammatory markers impact cognitive functions in bipolar depression","volume":"140","author":"Poletti","year":"2021","journal-title":"J. Psychiatr. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s00406-016-0731-4","article-title":"Kynurenine pathway and white matter microstructure in bipolar disorder","volume":"268","author":"Poletti","year":"2016","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.jad.2019.08.034","article-title":"Grey and white matter structure associates with the activation of the tryptophan to kynurenine pathway in bipolar disorder","volume":"259","author":"Poletti","year":"2019","journal-title":"J. Affect. Disord."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6099","DOI":"10.1111\/febs.16086","article-title":"Indoleamine 2,3-dioxygenase 1 (IDO1): An up-to-date overview of an eclectic immunoregulatory enzyme","volume":"289","author":"Pallotta","year":"2022","journal-title":"FEBS J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1017\/S0033291717000745","article-title":"Immunopsychiatry: Important facts","volume":"47","author":"Khandaker","year":"2017","journal-title":"Psychol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S2215-0366(21)00466-1","article-title":"Immunopsychiatry in 2021: Premise to promise, and back again","volume":"9","author":"Pillinger","year":"2022","journal-title":"Lancet Psychiatry"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Khandaker, G., Harrison, N., Bullmore, E., and Dantzer, R. (2021). Textbook of Immunopsychiatry, Cambridge University Press.","DOI":"10.1017\/9781108539623"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Berk, M., Leboyer, M., and Sommer, I.E. (2021). Immuno-Psychiatry, Springer.","DOI":"10.1007\/978-3-030-71229-7"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/s41398-019-0570-y","article-title":"Inflammation-related biomarkers in major psychiatric disorders: A cross-disorder assessment of reproducibility and specificity in 43 meta-analyses","volume":"9","author":"Yuan","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/S2215-0366(21)00232-7","article-title":"Mental disorders and risk of COVID-19-related mortality, hospitalisation, and intensive care unit admission: A systematic review and meta-analysis","volume":"8","author":"Vai","year":"2021","journal-title":"Lancet Psychiatry"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s40263-022-00931-3","article-title":"Post-COVID-19 depressive symptoms: Epidemiology, pathophysiology, and pharmacological treatment","volume":"36","author":"Mazza","year":"2022","journal-title":"CNS Drugs"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.psyneuen.2014.08.002","article-title":"Herpesviruses, inflammatory markers and incident depression in a longitudinal study of Detroit residents","volume":"50","author":"Simanek","year":"2014","journal-title":"Psychoneuroendocrinology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.jad.2019.11.150","article-title":"Atypical immune response to Epstein-Barr virus in major depressive disorder","volume":"264","author":"Dickerson","year":"2020","journal-title":"J. Affect. Disord."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1192\/bjp.2019.40","article-title":"Seasonal variation in antidepressant prescriptions, environmental light and web queries for seasonal affective disorder","volume":"215","author":"Lightman","year":"2019","journal-title":"Br. J. Psychiatry"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"31918","DOI":"10.4088\/PCC.20m02790","article-title":"Seasonal variation in antidepressant prescribing: Year on year analysis for England","volume":"23","author":"Heald","year":"2021","journal-title":"Prim. Care Companion CNS Disord."},{"key":"ref_74","unstructured":"Avery, D., Roy-Bryne, P., and Solomon, D. (2024, April 12). Seasonal Affective Disorder: Treatment. (25 July 2017) [3 February 2019]. Available online: http:\/\/www.uptodate.com\/contents\/seasonal-affective-disordertreatment."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1097\/00008877-199000150-00001","article-title":"Seasonal and circadian variations of behavioural response to antidepressants in the forced swimming test in rats","volume":"1","author":"Borsini","year":"1990","journal-title":"Behav. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.jad.2017.03.028","article-title":"Season of treatment initiation with antidepressants and suicidal behavior: A population-based cohort study in Sweden","volume":"215","author":"Makris","year":"2017","journal-title":"J. Affect. Disord."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/j.jad.2011.11.012","article-title":"The association between sunshine duration and paroxetine response time in patients with major depressive disorder","volume":"136","author":"Tomita","year":"2012","journal-title":"J. Affect. Disord."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1177\/0269881109102919","article-title":"Evidence-based guidelines for treating bipolar disorder: Revised second edition\u2014Recommendations from the British Association for Psychopharmacology","volume":"23","author":"Goodwin","year":"2009","journal-title":"J. Psychopharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.encep.2014.11.002","article-title":"French Society for Biological Psychiatry and Neuropsychopharmacology task force. Formal consensus for the treatment of bipolar disorder: An update","volume":"41","author":"Samalin","year":"2014","journal-title":"L\u2019encephale"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1176\/ajp.151.12.1","article-title":"Practice guidelines for the treatment of patients with bipolar disorder","volume":"151","author":"Association","year":"1994","journal-title":"Am. J. Psychiatry"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/bdi.12609","article-title":"Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder","volume":"20","author":"Yatham","year":"2018","journal-title":"Bipolar Disord."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3109\/15622970903555881","article-title":"The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: Update 2010 on the treatment of acute bipolar depression","volume":"11","author":"Grunze","year":"2010","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1176\/appi.ajp.2009.09010105","article-title":"Gender and depressive symptoms in 711 patients with bipolar disorder evaluated prospectively in the Stanley Foundation bipolar treatment outcome network","volume":"167","author":"Altshuler","year":"2010","journal-title":"Am. J. Psychiatry"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/j.1399-5618.2007.00467.x","article-title":"Three times more days depressed than manic or hypomanic in both bipolar I and bipolar II disorder","volume":"9","author":"Kupka","year":"2007","journal-title":"Bipolar Disord."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1017\/S003329170500437X","article-title":"Chronotherapeutics (light and wake therapy) in affective disorders","volume":"35","author":"Benedetti","year":"2005","journal-title":"Psychol. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"401","DOI":"10.31887\/DCNS.2012.14.4\/fbenedetti","article-title":"Antidepressant chronotherapeutics for bipolar depression","volume":"14","author":"Benedetti","year":"2012","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_87","unstructured":"Wirz-Justice, A., Benedetti, F., and Terman, M. (2013). A Clinician\u2019s Manual for Light and Wake Therapy, Karger. [2nd ed.]."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1586\/ern.11.61","article-title":"Chronobiological therapy for mood disorders","volume":"11","author":"Dallaspezia","year":"2011","journal-title":"Expert Rev. Neurother."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"133","DOI":"10.4088\/JCP.13m08455","article-title":"Rapid treatment response of suicidal symptoms to lithium, sleep deprivation, and light therapy (chronotherapeutics) in drug-resistant bipolar depression","volume":"75","author":"Benedetti","year":"2014","journal-title":"J. Clin. Psychiatry"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.neuron.2023.09.023","article-title":"Circadian rhythms and mood disorders: Time to see the light","volume":"112","author":"Dollish","year":"2023","journal-title":"Neuron"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41583-018-0088-y","article-title":"Rhythms of life: Circadian disruption and brain disorders across the lifespan","volume":"20","author":"Logan","year":"2019","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Orozco-Solis, R., and Aguilar-Arnal, L. (2020). Circadian regulation of immunity through epigenetic mechanisms. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.00096"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/nri3386","article-title":"Circadian control of the immune system","volume":"13","author":"Scheiermann","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e59258","DOI":"10.7554\/eLife.59258","article-title":"Neutrophil infiltration regulates clock-gene expression to organize daily hepatic metabolism","volume":"9","author":"Crespo","year":"2020","journal-title":"Elife"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e20211604","DOI":"10.1084\/jem.20211604","article-title":"Neural control of immune cell trafficking","volume":"219","author":"Mueller","year":"2022","journal-title":"J. Exp. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.smrv.2016.06.007","article-title":"Chronotype and circadian rhythm in bipolar disorder: A systematic review","volume":"34","author":"Melo","year":"2017","journal-title":"Sleep Med. Rev."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.1210\/jc.2004-1667","article-title":"Major depression is associated with significant diurnal elevations in plasma interleukin-6 levels, a shift of its circadian rhythm, and loss of physiological complexity in its secretion: Clinical implications","volume":"90","author":"Alesci","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jad.2020.03.073","article-title":"Increased inflammatory biomarkers and changes in biological rhythms in bipolar disorder: A case-control study","volume":"271","author":"Bavaresco","year":"2020","journal-title":"J. Affect. Disord."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"740686","DOI":"10.3389\/fphys.2021.740686","article-title":"Effective Antidepressant Chronotherapeutics (Sleep Deprivation and Light Therapy) Normalize the IL-1\u03b2:IL-1ra Ratio in Bipolar Depression","volume":"12","author":"Benedetti","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s41398-019-0671-7","article-title":"Longitudinal transcriptome-wide gene expression analysis of sleep deprivation treatment shows involvement of circadian genes and immune pathways","volume":"9","author":"Foo","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.euroneuro.2020.11.016","article-title":"Brain-immune crosstalk in the treatment of major depressive disorder","volume":"45","author":"Branchi","year":"2021","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_102","first-page":"346","article-title":"Perspectives in affective disorders: Clocks and sleep","volume":"51","author":"Benedetti","year":"2019","journal-title":"Eur. J. Neurosci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"249","DOI":"10.31887\/DCNS.2015.17.3\/ggoodwin","article-title":"The overlap between anxiety, depression, and obsessive-compulsive disorder","volume":"17","author":"Goodwin","year":"2015","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.pnpbp.2018.03.012","article-title":"Neutrophil\/lymphocyte ratio and platelet\/lymphocyte ratio in mood disorders: A meta-analysis","volume":"84","author":"Mazza","year":"2018","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Dadouli, K., Janho, M.B., Hatziefthimiou, A., Voulgaridi, I., Piaha, K., Anagnostopoulos, L., Ntellas, P., Mouchtouri, V.A., Bonotis, K., and Christodoulou, N. (2022). Neutrophil-to-Lymphocyte, Monocyte-to-Lymphocyte, Platelet-to-Lymphocyte Ratio and Systemic Immune-Inflammatory Index in Different States of Bipolar Disorder. Brain Sci., 12.","DOI":"10.3390\/brainsci12081034"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1080\/08039488.2021.1919201","article-title":"The severity of inflammation in major neuropsychiatric disorders: Comparison of neutrophil\u2013lymphocyte and platelet\u2013lymphocyte ratios between schizophrenia, bipolar mania, bipolar depression, major depressive disorder, and obsessive compulsive disorder","volume":"75","author":"Bulut","year":"2021","journal-title":"Nord. J. Psychiatry"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"McCullagh, P., and Nelder, J.A. (1989). Generalized Linear Models, Chapman & Hall. [2nd ed.].","DOI":"10.1007\/978-1-4899-3242-6"},{"key":"ref_108","unstructured":"Field, A. (2002). How to Design and Report Experiments, Sage Publications Ltd."},{"key":"ref_109","unstructured":"American Psychological Association (2005). Concise Rules of APA Style, Amer Psychological Assn."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Cohen, J. (2013). Statistical Power Analysis for the Behavioral Sciences, Academic Press.","DOI":"10.4324\/9780203771587"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.bbi.2021.02.031","article-title":"Relationship between body mass index and neuropsychiatric symptoms: Evidence and inflammatory correlates","volume":"94","author":"Huet","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/nyas.13712","article-title":"Inflammation in psychiatric disorders: What comes first?","volume":"1437","author":"Bauer","year":"2019","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/bdi.12484","article-title":"Body mass index associates with white matter microstructure in bipolar depression","volume":"19","author":"Mazza","year":"2017","journal-title":"Bipolar Disord."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"6743","DOI":"10.1017\/S0033291723000223","article-title":"Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants","volume":"53","author":"McWhinney","year":"2023","journal-title":"Psychol. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"6806","DOI":"10.1038\/s41380-021-01098-x","article-title":"Association between body mass index and subcortical brain volumes in bipolar disorders\u2013ENIGMA study in 2735 individuals","volume":"26","author":"McWhinney","year":"2021","journal-title":"Mol. Psychiatry"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/8\/4310\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:27:28Z","timestamp":1760106448000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/8\/4310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,13]]},"references-count":115,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["ijms25084310"],"URL":"https:\/\/doi.org\/10.3390\/ijms25084310","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,13]]}}}