<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">ppan</journal-id><journal-title-group><journal-title xml:lang="en">Personalized Psychiatry and Neurology</journal-title><trans-title-group xml:lang="ru"><trans-title>Personalized Psychiatry and Neurology</trans-title></trans-title-group></journal-title-group><issn pub-type="epub">2712-9179</issn><publisher><publisher-name>V. M. Bekhterev National Medical Research Centre for Psychiatry and Neurology of the Ministry of Health of the Russian Federation (Bekhterev NMRC PN)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.52667/2712-9179-2026-6-1-37-48</article-id><article-id custom-type="elpub" pub-id-type="custom">ppan-162</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ARTICLE</subject></subj-group></article-categories><title-group><article-title>Sex-Specific Links Between Peripheral Inflammation and Metabolic Risk in Bipolar Disorder: Towards Risk Stratification</article-title><trans-title-group xml:lang="ru"><trans-title></trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="western" xml:lang="en"><surname>Popov</surname><given-names>Mikhail Yu.</given-names></name></name-alternatives><bio xml:lang="en"><p>192019, Saint-Petersburg</p></bio><email xlink:type="simple">popocmikhail@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="western" xml:lang="en"><surname>Lepik</surname><given-names>Olga V.</given-names></name></name-alternatives><bio xml:lang="en"><p>192019, Saint-Petersburg</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="western" xml:lang="en"><surname>Yakovleva</surname><given-names>Yulia A.</given-names></name></name-alternatives><bio xml:lang="en"><p>192019, Saint-Petersburg</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="western" xml:lang="en"><surname>Kosterin</surname><given-names>Dmitry N.</given-names></name></name-alternatives><bio xml:lang="en"><p>192019, Saint-Petersburg</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="western" xml:lang="en"><surname>Yanushko</surname><given-names>Maria G.</given-names></name></name-alternatives><bio xml:lang="en"><p>192019, Saint-Petersburg</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="western" xml:lang="en"><surname>Lutova</surname><given-names>Natalia B.</given-names></name></name-alternatives><bio xml:lang="en"><p>192019, Saint-Petersburg</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="western" xml:lang="en"><surname>Burdeynaya</surname><given-names>Anastasia S.</given-names></name></name-alternatives><bio xml:lang="en"><p>192019, Saint-Petersburg</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="western" xml:lang="en"><surname>Kasyanov</surname><given-names>Evgeny D.</given-names></name></name-alternatives><bio xml:lang="en"><p>192019, Saint-Petersburg</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="western" xml:lang="en"><surname>Pinakhina</surname><given-names>Daria V.</given-names></name></name-alternatives><bio xml:lang="en"><p>192019, Saint-Petersburg</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="western" xml:lang="en"><surname>Mazo</surname><given-names>Galina E.</given-names></name></name-alternatives><bio xml:lang="en"><p>192019, Saint-Petersburg</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="en">V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2026</year></pub-date><pub-date pub-type="epub"><day>16</day><month>03</month><year>2026</year></pub-date><volume>1</volume><issue>6</issue><fpage>37</fpage><lpage>48</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Popov M.Y., Lepik O.V., Yakovleva Y.A., Kosterin D.N., Yanushko M.G., Lutova N.B., Burdeynaya A.S., Kasyanov E.D., Pinakhina D.V., Mazo G.E., 2026</copyright-statement><copyright-year>2026</copyright-year><copyright-holder xml:lang="ru">Popov M.Y., Lepik O.V., Yakovleva Y.A., Kosterin D.N., Yanushko M.G., Lutova N.B., Burdeynaya A.S., Kasyanov E.D., Pinakhina D.V., Mazo G.E.</copyright-holder><copyright-holder xml:lang="en">Popov M.Y., Lepik O.V., Yakovleva Y.A., Kosterin D.N., Yanushko M.G., Lutova N.B., Burdeynaya A.S., Kasyanov E.D., Pinakhina D.V., Mazo G.E.</copyright-holder><license license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.jppn.ru/jour/article/view/162">https://www.jppn.ru/jour/article/view/162</self-uri><abstract><p>Bipolar disorder (BD) is associated with elevated cardiometabolic morbidity and mortality, partly mediated by systemic inflammation. Sex differences in immune function and metabolic regulation are well-established, yet their impact on inflammation-related metabolic risk during pharmacotherapy remains understudied. Objective: To examine sex-specific associations between peripheral inflammatory indices and individual components of metabolic syndrome in patients with BD, testing the hypothesis that immuno-metabolic patterns differ between men and women. Materials and Methods: In this retrospective cross-sectional study 102 patients with BD (41 men, 61 women) were included. We assessed associations between inflammatory markers—including absolute cell counts, derived hematological ratios, and composite indices based on high-density lipoprotein cholesterol (HDL-C)—and individual components of metabolic syndrome (hyperglycemia, low HDL-C, hypertriglyceridemia, increased waist circumference). Results: Sex-specific patterns emerged: men with hyperglycemia demonstrated elevated neutrophil-to-lymphocyte ratio (p = 0.014) and absolute neutrophil counts (p-value = 0.044); men with hypertriglyceridemia exhibited elevated absolute lymphocytes (p-value = 0.010) and white blood cells (p-value = 0.031). In women, low HDL-C was associated with elevated neutrophil-to-HDL-C ratio (p-value = 0.031) and platelet-to-HDL-C ratio     (p-value = 0.009); hypertriglyceridemia with elevated neutrophil-to-HDL-C ratio (p-value = 0.042) and lymphocyte-to-HDL-C ratio (p-value = 0.027). No associations were found for cellular inflammatory markers in women, nor for increased waist circumference in either sex. Conclusions: Inflammation-metabolism relationships in BD are sex-specific: men exhibit cellular inflammatory markers linked to glucose and triglyceride dysregulation, while women show lipid-dependent inflammatory indices associated with HDL-C and triglyceride abnormalities. These preliminary findings suggest that risk stratification and metabolic monitoring during BD pharmacotherapy may benefit from sex-specific approaches, though replication in prospective cohorts is required before clinical translation.</p></abstract><kwd-group xml:lang="en"><kwd>bipolar disorder</kwd><kwd>sex differences</kwd><kwd>metabolic syndrome</kwd><kwd>inflammatory markers</kwd><kwd>cardiometabolic risk</kwd><kwd>pharmacotherapy</kwd></kwd-group><funding-group xml:lang="en"><funding-statement>This work was supported by the Government Assignment of the Ministry of Health of the Russian Federation to the V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology (2024-2026 XSOZ 2024 0012).</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Tekdemir R., Ergün M.T., Güler, H.A. Antipsychotic dosage and frequency of manic episodes as predictors of metabolic syndrome in bipolar disorder: a one-year follow-up. European Psychiatry. 2025; 68(S1): S107-S107. https://doi.org/10.1192/j.eurpsy.2025.314.</mixed-citation><mixed-citation xml:lang="en">Tekdemir R., Ergün M.T., Güler, H.A. Antipsychotic dosage and frequency of manic episodes as predictors of metabolic syndrome in bipolar disorder: a one-year follow-up. European Psychiatry. 2025; 68(S1): S107-S107. https://doi.org/10.1192/j.eurpsy.2025.314.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Kibitov A.O., Mazo, G.E. Metabolic side effects of atypical antipsychotics: individual variability and genetic risk. Social and Clinical Psychiatry. 2018; 28(1):90-100. (In Russian)</mixed-citation><mixed-citation xml:lang="en">Kibitov A.O., Mazo, G.E. Metabolic side effects of atypical antipsychotics: individual variability and genetic risk. Social and Clinical Psychiatry. 2018; 28(1):90-100. (In Russian)</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Rognoni C., Bertolani A., Jommi C. Second-generation antipsychotic drugs for patients with schizophrenia: systematic lit-erature review and meta-analysis of metabolic and cardiovascular side effects. Clinical Drug Investigation. 2021; 41(4): 303-319. https://doi.org/10.1007/s40261-021-01000-1.</mixed-citation><mixed-citation xml:lang="en">Rognoni C., Bertolani A., Jommi C. Second-generation antipsychotic drugs for patients with schizophrenia: systematic lit-erature review and meta-analysis of metabolic and cardiovascular side effects. Clinical Drug Investigation. 2021; 41(4): 303-319. https://doi.org/10.1007/s40261-021-01000-1.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Tao H., Shen D., Zhou Y., et al. A Systematic review and meta-analysis of metabolic syndrome prevalence in Chinese inpa-tients with bipolar disorder. Hormone and Metabolic Research. 2022; 54(9):587-592. https://doi.org/10.1055/a-1882-8423.</mixed-citation><mixed-citation xml:lang="en">Tao H., Shen D., Zhou Y., et al. A Systematic review and meta-analysis of metabolic syndrome prevalence in Chinese inpa-tients with bipolar disorder. Hormone and Metabolic Research. 2022; 54(9):587-592. https://doi.org/10.1055/a-1882-8423.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Sarangi S.C., Pattnaik S.S., Dash Y., et al. Is there any concern of insulin resistance and metabolic dysfunctions with anti-seizure medications? A prospective comparative study of valproate vs. levetiracetam. Seizure. 2024; 121: 123-132. https://doi.org/10.1016/j.seizure.2024.08.003.</mixed-citation><mixed-citation xml:lang="en">Sarangi S.C., Pattnaik S.S., Dash Y., et al. Is there any concern of insulin resistance and metabolic dysfunctions with anti-seizure medications? A prospective comparative study of valproate vs. levetiracetam. Seizure. 2024; 121: 123-132. https://doi.org/10.1016/j.seizure.2024.08.003.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Vancampfort D., Stubbs B., Mitchell A.J., et al. Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: a systematic review and meta-analysis. World Psychiatry. 2015; 14(3): 339-347. https://doi.org/10.1002/wps.20252.</mixed-citation><mixed-citation xml:lang="en">Vancampfort D., Stubbs B., Mitchell A.J., et al. Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: a systematic review and meta-analysis. World Psychiatry. 2015; 14(3): 339-347. https://doi.org/10.1002/wps.20252.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Nayerifard R., Bureng M.A., Zahiroddin A., et al. Comparison of metabolic syndrome prevalence in patients with schizo-phrenia and bipolar I disorder. Diabetes &amp; Metabolic Syndrome: Clinical Research &amp; Reviews. 2017; 11(Suppl. 1): S411-S416. https://doi.org/10.1016/j.dsx.2017.03.027.</mixed-citation><mixed-citation xml:lang="en">Nayerifard R., Bureng M.A., Zahiroddin A., et al. Comparison of metabolic syndrome prevalence in patients with schizo-phrenia and bipolar I disorder. Diabetes &amp; Metabolic Syndrome: Clinical Research &amp; Reviews. 2017; 11(Suppl. 1): S411-S416. https://doi.org/10.1016/j.dsx.2017.03.027.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Chan J.K.N., Tong C.H.Y., Wong C.S.M., et al. Life expectancy and years of potential life lost in bipolar disorder: systematic review and meta-analysis. British Journal of Psychiatry. 2022; 221(3): 567-576. https://doi.org/10.1192/bjp.2022.19.</mixed-citation><mixed-citation xml:lang="en">Chan J.K.N., Tong C.H.Y., Wong C.S.M., et al. Life expectancy and years of potential life lost in bipolar disorder: systematic review and meta-analysis. British Journal of Psychiatry. 2022; 221(3): 567-576. https://doi.org/10.1192/bjp.2022.19.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">de Melo L.G.P., Nunes S.O.V., Anderson G., et al. Shared metabolic and immune-inflammatory, oxidative and nitrosative stress pathways in the metabolic syndrome and mood disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2017; 78: 34-50. https://doi.org/10.1016/j.pnpbp.2017.04.027.</mixed-citation><mixed-citation xml:lang="en">de Melo L.G.P., Nunes S.O.V., Anderson G., et al. Shared metabolic and immune-inflammatory, oxidative and nitrosative stress pathways in the metabolic syndrome and mood disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2017; 78: 34-50. https://doi.org/10.1016/j.pnpbp.2017.04.027.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Sayuri Yamagata A., Brietzke E., Rosenblat J.D., et al. Medical comorbidity in bipolar disorder: the link with metabol-ic-inflammatory systems. Journal of Affective Disorders. 2017; 211: 99-106. https://doi.org/10.1016/j.jad.2016.12.059.</mixed-citation><mixed-citation xml:lang="en">Sayuri Yamagata A., Brietzke E., Rosenblat J.D., et al. Medical comorbidity in bipolar disorder: the link with metabol-ic-inflammatory systems. Journal of Affective Disorders. 2017; 211: 99-106. https://doi.org/10.1016/j.jad.2016.12.059.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang Y., Wang J., Ye Y., et al. Peripheral cytokine levels across psychiatric disorders: a systematic review and network meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2023; 125: 110740. https://doi.org/10.1016/j.pnpbp.2023.110740.</mixed-citation><mixed-citation xml:lang="en">Zhang Y., Wang J., Ye Y., et al. Peripheral cytokine levels across psychiatric disorders: a systematic review and network meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2023; 125: 110740. https://doi.org/10.1016/j.pnpbp.2023.110740.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Pinzi M., Fagiolini A., Koukouna D., et al. Inflammatory and immune biomarkers in mood disorders: from mechanistic pathways to clinical translation. Cells. 2025; 14(19): 1558. https://doi.org/10.3390/cells14191558.</mixed-citation><mixed-citation xml:lang="en">Pinzi M., Fagiolini A., Koukouna D., et al. Inflammatory and immune biomarkers in mood disorders: from mechanistic pathways to clinical translation. Cells. 2025; 14(19): 1558. https://doi.org/10.3390/cells14191558.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Al-Mansoori L., Al-Jaber H., Prince M.S., Elrayess M.A. Role of inflammatory cytokines, growth factors and adipokines in adipogenesis and insulin resistance. Inflammation. 2022; 45(1): 31-44. https://doi.org/10.1007/s10753-021-01559-z.</mixed-citation><mixed-citation xml:lang="en">Al-Mansoori L., Al-Jaber H., Prince M.S., Elrayess M.A. Role of inflammatory cytokines, growth factors and adipokines in adipogenesis and insulin resistance. Inflammation. 2022; 45(1): 31-44. https://doi.org/10.1007/s10753-021-01559-z.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Bhatia K., Gupta V.K., Upadhyay S.K. Obesity and type 2 diabetes as chronic inflammation: how does the cytokine evidence align? Frontiers in Endocrinology. 2026; 17: 1721206. https://doi.org/10.3389/fendo.2026.1721206.</mixed-citation><mixed-citation xml:lang="en">Bhatia K., Gupta V.K., Upadhyay S.K. Obesity and type 2 diabetes as chronic inflammation: how does the cytokine evidence align? Frontiers in Endocrinology. 2026; 17: 1721206. https://doi.org/10.3389/fendo.2026.1721206.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang Q., He M., Deng C., et al. Effects of olanzapine on the elevation of macrophage infiltration and pro-inflammatory cytokine expression in female rats. Journal of Psychopharmacology. 2014; 28(12): 1161-1169. https://doi.org/10.1177/0269881114555250.</mixed-citation><mixed-citation xml:lang="en">Zhang Q., He M., Deng C., et al. Effects of olanzapine on the elevation of macrophage infiltration and pro-inflammatory cytokine expression in female rats. Journal of Psychopharmacology. 2014; 28(12): 1161-1169. https://doi.org/10.1177/0269881114555250.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Li H., Peng S., Li S., et al. Chronic olanzapine administration causes metabolic syndrome through inflammatory cytokines in rodent models of insulin resistance. Scientific Reports. 2019; 9(1): 1582. https://doi.org/10.1038/s41598-018-36930-y.</mixed-citation><mixed-citation xml:lang="en">Li H., Peng S., Li S., et al. Chronic olanzapine administration causes metabolic syndrome through inflammatory cytokines in rodent models of insulin resistance. Scientific Reports. 2019; 9(1): 1582. https://doi.org/10.1038/s41598-018-36930-y.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Rainville J.R., Hodes G.E. Inflaming sex differences in mood disorders. Neuropsychopharmacology. 2019; 44(1): 184-199. https://doi.org/10.1038/s41386-018-0124-7.</mixed-citation><mixed-citation xml:lang="en">Rainville J.R., Hodes G.E. Inflaming sex differences in mood disorders. Neuropsychopharmacology. 2019; 44(1): 184-199. https://doi.org/10.1038/s41386-018-0124-7.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Rubinow D.R., Schmidt P.J. Sex differences and the neurobiology of affective disorders. Neuropsychopharmacology. 2019; 44(1): 111-128. https://doi.org/10.1038/s41386-018-0148-z.</mixed-citation><mixed-citation xml:lang="en">Rubinow D.R., Schmidt P.J. Sex differences and the neurobiology of affective disorders. Neuropsychopharmacology. 2019; 44(1): 111-128. https://doi.org/10.1038/s41386-018-0148-z.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Puzikova O.Z., Churyukina E.V., Moskovkina A.V., et al. Sex hormone role in the regulation of innate immunity. Russian Medical Inquiry. 2025; 9(2): 119-124. (In Russian) https://doi.org/10.32364/2587-6821-2025-9-2-4.</mixed-citation><mixed-citation xml:lang="en">Puzikova O.Z., Churyukina E.V., Moskovkina A.V., et al. Sex hormone role in the regulation of innate immunity. Russian Medical Inquiry. 2025; 9(2): 119-124. (In Russian) https://doi.org/10.32364/2587-6821-2025-9-2-4.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Diflorio A., Jones I. Is sex important? Gender differences in bipolar disorder. International Review of Psychiatry. 2010; 22(5): 437-452. https://doi.org/10.3109/09540261.2010.514601.</mixed-citation><mixed-citation xml:lang="en">Diflorio A., Jones I. Is sex important? Gender differences in bipolar disorder. International Review of Psychiatry. 2010; 22(5): 437-452. https://doi.org/10.3109/09540261.2010.514601.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Buoli M., Cesana B.M., Dell'Osso B., et al. Gender-related differences in patients with bipolar disorder: a nationwide study. CNS Spectrums. 2019; 24(6): 589-596. https://doi.org/10.1017/S1092852918001529.</mixed-citation><mixed-citation xml:lang="en">Buoli M., Cesana B.M., Dell'Osso B., et al. Gender-related differences in patients with bipolar disorder: a nationwide study. CNS Spectrums. 2019; 24(6): 589-596. https://doi.org/10.1017/S1092852918001529.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Dell'Osso B., Cafaro R., Ketter T.A. Has bipolar disorder become a predominantly female gender related condition? Analysis of recently published large sample studies. International Journal of Bipolar Disorders. 2021; 9(1): 3. https://doi.org/10.1186/s40345-020-00207-z.</mixed-citation><mixed-citation xml:lang="en">Dell'Osso B., Cafaro R., Ketter T.A. Has bipolar disorder become a predominantly female gender related condition? Analysis of recently published large sample studies. International Journal of Bipolar Disorders. 2021; 9(1): 3. https://doi.org/10.1186/s40345-020-00207-z.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Liu Q., Wang L., Zhen F., An C. Occurrence of metabolic syndrome in untreated bipolar disorders: a cross-sectional study. Acta Neuropsychiatrica. 2024; 36: 357-362. https://doi.org/10.1017/neu.2023.47.</mixed-citation><mixed-citation xml:lang="en">Liu Q., Wang L., Zhen F., An C. Occurrence of metabolic syndrome in untreated bipolar disorders: a cross-sectional study. Acta Neuropsychiatrica. 2024; 36: 357-362. https://doi.org/10.1017/neu.2023.47.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Ercis M., Sanchez-Ruiz J.A., Webb L.M., et al. Sex differences in effectiveness and adverse effects of mood stabilizers and antipsychotics: a systematic review. Journal of Affective Disorders. 2024; 352: 171-192. https://doi.org/10.1016/j.jad.2024.02.038.</mixed-citation><mixed-citation xml:lang="en">Ercis M., Sanchez-Ruiz J.A., Webb L.M., et al. Sex differences in effectiveness and adverse effects of mood stabilizers and antipsychotics: a systematic review. Journal of Affective Disorders. 2024; 352: 171-192. https://doi.org/10.1016/j.jad.2024.02.038.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Piccirilli L., Capuzzi E., Legnani F., et al. Gender differences in clinical and biochemical variables of patients affected by bipolar disorder. Brain Sciences. 2025; 15(2): 214. https://doi.org/10.3390/brainsci15020214.</mixed-citation><mixed-citation xml:lang="en">Piccirilli L., Capuzzi E., Legnani F., et al. Gender differences in clinical and biochemical variables of patients affected by bipolar disorder. Brain Sciences. 2025; 15(2): 214. https://doi.org/10.3390/brainsci15020214.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Zahorec R. Neutrophil-to-lymphocyte ratio, past, present and future perspectives. Bratislavské Lekárske Listy. 2021; 122(7): 474-488. https://doi.org/10.4149/BLL_2021_078.</mixed-citation><mixed-citation xml:lang="en">Zahorec R. Neutrophil-to-lymphocyte ratio, past, present and future perspectives. Bratislavské Lekárske Listy. 2021; 122(7): 474-488. https://doi.org/10.4149/BLL_2021_078.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Wei Y., Feng J., Ma J., et al. Neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios in patients with affective disorders. Journal of Affective Disorders. 2022; 309: 221-228. https://doi.org/10.1016/j.jad.2022.04.092.</mixed-citation><mixed-citation xml:lang="en">Wei Y., Feng J., Ma J., et al. Neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios in patients with affective disorders. Journal of Affective Disorders. 2022; 309: 221-228. https://doi.org/10.1016/j.jad.2022.04.092.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Mazza M.G., Lucchi S., Tringali A.G.M., et al. Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: a meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2018; 84(Pt A): 229-236. https://doi.org/10.1016/j.pnpbp.2018.03.012.</mixed-citation><mixed-citation xml:lang="en">Mazza M.G., Lucchi S., Tringali A.G.M., et al. Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: a meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2018; 84(Pt A): 229-236. https://doi.org/10.1016/j.pnpbp.2018.03.012.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Sanchez-Autet M., Arranz B., Sierra P., et al. Association between neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and C-reactive protein levels and metabolic status in patients with a bipolar disorder. The World Journal of Biological Psychiatry. 2022; 23(6): 464-474. https://doi.org/10.1080/15622975.2021.2013089.</mixed-citation><mixed-citation xml:lang="en">Sanchez-Autet M., Arranz B., Sierra P., et al. Association between neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and C-reactive protein levels and metabolic status in patients with a bipolar disorder. The World Journal of Biological Psychiatry. 2022; 23(6): 464-474. https://doi.org/10.1080/15622975.2021.2013089.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Mahmood A., Haider H., Samad S., et al. Association of white blood cell parameters with metabolic syndrome: a systematic review and meta-analysis of 168,000 patients. Medicine (Baltimore). 2024; 103(10): e37331. https://doi.org/10.1097/MD.0000000000037331.</mixed-citation><mixed-citation xml:lang="en">Mahmood A., Haider H., Samad S., et al. Association of white blood cell parameters with metabolic syndrome: a systematic review and meta-analysis of 168,000 patients. Medicine (Baltimore). 2024; 103(10): e37331. https://doi.org/10.1097/MD.0000000000037331.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Qiu Z., Huang C., Xu C., Xu Y. Predictive role of neutrophil-to-lymphocyte ratio in metabolic syndrome: meta-analysis of 70,937 individuals. BMC Endocrine Disorders. 2024; 24(1): 155. https://doi.org/10.1186/s12902-024-01689-z.</mixed-citation><mixed-citation xml:lang="en">Qiu Z., Huang C., Xu C., Xu Y. Predictive role of neutrophil-to-lymphocyte ratio in metabolic syndrome: meta-analysis of 70,937 individuals. BMC Endocrine Disorders. 2024; 24(1): 155. https://doi.org/10.1186/s12902-024-01689-z.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Popov M.Yu., Pinakhina D.V., Prusova T.I., et al. Gender differences in the associations between inflammatory hematological ratios and metabolic disturbances in patients with bipolar disorder. Russian Psychiatric Journal. 2025; (4): 24-34. (In Russian)</mixed-citation><mixed-citation xml:lang="en">Popov M.Yu., Pinakhina D.V., Prusova T.I., et al. Gender differences in the associations between inflammatory hematological ratios and metabolic disturbances in patients with bipolar disorder. Russian Psychiatric Journal. 2025; (4): 24-34. (In Russian)</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Alberti K.G., Zimmet P., Shaw J. Metabolic syndrome--a new world-wide definition. A Consensus Statement from the In-ternational Diabetes Federation. Diabetic Medicine. 2006; 23(5): 469-480. https://doi.org/10.1111/j.1464-5491.2006.01858.x.</mixed-citation><mixed-citation xml:lang="en">Alberti K.G., Zimmet P., Shaw J. Metabolic syndrome--a new world-wide definition. A Consensus Statement from the In-ternational Diabetes Federation. Diabetic Medicine. 2006; 23(5): 469-480. https://doi.org/10.1111/j.1464-5491.2006.01858.x.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Marra A., Bondesan A., Caroli D., Sartorio A. Complete blood count (CBC)-derived inflammation indexes are useful in predicting metabolic syndrome in adults with severe obesity. Journal of Clinical Medicine. 2024; 13(5): 1353. https://doi.org/10.3390/jcm13051353.</mixed-citation><mixed-citation xml:lang="en">Marra A., Bondesan A., Caroli D., Sartorio A. Complete blood count (CBC)-derived inflammation indexes are useful in predicting metabolic syndrome in adults with severe obesity. Journal of Clinical Medicine. 2024; 13(5): 1353. https://doi.org/10.3390/jcm13051353.</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Chen H.L., Wu C., Cao L., et al. The association between the neutrophil-to-lymphocyte ratio and type 2 diabetes mellitus: a cross-sectional study. BMC Endocrine Disorders. 2024; 24(1): 107. https://doi.org/10.1186/s12902-024-01637-x.</mixed-citation><mixed-citation xml:lang="en">Chen H.L., Wu C., Cao L., et al. The association between the neutrophil-to-lymphocyte ratio and type 2 diabetes mellitus: a cross-sectional study. BMC Endocrine Disorders. 2024; 24(1): 107. https://doi.org/10.1186/s12902-024-01637-x.</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Wang M., Ma G., Tao Z. The association of neutrophil-to-lymphocyte ratio with cardiovascular and all-cause mortality among the metabolic syndrome population. BMC Cardiovascular Disorders. 2024; 24(1): 594. https://doi.org/10.1186/s12872-024-04284-1.</mixed-citation><mixed-citation xml:lang="en">Wang M., Ma G., Tao Z. The association of neutrophil-to-lymphocyte ratio with cardiovascular and all-cause mortality among the metabolic syndrome population. BMC Cardiovascular Disorders. 2024; 24(1): 594. https://doi.org/10.1186/s12872-024-04284-1.</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Chen H., Chen Y.H., Liu X.B. Gender differences in prevalence and clinical correlates of initial-treatment and drug-naïve bipolar disorder patients with metabolic syndrome: a cross-sectional study. Alpha Psychiatry. 2025; 26(5): 39112. https://doi.org/10.31083/AP39112.</mixed-citation><mixed-citation xml:lang="en">Chen H., Chen Y.H., Liu X.B. Gender differences in prevalence and clinical correlates of initial-treatment and drug-naïve bipolar disorder patients with metabolic syndrome: a cross-sectional study. Alpha Psychiatry. 2025; 26(5): 39112. https://doi.org/10.31083/AP39112.</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Stamoula E., Stamatellos V.P., Vavilis T., et al. Weight gain, gender, and antipsychotics: a disproportionality analysis of the FDA Adverse Event Reporting System database (FAERS). Expert Opinion on Drug Safety. 2024; 23(2): 239-245. https://doi.org/10.1080/14740338.2023.2248873.</mixed-citation><mixed-citation xml:lang="en">Stamoula E., Stamatellos V.P., Vavilis T., et al. Weight gain, gender, and antipsychotics: a disproportionality analysis of the FDA Adverse Event Reporting System database (FAERS). Expert Opinion on Drug Safety. 2024; 23(2): 239-245. https://doi.org/10.1080/14740338.2023.2248873.</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Johansen I.T., Steen N.E., Haram M., et al. Sex differences in antipsychotic-related triglyceride levels are associated with metabolic hormone differences in patients with severe mental disorders. Schizophrenia Research. 2022; 243: 55-63. https://doi.org/10.1016/j.schres.2022.02.015.</mixed-citation><mixed-citation xml:lang="en">Johansen I.T., Steen N.E., Haram M., et al. Sex differences in antipsychotic-related triglyceride levels are associated with metabolic hormone differences in patients with severe mental disorders. Schizophrenia Research. 2022; 243: 55-63. https://doi.org/10.1016/j.schres.2022.02.015.</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Pettersson U.S., Waldén T.B., Carlsson P.O., et al. Female mice are protected against high-fat diet induced metabolic syn-drome and increase the regulatory T cell population in adipose tissue. PLoS ONE. 2012; 7(9): e46057. https://doi.org/10.1371/journal.pone.0046057.</mixed-citation><mixed-citation xml:lang="en">Pettersson U.S., Waldén T.B., Carlsson P.O., et al. Female mice are protected against high-fat diet induced metabolic syn-drome and increase the regulatory T cell population in adipose tissue. PLoS ONE. 2012; 7(9): e46057. https://doi.org/10.1371/journal.pone.0046057.</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Shepherd R., Cheung A.S., Pang K., et al. Sexual dimorphism in innate immunity: the role of sex hormones and epigenetics. Frontiers in Immunology. 2021; 11: 604000. https://doi.org/10.3389/fimmu.2020.604000.</mixed-citation><mixed-citation xml:lang="en">Shepherd R., Cheung A.S., Pang K., et al. Sexual dimorphism in innate immunity: the role of sex hormones and epigenetics. Frontiers in Immunology. 2021; 11: 604000. https://doi.org/10.3389/fimmu.2020.604000.</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Nowak T.J., Muehlenbein M.P. Toward understanding sexual immune dimorphism in humans. Frontiers in Immunology. 2025; 16: 1570565. https://doi.org/10.3389/fimmu.2025.1570565.</mixed-citation><mixed-citation xml:lang="en">Nowak T.J., Muehlenbein M.P. Toward understanding sexual immune dimorphism in humans. Frontiers in Immunology. 2025; 16: 1570565. https://doi.org/10.3389/fimmu.2025.1570565.</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Hunjadi M., Lamina C., Kahler P., et al. HDL cholesterol efflux capacity is inversely associated with subclinical cardiovascular risk markers in young adults: the cardiovascular risk in young Finns study. Scientific Reports. 2020; 10(1): 19223. https://doi.org/10.1038/s41598-020-76146-7.</mixed-citation><mixed-citation xml:lang="en">Hunjadi M., Lamina C., Kahler P., et al. HDL cholesterol efflux capacity is inversely associated with subclinical cardiovascular risk markers in young adults: the cardiovascular risk in young Finns study. Scientific Reports. 2020; 10(1): 19223. https://doi.org/10.1038/s41598-020-76146-7.</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Gardner C.D., Tribble D.L., Young D.R., et al. Population frequency distributions of HDL, HDL(2), and HDL(3) cholesterol and apolipoproteins A-I and B in healthy men and women and associations with age, gender, hormonal status, and sex hormone use: the Stanford Five City Project. Preventive Medicine. 2000; 31(4): 335-345. https://doi.org/10.1006/pmed.2000.0715.</mixed-citation><mixed-citation xml:lang="en">Gardner C.D., Tribble D.L., Young D.R., et al. Population frequency distributions of HDL, HDL(2), and HDL(3) cholesterol and apolipoproteins A-I and B in healthy men and women and associations with age, gender, hormonal status, and sex hormone use: the Stanford Five City Project. Preventive Medicine. 2000; 31(4): 335-345. https://doi.org/10.1006/pmed.2000.0715.</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Park S., Hong S.M., Ahn I.S., Kim S.H. Olanzapine, not risperidone, exacerbates beta-cell function and mass in ovariecto-mized diabetic rats and estrogen replacement reverses them. Journal of Psychopharmacology. 2010; 24(7): 1105-1114. https://doi.org/10.1177/0269881109348167.</mixed-citation><mixed-citation xml:lang="en">Park S., Hong S.M., Ahn I.S., Kim S.H. Olanzapine, not risperidone, exacerbates beta-cell function and mass in ovariecto-mized diabetic rats and estrogen replacement reverses them. Journal of Psychopharmacology. 2010; 24(7): 1105-1114. https://doi.org/10.1177/0269881109348167.</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Davey K.J., O'Mahony S.M., Schellekens H., et al. Gender-dependent consequences of chronic olanzapine in the rat: effects on body weight, inflammatory, metabolic and microbiota parameters. Psychopharmacology (Berl). 2012; 221(1): 155-169. https://doi.org/10.1007/s00213-011-2555-2.</mixed-citation><mixed-citation xml:lang="en">Davey K.J., O'Mahony S.M., Schellekens H., et al. Gender-dependent consequences of chronic olanzapine in the rat: effects on body weight, inflammatory, metabolic and microbiota parameters. Psychopharmacology (Berl). 2012; 221(1): 155-169. https://doi.org/10.1007/s00213-011-2555-2.</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Straub R.H. The complex role of estrogens in inflammation. Endocrine Reviews. 2007; 28(5): 521-574. https://doi.org/10.1210/er.2007-0001.</mixed-citation><mixed-citation xml:lang="en">Straub R.H. The complex role of estrogens in inflammation. Endocrine Reviews. 2007; 28(5): 521-574. https://doi.org/10.1210/er.2007-0001.</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Kolahi Ahari R., Akbari N., Babaeepoor N., et al. Association of three novel inflammatory markers: lymphocyte to HDL-C ratio, high-sensitivity C-reactive protein to HDL-C ratio and high-sensitivity C-reactive protein to lymphocyte ratio with metabolic syndrome. Endocrinology, Diabetes &amp; Metabolism. 2024; 7(3): e00479. https://doi.org/10.1002/edm2.479.</mixed-citation><mixed-citation xml:lang="en">Kolahi Ahari R., Akbari N., Babaeepoor N., et al. Association of three novel inflammatory markers: lymphocyte to HDL-C ratio, high-sensitivity C-reactive protein to HDL-C ratio and high-sensitivity C-reactive protein to lymphocyte ratio with metabolic syndrome. Endocrinology, Diabetes &amp; Metabolism. 2024; 7(3): e00479. https://doi.org/10.1002/edm2.479.</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Rojnic Kuzman M., Nordentoft M., Raballo A., et al. Schizophrenia treatment preferences of psychiatrists versus guidelines: A European perspective. European Psychiatry. 2025; 68(1): e107. https://doi.org/10.1192/j.eurpsy.2025.10072.</mixed-citation><mixed-citation xml:lang="en">Rojnic Kuzman M., Nordentoft M., Raballo A., et al. Schizophrenia treatment preferences of psychiatrists versus guidelines: A European perspective. European Psychiatry. 2025; 68(1): e107. https://doi.org/10.1192/j.eurpsy.2025.10072.</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Fusar-Poli L., Amerio A., Cimpoesu P., et al. Gender differences in complete blood count and inflammatory ratios among patients with bipolar disorder. Brain Sciences. 2021; 11(3): 363. https://doi.org/10.3390/brainsci11030363.</mixed-citation><mixed-citation xml:lang="en">Fusar-Poli L., Amerio A., Cimpoesu P., et al. Gender differences in complete blood count and inflammatory ratios among patients with bipolar disorder. Brain Sciences. 2021; 11(3): 363. https://doi.org/10.3390/brainsci11030363.</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Smolensky I., Inta D., Su K.-P., Marx W. Sex differences in nutritional psychiatry: are omega-3 fatty acids more effective in women with MDD? Nutritional Psychiatry. 2026; 1: 100003. https://doi.org/10.1016/j.nupsyc.2025.100003.</mixed-citation><mixed-citation xml:lang="en">Smolensky I., Inta D., Su K.-P., Marx W. Sex differences in nutritional psychiatry: are omega-3 fatty acids more effective in women with MDD? Nutritional Psychiatry. 2026; 1: 100003. https://doi.org/10.1016/j.nupsyc.2025.100003.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
