Sex-Specific Links Between Peripheral Inflammation and Metabolic Risk in Bipolar Disorder: Towards Risk Stratification
https://doi.org/10.52667/2712-9179-2026-6-1-37-48
Abstract
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.
Keywords
bipolar disorder,
sex differences,
metabolic syndrome,
inflammatory markers,
cardiometabolic risk,
pharmacotherapy
Supporting agencies: 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).
About the Authors
Mikhail Yu. Popov
V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology
Russian Federation
Russian Federation
192019, Saint-Petersburg
Olga V. Lepik
V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology
Russian Federation
Russian Federation
192019, Saint-Petersburg
Yulia A. Yakovleva
V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology
Russian Federation
Russian Federation
192019, Saint-Petersburg
Dmitry N. Kosterin
V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology
Russian Federation
Russian Federation
192019, Saint-Petersburg
Maria G. Yanushko
V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology
Russian Federation
Russian Federation
192019, Saint-Petersburg
Natalia B. Lutova
V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology
Russian Federation
Russian Federation
192019, Saint-Petersburg
Anastasia S. Burdeynaya
V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology
Russian Federation
Russian Federation
192019, Saint-Petersburg
Evgeny D. Kasyanov
V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology
Russian Federation
Russian Federation
192019, Saint-Petersburg
Daria V. Pinakhina
V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology
Russian Federation
Russian Federation
192019, Saint-Petersburg
Galina E. Mazo
V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology
Russian Federation
Russian Federation
192019, Saint-Petersburg
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Popov M.Yu., Lepik O.V., Yakovleva Yu.A., Kosterin D.N., Yanushko M.G., Lutova N.B., Burdeynaya A.S., Kasyanov E.D., Pinakhina D.V., Mazo G.E. Sex-Specific Links Between Peripheral Inflammation and Metabolic Risk in Bipolar Disorder: Towards Risk Stratification. Personalized Psychiatry and Neurology. 2026;6(1):37-48. https://doi.org/10.52667/2712-9179-2026-6-1-37-48
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