Advances in Mendelian Randomization Studies on the Causal Relationship Between Immune Cells and Psychiatric Disorders
Abstract
In recent years, the incidence of psychiatric disorders has been steadily increasing, posing significant challenges to both individual health and social stability. Emerging evidence has highlighted a close association between immune cells and the onset and progression of various psychiatric conditions. Traditional approaches for inferring causality, such as randomized controlled trials and observational studies, are often limited by feasibility, bias, and confounding factors. Mendelian randomization (MR), which leverages genetic variants as instrumental variables, provides a powerful alternative for assessing causal relationships between immune cells and psychiatric disorders. This review summarizes recent advances in MR studies investigating the causal links between immune cell profiles and psychiatric disorders, including anxiety, depression, and schizophrenia. By integrating current evidence from MR studies, this review aims to provide new insights and reference points for future research exploring the relationship between immune cells and psychiatric disorders.
1. Collaborators C-MD. Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic. Lancet. 2021;398:1700-1712.
2. GBD Diseases and Injuries Collaborators. Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990-2021: A systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024;403:2133-2161.
3. Stoewen DL. Nature, nurture, and mental health Part 1: The influence of genetics, psychology, and biology. Can Vet J. 2022;63:427-430.
4. Magomedova A, Fatima G. Mental health and well-being in the modern era: A comprehensive review of challenges and interventions. Cureus. 2025;17:e77683.
5. Catalina GR, Gheorman V, Gheorman V, Fortofoiu MC. The role of neuroinflammation in the comorbidity of psychiatric disorders and internal diseases. Healthcare (Basel). 2025;13:837.
6. Ma WR, Zhang LL, Ma JY, Yu F, Hou YQ, Feng XR, et al. Mendelian randomization studies of depression: Evidence, opportunities, and challenges. Ann Gen Psychiatry. 2023;22:47.
7. Yang J, Wang Q, Jiang W. Association between immune cells in peripheral blood and psychiatric symptoms. Front Psychiatry. 2023;14:1198734.
8. Thela L, Paruk S, Nkambule BB, Ntlantsana V, Abbai NS, Msibi Z, et al. Longitudinal analysis of proinflammatory and anti-inflammatory cytokines in the cerebrospinal fluid and peripheral blood of treatment-naïve first-episode psychosis patients, and their correlation with psychosis severity and cognitive impairment in sub-Saharan Africa. BMJ Open. 2025;15:e098347.
9. Zhang S, Gao Y, Zhao Y, Huang TY, Zheng Q, Wang X. Peripheral and central neuroimmune mechanisms in Alzheimer’s disease pathogenesis. Mol Neurodegener. 2025;20:22.
10. Jie J, Yao X, Deng H, Zhou Y, Jiang X, Dai X, et al. Regulatory T cells in neurological disorders and tissue regeneration: Mechanisms of action and therapeutic potentials. Neural Regen Res. 2026;21:1277-1291.
11. Shi Y, Wei B, Li L, Wang B, Sun M. Th17 cells and inflammation in neurological disorders: Possible mechanisms of action. Front Immunol. 2022;13:932152.
12. Zeitoun T, El-Sohemy A. Using Mendelian randomization to study the role of iron in health and disease. Int J Mol Sci. 2023;24:13458.
13. Larsson SC, Butterworth AS, Burgess S. Mendelian randomization for cardiovascular diseases: Principles and
applications. Eur Heart J. 2023;44:4913-4924.
14. Sekula P, Del Greco MF, Pattaro C, Köttgen A. Mendelian randomization as an approach to assess causality using observational data. J Am Soc Nephrol. 2016;27:3253-3265.
15. Bowden J, Holmes MV. Meta-analysis and Mendelian randomization: A review. Res Synth Methods. 2019;10:486-496.
16. Burgess S, Thompson SG. Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol. 2017;32:377-389.
17. Wang C, Zhu D, Zhang D, Zuo X, Yao L, Liu T, et al. Causal role of immune cells in schizophrenia: Mendelian randomization (MR) study. BMC Psychiatry. 2023;23:590.
18. Liberman JN, Pesa J, Rui P, Teeple A, Lakey S, Wiggins E, et al. Predicting poor outcomes among individuals seeking care for major depressive disorder. Psychiatr Res Clin Pract. 2022;4:102-112.
19. Chan KL, Poller WC, Swirski FK, Russo SJ. Central regulation of stress-evoked peripheral immune responses. Nat Rev Neurosci. 2023;24:591-604.
20. Cicchese JM, Evans S, Hult C, Joslyn LR, Wessler T, Millar JA, et al. Dynamic balance of pro- and anti-inflammatory signals controls disease and limits pathology. Immunol Rev. 2018;285:147-167.
21. Zhang Y, Wang SW, Ding J, Wen X, Li T, Yang L, et al. Causal role of immune cells in major depressive disorder and bipolar disorder: Mendelian randomization (MR) study. J Affect Disord. 2024;361:165-171.
22. Bekhbat M, Ulukaya GB, Bhasin MK, Felger JC, Miller AH. Cellular and immunometabolic mechanisms of inflammation in depression: Preliminary findings from single cell RNA sequencing and a tribute to Bruce McEwen. Neurobiol Stress. 2022;19:100462.
23. Maes M, Rachayon M, Jirakran K, Sughondhabirom A, Almulla AF, Sodsai P. Role of T and B lymphocyte cannabinoid type 1 and 2 receptors in major depression and suicidal behaviours. Acta Neuropsychiatr. 2024;36:287-298.
24. Kappelmann N, Arloth J, Georgakis MK, Czamara D, Rost N, Ligthart S, et al. Dissecting the association between inflammation, metabolic dysregulation, and specific depressive symptoms: A genetic correlation and 2-sample Mendelian randomization study. JAMA Psychiatry. 2021;78:161-170.
25. Palmos AB, Hübel C, Lim KX, Hunjan AK, Coleman JRI, Breen G. Assessing the evidence for causal associations between body mass index, C-reactive protein, depression, and reported trauma using Mendelian randomization. Biol Psychiatry Glob Open Sci. 2023;3:110-118.
26. Cao Y, Li X, Gao J, Zhang N, Zhang G, Li S. Revealing the causal relationship between differential white blood cell counts and depression: A bidirectional two-sample Mendelian randomization study. Depress Anxiety. 2025;2025:3131579.
27. Xia X, Li KQ, Zou W, Wang L. The central role of microglia in major depressive disorder and its potential as a therapeutic target. Front Behav Neurosci. 2025;19:1598178.
28. Wang H, He Y, Sun Z, Ren S, Liu M, Wang G, et al. Microglia in depression: An overview of microglia in the pathogenesis and treatment of depression. J Neuroinflammation. 2022;19:132.
29. DeGeorge KC, Grover M, Streeter GS. Generalized anxiety disorder and panic disorder in adults. Am Fam Physician. 2022;106:157-164.
30. Sah A, Singewald N. The (neuro)inflammatory system in anxiety disorders and PTSD: Potential treatment targets. Pharmacol Ther. 2025;269:108825.
31. Won E, Kim YK. Neuroinflammation-associated alterations of the brain as potential neural biomarkers in anxiety disorders. Int J Mol Sci. 2020;21:6546.
32. Ma Z, Zhao M, Zhao H, Qu N. Causal role of immune cells in generalized anxiety disorder: Mendelian randomization study. Front Immunol. 2023;14:1338083.
33. Chen C, Zhang D, Wu D, Chen F, Li Z, Hu Y. Gut microbiome and immune cells mediated effect on depression: A two-step, two-sample Mendelian randomization analysis. Exp Gerontol. 2024;195:112530.
34. Li H, Yi J, Xu X, Ma Y, Xiang J, Shu Y, et al. Dysfunction in neuro-mesenchymal units impairs the development of bone marrow B cells in mice with anxiety. Brain Behav Immun. 2025;124:305-320.
35. Mac Giollabhui N, Slaney C, Hemani G, Foley EM, van der Most PJ, Nolte IM, et al. Role of inflammation in depressive and anxiety disorders, affect, and cognition: Genetic and non-genetic findings in the Lifelines cohort study. Transl Psychiatry. 2025;15:164.
36. Naude PJW, Roest AM, Stein DJ, de Jonge P, Doornbos B. Anxiety disorders and CRP in a population cohort study with 54,326 participants: The LifeLines study. World J Biol Psychiatry. 2018;19:461-470.
37. Vogelzangs N, Beekman AT, de Jonge P, Penninx BW. Anxiety disorders and inflammation in a large adult cohort. Transl Psychiatry. 2013;3:e249.
38. Miola A, Fountoulakis KN, Baldessarini RJ, Veldic M, Solmi M, Rasgon N, et al. Prevalence and outcomes of rapid cycling bipolar disorder: Mixed method systematic meta-review. J Psychiatr Res. 2023;164:404-415.
39. Herrera-Rivero M, Gutierrez-Fragoso K, International Consortium on Lithium Genetics, Kurtz J, Baune BT. Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder. Transl Psychiatry. 2024;14:174.
40. Martinson JJ, Nejentsev S, Speed D, Fischer A, Mick E, Walker BR, et al. Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data. Am J Med Genet B Neuropsychiatr Genet. 2018;177(5):641-57.
41. Pereira AC, Oliveira J, Silva S, Madeira N, Pereira CMF, Cruz MT. Inflammation in bipolar disorder (BD): Identification of new therapeutic targets. Pharmacol Res. 2021;163(5):105325.
42. Rosenblat JD, McIntyre RS. Bipolar disorder and immune dysfunction: Epidemiological findings, proposed pathophysiology and clinical implications. Brain Sci. 2017;7:144.
43. Owen MJ, Legge SE, Rees E, Walters JTR, O’Donovan MC. Genomic findings in schizophrenia and their implications. Mol Psychiatry. 2023;28:3638-3647.
44. Ermakov EA, Mednova IA, Boiko AS, Buneva VN, Ivanova SA. Chemokine dysregulation and neuroinflammation in schizophrenia: A systematic review. Int J Mol Sci. 2023;24:2215.
45. Vallée A. Neuroinflammation in schizophrenia: The key role of the WNT/β-catenin pathway. Int J Mol Sci. 2022;23:2810.
46. Duncan LE, Li T, Salem M, Li W, Mortazavi L, Senturk H, et al. Mapping the cellular etiology of schizophrenia and complex brain phenotypes. Nat Neurosci. 2025;28:248-258.
47. Megha KB, Joseph X, Akhil V, Mohanan PV. Cascade of immune mechanism and consequences of inflammatory disorders. Phytomedicine. 2021;91:153712.
48. Halstead S, Siskind D, Amft M, Wagner E, Yakimov V, Shih-Jung Liu Z, et al. Alteration patterns of peripheral concentrations of cytokines and associated inflammatory proteins in acute and chronic stages of schizophrenia: A systematic review and network meta-analysis. Lancet Psychiatry. 2023;10:260-271.
49. Perry BI, Upthegrove R, Kappelmann N, Jones PB, Burgess S, Khandaker GM. Associations of immunological proteins/traits with schizophrenia, major depression and bipolar disorder: A bi-directional two-sample Mendelian randomization study. Brain Behav Immun. 2021;97:176-185.
50. Du J, Baranova A, Zhang G, Zhang F. The causal relationship between immune cell traits and schizophrenia: A Mendelian randomization analysis. Front Immunol. 2024;15:1452214.
51. Ermakov EA, Melamud MM, Buneva VN, Ivanova SA. Immune system abnormalities in schizophrenia: An integrative view and translational perspectives. Front Psychiatry. 2022;13:880568.
52. Chi H, Pepper M, Thomas PG. Principles and therapeutic applications of adaptive immunity. Cell. 2024;187:2052-2078.
53. Tanabe S, Yamashita T. B-1a lymphocytes promote oligodendrogenesis during brain development. Nat Neurosci. 2018;21:506-516.
54. Joshi I, Carney WP, Rock EP. Utility of monocyte HLA-DR and rationale for therapeutic GM-CSF in sepsis immunoparalysis. Front Immunol. 2023;14(2):1130214.
55. Li Y, Sun G, Cui Y, Ji S and Kan T. Causal associations between immune cells and psychiatric disorders: a bidirectional Mendelian randomization analysis. Naunyn Schmiedebergs Arch Pharmacol. 2025; -14.
56. Chen X, Yao T, Cai J, Fu X, Li H and Wu J. Systemic inflammatory regulators and 7 major psychiatric disorders: A two-sample Mendelian randomization study. Prog Neuropsychopharmacol Biol Psychiatry. 2022;116:110534.
57. Fang C, Sun Y, Fan C and Lei D. The relationship of immune cells with autism spectrum disorder: a bidirectional Mendelian randomization study. BMC Psychiatry. 2024;24:477.
58. Wang J, Shao Y, Deng X and Du J. Causal Relationship Between Post-Traumatic Stress Disorder and Immune Cell Traits: A Mendelian Randomization Study. Brain Behav. 2024;14:e70073.
59. Poletti S, Mazza MG and Benedetti F. Inflammatory mediators in major depression and bipolar disorder. Transl Psychiatry. 2024;14:247.
60. Croese T, Castellani G and Schwartz M. Immune cell compartmentalization for brain surveillance and protection. Nat Immunol. 2021;22:1083-92.
61. Furlan R, Melloni E, Finardi A, Vai B, Di Toro S, Aggio V, Battistini L, Borsellino G, Manfredi E and Falini A. Natural killer cells protect white matter integrity in bipolar disorder. Brain Behav Immun. 2019;81:410-21.
62. [62] Magioncalda P, Martino M, Tardito S, Sterlini B, Conio B, Marozzi V, Adavastro G, Capobianco L, Russo D and Parodi A. White matter microstructure alterations correlate with terminally differentiated CD8+ effector T cell depletion in the peripheral blood in mania: combined DTI and immunological investigation in the different phases of bipolar disorder. Brain, Behavior, and Immunity. 2018;73:192-204.
63. Spoelma MJ, Serafimovska A and Parker G. Differentiating melancholic and non-melancholic depression via biological markers: A review. World J Biolo Psychiatry. 2023;24:761-810.
64. Köhler CA, Freitas TH, Maes Md, De Andrade N, Liu CS, Fernandes BS, Stubbs B, Solmi M, Veronese N and Herrmann N. Peripheral cytokine and chemokine alterations in depression: a meta‐analysis of 82 studies. Acta Psychiatrica Scandinavica 2017; 35: 373-387.
65. Poletti S, Vai B, Mazza MG, Zanardi R, Lorenzi C, Calesella F, Cazzetta S, Branchi I, Colombo C and Furlan R. A peripheral inflammatory signature discriminates bipolar from unipolar depression: a machine learning approach. Prog Neuropsychopharmacol Biol Psychiatry. 2021;105(14):110136.
66. Iakunchykova O, Leonardsen EH and Wang Y. Genetic evidence for causal effects of immune dysfunction in psychiatric disorders: where are we? Transl Psychiatry. 2024;14:63.
67. Morrison J, Knoblauch N, Marcus JH, Stephens M and He X. Mendelian randomization accounting for correlated and uncorrelated pleiotropic effects using genome-wide summary statistics. Nat Genet. 2020;52(5):740-7.
2. GBD Diseases and Injuries Collaborators. Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990-2021: A systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024;403:2133-2161.
3. Stoewen DL. Nature, nurture, and mental health Part 1: The influence of genetics, psychology, and biology. Can Vet J. 2022;63:427-430.
4. Magomedova A, Fatima G. Mental health and well-being in the modern era: A comprehensive review of challenges and interventions. Cureus. 2025;17:e77683.
5. Catalina GR, Gheorman V, Gheorman V, Fortofoiu MC. The role of neuroinflammation in the comorbidity of psychiatric disorders and internal diseases. Healthcare (Basel). 2025;13:837.
6. Ma WR, Zhang LL, Ma JY, Yu F, Hou YQ, Feng XR, et al. Mendelian randomization studies of depression: Evidence, opportunities, and challenges. Ann Gen Psychiatry. 2023;22:47.
7. Yang J, Wang Q, Jiang W. Association between immune cells in peripheral blood and psychiatric symptoms. Front Psychiatry. 2023;14:1198734.
8. Thela L, Paruk S, Nkambule BB, Ntlantsana V, Abbai NS, Msibi Z, et al. Longitudinal analysis of proinflammatory and anti-inflammatory cytokines in the cerebrospinal fluid and peripheral blood of treatment-naïve first-episode psychosis patients, and their correlation with psychosis severity and cognitive impairment in sub-Saharan Africa. BMJ Open. 2025;15:e098347.
9. Zhang S, Gao Y, Zhao Y, Huang TY, Zheng Q, Wang X. Peripheral and central neuroimmune mechanisms in Alzheimer’s disease pathogenesis. Mol Neurodegener. 2025;20:22.
10. Jie J, Yao X, Deng H, Zhou Y, Jiang X, Dai X, et al. Regulatory T cells in neurological disorders and tissue regeneration: Mechanisms of action and therapeutic potentials. Neural Regen Res. 2026;21:1277-1291.
11. Shi Y, Wei B, Li L, Wang B, Sun M. Th17 cells and inflammation in neurological disorders: Possible mechanisms of action. Front Immunol. 2022;13:932152.
12. Zeitoun T, El-Sohemy A. Using Mendelian randomization to study the role of iron in health and disease. Int J Mol Sci. 2023;24:13458.
13. Larsson SC, Butterworth AS, Burgess S. Mendelian randomization for cardiovascular diseases: Principles and
applications. Eur Heart J. 2023;44:4913-4924.
14. Sekula P, Del Greco MF, Pattaro C, Köttgen A. Mendelian randomization as an approach to assess causality using observational data. J Am Soc Nephrol. 2016;27:3253-3265.
15. Bowden J, Holmes MV. Meta-analysis and Mendelian randomization: A review. Res Synth Methods. 2019;10:486-496.
16. Burgess S, Thompson SG. Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol. 2017;32:377-389.
17. Wang C, Zhu D, Zhang D, Zuo X, Yao L, Liu T, et al. Causal role of immune cells in schizophrenia: Mendelian randomization (MR) study. BMC Psychiatry. 2023;23:590.
18. Liberman JN, Pesa J, Rui P, Teeple A, Lakey S, Wiggins E, et al. Predicting poor outcomes among individuals seeking care for major depressive disorder. Psychiatr Res Clin Pract. 2022;4:102-112.
19. Chan KL, Poller WC, Swirski FK, Russo SJ. Central regulation of stress-evoked peripheral immune responses. Nat Rev Neurosci. 2023;24:591-604.
20. Cicchese JM, Evans S, Hult C, Joslyn LR, Wessler T, Millar JA, et al. Dynamic balance of pro- and anti-inflammatory signals controls disease and limits pathology. Immunol Rev. 2018;285:147-167.
21. Zhang Y, Wang SW, Ding J, Wen X, Li T, Yang L, et al. Causal role of immune cells in major depressive disorder and bipolar disorder: Mendelian randomization (MR) study. J Affect Disord. 2024;361:165-171.
22. Bekhbat M, Ulukaya GB, Bhasin MK, Felger JC, Miller AH. Cellular and immunometabolic mechanisms of inflammation in depression: Preliminary findings from single cell RNA sequencing and a tribute to Bruce McEwen. Neurobiol Stress. 2022;19:100462.
23. Maes M, Rachayon M, Jirakran K, Sughondhabirom A, Almulla AF, Sodsai P. Role of T and B lymphocyte cannabinoid type 1 and 2 receptors in major depression and suicidal behaviours. Acta Neuropsychiatr. 2024;36:287-298.
24. Kappelmann N, Arloth J, Georgakis MK, Czamara D, Rost N, Ligthart S, et al. Dissecting the association between inflammation, metabolic dysregulation, and specific depressive symptoms: A genetic correlation and 2-sample Mendelian randomization study. JAMA Psychiatry. 2021;78:161-170.
25. Palmos AB, Hübel C, Lim KX, Hunjan AK, Coleman JRI, Breen G. Assessing the evidence for causal associations between body mass index, C-reactive protein, depression, and reported trauma using Mendelian randomization. Biol Psychiatry Glob Open Sci. 2023;3:110-118.
26. Cao Y, Li X, Gao J, Zhang N, Zhang G, Li S. Revealing the causal relationship between differential white blood cell counts and depression: A bidirectional two-sample Mendelian randomization study. Depress Anxiety. 2025;2025:3131579.
27. Xia X, Li KQ, Zou W, Wang L. The central role of microglia in major depressive disorder and its potential as a therapeutic target. Front Behav Neurosci. 2025;19:1598178.
28. Wang H, He Y, Sun Z, Ren S, Liu M, Wang G, et al. Microglia in depression: An overview of microglia in the pathogenesis and treatment of depression. J Neuroinflammation. 2022;19:132.
29. DeGeorge KC, Grover M, Streeter GS. Generalized anxiety disorder and panic disorder in adults. Am Fam Physician. 2022;106:157-164.
30. Sah A, Singewald N. The (neuro)inflammatory system in anxiety disorders and PTSD: Potential treatment targets. Pharmacol Ther. 2025;269:108825.
31. Won E, Kim YK. Neuroinflammation-associated alterations of the brain as potential neural biomarkers in anxiety disorders. Int J Mol Sci. 2020;21:6546.
32. Ma Z, Zhao M, Zhao H, Qu N. Causal role of immune cells in generalized anxiety disorder: Mendelian randomization study. Front Immunol. 2023;14:1338083.
33. Chen C, Zhang D, Wu D, Chen F, Li Z, Hu Y. Gut microbiome and immune cells mediated effect on depression: A two-step, two-sample Mendelian randomization analysis. Exp Gerontol. 2024;195:112530.
34. Li H, Yi J, Xu X, Ma Y, Xiang J, Shu Y, et al. Dysfunction in neuro-mesenchymal units impairs the development of bone marrow B cells in mice with anxiety. Brain Behav Immun. 2025;124:305-320.
35. Mac Giollabhui N, Slaney C, Hemani G, Foley EM, van der Most PJ, Nolte IM, et al. Role of inflammation in depressive and anxiety disorders, affect, and cognition: Genetic and non-genetic findings in the Lifelines cohort study. Transl Psychiatry. 2025;15:164.
36. Naude PJW, Roest AM, Stein DJ, de Jonge P, Doornbos B. Anxiety disorders and CRP in a population cohort study with 54,326 participants: The LifeLines study. World J Biol Psychiatry. 2018;19:461-470.
37. Vogelzangs N, Beekman AT, de Jonge P, Penninx BW. Anxiety disorders and inflammation in a large adult cohort. Transl Psychiatry. 2013;3:e249.
38. Miola A, Fountoulakis KN, Baldessarini RJ, Veldic M, Solmi M, Rasgon N, et al. Prevalence and outcomes of rapid cycling bipolar disorder: Mixed method systematic meta-review. J Psychiatr Res. 2023;164:404-415.
39. Herrera-Rivero M, Gutierrez-Fragoso K, International Consortium on Lithium Genetics, Kurtz J, Baune BT. Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder. Transl Psychiatry. 2024;14:174.
40. Martinson JJ, Nejentsev S, Speed D, Fischer A, Mick E, Walker BR, et al. Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data. Am J Med Genet B Neuropsychiatr Genet. 2018;177(5):641-57.
41. Pereira AC, Oliveira J, Silva S, Madeira N, Pereira CMF, Cruz MT. Inflammation in bipolar disorder (BD): Identification of new therapeutic targets. Pharmacol Res. 2021;163(5):105325.
42. Rosenblat JD, McIntyre RS. Bipolar disorder and immune dysfunction: Epidemiological findings, proposed pathophysiology and clinical implications. Brain Sci. 2017;7:144.
43. Owen MJ, Legge SE, Rees E, Walters JTR, O’Donovan MC. Genomic findings in schizophrenia and their implications. Mol Psychiatry. 2023;28:3638-3647.
44. Ermakov EA, Mednova IA, Boiko AS, Buneva VN, Ivanova SA. Chemokine dysregulation and neuroinflammation in schizophrenia: A systematic review. Int J Mol Sci. 2023;24:2215.
45. Vallée A. Neuroinflammation in schizophrenia: The key role of the WNT/β-catenin pathway. Int J Mol Sci. 2022;23:2810.
46. Duncan LE, Li T, Salem M, Li W, Mortazavi L, Senturk H, et al. Mapping the cellular etiology of schizophrenia and complex brain phenotypes. Nat Neurosci. 2025;28:248-258.
47. Megha KB, Joseph X, Akhil V, Mohanan PV. Cascade of immune mechanism and consequences of inflammatory disorders. Phytomedicine. 2021;91:153712.
48. Halstead S, Siskind D, Amft M, Wagner E, Yakimov V, Shih-Jung Liu Z, et al. Alteration patterns of peripheral concentrations of cytokines and associated inflammatory proteins in acute and chronic stages of schizophrenia: A systematic review and network meta-analysis. Lancet Psychiatry. 2023;10:260-271.
49. Perry BI, Upthegrove R, Kappelmann N, Jones PB, Burgess S, Khandaker GM. Associations of immunological proteins/traits with schizophrenia, major depression and bipolar disorder: A bi-directional two-sample Mendelian randomization study. Brain Behav Immun. 2021;97:176-185.
50. Du J, Baranova A, Zhang G, Zhang F. The causal relationship between immune cell traits and schizophrenia: A Mendelian randomization analysis. Front Immunol. 2024;15:1452214.
51. Ermakov EA, Melamud MM, Buneva VN, Ivanova SA. Immune system abnormalities in schizophrenia: An integrative view and translational perspectives. Front Psychiatry. 2022;13:880568.
52. Chi H, Pepper M, Thomas PG. Principles and therapeutic applications of adaptive immunity. Cell. 2024;187:2052-2078.
53. Tanabe S, Yamashita T. B-1a lymphocytes promote oligodendrogenesis during brain development. Nat Neurosci. 2018;21:506-516.
54. Joshi I, Carney WP, Rock EP. Utility of monocyte HLA-DR and rationale for therapeutic GM-CSF in sepsis immunoparalysis. Front Immunol. 2023;14(2):1130214.
55. Li Y, Sun G, Cui Y, Ji S and Kan T. Causal associations between immune cells and psychiatric disorders: a bidirectional Mendelian randomization analysis. Naunyn Schmiedebergs Arch Pharmacol. 2025; -14.
56. Chen X, Yao T, Cai J, Fu X, Li H and Wu J. Systemic inflammatory regulators and 7 major psychiatric disorders: A two-sample Mendelian randomization study. Prog Neuropsychopharmacol Biol Psychiatry. 2022;116:110534.
57. Fang C, Sun Y, Fan C and Lei D. The relationship of immune cells with autism spectrum disorder: a bidirectional Mendelian randomization study. BMC Psychiatry. 2024;24:477.
58. Wang J, Shao Y, Deng X and Du J. Causal Relationship Between Post-Traumatic Stress Disorder and Immune Cell Traits: A Mendelian Randomization Study. Brain Behav. 2024;14:e70073.
59. Poletti S, Mazza MG and Benedetti F. Inflammatory mediators in major depression and bipolar disorder. Transl Psychiatry. 2024;14:247.
60. Croese T, Castellani G and Schwartz M. Immune cell compartmentalization for brain surveillance and protection. Nat Immunol. 2021;22:1083-92.
61. Furlan R, Melloni E, Finardi A, Vai B, Di Toro S, Aggio V, Battistini L, Borsellino G, Manfredi E and Falini A. Natural killer cells protect white matter integrity in bipolar disorder. Brain Behav Immun. 2019;81:410-21.
62. [62] Magioncalda P, Martino M, Tardito S, Sterlini B, Conio B, Marozzi V, Adavastro G, Capobianco L, Russo D and Parodi A. White matter microstructure alterations correlate with terminally differentiated CD8+ effector T cell depletion in the peripheral blood in mania: combined DTI and immunological investigation in the different phases of bipolar disorder. Brain, Behavior, and Immunity. 2018;73:192-204.
63. Spoelma MJ, Serafimovska A and Parker G. Differentiating melancholic and non-melancholic depression via biological markers: A review. World J Biolo Psychiatry. 2023;24:761-810.
64. Köhler CA, Freitas TH, Maes Md, De Andrade N, Liu CS, Fernandes BS, Stubbs B, Solmi M, Veronese N and Herrmann N. Peripheral cytokine and chemokine alterations in depression: a meta‐analysis of 82 studies. Acta Psychiatrica Scandinavica 2017; 35: 373-387.
65. Poletti S, Vai B, Mazza MG, Zanardi R, Lorenzi C, Calesella F, Cazzetta S, Branchi I, Colombo C and Furlan R. A peripheral inflammatory signature discriminates bipolar from unipolar depression: a machine learning approach. Prog Neuropsychopharmacol Biol Psychiatry. 2021;105(14):110136.
66. Iakunchykova O, Leonardsen EH and Wang Y. Genetic evidence for causal effects of immune dysfunction in psychiatric disorders: where are we? Transl Psychiatry. 2024;14:63.
67. Morrison J, Knoblauch N, Marcus JH, Stephens M and He X. Mendelian randomization accounting for correlated and uncorrelated pleiotropic effects using genome-wide summary statistics. Nat Genet. 2020;52(5):740-7.
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How to Cite
1.
Xie T, Li Z. Advances in Mendelian Randomization Studies on the Causal Relationship Between Immune Cells and Psychiatric Disorders. Iran J Allergy Asthma Immunol. 2026;:1-11.
