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Markers of inflammation in patients with generalized anxiety disorder

Year 2024, Volume: 49 Issue: 4, 908 - 915, 30.12.2024
https://doi.org/10.17826/cumj.1510275

Abstract

Purpose: The aim of this study was to analyze the systemic immune response index, systemic immune inflammation index, neutrophil/HDL, lymphocyte/HDL, platelet/HDL, and monocyte/HDL ratio, used as inflammatory markers in patients with generalized anxiety disorder (GAD).
Materials and Methods: A total of 864 participants, including 432 healthy controls and 432 patients diagnosed with GAD, were included in this study. High-density lipoprotein (HDL-c) levels, neutrophil, monocyte, lymphocyte, and platelet counts; systemic inflammatory response index (SIRI), systemic immune-inflammatory index (SII), neutrophil/high-density lipoprotein ratio (NHR), lymphocyte/high-density lipoprotein ratio (LHR), monocyte/high-density lipoprotein ratio (MHR), and platelet/high-density lipoprotein ratio (PHR) were calculated.
Results: The median age of the case group was 35.50 (interquartile range: 28.00-44.00), while the median age of the control group was 35.00 (interquartile range: 28.00-44.00). In the GAD group, neutrophils, monocytes, SII, SIRI, NHR, LHR, MHR, and PHR were significantly higher, while platelets and HDL were significantly lower.
Conclusions: This study highlights that elevated systemic inflammation markers, such as SII and SIRI, along with altered HDL ratios, may be associated with GAD. The findings support the hypothesis that inflammation plays a role in the etiopathogenesis of GAD, potentially contributing to both diagnosis and management.

References

  • American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Washington DC, American Psychiatric Association. 2013.
  • Maron E, Nutt D. Biological markers of generalized anxiety disorder. Dialogues Clin Neurosci. 2017;19:147-58.
  • Ruscio AM, Hallion LS, Lim CCW, Aguilar-Gaxiola S, Al-Hamzawi A, Alonso J et al. Cross-sectional comparison of the epidemiology of DSM-5 generalized anxiety disorder across the globe. JAMA Psychiatry. 2017;74:465-75.
  • Korkut Bayindir S, Ünsal A. Nursing diagnosis and interventions in the common mental diseases. J Duzce Univ Heal Sci Inst. 2016;6:115-19.
  • DeMartini J, Patel G, Fancher TL. Generalized anxiety disorder. Ann Intern Med. 2019;170:9:64.
  • Michopoulos V, Powers A, Gillespie CF, Ressler KJ, Jovanovic T. Inflammation in fear- and anxiety-based disorders: PTSD, GAD, and beyond. Neuropsychopharmacology. 2017;42:254-70.
  • Munir S, Takov V. Generalized anxiety disorder.. In: StatPearls [Internet]. Treasure Island (FL), StatPearls Publishing; 2024.
  • Yehuda R. Status of glucocorticoid alterations in post-traumatic stress disorder. Ann N Y Acad Sci. 2009;1179:56-69.
  • Nance DM, Sanders VM. Autonomic innervation and regulation of the immune system (1987-2007). Brain Behav Immun. 2007;21:736-45.
  • Won E, Kim YK. Neuroinflammation-associated alterations of the brain as potential neural biomarkers in anxiety disorders. Int J Mol Sci. 2020;21:6546.
  • Felger JC. Imaging the role of inflammation in mood and anxiety-related disorders. Curr Neuropharmacol. 2018;16:533-58.
  • Costello H, Gould RL, Abrol E, Howard R. Systematic review and meta-analysis of the association between peripheral inflammatory cytokines and generalised anxiety disorder. BMJ Open. 2019;9:e027925.
  • Yıldız S, Kazğan A, Tabara M, Atmaca M. The relationship between impulsivity level and neutrophil/lymphocyte ratio, platelet/lymphocyte ratio and mean platelet volume in individuals diagnosed with gambling disorder. Medical Records. 2021;3:177-83.
  • Inaltekin A, Yağci İ. Evaluation of simple markers of inflammation and systemic immune inflammation index in schizophrenia, bipolar disorder patients and healthy controls. Turk Psikiyatri Derg. 2023;34:11-15.
  • Kong F, Huang J, Xu C, Huang T, Wen G, Cheng W. System inflammation response index: a novel inflammatory indicator to predict all-cause and cardiovascular disease mortality in the obese population. Diabetol Metab Syndr. 2023;15:195.
  • Cheng W, Bu X, Xu C, Wen G, Kong F, Pan H et al. Higher systemic immune-inflammation index and systemic inflammation response index levels are associated with stroke prevalence in the asthmatic population: a cross-sectional analysis of the NHANES 1999-2018. Front Immunol. 2023;14:1191130.
  • Wei Y, Wang T, Li G, Feng J, Deng L, Xu H et al. Investigation of systemic immune-inflammation index, neutrophil/high-density lipoprotein ratio, lymphocyte/high-density lipoprotein ratio, and monocyte/high-density lipoprotein ratio as indicators of inflammation in patients with schizophrenia and bipolar disorder. Front Psychiatry. 2022;13:941728.
  • Bonizzi A, Piuri G, Corsi F, Cazzola R, Mazzucchelli S. HDL dysfunctionality: clinical relevance of quality rather than quantity. Biomedicines. 2021;9:729.
  • Cheng N, Ma H, Zhang K, Zhang C, Geng D. The predictive value of monocyte/high-density lipoprotein ratio (MHR) and positive symptom scores for aggression in patients with schizophrenia. Medicina (Kaunas). 2023;59:503.
  • Korkmaz ŞA, Kızgın S. Neutrophil/high-density lipoprotein cholesterol (HDL), monocyte/HDL and platelet/HDL ratios are increased in acute mania as markers of inflammation, even after controlling for confounding factors. Curr Med Res Opin. 2023;39:1383-90.
  • Bodaghi A, Fattahi N, Ramazani A. Biomarkers: Promising and valuable tools towards diagnosis, prognosis and treatment of Covid-19 and other diseases. Heliyon. 2023;9:13323.
  • Agnello L, Giglio RV, Bivona G, Scazzone C, Gambino CM, Iacona A et al. The value of a complete blood count (CBC) for sepsis diagnosis and prognosis. Diagnostics (Basel). 2021;11:1881.
  • Tekin S, Avcı E, Nar R, Değirmenci E, Demir S, Şenol H. Are monocyte/HDL, lymphocyte/monocyte and neutrophil/lymphocyte ratios prognostic or follow-up markers in ischemic cerebrovascular patients?. J Basic Clin Health Sci. 2020;4:38-43
  • Šagud M, Madžarac Z, Nedic Erjavec G, Šimunović Filipčić I, Mikulić FL, Rogić D et al. The associations of neutrophil-lymphocyte, platelet-lymphocyte, monocyte-lymphocyte ratios and immune-inflammation index with negative symptoms in patients with schizophrenia. Biomolecules. 2023;13:297.
  • Zhu X, Zhou J, Zhu Y, Yan F, Han X, Tan Y et al. Neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios in schizophrenia. Australas Psychiatry. 2022;30:95-99.
  • Cheng Y, Wang Y, Wang X, Jiang Z, Zhu L, Fang S. Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio in depression: an updated systematic review and meta-analysis. Front Psychiatry. 2022;13:893097.
  • Uzun N, Akıncı MA. Hemogram parameters in childhood anxiety disorders: Could anxiety disorders be related with inflammation? Med Hypotheses. 2021;146:110440.
  • Li B, Qu Y, Fan Z, Gong X, Xu H, Wu L et al. Causal relationships between blood lipids and major psychiatric disorders: Univariable and multivariable mendelian randomization analysis. BMC Med Genomics. 2023;16:250.
  • Ramachandran Pillai R, Wilson AB, Premkumar NR, Kattimani S, Sagili H, Rajendiran S. Low serum levels of high-density lipoprotein cholesterol (HDL-c) as an indicator for the development of severe postpartum depressive symptoms. PLoS One. 2018;13:0192811.
  • Torsvik A, Brattbakk HR, Trentani A, Holdhus R, Stansberg C, Bartz-Johannessen CA et al. Patients with schizophrenia and bipolar disorder display a similar global gene expression signature in whole blood that reflects elevated proportion of immature neutrophil cells with association to lipid changes. Transl Psychiatry. 2023;13:147.
  • Candemir M, Cansız A. Predictive value of monocyte to high-density lipoprotein cholesterol ratio (MHR) in schizophrenia patients with stable coronary artery disease. Genel Tıp Dergisi. 2022;32:77-83.
  • Cui S, Li J, Liu Y, Yao G, Wu Y, Liu Z et al. Correlation of systemic immune-inflammation index and moderate/major depression in patients with depressive disorders: a large sample cross-sectional study. Front Psychiatry. 2023;14:1159889.
  • Sırlıer Emir B, Yıldız S, Kazğan Kılıçaslan A, Kurt O, Uğur K, Tabara MF et al. Inflammation markers in patients with bipolar disorder who have committed offenses and their relationship with criminal behavior. Medicina (Kaunas). 2023;59:1725.
  • Canlı D. Evaluation of systemic immune-inflammation index, systemic inflammatory response index and hematologic inflammatory parameters in generalized anxiety disorder: a controlled study. Anadolu Current Medical Journal. 2024;6:161-67.
  • Sahpolat M, Ayar D, Ari M, Karaman MA. Elevated monocyte to high-density lipoprotein ratios as an inflammation markers for schizophrenia patients. Clin Psychopharmacol Neurosci. 2021;19:112-16.
  • Dawidowski B, Grelecki G, Biłgorajski A, Podwalski P, Misiak B, Samochowiec J. Effect of antipsychotic treatment on neutrophil-to-lymphocyte ratio during hospitalization for acute psychosis in the course of schizophrenia-a cross-sectional retrospective study. J Clin Med. 2021;11:232.
  • Paolini M, Harrington Y, Raffaelli L, Poletti S, Zanardi R, Colombo C et al. Neutrophil to lymphocyte ratio and antidepressant treatment response in patients with major depressive disorder: Effect of sex and hippocampal volume. Eur Neuropsychopharmacol 223;76:52-60.
  • Watkins DC, Johnson NC. Age and gender differences in psychological distress among african americans and whites: findings from the 2016 National Health Interview Survey. Healthcare (Basel). 2018;6:6.
  • Esposito CM, De Cagna F, Caldiroli A, Capuzzi E, Ceresa A, Di Paolo M et al. Gender differences in clinical and biochemical parameters among patients hospitalized for schizophrenia: towards precision medicine. Eur Arch Psychiatry Clin Neurosci. 2024;274:1093-103.
  • Wong GCL, Ng TKS, Lee JL, Lim PY, Chua SKJ, Tan C et al. Horticultural therapy reduces biomarkers of immunosenescence and inflammaging in community‐dwelling older adults: A feasibility pilot randomized controlled trial. J Gerontol A Biol Sci Med Sci. 2021;76:307‐17.
  • Liu Y, Zhao W, Lu Y, Zhao Y, Zhang Y, Dai M et al. Systematic metabolic characterization of mental disorders reveals age-related metabolic disturbances as potential risk factors for depression in older adults. MedComm (2020). 2022;3:165

Yaygın anksiyete bozukluğu tanılı hastalarda inflamasyon belirteçleri

Year 2024, Volume: 49 Issue: 4, 908 - 915, 30.12.2024
https://doi.org/10.17826/cumj.1510275

Abstract

Amaç: Bu çalışmada yaygın anksiyete bozukluğu (YAB) hastalarında inflamasyon belirteçleri olarak kullanılan sistemik immün cevap indeksi, sistemik immün inflamasyon indeksi, nötrofil/HDL, lenfosit/HDL, platelet/HDL ve monosit/HDL oranını incelemeyi amaçlanmıştır.
Gereç ve Yöntem: Bu çalışmaya 432 sağlıklı kontrol ve 432 YAB tanılı hasta olmak üzere toplam 864 katılımcı dahil edildi. Yüksek yoğunluklu lipoprotein (HDL-c) seviyeleri, nötrofil, monosit, lenfosit ve trombosit sayıları; sistemik inflamatuar yanıt indeksi (SIRI), sistemik immün-inflamatuar indeks (SII), nötrofil/yüksek yoğunluklu lipoprotein oranı (NHR), lenfosit/yüksek yoğunluklu lipoprotein oranı (LHR), monosit/yüksek yoğunluklu lipoprotein oranı (MHR), trombosit/yüksek yoğunluklu lipoprotein oranı (PHR) hesaplandı.
Bulgular: Vaka grubunun ortanca yaşı 35.50 (çeyrekler arası aralık: 28.00-44.00), kontrol grubunun ortanca yaşı ise 35.00 (çeyrekler arası aralık: 28.00-44.00) idi. GAD grubunda nötrofil, monosit, SII, SIRI, NHR, LHR, MHR ve PHR değeri kontrol grubundan anlamlı şekilde yüksek; trombosit ve HDL değeri ise anlamlı şekilde düşük bulunmuştur.
Sonuç: Bu çalışma, SII ve SIRI gibi yüksek sistemik inflamasyon belirteçlerinin, değişmiş HDL oranları ile birlikte, YAB ile ilişkili olabileceğini vurgulamaktadır. Bulgular, inflamasyonun YAB'nin etiyopatogenezinde rol oynadığı hipotezini desteklemekte ve potansiyel olarak hem tanıya hem de tedaviye katkıda bulunmaktadır.

References

  • American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Washington DC, American Psychiatric Association. 2013.
  • Maron E, Nutt D. Biological markers of generalized anxiety disorder. Dialogues Clin Neurosci. 2017;19:147-58.
  • Ruscio AM, Hallion LS, Lim CCW, Aguilar-Gaxiola S, Al-Hamzawi A, Alonso J et al. Cross-sectional comparison of the epidemiology of DSM-5 generalized anxiety disorder across the globe. JAMA Psychiatry. 2017;74:465-75.
  • Korkut Bayindir S, Ünsal A. Nursing diagnosis and interventions in the common mental diseases. J Duzce Univ Heal Sci Inst. 2016;6:115-19.
  • DeMartini J, Patel G, Fancher TL. Generalized anxiety disorder. Ann Intern Med. 2019;170:9:64.
  • Michopoulos V, Powers A, Gillespie CF, Ressler KJ, Jovanovic T. Inflammation in fear- and anxiety-based disorders: PTSD, GAD, and beyond. Neuropsychopharmacology. 2017;42:254-70.
  • Munir S, Takov V. Generalized anxiety disorder.. In: StatPearls [Internet]. Treasure Island (FL), StatPearls Publishing; 2024.
  • Yehuda R. Status of glucocorticoid alterations in post-traumatic stress disorder. Ann N Y Acad Sci. 2009;1179:56-69.
  • Nance DM, Sanders VM. Autonomic innervation and regulation of the immune system (1987-2007). Brain Behav Immun. 2007;21:736-45.
  • Won E, Kim YK. Neuroinflammation-associated alterations of the brain as potential neural biomarkers in anxiety disorders. Int J Mol Sci. 2020;21:6546.
  • Felger JC. Imaging the role of inflammation in mood and anxiety-related disorders. Curr Neuropharmacol. 2018;16:533-58.
  • Costello H, Gould RL, Abrol E, Howard R. Systematic review and meta-analysis of the association between peripheral inflammatory cytokines and generalised anxiety disorder. BMJ Open. 2019;9:e027925.
  • Yıldız S, Kazğan A, Tabara M, Atmaca M. The relationship between impulsivity level and neutrophil/lymphocyte ratio, platelet/lymphocyte ratio and mean platelet volume in individuals diagnosed with gambling disorder. Medical Records. 2021;3:177-83.
  • Inaltekin A, Yağci İ. Evaluation of simple markers of inflammation and systemic immune inflammation index in schizophrenia, bipolar disorder patients and healthy controls. Turk Psikiyatri Derg. 2023;34:11-15.
  • Kong F, Huang J, Xu C, Huang T, Wen G, Cheng W. System inflammation response index: a novel inflammatory indicator to predict all-cause and cardiovascular disease mortality in the obese population. Diabetol Metab Syndr. 2023;15:195.
  • Cheng W, Bu X, Xu C, Wen G, Kong F, Pan H et al. Higher systemic immune-inflammation index and systemic inflammation response index levels are associated with stroke prevalence in the asthmatic population: a cross-sectional analysis of the NHANES 1999-2018. Front Immunol. 2023;14:1191130.
  • Wei Y, Wang T, Li G, Feng J, Deng L, Xu H et al. Investigation of systemic immune-inflammation index, neutrophil/high-density lipoprotein ratio, lymphocyte/high-density lipoprotein ratio, and monocyte/high-density lipoprotein ratio as indicators of inflammation in patients with schizophrenia and bipolar disorder. Front Psychiatry. 2022;13:941728.
  • Bonizzi A, Piuri G, Corsi F, Cazzola R, Mazzucchelli S. HDL dysfunctionality: clinical relevance of quality rather than quantity. Biomedicines. 2021;9:729.
  • Cheng N, Ma H, Zhang K, Zhang C, Geng D. The predictive value of monocyte/high-density lipoprotein ratio (MHR) and positive symptom scores for aggression in patients with schizophrenia. Medicina (Kaunas). 2023;59:503.
  • Korkmaz ŞA, Kızgın S. Neutrophil/high-density lipoprotein cholesterol (HDL), monocyte/HDL and platelet/HDL ratios are increased in acute mania as markers of inflammation, even after controlling for confounding factors. Curr Med Res Opin. 2023;39:1383-90.
  • Bodaghi A, Fattahi N, Ramazani A. Biomarkers: Promising and valuable tools towards diagnosis, prognosis and treatment of Covid-19 and other diseases. Heliyon. 2023;9:13323.
  • Agnello L, Giglio RV, Bivona G, Scazzone C, Gambino CM, Iacona A et al. The value of a complete blood count (CBC) for sepsis diagnosis and prognosis. Diagnostics (Basel). 2021;11:1881.
  • Tekin S, Avcı E, Nar R, Değirmenci E, Demir S, Şenol H. Are monocyte/HDL, lymphocyte/monocyte and neutrophil/lymphocyte ratios prognostic or follow-up markers in ischemic cerebrovascular patients?. J Basic Clin Health Sci. 2020;4:38-43
  • Šagud M, Madžarac Z, Nedic Erjavec G, Šimunović Filipčić I, Mikulić FL, Rogić D et al. The associations of neutrophil-lymphocyte, platelet-lymphocyte, monocyte-lymphocyte ratios and immune-inflammation index with negative symptoms in patients with schizophrenia. Biomolecules. 2023;13:297.
  • Zhu X, Zhou J, Zhu Y, Yan F, Han X, Tan Y et al. Neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios in schizophrenia. Australas Psychiatry. 2022;30:95-99.
  • Cheng Y, Wang Y, Wang X, Jiang Z, Zhu L, Fang S. Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio in depression: an updated systematic review and meta-analysis. Front Psychiatry. 2022;13:893097.
  • Uzun N, Akıncı MA. Hemogram parameters in childhood anxiety disorders: Could anxiety disorders be related with inflammation? Med Hypotheses. 2021;146:110440.
  • Li B, Qu Y, Fan Z, Gong X, Xu H, Wu L et al. Causal relationships between blood lipids and major psychiatric disorders: Univariable and multivariable mendelian randomization analysis. BMC Med Genomics. 2023;16:250.
  • Ramachandran Pillai R, Wilson AB, Premkumar NR, Kattimani S, Sagili H, Rajendiran S. Low serum levels of high-density lipoprotein cholesterol (HDL-c) as an indicator for the development of severe postpartum depressive symptoms. PLoS One. 2018;13:0192811.
  • Torsvik A, Brattbakk HR, Trentani A, Holdhus R, Stansberg C, Bartz-Johannessen CA et al. Patients with schizophrenia and bipolar disorder display a similar global gene expression signature in whole blood that reflects elevated proportion of immature neutrophil cells with association to lipid changes. Transl Psychiatry. 2023;13:147.
  • Candemir M, Cansız A. Predictive value of monocyte to high-density lipoprotein cholesterol ratio (MHR) in schizophrenia patients with stable coronary artery disease. Genel Tıp Dergisi. 2022;32:77-83.
  • Cui S, Li J, Liu Y, Yao G, Wu Y, Liu Z et al. Correlation of systemic immune-inflammation index and moderate/major depression in patients with depressive disorders: a large sample cross-sectional study. Front Psychiatry. 2023;14:1159889.
  • Sırlıer Emir B, Yıldız S, Kazğan Kılıçaslan A, Kurt O, Uğur K, Tabara MF et al. Inflammation markers in patients with bipolar disorder who have committed offenses and their relationship with criminal behavior. Medicina (Kaunas). 2023;59:1725.
  • Canlı D. Evaluation of systemic immune-inflammation index, systemic inflammatory response index and hematologic inflammatory parameters in generalized anxiety disorder: a controlled study. Anadolu Current Medical Journal. 2024;6:161-67.
  • Sahpolat M, Ayar D, Ari M, Karaman MA. Elevated monocyte to high-density lipoprotein ratios as an inflammation markers for schizophrenia patients. Clin Psychopharmacol Neurosci. 2021;19:112-16.
  • Dawidowski B, Grelecki G, Biłgorajski A, Podwalski P, Misiak B, Samochowiec J. Effect of antipsychotic treatment on neutrophil-to-lymphocyte ratio during hospitalization for acute psychosis in the course of schizophrenia-a cross-sectional retrospective study. J Clin Med. 2021;11:232.
  • Paolini M, Harrington Y, Raffaelli L, Poletti S, Zanardi R, Colombo C et al. Neutrophil to lymphocyte ratio and antidepressant treatment response in patients with major depressive disorder: Effect of sex and hippocampal volume. Eur Neuropsychopharmacol 223;76:52-60.
  • Watkins DC, Johnson NC. Age and gender differences in psychological distress among african americans and whites: findings from the 2016 National Health Interview Survey. Healthcare (Basel). 2018;6:6.
  • Esposito CM, De Cagna F, Caldiroli A, Capuzzi E, Ceresa A, Di Paolo M et al. Gender differences in clinical and biochemical parameters among patients hospitalized for schizophrenia: towards precision medicine. Eur Arch Psychiatry Clin Neurosci. 2024;274:1093-103.
  • Wong GCL, Ng TKS, Lee JL, Lim PY, Chua SKJ, Tan C et al. Horticultural therapy reduces biomarkers of immunosenescence and inflammaging in community‐dwelling older adults: A feasibility pilot randomized controlled trial. J Gerontol A Biol Sci Med Sci. 2021;76:307‐17.
  • Liu Y, Zhao W, Lu Y, Zhao Y, Zhang Y, Dai M et al. Systematic metabolic characterization of mental disorders reveals age-related metabolic disturbances as potential risk factors for depression in older adults. MedComm (2020). 2022;3:165
There are 41 citations in total.

Details

Primary Language English
Subjects Psychiatry
Journal Section Research
Authors

Sevler Yıldız 0000-0002-9951-9093

Aslı Kazğan Kılıçaslan 0000-0002-0312-0476

Burcu Sırlıer Emir 0000-0002-3389-5790

Muhammed Fatih Tabara 0000-0002-7479-5622

Osman Kurt 0000-0003-4164-3611

Şeyma Sehlikoğlu 0000-0002-9512-713X

Kerim Uğur 0000-0002-3131-6564

Publication Date December 30, 2024
Submission Date July 4, 2024
Acceptance Date November 17, 2024
Published in Issue Year 2024 Volume: 49 Issue: 4

Cite

MLA Yıldız, Sevler et al. “Markers of Inflammation in Patients With Generalized Anxiety Disorder”. Cukurova Medical Journal, vol. 49, no. 4, 2024, pp. 908-15, doi:10.17826/cumj.1510275.