Regulation of inflammatory pathways in schizophrenia: A comparative study with bipolar disorder and healthy controls

García-Álvarez, Leticia; Caso, Javier R.; García-Portilla, María Paz; Fuente-Tomás, Lorena de la; González‐Blanco, Leticia; Martínez, P. Sáiz; Leza, Juan C.; Bobes, Julio

doi:10.1016/j.eurpsy.2017.09.007

Cited by 33 publications

(21 citation statements)

References 69 publications

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“…Neuroinflammatory processes are an essential pathophysiologic mechanism of chronic diseases including severe mental disorders [6,7]. There is now evidence that major depressive disorder (MDD) is characterized by activation of the immune-inflammatory response system, as indicated by increased levels of pro-inflammatory cytokines including interleukin (IL)-6 and IL-10 [8].…”

Section: Introductionmentioning

confidence: 99%

Neutrophil-to-lymphocyte ratio: A potential new peripheral biomarker of suicidal behavior

et al. 2020

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Background. Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) have emerged as important peripheral inflammatory biomarkers. Recent data suggest a possible role of the immune system in the pathophysiology of suicidal behavior (SB). The aim of this study is to evaluate the association among NLR, MLR, and PLR and SB in patients with major depressive disorder (MDD), and to test its validity as a biomarker for suicidality. Methods. We evaluated 538 patients with MDD (mean age [standard deviation] = 43.87 [14.36] years; females: 68.8%). A logistic regression model was estimated to determine the independent factors associated with suicide risk in patients with and without a history of suicide attempt (SA). Results. Three hundred ninety-three patients (74.7%) had a personal history of SA. Patients with a previous SA were more frequently female (71.9% vs. 59.6%; p = 0.007), significantly younger (41.20 vs. 51.77 years; p < 0.001), had lower depression severity at enrolment (15.58 vs. 18.42; p < 0.000), and significantly higher mean NLR and PLR ratios (2.27 vs. 1.68, p = 0.001; 127.90 vs. 109.97, p = 0.007, respectively). In the final logistic regression model, after controlling for age, sex, and depression severity, NLR was significantly associated with SB (β = 0.489, p = 0.000; odds ratio [95% confidence intervals] = 1.631 [1.266–2.102]). We propose a cut-off value of NLR = 1.30 (sensitivity = 75% and specificity = 35%). Conclusions. Our data suggest that NLR may be a valuable, reproducible, easily accessible, and cost-effective strategy to determine suicide risk in MDD.

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Section: Introductionmentioning

confidence: 99%

Neutrophil-to-lymphocyte ratio: A potential new peripheral biomarker of suicidal behavior

et al. 2020

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“…The diagnostic criteria are based on descriptive phenomenology of clinical symptoms and clinical course due to the lack of reliable and specific biomarkers (1). However, in recent decades, several biological parameters such as inflammatory, metabolic, and neuroimaging biomarkers have been described in this population towards the goal of personalized, precision psychiatry (2)(3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress biomarkers and clinical dimensions in first 10 years of schizophrenia

González‐Blanco

García-Portilla

García-Álvarez

et al. 2018

Revista de Psiquiatría y Salud Mental (English Edition)

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BIOMARCADORES DE ESTRÉS OXIDATIVO Y DIMENSIONES CLÍNICAS EN LOS DIEZ PRIMEROS AÑOS DE ESQUIZOFRENIA ResumenIntroducción: Diversos estudios han encontrado un aumento de los parámetros de estrés oxidativo en pacientes con esquizofrenia. Los objetivos de este estudio han sido identificar potenciales biomarcadores de estrés oxidativo en pacientes estables con esquizofrenia durante los primeros 10 años de enfermedad, y determinar si se asocian con dimensiones clínicas específicas. Material y métodos:Se evaluaron 73 pacientes clínicamente estables y 73 controles sanos apareados por edad y sexo. Se recogieron datos sociodemográficos, clínicos y parámetros biológicos. Los biomarcadores sanguíneos incluyeron homocisteína, porcentaje de hemólisis, subproductos de peroxidación lipídica y, como biomarcador antioxidante, actividad de la catalasa en eritrocitos.Resultados: Los análisis comparativos tras controlar por tabaquismo y síndrome metabólico evidenciaron un aumento significativo en la actividad de la catalasa en pacientes. Así mismo, niveles inferiores de peroxidación lipídica mostraron una asociación con la sintomatología negativa. Conclusiones: Como conclusión, los mecanismos compensatorios antioxidantes podrían estar aumentados en pacientes estables con esquizofrenia durante las fases iniciales. Además, podría existir una relación inversa entre el estrés oxidativo y la dimensión negativa. Palabras clave *Manuscrito anónimo (Manuscript) 2 3 4 5 6 7 8 Abstract Introduction: Several studies have described increased oxidative stress parameters in patients with schizophrenia. The objectives of the current study were to identify potential oxidative stress biomarkers in stable patients during first ten years of schizophrenia and determine if they are associated with specific clinical dimensions. Material and methods: Seventy-three clinically stable outpatients with schizophrenia and 73 sex and age-matched healthy controls were recruited. Sociodemographic, clinical and biological data were collected at enrollment. Blood biomarkers included homocysteine, the percentage of hemolysis, lipid peroxidation subproducts, and as an antioxidant biomarker, catalase activity in erythrocytes.Results: Comparative analyses after controlling for smoking and metabolic syndrome evidenced a significant increase in catalase activity in patients. Also, lower lipid peroxidation levels showed an association with negative symptoms. Conclusions:In conclusion, compensatory antioxidant mechanisms might be increased in stable patients with schizophrenia at early stages. Furthermore, there may be an inverse relationship between oxidative stress and negative dimension.One of the probable reasons for these inconsistent results is the heterogeneity of schizophrenia and the difficulty of accurate categorization. Another underlying obstacle to studying peripheral markers is that different clinical disease stages may be associated with distinctive biomarkers, and they could fluctuate depending on whether patients are in their first-episode, an acute relapse,...

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“…In patients with established schizophrenia, NFκB, iNOS, COX‐1, COX‐2, TLR4, and PGE2 expression were found to be elevated, while the anti‐inflammatory prostaglandin 15d‐PGJ 2 and its nuclear receptor PPARγ were decreased . A recent study found higher levels of COX‐1 in BD patients compared with healthy controls, while TLR4 genetic variations have been associated with this disorder . Finally, patients with MDD showed higher expression of TLR4 and elevated TRIF and MyD88 .…”

mentioning

confidence: 97%

“…In particular, patients in an early phase of a psychotic disorder showed increased levels of pro‐inflammatory NFκB, iNOS, and COX‐2, while the anti‐inflammatory inhibitory subunit of NFκB, 15d‐PGJ 2 , and PPARγ expression and transcriptional activity were lower . In patients with established schizophrenia, NFκB, iNOS, COX‐1, COX‐2, TLR4, and PGE2 expression were found to be elevated, while the anti‐inflammatory prostaglandin 15d‐PGJ 2 and its nuclear receptor PPARγ were decreased . A recent study found higher levels of COX‐1 in BD patients compared with healthy controls, while TLR4 genetic variations have been associated with this disorder .…”

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confidence: 98%

Effects of electroconvulsive therapy in the systemic inflammatory balance of patients with severe mental disorder

Bioque

MacDowell

Meseguer

et al. 2019

Psychiatry Clin Neurosci

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Aim: There is a great interest in the role of the immune system and the inflammatory balance as key mechanisms involved in the pathophysiology of severe mental disorders. Previous studies have indicated that electroconvulsive therapy (ECT) produces changes in certain inflammatory mediators or in the immune system response. This study aimed to explore the effects of ECT on the nuclear transcription factor κB (NFκB) pathway, a main regulatory pathway of the inflammatory/immune response.Methods: Thirty subjects with a severe mental disorder receiving treatment with ECT in our center were included. Thirteen systemic biomarkers related to the NFκB pathway were analyzed right before and 2 h after a single ECT session.Results: An ECT session significantly decreased the expression of NFκB (P = 0.035) and of the inducible nitric oxide synthase (P = 0.012), and the plasma levels of nitrites (P = 0.027), prostaglandin E 2 (P = 0.049), and 15-deoxy-PGJ 2 (P < 0.001). Decrease in plasmatic levels of nitrites was greater in females than in males (P = 0.021). A positive correlation between the ECT stimulus load and changes in the expression of NFkB was found (P = 0.036). Thiobarbituric acid reactive substance levels were decreased in treatment responders and increased in non-responders (P = 0.047). Conclusion:Our study shows the effects that a single session of ECT produces on a canonical regulatory pathway of the inflammatory/innate immune system and the inflammatory balance. These biomarkers could be useful as treatment response targets and could help to clarify the biological basis of ECT action. These findings warrant greater attention in future investigations and in the translational significance of these data.

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Regulation of inflammatory pathways in schizophrenia: A comparative study with bipolar disorder and healthy controls

Abstract: This study suggests a specific immune-inflammatory biomarker pattern for established SCH (NFκB, PGE2, iNOS, and COX-2) that differentiates it from BD and HC. In future, their pharmacological modulation may constitute a promising therapeutic target.

Cited by 33 publications

References 69 publications

Neutrophil-to-lymphocyte ratio: A potential new peripheral biomarker of suicidal behavior

Neutrophil-to-lymphocyte ratio: A potential new peripheral biomarker of suicidal behavior

Oxidative stress biomarkers and clinical dimensions in first 10 years of schizophrenia

Effects of electroconvulsive therapy in the systemic inflammatory balance of patients with severe mental disorder

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