Associations of Genetic Polymorphisms and Neuroimmune Markers With Some Parameters of Frontal Lobe Dysfunction in Schizophrenia

Morozova, Аnna; Zorkina, Yana; Павлов, К. А.; Pavlova, Olga V.; Abramova, Olga; Ushakova, Valeria; Mudrak, Alexander V.; Zozulya, S A; Otman, I.; Sarmanova, Zoya; Klyushnik, T. P.; Reznik, A. M.; Kostyuk, Georgiy; Чехонин, В. П.

doi:10.3389/fpsyt.2021.655178

Cited by 12 publications

(7 citation statements)

References 56 publications

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“…Nonetheless, those authors explain that these results should be interpreted with caution because these are first-time studies, and the sample size is small [14]. The involvement of the immune system in the pathophysiology of schizophrenia is supported by the following findings: (a) an imbalance between pro-and anti-inflammatory cytokines and an effect of antipsychotic medication on their levels [15][16][17][18]; (b) activation of microglia, as confirmed by animal studies, postmortem brain studies, and positron emission tomography [19][20][21]; (c) higher prevalence of autoantibodies [22,23]; (d) activation of inflammation-related genes in the brain [24,25]; and (e) increased expression of proinflammatory genes in circulating monocytes [26]. Peripheral cytokines can cross the blood-brain barrier in patients with schizophrenia after damage but also bind to specific transporters, penetrate via afferent vagal fibers, and get access through circumventricular organs [27,28].…”

Section: Introductionmentioning

confidence: 99%

Cytokines as Potential Biomarkers of Clinical Characteristics of Schizophrenia

Mednova

Boiko

Kornetova

et al. 2022

Life

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Immune activation plays a major role in the pathogenesis of schizophrenia, as confirmed by many studies, systematic reviews, and meta-analyses. The important role of neuroinflammation in the formation of the relation between impaired neurobiological processes and schizophrenia psychopathology is being actively discussed. We quantified serum concentrations of 22 cytokines in 236 patients with schizophrenia and 103 mentally and somatically healthy individuals by a multiplex assay. We found higher TGF-α (p = 0.014), IFN-γ (p = 0.036), IL-5 (p < 0.001), IL-6 (p = 0.047), IL-8 (p = 0.005), IL-10 (p <0.001), IL-15 (p = 0.007), IL-1RA (p = 0.007), and TNF-α (p < 0.001) levels in patients with schizophrenia than in healthy individuals. Subgroup analysis revealed a much greater number of statistically significant differences in cytokine levels among females than among males. Patients with a continuous course of schizophrenia showed statistically significantly higher levels of IL-12p70 (p = 0.019), IL-1α (p = 0.046), and IL-1β (p = 0.035) compared with patients with an episodic course. Most cytokines were positively correlated with positive, general, and total PANSS scores. In patients with a duration of schizophrenia of 10 years or more, the level of IL-10 was higher than that in patients with a disease duration of 5 years or less (p = 0.042). Thus, an imbalance in cytokines was revealed in patients with schizophrenia, depending on sex and clinical characteristics of the disease.

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Section: Introductionmentioning

confidence: 99%

Cytokines as Potential Biomarkers of Clinical Characteristics of Schizophrenia

Mednova

Boiko

Kornetova

et al. 2022

Life

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“…Certain BDNF isoforms at low levels were consistently found to correlate with cognitive impairment in individuals with schizophrenia compared to controls ( 56 ). In line with these findings, Morozova ( 40 ) found that patients with genotype T/T (Met66Met polymorphism) demonstrated higher scores on PANSS, reflecting more severe symptoms, regardless of age. None of the other studies found a significant association between positive and negative PANSS scores and the Val66Met polymorphism, most focusing on the risk for schizophrenia or association with cognitive functions.…”

Section: Discussionmentioning

confidence: 72%

“…Looking at the association between the BDNF rs6265 and the TNF-α rs1799964 polymorphism in patients with schizophrenia, Zhang ( 28 ) found that the interaction of these two genes contributes to cognitive dysfunction, possibly by decreasing the expression of BDNF in the hippocampus. Only one study – Morozova ( 40 ) assessed immunological parameters along with their primary assessments, finding no association between genotype and immune status of patients, contrary to recent literature suggesting the contrary ( 3 ). Patients with schizophrenia have been found in numerous studies to present with upregulated genes for inflammatory cytokines and downregulated BDNF gene transcription ( 57 , 58 ).…”

Section: Discussionmentioning

confidence: 85%

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BDNF gene Val66Met polymorphisms as a predictor for clinical presentation in schizophrenia – recent findings

Farcas,

Hindmarch,

Iftene

2023

Front. Psychiatry

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Schizophrenia is a highly heritable, severe psychiatric disorder that involves dysfunctions in thinking, emotions, and behavior, with a profound impact on a person’s ability to function normally in their daily life. Research efforts continue to focus on elucidating possible genetic underlying mechanisms of the disorder. Although the genetic loci identified to date to be significantly associated with schizophrenia risk do not represent disease-causing factors, each one of them could be seen as a possible incremental contributor. Considering the importance of finding new and more efficient pharmacological approaches to target the complex symptomatology of this disorder, in this scoping review, we are focusing on the most recent findings in studies aiming to elucidate the contribution of one of the genetic factors involved – the BDNF gene Val66Met polymorphisms. Here we performed a systematic search in Pubmed, Embase, and Web of Science databases with the search terms: (BDNF gene polymorphism) AND (schizophrenia) for articles published in the last 5 years. To be selected for this review, articles had to report on studies where genotyping for the BDNF Val66Met polymorphism was performed in participants diagnosed with schizophrenia (or schizophrenia spectrum disorders or first-episode psychosis). The search provided 35 results from Pubmed, 134 results from Embase, and 118 results from the Web of Science database. Twenty-two articles were selected to be included in this review, all reporting on studies where an implication of the BDNF Val66Met polymorphisms in the disorder’s pathophysiology was sought to be elucidated. These studies looked at BDNF gene Val66Met polymorphism variants, their interactions with other genes of interest, and different facets of the illness. The Met/Met genotype was found to be associated with higher PANSS positive scores. Furthermore, Met/Met homozygous individuals appear to present with worse cognitive function and lower levels of serum BDNF. In the Val/Val genotype carriers, increased BDNF levels were found to correlate with weight gain under Risperidone treatment. However, due to heterogeneous results, the diversity in study populations and studies’ small sample sizes, generalizations cannot be made. Our findings emphasize the need for further research dedicated to clarifying the role of gene polymorphisms in antipsychotic treatment to enhance specificity and efficacy in the treatment of schizophrenia.

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“…In schizophrenia, a wide range of antinuclear antibodies, antineuronal antibodies [ 19 ], and antibodies to myelin are found [ 20 ]. Research by Kliushnik, T. et al indicated that antibodies to MBP may be related to the diagnosis of schizophrenia [ 21 , 22 ], and associated with the severity of clinical symptoms [ 23 ]. The different dynamics of immune markers, including autoantibodies to MBP, correspond to different features of clinical remission after first-episode psychosis in young patients [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

The Influence of Antipsychotic Treatment on the Activity of Abzymes Targeting Myelin and Levels of Inflammation Markers in Patients with Schizophrenia

et al. 2023

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Catalytic antibodies, or abzymes, are capable of not only binding but also hydrolyzing various proteins. Previously, an increase in the level of myelin basic protein (MBP)-hydrolyzing activity of antibodies was shown in patients with a number of neurological and mental disorders, including schizophrenia. Furthermore, antipsychotic therapy is known to induce a change in cytokine levels in patients with schizophrenia, which affects regulation of the immune response and inflammatory status. This study investigated the influence of typical and atypical antipsychotics on catalytic antibody activity and the 10 major pro- and anti-inflammatory serum cytokine levels. The study included 40 patients with schizophrenia: 15 treated with first-generation antipsychotics and 25 treated with atypical antipsychotics for 6 weeks. It was found that treatment with atypical antipsychotics changed the levels of some pro-inflammatory cytokines. Antipsychotic therapy also caused a significant decrease in MBP-hydrolyzing activity in patients with schizophrenia (p = 0.0002), and associations of catalytic activity with interleukins were observed.

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Associations of Genetic Polymorphisms and Neuroimmune Markers With Some Parameters of Frontal Lobe Dysfunction in Schizophrenia

Cited by 12 publications

References 56 publications

Cytokines as Potential Biomarkers of Clinical Characteristics of Schizophrenia

Cytokines as Potential Biomarkers of Clinical Characteristics of Schizophrenia

BDNF gene Val66Met polymorphisms as a predictor for clinical presentation in schizophrenia – recent findings

The Influence of Antipsychotic Treatment on the Activity of Abzymes Targeting Myelin and Levels of Inflammation Markers in Patients with Schizophrenia

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