Association of Tumor Necrosis Factor –308G/A Promoter Polymorphism with Schizophrenia and Bipolar Affective Disorder in a Polish Population

Czerski, Piotr M.; Rybakowski, Filip; Kapelski, Paweł; Rybakowski, Janusz; Dmitrzak‐Węglarz, Monika; Leszczyńska-Rodziewicz, Anna; Słopień, Agnieszka; Skibińska, Maria; Kaczmarkiewicz-Fass, Magdalena; Hauser, Joanna

doi:10.1159/000135642

Cited by 50 publications

(25 citation statements)

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“…Increased mRNA expression of TNFa as well as TNF-R1 and TNR-R2 is also reported in BD as well as unaffected offspring (Padmos et al 2008). Abnormalities in the TNFA*2 allele and TNFa -G308A polymorphism in BD provide further support for scrutinizing the TNF pathway as a target for novel treatment development (Czerski et al 2008;Pae et al 2004;Meira-Lima et al 2003). A recent meta-analysis has identified only TNFa and IL-6 concentrations as significantly elevated in medically healthy, medication-free DSM-III-R/IV-defined patients with MDD when compared to non-depressed individuals (Dowlati et al 2010).…”

Section: Altered Cytokine Levelsmentioning

confidence: 83%

Mood Disorders and Obesity: Understanding Inflammation as a Pathophysiological Nexus

et al. 2010

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The aim of this review is to evaluate the evidentiary base supporting the hypothesis that the increased hazard for obesity in mood disorder populations (and vice versa) is a consequence of shared pathophysiological pathways. We conducted a PubMed search of all English-language articles with the following search terms: obesity, inflammation, hypothalamic-pituitary-adrenal axis, insulin, cognition, CNS, and neurotransmitters, cross-referenced with major depressive disorder and bipolar disorder. The frequent co-occurrence of mood disorders and obesity may be characterized by interconnected pathophysiology. Both conditions are marked by structural and functional abnormalities in multiple cortical and subcortical brain regions that subserve cognitive and/or affective processing. Abnormalities in several interacting biological networks (e.g. immuno-inflammatory, insulin signaling, and counterregulatory hormones) contribute to the co-occurence of mood disorders and obesity. Unequivocal evidence now indicates that obesity and mood disorders are chronic low-grade pro-inflammatory states that result in a gradual accumulation of allostatic load. Abnormalities in key effector proteins of the pro-inflammatory cascade include, but are not limited to, cytokines/adipokines such as adiponectin, leptin, and resistin as well as tumor necrosis factor alpha and interleukin-6. Taken together, the bidirectional relationship between obesity and mood disorders may represent an exophenotypic manifestation of aberrant neural and inflammatory networks. The clinical implications of these observations are that, practitioners should screen individuals with obesity for the presence of clinically significant depressive symptoms (and vice versa). This clinical recommendation is amplified in individuals presenting with biochemical indicators of insulin resistance and other concurrent conditions associated with abnormal inflammatory signaling (e.g. cardiovascular disease).

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Section: Altered Cytokine Levelsmentioning

confidence: 83%

Mood Disorders and Obesity: Understanding Inflammation as a Pathophysiological Nexus

et al. 2010

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“…On the other hand, some reports indicated the association of allele G of TNF-α (−308G/A) with schizophrenia in German,41 Finnish male,42 Australian,43 and Polish populations 44. Contrarily, several reports indicated no association of TNF-α (−308G/A) polymorphism with the susceptibility or pathogenesis of schizophrenia in the German,45 Korean,46 Australian, Indian Fijian, Indigenous Fijian, and Brahmin populations of India47 and in Taiwanese,48 Japanese,49,50 Chinese Han,51 Finnish,42,52 American Caucasian,53 and Canadian populations 54.…”

Section: Discussionmentioning

confidence: 99%

Tumor necrosis factor-α and -β genetic polymorphisms as a risk factor in Saudi patients with schizophrenia

Kadasah¹,

Arfin²,

Rizvi³

et al. 2017

NDT

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BackgroundSchizophrenia is one of the most common devastating psychiatric disorders that negatively affects the quality of life and psychosocial functions. Its etiology involves the interplay of complex polygenic influences and environmental risk factors. Inflammatory markers are well-known etiological factors for psychiatric disorders, including schizophrenia.ObjectiveThe aim of this study was to investigate the association of proinflammatory cytokine genes, tumor necrosis factor (TNF)-α (−308G/A) and TNF-β (+252A/G) polymorphisms with schizophrenia susceptibility.Subjects and methodsTNF-α and TNF-β genes were amplified using amplification refractory mutation system primers in 180 schizophrenia patients and 200 healthy matched controls recruited from the Psychiatry Clinic of Prince Sultan Military Medical City, Riyadh. The frequencies of alleles and genotypes of TNF-α (−308G/A) and TNF-β (+252A/G) polymorphisms in patients were compared with those in controls.ResultsThe frequencies of TNF-α (−308) allele A and genotype GA were significantly higher, while those of allele G and genotype GG were lower in schizophrenia patients as compared to controls, indicating that genotype GA and allele A of TNF-α (−308G/A) may increase susceptibility to schizophrenia, while genotype GG and allele G may reduce it. On the other hand, the distribution of alleles and genotypes of TNF-β (+252A/G) polymorphism does not differ significantly in patients from controls; however, the frequency of genotype GG of TNF-β (+252A/G) was significantly higher in male patients than in female patients. The distribution of TNF-α (−308G/A) and TNF-β (+252A/G) polymorphisms was almost similar in schizophrenia patients with negative or positive symptoms.ConclusionTNF-α (−308G/A) and TNF-β (+252G/A) polymorphisms may increase the susceptibility to schizophrenia in Saudi patients and could be a potential risk factor for its etiopathogenesis. However, further studies are warranted involving a larger sample size to strengthen our findings.

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“…Small studies suggest an association 59-61. Conversely, other reports no association with MDD but a possible protective association with bipolar II disorder 62.…”

Section: Introductionmentioning

confidence: 95%

Labile Anger During Interferon Alfa Treatment is Associated With a Polymorphism in Tumor Necrosis Factor α

Lotrich¹,

Ferrell²,

Rabinovitz³

et al. 2010

Clinical Neuropharmacology

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Objective-Inflammatory cytokines may influence both labile anger and depression. Both psychiatric conditions can occur during interferon-alpha (IFN-α) based treatments. Evidence also indicates a central nervous system role for TNF-α, whose expression may be increased by IFN-α. A polymorphism in the promoter region of TNF-α has been associated with various inflammatory illnesses. We therefore hypothesized that this TNF-α polymorphism would influence susceptibility to psychiatric symptoms during IFN-α therapy.Methods-105 patients with hepatitis C, initially without active major depression (MDD), were treated with IFN-α and then prospectively monitored using the Structured Clinical Interview for DSM-IV, the Beck Depression Inventory-II (BDI), the Anger Irritability and Assault Questionnaire, and circulating TNF-α levels. The A-308G polymorphism (rs1800629) was determined using the 5′-nuclease assay. Repeated-measure mixed-effect analyses compared changes in symptoms over time.Result-BDI increased during IFN-α therapy (F = 6.2; p<0.001), with 27% developing MDD. The TNF-α A allele was associated with worsened labile anger (F = 2.5; p<0.05) and fatigue (F = 2.9; p<0.05) during treatment, but not with major depression incidence (X 2 = 0.0; p=0.99) or increased BDI (F = 1.2; p=0.31). Labile anger was not predicted by the serotonin transporter polymorphism (F = 0.8; p=0.59).Discussion-During treatment with an exogenous cytokine, vulnerability to worsening labile anger --distinct from major depression --is associated with genetic variability in TNF-α. This has implications both for patients being treated with IFN-α, as well as our understanding of genetic vulnerability for different subtypes of dysphoric and mood disorders.

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Association of Tumor Necrosis Factor –308G/A Promoter Polymorphism with Schizophrenia and Bipolar Affective Disorder in a Polish Population

Cited by 50 publications

References 117 publications

Mood Disorders and Obesity: Understanding Inflammation as a Pathophysiological Nexus

Mood Disorders and Obesity: Understanding Inflammation as a Pathophysiological Nexus

Tumor necrosis factor-α and -β genetic polymorphisms as a risk factor in Saudi patients with schizophrenia

Labile Anger During Interferon Alfa Treatment is Associated With a Polymorphism in Tumor Necrosis Factor α

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Association of Tumor Necrosis Factor –308G/A Promoter Polymorphism with Schizophrenia and Bipolar Affective Disorder in a Polish Population

Cited by 50 publications

References 117 publications

Mood Disorders and Obesity: Understanding Inflammation as a Pathophysiological Nexus

Mood Disorders and Obesity: Understanding Inflammation as a Pathophysiological Nexus

Tumor necrosis factor-&alpha; and -&beta; genetic polymorphisms as a risk factor in Saudi patients with schizophrenia

Labile Anger During Interferon Alfa Treatment is Associated With a Polymorphism in Tumor Necrosis Factor α

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Tumor necrosis factor-α and -β genetic polymorphisms as a risk factor in Saudi patients with schizophrenia