An Interleukin-1 beta (IL1B) haplotype linked with psychosis transition is associated with IL1B gene expression and brain structure

Mostaid, Shaki; Dimitrakopoulos, Stefanos; Wannan, Cassandra; Cropley, Vanessa; Weickert, Cynthia Shannon; Everall, Ian; Pantelis, Christos; Bousman, Chad

doi:10.1016/j.schres.2018.09.008

Cited by 12 publications

(13 citation statements)

References 24 publications

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“…The A-G-T haplotype incorporated by rs16944, rs4848306 and rs12621220 have been previously reported as markers for psychosis transition, higher IL-1β mRNA expression, and duration of illness in schizophrenia (Papiol et al, 2004;Shirts et al, 2006;Xu and He, 2010;Yoshida et al, 2012;Bousman et al, 2018;Mostaid et al, 2019). The current study suggests that this haplotype is likely also significantly associated with the risk of BD in our sample.…”

Section: Discussionsupporting

confidence: 65%

“…As mentioned earlier, the five promoter SNPs were in moderate to high LD, whereas the functional exonic SNP rs1143634 showed quite low LD with the others. Given that a haplotype constructed by three IL-1β promoter SNPs (rs16944, rs4848306, rs12621220) was previously found to be significantly associated with IL-1β mRNA expression and risk of psychosis transition (Yoshida et al, 2012;Bousman et al, 2018;Mostaid et al, 2019), we herein also examined the association between this haplotype and risk of BD in our samples. Briefly, haplotypes with the frequencies lower than 0.005 in either cases or controls were discarded, and four haplotypes eventually underwent further analyses.…”

Section: Resultsmentioning

confidence: 99%

“…Despite the essential roles of IL-1β in the central nervous system, its involvement in BD is also supported by studies using both the clinical samples and cell lines. Firstly, the mRNA and protein levels of IL-1β are significantly higher in the lymphocytes or peripheral blood of BD patients compared with healthy subjects (Pandey et al, 2015;Miklowitz et al, 2016;Ghafouri-Fard et al, 2019); preclinical studies have shown that IL-1β has an effect on the behavioral, emotional and neurochemical responses relevant to mood disorders (Anisman et al, 2008;Koo and Duman, 2009;Hannestad et al, 2011); in addition, genetic variations and haplotypes in the IL-1β promoter region not only affect IL-1β transcription in vitro (Chen et al, 2006) and in vivo (Yoshida et al, 2012;Mostaid et al, 2019), but are also linked with psychiatric disorders and psychosis transition (Papiol et al, 2004;Shirts et al, 2006;Xu and He, 2010;Yoshida et al, 2012;Bousman et al, 2018), dorsolateral prefrontal cortex (DLPFC) activity (Papiol et al, 2007;Fatjó-Vilas et al, 2012), impaired emotion processing (Baune et al, 2010), and frontal gray matter deficits (Meisenzahl et al, 2001;Papiol et al, 2008). Nevertheless, this gene has been primarily investigated in European populations, and its correlation with BD remains less conclusive in other ethnic groups.…”

Section: Introductionmentioning

confidence: 99%

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The functional polymorphisms linked with interleukin-1β gene expression are associated with bipolar disorder

et al. 2021

Psychiatric Genetics

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Background Bipolar disorder (BD) is a severe psychiatric illness attributable to multifactorial risk components (e.g. environmental stimuli, neuroinflammation, etc.), and genetic variations affecting these risk components are considered pivotal predisposing factors. The interleukin-1β (IL-1β) gene and its protein product have been repeatedly highlighted in the pathogenesis of BD. As functional polymorphisms and haplotypes linked with IL-1β mRNA expression have been reported, whether they are correlated with the risk of developing BD remains to be tested. MethodsTo examine whether variations in the IL-1β gene locus confer genetic risk of BD, we recruited 930 BD patients and 912 healthy controls for the current study. All subjects were Han Chinese, and were age-and gendermatched. We tested seven functional single nucleotide polymorphisms (SNPs) spanning the IL-1β gene and one haplotype composed of three SNPs for their associations with risk of BD. ResultsWe found that the functional SNPs in the promoter region of IL-1β gene were significantly associated with risk of BD. The haplotype analyses further supported the involvement of IL-1β promoter SNPs in BD. The BD risk SNPs in our study have been previously reported to predict higher IL-1β levels in the brain and peripheral blood, which is consistent with the clinical observation of elevated IL-1β levels in the lymphocytes or peripheral blood of patients with BD compared with healthy subjects. ConclusionOur results support the contention that IL-1β is likely a risk gene for BD, and further investigations on this gene may promote our understanding and clinical management of this illness.

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Section: Discussionsupporting

confidence: 65%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The functional polymorphisms linked with interleukin-1β gene expression are associated with bipolar disorder

et al. 2021

Psychiatric Genetics

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“…One of these genetic studies confirmed association of interacting GSK3β and fragile X mental retardation-related protein 1 (FXR1) [230] with the level of mania in acute periods and depression in stabilized periods in BD patients [231]. Another study revealed the haplotype A-G-T in the promoter of the IL-1β gene that is associated not only with higher levels of expression of this cytokine in the dorsolateral prefrontal cortex (DLPFC) and a reduction of the total grey matter volume in schizophrenic patients and healthy controls [215], but also with transition to psychosis [214], which makes it a potential prognostic genetic biomarker. A further study investigated association between 1536 SNPs in 94 candidate genes and 16 primary and secondary neurophysiological and neurocognitive measurements in patients with SCZ [232,233].…”

Section: Association Studiesmentioning

confidence: 99%

Current challenges and possible future developments in personalized psychiatry with an emphasis on psychotic disorders

Levchenko

Nurgaliev

Kanapin

et al. 2020

Heliyon

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A personalized medicine approach seems to be particularly applicable to psychiatry. Indeed, considering mental illness as deregulation, unique to each patient, of molecular pathways, governing the development and functioning of the brain, seems to be the most justified way to understand and treat disorders of this medical category.In order to extract correct information about the implicated molecular pathways, data can be drawn from sampling phenotypic and genetic biomarkers and then analyzed by a machine learning algorithm. This review describes current difficulties in the field of personalized psychiatry and gives several examples of possibly actionable biomarkers of psychotic and other psychiatric disorders, including several examples of genetic studies relevant to personalized psychiatry. Most of these biomarkers are not yet ready to be introduced in clinical practice. In a next step, a perspective on the path personalized psychiatry may take in the future is given, paying particular attention to machine learning algorithms that can be used with the goal of handling multidimensional datasets.

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“…One of the key mediators of inflammatory response is interleukin-1β (IL-1β) [18, 19], a pleiotropic cytokine that is produced predominantly in the periphery by activated immune cells [20]. This cytokine is expressed both in peripheral tissues and brain structures, such as the hippocampus and hypothalamus, as seen in rat models [21], and in the dorsolateral prefrontal cortex [22-24]. In the CNS, a psychosocial or an oxidative stress may act as a trigger for microglia activation resulting in increased IL-1β levels [25-28].…”

Section: Introductionmentioning

confidence: 99%

Cognition in Schizophrenia: Modeling the Interplay between Interleukin-1β C-511T Polymorphism, Metabolic Syndrome, and Sex

et al. 2021

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Introduction: Cognitive deficits and metabolic disturbances are among the main determinants of functional impairment and reduced life expectancy in patients with schizophrenia, and they may share underlying biological mechanisms. Among these, interleukin-1β (IL-1β), a key mediator of inflammatory response, is of particular interest. IL-1β C-511T polymorphism has been associated with neuropsychiatric conditions and, in the general population, with cognitive and metabolic alterations. This study aims to evaluate the effects of the IL-1β C-511T polymorphism on both cognition and metabolic syndrome in a sample of patients affected by schizophrenia, with a focus on sex differences. Methods: 138 patients with schizophrenia were assessed for metabolic parameters and neurocognitive measures by means of the Brief Assessment of Cognition Scale. The effects of IL-1β C-511T polymorphism on cognition and metabolic syndrome were evaluated in the context of general linear models. Results: The analysis showed a significant interaction between IL-1β genotype and sex on 2 core cognitive domains. In detail, among CC homozygous, females outperformed males on processing speed, while among T carriers, males outperformed females on executive functions. A significant interaction also emerged between metabolic syndrome, sex, and IL-1β genotype for executive functions, with worse performance for T carrier females with metabolic syndrome. No significant direct effect was observed for metabolic syndrome on cognition. Conclusion: These findings support the hypothesis that IL-1β polymorphism could play a key role in mediating the complex and refined relationship between metabolic syndrome and cognitive performance.

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An Interleukin-1 beta (IL1B) haplotype linked with psychosis transition is associated with IL1B gene expression and brain structure

Cited by 12 publications

References 24 publications

The functional polymorphisms linked with interleukin-1β gene expression are associated with bipolar disorder

The functional polymorphisms linked with interleukin-1β gene expression are associated with bipolar disorder

Current challenges and possible future developments in personalized psychiatry with an emphasis on psychotic disorders

Cognition in Schizophrenia: Modeling the Interplay between Interleukin-1β C-511T Polymorphism, Metabolic Syndrome, and Sex

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