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- Strenn, Nina, 1984, et al.
(författare)
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Associations between autistic-like traits and polymorphisms in NFKBIL1
- 2019
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Ingår i: Acta Neuropsychiatrica. - : Cambridge University Press (CUP). - 0924-2708 .- 1601-5215. ; 31:4, s. 220-229
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Tidskriftsartikel (refereegranskat)abstract
- Objective:The immune system has been suggested to be associated with neuropsychiatric disorders; for example, elevated levels of cytokines and the inflammation-related transcription factor nuclear factor kappa-B (NF-κB) have been reported in individuals with autism spectrum disorder (ASD). The aim of this study was to investigate possible associations between autistic-like traits (ALTs) and single nucleotide polymorphisms (SNPs) in NFKB1 (encoding a subunit of the NF-κB protein complex) and NF-κB inhibitor-like protein 1 (NFKBIL1).Methods:The study was conducted in a cohort from the general population: The Child and Adolescent Twin Study in Sweden (CATSS, n = 12 319, 9-12 years old). The subjects were assessed by the Autism-Tics, ADHD, and Other Comorbidities Inventory. Five SNPs within the two genes were genotyped (NFKBIL1: rs2857605, rs2239707, rs2230365 and rs2071592; NFKB1: rs4648022).Results:We found significant associations for two SNPs in NFKBIL1: rs2239707 showed a significant distribution of genotype frequencies in the case-control analysis both for all individuals combined and in boys only, and rs2230365 was significantly associated with the ALTs-module language impairment in boys only. Furthermore, we found nominal association in the case-control study for rs2230365, replicating earlier association between this SNP and ASD in an independent genome-wide association study.Conclusion:The shown associations between polymorphisms in NFKBIL1 and ALTs are supporting an influence of the immune system on neuropsychiatric symptoms. © Scandinavian College of Neuropsychopharmacology 2019.
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| 2. |
- Strenn, Nina, 1984, et al.
(författare)
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Associations between NFKB and NFKBIL1 polymorphisms and autistic-like traits in a Swedish population of twins
- 2014
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Ingår i: 29th World Congress of the International College of Neuropsychopharmacology (CINP), 22-26 June 2014; Vancouver, Canada.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objectives Autism spectrum disorders are a complex group of neurodevelopmental disorders which are characterized by impairments in social interactions and both verbal and nonverbal communication. The immune system has been suggested to be of importance for the development of neuropsychiatric symptoms; for example, elevated levels of cytokines and the inflammation-related transcription factor nuclear factor kappa-B (NFKB) have been reported in autistic individuals. The aim of this study was to investigate possible associations between single nucleotide polymorphisms (SNPs) in NFKB and NFKB inhibitor-like protein 1 (NFKBIL1) and autistic-like traits in a Swedish population of twins. Methods The subjects in this study (n=12426, 9-12 years old) are from “The Child and Adolescent Twin Study in Sweden” (CATSS). Their parents participated in a telephone interview where the children were assessed by the Autism-Tics, ADHD, and Other Comorbidities Inventory (A-TAC) where autistic-like traits are measured using a continuous scale. DNA was extracted from saliva samples and polymorphisms were genotyped. Statistical analyses were performed in the SAS 9.3 (SAS Institute, Inc., Cary, NC) softwear. Results Four out of the five investigated SNPs (NFKB: rs4648022; NFKBIL1: rs2230365, 2239797 and rs2857605) showed significant associations with the A-TAC total autistic-like traits score. Conclusions To our best knowledge, polymorphisms in the genes encoding NFKB and NFKBIL1 have not been studied previously in relation to autism. These proteins may be involved in neuronal development and our findings support the hypothesis of the immune system being important in the aetiology of neuropsychiatric symptoms.
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| 3. |
- Strenn, Nina, 1984, et al.
(författare)
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Expression of inflammatory markers in a genetic rodent model of depression
- 2015
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 281, s. 348-357
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Tidskriftsartikel (refereegranskat)abstract
- The complex bidirectional communication between the central nervous system and the peripheral immune system is of possible relevance for both normal brain functions and the development of psychiatric disorders. The aim of this investigation was to study central expression of inflammatory markers in a genetic rat model of depression (the Flinders Sensitive line (FSL) and its control, the Flinders Resistant line (FRL)). A peripheral immune activation was induced by lipopolysaccharide (LPS) in order to investigate possible differences in immune reactions between the two rat lines. To confirm behavioural differences between the rat lines the forced swim test was performed, a test to assess depressive-like behaviour. Expression of candidate inflammatory genes was measured in amygdala, hippocampus, hypothalamus, prefrontal cortex and striatum using quantitative real time PCR. Our results show, for the first time, significantly lower central expression of the glial-specific protein S100B and complement factor C3 in several brain regions of the FSL rats compared to controls, both at baseline and after peripheral immune stimulation. No significant differences in immune responses to LPS were observed between the rats lines. Both S100B and C3 have been suggested to be of relevance for brain development and plasticity as well as brain disorders. These proteins may be of importance for the behavioural differences between the FSL and FRL rats, and this model may be useful in studies exploring the influence of the immune system on brain functions.
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| 4. |
- Strenn, Nina, 1984, et al.
(författare)
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Influence of genetic variations in IL1B on brain region volumes in bipolar patients and controls.
- 2021
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Ingår i: Psychiatry research. - : Elsevier BV. - 1872-7123 .- 0165-1781. ; 296
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Tidskriftsartikel (refereegranskat)abstract
- Involvement of the immune system has been implicated in the etiology and pathophysiology of mood disorders, including bipolar disorder. Neuroimaging studies have reported structural brain pathology in bipolar disorder patients, and both levels of and genetic variants in cytokines have been associated with altered volumes of brain regions. The aim of this study was to investigate associations between single nucleotide polymorphisms in the gene coding for the pro-inflammatory cytokine interleukin-1 beta (IL1B) and whole brain grey matter volume, as well as volumes of several brain regions shown to be of importance in mood disorders. Structural magnetic resonance imaging and vertex-based morphometry were used to obtain volume of different brain regions in subjects with bipolar disorder (n=188) and healthy controls (n=54). Four IL1B polymorphisms were genotyped: rs1143623, rs1143627, and rs16944 in the promoter region together with the synonymous variant rs1143634 in the IL1B gene. The genotype distribution did not differ between bipolar subjects and controls. The T allele at rs16944 and the C allele at rs1143627 were associated with increased volumes of the putamen of the left hemisphere in patients and controls, which lends support to the role of this immune system mediator for brain structure.
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| 5. |
- Strenn, Nina, 1984
(författare)
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On Neuroimmunology and Brain Function: Experimental and Clinical Studies
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The immune system has been implicated in the mechanisms underlying many psychiatric disorders. Immune mediators are expressed in the central nervous system (CNS) not only in response to harmful stimuli, but also in a constitutive manner, and serve as important plasticity factors during development. There is complex bidirectional communication between the immune system and the CNS throughout life which is based on interactions between neurotransmitters, neuroendocrine hormones, cytokines, and their respective receptors. Exploring the interplay between brain, behaviour and immunity is central to our understanding of the pathology of psychiatric morbidity. The aim of this thesis is to investigate the role of some aspects of the immune system in several psychiatric conditions, both in experimental and clinical contexts. We used the Flinders sensitive line (FSL), a genetic animal model of depression, to study central gene expression of markers related to immune response and neurotransmission following immune stimulation and antidepressant treatment. Several genes were found to be expressed differently in rats displaying depressive-like behaviour compared to their controls (Paper I), a finding that we replicated in Paper II. Additionally, we showed that antidepressant treatment with escitalopram altered expression of several genes, notably the astrocyte-derived protein S100B, and the serotonin receptor 5-HT2A, in the amygdala and hypothalamus (Paper II), two brain regions that have been shown to be of relevance for the effect of antidepressant treatment. Our results support the use of the FSL model for studying the role of these immune-related markers in depression and antidepressant treatment. In the clinical studies included in this thesis, we found that genetic variants in immune-related genes were associated with neuropsychiatric traits and the volume of certain brain regions. The gene encoding the NF-kB inhibitor-like protein 1 (NFKBIL1) was found to be associated with autistic-like traits, as well as with language impairment in a cohort from the general population (Paper III). We further investigated the effect of genetic variation in the gene coding for interleukin-1beta (IL1B) on the volume of several brain regions in a case-control population of patients diagnosed with bipolar disorder (Paper IV). Genotype distribution did not differ between patients and controls, suggesting that variants in IL1B may not be associated with bipolar disorder. However, we found associations between IL1B polymorphisms and the volume of the putamen in the left hemisphere in patients and controls, suggesting that genetic variation in IL1B may influence neurodevelopment. In conclusion, this thesis demonstrates associations between immune mediators and mental functions, as well as altered brain development in humans. Also, insight is gained into the use of the FSL animal model for investigating the impact of the immune system for depression. Taken together, our findings confirm the importance of the immune system for the development of psychiatric disorders.
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