| 1. |
- Bryn, V., et al.
(författare)
-
Cytokine Profile in Autism Spectrum Disorders in Children
- 2017
-
Ingår i: Journal of Molecular Neuroscience. - : Springer Science and Business Media LLC. - 0895-8696 .- 1559-1166. ; 61:1, s. 1-7
-
Tidskriftsartikel (refereegranskat)abstract
- The pathogenesis of autism spectrum disorders (ASD) is not completely understood, but there is evidence of associations with altered immune responses. The aim of this study was to determine the serum levels of various cytokines in children with ASD and in healthy controls, in order to determine their role in ASD and its diagnostic subgroups. Sixty-five ASD patients were enrolled from an epidemiological survey in Norway, of which 30 were diagnosed with childhood autism, 16 with Asperger syndrome, 12 with atypical autism, 1 with Rett syndrome, and 6 with another ASD diagnosis. The serum levels of 12 cytokines were measured in all of the patients and in 30 healthy children. The cytokine levels did not differ significantly between the ASD group and the healthy controls. However, the interleukin-8 (IL-8) level was significantly higher (6.82 vs 4.58 pg/ml, p = 0.017) while that of IL-10 was significantly lower (2.24 vs 6.49 pg/ml, p = 0.009) in patients with childhood autism than in controls. Furthermore, the IL-8 level was significantly higher in childhood autism than in Asperger syndrome (6.82 vs 4.05 pg/ml, p = 0.013). Our study shows that the cytokine profile of children diagnosed with ASD, regardless of the subdiagnosis, does not differ from healthy controls. However, differentiation into different diagnostic subgroups reveals significantly different levels of IL-8 and IL-10. This indicates that different mechanisms may underlie the different ASD subdiagnoses. Future research into the pathophysiological mechanisms of ASD should pay more attention to the different subdiagnoses of ASD.
|
|
| 2. |
- Bryn, V., et al.
(författare)
-
Kynurenine Pathway in Autism Spectrum Disorders in Children
- 2018
-
Ingår i: Neuropsychobiology. - : S. Karger AG. - 0302-282X .- 1423-0224. ; 76:2, s. 82-88
-
Tidskriftsartikel (refereegranskat)abstract
- Background: There is increasing evidence that altered immune responses play a role in the pathogenesis of autism spectrum disorders (ASD), together with dysfunction of the serotonergic and glutamatergic systems. Since the kynurenine (KYN) pathway that degrades tryptophan (TRP) is activated in various neuroinflammatory states, we aimed to determine whether this pathway is activated in ASD. Methods: Sixty-five pediatric ASD patients (including 52 boys) were enrolled from an epidemiological survey covering 2 counties in Norway; 30 (46.5%) of these patients were diagnosed with childhood autism, 16 (24.6%) with Asperger syndrome, 12 (18.5%) with atypical autism, 1 (1.5%) with Rett syndrome, and 6 (9.2%) with other ASD. The serum levels of the following markers were measured in the children with ASD and compared to those in 30 healthy children: TRP, KYN, kynurenic acid (KA), 3-hydroxykynurenine, and quinolinic acid. Results: The mean serum level of KA was significantly lower in the ASD group than in the healthy controls (28.97 vs. 34.44 nM, p = 0.040), while the KYN/KA ratio was significantly higher in the ASD group (61.12 vs. 50.39, p = 0.006). The same relative values were found when comparing the childhood autism subgroup with the controls. Also, the mean serum level of TRP was significantly lower in children with a subdiagnosis of childhood autism than in those with Asperger syndrome (67.26 vs. 77.79 mu m, p = 0.020). Conclusion: Our study indicates that there is an increased neurotoxic potential and also a possible lower KYN aminotransferase activity in ASD. (C) 2018 S. Karger AG, Basel
|
|
| 3. |
- Henriksen, M. W., et al.
(författare)
-
Epilepsy in classic Rett syndrome: Course and characteristics in adult age
- 2018
-
Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211. ; 145, s. 134-139
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Rett syndrome (RTT) is a neurodevelopmental disorder that almost exclusively affects females. Epilepsy is a major clinical feature, but its long-term course in RTT has not been sufficiently explored. This study addresses the development of the epilepsy in adults with KIT. Methods: Available females diagnosed with RTT in Norway were asked to participate. Parents/caregivers were interviewed, the girls/women were examined and their medical records reviewed. Participants were categorized according to age, epilepsy, seizure patterns and mutation severity groups. RTT severity was assessed (epilepsy score excluded). Results: 70 females with classic RTT were included. A presumed pathogenic mutation in MECP2 was found in 96%. The presence of active epilepsy (seizures last five years) was similar in all age groups above the age of ten: 11 (65%) in adolescents (11-20 years), 9 (60%) in young adults (21-30 years) and 14 (67%) in participants above 30 years of age. Tonic-clonic seizures within the last year were present in 55, 67 and 64%, and >= weekly seizures occurred in 27, 45 and 50% in the respective age groups. Among participants with active epilepsy, 69% had unremitting seizures, whereas 31% had experienced remissions for more than six months during the last five years. In the oldest group ( > 30 years), only 19% had obtained seizure control for > 5 years, and 14% had never experienced seizures. Seizure activity correlated with RTT severity score, whereas the relationship to mutation type remained ambiguous. Conclusion: Epilepsy continues to be a major concern in adults with RTT. Two thirds of women above 30 years of age remained with active epilepsy and 50% of them had seizures at least weekly.
|
|
| 4. |
- Henriksen, M. W., et al.
(författare)
-
Genetic and clinical variations in a Norwegian sample diagnosed with Rett syndrome
- 2020
-
Ingår i: Brain & Development. - : Elsevier BV. - 0387-7604. ; 42:7, s. 484-495
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Rett syndrome (RTT) is a neurodevelopmental disorder mainly caused by mutations in MECP2. The diagnostic criteria of RTT are clinical; mutations in MECP2 are neither diagnostic nor necessary, and a mutation in another gene does not exclude RTT. We attempted to correlate genotype and phenotype to see if there are significant clinical associations. Methods: All available females diagnosed with RTT in Norway were invited to the study. Parents were interviewed, the girl or woman with RTT examined and medical records reviewed. All diagnoses were revisited according to the current diagnostic criteria and exome-based sequencing analyses were performed in individuals without an identified causative mutation. Participants were categorized according to genotypes and RTT diagnosis. Individuals with RTT with and without mutations in MECP2 were compared. Results: Ninety-one individuals were included. A presumed causative mutation was identified in 86 individuals, of these, mutations in MECP2 in 77 individuals and mutations in SMC1A, SYNGAP1, SCN1A, CDKL5, FOXG1 or chromosome 13q in nine. Seventy-two individuals fulfilled the diagnostic criteria for classic and 12 for atypical RTT. Significant differences in early development, loss of hand use and language, intense eye gaze and the presence of early onset epilepsy were revealed in individuals with RTT according to their MECP2 genotypic status. Conclusion: Using the current diagnostic criteria, genetic and clinical variation in RTT is considerable. Significant differences between individuals with RTT with and without MECP2 mutations indicate that MECP2 is a major determinant for the clinical phenotype in individuals with RTT. (C) 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
|
|
| 5. |
- Henriksen, M. W., et al.
(författare)
-
Medical Issues in Adults with Rett Syndrome–A National Survey
- 2020
-
Ingår i: Developmental Neurorehabilitation. - : Informa UK Limited. - 1751-8423 .- 1751-8431. ; 23:2, s. 106-112
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To examine main health issues in a population of females with Rett syndrome, with a focus on individuals aged 36 or older. Methods: A national survey including 85 females, divided into a younger (1–20 years), a middle (21–35 years) and an older group (36–66 years). Data include clinical examination, medical records and parental interviews. Prevalences of six main medical issues (scoliosis, ambulation, growth, respiration, gastrointestinal dysmobility and epilepsy) and severity scores in the three groups were compared. Results: Mean severity scores were 11.8, 15.1 and 13.7 (from younger to older), and the difference between the younger and the middle group was significant. No other major significant prevalence differences were observed. Conclusions: Most main medical issues in Rett syndrome continued to be a major concern in adulthood, but health did not seem to decline with increasing age. The results emphasize the need for clinical follow-up throughout adulthood. © 2019, © 2019 Taylor & Francis Group, LLC.
|
|
| 6. |
- Ormstad, H., et al.
(författare)
-
Role of the Immune System in Autism Spectrum Disorders (ASD)
- 2018
-
Ingår i: Cns & Neurological Disorders-Drug Targets. - : Bentham Science Publishers Ltd.. - 1871-5273. ; 17:7, s. 489-495
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The evidence based supports that multifactorial and complex immune interactions play a role in autism spectrum disorders (ASD), but contradictory findings are also reported. Objective: The aim of this selective review was to identify trends in the research literature on this topic, focusing on immunology and other aberrations with respect to the different ASD subtypes. Methods: This selective review is based on original and review articles written in English and identified in literature searches of PubMed. Results: Several studies have found that the risk of ASD is greater among children whose mothers suffered from autoimmune diseases while pregnant. Moreover, individuals with ASD show increased levels of antibodies that are specific for several specific proteins. Studies also show that mothers of children with ASD have antibodies against fetal brain proteins. There are also reports on the associations between increased levels of proinflammatory cytokines and ASD. Finally, infections in mothers during pregnancy are linked to an increased risk of ASD. Conclusion: We propose that the large inconsistencies in findings among studies in the field are due to differences in subdiagnoses among the included children with ASD. Well-phenotyped ASD samples are needed to understand the biological and immunological mechanisms underpinning ASD and its subdiagnoses. Future research should apply new strategies to scrutinize the link between ASD and changes in immune responsivity. Important new research avenues are to investigate the associations (a) between different ASD phenotypes and aberrations in (auto) immune pathways and (b) between reduced natural regulatory autoimmune responses during pregnancy, which are in turn associated with increased oxidative and nitrosative stress in maternal blood and putative detrimental effects in the offspring.
|
|
| 7. |
- Ormstad, H., et al.
(författare)
-
Serum Tryptophan, Tryptophan Catabolites and Brain-derived Neurotrophic Factor in Subgroups of Youngsters with Autism Spectrum Disorders
- 2018
-
Ingår i: Cns & Neurological Disorders-Drug Targets. - : Bentham Science Publishers Ltd.. - 1871-5273. ; 17:8, s. 626-639
-
Tidskriftsartikel (refereegranskat)abstract
- Background: There is evidence that changes in neuro-immune responses coupled with dysfunctions in serotonin metabolism underpin the pathophysiology of autism spectrum disorders (ASD). Objective: This study aimed to delineate whether ASD subgroups or characteristics show aberrations in tryptophan and brain-derived neurotrophic factor (BDNF) metabolism. Methods: 65 individuals with ASD (diagnosed according to ICD criteria) and 30 healthy control patients were included. Measured were serum levels of tryptophan, kynurenine (KYN), kynurenic acid (KA), quinolinic acid (QA), BDNF and PRO-BDNF and total blood 5-HT and 5-OH-tryptophan (5-HTP). Results: Elevated BDNF levels and lower tryptophan and KA levels were characteristics of both childhood autism and intellectual disability disorder, whilst elevated tryptophan and lower 5-HT synthesis were hallmarks of Asperger syndrome. A pathological MRI was associated with elevated tryptophan and lowered KA. Abnormal EEG results and dysmorphology were both associated with an elevated BDNF/ PRO-BDNF ratio. Any brain pathology and gastro-intestinal symptoms were accompanied by lowered KA. Conclusions: Increased BDNF production and changes in the metabolism of tryptophan are associated with many ASD characteristics, showing particularly strong associations with childhood autism and Intellectual and Developmental Disabilities. Peripheral BDNF and tryptophan metabolism appear to take part in the pathophysiology of autism spectrum disorders and their phenotypes.
|
|
| 8. |
- Bakken, K. S., et al.
(författare)
-
Higher risk for adverse obstetric outcomes among immigrants of African and Asian Descent: A comparison study at a low-risk maternity hospital in Norway
- 2015
-
Ingår i: Birth. - : Wiley. - 0730-7659 .- 1523-536X. ; 42:2, s. 132-140
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Immigrants have higher risks for some adverse obstetric outcomes, and 40 percent of women giving birth at the low-risk maternity ward in Baerum Hospital, Norway, are immigrants. This study compared obstetric outcomes between immigrants and ethnic Norwegians giving birth in a low-risk setting. Methods: This was a population-based study linking the Medical Birth Registry of Norway to Statistics Norway. The study included the first registered birth during the study period to immigrant and ethnic Norwegian women at Baerum Hospital from 2006 to 2010. The main outcome measures were onset of labor, operative vaginal delivery, cesarean delivery, episiotomy, postpartum bleeding > 500 mL, epidural analgesia, labor dystocia, gestational age, meconium-stained liquor, 5-minute Apgar score, birthweight, and transfer to a neonatal intensive care unit. Results: A total of 11,540 women originating from 141 countries were divided into seven groups. Compared with Norwegians, women from East, Southeast, and Central Asia had increased risk for operative vaginal delivery, postpartum bleeding, and low Apgar score. The African women had increased risk for postterm birth, meconium-stained liquor, episiotomy, operative vaginal delivery, emergency cesarean delivery, postpartum bleeding, low Apgar score, and low birthweight. Women from South and Western Asia had increased risk for low birthweight. Conclusion: Obstetric outcomes of immigrants differ significantly from those of Norwegians, even in a low-risk maternity unit. Thus, immigrant women would benefit from more targeted care during pregnancy and childbirth, even in low-risk settings. © 2015 Wiley Periodicals, Inc.
|
|
| 9. |
- Bakken, K. S., et al.
(författare)
-
Immigrants from conflict-zone countries: an observational comparison study of obstetric outcomes in a low-risk maternity ward in Norway
- 2015
-
Ingår i: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 15
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Immigrants have higher risks for some adverse obstetric outcomes. Furthermore, refugees are reported to be the most vulnerable group. This study compared obstetric outcomes between immigrant women originating from conflict-zone countries and ethnic Norwegians who gave birth in a low-risk setting. Methods: This was a population-based study linking the Medical Birth Registry of Norway to Statistics Norway. The study included the first registered birth during the study period of women from Somalia (n = 278), Iraq (n = 166), Afghanistan (n = 71), and Kosovo (n = 67) and ethnic Norwegians (n = 6826) at Baerum Hospital from 2006-2010. Background characteristics and obstetric outcomes of each immigrant group were compared with ethnic Norwegians with respect to proportions and risks calculated by logistic regression models. Results: In total, 7408 women and their births were analyzed. Women from Somalia were most at risk for adverse obstetric outcomes. Compared with ethnic Norwegians, they had increased odds ratios (OR) for emergency cesarean section (OR 1.81, CI 1.17-2.80), postterm birth (OR 1.93, CI 1.29-2.90), meconium-stained liquor (OR 2.39, CI 1.76-3.25), and having a small-for-gestational-age infant (OR 3.97, CI 2.73-5.77). They had a reduced OR for having epidural analgesia (OR 0.40, CI 0.28-0.56) and a large-for-gestational-age infant (OR 0.32, CI 0.16-0.64). Women from Iraq and Afghanistan had increased risk of having a small-for-gestational-age infant with OR of 2.21 (CI 1.36-3.60) and 2.77 (CI 1.42-5.39), respectively. Iraqi women also had reduced odds ratio of having a large-for-gestational-age infant (OR 0.35, CI 0.15-0.83). Women from Kosovo did not differ from ethnic Norwegians in any of the outcomes we tested. Conclusions: Even in our low-risk maternity ward, women originating from Somalia were at the greatest risk for adverse obstetric outcomes in the compared groups. We could not find the same risk among the other immigrant women, also originating from conflict-zone countries. Several factors may influence these findings, and this study suggests that immigrant women from Somalia need more targeted care during pregnancy and childbirth.
|
|
| 10. |
- Bakken, Kjersti S., et al.
(författare)
-
Obstetric Outcomes of First- and Second-Generation Pakistani Immigrants: A Comparison Study at a Low-Risk Maternity Ward in Norway
- 2017
-
Ingår i: Journal of Immigrant and Minority Health. - : Springer Science and Business Media LLC. - 1557-1912 .- 1557-1920. ; 19, s. 33-40
-
Tidskriftsartikel (refereegranskat)abstract
- © 2015, Springer Science+Business Media New York. This population-based study compares obstetric outcomes of first- and second-generation Pakistani immigrants and ethnic Norwegians who gave birth at the low-risk maternity ward in Baerum Hospital in Norway from 2006 to 2013. We hypothesized that second-generation Pakistani immigrants are more similar to the ethnic Norwegians because of increased acculturation. Outcome measures were labor onset, epidural analgesia, labor dystocia, episiotomy, vaginal/operative delivery, postpartum hemorrhage, preterm birth, birth weight, transfer to a neonatal intensive care unit, and neonatal jaundice. Compared to first-generation Pakistani immigrants, the second-generation reported more health issues before pregnancy, and they had a higher proportion of preterm births compared to Norwegians. Newborns of first-generation immigrants were more often transferred to a neonatal intensive care compared to Norwegian newborns. Few intergenerational differences in the obstetric outcomes were found between the two generations. A high prevalence of consanguinity in second-generation immigrants suggests the maintenance of a traditional Pakistani marriage pattern.
|
|
