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| 2. |
- Brundin, Peik M., et al.
(författare)
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Expression of Sex Hormone Receptor and Immune Response Genes in Peripheral Blood Mononuclear Cells During the Menstrual Cycle
- 2021
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Sex hormones are known to interact with the immune system on multiple levels but information on the types of sex hormone receptors (SHR) and their expression levels in immune cells is scarce. Estrogen, testosterone and progesterone are all considered to interact with the immune system through their respective cell receptors (ERα and ERβ including the splice variant ERβ2, AR and PGR). In this study expression levels of SHR genes in peripheral blood mononuclear cells (PBMCs) and cell subsets (CD4+ and CD8+ T-cells, CD56+ NK-cells, CD14+ monocytes and CD19+ B-cells) were analyzed using standard manual qPCR or a qPCR array (TLDA). Nine healthy individuals including men (n = 2), premenopausal (Pre-MP, n = 5) and postmenopausal (post-MP, n = 2) women were sampled for PBMCs which were separated to cell subsets using FACS. Ten Pre-MP women were longitudinally sampled for total PBMCs at different phases of the menstrual cycle. We found that ERα was most abundant and, unexpectedly, that ERβ2 was the dominant ERβ variant in several FACS sorted cell subsets. In total PBMCs, SHR (ERα, ERβ1, ERβ2, and AR) expression did not fluctuate according to the phase of the menstrual cycle and PGR was not expressed. However, several immune response genes (GATA3, IFNG, IL1B, LTA, NFKB1, PDCD1, STAT3, STAT5A, TBX21, TGFB1, TNFA) were more expressed during the ovulatory and mid-luteal phases. Sex hormone levels did not correlate significantly with gene expression of SHR or immune response genes, but sex hormone-binding globulin (SHBG), a steroid hormone transporting protein, was positively correlated to expression of ERβ1 gene. This study provides new insights in the distribution of ERs in immune cells. Furthermore, expression patterns of several immune response genes differ significantly between phases of the menstrual cycle, supporting a role for sex hormones in the immune response.
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| 3. |
- Cundari, Maurizio, et al.
(författare)
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Neurocognitive and cerebellar function in ADHD, autism and spinocerebellar ataxia
- 2023
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Ingår i: Frontiers in Systems Neuroscience. - 1662-5137. ; 17, s. 1-20
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Forskningsöversikt (refereegranskat)abstract
- The cerebellum plays a major role in balance, motor control and sensorimotor integration, but also in cognition, language, and emotional regulation. Several neuropsychiatric disorders such as attention deficit-hyperactivity disorder (ADHD), autism spectrum disorder (ASD), as well as neurological diseases such as spinocerebellar ataxia type 3 (SCA3) are associated with differences in cerebellar function. Morphological abnormalities in different cerebellar subregions produce distinct behavioral symptoms related to the functional disruption of specific cerebro-cerebellar circuits. The specific contribution of the cerebellum to typical development may therefore involve the optimization of the structure and function of cerebro-cerebellar circuits underlying skill acquisition in multiple domains. Here, we review cerebellar structural and functional differences between healthy and patients with ADHD, ASD, and SCA3, and explore how disruption of cerebellar networks affects the neurocognitive functions in these conditions. We discuss how cerebellar computations contribute to performance on cognitive and motor tasks and how cerebellar signals are interfaced with signals from other brain regions during normal and dysfunctional behavior. We conclude that the cerebellum plays a role in many cognitive functions. Still, more clinical studies with the support of neuroimaging are needed to clarify the cerebellum's role in normal and dysfunctional behavior and cognitive functioning.
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| 7. |
- Fernell, Elisabeth, 1948, et al.
(författare)
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Bumetanide for autism: Open-label trial in six children
- 2021
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 110:5, s. 1548-1553
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Bumetanide, a diuretic agent, that reduces intracellular chloride-thereby reinforcing GABAergic inhibition-has been reported to improve core symptoms of autism in children. Given the positive results reported from French trials of bumetanide in children with autism, we decided to evaluate its effects in a small-scale pilot study, in advance of a larger randomised controlled study (RCT). Methods: This was an open-label three-month trial of bumetanide on six children (five boys), aged 3-14 years with autism. Ratings according to the Parental Satisfaction Survey (PASS) were used after four and twelve weeks to assess symptom change. Blood electrolyte status was monitored. Results: Improvement in the PASS domain "Communicative and cognitive abilities" was marked or very marked in four children, and two had some improvements. Few negative side effects were reported. Conclusion: Our small cohort responded well to bumetanide, particularly with regard to "Communicative and cognitive abilities". Taken with the evidence from larger-scale RCTs, we suggest that bumetanide should be considered for inclusion in ethically approved treatment/management trials for children with autism, subject to rigorous follow-up in large-scale RCTs.
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| 8. |
- Flanagan, Erin, et al.
(författare)
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Exposure to local, source-specific ambient air pollution during pregnancy and autism in children : a cohort study from southern Sweden
- 2023
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Evidence of air pollution exposure, namely, ambient particulate matter (PM), during pregnancy and an increased risk of autism in children is growing; however, the unique PM sources that contribute to this association are currently unknown. The aim of the present study was to investigate local, source-specific ambient PM exposure during pregnancy and its associations with childhood autism, specifically, and autism spectrum disorders (ASD) as a group. A cohort of 40,245 singleton births from 2000 to 2009 in Scania, Sweden, was combined with data on locally emitted PM with an aerodynamic diameter < 2.5 µm (PM2.5). A flat, two-dimensional dispersion model was used to assess local PM2.5 concentrations (all-source PM2.5, small-scale residential heating- mainly wood burning, tailpipe exhaust, and vehicle wear-and-tear) at the mother’s residential address during pregnancy. Associations were analyzed using binary logistic regression. Exposure to local PM2.5 during pregnancy from each of the investigated sources was associated with childhood autism in the fully adjusted models. For ASD, similar, but less pronounced, associations were found. The results add to existing evidence that exposure to air pollution during pregnancy may be associated with an increased risk of childhood autism. Further, these findings suggest that locally produced emissions from both residential wood burning and road traffic-related sources (tailpipe exhaust and vehicle wear-and-tear) contribute to this association.
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| 9. |
- Gillberg, Christopher, 1950, et al.
(författare)
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Long-term stimulant treatment of children with attention-deficit hyperactivity disorder symptoms. A randomized, double-blind, placebo-controlled trial.
- 1997
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Ingår i: Archives of general psychiatry. - : American Medical Association (AMA). - 0003-990X. ; 54, s. 857-
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Tidskriftsartikel (refereegranskat)abstract
- Background: We wanted to study the effects of amphetamine on symptoms of attention-deficit hyperactivity disorder (ADHD) over a longer period than has been reported in previous studies of central stimulants in this condition. Methods: Sixty-two children, aged 6 to 11 years, meeting DSM-III-R symptom criteria for ADHD participated in a parallel-group design, randomized, double-blind, placebo-controlled study of amphetamine treatment. Treatment was not restricted to children with "pure" ADHD, ie, some had comorbid diagnoses. In the amphetamine group, children received active treatment for 15 months. Results: Amphetamine was clearly superior to placebo in reducing inattention, hyperactivity, and other disruptive behavior problems and tended to lead to improved results on the Wechsler Intelligence Scale for Children—Revised. Treatment failure rate was considerably lower and time to treatment failure was longer in the amphetamine group. Adverse effects were few and relatively mild. Conclusion: The results of this long-term, placebo-controlled study of the central stimulant amphetamine in the treatment of ADHD indicate that there are remaining positive effects of the drug 15 months after starting treatment.
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| 10. |
- Gustafsson, Peik, et al.
(författare)
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ADHD symptoms and maturity - a follow-up study in school children.
- 2010
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Ingår i: Acta paediatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 99:10, s. 1536-1539
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Aim: To test the hypothesis that there is a subgroup of children with attention deficit hyperactivity disorder (ADHD) who show a decline in ADHD-symptoms that is associated with signs of biological maturation, a phenomenon referred to as a 'maturation catch-up'. Methods: The parents of 147 children who were given an examination in grades one and two 1999-2000 that included assessment of ADHD-symptoms and estimation of skeletal bone-age by use of hand radiographs (which was repeated in the eighth grade), were contacted 2008-2009 and were asked to answer questions concerning ADHD-symptoms and behavioural maturity in their children. The response frequency was 67%. A complete dataset was achieved in 57 children. A reduction of Conners scores for ADHD-symptoms of eight or more between the evaluations was defined as a marked reduction in symptoms. Results: When the children with a marked symptom reduction (n = 6) were compared with children without such a reduction (n = 51), we found a significant difference in skeletal maturation (p < 0.05). Conclusion: This study gives support to the theory that there is a group of children with ADHD-symptoms who have a biological maturational-lag who will show a decrease in their ADHD-symptoms as they show a maturation catch-up with increasing age.
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