FMR1 and Autism, an Intriguing Connection Revisited.
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ABSTRACT:
SUBMITTER: Fyke W
PROVIDER: S-EPMC8394635 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe Friendship Questionnaire (FQ) is a widely used measure of friendships in autism research and beyond. This study sought to revisit the original paper where the measure was presented, using a larger sample of both autistic and non-autistic participants to examine gender differences in scoring. It also sought to expand upon the original paper by comparing FQ results to those of the Unidimensional Relationship Closeness Scale (URCS), to examine whether there are differences in how autistic people report on their general friendships in contrast to their most significant relationships.MethodsParticipants were recruited for an online study, and 949 people (532 autistic, 417 non-autistic) aged between 18 and 81 took part. Participants completed a demographic questionnaire, the Autism Quotient-28, the Friendship Questionnaire, and the Unidimensional Relationship Closeness Scale.ResultsWe used robust regressions and Pearson's correlational analyses, conducted in R. Autistic people scored lower than non-autistic people on the FQ, and similar gender differences in the pattern of FQ scores were seen in both groups. There was a significant negative correlation between AQ and FQ scores in both groups. On the URCS, we took the data from those who rated specific close relationships and found that autistic people scored this relationship more highly than non-autistic adults did. There was a significant negative correlation between AQ and URCS scores in both groups. Also, in both groups, there was a significant positive correlation between FQ and URCS scores.LimitationsThe data is entirely self-report, and diagnoses could not be verified with a clinician, although AQ scores support self-identification as autistic. Also, the groups were not evenly matched on age and other demographic variables, although this was controlled for in analyses. It is also the case that more autistic than non-autistic people were unable to specify a close relationship to score on the URCS, meaning that a certain set of experiences are not represented in this data.ConclusionsWe conclude that our data replicates the core finding of the original FQ paper that autistic people score lower on the FQ. In contrast to that paper, however, we found that there were gender differences among the autistic population. Also, our inclusion of the URCS suggests that the intimate romantic relationships and best-friendships of autistic people can be of similar quality to those of non-autistic people, suggesting that there may be important differences in autistic people's relations with friends in general versus close friends and romantic partners.
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Project description:Background: Autism spectrum disorders (ASD) are complex psychiatric disorders, with gene environment interaction being in the basis of their etiology. The association of perinatal complications and ASD is well established. Recent findings suggested that oxidative stress and polymorphism in genes encoding antioxidant enzymes might be involved in the development of ASD. Glutathione transferases (GSTs) have an important role in the antioxidant defense system. We aimed to establish whether the predictive effects of prenatal and perinatal complications (as possible oxidative stress inducers) on ASD risk are dependent on GST polymorphisms. Methods: The study included 113 ASD cases and 114 age- and sex group-matched healthy controls. All participants were genotyped for GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms. The questionnaire regarding prenatal and perinatal risk factors and complications was administered for all the subjects in the study. Results: The evaluated perinatal complications as a group significantly increased the risk of ASD [odds ratio (OR) = 9.415; p = 0.000], as well as individual perinatal complications, such as prematurity (OR = 11.42; p = 0.001), neonatal jaundice (OR = 8.774; p = 0.000), respiratory distress syndrome (OR = 4.835; p = 0.047), and the use of any medication during pregnancy (OR = 2.413; p = 0.03). In logistic regression model, adding GST genotypes did not modify the significant effects found for prematurity and neonatal jaundice as risk factors in ASD. However, there was a significant interaction of GST genotype with medication use during pregnancy and the use of tocolytics during pregnancy, which was predictive of ASD risk only in carriers of GSTM1-null, as opposed to carriers of GSTM1-active genotype. Conclusion: Specific perinatal complications may be significant risk factors for ASD. GSTM1 genotype may serve as a moderator of the effect of some prenatal factors on the risk of ASD such as using medication during pregnancy. It may be speculated that different oxidative stress-related genetic and environmental factors could lead to development of ASD. Apart from etiological mechanisms, possible therapeutic implications in ASD are also discussed.
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Project description:RNA-seq analysis was performed between WT and alphaT-cat KO mouse cerebella aiming to discover gene transcripts altered by the loss of alphaT-cat These altered gene transcripts could be associated with several neurologic disease-relevant pathways
2016-06-08 | GSE83084 | GEO
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Project description:Fragile X syndrome and tuberous sclerosis are genetic syndromes that both have a high rate of co-morbidity with autism spectrum disorders. Several lines of evidences suggest that these two monogenic disorders may converge at a molecular level through the dysfunction of activity-dependent synaptic plasticity. We utilized mouse models of these monogenic disorders to identify genome-wide transcriptional changes in cerebellum and blood and characterize the (dis-)similarity of their molecular signatures. Differentially expressed genes and enriched pathways were distinct for the two mouse models examined, with the exception of immune system related pathways. In the cerebellum of the Fmr1 knockout (Fmr1-KO) model, the neuroactive ligand receptor interaction pathway and gene sets associated with synaptic plasticity such as long term potentiation, gap junction, and axon guidance were the most significantly perturbed pathways. The phosphatidylinositol signaling pathway was significantly dysregulated in both blood and brain of Fmr1-KO mice. In both the blood and brain of the Tsc2 heterozygous mouse model, immune system related pathways, genes encoding ribosomal proteins, and glycolipid metabolism pathways were significantly perturbed. Our data suggest that distinct molecular pathways may be involved in autism spectrum disorders with known but different genetic causes, and that blood gene expression profiles of Fmr1-knockout and Tsc2+/- mice mirror some, but not all, of the perturbed molecular pathways in the brain. For the Fmr1-KO model, 10 mice, consisting of 5 KO and 5 WT mice, were profiled. Thus, 10 pairs of blood and cerebella samples were profiled. Likewise, for the Tsc+/- model, 3 transgenic and 3 WT mice were sacrificed and paired blood and cerebella samples were prepared for gene expression profiling. All samples were profiled using the Affymetrix Mouse Gene ST 1.0 ST arrays. Three factors—tissue (i.e. blood vs. cerebellum), treatment (i.e. knockout vs. wildtype), and genetic background (Fmr1-KO vs. Tsc2+/-)—were analyzed with analysis of variance (ANOVA). Subsequently, we compared blood and brain gene expression changes in Fmr1 and Tsc2 knockout mice models using WT littermates as controls using t-tests with unequal variances. The false discovery rate (FDR) was calculated using Storey and Tibshirani’s method.
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