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Translational Psychiatry Jul 2020There is great phenotypic heterogeneity within autism spectrum disorders (ASD), which has led to question their classification into a single diagnostic category. The...
There is great phenotypic heterogeneity within autism spectrum disorders (ASD), which has led to question their classification into a single diagnostic category. The study of the common genetic variation in ASD has suggested a greater contribution of other psychiatric conditions in Asperger syndrome (AS) than in the rest of the DSM-IV ASD subtypes (Non_AS). Here, using available genetic data from previously performed genome-wide association studies (GWAS), we aimed to study the genetic overlap between five of the most related disorders (schizophrenia (SCZ), major depression disorder (MDD), attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorders (OCD) and anxiety (ANX)), and AS, comparing it with the overlap in Non_AS subtypes. A Spanish cohort of autism trios (N = 371) was exome sequenced as part of the Autism Sequencing Consortium (ASC) and 241 trios were extensively characterized to be diagnosed with AS following DSM-IV and Gillberg's criteria (N = 39) or not (N = 202). Following exome imputation, polygenic risk scores (PRS) were calculated for ASD, SCZ, ADHD, MDD, ANX, and OCD (from available summary data from Psychiatric Genomic Consortium (PGC) repository) in the Spanish trios' cohort. By using polygenic transmission disequilibrium test (pTDT), we reported that risk for SCZ (P= 0.008, corrected-P = 0.0409), ADHD (P = 0.021, corrected-P = 0.0301), and MDD (P = 0.039, corrected-P = 0.0501) is over-transmitted to children with AS but not to Non_AS. Indeed, agnostic clustering procedure with deviation values from pTDT tests suggested two differentiated clusters of subjects, one of which is significantly enriched in AS (P = 0.025). Subsequent analysis with S-Predixcan, a recently developed software to predict gene expression from genotype data, revealed a clear pattern of correlation between cortical gene expression in ADHD and AS (P < 0.001) and a similar strong correlation pattern between MDD and AS, but also extendable to another non-brain tissue such as lung (P < 0.001). Altogether, these results support the idea of AS being qualitatively distinct from Non_AS autism and consistently evidence the genetic overlap between AS and ADHD, MDD, or SCZ.
Topics: Asperger Syndrome; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Autistic Disorder; Child; Genome-Wide Association Study; Humans; Multifactorial Inheritance
PubMed: 32732888
DOI: 10.1038/s41398-020-00939-7 -
Journal of Autism and Developmental... Jul 2020Recent allegations that pediatrician Hans Asperger legitimized Nazi policies, including forced sterilization and child euthanasia, are refuted with newly translated and...
Recent allegations that pediatrician Hans Asperger legitimized Nazi policies, including forced sterilization and child euthanasia, are refuted with newly translated and chronologically-ordered information that takes into account Hitler's deceptive 'halt' to the T4 euthanasia program in 1941. It is highly unlikely that Asperger was aware of the T4 program when he referred Herta Schreiber to Am Spiegelgrund or when he mentioned that institution 4 months later on the medical chart of another (unrelated) girl, Elisabeth Schreiber. Asperger campaigned vigorously from 1938 to 1943 to have his specialization, Curative Education, take priority in the diagnosis and treatment of disabled children over other fields that promoted Nazi racial hygiene policies. He neither disparaged his patients nor was he sexist. By 1938, he had identified the essentials of Asperger syndrome and described an unnamed boy whom he later profiled (as Ernst K.) in 1944. Rather than doing 'thin' research, Asperger made discoveries that were prescient, and some of his activities conformed to definitions of "individual resistance."
Topics: Asperger Syndrome; Austria; Child; Child, Preschool; Complicity; Eugenics; Female; History, 20th Century; Humans; Infant; Male; National Socialism; Pediatricians; Policy; Social Behavior
PubMed: 30887409
DOI: 10.1007/s10803-019-03981-7 -
Journal of Psychiatric Research Oct 2022Oxytocin (OXT) is a hypothalamic neuropeptide that is released from the posterior pituitary gland and at specific targets in the central nervous system (CNS). The... (Review)
Review
PURPOSE
Oxytocin (OXT) is a hypothalamic neuropeptide that is released from the posterior pituitary gland and at specific targets in the central nervous system (CNS). The prosocial effects of OXT acting in the CNS present it as a potential therapeutic agent for the treatment of aspects of autism spectrum disorder (ASD). In this article, we systematically review the functional MRI (fMRI) literature that reports task-state and resting-state fMRI (rsfMRI) studies of the neural effects of single or multiple dose intranasal OXT (IN-OXT) administration in individuals with ASD.
METHOD
We searched four databases for relevant documents (PubMed, Web of Science, Scopus, and Google Scholar) using the keywords "autism spectrum disorder", "Asperger Syndrome", "oxytocin", and "fMRI". Moreover, we made a manual search to assess the quality of our automatic search. The search was confined to English language articles published in the interval February 2013 until March 2021.
RESULTS
The search yielded 12 fMRI studies with OXT intervention, including 288 individuals with ASD (age 8-55 years) enrolled in randomized, double-blind, placebo-controlled, parallel designs, within-subject-crossover experimental OXT trials. Studies reporting activation task and rsfMRI were summarized with region of interest (ROI) or whole-brain voxel wise analysis. The systematic review of the 12 studies supported the proposition that IN-OXT administration alters brain activation in individuals with ASD. The effects of IN-OXT interacted with the type of the task and the overall results did not indicate restoration of normal brain activation in ASD signature regions albeit the lack of statistical evidence.
CONCLUSION
A large body of evidence consistently indicates that OXT alters activation to fMRI in brain networks of individuals with ASD, but with uncertain implications for alleviation of their social deficits.
Topics: Administration, Intranasal; Adolescent; Adult; Autism Spectrum Disorder; Autistic Disorder; Child; Humans; Magnetic Resonance Imaging; Middle Aged; Oxytocin; Randomized Controlled Trials as Topic; Young Adult
PubMed: 35933858
DOI: 10.1016/j.jpsychires.2022.06.033 -
Genes Jan 2023Asperger syndrome (AS) is a pervasive developmental disorder characterized by general impairment in socialization, stereotypical behavior, defective adaptation to the...
Asperger syndrome (AS) is a pervasive developmental disorder characterized by general impairment in socialization, stereotypical behavior, defective adaptation to the social context usually without intellectual disability, and some high functioning areas related to memory and mathematics. Clinical criteria are not well defined and the etiology is heterogeneous and mostly unknown. Like in typical autism spectrum disorders (ASD), the genetic background plays a crucial role in AS, and often an almost mendelian segregation can be observed in some families. We performed a whole exome sequencing (WES) in three relatives of a family with vertical transmission of AS-ASD to identify variants in candidate genes segregating with the phenotype. Variant p.(Cys834Ser) in the gene was the only one segregating among all the affected family members. This gene encodes a single-strand DNA binding factor, which mediates the recruitment of genome maintenance proteins to sites of replication stress. Replication stress and genome instability have been reported recently in neural progenitor cells derived from ASD patients, leading to a disruption of long neural genes involved in cell-cell adhesion and migration. We propose as a new gene that when mutated could represent a predisposing factor to AS-ASD.
Topics: Humans; Asperger Syndrome; Autism Spectrum Disorder; Proteins; Intellectual Disability; Phenotype
PubMed: 36833228
DOI: 10.3390/genes14020301 -
International Journal of Molecular... Mar 2021Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders whose pathogenesis seems to be related to an imbalance of excitatory and inhibitory... (Review)
Review
Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders whose pathogenesis seems to be related to an imbalance of excitatory and inhibitory synapses, which leads to disrupted connectivity during brain development. Among the various biomarkers that have been evaluated in the last years, metabolic factors represent a bridge between genetic vulnerability and environmental aspects. In particular, cholesterol homeostasis and circulating fatty acids seem to be involved in the pathogenesis of ASDs, both through the contribute in the stabilization of cell membranes and the modulation of inflammatory factors. The purpose of the present review is to summarize the available data about the role of cholesterol and fatty acids, mainly long-chain ones, in the onset of ASDs. A bibliographic research on the main databases was performed and 36 studies were included in our review. Most of the studies document a correlation between ASDs and hypocholesterolemia, while the results concerning circulating fatty acids are less univocal. Even though further studies are necessary to confirm the available data, the metabolic biomarkers open to new treatment options such as the modulation of the lipid pattern through the diet.
Topics: Autism Spectrum Disorder; Cholesterol; Fatty Acids; Humans
PubMed: 33805572
DOI: 10.3390/ijms22073550 -
Frontiers in Psychology 2020This study examines how advertising material and brands related to organizational communication are perceived by people with Asperger syndrome, a form of autism. The...
This study examines how advertising material and brands related to organizational communication are perceived by people with Asperger syndrome, a form of autism. The main objective of the study was to understand whether the perception of advertising differs between individuals with AS and a neurotypical population. Neuromarketing techniques were used to examine two key variables, attention and emotion, which were also measured by physiological and biometric variables. The results were compared with those of a control group from a neurotypical population; i.e., participants who had not been diagnosed with any type of developmental disorder. Commercial advertisements were the preferred material used in this research although social-themed advertisements were also included, some produced by commercial companies and others by institutional advertisers (NGOs and foundations). Qualitative techniques were also used to explain the observed phenomena. Data revealed significant differences between the two groups in their perception of advertising and organizational communication with respect to attention and emotion variables.
PubMed: 33117205
DOI: 10.3389/fpsyg.2020.02103 -
Journal of Autism and Developmental... Jun 2021Thunberg's increased media attention coupled with her diagnosis-Asperger Syndrome (AS)-may foster help-seeking behaviors among those with similar psychiatric disorders....
Thunberg's increased media attention coupled with her diagnosis-Asperger Syndrome (AS)-may foster help-seeking behaviors among those with similar psychiatric disorders. Using Google Trends data, we compared values of AS from the week of the UN Climate Summit through the end of the year compared to an ARIMA model predicting search interest had Thunberg not been in the media. The search trend for AS at peak was 254.07% higher than predicted and was on average 10.61 points above the projected model during this time. As the primary goal of AS intervention focuses on improving quality of life and preventing common comorbidities such as depression and anxiety, capitalizing on increased public interest in AS and help-seeking behaviors is imperative.
Topics: Asperger Syndrome; Consumer Health Information; Famous Persons; Female; Health Knowledge, Attitudes, Practice; Humans; Mass Media; Search Engine
PubMed: 32812193
DOI: 10.1007/s10803-020-04651-9 -
Psychiatria Polska Oct 2022Goal: to evaluate changes in the grey matter volume using the VBM method in a group of adolescents with ASD, who met the criteria for Asperger's Syndrome.
OBJECTIVES
Goal: to evaluate changes in the grey matter volume using the VBM method in a group of adolescents with ASD, who met the criteria for Asperger's Syndrome.
METHODS
Material and methods: Morphometric evaluations based on Voxel Based Morphometry (VBM) were performed on 37 male adolescents aged 12 to 19 (M = 14.3 ± 2.0), with autism spectrum disorders, who met the DSM-IV-TR criteria for Asperger's Syndrome and 15 neurotypical adolescents matched by age. Significance was set at p<0.007 without FWE correction and p<0.05 with FWE correction.
RESULTS
Results: the decrease in the volume of the grey matter was observed in ASD group including the pre- and postcentral gyrus, the superior and middle frontal gyrus, the inferior and superior parietal lobule, the praecuneus, the anterior and posterior cingulate cortex, the fusiform gyrus, the parahippocampal gyrus, the lingual gyrus, the middle occipital region, the cuneus and the angular gyrus, the regions of calcarine sulcus and the cerebellum. The majority of changes was localized bilaterally.
CONCLUSIONS
Conclusions: the decrease in the volume of grey matter observed in ASD group can be related functionally with the characteristics of deficits observed in autism spectrum disorders which highlights the role of abnormal organization of numerous CNS structures in the genesis of symptoms observed in cognitive and behavioural domains.
Topics: Humans; Male; Adolescent; Autism Spectrum Disorder; Asperger Syndrome; Gyrus Cinguli; Frontal Lobe; Magnetic Resonance Imaging; Brain
PubMed: 37074856
DOI: 10.12740/PP/OnlineFirst/132704 -
Cells Apr 2021Understanding the autistic brain and the involvement of genetic, non-genetic, and numerous signaling pathways in the etiology and pathophysiology of autism spectrum... (Review)
Review
Understanding the autistic brain and the involvement of genetic, non-genetic, and numerous signaling pathways in the etiology and pathophysiology of autism spectrum disorder (ASD) is complex, as is evident from various studies. Apart from multiple developmental disorders of the brain, autistic subjects show a few characteristics like impairment in social communications related to repetitive, restricted, or stereotypical behavior, which suggests alterations in neuronal circuits caused by defects in various signaling pathways during embryogenesis. Most of the research studies on ASD subjects and genetic models revealed the involvement of mutated genes with alterations of numerous signaling pathways like Wnt, hedgehog, and Retinoic Acid (RA). Despite significant improvement in understanding the pathogenesis and etiology of ASD, there is an increasing awareness related to it as well as a need for more in-depth research because no effective therapy has been developed to address ASD symptoms. Therefore, identifying better therapeutic interventions like "novel drugs for ASD" and biomarkers for early detection and disease condition determination are required. This review article investigated various etiological factors as well as the signaling mechanisms and their alterations to understand ASD pathophysiology. It summarizes the mechanism of signaling pathways, their significance, and implications for ASD.
Topics: Animals; Autism Spectrum Disorder; Embryonic Development; Humans; Models, Biological; Nervous System; Signal Transduction
PubMed: 33924211
DOI: 10.3390/cells10040958 -
Frontiers in Psychiatry 2023Autism spectrum disorder (ASD) is a neurodevelopmental disorder that persists into adulthood with both social and cognitive disturbances. Asperger's syndrome (AS) was a...
INTRODUCTION
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that persists into adulthood with both social and cognitive disturbances. Asperger's syndrome (AS) was a distinguished subcategory of autism in the DSM-IV-TR defined by specific symptoms including difficulties in social interactions, inflexible thinking patterns, and repetitive behaviour without any delay in language or cognitive development. Studying the functional brain organization of individuals with these specific symptoms may help to better understand Autism spectrum symptoms.
METHODS
The aim of this study is therefore to investigate functional connectivity as well as functional network organization characteristics using graph-theory measures of the whole brain in male adults with AS compared to healthy controls (HC) (AS: = 15, age range 21-55 (mean ± sd: 39.5 ± 11.6), HC: = 15, age range 22-57 [mean ± sd: 33.5 ± 8.5]).
RESULTS
No significant differences were found when comparing the region-by-region connectivity at the whole-brain level between the AS group and HC. However, measures of "transitivity," which reflect local information processing and functional segregation, and "assortativity," indicating network resilience, were reduced in the AS group compared to HC. On the other hand, global efficiency, which represents the overall effectiveness and speed of information transfer across the entire brain network, was increased in the AS group.
DISCUSSION
Our findings suggest that individuals with AS may have alterations in the organization and functioning of brain networks, which could contribute to the distinctive cognitive and behavioural features associated with this condition. We suggest further research to explore the association between these altered functional patterns in brain networks and specific behavioral traits observed in individuals with AS, which could provide valuable insights into the underlying mechanisms of its symptomatology.
PubMed: 37701094
DOI: 10.3389/fpsyt.2023.1223147