DOCSLIB.ORG

The Role of the Fusiform-Amygdala System in the Pathophysiology of Autism

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Role of the Fusiform-Amygdala System in the Pathophysiology of Autism ORIGINAL ARTICLE The Role of the Fusiform-Amygdala System in the Pathophysiology of Autism Isabel Dziobek, PhD; Markus Bahnemann, MD; Antonio Convit, MD; Hauke R. Heekeren, MD, PhD Context: Autism is a condition of unknown origin with cal findings by analyzing correlations with emotional face– well-documented impairments in social perception and processing performance. cognition. Main Outcome Measures: Fusiform gyrus cortical Objective: To assess the relevance of the fusiform- thickness, amygdala volume, emotional face processing. amygdala system to the pathophysiology of autism spec- Results: We found a specific local increase in cortical trum conditions. thickness of the fusiform gyrus and associated impair- ments in face processing in individuals with autism. Ana- Design: Cross-sectional case-control study. tomical covariance between amygdala volume and the in- crease in fusiform gyrus local thickness was significantly Setting: University hospital. smaller in the group with autism spectrum conditions. Participants: A total of 27 adults with autism spec- Conclusions: Our data provide the first anatomical evi- trum conditions and 29 age-, sex-, and intelligence quo- dence of an abnormal amygdala-fusiform system and its tient–matched typically developed healthy controls. Pa- behavioral relevance to face-processing deficits in au- tients were assessed according to DSM-IV criteria using tism spectrum conditions. In light of recent evidence of the Autism Diagnostic Interview–Revised. the involvement of the fusiform gyrus and amygdala in social perception as well as the areas of social cognition Interventions: We applied an automated measure- and emotional awareness, all of which are relevant to au- ment to estimate fusiform gyrus cortical thickness and a tism, our findings might represent a core pathophysi- manual tracing method to obtain amygdala volumes. We ological mechanism of autism. analyzed volumetric covariance among these brain re- gions and assessed the functional relevance of anatomi- Arch Gen Psychiatry. 2010;67(4):397-405 UTISM SPECTRUM CONDI- meaning from faces. The amygdala is an im- Author Affiliations: tions (ASC) involve severe portant part of this system and plays a cen- Max Planck Institute for abnormalities in social tral role in processing the social relevance Human Development, Berlin, interaction, communica- of information gleaned from faces.6,8 Ani- Germany (Drs Dziobek, tion, and repetitive behav- mal studies have identified strong recipro- Bahnemann, and Heekeren); ior.1 Deficits in face processing are among cal projections between the amygdala and Max Planck Institute for A 2-4 9,10 the core features of ASC. Although these fusiform gyrus, and recent functional Human Cognitive and Brain impairments represent only a small frac- magnetic resonance imaging studies have Sciences, Leipzig, and Cluster tion of the reported deficits in social per- provided evidence of fusiform activity of Excellence, Languages of 5 11-13 Emotion, Freie Universität ception and social cognition, their assess- modulation by the amygdala. In fact, Berlin, Berlin, Germany ment is of particular importance because viewing emotional faces increases the cou- (Drs Dziobek and Heekeren); faces represent a crucial primary source of pling between the amygdala and fusiform Berlin NeuroImaging Center, social information, and their decoding is a gyrus.14 Notably, patients with amygdala le- Department of Neurology, precursor for more complex social inference. sions do not show increased activation in Charite´ University Medicine In typically developed individuals, face the fusiform cortex when shown fearful Berlin, Berlin, Germany perception involves a distributed set of brain faces.11 Together, these findings empha- (Drs Bahnemann and regions comprising a core and an ex- size that the concerted action of the amyg- Heekeren); and Center for Brain tended system.6 The core system mediates dala and fusiform gyrus is crucial for emo- Health, New York University the visual analysis of faces and comprises, tional face processing. School of Medicine, New York, 15 and Nathan Kline Institute for among other parts, the lateral fusiform gy- Schultz recently presented a patho- 7 Psychiatric Research, rus (fusiform face area [FFA] ). The ex- physiological model of autism based on Orangeburg, New York tended system consists of regions acting in concerted functioning of the amygdala and (Dr Convit). concert with the core system to extract FFA. This model postulates that a poten- (REPRINTED) ARCH GEN PSYCHIATRY/ VOL 67 (NO. 4), APR 2010 WWW.ARCHGENPSYCHIATRY.COM 397 Downloaded from www.archgenpsychiatry.com at Mt Sinai School Of Medicine, on April 8, 2010 ©2010 American Medical Association. All rights reserved. nicians to participate in the study. Each subject underwent a Table. Demographic Variables of Participants With ASC videotaped diagnostic interview based on which diagnoses of and Controls ASC were made according to DSM-IV criteria1 by consensus of 1 psychiatrist (A.C.) and 1 psychologist (I.D.). Diagnostic dis- Mean (SD) crepancies were resolved based on the video material by in- cluding a third person trained in diagnosing autism spectrum ASC Control a conditions in adults. In addition, diagnoses were confirmed with Variable (n=27) (n=29) P Value the Autism Spectrum Quotient25 and the Autism Diagnostic In- Sex terview-Revised (ADI-R)26 in the 18 participants with avail- Male 20 22 .88 able parental informants. A group of 29 healthy controls (22 Female 7 7 men and 7 women), chosen to match the ASC group as closely Age, y 42.0 (11.3) 44.9 (14.6) .39 as possible with respect to age, education, and intelligence quo- Education, y 16.5 (1.6) 16.4 (1.5) .81 tient (IQ), also participated in the study (Table). Estimated WAIS-R IQ 111 (8) 113 (7) .17 b Ͻ All study participants had medical (including electrocar- Face processing 21.7 (3.4) 25.4 (1.9) .001 diogram, blood pressure, and routine blood tests), neurologi- Mental rotationc 17.2 (8.6) 20.2 (9.7) .23 cal, neuropsychological, psychiatric, and neuroradiologic (mag- Spatial visualizationc 25.7 (8.2) 26.9 (7.1) .57 netic resonance imaging) examinations. Any present or prior evidence of significant neurological, psychiatric, or medical dis- Abbreviations: ASC, autism spectrum condition; WAIS-R IQ, Wechsler Adult Intelligence Scale–Revised Intelligence Quotient. ease led to exclusion from the study. All participants gave in- a P values reflect level of significance from independent samples t test and formed written consent, and the research protocol was ap- ␹2 as appropriate. proved by the local ethics committee. b Maximum score, 28. c Maximum score, 40. MEASURES AND STATISTICAL ANALYSIS tial congenital abnormality of the amygdala in ASC would lead to a lack of orienting responses to socially salient Neuropsychology stimuli such as faces, which would then prevent the de- Intellectual Functioning. To assess intellectual functioning, we velopment of an expertise for faces mediated by the FFA. used the Shipley Institute of Living Scale,27 comprising a vo- In support of that model, structural magnetic resonance cabulary and an abstract thinking test. Based on a sum of the 16,17 imaging studies have provided evidence of amygdala raw scores of the tests, we estimated Wechsler Adult Intelli- abnormalities in individuals with ASC. In addition, there gence Scale–Revised IQs.28 is recent evidence from voxel-based morphometry stud- ies of increased gray-matter volume in the fusiform gy- Facial Emotion Recognition. Participants were given 28 pic- rus in individuals with ASC.18,19 Several functional neu- tures of facial expressions of happiness, sadness, anger, fear, sur- roimaging studies have also shown reduced activation of prise, disgust, and neutral expressions.29 A word list of these ba- the FFA20,21 and altered amygdala function21,22 in indi- sic emotional states was displayed simultaneously, and the subject viduals with autism during face processing. was required to correctly identify the displayed emotion. Evidence of pathophysiological involvement of the General Visual Processing. To ascertain the specificity of vi- amygdala-fusiform system in ASC can only be convinc- sual processing impairments to faces, we gave a mental rotation ing, however, if structural changes in this system can be test and a spatial visualization test.30 Specifically, in the mental related to functional deficits in social perception and/or rotation task, participants were required to mentally rotate let- social cognition. In the present study, we used a direct ters 0°, 60°, 120°, or 180° to indicate if they were displayed as measurement of cortical thickness of the fusiform gy- mirror images for a period of 120 seconds. In the spatial visual- rus, given that it might be more sensitive to subtle changes ization task, participants were asked to count surfaces of increas- than voxel-based morphometry, which involves con- ingly complex 3-dimensional objects for a period of 240 seconds. founding factors introduced by normalization,23 in 27 Group differences were assessed with independent samples ␣ Ͻ adults with ASC and 29 controls. To obtain amygdala vol- t tests. Analyses were 2-tailed and the level was set at P .05. umes, we used a well-validated and highly reliable manual All statistical procedures were performed using the Statistical tracing method.24 Furthermore, we ascertained anatomi- Package for the Social Sciences version 15.0 (SPSS Inc, Chi- cago, Illinois). cal relationships between the fusiform gyrus and the amyg- dala by
Load more

Recommended publications
  • Parent-Of-Origin Effects in Autism Identified Through Genome-Wide Linkage Analysis of 16,000 Snps
    Parent-Of-Origin Effects in Autism Identified through Genome-Wide Linkage Analysis of 16,000 SNPs Delphine Fradin1,2, Keely Cheslack-Postava3, Christine Ladd-Acosta2, Craig Newschaffer4, Aravinda Chakravarti5, Dan E. Arking5, Andrew Feinberg2, M. Daniele Fallin1* 1 Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America, 2 Department of Medicine, Center for Epigenetics, Institute for Basic Biomedical Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, 3 Robert Wood Johnson Foundation Health & Society Scholars, Columbia University, New York, New York, United States of America, 4 Department of Epidemiology, Drexel University, Philadelphia, Pennsylvania, United States of America, 5 Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America Abstract Background: Autism is a common heritable neurodevelopmental disorder with complex etiology. Several genome-wide linkage and association scans have been carried out to identify regions harboring genes related to autism or autism spectrum disorders, with mixed results. Given the overlap in autism features with genetic abnormalities known to be associated with imprinting, one possible reason for lack of consistency would be the influence of parent-of-origin effects that may mask the ability to detect linkage and association. Methods and Findings: We have performed a genome-wide linkage scan that accounts for potential parent-of-origin effects using 16,311 SNPs among families from the Autism Genetic Resource Exchange (AGRE) and the National Institute of Mental Health (NIMH) autism repository. We report parametric (GH, Genehunter) and allele-sharing linkage (Aspex) results using a broad spectrum disorder case definition.
    [Show full text]
  • Decreased Amygdala Functional Connectivity in Adolescents with Autism a Resting-State Fmri Study
    Psychiatry Research: Neuroimaging 257 (2016) 47–56 Contents lists available at ScienceDirect Psychiatry Research Neuroimaging journal homepage: www.elsevier.com/locate/psychresns Decreased amygdala functional connectivity in adolescents with autism: A resting-state fMRI study crossmark ⁎ Xiaonan Guo, Xujun Duan , Zhiliang Long1, Heng Chen1, Yifeng Wang, Junjie Zheng, ⁎ Youxue Zhang, Rong Li, Huafu Chen Center for Information in BioMedicine, Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, PR China ARTICLE INFO ABSTRACT Keywords: The human brain undergoes dramatic changes in amygdala-related functional connectivity network during Amygdala Theory of Autism adolescence. Given that the amygdala is a vital component of the “social brain”, the Amygdala Theory of Autism Thalamus has been proposed to account for atypical patterns of socio-emotional behavior in autism. Most of the previous Putamen neuroimaging evidence has concentrated on local functional or structural abnormalities of the amygdala in relation to social deficits in autism, rather than on its integrated role as part of larger brain networks. To examine whether functional integration pattern of the amygdala is altered in autism, the current study examined sixty-five adolescent subjects (30 autism and 35 healthy controls, 12–18 years old) from two independent datasets (UCLA and Leuven) of the Autism Brain Imaging Data Exchange. Whole-brain resting- state functional connectivity maps seeded in the amygdala were calculated and compared between patient and control groups. Compared with healthy controls, adolescents with autism showed decreased functional connectivity between the amygdala and subcortical regions in both datasets, including the bilateral thalamus and right putamen.
    [Show full text]
  • The Developmental Trajectory of Contour Integration in Autism Spectrum Disorders
    City University of New York (CUNY) CUNY Academic Works All Dissertations, Theses, and Capstone Projects Dissertations, Theses, and Capstone Projects 2-2014 The Developmental Trajectory of Contour Integration in Autism Spectrum Disorders Ted S. Altschuler Graduate Center, City University of New York How does access to this work benefit ou?y Let us know! More information about this work at: https://academicworks.cuny.edu/gc_etds/1417 Discover additional works at: https://academicworks.cuny.edu This work is made publicly available by the City University of New York (CUNY). Contact: [email protected] The developmental trajectory of contour integration in autism spectrum disorders By TED S. ALTSCHULER A dissertation submitted to the Graduate Faculty in Psychology, sub program in Cognitive Neuroscience, in partial fulfillment of the requirements for the degree of Doctor of Philosophy, The City University of New York 2014 © 2014 TED S. ALTSCHULER All Rights Reserved ii The manuscript has been read and accepted for the Graduate Faculty in Psychology in satisfaction of the Dissertation requirements for the degree of Doctor of Philosophy John J. Foxe, PhD Chair of Examining Committee Maureen O’Connor, PhD Executive Officer Sophie Molholm, PhD Jennifer Mangels, PhD Hilary Gomes, PhD Lynne E. Bernstein, Phd Supervisory Committee THE CITY UNIVERSITY OF NEW YORK iii Abstract The developmental trajectory of contour integration in autism spectrum disorders by TED S. ALTSCHULER Adviser: John J. Foxe, PhD Sensory input is inherently ambiguous and complex, so perception is believed to be achieved by combining incoming sensory information with prior knowledge. One model envisions the grouping of sensory features (the local dimensions of stimuli) to be the outcome of a predictive process relying on prior experience (the global dimension of stimuli) to disambiguate possible configurations those elements could take.
    [Show full text]
  • 1L1 an Outsider S Take on Autism Spectrum Disorders
    Plenary Lecture 特別講演 1L1 An outsider’s take on autism spectrum disorders ○Martin Raff MRC LMCB, University College London Autism spectrum disorders（ASDs）are among the commonest neuropsychiatric disorders. Although, until re- cently, ASDs were one of the least understood of these disorders, they are now one of the best understood. Pro- gress has come largely through recent advances in human genetics that have identified rare large!effect muta- tions that cause or greatly increase the risk of these disorders, together with studies of genetic mouse models based on these mutations. Remarkably, in a number of mouse models caused by single mutations, correction of the problem in the adult brain（with either drugs or genetic manipulations）largely reverses many of the behav- ioral and neurobiological abnormalities, providing hope for the development of therapies for individuals with ASDs. In my talk, I will review the basic features of ASDs, using home videos of the development of my 13!year! old autistic grandson as an example, and I will discuss some of the recent advances in ASD research, consider current puzzles, and speculate on possible ways forward. Plenary Lecture 特別講演 2L1 A role of drebrin A in the activity!dependent trafficking of NMDA receptors to the plasma membrane ○Chiye Aoki1，Sho Fujisawa1，Kei Tateyama1，Yi!Wen Chen1，Tomoaki Shirao2 1Center for Neural Science, New York University 2Dept of Neurobiology and Behavior, Gunma Univ Graduate School of Medicine NMDA receptors（NMDARs）are central molecular agents that enable the activity!dependent modification of synaptic strengths at excitatory synapses. However, relatively little is known about the molecular mechanisms regulating NMDAR levels at each synapse.
    [Show full text]
  • Neuroinflammation in Autism Spectrum Disorders Afaf El-Ansary1,2,3,5* and Laila Al-Ayadhi2,3,4
    El-Ansary and Al-Ayadhi Journal of Neuroinflammation 2012, 9:265 JOURNAL OF http://www.jneuroinflammation.com/content/9/1/265 NEUROINFLAMMATION RESEARCH Open Access Neuroinflammation in autism spectrum disorders Afaf El-Ansary1,2,3,5* and Laila Al-Ayadhi2,3,4 Abstract Objectives: The neurobiological basis for autism remains poorly understood. However, research suggests that environmentalfactors and neuroinflammation, as well as genetic factors, are contributors. This study aims to test the role that might be played by heat shock protein (HSP)70, transforming growth factor (TGF)-β2, Caspase 7 and interferon-γ (IFN-γ)in the pathophysiology of autism. Materials and methods: HSP70, TGF-β2, Caspase 7 and INF-γ as biochemical parameters related to inflammation were determined in plasma of 20 Saudi autistic male patients and compared to 19 age- and gender-matched control samples. Results: The obtained data recorded that Saudi autistic patients have remarkably higher plasma HSP70, TGF-β2, Caspase 7 and INF-γ compared to age and gender-matched controls. INF-γ recorded the highest (67.8%) while TGF-β recorded the lowest increase (49.04%). Receiver Operating Characteristics (ROC) analysis together with predictiveness diagrams proved that the measured parameters recorded satisfactory levels of specificity and sensitivity and all could be used as predictive biomarkers. Conclusion: Alteration of the selected parameters confirm the role of neuroinflammation and apoptosis mechanisms in the etiology of autism together with the possibility of the use of HSP70, TGF-β2, Caspase 7 and INF-γ as predictive biomarkers that could be used to predict safety, efficacy of a specific suggested therapy or natural supplements, thereby providing guidance in selecting it for patients or tailoring its dose.
    [Show full text]
  • Open Trevor Lovell - Honors Thesis.Pdf
    THE PENNSYLVANIA STATE UNIVERSITY SCHREYER HONORS COLLEGE SCHOOL OF SCIENCE, ENGINEERING, AND TECHNOLOGY ALTERED RESTING-STATE BRAIN ACTIVITY IN A POSTNATALLY DEVELOPING VALPROIC ACID MOUSE MODEL OF AUTISM TREVOR LOVELL Spring 2018 A thesis submitted in partial fulfillment of the requirements for baccalaureate degree in Biology with honors in Biology Reviewed and approved* by the following: Yongsoo Kim Assistant Professor of Neural and Behavioral Sciences Thesis Supervisor Michael Chorney Professor of Biology Faculty Reader David Witwer Director of Capital College Honors Honors Adviser * Signatures are on file in the Schreyer Honors College. i ABSTRACT Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder characterized by difficulties with social communication, coinciding with restricted or repetitive interests or behaviors. The symptoms of ASD are heterogeneous between those clinically diagnosed, however these symptoms consistently emerge early in childhood. Previous research has identified significant neuroanatomical and neurophysiological alterations in ASD brains, but the underlying neural mechanisms behind these changes are poorly understood. One of the most widely-researched theories of ASD is the imbalance of excitatory and inhibitory (E/I) neurons within the brain. Despite its significance, E/I balance in early postnatally developing brains has not been examined. In order to test the potential imbalance, we analyzed the neural activation levels in early postnatal mouse brains that were prenatally exposed to valproic acid, an environmental animal model of ASD. We measured endogenous c-Fos, a transcription factor and marker for activated neurons, in mice at postnatal (P) days 7 and 14 using serial two-photon tomography, a novel fluorescence microscopy method that enables us to achieve brain- wide imaging at cellular resolution.
    [Show full text]
  • A Bioinformatics Model of Human Diseases on the Basis Of
    SUPPLEMENTARY MATERIALS A Bioinformatics Model of Human Diseases on the basis of Differentially Expressed Genes (of Domestic versus Wild Animals) That Are Orthologs of Human Genes Associated with Reproductive-Potential Changes Vasiliev1,2 G, Chadaeva2 I, Rasskazov2 D, Ponomarenko2 P, Sharypova2 E, Drachkova2 I, Bogomolov2 A, Savinkova2 L, Ponomarenko2,* M, Kolchanov2 N, Osadchuk2 A, Oshchepkov2 D, Osadchuk2 L 1 Novosibirsk State University, Novosibirsk 630090, Russia; 2 Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia; * Correspondence: [email protected]. Tel.: +7 (383) 363-4963 ext. 1311 (M.P.) Supplementary data on effects of the human gene underexpression or overexpression under this study on the reproductive potential Table S1. Effects of underexpression or overexpression of the human genes under this study on the reproductive potential according to our estimates [1-5]. ↓ ↑ Human Deficit ( ) Excess ( ) # Gene NSNP Effect on reproductive potential [Reference] ♂♀ NSNP Effect on reproductive potential [Reference] ♂♀ 1 increased risks of preeclampsia as one of the most challenging 1 ACKR1 ← increased risk of atherosclerosis and other coronary artery disease [9] ← [3] problems of modern obstetrics [8] 1 within a model of human diseases using Adcyap1-knockout mice, 3 in a model of human health using transgenic mice overexpressing 2 ADCYAP1 ← → [4] decreased fertility [10] [4] Adcyap1 within only pancreatic β-cells, ameliorated diabetes [11] 2 within a model of human diseases
    [Show full text]
  • United States Patent (19) 11 Patent Number: 6,020,310 Beck Et Al
    US00602031 OA United States Patent (19) 11 Patent Number: 6,020,310 Beck et al. (45) Date of Patent: Feb. 1, 2000 54 METHOD FOR ASSISTING IN Fara, Madden, “Effect of secretin and cholecystokinin on DIFFERENTIAL DIAGNOSIS AND small intestinal blood flow distribution,” Am. J. Physiology, TREATMENT OF AUTISTC SYNDROMES 1975; 229(5):1365–70. Dollinger, Berz, Raptis, von Uexkill, Goebell, “Effects of 75 Inventors: Victoria Beck, Bedford, N.H.; Karoly Secretin and Cholecystokinin on Motor Activity of Human Horvath, Baltimore, Md. Jejunum, Digestion 12:1975, pp. 9-16. Horvath, Stefanatos,Sokolski, Wachtel, Nabors, Tildon, 73 Assignee: Repligen Corporation, Needham, “Improved Social and language skills after Secretin admin Mass. istration in patients with autistic Spectrum disorders”, J. ASSOc. for Academic Minority Physicians 9(1):1998, pp. 21 Appl. No.: 09/080,631 9-15. Raymond, Bauman, Kemper, “Hippocampus in autism: a 22 Filed: May 19, 1998 Golgi analysis”, Acta Neuropathologica, 1996; 91(1): 117-9. Charlton, O'Donohue, Miller, Jacobowitz, "Secretin immu Related U.S. Application Data noreactivity in rat and pig brain', Peptides, 1981; 2 Suppl 60 Provisional application No. 60/047,049, May 19, 1997. 1:45-9. Fremeau, Korman, Moody, “Secretin stimulates cyclic AMP (51) Int. Cl." ..................................................... A61K 38/00 formation in the rat brain”, Journal of Neurochemistry, 52 U.S. Cl. ................................... 514/12; 514/2; 436/63; 1986; 46(6):1947–55. 436/86; 436/87; 424/198.1 Fremeau, Jensen, Charlton, Miller, O'Donohue, Moody, 58 Field of Search .................................. 436/63, 86, 87, “Secretin: specific binding to rat brain membranes”,Journal 436/501; 424/1841, 198.1, 514/2-21, 254 of Neuroscience, 1983; 3(8):162-05.
    [Show full text]
  • Plasma Levels of Glial Cell Marker S100B in Children with Autism
    Physiol. Res. 68 (Suppl. 3): S315-S323, 2019 https://doi.org/10.33549/physiolres.934350 Plasma Levels of Glial Cell Marker S100B in Children With Autism A. TOMOVA1, P. KEMÉNYOVÁ1, D. FILČÍKOVÁ1, Ž. SZAPUOVÁ1, A. KOVÁČ2, K. BABINSKÁ1, D. OSTATNÍKOVÁ1 1Institute of Physiology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovak Republic, 2Slovak Academy of Sciences, Institute of Neuroimmunology, Bratislava, Slovak Republic Received March 21, 2019 Accepted September 26, 2019 Summary interaction in the presence of restricted, repetitive Autism spectrum disorder (ASD) is a neurodevelopmental behaviors or interests. ASD is of expanding worldwide condition with increasing incidence. Recent evidences suggest medical and social concern because of its increasing glial cells involvement in autism pathophysiology. S100B is incidence (Onaolapo and Onaolapo 2017, Baio et al. a calcium binding protein, mainly found in astrocytes and 2018). Despite recent scientific interest, etiology and therefore used as a marker of their activity. In our study, children pathogenesis of ASD remain unclear what obstructs the with autism had higher plasma concentrations of S100B prevention, diagnostics and treatment of people with compared to non-autistic controls. No association of S100B these disorders. According to current hypotheses, plasma levels with behavioral symptoms (ADI-R and ADOS-2 etiology of ASD involves multiple mechanisms, scales) was found. Plasma S100B concentration significantly including genetic predisposition and environmental correlated with urine serotonin, suggesting their interconnection. factors. Their combination may lead to alterations in Correlation of plasma S100B levels with stool calprotectin epigenetic gene regulation, with consequences including concentrations was found, suggesting not only brain astrocytes, impairments in neuron-glia interactions (Zeidan-Chulia but also enteric glial cells may take part in autism pathogenesis.
    [Show full text]
  • Brain Serotonin and Dopamine Transporter Bindings in Adults with High-Functioning Autism
    ORIGINAL ARTICLE Brain Serotonin and Dopamine Transporter Bindings in Adults With High-Functioning Autism Kazuhiko Nakamura, MD, PhD; Yoshimoto Sekine, MD, PhD; Yasuomi Ouchi, MD, PhD; Masatsugu Tsujii, MA; Etsuji Yoshikawa, BS; Masami Futatsubashi, BS; Kenji J. Tsuchiya, MD, PhD; Genichi Sugihara, MD, PhD; Yasuhide Iwata, MD, PhD; Katsuaki Suzuki, MD, PhD; Hideo Matsuzaki, MD, PhD; Shiro Suda, MD, PhD; Toshiro Sugiyama, MD, PhD; Nori Takei, MD, PhD; Norio Mori, MD, PhD Context: Autism is a neurodevelopmental disorder that Results: Serotonin transporter binding was signifi- is characterized by repetitive and/or obsessive interests and cantly lower throughout the brain in autistic individu- behavior and by deficits in sociability and communica- als compared with controls (PϽ.05, corrected). Specifi- tion. Although its neurobiological underpinnings are pos- cally, the reduction in the anterior and posterior cingulate tulated to lie in abnormalities of the serotoninergic and cortices was associated with the impairment of social cog- dopaminergic systems, the details remain unknown. nition in the autistic subjects (PϽ.05, corrected). A sig- nificant correlation was also found between repetitive Objective: To determine the occurrence of changes in and/or obsessive behavior and interests and the reduc- the binding of serotonin and dopamine transporters, tion of serotonin transporter binding in the thalamus which are highly selective markers for their respective (PϽ.05, corrected). In contrast, the dopamine trans- neuronal systems. porter binding
    [Show full text]
  • Enhanced Brain Signal Variability in Children with Autism Spectrum Disorder During Early Childhood
    r Human Brain Mapping 37:1038–1050 (2016) r Enhanced Brain Signal Variability in Children with Autism Spectrum Disorder During Early Childhood Tetsuya Takahashi,1* Yuko Yoshimura,1 Hirotoshi Hiraishi,1 Chiaki Hasegawa,1 Toshio Munesue,1,2 Haruhiro Higashida,1 Yoshio Minabe,1,2 and Mitsuru Kikuchi1,2 1Research Center for Child Mental Development, Kanazawa University, Japan 2Department of Psychiatry and Neurobiology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan r r Abstract: Extensive evidence shows that a core neurobiological mechanism of autism spectrum disorder (ASD) involves aberrant neural connectivity. Recent advances in the investigation of brain signal variabili- ty have yielded important information about neural network mechanisms. That information has been applied fruitfully to the assessment of aging and mental disorders. Multiscale entropy (MSE) analysis can characterize the complexity inherent in brain signal dynamics over multiple temporal scales in the dynam- ics of neural networks. For this investigation, we sought to characterize the magnetoencephalography (MEG) signal variability during free watching of videos without sound using MSE in 43 children with ASD and 72 typically developing controls (TD), emphasizing early childhood to older childhood: a critical period of neural network maturation. Results revealed an age-related increase of brain signal variability in a specific timescale in TD children, whereas atypical age-related alteration was observed in the ASD group. Additionally, enhanced brain signal variability was observed in children with ASD, and was con- firmed particularly for younger children. In the ASD group, symptom severity was associated region- specifically and timescale-specifically with reduced brain signal variability. These results agree well with a recently reported theory of increased brain signal variability during development and aberrant neural con- nectivity in ASD, especially during early childhood.
    [Show full text]
  • UCC Library and UCC Researchers Have Made This Item Openly Available. Please Let Us Know How This Has Helped You. Thanks! Downlo
    UCC Library and UCC researchers have made this item openly available. Please let us know how this has helped you. Thanks! Title Opposite expression patterns of Spry3 and p75NTR in cerebellar vermis suggest a male-specific mechanism of autism pathogenesis Spry3 and p75NTR in autism Author(s) Ning, Zhenfei; Williams, John M.; Kumari, Romika; Baranov, Pavel V.; Moore, Tom Publication date 2019-06-18 Original citation Ning, Z., Williams, J.M., Kumari, R., Baranov, P.V. and Moore, T., 2019. Opposite expression patterns of Spry3 and p75NTR in cerebellar vermis suggest a male-specific mechanism of autism pathogenesis. Frontiers in Psychiatry, 10, (416). DOI:10.3389/fpsyt.2019.00416 Type of publication Article (peer-reviewed) Link to publisher's https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00416 version http://dx.doi.org/10.3389/fpsyt.2019.00416 Access to the full text of the published version may require a subscription. Rights © 2019 Ning, Williams, Kumari, Baranov and Moore https://creativecommons.org/licenses/by/4.0/ Item downloaded http://hdl.handle.net/10468/9135 from Downloaded on 2020-06-06T01:13:11Z ORIGINAL RESEARCH published: 18 June 2019 doi: 10.3389/fpsyt.2019.00416 Opposite Expression Patterns of Spry3 and p75NTR in Cerebellar Vermis Suggest a Male-Specific Mechanism of Autism Pathogenesis Zhenfei Ning, John M. Williams, Romika Kumari †, Pavel V. Baranov and Tom Moore * School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland Edited by: Autism is a genetically complex neurobehavioral disorder with a population prevalence Yu-Qiang Ding, of more than 1%. Cerebellar abnormalities, including Purkinje cell deficits in the vermis, Tongji University, China are consistently reported, and rodent models of cerebellar dysfunction exhibit features Reviewed by: analogous to human autism.
    [Show full text]