{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T15:00:33Z","timestamp":1774450833498,"version":"3.50.1"},"reference-count":64,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T00:00:00Z","timestamp":1576540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"RS Macdonald Charitable Trust","award":["J21414"],"award-info":[{"award-number":["J21414"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and autism spectrum disorder, and among those with fragile X syndrome, approximately 1\/3rd meet a threshold for an autism spectrum disorder (ASD) diagnosis. Previous functional imaging studies of fragile X syndrome have typically focused on those with fragile X syndrome compared to either neurotypical or autism spectrum disorder control groups. Further, the majority of previous studies have tended to focus on those who are more intellectually able than is typical for fragile X syndrome. In this study, we examine the impact of autistic traits in individuals with fragile X syndrome on a paradigm looking at facial emotion processing. The study included 17 individuals with fragile X syndrome, of whom 10 met criteria for autism as measured by the Autism Diagnostic Observation Schedule (ADOS). Prior to the scan, participants rehearsed on a mock scanner to help acclimatize to the scanner environment and thus allow more severely affected individuals to participate. The task examined the blood-oxygen-level-dependent (BOLD) response to fearful and neutral faces taken from the Ekman faces series. Individuals in the autism group had a region of significantly reduced activity centered on the left superior temporal gyrus, compared to those with FXS alone, in response to the fearful faces. We suggest that autism in individuals with fragile X syndrome is associated with similar changes in the neurobiology of facial emotion processing as seen in idiopathic autism.<\/jats:p>","DOI":"10.3390\/genes10121052","type":"journal-article","created":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T03:19:36Z","timestamp":1576811976000},"page":"1052","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Autism in Fragile X Syndrome; A Functional MRI Study of Facial Emotion-Processing"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4273-9906","authenticated-orcid":false,"given":"Andrew G.","family":"McKechanie","sequence":"first","affiliation":[{"name":"The Patrick Wild Centre, The University of Edinburgh, Edinburgh EH10 5HF, UK"},{"name":"NHS Lothian, Edinburgh EH1 3EG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonya","family":"Campbell","sequence":"additional","affiliation":[{"name":"The Patrick Wild Centre, The University of Edinburgh, Edinburgh EH10 5HF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah E. A.","family":"Eley","sequence":"additional","affiliation":[{"name":"The Patrick Wild Centre, The University of Edinburgh, Edinburgh EH10 5HF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew C.","family":"Stanfield","sequence":"additional","affiliation":[{"name":"The Patrick Wild Centre, The University of Edinburgh, Edinburgh EH10 5HF, UK"},{"name":"NHS Lothian, Edinburgh EH1 3EG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1086\/302260","article-title":"Prevalence and phenotype consequence of FRAXA and FRAXE alleles in a large, ethnically diverse, special education-needs population","volume":"64","author":"Crawford","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/S0140-6736(82)90231-8","article-title":"Association of fragile X syndrome with autism","volume":"1","author":"Brown","year":"1982","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/BF01531374","article-title":"Infantile autism associated with the fragile-X syndrome","volume":"12","author":"Meryash","year":"1982","journal-title":"J. Autism Dev. Disord."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1097\/00004703-198309000-00002","article-title":"Autism and the fragile X syndrome","volume":"4","author":"Levitas","year":"1983","journal-title":"J. Dev. Behav. Pediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1111\/j.1399-0004.1984.tb01099.x","article-title":"The fragile X syndrome. A study of 83 families","volume":"26","author":"Fryns","year":"1984","journal-title":"Clin. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/ajmg.1320230128","article-title":"An analysis of autism in fifty males with the fragile X syndrome","volume":"23","author":"Hagerman","year":"1986","journal-title":"Am. J. Med. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/j.1399-0004.1987.tb03351.x","article-title":"Fragile (X) syndrome: A study of the psychological profile in 23 prepubertal patients","volume":"32","author":"Borghgraef","year":"1987","journal-title":"Clin. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/ajmg.1320230126","article-title":"Fragile X and autism: A multicenter survey","volume":"23","author":"Brown","year":"1986","journal-title":"Am. J. Med. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1176\/ajp.142.1.108","article-title":"Association of fragile X syndrome with autism","volume":"142","author":"Goldfine","year":"1985","journal-title":"Am. J. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1002\/ajmg.1320230127","article-title":"Infantile-Autism\u2014An Occasional Manifestation of Fragile-(X) Mental-Retardation","volume":"23","author":"Mcgillivray","year":"1986","journal-title":"Am. J. Med. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/BF01531503","article-title":"Screening-Children with Autism for Fragile-X Syndrome and Phenylketonuria","volume":"15","author":"Pueschel","year":"1985","journal-title":"J. Autism Dev. Disord."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/ajmg.1320230132","article-title":"Infantile autism and the fragile X. A Swedish multicenter study","volume":"23","author":"Wahlstrom","year":"1986","journal-title":"Am. J. Med. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1056\/NEJM198405313102214","article-title":"Fragile X in a survey of 75 autistic males","volume":"310","author":"Watson","year":"1984","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1177\/0009922811406261","article-title":"Diagnostic Yield of Genetic Testing in Children Diagnosed With Autism Spectrum Disorders at a Regional Referral Center","volume":"50","author":"Roesser","year":"2011","journal-title":"Clin. Pediatr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"E727","DOI":"10.1542\/peds.2009-1684","article-title":"Clinical Genetic Testing for Patients With Autism Spectrum Disorders","volume":"125","author":"Shen","year":"2010","journal-title":"Pediatrics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1007\/s10803-011-1398-3","article-title":"Diagnostic Yield of Chromosomal Microarray Analysis in an Autism Primary Care Practice: Which Guidelines to Implement?","volume":"42","author":"McGrew","year":"2012","journal-title":"J. Autism Dev. Disord."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"61","DOI":"10.2174\/157339607779941660","article-title":"Fragile X Syndrome and Autism: Common Developmental Pathways?","volume":"3","author":"Cornish","year":"2007","journal-title":"Curr. Pediatr. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"355","DOI":"10.3389\/fgene.2014.00355","article-title":"The fragile X syndrome-autism comorbidity: What do we really know?","volume":"5","author":"Abbeduto","year":"2014","journal-title":"Front. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/j.jaac.2010.07.001","article-title":"Autism in fragile X syndrome: A category mistake?","volume":"49","author":"Hall","year":"2010","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"ref_20","unstructured":"Dean, S.R. (1973). Infantile Autism and the Schizophrenias. Schizophrenia: The First Ten Dean Award Lectures, MSS Information Corporation."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1007\/s11065-010-9138-6","article-title":"Facial emotion recognition in autism spectrum disorders: A review of behavioral and neuroimaging studies","volume":"20","author":"Harms","year":"2010","journal-title":"Neuropsychol. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1037\/a0014124","article-title":"Autism and the extraction of emotion from briefly presented facial expressions: Stumbling at the first step of empathy","volume":"8","author":"Clark","year":"2008","journal-title":"Emotion"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1076\/chin.7.1.1.3150","article-title":"Impaired categorical perception of facial expressions in high-functioning adolescents with autism","volume":"7","author":"Teunisse","year":"2001","journal-title":"Child Neuropsychol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0065-2407(06)80008-X","article-title":"The development and neural bases of facial emotion recognition","volume":"34","author":"Leppanen","year":"2006","journal-title":"Adv. Child Dev. Behav."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.neubiorev.2011.10.008","article-title":"A systematic review and meta-analysis of the fMRI investigation of autism spectrum disorders","volume":"36","author":"Philip","year":"2012","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.biopsych.2008.09.022","article-title":"Functional brain correlates of social and nonsocial processes in autism spectrum disorders: An activation likelihood estimation meta-analysis","volume":"65","author":"Ross","year":"2009","journal-title":"Biol. Psychiatry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1093\/brain\/124.10.2059","article-title":"Face processing occurs outside the fusiform \u2018face area\u2019 in autism: Evidence from functional MRI","volume":"124","author":"Pierce","year":"2001","journal-title":"Brain"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1093\/scan\/nsm010","article-title":"Perception of dynamic changes in facial affect and identity in autism","volume":"2","author":"Pelphrey","year":"2007","journal-title":"Soc. Cogn. Affect. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/aur.1","article-title":"Cortical patterns of category-selective activation for faces, places and objects in adults with autism","volume":"1","author":"Humphreys","year":"2008","journal-title":"Autism Res."},{"key":"ref_30","first-page":"26","article-title":"Location, Location, Location: Alterations in the Functional Topography of Face-but not Object- or Place-Related Cortex in Adolescents with Autism","volume":"4","author":"Scherf","year":"2010","journal-title":"Front. Hum. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1080\/17470911003683185","article-title":"Experimental manipulation of face-evoked activity in the fusiform gyrus of individuals with autism","volume":"6","author":"Perlman","year":"2011","journal-title":"Soc. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1002\/hbm.20283","article-title":"Abnormal activation of the social brain during face perception in autism","volume":"28","author":"Hadjikhani","year":"2007","journal-title":"Hum. Brain Mapp."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.neuropsychologia.2006.04.014","article-title":"Differential activation of the amygdala and the \u2018social brain\u2019 during fearful face-processing in\n\t\t  Asperger Syndrome","volume":"45","author":"Ashwin","year":"2007","journal-title":"Neuropsychologia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1176\/appi.ajp.2014.13111464","article-title":"Aberrant Face and Gaze Habituation in Fragile X Syndrome","volume":"171","author":"Bruno","year":"2014","journal-title":"Am. J. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/aur.32","article-title":"Brain Function and Gaze Fixation During Facial-Emotion Processing in Fragile X and Autism","volume":"1","author":"Dalton","year":"2008","journal-title":"Autism Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1001\/archpsyc.61.3.281","article-title":"Here\u2019s looking at you, kid: Neural systems underlying face and gaze processing in fragile X syndrome","volume":"61","author":"Garrett","year":"2004","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1097\/CHI.0b013e3181886e92","article-title":"Aberrant Neural Function During Emotion Attribution in Female Subjects With Fragile X Syndrome","volume":"47","author":"Hagan","year":"2008","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.neuroimage.2008.08.009","article-title":"Prefrontal social cognition network dysfunction underlying face encoding and social anxiety in fragile X syndrome","volume":"43","author":"Holsen","year":"2008","journal-title":"Neuroimage"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1093\/cercor\/bhs341","article-title":"Fear-Specific Amygdala Function in Children and Adolescents on the Fragile X Spectrum: A Dosage Response of the FMR1 Gene","volume":"24","author":"Kim","year":"2014","journal-title":"Cereb. Cortex"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1001\/archpsyc.65.11.1315","article-title":"Aberrant Brain Activation During Gaze Processing in Boys With Fragile X Syndrome","volume":"65","author":"Watson","year":"2008","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s11689-009-9007-x","article-title":"The neural basis of auditory temporal discrimination in girls with fragile X syndrome","volume":"1","author":"Hall","year":"2009","journal-title":"J. Neurodev. Disord."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.bandc.2004.02.017","article-title":"Do women with fragile X syndrome have problems in switching attention: Preliminary findings from ERP and fMRI","volume":"54","author":"Cornish","year":"2004","journal-title":"Brain Cognit."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1097\/01.wnr.0000134472.44362.be","article-title":"Reduced basal forebrain and hippocampal activation during memory encoding in girls with fragile X syndrome","volume":"15","author":"Greicius","year":"2004","journal-title":"Neuroreport"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1002\/hbm.20406","article-title":"Fronto-striatal dysfunction and potential compensatory mechanisms in male adolescents with fragile X syndrome","volume":"28","author":"Hoeft","year":"2007","journal-title":"Hum. Brain Mapp."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.pscychresns.2015.06.009","article-title":"Examining the neural correlates of emergent equivalence relations in fragile X syndrome","volume":"233","author":"Klabunde","year":"2015","journal-title":"Psychiatry Res. Neuroimaging"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1176\/appi.ajp.158.7.1040","article-title":"Functional neuroanatomy of visuospatial working memory in fragile X syndrome: Relation to behavioral and molecular measures","volume":"158","author":"Kwon","year":"2001","journal-title":"Am. J. Psychiatry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3615","DOI":"10.1073\/pnas.0304544101","article-title":"Frontostriatal deficits in fragile X syndrome: Relation to FMR1 gene expression","volume":"101","author":"Menon","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/hbm.10048","article-title":"Functional brain activation during arithmetic processing in females with fragile X Syndrome is related to FMRI protein expression","volume":"16","author":"Rivera","year":"2002","journal-title":"Hum. Brain Mapp."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1162\/089892902317236812","article-title":"fMRI study of cognitive interference processing in females with fragile X syndrome","volume":"14","author":"Tamm","year":"2002","journal-title":"J. Cogn. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1001\/jamapsychiatry.2013.247","article-title":"Identifying large-scale brain networks in fragile X syndrome","volume":"70","author":"Hall","year":"2013","journal-title":"JAMA Psychiatry"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Isanova, E., Petrovskiy, E., Savelov, A., Yudkin, D., and Tulupov, A. (2017). Resting-state fMRI study of patients with fragile X syndrome. J. Phys. Conf. Ser., 886.","DOI":"10.1088\/1742-6596\/886\/1\/012007"},{"key":"ref_52","unstructured":"Hagerman, P.J., Randol, J., Kim, K., Espinal, G., Hessl, D., Schneider, A., Protic, D., Aydin, Y., and Hagerman, R. (2019, January 18\u201321). Relationship between Fragile X protein (FMRP) and IQ using a quantitative FRET\u2014Based method for determining FMRP levels. Proceedings of the 19th International Workshop on Fragile X and Other Neurodevelopmental Disorders, Sorrento, Italy."},{"key":"ref_53","unstructured":"Ekman, P., and Friesen, W.V. (1976). Pictures of Facial Affect, Consulting Psychologists Press."},{"key":"ref_54","unstructured":"Mazaika, P. (2015). ArtRepair, Center for Interdisciplinary Brain Science Research; Stanford University. Version 5b3."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"S58","DOI":"10.1016\/S1053-8119(09)70238-1","article-title":"Methods and Software for fMRI Analysis for Clinical Subjects","volume":"47","author":"Mazaika","year":"2009","journal-title":"Neuroimage"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Kaufman, A.S., and Kaufman, N.L. (2004). Kaufman Brief Intelligence Test, Pearson Clinical Assessment. [2nd ed.].","DOI":"10.1037\/t27706-000"},{"key":"ref_57","unstructured":"Lord, C., Rutter, M., DiLavore, P.C., Risi, S., Gotham, K., and Bishop, S. (2012). Autism Diagnostic Observation Schedule, Western Psychological Services. [2nd ed.]."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1007\/s10803-014-2080-3","article-title":"The autism diagnostic observation schedule, module 4: Revised algorithm and standardized severity scores","volume":"44","author":"Hus","year":"2014","journal-title":"J. Autism Dev. Disord."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1093\/brain\/123.11.2203","article-title":"The functional neuroanatomy of social behaviour: Changes in cerebral blood flow when people with autistic disorder process facial expressions","volume":"123","author":"Critchley","year":"2000","journal-title":"Brain"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.biopsych.2006.09.037","article-title":"An event related functional magnetic resonance imaging study of facial emotion processing in Asperger syndrome","volume":"62","author":"Deeley","year":"2007","journal-title":"Biol. Psychiatry"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1016\/j.neuropsychologia.2009.02.021","article-title":"A failure to grasp the affective meaning of actions in autism spectrum disorder subjects","volume":"47","author":"Grezes","year":"2009","journal-title":"Neuropsychologia"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.rasd.2006.07.002","article-title":"The role of MT+\/V5 during biological motion perception in Asperger Syndrome: An fMRI study","volume":"1","author":"Herrington","year":"2007","journal-title":"Res. Autism Spectr. Disord."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.neuroimage.2013.09.033","article-title":"Social cognition and the cerebellum: A meta-analysis of over 350 fMRI studies","volume":"86","author":"Baetens","year":"2014","journal-title":"Neuroimage"},{"key":"ref_64","unstructured":"Mazaika, P. (2009). Motion Correction and Despike Functions, Stanford University."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/10\/12\/1052\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:43:10Z","timestamp":1760190190000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/10\/12\/1052"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,17]]},"references-count":64,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["genes10121052"],"URL":"https:\/\/doi.org\/10.3390\/genes10121052","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,17]]}}}