Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Neurodevelopmental Disorders
Published in: Journal of Neurodevelopmental Disorders 1/2013

Open Access 01-12-2013 | Research

Repetitive and self-injurious behaviors: associations with caudate volume in autism and fragile X syndrome

Authors: Jason J Wolff, Heather C Hazlett, Amy A Lightbody, Allan L Reiss, Joseph Piven

Published in: Journal of Neurodevelopmental Disorders | Issue 1/2013

Login to get access

Abstract

Background

Following from previous work suggesting that neurobehavioral features distinguish fragile X and idiopathic variants of autism, we investigated the relationships between four forms of repetitive behavior (stereotypy, self-injury, compulsivity, ritual behavior) and caudate nuclei volume in two groups: boys with fragile X syndrome, a subset of whom met criteria for autism, and a comparison group of boys with idiopathic autism.

Methods

Bilateral caudate nuclei volumes were measured in boys aged 3 to 6 years with fragile X syndrome (n = 41), the subset of boys with fragile X syndrome and autism (n = 16), and boys with idiopathic autism (n = 30). Repetitive behaviors were measured using the Repetitive Behavior Scales-Revised.

Results

For boys with idiopathic autism, left caudate volume was modestly associated with self-injury, while both compulsive and ritual behaviors showed significant positive correlations with bilateral caudate nuclei volumes, replicating previous results. For boys with fragile X syndrome, there was no such association between caudate volume and compulsive behaviors. However, we did identify significant positive correlations between self-injury total scores and number of self-injury topographies with bilateral caudate nuclei volumes.

Conclusions

These findings suggest a specific role for the caudate nucleus in the early pathogenesis of self-injurious behavior associated with both idiopathic autism and fragile X syndrome. Results further indicate that the caudate may be differentially associated with compulsive behavior, highlighting the utility of isolating discrete brain-behavior associations within and between subtypes of autism spectrum disorder.
Appendix
Available only for authorised users
Literature
1.
Hall SS, Lightbody AA, Reiss AL: Compulsive, self-injurious, and autistic behavior in children and adolescents with fragile X syndrome. Am J Ment Retard. 2008, 113: 44-53. 10.1352/0895-8017(2008)113[44:CSAABI]2.0.CO;2.CrossRefPubMed
2.
Symons FJ, Clark RD, Hatton DD, Skinner M, Bailey DB: Self-injurious behavior in young boys with fragile X syndrome. Am J Med Genet A. 2003, 118A: 115-121. 10.1002/ajmg.a.10078.CrossRefPubMed
3.
Baghdadli A, Pascal C, Grisi S, Aussilloux C: Risk factors for self-injurious behaviours among 22 young children with autistic disorders. J Intellect Disabil Res. 2003, 47: 622-627. 10.1046/j.1365-2788.2003.00507.x.CrossRefPubMed
4.
Duerden EG, Oatley HK, Mak-Fan KM, McGrath PA, Taylor MJ, Szatmari P, Roberts SW: Risk factors associated with self-injurious behaviors in children and adolescents with autism spectrum disorders. J Autism Dev Disord. 2012, 42: 2460-2470. 10.1007/s10803-012-1497-9.CrossRefPubMed
5.
Berkson G, Tupa M, Sherman L: Early development of stereotyped and self-injurious behaviors: I. Incidence. Am J Ment Retard. 2001, 106: 539-547. 10.1352/0895-8017(2001)106<0539:EDOSAS>2.0.CO;2.CrossRefPubMed
6.
Lewis M, Kim S: The pathophysiology of restricted repetitive behavior. J Neurodevelop Disord. 2009, 1: 114-132. 10.1007/s11689-009-9019-6.CrossRef
7.
Turner CA, Lewis MH: Dopaminergic mechanisms in self-injurious behaviors and related disorders. Self-Injurious Behavior: Gene-Brain-Behavior Relationships. Edited by: Schroeder SR, Oster-Granite ML, Thompson T. 2002, Washington, DC: American Psychological Association, 165-179.CrossRef
8.
Devine DP: Animal models of self-injurious behaviour: an overview. Methods Mol Biol. 2012, 829: 65-84. 10.1007/978-1-61779-458-2_4.CrossRefPubMed
9.
Wong DF, Harris JC, Naidu S, Yokoi F, Marenco S, Dannals RF, Ravert HT, Yaster M, Evans A, Rousset O, Bryan RN, Gjedde A, Kuhar MJ, Breese GR: Dopamine transporters are markedly reduced in Lesch-Nyhan disease in-vivo. Proc Natl Acad Sci USA. 1996, 93: 5539-5543. 10.1073/pnas.93.11.5539.PubMedCentralCrossRefPubMed
10.
Hazlett HC, Poe MD, Lightbody AA, Gerig G, MacFall JR, Ross AK, Provenzale J, Arianna M, Reiss AL, Piven J: Teasing apart the heterogeneity of autism: same behavior, different brains in toddlers with fragile X syndrome and autism. J Neurodev Disord. 2009, 1: 81-90. 10.1007/s11689-009-9009-8.PubMedCentralCrossRefPubMed
11.
Hoeft F, Lightbody AA, Hazlett HC, Patnaik S, Piven J, Reiss AL: Morphometric spatial patterns differentiate fragile X syndrome, typical developing and developmentally delayed boys ages one to three. Arch Gen Psychiatry. 2008, 65: 1087-1097. 10.1001/archpsyc.65.9.1087.PubMedCentralCrossRefPubMed
12.
Hazlett HC, Poe MD, Lightbody AA, Styner M, MacFall JR, Reiss AL, Piven J: Trajectories of early brain volume development in fragile X syndrome and autism. J Am Acad Child Adolesc Psychiatry. 2012, 51: 921-933. 10.1016/j.jaac.2012.07.003.PubMedCentralCrossRefPubMed
13.
Roberts JE, Symons FJ, Johnson AM, Hatton DD, Boccia ML: Blink rate in boys with fragile X syndrome: preliminary evidence for altered dopamine function. J Intellect Disabil Res. 2005, 49: 647-656. 10.1111/j.1365-2788.2005.00713.x.CrossRefPubMed
14.
Wang H, Wu L, Kim SS, Lee FJS, Gong B, Toyoda H, Ren M, Shang Y, Xu H, Liu F, Zhao M, Zhuo M: FMRP acts as a key messenger for dopamine modulation in the forebrain. Neuron. 2008, 59: 634-647. 10.1016/j.neuron.2008.06.027.CrossRefPubMed
15.
Gothelf D, Furfaro JA, Hoeft F, Echert MA, Hall SS, O’Hara R, Erba HW, Ringel J, Hayashi KM, Patnaik S, Golianu B, Kraemer HC, Thompsom PM, Piven J, Reiss AL: Neuroanatomy of fragile X syndrome is associated with aberrant behavior and the fragile X mental retardation protein (FMRP). Ann Neurol. 2008, 63: 40-51. 10.1002/ana.21243.PubMedCentralCrossRefPubMed
16.
Sears LL, Vest C, Mohamed S, Bailey J, Ranson BL, Piven J: An MRI study of the basal ganglia in autism. Prog Neuropsychopharmacol Biol Psychiatry. 1999, 23: 613-624. 10.1016/S0278-5846(99)00020-2.CrossRefPubMed
17.
Hollander E, Evdokia A, Chaplin W, Esposito K, Haznedar MM, Licalzi E, Wasserman S, Soorya L, Buchsbaum M: Striatal volume on magnetic resonance imaging and repetitive behavior in autism. Biol Psychiatry. 2005, 58: 226-232. 10.1016/j.biopsych.2005.03.040.CrossRefPubMed
18.
Rojas DC, Peterson E, Winterrowd E, Reite ML, Rogers SJ, Tregellas JR: Regional gray matter volumetric changes in autism associated with social and repetitive behavior symptoms. BMC Psychiatry. 2006, 6: 56-69. 10.1186/1471-244X-6-56.PubMedCentralCrossRefPubMed
19.
Langen M, Schnack HG, Nederveen H, Bos D, Lahuis BE, de Jonge MV, van Engeland H, Durston S: Changes in the developmental trajectories of striatum in autism. Biol Psychiatry. 2009, 66: 327-333. 10.1016/j.biopsych.2009.03.017.CrossRefPubMed
20.
Reiss AL, Abrams MT, Greenlaw R, Freund L, Denckla MB: Neurodevelopmental effects of the FMR-1 full mutation in humans. Nat Med. 1995, 1: 159-167. 10.1038/nm0295-159.CrossRefPubMed
21.
Eliez S, Blasey CM, Freund LS, Hastie T, Reiss AL: Brain anatomy, gender, and IQ in children and adolescents with fragile X syndrome. Brain. 2001, 124: 1610-1618. 10.1093/brain/124.8.1610.CrossRefPubMed
22.
Hoeft F, Walter E, Lightbody AA, Hazlett HC, Chang C, Piven J, Reiss AL: Neuroanatomical differences in toddler boys with fragile X syndrome and idiopathic autism. Arch Gen Psychiatry. 2011, 68: 295-305. 10.1001/archgenpsychiatry.2010.153.PubMedCentralCrossRefPubMed
23.
Wolff JJ, Bodfish JW, Hazlett HC, Lightbody AA, Reiss AL, Piven J: Evidence of a distinct behavioral phenotype in young boys with fragile X syndrome and autism. J Am Acad Child Adolesc Psychiatry. 2012, 51: 1324-1332. 10.1016/j.jaac.2012.09.001.PubMedCentralCrossRefPubMed
24.
Bodfish JW, Symons FJ, Parker DE, Lewis MH: Varieties of repetitive behavior in autism: comparisons to mental retardation. J Autism Dev Disord. 2000, 30: 237-243. 10.1023/A:1005596502855.CrossRefPubMed
25.
Lord C, Risi S, Lambrecht L, Cook EH, Leventhal BL, DiLavore PC, Pickles A, Rutter M: The Autism Diagnostic Observation Schedule-Generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord. 2000, 30: 205-223. 10.1023/A:1005592401947.CrossRefPubMed
26.
Lord C, Rutter M, LeCouteur A: Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord. 1994, 24: 659-685. 10.1007/BF02172145.CrossRefPubMed
27.
Mirenda P, Smith IM, Vailancourt T, Georgiades S, Duku E, Szatmari P, Bryson S, Fombinne E, Roberts W, Volden J, Waddell C, Zwaigenbaum L, The Pathways in ASD Study Team: Validating the Repetitive Behavior Scale-Revised in young children with autism spectrum disorders. J Autism Dev Disord. 2009, 40: 1521-1530.CrossRef
28.
Mullen EM: Mullen Scales of Early Learning: AGS edition. 1995, Circle Pines, MN: AGS Publishing
29.
Van Leemput K, Maes F, Vandermeulen D, Suetens P: Automated model-based tissue classification of MR images of the brain. IEEE Trans Med Imaging. 1999, 18: 897-908. 10.1109/42.811270.CrossRefPubMed
30.
Park J, Gerig G, Chakos M, Vandermeulen D, Lieberman JA: Neuroimaging of psychiatry disease: reliable and efficient automatic brain tissue segmentation for increased sensitivity. Schizophr Res. 2001, 49: 163-
31.
Ho S, Bullit E, Gerig G: Level Set Evolution With Region Competition: Automatic 3-D Segmentation of Brain Tumors. Proceedings of the 16th International Conference on Pattern Recognition. 2002, ICPR: IEEE Computer Society
32.
Yushkevich PA, Piven J, Hazlett HC, Smith RG, Ho S, Gee JC, Gerig G: User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability. Neuroimage. 2006, 31: 1116-1128. 10.1016/j.neuroimage.2006.01.015.CrossRefPubMed
33.
Smith LE, Barker ET, Seltzer MM, Abbeduto L, Greenberg JS: Behavioral phenotype of fragile X syndrome in adolescence and adulthood. Am J Intellect Dev Disabil. 2012, 117: 1-17. 10.1352/1944-7558-117.1.1.PubMedCentralCrossRefPubMed
34.
Comery TA, Harris JB, Willems PJ, Oostra BA, Irwin SA, Weiler IJ, Greenough WT: Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits. Proc Natl Acad Sci USA. 1997, 94: 5401-5404. 10.1073/pnas.94.10.5401.PubMedCentralCrossRefPubMed
35.
Pan F, Aldridge GM, Grennough WT, Gan WB: Dendritic spine instability and insensitivity to modulation by sensory experience in a mouse model of fragile X syndrome. Proc Natl Acad Sci USA. 2010, 107: 17768-17773. 10.1073/pnas.1012496107.PubMedCentralCrossRefPubMed
36.
Huttenlocher PR: Synaptic density in human frontal cortex - developmental change and effects of aging. Brain Res. 1979, 163: 195-205. 10.1016/0006-8993(79)90349-4.CrossRefPubMed
37.
Andersson C, Hamer RM, Lawler CP, Mailman RB, Lieberman JA: Striatal volume changes in the rat following long-term administration of typical and atypical antipsychotic drugs. Neuropsychopharmacology. 2002, 27: 143-151. 10.1016/S0893-133X(02)00287-7.CrossRefPubMed
38.
Magnusson JE, Fisher K: The involvement of dopamine in nociception: the role of D1 and D2 receptors in the dorsolateral striatum. Brain Res. 2000, 855: 260-266. 10.1016/S0006-8993(99)02396-3.CrossRefPubMed
39.
Symons FJ, Wendelschafer-Crabb G, Kennedy W, Hardict R, Dahl N, Bodfish JW: Evidence of altered epidermal nerve fiber morphology in adults with self-injurious behavior and neurodevelopmental disorders. Pain. 2008, 134: 232-237. 10.1016/j.pain.2007.07.022.PubMedCentralCrossRefPubMed
40.
Symons FJ, Wendelschafer-Crabb G, Kennedy W, Heeth W, Bodfish JW: Degranulated mast cells in the skin of adults with self-injurious behavior and neurodevelopmental disorders. Brain Behav Immun. 2009, 23: 365-370. 10.1016/j.bbi.2008.11.003.CrossRefPubMed
41.
Oswald LM, Wong DF, McCaul M, Zhou Y, Kuwabara H, Choi L, Brasic J, Wand GS: Relationships among ventral striatal dopamine release, cortisol secretion, and subjective responses to amphetamine. Neuropsychopharmacology. 2005, 30: 821-832.PubMed
42.
Novak MA: Self-injurious behavior in rhesus monkeys: new insights into its etiology, physiology, and treatment. Am J Primatol. 2003, 59: 3-19. 10.1002/ajp.10063.CrossRefPubMed
43.
Symons FJ, Wolff JJ, Stone LS, Lim TK, Bodfish JW: Salivary biomarkers of HPA axis and autonomic activity in adults with intellectual disability with and without stereotyped and self-injurious behavior disorders. J Neurodev Disord. 2011, 3: 144-151. 10.1007/s11689-011-9080-9.PubMedCentralCrossRefPubMed
44.
Verhoeven WM, Tuinier S, van den Berg YW, Coppus AM, Fekkes D, Peppelinkhuizen L, Thijssen JH: Stress and self-injurious behavior: hormonal and serotonergic parameters in mentally retarded subjects. Pharmacopsychiatry. 1999, 32: 13-20. 10.1055/s-2007-979183.CrossRefPubMed
45.
Hoeft F, Carter JC, Lightbody AA, Cody Hazlett H, Piven J, Reiss AL: Region-specific alterations in brain development in one- to three-year-old boys with fragile X syndrome. Proc Natl Acad Sci USA. 2010, 107: 9335-9339. 10.1073/pnas.1002762107.PubMedCentralCrossRefPubMed
46.
Oliver C: Annotation: self-injurious behavior in children with learning disabilities: recent advances in assessment and intervention. J Child Psychol Psychiat. 1995, 30: 909-927.CrossRef
47.
Wolff JJ, Clary J, Harper VN, Bodfish JW, Symons FJ: Evidence for reciprocal interaction effects among adults with self-injury and their caregivers. Am J Intellect Dev Disabil. 2012, 117: 225-232. 10.1352/1944-7558-117.3.225.PubMedCentralCrossRefPubMed
48.
Michalon A, Sidorov M, Ballard TM, Ozmen L, Spooren W, Wettstein JG, Jaeschke G, Bear MF, Lindemann L: Chronic pharmacological mGlu5 inhibition corrects fragile X in adult mice. Neuron. 2012, 74: 49-56. 10.1016/j.neuron.2012.03.009.CrossRefPubMed
49.
Silverman JL, Smith DG, Rizzo SJ, Karras MN, Turner SM, Tolu SS, Bryce DK, Smith DL, Fonseca K, Ring RH, Crawley JN: Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism. Sci Trans Med. 2012, 4: 131ra51-10.1126/scitranslmed.3003501.CrossRef
50.
Richman DM: Early intervention and prevention of self-injurious behaviour exhibited by young children with developmental disabilities. J Intellect Disabil Res. 2008, 52: 3-17.CrossRefPubMed
51.
Hall SS, Lightbody AA, Hirt M, Rezvani A, Reiss AL: Autism in fragile X syndrome: a category mistake?. J Am Acad Child Adolesc Psychiatry. 2010, 49: 921-933. 10.1016/j.jaac.2010.07.001.PubMedCentralCrossRefPubMed
Metadata
Title
Repetitive and self-injurious behaviors: associations with caudate volume in autism and fragile X syndrome
Authors
Jason J Wolff
Heather C Hazlett
Amy A Lightbody
Allan L Reiss
Joseph Piven
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Neurodevelopmental Disorders / Issue 1/2013
Print ISSN: 1866-1947
Electronic ISSN: 1866-1955
DOI
https://doi.org/10.1186/1866-1955-5-12

Other articles of this Issue 1/2013

Journal of Neurodevelopmental Disorders 1/2013 Go to the issue

Research

Neurodevelopmental alcohol exposure elicits long-term changes to gene expression that alter distinct molecular pathways dependent on timing of exposure

Research

Spontaneous and cued gaze-following in autism and Williams syndrome

Research

Organization of brain networks governed by long-range connections index autistic traits in the general population

Research

Dementia in Down’s syndrome: an MRI comparison with Alzheimer’s disease in the general population

Review

Sensory and motor secondary symptoms as indicators of brain vulnerability

Research

Behavioral profile of adults with Prader-Willi syndrome: correlations with individual and environmental variables