Abstract
Rationale
Self-injurious behaviour is not one of the three core symptoms that define autism. However, children on the autism spectrum appear to be particularly vulnerable. Afflicted children typically slap their faces, punch or bang their heads, and bite or pinch themselves. These behaviours can be extremely destructive, and they interfere with normal social and educational activities. However, the neurobiological mechanisms that confer vulnerability in children with autism have not been adequately described.
Objectives
This review explores behavioural and neurobiological characteristics of children with autism that may be relevant for an increased understanding of their vulnerability for self-injurious behaviour.
Methods
Behavioural characteristics that are co-morbid for self-injurious behaviour in children with autism are examined. In addition, the contributions of social and environmental deprivation in self-injurious institutionalized orphans, isolated rhesus macaques, and additional animal models are reviewed.
Results
There is extensive evidence that social and environmental deprivation promotes self-injurious behaviour in both humans (including children with autism) and animal models. Moreover, there are multiple lines of convergent neuroanatomical, neurophysiological, and neurochemical data that draw parallels between self-injurious children with autism and environmentally deprived humans and animals.
Conclusions
A hypothesis is presented that describes how the core symptoms of autism make these children particularly vulnerable for self-injurious behaviour. Relevant neurodevelopmental pathology is described in cortical, limbic, and basal ganglia brain regions, and additional research is suggested.
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Aman MG, Arnold LE, McDougle CJ, Vitiello B, Scahill L, Davies M, McCracken JT, Tierney E, Nash PL, Posey DJ, Chuang S, Martin A, Shah B, Gonzalez NM, Swiezy NB, Ritz L, Koenig K, McGough J, Ghuman JK, Lindsay RL (2005) Acute and long-term safety and tolerability of risperidone in children with autism. J Child Adolesc Psychopharmacol 15:869–884
Aman MG, McDougle CJ, Scahill L, Handen B, Arnold LE, Johnson C, Stigler KA, Bearss K, Butter E, Swiezy NB, Sukhodolsky DD, Ramadan Y, Pozdol SL, Nikolov R, Lecavalier L, Kohn AE, Koenig K, Hollway JA, Korzekwa P, Gavaletz A, Mulick JA, Hall KL, Dziura J, Ritz L, Trollinger S, Yu S, Vitiello B, Wagner A (2009) Medication and parent training in children with pervasive developmental disorders and serious behavior problems: results from a randomized clinical trial. J Am Acad Child Adolesc Psychiatry 48:1143–1154
Andersen PH (1989) The dopamine inhibitor GBR 12909: selectivity and molecular mechanism of action. Eur J Pharmacol 166:493–504
Ando H, Yoshimura I (1979) Speech skill levels and prevalence of maladaptive behaviors in autistic and mentally retarded children: a statistical study. Child Psychiatry Hum Dev 10:85–90
Archer DC, Pinchbeck GL, French NP, Proudman CJ (2008) Risk factors for epiploic foramen entrapment colic in a UK horse population: a prospective case–control study. Equine Vet J 40:405–410
Arron K, Oliver C, Moss J, Berg K, Burbidge C (2011) The prevalence and phenomenology of self-injurious and aggressive behaviour in genetic syndromes. J Intellect Disabil Res 55:109–120
Autism and Developmental Disabilities Monitoring Network (2012) Prevalence of autism spectrum disorders. MMWR Surveill Summ 61:1–19
Baghdadli A, Pascal C, Grisi S, Aussilloux C (2003) Risk factors for self-injurious behaviours among 222 young children with autistic disorders. J Intellect Disabil Res 47:622–627
Bailey A, Luthert P, Dean A, Harding B, Janota I, Montgomery M, Rutter M, Lantos P (1998) A clinicopathological study of autism. Brain 121(Pt 5):889–905
Baranek GT (1999) Autism during infancy: a retrospective video analysis of sensory-motor and social behaviors at 9–12 months of age. J Autism Dev Disord 29:213–224
Baranek GT, David FJ, Poe MD, Stone WL, Watson LR (2006) Sensory Experiences Questionnaire: discriminating sensory features in young children with autism, developmental delays, and typical development. J Child Psychol Psychiatry 47:591–601
Barnea-Goraly N, Kwon H, Menon V, Eliez S, Lotspeich L, Reiss AL (2004) White matter structure in autism: preliminary evidence from diffusion tensor imaging. Biol Psychiatry 55:323–326
Barr CS, Newman TK, Becker ML, Parker CC, Champoux M, Lesch KP, Goldman D, Suomi SJ, Higley JD (2003) The utility of the non-human primate; model for studying gene by environment interactions in behavioral research. Genes Brain Behav 2:336–340
Barr CS, Newman TK, Shannon C, Parker C, Dvoskin RL, Becker ML, Schwandt M, Champoux M, Lesch KP, Goldman D, Suomi SJ, Higley JD (2004) Rearing condition and rh5-HTTLPR interact to influence limbic–hypothalamic–pituitary–adrenal axis response to stress in infant macaques. Biol Psychiatry 55:733–738
Bartak L, Rutter M (1976) Differences between mentally retarded and normally intelligent autistic children. J Autism Child Schizophr 6:109–120
Bauman M, Kemper TL (1985) Histoanatomic observations of the brain in early infantile autism. Neurol 35:866–874
Baumeister AA, Frye GD (1984) Self-injurious behavior in rats produced by intranigral microinjection of GABA agonists. Pharmacol Biochem Behav 21:89–95
Bayne K, Dexter S, Suomi S (1992) A preliminary surrvey of the incidence of abnormal behavior in rhesus monkeys (Macaca mulatta) relative to housing conditions. Lab Anim 21:38–46
Beckett C, Bredenkamp D, Castle J, Groothues C, O’Connor TG, Rutter M (2002) Behavior patterns associated with institutional deprivation: a study of children adopted from Romania. Dev Behav Pediatr 23:297–303
Behen ME, Muzik O, Saporta AS, Wilson BJ, Pai D, Hua J, Chugani HT (2009) Abnormal fronto-striatal connectivity in children with histories of early deprivation: a diffusion tensor imaging study. Brain Imaging Behav 3:292–297
Biersdorff KK (1991) Pain insensitivity and indifference: alternative explanations for some medical catastrophes. Ment Retard 29:359–362
Biersdorff KK (1994) Incidence of significantly altered pain experience among individuals with developmental disabilities. Am J Ment Retard 98:619–631
Blake BL, Muehlmann AM, Egami K, Breese GR, Devine DP, Jinnah HA (2007) Nifedipine suppresses self-injurious behaviors in animals. Dev Neurosci 29:241–250
Blundell J, Blaiss CA, Etherton MR, Espinosa F, Tabuchi K, Walz C, Bolliger MF, Sudhof TC, Powell CM (2010) Neuroligin-1 deletion results in impaired spatial memory and increased repetitive behavior. J Neurosci 30:2115–2129
Bodfish JW, Crawford TW, Powell SB, Parker DE, Golden RN, Lewis MH (1995) Compulsions in adults with mental retardation: prevalence, phenomenology, and comorbidity with stereotypy and self-injury. Am J Ment Retard 100:183–192
Bodfish JW, McCuller WR, Madison JM, Register M, Mailman RB, Lewis MH (1997) Placebo, double-blind evaluation of long-term naltrexone treatment effects for adults with mental retardation and self-injury. J Dev Phys Disabil 9:135–152
Borthwick SA, Meyers CE, Eyman RK (1981) Comparative adaptive and maladaptive behavior of mentally retarded clients of five residential settings in three Western states. Monogr Am Assoc Ment Defic 351–359
Borthwick-Duffy SA (1994) Prevalence of destructive behaviors: a study of aggression, self-injury, and property destruction. In: Thompson T, Gray DB (eds) Destructive behavior in developmental disabilities: diagnosis and treatment. Sage Publishing, Thousand Oaks, pp 3–23
Boyd BA, Baranek GT, Sideris J, Poe MD, Watson LR, Patten E, Miller H (2010) Sensory features and repetitive behaviors in children with autism and developmental delays. Autism Res 3:78–87
Brahm NC, Fast GA, Brown RC (2008) Buspirone for autistic disorder in a woman with an intellectual disability. Ann Pharmacother 42:131–137
Breau LM, Camfield CS, Symons FJ, Bodfish JW, Mackay A, Finley GA, McGrath PJ (2003) Relation between pain and self-injurious behavior in nonverbal children with severe cognitive impairments. J Pediatr 142:498–503
Breese GR, Baumeister AA, McCown TJ, Emerick SG, Frye GD, Mueller RA (1984) Neonatal-6-hydroxydopamine treatment: model of susceptibility for self-mutilation in the Lesch–Nyhan syndrome. Pharmacol Biochem Behav 21:459–461
Breese GR, Baumeister AA, Napier TC, Frye GD, Mueller RA (1985) Evidence that D-1 dopamine receptors contribute to the supersensitive behavioral responses induced by l-dihydroxyphenylalanine in rats treated neonatally with 6-hydroxydopamine. J Pharmacol & Exp Ther 235:287–295
Breese GR, Knapp DJ, Criswell HE, Moy SS, Papadeas ST, Blake BL (2005) The neonate-6-hydroxydopamine-lesioned rat: a model for clinical neuroscience and neurobiological principles. Brain Res Brain Res Rev 48:57–73
Bromley J, Emerson E (1995) Beliefs and emotional reactions of care staff working with people with challenging behaviour. J Intellect Disabil Res 39(Pt 4):341–352
Caixeta M, Caixeta L (2005) Topiramato reduz irritabilidade e automutilação em crianças autistas [Topiramate reduces irritability and self-injuries in autistic children-Portugese]. Rev Bras Psiquiatr 27:345–346
Calabresi P, Pisani A, Mercuri NB, Bernardi G (1996) The corticostriatal projection: from synaptic plasticity to dysfunctions of the basal ganglia. Trends Neurosci 19:19–24
Campbell M, Rapoport JL, Simpson GM (1999) Antipsychotics in children and adolescents. J Am Acad Child Adolesc Psychiatry 38:537–545
Canitano R (2005) Self injurious behavior in autism: clinical aspects and treatment with risperidone. J Neural Transm 113:425–431
Canitano R, Scandurra V (2011) Psychopharmacology in autism: an update. Prog Neuropsychopharmacol Biol Psychiatry 35:18–28
Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301:386–389
Champoux M, Bennett A, Shannon C, Higley JD, Lesch KP, Suomi SJ (2002) Serotonin transporter gene polymorphism, differential early rearing, and behavior in rhesus monkey neonates. Mol Psychiatry 7:1058–1063
Chen GL, Novak MA, Meyer JS, Kelly BJ, Vallender EJ, Miller GM (2010) TPH2 5′- and 3′-regulatory polymorphisms are differentially associated with HPA axis function and self-injurious behavior in rhesus monkeys. Genes Brain Behav 9:335–347
Chengappa KN, Suppes T, Berk M (2004) Treatment of bipolar mania with atypical antipsychotics. Expert Rev Neurother 4:S17–S25
Chugani HT, Behen ME, Muzik O, Juhasz C, Nagy F, Chugani DC (2001) Local brain functional activity following early deprivation: a study of postinstitutionalized Romanian orphans. Neuroimage 14:1290–1301
Consensus Statement NIH (1989) Treatment of destructive behaviors in persons with developmental disabilities. J Autism Dev Disord 20:403–429
Corbett BA, Mendoza S, Abdullah M, Wegelin JA, Levine S (2006) Cortisol circadian rhythms and response to stress in children with autism. Psychoneuroendo 31:59–68
Crair MC, Gillespie DC, Stryker MP (1998) The role of visual experience in the development of columns in cat visual cortex. Science 279:566–570
Cromwell HC, Witte EA, Crawford CA, Ly HT, Maidment NT, King BH (1996) Pemoline produces ipsilateral turning behavior in unilateral 6-OHDA-lesioned rats. Prog Neuropsychopharmacol Biol Psychiatry 20:503–514
Cromwell HC, King BH, Levine MS (1997) Pemoline alters dopamine modulation of synaptic responses of neostriatal neurons in vitro. Dev Neurosci 19:497–504
Cromwell HC, Levine MS, King BH (1999) Cortical damage enhances pemoline-induced self-injurious behavior in prepubertal rats. Pharmacol Biochem Behav 62:223–227
Crosland KA, Zarcone JR, Lindauer SE, Valdovinos MG, Zarcone TJ, Hellings JA, Schroeder SR (2003) Use of functional analysis methodology in the evaluation of medication effects. J Autism Dev Disord 33:271–279
Cross HA, Harlow HF (1965) Prolonged and progressive effects of partial isolation on the behavior of macaque monkeys. J Exp Res Pers 1:39–49
Davenport MD, Lutz CK, Tiefenbacher S, Novak MA, Meyer JS (2008) A rhesus monkey model of self-injury: effects of relocation stress on behavior and neuroendocrine function. Biol Psychiatry 63:990–996
Dawson G (2008) Early behavioral intervention, brain plasticity, and the prevention of autism spectrum disorder. Dev Psychopathol 20:775–803
Dawson G, Rogers S, Munson J, Smith M, Winter J, Greenson J, Donaldson A, Varley J (2010) Randomized, controlled trial of an intervention for toddlers with autism: the Early Start Denver Model. Pediatrics 125:e17–e23
Devine DP (2012a) Animal models of self-injurious behaviour: an overview. In: Kobeissy FH (ed) Psychiatric disorders: methods and protocols. Humana Press, New York, pp 65–84
Devine DP (2012b) The pemoline model of self-injurious behaviour. In: Kobeissy FH (ed) Psychiatric disorders: methods and protocols. Humana Press, New York, pp 155–163
Devine DP, Symons FJ (2013) Biological vulnerability and risk for self-injury in intellectual and developmental disabilities. In: Hastings R, Rojahn J (eds) International review of research in developmental disabilities: challenging behavior. Academic Press, New York, pp 37–68
Dixon PM, Dacre I (2005) A review of equine dental disorders. Vet J 169:165–187
Dodman NH, Normile JA, Shuster L, Rand W (1994) Equine self-mutilation syndrome (57 cases). J Am Vet Med Assoc 204:1219–1223
Dominick KC, Davis NO, Lainhart J, Tager-Flusberg H, Folstein S (2006) Atypical behaviors in children with autism and children with a history of language impairment. Res Dev Disabil 28:145–162
Eapen V, Crncec R, Walter A (2013) Clinical outcomes of an early intervention program for preschool children with Autism Spectrum Disorder in a community group setting. BMC Pediatr 13:1–9
Eluvathingal TJ, Chugani HT, Behen ME, Juhasz C, Muzik O, Maqbool M, Chugani DC, Makki M (2006) Abnormal brain connectivity in children after early severe socioemotional deprivation: a diffusion tensor imaging study. Pediatrics 117:2093–2100
Epstein LJ, Taubman MT, Lovaas OI (1985) Changes in self-stimulatory behaviors with treatment. J Abnorm Child Psychol 13:281–293
Eriksson PS, Hansson E, Rönnbäck L (1991) Mu and delta opiate receptors in neuronal and astroglial primary cultures from various regions of the brain-coupling with adenylate cyclase, localisation on the same neurones and association with dopamine (D1) receptor adenylate cyclase. Neuropharmacol 30:1233–1239
Etherton MR, Blaiss CA, Powell CM, Sudhof TC (2009) Mouse neurexin-1alpha deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments. Proc Natl Acad Sci U S A 106:17998–18003
Everett GM (1976) Comparative pharmacology of amphetamine and pemoline on biogenic amine systems. Fed Proc 35:405
Favell JE, Azrin NA, Baumeister AA, Carr EG, Dorsey MF, Forehand R, Foxx RM, Lovaas OI, Rincover A, Risley T, Romanczyk RG, Russo DC, Schroeder SR, Solnick JV (1982) The treatment of self-injurious behavior. Behav Ther 13:529–554
Ferrer I, Costell M, Grisolia S (1982) Lesch-Nyhan syndrome like behavior in rats from caffeine injestion. FEBS Lett 141:275–278
Findling RL (2005) Pharmacologic treatment of behavioral symptoms in autism and pervasive developmental disorders. J Clin Psychiatry 66(Suppl 10):26–31
Finger S, Heavens RP, Sirinathsinghji DJS, Kuehn MR, Dunnett SB (1988) Behavioral and neurochemical evaluation of a transgenic mouse model of Lesch-Nyhan syndrome. J Neurol Sci 86:203–213
Fontenot MB, Padgett EE III, Dupuy AM, Lynch CR, De Petrillo PB, Higley JD (2005) The effects of fluoxetine and buspirone on self-injurious and stereotypic behavior in adult male rhesus macaques. Comp Med 55:67–74
Gabriels RL, Agnew JA, Pan Z, Holt KD, Reynolds A, Laudenslager ML (2013) Elevated repetitive behaviors are associated with lower diurnal salivary cortisol levels in autism spectrum disorder. Biol Psychol 93:262–268
Gal E, Dyck MJ, Passmore A (2009) The relationship between stereotyped movements and self-injurious behavior in children with developmental or sensory disabilities. Res Dev Disabil 30:342–352
Genovese E, Napoli PA, Bolego-Zonta N (1969) Self-aggressiveness: a new type of behavioural change induced by pemoline. Life Sci 8:513–515
Gluck JP, Sackett GP (1974) Frustration and self-aggression in social isolate rhesus monkeys. J Abn Psychol 83:331–334
Gluck JP, Sackett GP (1976) Extinction deficits in socially isolated rhesus monkeys (Macaca mulatta). Dev Psychol 12:173–174
Goldstein M, Kuga S, Kusano N, Meller E, Dancis J, Schwartz R (1986) Dopamine agonist induced self-mutilative biting behavior in monkeys with unilateral ventromedial tegmental lesions of the brainstem: possible pharmacological model for Lesch–Nyhan syndrome. Brain Res 367:114–120
Goodall J (1986) The chimpanzees of Gombe: patterns of behavior. Bellknap Press of Harvard University Press, Cambridge
Graybiel AM (2008) Habits, rituals, and the evaluative brain. Annu Rev Neurosci 31:359–387
Guess D, Carr E (1991) Emergence and maintenance of stereotypy and self-injury. Am J Ment Retard 96:299–319
Hanley GP, Iwata BA, McCord BE (2003) Functional analysis of problem behavior: a review. J Appl Behav Anal 36:147–185
Harlow HF, Harlow MK (1962) Social deprivation in monkeys. Scient Am 207:136–146
Harlow HF, Dodsworth RO, Harlow MK (1965) Total social isolation in monkeys. Proc Natl Acad Sci U S A 54:90–97
Haznedar MM, Buchsbaum MS, Wei TC, Hof PR, Cartwright C, Bienstock CA, Hollander E (2000) Limbic circuitry in patients with autism spectrum disorders studied with positron emission tomography and magnetic resonance imaging. Am J Psychiatry 157:1994–2001
Haznedar MM, Buchsbaum MS, Hazlett EA, Licalzi EM, Cartwright C, Hollander E (2006) Volumetric analysis and three-dimensional glucose metabolic mapping of the striatum and thalamus in patients with autism spectrum disorders. Am J Psychiatry 163:1252–1263
Herman BH, Hammock MK, Arthur-Smith A, Egan J, Chatoor I, Werner A, Zelnick N (1987) Naltrexone decreases self-injurious behavior. Ann Neurol 22:550–552
Herman JP, Figueiredo H, Mueller NK, Ulrich-Lai Y, Ostrander MM, Choi DC, Cullinan WE (2003) Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo–pituitary–adrenocortical responsiveness. Front Neuroendocrinol 24:151–180
Hill BK, Bruininks RH (1984) Maladaptive behavior of mentally retarded individuals in residential facilities. Am J Ment Defic 88:380–387
Hof PR, Knabe R, Bovier P, Bouras C (1991) Neuropathological observations in a case of autism presenting with self-injury behavior. Acta Neuropathol 82:321–326
Hollander E, Anagnostou E, Chaplin W, Esposito K, Haznedar MM, Licalzi E, Wasserman S, Soorya L, Buchsbaum M (2005) Striatal volume on magnetic resonance imaging and repetitive behaviors in autism. Biol Psychiatry 58:226–232
Hollander E, Soorya L, Wasserman S, Esposito K, Chaplin W, Anagnostou E (2006) Divalproex sodium vs. placebo in the treatment of repetitive behaviours in autism spectrum disorder. Int J Neuropsychopharmacol 9:209–213
Hoshino Y, Ohno Y, Murata S, Yokoyama F, Kaneko M, Kumashiro H (1984) Dexamethasone suppression test in autistic children. Folia Psychiatr Neurol Jpn 38:445–449
Hoshino Y, Yokoyama F, Watanabe M, Murata S, Kaneko M, Kumashiro H (1987) The diurnal variation and response to dexamethasone suppression test of saliva cortisol level in autistic children. Jpn J Psychiatry Neurol 41:227–235
Houpt KA (1983) Self-directed aggression: a stallion behavior problem. Equine Practice 5:6–8
Iwata BA, Dorsey MF, Slifer KJ, Bauman KE, Richman GS (1982) Toward a functional analysis of self-injury. Analysis and Intervention in Developmental Disabilities 2:3–20
Jacobson JW (1982a) Problem behavior and psychiatric impairment within a developmentally disabled population I: behavior frequency. Appl Res Ment Retard 3:121–139
Jacobson JW (1982b) Problem behavior and psychiatric impairment within a developmentally disabled population. II: behavior severity. Appl Res Ment Retard 3:369–381
Jenkins JR (2001) Feather picking and self-mutilation in psittacine birds. Vet Clin North Am Exot Anim Pract 4:651–667
Jensen JB, Realmuto GM, Garfinkel BD (1985) The dexamethasone suppression test in infantile autism. J Am Acad Child Psychiatry 24:263–265
Jinnah HA, Yitta S, Drew T, Kim BS, Visser JE, Rothstein JD (1999) Calcium channel activation and self-biting in mice. Proc Natl Acad Sci U S A 96:15228–15232
Jones IH, Barraclough BM (1978) Auto-mutilation in animals and its relevance to self-injury in man. Acta Psychiat Scand 58:40–47
Jorgensen MJ, Kinsey JH, Novak MA (1998) Risk factors for self-injurious behavior in captive rhesus monkeys (Macaca mulatta). Am J Primatology 45:187
Kahng S, Iwata BA, Lewin A (2002) The impact of functional assessment on the treatment of self-injurious behavior. In: Schroeder SR, Oster-Granite ML, Thompson T (eds) Self-injurious behavior: gene-brain-behavior relationships. American Psychological Association, Washington, DC, pp 119–131
Kasim S, Khan Z, Jinnah HA (2002) A new animal model for Lesch–Nyhan syndrome: calcium channel activation with Bay K 8644. In: Schroeder SR, Oster-Granite ML, Thompson T (eds) Self-injurious behavior: gene–brain-behavior relationships. American Psychological Association, Washington, DC, pp 289–298
Kaufman J, Plotsky PM, Nemeroff CB, Charney DS (2000) Effects of early adverse experiences on brain structure and function: clinical implications. Biol Psychiatry 48:778–790
Keebaugh AC, Sullivan RT, Thomas JW (2007) Gene duplication and inactivation in the HPRT gene family. Genomics 89:134–142
Keebaugh AC, Mitchell HA, Gaval-Cruz M, Freeman KG, Edwards GL, Weinshenker D, Thomas JW (2011) PRTFDC1 is a genetic modifier of HPRT-deficiency in the mouse. PLoS ONE 6:e22381
Kemp AS, Fillmore PT, Lenjavi MR, Lyon M, Chicz-DeMet A, Touchette PE, Sandman CA (2008) Temporal patterns of self-injurious behavior correlate with stress hormone levels in the developmentally disabled. Psychiatry Res 157:181–189
Kemper TL, Bauman ML (1993) The contribution of neuropathologic studies to the understanding of autism. Neurol Clin 11:175–187
Kendler KS, Kuhn JW, Vittum J, Prescott CA, Riley B (2005) The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression: a replication. Arch Gen Psychiatry 62:529–535
Kennedy CH (2002) Evolution of stereotypy into self-injury. In: Schroeder SR, Oster-Granite ML, Thompson T (eds) Self-injurious behavior: gene–brain-behavior relationships. American Psychological Association, Washington, DC, pp 133–143
Kies SD, Devine DP (2004) Self-injurious behaviour: a comparison of caffeine and pemoline models in rats. Pharmacol Biochem Behav 79:587–598
Kies SD, Turner CA, Lewis MH, Devine DP (2002) Effects of environmental complexity in an animal model of self-injury. Soc Neurosci Abstr 28:207.8
King BH, Au D, Poland RE (1995) Pretreatment with MK-801 inhibits pemoline-induced self-biting behavior in prepubertal rats. Dev Neurosci 17:47–52
King BH, Cromwell HC, Lee HT, Behrstock SP, Schmanke T, Maidment NT (1998) Dopaminergic and glutamatergic interactions in the expression of self-injurious behavior. Dev Neurosci 20:180–187
Kuehn MR, Bradley A, Robertson EJ, Evans MJ (1987) A potential animal model for Lesch-Nyhan syndrome through introduction of HPRT mutations into mice. Nature 326:295–298
Kumsta R, Stevens S, Brookes K, Schlotz W, Castle J, Beckett C, Kreppner J, Rutter M, Sonuga-Barke E (2010) 5HTT genotype moderates the influence of early institutional deprivation on emotional problems in adolescence: evidence from the English and Romanian Adoptee (ERA) study. J Child Psychol Psychiatry 51:755–762
Langen M, Schnack HG, Nederveen H, Bos D, Lahuis BE, de Jonge MV, van Engeland H, Durston S (2009) Changes in the developmental trajectories of striatum in autism. Biol Psychiatry 66:327–333
Lesch M, Nyhan WL (1964) A familial disorder of uric acid metabolism and central nervous system function. Am J Med 36:561–570
Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Muller CR, Hamer DH, Murphy DL (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274:1527–1531
Lesch KP, Meyer J, Glatz K, Flugge G, Hinney A, Hebebrand J, Klauck SM, Poustka A, Poustka F, Bengel D, Mossner R, Riederer P, Heils A (1997) The 5-HT transporter gene-linked polymorphic region (5-HTTLPR) in evolutionary perspective: alternative biallelic variation in rhesus monkeys. Rapid communication. J Neural Transm 104:1259–1266
Lewis MH, Gluck JP, Beauchamp AJ, Keresztury MF, Mailman RB (1990) Long-term effects of early social isolation in Macaca-Mulatta: changes in dopamine receptor function following apomorphine challenge. Brain Res 513:67–73
Lindauer SE, DeLeon IG, Fisher WW (1999) Decreasing signs of negative affect and correlated self-injury in an individual with mental retardation and mood disturbances. J Appl Behav Anal 32:103–106
Lopez JF, Akil H, Watson SJ (1999) Neural circuits mediating stress. Biol Psychiatry 46:1461–1471
Lovaas OI (1987) Behavioral treatment and normal educational and intellectual functioning in young autistic children. J Consult Clin Psychol 55:3–9
Lutz C, Well A, Novak MA (2003) Stereotypic and self-injurious behavior in rhesus macaques: a survey and retrospective analysis of environment and early experience. Am J Primatol 60:1–15
Marcus RN, Owen R, Kamen L, Manos G, McQuade RD, Carson WH, Aman MG (2009) A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder. J Am Acad Child Adolesc Psychiatry 48:1110–1119
Marinovic-Curin J, Marinovic-Terzic I, Bujas-Petkovic Z, Zekan L, Skrabic V, Dogas Z, Terzic J (2008) Slower cortisol response during ACTH stimulation test in autistic children. Eur Child Adolesc Psychiatry 17:39–43
Martin LJ, Spicer DM, Lewis MH, Gluck JP, Cork LC (1991) Social deprivation of infant rhesus monkeys alters the chemoarchitecture of the brain: I: subcortical regions. J Neurosci 11:3344–3358
Matson JL, Nebel-Schwalm M (2007) Assessing challenging behaviors in children with autism spectrum disorders: a review. Res Dev Disabil 28:567–579
Matson JL, Baglio CS, Smiroldo BB, Hamilton M, Paclawskyj TR, Williams D, Kirkpatrick-Sanchez S (1996) Characteristics of autism as assessed by the Diagnostic Assessment for the Severely Handicapped-II (DASH-II). Res Dev Disabil 17:135–143
Matson JL, Sipes M, Fodstad JC, Fitzgerald ME (2011) Issues in the management of challenging behaviours of adults with autism spectrum disorder. CNS Drugs 25:597–606
McBride SD, Hemmings A (2005) Altered mesoaccumbens and nigro-striatal dopamine physiology is associated with stereotypy development in a non-rodent species. Behav Brain Res 159:113–118
McClintock K, Hall S, Oliver C (2003) Risk markers associated with challenging behaviours in people with intellectual disabilities: a meta-analytic study. J Intellect Disabil Res 47:405–416
McCracken JT, McGough J, Shah B, Cronin P, Hong D, Aman MG, Arnold LE, Lindsay R, Nash P, Hollway J, McDougle CJ, Posey D, Swiezy N, Kohn A, Scahill L, Martin A, Koenig K, Volkmar F, Carroll D, Lancor A, Tierney E, Ghuman J, Gonzalez NM, Grados M, Vitiello B, Ritz L, Davies M, Robinson J, McMahon D (2002) Research units on pediatric psychopharmacology autism network: risperidone in children with autism and serious behavioral problems. N Engl J Med 347:314–321
McDonnell SM (2008) Practical review of self-mutilation in horses. Anim Reprod Sci 107:219–228
McEachin JJ, Smith T, Lovaas OI (1993) Long-term outcome for children with autism who received early intensive behavioral treatment. Am J Ment Retard 97:359–372
McElroy SL, Keck PE Jr, Pope HG Jr, Hudson JI (1992) Valproate in the treatment of bipolar disorder: literature review and clinical guidelines. J Clin Psychopharmacol 12:42S–52S
Mitchell GD (1968) Persistent behavior pathology in rhesus monkeys following early social isolation. Folia Primatol 8:132–147
Mitchell GD, Clark DL (1968) Long-term effects of social isolation in nonsocially adapted Rhesus monkeys. J Genet Psychol 113:117–128
Molina VA, Orsingher OA (1981) Effects of Mg-pemoline on the central catecholaminergic system. Arch Int Pharmacodyn Ther 251:66–79
Muehlmann AM, Devine DP (2007) Characterization of drug titers and neurotransmitter concentrations during induction and maintenance of pharmacologically-induced self-injurious behavior. Soc Neurosci Abstr 33:799.20
Muehlmann AM, Devine DP (2008) Glutamate-mediated neuroplasticity in an animal model of self-injurious behaviour. Behav Brain Res 189:32–40
Muehlmann AM, Lewis MH (2012) Abnormal repetitive behaviours: shared phenomenology and pathophysiology. J Intellect Disabil Res 56:427–440
Muehlmann AM, Brown BD, Devine DP (2008) Pemoline-induced self-injurious behavior: a rodent model of pharmacotherapeutic efficacy. J Pharmacol Exp Ther 324:214–223
Muehlmann AM, Wilkinson JA, Devine DP (2011) Individual differences in vulnerability for self-injurious behavior: studies using an animal model. Behav Brain Res 217:148–154
Muehlmann AM, Edington G, Mihalik AC, Buchwald Z, Koppuzha D, Korah M, Lewis MH (2012a) Further characterization of repetitive behavior in C58 mice: developmental trajectory and effects of environmental enrichment. Behav Brain Res 235:143–149
Muehlmann AM, Kies SD, Turner CA, Lewis MH, Devine DP (2012b) Self-injurious behavior: limbic disregulation and stress effects in an animal model. J Intellect Disabil Res 56:490–500
Mueller K, Hsiao S (1980) Pemoline-induced self-biting in rats and self-mutilation in the deLange syndrome. Pharmacol Biochem Behav 13:627–631
Mueller K, Nyhan WL (1982) Pharmacologic control of pemoline induced self-injurious behavior in rats. Pharmacol Biochem Behav 16:957–963
Mueller K, Saboda S, Palmour RA, Nyhan WL (1982) Self-injurious behaviour produced in rats by daily caffeine and continuous amphetamine. Pharmacol Biochem Behav 17:613–617
Mueller K, Hollingsworth E, Pettit H (1986) Repeated pemoline produces self-injurious behavior in adult and weanling rats. Pharmacol Biochem Behav 25:933–938
Munafo MR, Brown SM, Hariri AR (2008) Serotonin transporter (5-HTTLPR) genotype and amygdala activation: a meta-analysis. Biol Psychiatry 63:852–857
Newell KM, Sprague RL, Pain MT, Deutsch KM, Meinhold P (1999) Dynamics of self-injurious behaviors. Am J Ment Retard 104:11–21
Newell KM, Challis JH, Boros RL, Bodfish JW (2002) Further evidence on the dynamics of self-injurious behaviors: impact forces and limb motions. Am J Ment Retard 107:60–68
Novak MA (2003) Self-injurious behavior in rhesus monkeys: new insights into its etiology, physiology, and treatment. Am J Primatol 59:3–19
Novak MA, Harlow HF (1975) Social recovery of monkeys isolated for the first year of life: 1. Rehabilitation and therapy. Dev Psychol 11:453–465
Novak MA, Suomi SJ (1988) Psychological well-being of primates in captivity. Am Psychol 43:765–773
Novak MA, Crockett CM, Sackett GP (2002) Self-injurious behavior in captive macaque monkeys. In: Schroeder SR, Oster-Granite ML, Thompson T (eds) Self-injurious behavior: gene–brain-behavior relationships. American Psychological Association, Washington, DC, pp 151–161
Novak MA, Hamel AF, Kelly BJ, Dettmer AM, Meyer JS (2013) Stress, the HPA axis, and nonhuman primate well-being: a review. Appl Anim Behav Sci 143:135–149
Nyhan WL (1973) The Lesch-Nyhan syndrome. Ann Rev Med 24:41–60
O’Connor TG, Rutter M, Beckett C, Keaveney L, Kreppner JM (2000) The effects of global severe privation on cognitive competence: extension and longitudinal follow-up. English and Romanian Adoptees Study Team. Child Dev 71:376–390
Oliver C, Hall S, Murphy G (2005) The early development of self-injurious behaviour: evaluating the role of social reinforcement. J Intellect Disabil Res 49:591–599
Oliver C, Petty J, Ruddick L, Bacarese-Hamilton M (2012) The association between repetitive, self-injurious and aggressive behavior in children with severe intellectual disability. J Autism Dev Disord 42:910–919
O’Reilly M, Sigafoos J, Lancioni G, Edrisinha C, Andrews A (2005) An examination of the effects of a classroom activity schedule on levels of self-injury and engagement for a child with severe autism. J Autism Dev Disord 35:305–311
Ornitz EM (1974) The modulation of sensory input and motor output in autistic children. Journal of Autism and Childhood Schizophrenia 4:197–215
Osterling JA, Dawson G, Munson JA (2002) Early recognition of 1-year-old infants with autism spectrum disorder versus mental retardation. Dev Psychopathol 14:239–251
Owen R, Sikich L, Marcus RN, Corey-Lisle P, Manos G, McQuade RD, Carson WH, Findling RL (2009) Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Pediatrics 124:1533–1540
Palmen SJ, van Engeland H, Hof PR, Schmitz C (2004) Neuropathological findings in autism. Brain 127:2572–2583
Panerai S, Zingale M, Trubia G, Finocchiaro M, Zuccarello R, Ferri R, Elia M (2009) Special education versus inclusive education: the role of the TEACCH program. J Autism Dev Disord 39:874–882
Peça J, Feliciano C, Ting JT, Wang W, Wells MF, Venkatraman TN, Lascola CD, Fu Z, Feng G (2011) Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature 472:437–442
Peters JM (1967) Caffeine-induced hemorrhagic automutilation. Arch Int Pharmacodyn Ther 169:139–146
Potter WZ, Ketter TA (1993) Pharmacological issues in the treatment of bipolar disorder: focus on mood-stabilizing compounds. Can J Psychiatry 38:S51–S56
Powell SB, Newman HA, McDonald TA, Bugenhagen P, Lewis MH (2000) Development of spontaneous stereotyped behavior in deer mice: effects of early and late exposure to a more complex environment. Dev Psychobiol 37:100–108
Ratey JJ, Sovner R, Mikkelsen E, Chmielinski HE (1989) Buspirone therapy for maladaptive behavior and anxiety in developmentally disabled persons. J Clin Psychiatry 50:382–384
Reinhardt V, Rossell M (2001) Self-biting in caged macaques: cause, effect, and treatment. J Appl Anim Welf Sci 4:285–294
Richards C, Oliver C, Nelson L, Moss J (2012) Self-injurious behaviour in individuals with autism spectrum disorder and intellectual disability. J Intellect Disabil Res 56:476–489
Richdale AL, Prior MR (1992) Urinary cortisol circadian rhythm in a group of high-functioning children with autism. J Autism Dev Disord 22:433–447
Richman DM, Lindauer SE (2005) Longitudinal assessment of stereotypic, proto-injurious, and self-injurious behavior exhibited by young children with developmental delays. Am J Ment Retard 110:439–450
Ricketts RW, Goza AB, Ellis CR, Singh YN, Chambers S, Singh NN, Cooke JC (1994) Clinical effects of buspirone on intractable self-injury in adults with mental retardation. J Am Acad Child Adolesc Psychiatry 33:270–276
Rinaman L, Levitt P, Card JP (2000) Progressive postnatal assembly of limbic–autonomic circuits revealed by central transneuronal transport of pseudorabies virus. J Neurosci 20:2731–2741
Rojahn J (1984) Self-injurious behavior in institutionalized severely/profoundly retarded adults: prevalence data and staff agreement. J Behav Assessment 6:13–27
Rojahn J (1986) Self-injurious and stereotypic behavior of noninstitutionalized mentally retarded people: prevalence and classification. Am J Ment Defic 91:268–276
Rojahn J, Esbensen AJ (2002) Epidemiology of self-injurious behavior in mental retardation: a review. In: Schroeder SR, Oster-Granite ML, Thompson T (eds) Self-injurious behavior: gene-brain-behavior relationships. American Psychological Association, Washington, DC, pp 41–77
Rubia K, Overmeyer S, Taylor E, Brammer M, Williams SC, Simmons A, Bullmore ET (1999) Hypofrontality in attention deficit hyperactivity disorder during higher-order motor control: a study with functional MRI. Am J Psychiatry 156:891–896
Ruedrich S, Swales TP, Fossaceca C, Toliver J, Rutkowski A (1999) Effect of divalproex sodium on aggression and self-injurious behaviour in adults with intellectual disability: a retrospective review. J Intellect Disabil Res 43(Pt 2):105–111
Rutter M (1998) Developmental catch-up, and deficit, following adoption after severe global early privation. English and Romanian Adoptees (ERA) study team. J Child Psychol Psychiatry 39:465–476
Rutter M, Andersen-Wood L, Beckett C, Bredenkamp D, Castle J, Groothues C, Kreppner J, Keaveney L, Lord C, O’Connor TG (1999) Quasi-autistic patterns following severe early global privation. English and Romanian Adoptees (ERA) study team. J Child Psychol Psychiatry 40:537–549
Rutter ML, Kreppner JM, O’Connor TG (2001) Specificity and heterogeneity in children’s responses to profound institutional privation. Br J Psychiatry 179:97–103
Rutter M, Kreppner J, Croft C, Murin M, Colvert E, Beckett C, Castle J, Sonuga-Barke E (2007) Early adolescent outcomes of institutionally deprived and non-deprived adoptees. III. Quasi-autism. J Child Psychol Psychiatry 48:1200–1207
Ryan BC, Young NB, Crawley JN, Bodfish JW, Moy SS (2010) Social deficits, stereotypy and early emergence of repetitive behavior in the C58/J inbred mouse strain. Behav Brain Res 208:178–188
Sanchez MM, Noble PM, Lyon CK, Plotsky PM, Davis M, Nemeroff CB, Winslow JT (2005) Alterations in diurnal cortisol rhythm and acoustic startle response in nonhuman primates with adverse rearing. Biol Psychiatry 57:373–381
Sandman CA, Barron JL, Colman H (1990) An orally administered opiate blocker, naltrexone, attenuates self-injurious behavior. Am J Ment Retard 95:93–102
Sandyk R (1985) Naloxone abolishes self-injuring in a mentally retarded child. Ann Neurol 17:520
Sansom D, Krishnan VH, Corbett J, Kerr A (1993) Emotional and behavioural aspects of Rett syndrome. Dev Med Child Neurol 35:340–345
Schroeder SR, Mulick JA, Rojahn J (1980) The definition, taxonomy, epidemiology, and ecology of self-injurious behavior. J Autism Dev Disord 10:417–432
Schroeder SR, Oster-Granite ML, Berkson G, Bodfish JW, Breese GR, Cataldo MF, Cook EH, Crnic LS, DeLeon I, Fisher W, Harris JC, Horner RH, Iwata BA, Jinnah HA, King BH, Lauder JM, Lewis MH, Newell K, Nyhan WL, Rojahn J, Sackett GP, Sandman C, Symons F, Tessel RE, Thompson T, Wong DF (2001) Self-injurious behavior: gene–brain-behavior relationships. Ment Retard Dev Disabil Res Rev 7:3–12
Schwartz S (2002) Separation anxiety syndrome in cats: 136 cases (1991–2000). J Am Vet Med Assoc 220:1028–1033
Schwartz S (2003) Separation anxiety syndrome in dogs and cats. J Am Vet Med Assoc 222:1526–1532
Singh NN (1977) Prevalence of self-injury in institutionalised retarded children. N Z Med J 86:325–327
Sivam SP (1995) GBR-12909-induced self-injurious behavior: role of dopamine. Brain Res 690:259–263
Sivam SP (1996) Dopamine, serotonin and tachykinin in self-injurious behavior. Life Sci 58:2367–2375
Smith T, Groen AD, Wynn JW (2000) Randomized trial of intensive early intervention for children with pervasive developmental disorder. Am J Ment Retard 105:269–285
Spratt EG, Nicholas JS, Brady KT, Carpenter LA, Hatcher CR, Meekins KA, Furlanetto RW, Charles JM (2012) Enhanced cortisol response to stress in children in autism. J Autism Dev Disord 42:75–81
Stevens SE, Sonuga-Barke EJ, Kreppner JM, Beckett C, Castle J, Colvert E, Groothues C, Hawkins A, Rutter M (2008) Inattention/overactivity following early severe institutional deprivation: presentation and associations in early adolescence. J Abnorm Child Psychol 36:385–398
Stigler KA, Erickson CA, Mullett JE, Posey DJ, McDougle CJ (2010) Paliperidone for irritability in autistic disorder. J Child Adolesc Psychopharmacol 20:75–78
Stigler KA, Mullett JE, Erickson CA, Posey DJ, McDougle CJ (2012) Paliperidone for irritability in adolescents and young adults with autistic disorder. Psychopharmacology (Berl) 223:237–245
Suomi SJ, Harlow HF (1972) Social rehabilitation of isolate-reared monkeys. Dev Psychol 6:487–496
Symons FJ (2011) Self-injurious behavior in neurodevelopmental disorders: relevance of nociceptive and immune mechanisms. Neurosci Biobehav Rev 35:1266–1274
Symons FJ, Clark RD, Hatton DD, Skinner M, Bailey DB Jr (2003) Self-injurious behavior in young boys with fragile X syndrome. Am J Med Genet 118A:115–121
Symons FJ, Thompson A, Rodriguez MC (2004) Self-injurious behavior and the efficacy of naltrexone treatment: a quantitative synthesis. Ment Retard Dev Disabil Res Rev 10:193–200
Symons FJ, Harper VN, McGrath PJ, Breau LM, Bodfish JW (2009) Evidence of increased non-verbal behavioral signs of pain in adults with neurodevelopmental disorders and chronic self-injury. Res Dev Disabil 30:521–528
Symons FJ, Byiers BJ, Raspa M, Bishop E, Bailey DB (2010a) Self-injurious behavior and fragile X syndrome: findings from the national fragile X survey. Am J Intellect Dev Disabil 115:473–481
Symons FJ, Harper V, Shinde SK, Clary J, Bodfish JW (2010b) Evaluating a sham-controlled sensory-testing protocol for nonverbal adults with neurodevelopmental disorders: self-injury and gender effects. J Pain 11:773–781
Tiefenbacher S, Novak MA, Jorgensen MJ, Meyer JS (2000) Physiological correlates of self-injurious behavior in captive, socially-reared rhesus monkeys. Psychoneuroendo 25:799–817
Tiefenbacher S, Novak MA, Marinus LM, Chase WK, Miller JA, Meyer JS (2004) Altered hypothalamic–pituitary–adrenocortical function in rhesus monkeys (Macaca mulatta) with self-injurious behavior. Psychoneuroendo 29:501–515
Tinklepaugh OL (1928) The self-mutilation of a male macacus rhesus monkey. Journal of Mammology 9:293–300
Tordjman S, Gutknecht L, Carlier M, Spitz E, Antoine C, Slama F, Carsalade V, Cohen DJ, Ferrari P, Roubertoux PL, Anderson GM (2001) Role of the serotonin transporter gene in the behavioral expression of autism. Mol Psychiatry 6:434–439
Turner CA, Lewis MH (2002) Dopaminergic mechanisms in self-injurious behavior and related disorders. In: Schroeder SR, Oster-Granite ML, Thompson T (eds) Self-injurious behavior: gene–brain-behavior relationships. American Psychological Association, Washington, DC, pp 165–179
Turner CA, Panksepp J, Bekkedal M, Borkowski C, Burgdorf J (1999) Paradoxical effects of serotonin and opioids in pemoline-induced self-injurious behavior. Pharmacol Biochem Behav 63:361–366
Turner CA, Yang MC, Lewis MH (2002) Environmental enrichment: effects on stereotyped behavior and regional neuronal metabolic activity. Brain Res 938:15–21
Turner KC, Frost L, Linsenbardt D, McIlroy JR, Müller RA (2006) Atypically diffuse functional connectivity between caudate nuclei and cerebral cortex in autism. Behav Brain Funct 2:34
Vollmer TR (1994) The concept of automatic reinforcement: implications for behavioral research in developmental disabilities. Res Dev Disabil 15:187–207
Welch JM, Lu J, Rodriguiz RM, Trotta NC, Peça J, Ding JD, Feliciano C, Chen M, Adams JP, Luo J, Dudek SM, Weinberg RJ, Calakos N, Wetsel WC, Feng G (2007) Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice. Nature 448:894–900
Whitnall MH (1993) Regulation of the hypothalamic corticotropin-releasing hormone neurosecretory system. Prog Neurobiol 40:573–629
Willemsen-Swinkels SHN, Buitelaar JK, Nijhof GJ, Van Engeland H (1995) Failure of naltrexone hydrochloride to reduce self-injurious and autistic behavior in mentally retarded adults—double-blind placebo-controlled studies. Arch Gen Psychiatry 52:766–773
Wolff JJ, Hazlett HC, Lightbody AA, Reiss AL, Piven J (2013) Repetitive and self-injurious behaviors: associations with caudate volume in autism and fragile X syndrome. J Neurodev Disord 5:12
Wong-Riley MT (1989) Cytochrome oxidase: an endogenous metabolic marker for neuronal activity. Trends Neurosci 12:94–101
Yatham LN (2003) Efficacy of atypical antipsychotics in mood disorders. J Clin Psychopharmacol 23:S9–14
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This work was supported by grant #AR093546 from the Department of Defense Autism Research Program (ARP) of the Office of the Congressionally Directed Medical Research Programs (CDMRP).
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Devine, D.P. Self-injurious behaviour in autistic children: a neuro-developmental theory of social and environmental isolation. Psychopharmacology 231, 979–997 (2014). https://doi.org/10.1007/s00213-013-3279-2
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DOI: https://doi.org/10.1007/s00213-013-3279-2