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The prodrome of autism: early behavioral and biological signs, regression, peri- and post-natal development and genetics

By Nurit Yirmiya and Tony Charman


Autism is one of the most heritable neurodevelopmental conditions and has an early onset, with symptoms being required to be present in the first 3 years of life in order to meet criteria for the ‘core’ disorder in the classification systems. As such, the focus on identifying a prodrome over the past 20 years has been on pre-clinical signs or indicators that will be present very early in life, certainly in infancy. A number of novel lines of investigation have been used to this end, including retrospective coding of home videos, prospective population screening and ‘high risk’ sibling studies; as well as the investigation of pre- and peri-natal, brain developmental and other biological factors. Whilst no single prodromal sign is expected to be present in all cases, a picture is emerging of indicative prodromal signs in infancy and initial studies are being undertaken to attempt to ameliorate the early presentation and even ‘prevent’ emergence of the full syndrome

Year: 2010
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  1. (2008). (in press). A prospective study of the emergence of early behavioral signs of autism. doi
  2. (2007). 15q11-13 GABAA receptor genes are normally biallelically Autism prodrome 64 of 89 expressed in brain yet are subject to epigenetic dysregulation in autismspectrum disorders. doi
  3. (1994). A case-control family history study of autism. doi
  4. (2008). A common genetic variant in the Neurexin superfamily member CNTNAP2 increases familial risk of autism. doi
  5. (2005). A cross-sectional study on prevalence and risk factors of disabilities in aged 0-6 years children in Beijing, China. Zhonghua Liu Xing Bing Xue Za Zhi,
  6. (1999). A genomic screen of autism: evidence for a multilocus etiology. doi
  7. (2005). A mechanism for impaired fear recognition after amygdala damage. doi
  8. (2004). A mixed epigenetic/genetic model for oligogenic inheritance of autism with a limited role for UBE3A. doi
  9. (2007). A parentreport instrument for identifying one-year-olds at risk for an eventual diagnosis of autism: the first year inventory. doi
  10. (2007). A prospective case series of high-risk infants who developed autism. doi
  11. (2007). A prospective study of response to name in infants at risk for autism. doi
  12. (2009). A prospective study of toddlers with ASD: Short-term diagnostic and cognitive outcomes. doi
  13. (2000). A screening instrument for autism at 18 months of age: A 6-year follow-up study. doi
  14. (1989). A twin study of autism in doi
  15. (2007). A unified genetic theory for sporadic and inherited autism. doi
  16. (2006). A view to regressive autism through home movies. Is early development really normal? doi
  17. (2007). Abnormal magnocellular pathway visual processing in infants at risk for autism. doi
  18. (2005). Accelerated head growth in early development of individuals with autism. doi
  19. (2008). Advances in autism genetics: on the threshold of a new neurobiology. doi
  20. (2006). Advances in autism neuroimaging research for the clinician and geneticist. doi
  21. (2006). Advancing paternal age and autism. doi
  22. American Academy of Pediatrics (2004). Is Your One-Year-Old Communicating With You? Elk Grove Village: Il.: American Academy of Pediatrics.
  23. (2009). An exploration of symmetry in early autism spectrum disorders: analysis of lying. doi
  24. (2006). Analysis of social interaction gestures in infants with autism. doi
  25. (2007). and the Council on Children with Disabilities doi
  26. (2005). Asperger syndrome: familial and pre- and perinatal factors. doi
  27. (2007). Assessing the early characteristics of autistic disorder using video analysis. doi
  28. (2002). Attentional skills during the first 6 months of age in autism spectrum disorder. doi
  29. (2009). Atypical face versus object processing and hemispheric asymmetries in 10-month-old infants at risk for autism. doi
  30. (2007). Autism and environmental influences: review and commentary. doi
  31. (2006). Autism and family home movies: a comprehensive review. doi
  32. (2004). Autism and head circumference in the first year of life. doi
  33. (1987). Autism and symbolic play. doi
  34. (1995). Autism as a strongly genetic disorder: evidence from a British twin study. doi
  35. (1994). Autism Diagnostic InterviewRevised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. doi
  36. (2002). Autism Diagnostic Observation Schedule (WPS edn.). Los Angeles: Western Psychological Services.
  37. (1999). Autism during infancy: A retrospective video analysis of sensory-motor and social behaviors at 9–12 months of age. doi
  38. (1999). Autism prodrome 56 of 89
  39. (2007). Autism spectrum disorders: developmental disconnection syndromes. doi
  40. (1993). Autism: syndrome definition and possible genetic mechanisms. doi
  41. (2005). Behavioral manifestations of autism in the first year of life. doi
  42. (2009). Behavioral outcomes of extremely low birth weight children at age 8 years. doi
  43. (2006). Behavioral theories and the neurophysiology of reward. doi
  44. (1998). Bipolar and antisocial disorders among relatives of ADHD children: parsing familial subtypes of illness. doi
  45. (1993). Blind ratings of early symptoms of autism based upon family home movies. doi
  46. (2007). Body length and head growth in the first year of life in autism. doi
  47. (2002). Brain structural abnormalities in young children with autism spectrum disorder. doi
  48. (2004). Brief report: Parental reporting of regression in children with pervasive developmental disorders. doi
  49. (2000). Brief report: recognition of autism spectrum disorder before one year of age: a retrospective study based on home videotapes.
  50. (1992). Can autism be detected at 18 months? The needle, the haystack, and the CHAT. doi
  51. (1998). Change and continuity in the development of children with autism. doi
  52. (2009). Clinical assessment and management of toddlers with suspected autism spectrum disorder: insights from studies of high-risk infants. doi
  53. (2008). Clinical assessment of autism in high-risk 18-month-olds. doi
  54. (2007). Cognitive and verbal abilities of 24-to 36-month-old siblings of children with autism. doi
  55. (2009). Common genetic variants on 5p14.1 associate with autism spectrum disorders. doi
  56. (1997). Conceptual issues in developmental screening and assessment. doi
  57. (2007). Contribution of SHANK3 mutations to autism spectrum disorder. doi
  58. (2003). Decreased N-acetylaspartate in children with familial bipolar disorder. doi
  59. (2002). Descriptive epidemiology of autism in a California population: who is at risk?
  60. (2006). Development in infants with autism spectrum disorders: a prospective study. doi
  61. (2000). Developmental regression in autism: maternal perception. doi
  62. Developmental trajectories in siblings of children with autism: cognition and Autism prodrome 62 of 89 language from 4 months to 7 years. doi
  63. (2002). Developmental trajectories of brain volume abnormalities in children and adolescents with Attention- Autism prodrome 58 of 89 Deficit/Hyperactivity Disorder. doi
  64. (2007). Disease Control and Prevention doi
  65. (1989). Disintegrative disorder or late onset autism. doi
  66. (2009). Disruption of contactin 4 in three subjects with autism spectrum disorder. doi
  67. (2008). Disruption of neurexin 1 associated with autism spectrum disorder. doi
  68. (2001). Early behavioral development in autistic children: the first 2 years of life through home movies. doi
  69. (2008). Early behavioral intervention, brain plasticity, and the prevention of autism spectrum disorder. doi
  70. (2004). Early indicators of autism spectrum disorders in the second year of life. doi
  71. (2006). Early language and communication development of infants later diagnosed with autism spectrum disorder. doi
  72. (2002). Early recognition of 1-year-old infants with autism spectrum disorder versus mental retardation. doi
  73. (1994). Early recognition of children with autism -a study of 1st birthday home videotapes. doi
  74. (2005). Early regression in social communication in autism spectrum disorders: a CPEA Study. doi
  75. (2004). Early social attention impairments in autism: Social orienting, joint attention, and attention to distress. doi
  76. (2006). Enhanced anxiety and stress-induced corticosterone release are associated with increased Crh expression in a mouse model of Rett syndrome. doi
  77. (1966). Epidemiology of autistic conditions in young children. doi
  78. (2009). Epidemiology of Pervasive Developmental Disorders. doi
  79. (2005). Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3. doi
  80. (2004). Epigenetic programming by maternal behavior. doi
  81. (2008). Epigenetic regulation and fetal programming. doi
  82. (2003). Evidence of brain overgrowth in the first year of life in autism. doi
  83. (2008). Evidenced-based comprehensive treatments for early autism. doi
  84. (2005). Factors associated with age of diagnosis among children with autism spectrum disorders. doi
  85. (1991). Family home movies: identification of early autistic signs in infants later diagnosed as autistics.
  86. (2008). fMRI investigation of working memory for faces in autism: visual coding and underconnectivity with frontal areas. doi
  87. (1993). From attention-goal psychology to belief-desire psychology: The development of a theory of mind and its dysfunction. In
  88. (2007). Functional and anatomical cortical underconnectivity in autism: evidence Autism prodrome 65 of 89 from an fMRI study of an executive function task and corpus callosum morphometry. doi
  89. (2009). Gaze behavior and affect at 6-months: predicting clinical outcomes and language development in typically developing infants and infants at-risk for autism. doi
  90. (2005). Gaze fixation and the neural circuitry of face processing in autism. doi
  91. (2008). General movements in infants with autism spectrum disorders.
  92. (2005). genes in autism and other neuropsychiatric patients. doi
  93. (1999). Genetics and child psychiatry: II Empirical research findings. doi
  94. (2008). Gross motor development, movement abnormalities, and early identification of autism. doi
  95. (2008). Growth of head circumference in autistic infants during the first year of life. doi
  96. (2008). Head circumference as an early predictor of autism symptoms in younger siblings of children with autism spectrum disorder. doi
  97. (1996). Head circumference in autism and other pervasive developmental disorders. doi
  98. (1996). Head circumference measurements in children with autism. doi
  99. (2005). How young children treat objects and people: An empirical study of the first year of life in autism. doi
  100. (2008). Identifying very early behavioral predictors of autism spectrum disorder (ASD) in NICU infants. Paper presented at the International Meeting for Autism Research,
  101. (2004). Imagery in sentence comprehension: an fMRI study. doi
  102. (2006). Impact of prenatal and/or postnatal growth problems in low birth weight preterm infants on school-age outcomes: an 8-year longitudinal evaluation. doi
  103. (2007). Increasing knowledge of PTEN germline mutations: Two additional patients with autism and macrocephaly. doi
  104. (2007). Infancy and autism: progress, prospects, and challenges. doi
  105. (1985). Infantile autism with speech loss before the age of thirty months. doi
  106. (1977). Infantile autism: a genetic study of 21 twin pairs. doi
  107. (2003). Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. doi
  108. (2007). Inhibitory control in highfunctioning autism: decreased activation and underconnectivity in inhibition networks. doi
  109. (2009). Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression. doi
  110. (2006). Is there a ‘regressive phenotype’of Autism Spectrum Disorder associated with the measles-mumps-rubella vaccine? A CPEA Study. doi
  111. (1995). Joint attention and social-emotional approach behavior in children with autism. doi
  112. (2001). Landau–Kleffner syndrome: course and correlates with outcome. doi
  113. (2003). Language and other regression: Assessment and timing. doi
  114. (2004). Language and phonological skills in children at high risk of reading difficulties. doi
  115. (2003). Less is more: meta-analyses of sensitivity and attachment interventions in early childhood. doi
  116. (2009). Longitudinal study of amygdala volume and joint attention in 2-to 4-year-old children with autism. doi
  117. (2009). Loss of language in early development of autism and specific language impairment. doi
  118. (2005). Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome. doi
  119. (2005). Magnetic resonance imaging and head circumference study of brain size in autism birth through age 2 years. doi
  120. (2000). Manual for the Child Behavior Checklist: Preschool forms and profiles.
  121. (2007). Mapping autism risk loci using genetic linkage and chromosomal rearrangements. doi
  122. (1995). Mullen scales of early learning. doi
  123. (2007). Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly. doi
  124. (2007). Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. doi
  125. (2003). Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. doi
  126. (2004). Neural correlates of facial affect processing in children and adolescents with autism spectrum disorder. doi
  127. (2008). Neurexin 1alpha structural variants associated with autism. doi
  128. (2004). New tool helps physicians diagnose autism early.
  129. (2001). No evidence for a new variant of measles-mumps-rubella-induced autism. doi
  130. (2009). Novel PTEN mutations in neurodevelopmental disorders and macrocephaly. Clinical Genetics: An doi
  131. (2005). Object play in infants with autism: methodological issues in retrospective video analysis. doi
  132. (2001). Obstetric complications and risk for severe psychopathology in childhood.
  133. (2001). On the allelic spectrum of human disease. doi
  134. (2005). Parental report of the early development of children with regressive autism: the delays-plus-regression phenotype. doi
  135. (2008). Perinatal and maternal risk factors for autism spectrum disorders in New South doi
  136. (2004). Perinatal factors and the development of autism: a population study. doi
  137. (2002). Perinatal risk factors for infantile autism. doi
  138. (2008). Positive screening for autism in ex-preterm infants: prevalence and risk factors. doi
  139. (2009). Positive screening on the modified checklist for autism in toddlers (M-CHAT) in extremely low gestational age newborns. doi
  140. (2002). Practitioner Review: Diagnosis of autism spectrum disorder in 2-and 3-year-old children. doi
  141. (2007). Prenatal and perinatal risk factors for autism: a review and integration of findings. doi
  142. (2008). Prenatal stress and risk for autism. doi
  143. (2003). Prevalence of autism and parentally reported triggers in a north east London population. doi
  144. (2006). Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: the Special Needs and Autism Project (SNAP). doi
  145. (2004). Prospective study of neurological abnormalities in offspring of women with psychosis: birth to adulthood. doi
  146. (2001). PTEN mutation in a family with Cowden syndrome and autism. doi
  147. (2007). Rate of head circumference growth as a function of autism diagnosis and history of autistic regression. doi
  148. (2007). Rate of head growth decelerates and symptoms worsen in the second year of life in autism. doi
  149. (2005). Recent advances in fragile X: a model for autism and neurodegeneration. doi
  150. (2007). Recent advances in the genetics of autism. doi
  151. (2008). Regression in autism: prevalence and associated factors in the CHARGE study. doi
  152. (1997). Regression in pervasive developmental disorders: seizures and epileptiform electroencephalogram correlates. doi
  153. (2008). Regression, developmental trajectory and associated problems in disorders in the autism spectrum: The SNAP study. doi
  154. (2007). Response to joint attention in toddlers at risk for autism spectrum disorder: a prospective study. doi
  155. (2009). Retrosplenial cortex connectivity in schizophrenia. doi
  156. (2005). Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status. doi
  157. (2002). Role of genotype in the cycle of violence in maltreated children. doi
  158. (1996). Screening for autism in a large population at 18 months of age: An investigation of the CHAT (Checklist for Autism in Toddlers).
  159. (2006). Screening for autism spectrum disorders in children 14-15 months. I: The development of Autism prodrome 79 of 89 the Early Screening of Autistic Traits Questionnaire (ESAT). doi
  160. (2006). Screening for autistic spectrum disorder in children aged 14-15 months. II: Population screening with the early screening of autistic traits questionnaire (ESAT). Design and general findings. doi
  161. (1990). Sensorimotor and action development in autistic children from infancy to early childhood. doi
  162. (2001). Short-term outcomes of children with febrile status epilepticus. doi
  163. (2007). Social and communication development in toddlers with early and later diagnosis of autism spectrum disorders. doi
  164. (2007). Stereotyped motor behaviors associated with autism in high-risk infants: a pilot videotape analysis of a sibling sample. doi
  165. (2007). Strong association of de novo copy number mutations with autism. doi
  166. (2006). Structural variation in the human genome. doi
  167. (2008). Structural variation of chromosomes in autism spectrum disorder. doi
  168. (1998). Symptoms of pervasive developmental disorders as observed in prediagnostic home videos of infants and toddlers. doi
  169. (2008). The Autism Observation Scale for Infants: scale development and reliability data. doi
  170. (2007). The broad autism phenotype questionnaire. doi
  171. (2008). The early development of joint attention in infants with autistic disorder using home video observations and parental interview. doi
  172. (2005). The etiology of autism: pre-, peri-, and neonatal factors. doi
  173. (2007). The first year inventory: retrospective parent responses to a questionnaire designed to identify one-year-olds at risk for autism. doi
  174. (2009). The genetic and neurobiologic compass points toward common signaling dysfunctions in autism spectrum disorders. doi
  175. (2004). The genetics of autism. doi
  176. (2007). The genetics of autistic disorders and its clinical relevance: a review of the literature. doi
  177. (1993). The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research. Geneva, Switzerland: World Health Organization. doi
  178. (2008). The Modified Checklist for Autism in Toddlers: a follow-up study investigating the early detection of autism spectrum disorders. doi
  179. (2001). The Modified Checklist for Autism in Toddlers: an initial study investigating the early detection of Autism prodrome 74 of 89 autism and pervasive developmental disorders. doi
  180. (2007). The new neurobiology of autism: cortex, connectivity, and neuronal organization. doi
  181. (2008). The onset of autism: patterns of symptom emergence in the first years of life. doi
  182. (1967). The Siege. N.Y.: Harcout Brace and World.
  183. (2007). The very early autism phenotype. doi
  184. (2008). Toward a better identification and treatment of schizophrenia prodrome. doi
  185. (1980). Toward objective classification of childhood autism: Childhood Autism Rating Scale (CARS). doi
  186. (1992). Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. doi
  187. (2001). Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study. doi
  188. (2008). Validation of the Infant-Toddler Checklist as a broadband screener for autism spectrum disorders from 9 to 24 months of age. doi
  189. (2005). Validation of the phenomenon of autistic regression using home videotapes. doi
  190. (2002). Validity and reliability of the Communication and Symbolic Behavior Scales Developmental Profile with very young children. doi
  191. (2007). Visual fixation patterns during reciprocal social interaction distinguish a subgroup of 6-month-old Autism prodrome 70 of 89 infants at-risk for autism from comparison infants. doi
  192. (1982). Vulnerable but not invincible: A longitudinal study of resilient children and youth.
  193. (2009). What are infant siblings teaching us about autism in infancy? doi
  194. (1992). World Health Organization. doi
  195. (2004). X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. doi