Regression Into Autism and Other ASDs

Advances in Autism Research
April 2010

A regression into autism is said to occur when an infant or toddler who had been developing normally (a) stops normal development, and/or (b) loses skills -- and thereby comes to possess traits consistent with an autism diagnosis.

The Pubmed search autis* AND regression generates > 500 citations. Here is a small sampling.

1. Developmental regression in children with an autism spectrum disorder identified by a population-based surveillance system
Wiggins LD, Rice CE, Baio J.
Centers for Disease Control and Prevention, Atlanta, USA.
Autism. 2009 Jul;13(4):357-74.
$ http://aut.sagepub.com/cgi/reprint/13/4/357

This study evaluated the phenomenon of autistic regression using population-based data. The sample comprised 285 children who met the autism spectrum disorder (ASD) case definition within an ongoing surveillance program. Results indicated that children with a previously documented ASD diagnosis had higher rates of autistic regression than children who met the ASD surveillance definition but did not have a clearly documented ASD diagnosis in their records (17-26 percent of surveillance cases). Most children regressed around 24 months of age and boys were more likely to have documented regression than girls. Half of the children with regression had developmental concerns noted prior to the loss of skills. Moreover, children with autistic regression were more likely to show certain associated features, including cognitive impairment.These data indicate that some children with ASD experience a loss of skills in the first few years of life and may have a unique symptom profile.

2. Regression in autism: prevalence and associated factors in the CHARGE Study.
Hansen RL et al.
Ambul Pediatr. 2008 Jan-Feb;8(1):25-31.

OBJECTIVE: The aim of this study was to examine the prevalence of regressive autism and associated demographic, medical, and developmental factors by using 2 different definitions of regression based on the Autism Diagnostic Interview, Revised. METHODS: Subjects were aged 2 to 5 years, with autism (AU) or autism spectrum disorder (ASD) confirmed by standardized measures. Children with regression, defined as a) loss of both language and social skills or b) loss of either language or social skills, were compared with each other and to children with AU or ASD with no reported loss of skills on developmental and adaptive functioning. Parents reported on seizure, gastrointestinal, and sleep concerns. RESULTS: Fifteen percent (50/333) of the combined AU-ASD group lost both language and social skills; 41% (138/333) lost either language or social skills. No differences were found between the 2 samples of children with regression. Few developmental, demographic, or medical differences were found between the combined regression group and children without loss of skills, in both the larger AU-ASD sample and the more homogeneous AU-only sample. Children with regression had significantly lower communication scores than children without regression. CONCLUSIONS: The prevalence of regression in a large sample of young children with AU and ASD varies depending on the definition used; requiring loss of language significantly underestimates the frequency of developmental regression. Children with regression performed significantly less well than those without regression on 2 measures of communication, but the clinical meaningfulness of these differences is uncertain because of the small effect sizes.

3. A Prospective Study of the Emergence of Early Behavioral Signs of Autism
Ozonoff S et al.
J Am Acad Child Adol Psychiatry 2010 Mar;49(3):256-266.
http://www.jaacap.com/article/S0890-8567%2809%2900031-8/abstract

Objective: To examine prospectively the emergence of behavioral signs of autism in the first years of life in infants at low and high risk for autism.
Method: A prospective longitudinal design was used to compare 25 infants later diagnosed with an autism spectrum disorder (ASD) with 25 gender-matched low-risk children later determined to have typical development. Participants were evaluated at 6, 12, 18, 24, and 36 months of age. Frequencies of gaze to faces, social smiles, and directed vocalizations were coded from video and rated by examiners.
Results: The frequency of gaze to faces, shared smiles, and vocalizations to others were highly comparable between groups at 6 months of age, but significantly declining trajectories over time were apparent in the group later diagnosed with ASD. Group differences were significant by 12 months of age on most variables. Although repeated evaluation documented loss of skills in most infants with ASD, most parents did not report a regression in their child's development.
Conclusions: These results suggest that behavioral signs of autism are not present at birth, as once suggested by Kanner, but emerge over time through a process of diminishment of key social communication behaviors. More children may present with a regressive course than previously thought, but parent report methods do not capture this phenomenon well. Implications for onset classification systems and clinical screening are also discussed.

4. Children with autism spectrum disorders: a comparison of those who regress vs. those who do not
Matson JL, Wilkins J, Fodstad JC.
Dev Neurorehabil. 2010 Oct;13(1):37-45
http://www.ncbi.nlm.nih.gov/pubmed/20067344

OBJECTIVE: While autism spectrum disorders (ASD) constitute a group of similar conditions, considerable heterogeneity in symptoms of these neurodevelopmental disorders have been noted. One of the most important, yet least studied, of these factors is developmental regression. METHODS: One-hundred and twenty-five children were studied and broken down into the following three groups: ASD children with and without substantial regression and typically developing children. In study one, the three groups were compared on global measures of ASD symptomatology, comorbid psychopathology, challenging behaviour and social skills. In study two, the two ASD groups were compared on each individual item from the dependent measures. RESULTS: Mean age when regression occurred was 27.76 months. The ASD children as a whole differed from the typically developing controls, showing more symptoms of ASD, as would be expected, and poorer social skills, while differences were also noted between the two ASD groups. CONCLUSIONS: It was determined that children with ASD who regress present with a distinct behavioural profile when compared to children with ASD who do not regress, which included greater levels of impairment on global measures of ASD symptomatology, comorbid psychopathology, challenging behaviour and social skills.

5. Clinical characteristics associated with language regression for children with autism spectrum disorders
Jones LA, Campbell JM.
J Autism Dev Disord. 2010 Jan;40(1):54-62.
http://www.ncbi.nlm.nih.gov/pubmed/19633940

We investigated correlates of language regression for children diagnosed with autism spectrum disorders (ASD). Using archival data, children diagnosed with ASD (N = 114, M age = 41.4 months) were divided into four groups based on language development (i.e., regression, plateau, general delay, no delay) and compared on developmental, adaptive behavior, symptom severity, and behavioral adjustment variables. Few overall differences emerged between groups, including similar non-language developmental history, equal risk for seizure disorder, and comparable behavioral adjustment. Groups did not differ with respect to autism symptomatology as measured by the Autism Diagnostic Observation Schedule and Autism Diagnostic Interview-Revised. Language plateau was associated with better adaptive social skills as measured by the Vineland Adaptive Behavior Scales. Implications and study limitations are discussed.

6. Regression of language and non-language skills in pervasive developmental disorders
Meilleur AA, Fombonne E.
J Intellect Disabil Res. 2009 Feb;53(2):115-24.
http://www.ncbi.nlm.nih.gov/pubmed/19054269

BACKGROUND: As part of the pervasive developmental disorders (PDD), there is a subgroup of individuals reported to have a different onset of symptom appearance consisting of an apparently normal early development, followed by a loss of verbal and/or non-verbal skills prior to 2 years of age. This study aims at comparing the symptomatology of children who displayed a regression and often an associated intellectual disability through investigation of two types of loss, namely language and other skill regression. METHODS: This study examined the occurrence of regression in 135 children with PDD, mean age 6.3 years. The sample was composed of 80 (59.4%) children diagnosed with autism, 44 (32.6%) with pervasive developmental disorder-not otherwise specified (PDD-NOS) and 11 (8%) with Asperger syndrome. The Autism Diagnostic Interview Revised (ADI-R) was used to evaluate the type of loss and to characterise associated factors including birth rank, gender and thimerosal exposure through vaccination. RESULTS: A total of 30 (22%) subjects regressed: nine (30%) underwent language regression alone, 17 (57%) lost a skill other than language and four (13%) lost both language and another skill. Significantly higher levels of regression were found in autism (30%) compared with PDD-NOS (14%) and Asperger syndrome (0%). Children who regressed in language skills spoke at a significantly earlier age ( = 12 months) than those who did not regress in this domain ( = 26 months). Parents and interviewers consistently reported developmental abnormalities prior to the loss. ADI-R domain mean scores indicated a more severe autistic symptomatology profile in children who regressed compared with those who did not, especially in the repetitive behaviour domain. Regression was not associated to thimerosal exposure, indirectly estimated by year of birth. CONCLUSIONS: A loss of skill, present in one out of five children with PDD, is associated with a slightly more severe symptomatology as measured by the ADI-R, particularly in the repetitive behaviours domain. Furthermore, although abnormalities are often noticed by the caregivers at the time of regression, the ADI-R reveals that other atypical behaviours were in fact present prior to the onset of regression in most cases. None of the secondary factors investigated were associated with regression. In children unexposed to thimerosal-containing vaccines, the rate of regression was similar to that reported in studies of samples exposed to thimerosal, suggesting that thimerosal has no specific association with regressive autism. (But see here & here)

7. Gastrointestinal symptoms in children with an autism spectrum disorder and language regression
Valicenti-McDermott MD, McVicar K, Cohen HJ, Wershil BK, Shinnar S.
Pediatr Neurol. 2008 Dec;39(6):392-8.
http://www.ncbi.nlm.nih.gov/pubmed/19027584

Few studies have compared gastrointestinal problems in children with an autism spectrum disorder with and without a history of language regression. A cross-sectional study was conducted with structured interviews in 100 children with autism spectrum disorder, using a gastrointestinal questionnaire and a familial autoimmune questionnaire. By parental report, children with language regression more frequently exhibited an abnormal stool pattern (40% vs 12%, P = 0.006) and had an increased family history of celiac disease or inflammatory bowel disease (24% vs 0%, P = 0.001) and of rheumatoid arthritis (30% vs 11%, P = 0.03). Among 35 children with a family history of autoimmune disease, an abnormal stool pattern was reported more frequently in those with language regression (78% vs 15%, P = 0.001) than in those without. An association was observed between children with language regression, a family history of autoimmune disease, and gastrointestinal symptoms. Additional studies are needed to examine a possible shared autoimmune process.

8. Complicated relationship between autism with regression and epilepsy
Oslejsková H, Dusek L, Makovská Z, Pejcochová J, Autrata R, Slapák I.
Neuro Endocrinol Lett. 2008 Aug;29(4):558-70.
http://www.ncbi.nlm.nih.gov/pubmed/18766162

We retrospectively evaluated a set of 205 children with autism and compared it to the partial sub-set of 71 (34.6%) children with a history of regression. From 71 children with regression, signs of epileptic processes were present in 43 (60.6%), 28 (65.12%) suffered clinical epileptic seizures, and 15 (34.9%) just had an epileptiform abnormality on the EEG. In our analysis, autistic regression is substantially more associated with epileptic process symptoms than in children with autism and no history of regression. More than 90% of children with a history of regression also show IQ < 70 and reduced functionality. Functionality and IQ further worsens with the occurrence of epileptic seizures (98% of children with regression and epilepsy have IQ < 70). We proved that low IQ and reduced functionality significantly correlate rather with epileptic seizures than just sub-clinical epileptiform abnormality on EEG. Clinical epileptic seizures associated with regression significantly influence the age of regression and its clinical type. The age of regression is higher compared to children with regression without epileptic seizures (in median: 35 months of age in patients with seizures while only 24 months in other patients). Patients with seizures revealed regression after 24th months of age in 68% of cases, while patients without seizures only in 27%. However, coincidence with epilepsy also increased the occurrence of regression before the 18th month of age (23% of patients), while only 4% of patients without epilepsy revealed regression before the 18th month. Epileptic seizures are significantly associated especially with behaviour regression rather than speech regression or regression in both behaviour and speech. Also epileptic seizures diagnosed before correct diagnosis of autism were significantly associated with delayed regression (both behavioural and speech regression).

9. Regression in autistic spectrum disorders
Stefanatos GA.
Neuropsychol Rev. 2008 Dec;18(4):305-19
http://www.ncbi.nlm.nih.gov/pubmed/18956241

A significant proportion of children diagnosed with Autistic Spectrum Disorder experience a developmental regression characterized by a loss of previously-acquired skills. This may involve a loss of speech or social responsitivity, but often entails both. This paper critically reviews the phenomena of regression in autistic spectrum disorders, highlighting the characteristics of regression, age of onset, temporal course, and long-term outcome. Important considerations for diagnosis are discussed and multiple etiological factors currently hypothesized to underlie the phenomenon are reviewed. It is argued that regressive autistic spectrum disorders can be conceptualized on a spectrum with other regressive disorders that may share common pathophysiological features. The implications of this viewpoint are discussed.

This document prepared by
Teresa Binstock
Researcher in Developmental & Behavioral Neuroanatomy
April 2010