autos (self) ismos (a suffix of action or of state)

Size: px

Start display at page:

Download "autos (self) ismos (a suffix of action or of state)"

Gordon Hamilton
5 years ago
Views:

1 Lenka Zedkova Psychiatry Resident PGY4 Review of autism and the search for the causes from a historical perspective Childhood vaccines and autism The impact of the suggested causal association Why does the debate continue? autos (self) ismos (a suffix of action or of state) The term first used by Bleuler to describe self-centered thinking leading to withdrawal in schizophrenia

Leo Kanner re-introduced the term in a 1943 paper, describing 11 children exhibiting extreme autistic aloneness Autistic Disturbances of Affective Contact, Nervous Child 2 (1943): 217-250 Peculiar

2 Leo Kanner re-introduced the term in a 1943 paper, describing 11 children exhibiting extreme autistic aloneness Autistic Disturbances of Affective Contact, Nervous Child 2 (1943): Peculiar language Social isolation Insistence on sameness Motor stereotypies Some misconceptions in this paper were hard to overcome: normal or higher than normal IQ without neurological impairments parents from higher social classes parents demeanours contribute to autism

3 Psychogenic theory: Autism is a reaction to parental rejection Kanner described parents as well educated, aloof, cold, obsessive, disdainful of frivolity, emotionally detached Psychoanalytic theories were very influential Bruno Bettelheim used the term refrigerator mothers Rejection of the psychogenic model in the 1960 s: Reports of the parents characteristics were anecdotal in nature Parents of autistic children did not differ from the normal profile on the MMPI Some parental characteristics can be a result rather than the cause of the disorder Sampling bias in Kanner s group of parents Research has shifted from the parents behavior to organic causes Autism was re-conceptualized as a neurodevelopmental condition Genetic twin, family pedigree and imaging studies strongly point to the importance of genetics Broader phenotype may be inherited

4 Greater intellectual and language impairment Kanner s original criteria aloofness and indifference to others resistance to change in repetitive elaborate routines features present by 24 months Higher functioning Triad of impairments: social interaction communication flexible social imagination (Wing and Gould, 1979) DSM-III (1980): Pervasive developmental disorders (PDD) Infantile autism: onset before 30 months Childhood onset PDD: onset between 30 months and 12 years DSM-III-R (1987): Autistic disorder PDD not otherwise specified DSM-IV and DSM-IV-TR (1994, 2000) Introduction of new subgroups Autistic disorder Rett s disorder Childhood disintegrative disorder Asperger s disorder PDD NOS

5 Qualitative impairment in social interaction Qualitative impairment in communication Restrictive repetitive and stereotyped patterns of behavior, interests and activities Delays or abnormal functioning in either Social interaction Language as used in social communication Symbolic or imaginative play Onset prior to age 3 years The effect of diagnostic criteria on the rate of autism: Criteria used in studies Number of studies Mean rate of autism per Kanner DSM-III DSM-III-R DSM-IV/ICD DSM-IV/ICD-10* *Studies in Assessment of autism spectrum disorders Goldstein, Naglieri, Ozonoff, (Eds), 2008 Younger age at diagnosis Improved detection in schools and developmental evaluation centers (increased awareness) Actual increase in incidence? notion of an autism epidemic especially among parents of autistic children

6 Frustration among parents Slow pace of research on the causes of autism Evidence of genetic involvement and neurological abnormalities offers no quick fix Notion of an autism epidemic Search for environmental factors constituents of diet (casein, gluten) antibiotics allergies environmental pollutants vaccines Wakefield et al (Lancet, 1998): Described chronic enterocolitis and ileallymphoid-nodular hyperplasia in 12 children with developmental regression, mostly autism. In 8 children parents or pediatricians believed that MMR vaccine contributed to the behavioral symptoms (onset within 2 weeks post-vaccine) A regressive variant of autism, autistic enterocolitis was proposed Lancet 1998:351:

7 Measles virus nucleic acid sequences were found in the blood cells and intestines of some of the affected children. (Kawashimi et al 2000; Uhlmann et al 2002) No measles virus genome sequences detected in leukocytes of autistic children after MMR vaccinations. (D Souza et al 2006) Comparison of 3 samples: 1. Epidemiological data on 96 children with PDD immunized with MMR born between Clinical sample of 68 children with PDD immunized with MMR born between Clinical sample of 98 probands with PDD not immunized with MMR born between (Fombonne and Chakrabarti 2001)

8 The mean age of first parental concern for autistic children who were exposed to MMR (19.3 and 19.2 months) was not closer to the mean immunization age than in children who were not exposed to MMR (19.5 months) The rate of developmental regression in the post- MMR samples was similar to that in the pre-mmr sample (15.6% vs 18.4%). In the post-mmr samples, there was no association between developmental regression and GI symptoms Conclusion: No evidence for a new MMR-induced regressive variant of autism (Fombonne and Chakrabarti, 2001) Ecological studies comparing temporal trends in MMR vaccination coverage and corresponding trends in autism prevalence did not find a positive correlation: UK (Kaye et al 2001) USA (Dales et al 2001) Japan (Honda et al 2005) Montreal, Canada (Fombonne et al 2006)

9 (Dales et al, JAMA 2001) Epidemiological studies A retrospective cohort study from Denmark over children including over not vaccinated with MMR. Relative risk associated with MMR 0.92 for autistic disorder 0.83 for other autism spectrum disorder (ICD-10). (Madsen et al 2002) Ten of the original 13 authors published a formal retraction of the conclusion of the original 1998 article in The Lancet Murch SH et al, Retraction of an interpretation. Lancet 363:750 This followed a disclosure that A. Wakefield was advising and paid by lawyers of parents who alleged that immunizations caused their children s autism

10 Thimerosal: Ethylmercury bound to thiosalicylate (50% mercury by weight) Used as a germicide in pre-antibiotic era Patented in 1928 by Eli Lilly Well tolerated by patients during an epidemic of meningococcal meningitis Thimerosal: Incorporated in many biological products in the 1920 s as a preservative In 1940 incorporated into diphteria toxoid, meningococcal serum and pertussis vaccine FDA concluded in 1976 that no dangerous quantity of mercury was likely to be received from vaccines over a lifetime Thimerosal: In 1997 the FDA assessed drugs and foods for mercury content It was found that by 6 months infants could receive up to 187.5μg of ethylmercury, exceeding the safety guidelines for methylmercury 3 doses of diphteria-tetanus-pertussis, 3 doses of Haemophilus influenzae type b 3 doses of hepatitis B vaccine

11 Methylmercury: Minamata Bay Disaster (1960 s) congenital Minamata disease: spasticity, seizures, deafness, severe mental retardation Iraq disaster (1971): 459 deaths Bread from seed wheat contaminated by fungicide Continuum of toxicity in infants Studies of children exposed to methylmercury in utero: effects on speech, dexterity, attention and visuospatial abilities (Grandjean et al 1999) In a joint statement in 1999 the American Academy of Pediatrics and the Public Health Service called for the removal of thimerosal from infant vaccines as a precautionary measure Parents should not worry about the safety of vaccines. The current levels of thimerosal will not hurt children but reducing those levels will make safe vaccines even safer. This removal attracted attention to thimerosal: Many parents of autistic children saw thimerosal as the cause of the autism epidemic

12 Country, year published Source Analysis, Years of study UK 2004 Andrews et al Retrospective cohort UK 2004 Heron et al Prospective cohort USA 2003 Verstraeten et al Retrospective cohort Denmark 2003 Hviid et al Retrospective cohort USA 2003 Geier and Geier Retrospective cohort USA 2003 Geier and Geier Retrospective cohort Sweden/Denmark 2003 Stehr-Green et al Ecological Denmark 2003 Madsen et al 2003 Ecological USA 2008 Schechter and Grether Ecological Rigorous review of epidemiological studies reporting original data: The preponderance of epidemiological evidence does not support an association between thimerosal-containing vaccines and ASD. Studies that support an association are of poor quality and cannot be interpreted. (Parker et al, Pediatric 2004) Pharmacokinetic studies half-life of ethylmercury (7 days) is significantly shorter than that of methylmercury (up to 70 days) post-vaccination levels in infants are not in the range of known toxicity, making neurological damage in vaccines unlikely. (Stajich et al 2000; Pichichero et al 2002)

13 Standardized tests assessing 42 neuropsychological outcomes were administered to1047 children between the ages 7 and 10 years Association between their performance and the exposure to thimerosal during the prenatal, the neonatal (birth to 28 days) and the first 7 months of life was assessed (N Engl J Med 2007; 357: ) Vaccines and immune globulins were identified HMO computerized immunization records paper medical records personal immunization records and maternal interviews Prenatal exposure: All known exposure of the mother to thimerosal-containing vaccines and immune globulins in pregnancy Outcome measures: Speech and language indexes Verbal memory Achievement Fine motor coordination Visuospatial ability Attention and executive functioning Behavior regulation Tics General intellectual functioning

14 The detected associations between performance and exposure to thimerosal were small, equally divided between positive and negative The study did not support a causal link between early exposure to thimerosal and deficits in neuropsychological functioning at the age of 7 to 10 years. In 2004 the Immunization Safety Review Committee of the Institute of Medicine rejected a causal realtionship between MMR vaccine and thimerosal-containing vaccines and autism. McCornick M et al. Report of the Institute of Medicine. Immunization Safety Review. Vaccines and Autism. Washington DC: National Academy Press; 2004 Public Health-UK Dramatic decrease in the proportion of children given the MMR vaccine in the UK. The MMR immunization program was introduced in 1988 in the UK MMR coverage was 92% in % in % in 2004 The number of cases of measles in the UK increased from 56 in 1998 to 971 in 2007, including 1 death.

15 Smith et al, Pediatrics, 2008 Public Health - Canada National Immunization Survey reported 91% MMR coverage rates in 2006 (94% in 1997). Only Manitoba has a formal system that requires physicians to record in a province-wide registry every immunization administered. Less than 70% of Canadian 2-year olds receive their full range of vaccines Public Health After the announcement that thimerosal should be removed from vaccines, about 10% of hospitals suspended use of the hepatitis B vaccine for all newborns (including those born to seropositive mothers) A 3-month-old child born to a seropositive mother died in Michigan Infants who acquire hepatitis B infection at birth have a high chance of developing chronic hepatitis (90%), with a significant risk of liver cancer (25%).

16 Public Health About autistic children in the US receive mercury-chelating agents every year. A 5-year old boy in Pittsburgh died from arrhythmia caused by the injection of the chelating agent EDTA. (Offit, 2007) Some influenza vaccines still contain thimerosal; some parents are reluctant to have their children receive the flu shot Legal battles In the US more than 5000 families of autistic children have filed claims with the federal Vaccine Injury Compensation Program (VICP) launched in 1988 To be compensated, the claimant must show a causal connection between a vaccine and a serious condition Families of autistic children are backed up by support groups, organized personal injury lawyers, prominent senators and congressmen, antivaccine organizations Hannah Poling case Autism is a life-long neurodevelopmental disorder, which occurs along a broad continuum of severity It has a strong genetic component and is associated with neurological defects which may occur early in embryonic development. Some parents, frustrated with the slow pace of mainline research offering no cure, continue to search for environmental causes and popularized the concept that autism is epidemic and caused (at least some forms) by certain vaccines

17 Despite the accumulation of scientific evidence rejecting a causal association between vaccines and autism, and the negative impact of this controversy on public health, the debate continues, facilitated by media, lawyers, politicians, celebrities, and the atmosphere of distrust between some parents and professionals in the autism field.

AUTISM SPECTRUM DISORDER: DSM-5 DIAGNOSTIC CRITERIA. Lisa Joseph, Ph.D.

AUTISM SPECTRUM DISORDER: DSM-5 DIAGNOSTIC CRITERIA Lisa Joseph, Ph.D. Autism Spectrum Disorder Neurodevelopmental disorder Reflects understanding of the etiology of disorder as related to alterations