Discuss Whether Nature or Nurture Contribute to Special Needs in Children? Select One Type of Developmental Difficulties / Special Needs: Autism

There is an ongoing debate about whether human afflictions or conditions are caused by genetic / innate factors and inherited (nature) or influenced by environmental factors (nurture). For some psychologists human characteristics are fixed, whilst others argue that our characteristics are susceptible to environmental factors and can be changed. Finding answers to these questions are at the center of ‘nature versus nurture’ debates.

This essay discusses the part that nature and nurture plays in the etiology of autism spectrum disorder in children. The essay begins with brief information on how autistic spectrum disorder is conceptualized.

Levy et al (2009, pp. 1627–1638)  explains autism spectrum disorder (ASD) to include  “pervasive neurodevelopmental disorders that involve moderately to severely disrupted functioning in regard to social skills and socialisation, expressive and receptive communication, and repetitive or stereotyped behaviours and interests”. ASD is explained to occur gradually and take various forms including physical limitations, cognitive deficits and learning difficulties.  

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 An early attempt to explain autism linked the etiology of autism to bad parenting (Kanner, 1943). Parental coldness, lack of empathy and care and overprotectiveness were explained to be some of the contributory factors to the development of autism in children. Further attempts to explain the causes of autism however rejected the Kanner’s explanation and linked autism to adverse biological factors (Hulme and Snowling, 2009); Arora et al, 2017; Grandjean and Landrigan, 2006).

Grandjean and Landrigan (2006, p.2167–2178) research linked foetal and early exposure to toxic metals, dietary and nutritional deficiencies to be some of the contributory factors of ASD. Grabrucker (2012) and Modabbernia et al (2016) also explained exposure to adverse environmental conditions to be some of the etiological factors of ASD. Modabbernia et al (ibid) found exposure to or presence of various metals in the body to affect brain development and autism.  Krakowiak et al (2012) also found mothers with metabolic conditions, obesity, hypertension, or diabetes to frequently give birth to children with ASD.  Gardener et al (2009) meta-analysis research of pregnant women with diabetes found diabetes to produce possible autistic risk in children.

Hobson and Bishop (2003) and Mukaddes et al (2007) studies on the other hand found several hereditary autistic spectrum features in mentally and visually impaired children. This was researched by Landrigan (2010) and they found biological / genetic and environmental conditions to be familial factors in the causation of autism (Bailey et al, 1995) Folstein and Rosen-Sheidley (2001) research also found autism in monozygotic twins to be as high as 70% and when the broader phenotype of autism was considered, the autism concordance in monozygotic twins were found to be approximately 90%. Concordance rates for autism in dizygotic twins were however no higher than among singleton siblings.

In the nature and nurture debate, the risk of children developing autistic conditions has also been linked to parents age (Croen et al,2007;  Grether et al, 2009;  Reichenberg et al, 2010).  Possible risk of children with parents with advanced age developing autism was found by Gardener et al (2009), Shelton et al (2010), Sandin et al (2012) and Kong et al (2012).The latter study revealed children with older fathers to be more predisposed to autism and explained this as due to the fact that males transmit a much higher number of mutations to their children than women and are therefore the dominant parent in determining the number of ‘de novo mutations’ in children.

Other risk factors are cited to involve pregnancy complications (Gardener et al, 2009; Enstrom et al, 2009). Pro-inflammatory cytokines arising from maternal autoimmunity and aberrant neuronal growth are for example explained to cause foetal brain disorders in children (Buehler, 2011). Birth complications, trauma or ischemia, maternal obesity and diabetes are also said to produce higher risk of ASD (====) 

======meta-analysis of epidemiological studies involving 25,687 ASD cases and 8,655,576 control sample found association between advanced maternal age of parents and possible risk of autism in their children.

In the nature vs nurture debate, there is also the view that autism are caused by vaccines that children receive at an early age. Vaccines were proposed to cause ASD in the 1990s. Wakefield et al (1998) (gastroenterologist) cohort researches published in the Lancet argued that children vaccinated with the measles-mumps-rubella (MMR) vaccines were more likely to have bowel disease. They argued that linked vaccine viruses to cause disruption of intestinal tissues, bowel and neuropsychiatric diseases and produce autism. They claimed that they found evidence in many of the 12 cases they studied about measles virus in the digestive systems of children and that the children exhibited autism symptoms after MMR vaccination (Thompson et al, 1995). Wakefield et al recommended for the suspension of MMR vaccines to be suspended and a single-antigen vaccinations to be given. Fudenberg (1996) in a small pilot study also linked MMR vaccines to autism as did Gupta (2000) in a review of possible treatments for autism. Press coverage in Britain and the United States about this causal relationship gave rise to parents delaying or completely refusing MMR vaccination for their children (Offit, 2008). 

Subsequent studies however found no link between MMR and autism nor confirmed Wakefield’s findings (Immunisation Safety Review Committee, Institute of Medicine 2001; Children’s Hospital of Philadelphia Vaccine Education Centre, 2019). The Editors of the Lancet (2010) including Dr Horton argued in 2004 television interview that Wakefield’s research was “fatally flawed.” (Laurance, 2004). Wakefield was found to have filed for a patent for a single-antigen measles vaccine in 1997 and accused of conflict of interest (Deer, 1997; 2011).  This led to the Britain General Medical Council banning Dr Wakefield from practicing medicine in Britain on the basis that he had shown “callous disregard” for children in the course of his research (Meikle and Boseley, 2010). Other vaccines such as thimerosal (mercury-containing vaccines) however continued to be linked to autism but thimerosal was not found in MMR vaccines or as antimicrobial agents (World Health Organization, 2011). Studies conducted by Danish researchers on vaccines and autism in children (cited in Hviid et al, 2019) also rejected the linkage of vaccines to autism. The Danish researchers analysed data from a sample of more than 650,000 children but found no overall increase of autism among children who received vaccines. This contradicted claims by anti-vaccination advocates that autism is caused by MMR vaccine. MMR vaccination was therefore not regarded as posing any risk factor for the development of autism (Doja and Roberts, 2006). Miller and Reynolds, 2009 and Flaherty, 2011) used evidence based information from several rigorous scientific researches in the examination of the association between vaccines and autism and found no compelling link.

The rising rates of autism (Centres for Disease Control and Prevention, 2019) caused critics to shift their attention to mercury exposure and other connections when other vaccines were added to children’s immunisation schedule. Aluminium adjuvant in some vaccines was explained as a potential cause of autism. The amounts of aluminium used in vaccines were however found to be very small in comparison to other exposures such as in breast milk (The Children’s Hospital of Philadelphia, 2018) and no compelling evidence of an association between exposure to aluminium and autism was however found (DeStefano et al, 2013).

The use of certain medication by pregnant women has also been linked with ASD in children but researchers found mixed results. Gentile (2014) study for evidence of association between the use of maternal valproate medication for epilepsy and bipolar disorder found children of mothers that use the medication to have poor neuro-development but this finding was complicated by several confounders including dosage. Kobayashi et al (2016) review of five case-control cohort studies also found 50% increase of risk of ASD in children of mothers who took Serotonin Reuptake Inhibitor (SRI) but when the researchers conducted a sensitivity analysis by comparing SRI-exposed group to SRI non-exposed group in mothers with psychiatric conditions, they found no significant increase in risk of ASD in offspring. This led the researchers to conclude the relation between SRI and ASD to be largely due to confounding factors. Rosen et al (2015) meta-analysis of 15 studies also found no association between maternal smoking and risk of ASD in children. This lack of association was however complicated by postnatal assessment of prenatal smoking that found a slight increase in risk but this was attributed to possible recall bias.

Several studies sought to find whether there is association between nutritional elements such as folic acid or vitamin D produce ASD risk (Sharp et al 2013; Babaknejad et al 2016) and autism. A meta-analysis by Sharp et al (ibid) found significantly lower protein and calcium intake in children with ASD but the estimates were found to be inconsistent.  A meta-analysis of 12 studies by Babaknejad et al (2016) also found significantly lower zinc levels in children with ASD. Wang et al. (2016) meta-analysis of 11 vitamin D and ASD studies also found significantly lower levels of serum 25-hydroxy vitamin D in subjects with ASD than those in controls. Gastrointestinal abnormalities and “Leaky gut syndrome” are also cited as risk factors for autism based on pregnant mothers reporting gastrointestinal disturbances (Liu et al., 2005; Lebba et al., 2011).  Studies on nutritional elements such as deficiency in folic acid and omega 3 however showed inconclusive detrimental effects on ASD. Whilst Castro et al (2016) systematic review of evidence for folic acid and risk of ASD found some association between folate deficiency and ASD-like traits, the self-report findings in the majority of the studies were found to be inconsistent.

Other studies enquired about whether exposure to toxic air pollution, thimerosal (ethylmercury), inorganic mercury, and heavy metals cause ASD. Lam et al (2016) meta-analysis of researches found a small association between prenatal exposure to particular matters and risk of ASD but the risk was found to be inconsistent across studies when exposure was measured via indirect methods. De Palma et al (2012) meta-analysis studies compared hair concentration of heavy metals between patients with ASD and a control sample and found little association of hair metal concentration of mercury, copper, cadmium, selenium, and chromium with ASD. Whilst significant higher levels of lead were found in the hair of patients with ASD than the control group, the estimates were found to be inconsistent across the studies analysed. Yoshimasu et al (2014) also found no association between thimerosal exposure and ASD and suggested that early life exposure to mercury by vaccination did not increase the risk of ASD. The researchers however concluded that exposure to inorganic mercury in the environment might be associated with an increased risk of ASD.

Autistic children are known to manifest learning difficulties (===)  but Bandura (1977) social learning theory and Bowlby (1969) attachment theory depart from purely genetic or biological causes for this and cites environmental factors including poor attachment or bonding relationship between a child and mother/caregiver, lack of social interactions, observation and imitation to influence children’s learning and acquisition of knowledge.  This theory explains a person to grow through positive attachment relations with parents during developmental stages, become more aware and learns about their surroundings (Armstrong, 2012, p77). Froehlich (2013) revisited this environmental proposition and revealed that autistic twins mimics each other‘s behaviours and actions and that separation causes autistic twins to manifest differential and distinctive behaviours. This finding argues about the prominent role that environmental exposures play in the causation of autism (Daniels, 2006). Environment factors are argued to act in concert with inherited susceptibilities and epigenetic to produce ASD (Mehler, 2008; Nikehasani, 2018).

Karimi et al (2017) research on environmental factors considered the link between poor families’ economic, social, educational and psychological factors and autism in children (Lee et al, 2008).  Families experiencing poverty and challenging life conditions including financial problems were found to experience anxieties and psychological stresses (Adler and Newman, 2002). These and inaccessible health care facilities were found to impair the health and welfare of families (Kaczynski and Henderson, 2008). Children of pregnant women exposed to stressors and anxieties were found to be susceptible to autism (Ladd et al, 2004). Other human and animal studies have also found prenatal and perinatal stressors to activate hypothalamic-pituitary-adrenal (HPA) axis on postnatal behaviour in human and animal studies (Ward, 1990; Beversdorf et al., 2005) argued that HPA act as possible cause, type and severity of autism in children. Significant changes were found in the regulation of the HPA axis of animals, regardless of the specific prenatal stressor studied.

Prenatal stressors were also found to produce behaviours resembling symptoms of autism (Kinney et al., 2008). Prenatal exposure to stress, hormones and psychological stress of mother rhesus monkeys were found to result in abnormalities in postnatal immune function in infants and late childhood (Coe et al, 1999). Whilst immune functions such as proliferation of lymphocytes, natural killer cell activity and production of cytokines might decrease or resist viral and bacterial infections, pathological mechanisms of prenatal infection and stress were found to increase the risk of autism. Stress was said to produce complications of during child birth and linked to greater risk of hypoxia and cerebral haemorrhage in the new-born.  Limperopoulos et al (2007) study for example revealed that children that survived cerebellar haemorrhagic injury had a significantly high risk of developing autism. What the information on maternal stressors indicates is that children born with autism were predisposed to a variety of adverse prenatal factors that act as contributory factors of ASD development.

Autism has also been linked to parental use of opiates (Sahley and Panksepp, 1987). The opiate proposition explains digestive disorder and gluten to react or convert to opioid peptides gliadorphin and casomorphin to influence the development of autism in children, more evidence (e.g. in control studies) are however needed to verify gastrointestinal pathologies.

In the nature and nurture debate, abnormal melatonin synthesis, most particularly abnormalities in melatonin secretion is said to play a significant part in the development of autism. Melatonin is an endogenous neurohormone produced predominantly in the pineal gland and levels of melatonin or melatonin derivatives often below average in individuals have been proposed to cause ASD (Rossignol and Frye, 2011). Cortesi (2010) argued that as low melatonin level can be found in healthy individuals, it cannot be considered as a direct cause of ASD, but a susceptibility factor. Cortesi advised for the proposed effects and link of maternal melatonin deficiency on offspring to  ASD should be subjected to further investigation.

Children with ASD have also been found to have a higher prevalence of sleep abnormalities including longer “sleep onset latency,” frequent night-time awakenings and reduced sleep duration (Rossignol and Frye, ibid). Cortesi et al (2010) however explain sleeping problems to sometimes occur as a result of complex interactions between genetic and social/environmental factors.

Mothers’ social isolation, lack of social interaction and breakdown in communications with social networks are explained to have negative affect or endanger pregnant mother’s psychological state and embryo’s health can cause ASD risk. (Samadi and McConkey, 2011).

Lee et al (2008) evaluated studies on the relationship between parental education and risk of autism in children and found variable conclusions including low levels and differential correlation of parental education and risk of autism. King and Bearman (2011) however found high correlation between parental education and incidence of autism. It appears the assumption is that parents with higher education may be better placed to understand and avoid risk factors associated with the development of ASD in their children. 

The nature and nurture debate information presented show that epigenetics / biological factors including cytogenetic abnormalities on chromosome and genome-wide association (Sutcliffe, 2008), hereditary and environmental factors are all contributory factors of the aetiology of autistic spectrum disorder in children.  What this shows is that in the nature and debate about the aetiology of ASD,  no single cause for autism can adequately explain the differential collection of genetic and environmental factors that give rise to the etiology of autism (Shah and Frith, 2003; Happe and Frith, 2006). Existential sporadic cases, wide heterogeneity in clinical presentation, discordant development in monozygotic twins, adverse environmental conditions and occurrences within family members with fully developed autism and others that only manifest ‘autistic traits’ are all cited as significant factors in nature and nurture debates. This shows that biology and environmental factors do not exist in isolation. Genetically induced or hereditary factors including family-based genes and mutations, notably in SHANK3, a gene that encodes a synaptic scaffolding protein and adverse environmental factors can all be conceptualised to contribute or put children possible risk of developing ASD.  

What the information presented also shows is that despite advances in the understanding of biological or genetic contribution to the aetiology of autism (Barton and Volkmar, 1998; Lamb, 2002; Muhle et al, 2004; Santangelo et al, 2005), a purely genetic or biological explanation of causation of autism can therefore be considered to be inadequate.  Differential clinical and epidemiological factors, discordant development in monozygotic twins and occurrences within family members with fully developed autism whilst others only manifest ‘autistic traits’ and environmental factors all draw attention to the aetiology of ASD to involve both nature and nurture causation.

REFERENCES

Adler NE, Newman K (2002) Socioeconomic disparities in health: Pathways and policies. Health Aff (Millwood) 21, 60–76.

Armstrong T. (2012) Neurodiversity in the Classroom: Strength-based strategies to help students with special needs succeed in school and life. Alexandria, VA: Association for Supervision and Curriculum Development

Arora M., Reichenberg A., Willfors C., Austin C., Gennings C., Berggren S.,  Lichtenstein P., Anckarsäter H., Tammimies K., Bölte, S. (2017). Fetal and postnatal metal dysregulation in autism.  Nature communications.  8, 15493.

Babaknejad N, Sayehmiri F, Sayehmiri K, Mohamadkhani A, Bahrami S. (2016) The relationship between zinc levels and autism: a systematic review and meta-analysis. Iran J Child Neurol. 10(4),1–9.

Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E, Rutter M. (1995) Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 25, 63–77.

Bandura, A. (1977). Social learning theory. Englewood Cliffs, NJ: Prentice Hall.

Barton M and Volkmar F. (1998) How commonly are known medical conditions associated with autism? Journal of Autism Developmental Disorders 28, 273–278.

Beversdorf, D. Q., Manning, S. E., Hillier, A., Anderson, S. L., Nordgren, R. E., Walters, S. E., et al. (2005). Timing of prenatal stressors and autism. J. Autism Dev. Disord. 35, 471–478.

Buehler, M. R. (2011). A proposed mechanism for autism: an aberrant neuroimmune response manifested as a psychiatric disorder. Med. Hypotheses 76, 863–870

Buizer-Voskamp, J. E., Laan, W., Staal, W. G., Hennekam, E. A., Aukes, M. F., Termorshuizen, F., et al. (2011). Paternal age and psychiatric disorders: findings from a Dutch population registry. Schizophr. Res. 129, 128–132.

Castro K, Klein Lda S, Baronio D, Gottfried C, Riesgo R, Perry IS. (2016) Folic acid and autism: what do we know? Nutr Neurosci. 19 (7), 310–7.

Children’s Hospital of Philadelphia Vaccine Education Center  (2018) Vaccines ingredients: Aluminium. Retrieved from: https://www.chop.edu/centers-programs/vaccine-education-center/vaccine-ingredients/aluminum#.V4f18pMrIUM

Children’s Hospital of Philadelphia (2019) Vaccines and autism: What you should know. Retrieved from: https://media.chop.edu/data/files/pdfs/vaccine-education-center-autism.pdf

Coe, C. L., Lubach, G. R., and Karaszewski, J. W. (1999). Prenatal stress and immune recognition of self and nonself in the primate neonate. Biol. Neonate 76, 301–310.

Cortesi, F., Giannotti, F., Ivanenko, A., and Johnson, K. (2010). Sleep in children with autistic spectrum disorder. Sleep Med. 11, 659–664.

Croen, L. A., Najjar, D. V., Fireman, B., and Grether, J. K. (2007). Maternal and paternal age and risk of autism spectrum disorders. Arch. Pediatr. Adolesc. Med. 161, 334–340.

Daniels JL (2006) Autism and the environment. Environment Health Perspective. 114, A396.

De Palma G, Catalani S, Franco A, Brighenti M, Apostoli P. (2012) Lack of correlation between metallic elements analyzed in hair by ICP-MS and autism. J Autism Dev Disord. 42(3), 342–53.

Deer, B. (1997) Revealed: Wakefield’s secret first MMR patent claims “safer measles vaccine.” Retrieved from: http://briandeer.com/wakefield/vaccine-patent.htm

Deer, B. (1998) Royal Free MMR video news release: Royal free facilitates attack on MMR in medical school single shots videotape. Retrieved from: http://briandeer.com/wakefield/royal-video.htm

Deer, B. (2011) How the case against the MMR vaccine was fixed. BMJ.  342, c5347.

DeStefano, F., Price, C.S., Weintraub, E.S. (2013) Increasing exposure to antibody-stimulating proteins and polysaccharides in vaccines is not associated with risk of autism. The Journal of Pediatrics. 163(2), 561-567.

Doja, A., and Roberts, W. (2006). Immunizations and autism: a review of the literature. Can. J. Neurol. Sci. 33, 341–346.

Enstrom, A. M., Van de Water, J. A., and Ashwood, P. (2009). Autoimmunity in autism.Curr. Opin. Investig. Drugs 10, 463–473.

Flaherty, D. K. (2011). The vaccineautism connection: a public health crisis caused by unethical medical practices and fraudulent science. Ann. Pharmacother. 45, 1302–1304.

Folstein SE, Rosen-Sheidley B. (2001) Genetics of autism: complex aetiology for a heterogeneous disorder. Nat Rev Genet 2, 943–955.

Froehlich, W., Cleveland, S., Torres, A., Phillips, J., Cohen, B., Torigoe, T., Hallmayer, J. (2013). Head circumferences in twins with and without Autism Spectrum Disorders. Journal of autism and developmental disorders, 43(9), 2026–2037.

Fudenberg, H.H. (1996) Dialysable lymphocyte extract (DLyE) in infantile onset autism: a pilot study. Biotherapy. 9 (1-3), 143-147.

Gardener, H., Spiegelman, D., and Buka, S. L. (2009). Prenatal risk factors for autism: comprehensive meta-analysis. Br. J. Psychiatry 195, 7–14.

Gentile S. (2014)Risks of neurobehavioral teratogenicity associated with prenatal exposure to valproate monotherapy: a systematic review with regulatory repercussions. Cns Spectrums. 19(4), 305–15.

Grandjean, P. and Landrigan, P. J. (2006).Developmental neurotoxicity of industrial chemicals. Lancet 368, 2167–2178

Grabrucker, A. M. (2012). Environmental factors in autism. Front. Psych. 3, 118–122

Grether, J. K., Anderson, M. C., Croen, L. A., Smith, D., andWindham, G. C. (2009). Risk of autism and increasing maternal and paternal age in a large north American population. Am. J. Epidemiol. 170, 1118–1126.

Gupta, S. (2000) “Immunological treatments for autism”, J. Autism Dev. Disord. 30(5), 475–479.

Happe, F. and Frith, U. (2006) The weak coherence account: Detail-focused cognitive style in autism spectrum disorders. Journal of Autism and Developmental Disorders, 36(1), 5-25

Hobson, RP, Bishop, M (2003) The pathogenesis of autism: insights from congenital blindness. Philosophical Transactions of the Royal Society B: Biological Sciences 358, 335–344. 

Horton, R. (2004) A statement by the editors of The Lancet. The Lancet.  363 (9411), 820-821.

Hulme, C. and Snowling,M. (2009) Developmental disorders of language learning and cognition. Oxford: Blackwell-Wiley.

Hviid A, Hansen JV, Frisch M, Melbye M. (2019) Measles, Mumps, Rubella Vaccination and Autism: A Nationwide Cohort Study. Annals of Internal Medicine. 170, 513–520.

Immunisation Safety Review Committee, Institute of Medicine. (2001). Immunisation safety review: measles-mumps-rubella vaccine and autism. National Academies Press. Retrieved from: http://www.nationalacademies.org/hmd/Reports/2001/Immunization-Safety-Review-Measles-Mumps-Rubella-Vaccine-and-Autism.aspx

Immunisation Safety Review Committee, Institute of Medicine (2004) Immunisation safety review: vaccines and autism. National Academies Press. Retrieved from: http://www.nationalacademies.org/hmd/Reports/2004/Immunization-Safety-Review-Vaccines-and-Autism.aspx

Kaczynski AT, Henderson KA (2008) Parks and recreation settings and active living: A review of associations with physical activity function and intensity. J Phys Act Health. 5, 619–32.

Kanner, L. (1943) Autistic disturbances of affective contact. Nervous Child 2, 217-250

Karimi, P., Kamali, E., Mousavi, S. M., & Karahmadi, M. (2017). Environmental factors influencing the risk of autism. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences, 22, 27.

King MD, Bearman PS (2011) Socioeconomic status and the increased prevalence of autism in California. Am Sociol Rev. 76, 320–46.

Kinney, D. K., Munir, K. M., Crowley, D. J., and Miller, A. M. (2008). Prenatal stress and risk for autism. Neurosci. Biobehav. Rev. 32, 1519–1532

Kobayashi T, Matsuyama T, Takeuchi M, Ito S. (2016) Autism spectrum disorder and prenatal exposure to selective serotonin reuptake inhibitors: a systematic review and meta-analysis. Reprod Toxicol. 65,170–8.

Kong, A., Frigge, M. L., Masson, G., Besenbacher, S., Sulem, P., Magnusson, G., et al. (2012). Rate of de novo mutations and the importance of father’s age to disease risk. Nature 488, 471–475.

Krakowiak, P., Walker, C. K., Bremer, A. A., Baker, A. S., Ozonoff, S., Hansen, R. L., et al. (2012). Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics 129, e1121–e1128.

Ladd CO, Huot RL, Thrivikraman KV, Nemeroff CB, Plotsky PM (2004) Long-term adaptations in glucocorticoid receptor and mineralocorticoid receptor mRNA and negative feedback on the hypothalamo-pituitary-adrenal axis following neonatal maternal separation. Biol Psychiatry. 55, 367–75.

Lamb JA, Parr JR, Bailey AJ, et al. (2002) Autism: in search of susceptibility genes. Neuromolecular Med 2, 11–28.

Lam J, Sutton P, Kalkbrenner A, Windham G, Halladay A, Koustas E, Lawler C, Davidson L, Daniels N, Newschaffer C, Woodruff T. (2016) A systematic review and meta-analysis of multiple airborne pollutants and autism spectrum disorder. PLoS One. 11(9), e0161851. 

Landrigan, P.J. (2010) What causes autism? Exploring the environmental contribution. Current Opinion in Pediatrics Volume 22 – Issue 2 – p 219–225

Laurance, J. (2004) How was the MMR scare sustained for so long when the evidence showed that it was unfounded? The Independent.

Lee LC, Harrington RA, Louie BB, Newschaffer CJ. (2008) Children with autism: Quality of life and parental concerns. Journal of Autism Developmental Disorders.  38, 1147–60.

Levy, S. E.  Mandell, D. S. and Schultz  R. T. (2009) Autism. The Lancet, vol. 374, no. 9701.  

Liu, Z., Li, N., and Neu, J. (2005). Tight junctions, leaky intestines, and pediatric diseases. Acta Paediatr. 94, 386–393.

Liu, K. Y., King, M., & Bearman, P. S. (2010). Social influence and the autism epidemic. AJS; American journal of sociology, 115 (5), 1387–1434.

Limperopoulos, C., Bassan, H., Gauvreau, K., Robertson, R. L., Sullivan, N. R., Benson, C. B., et al. (2007). Does cerebellar injury in premature infants contribute to the high prevalence of long-term cognitive, learning, and behavioral disability in survivors? Pediatrics 120, 584–593.

Mehler MF (2008) Epigenetics and the nervous system. Ann Neurol 64, 602– 617

Meikle, J., Boseley, S. (2010) MMR row doctor Andrew Wakefield struck off register. Retrieved from: https://www.theguardian.com/society/2010/may/24/mmr-doctor-andrew-wakefield-struck-off

Miller, L., and Reynolds, J. (2009). Autism and vaccination-the current evidence. J. Spec. Pediatr. Nurs. 14, 166–172.

Modabbernia, A., Arora, M. & Reichenberg, A. (2016). Exposure to metals and Psychosis. Curr. Op. Peds. 28, 243–249

Modabbernia, A. Velthorst, E  and Reichenberg, A.  (2017) Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses. Molecular Autism volume 8, Article number: 13 

Muhle R, Trentacoste SV, Rapin I. (2004) The genetics of autism. Pediatrics 113, e472–e486.

Mukaddes NM1, Kilincaslan A, Kucukyazici G, Sevketoglu T, Tuncer S. (2007) Autism in visually impaired individuals. Psychiatry Clin Neurosci. 61(1) 39-44.

Nikehasani, M. (2018) Nature versus nurture. The Graduate Center, CUNY Academic Works. City University of New York. https://academicworks.cuny.edu/cgi/viewcontent.cgi?article=3801&context=gc_etds

Offit, P.A. (2008). Autism’s False Profits. New York: Columbia University PressSee Chapters 2 and 3.

Parner, E. T., Baron-Cohen, S., Lauritsen, M. B., Jørgensen, M., Schieve, L. A., Yeargin-Allsopp, M., et al. (2012). Parental age and autism spectrum disorders. Ann. Epidemiol. 22, 143–150.

Reichenberg, A., Gross, R., Sandin, S., and Susser, E. S. (2010). Advancing paternal and maternal age are both important for autism risk. Am. J. Public Health 100, 772–773.

Rosen BN, Lee BK, Lee NL, Yang Y, Burstyn I. (2015) Maternal smoking and autism spectrum disorder: a meta-analysis. J Autism Dev Disord. 45(6) 1689–98.

Rossignol, D. A., and Frye, R. E. (2011). Melatonin in autism spectrum disorders: a systematic review and meta-analysis. Dev. Med. Child Neurol. 53, 783–792.

Rossignol DA, Genuis SJ, Frye RE (2014) Environmental toxicants and autism spectrum disorders: a systematic review. Transl Psychiatry. 4,e360.

Sahley, T. L., and Panksepp, J. (1987). Brain opioids and autism: an updated analysis of possible linkages. J. Autism Dev. Disord. 17, 201–216.

Samadi SA, McConkey R. (2011) Autism in developing countries: Lessons from iran. Autism Res Treat. 145359

Sandin, S., Hultman, C. M., Kolevzon, A., Gross, R., MacCabe, J. H., and Reichenberg,A. (2012). Advancing maternal age is associated with increasing risk for autism: a review and meta-analysis. J. Am. Acad. Child Adolesc. Psychiatry 51, 477.e1– 486.e1.

Shah A and Frith U (1993) Why do autistic individuals show superior performance on the block design task? J Child Psychol Psychiatry 34 (8), 1351–1364

Sharp WG, Berry RC, McCracken C, Nuhu NN, Marvel E, Saulnier CA, Klin A, Jones W, Jaquess DL. (2013) Feeding problems and nutrient intake in children with autism spectrum disorders: a meta-analysis and comprehensive review of the literature. J Autism Dev Disord. 43(9),2159–73.

Shelton, J. F., Tancredi, D. J., and Hertz-Picciotto, I. (2010). Independent and dependent contributions of advanced maternal and paternal ages to autism risk. Autism Res. 3, 30–39.

The Editors of The Lancet (2010) Comment: RETRACTION:—Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. The Lancet.  375 (9713), 445.

Thompson, N.P., Pounder, R.E., Wakefield, A.J., & Montgomery, S.M. (1995) Is measles vaccination a risk factor for inflammatory bowel disease? The Lancet. 345 (8957), 1071-1074.

van Balkom, I. D., Bresnahan, M., Vuijk, P. J., Hubert, J., Susser, E., and Hoek, H. W. (2012). Paternal age and risk of autism in an ethnically diverse, non-industrialized setting: aruba. PLoS ONE 7,e45090.

Wakefield A, Murch SH, Anthony A, Linnell J, Casson DM, Malik M, Berelowitz M, Dhillon AP, Thomson MA, Harvey P, Valentine A, Davies SE, Walker-Smith ( JA (1998) RETRACTED:—Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet. 351(9103), 637-641.

Wang T, Shan L, Du L, Feng J, Xu Z, Staal WG, Jia F (2016) Serum concentration of 25-hydroxyvitamin D in autism spectrum disorder: a systematic review and meta-analysis. Eur Child Adolesc Psychiatry. 25(4),341–50.

Ward, A. J. (1990). A comparison and analysis of the presence of family problems during pregnancy of mothers of “autistic” children and mothers of normal children. Child Psychiatry Hum. Dev. 20, 279–288.

Yoshimasu K, Kiyohara C, Takemura S, Nakai K. (2014) A meta-analysis of the evidence on the impact of prenatal and early infancy exposures to mercury on autism and attention deficit/hyperactivity disorder in the childhood. Neurotoxicology. 44,121–31.