Maternal migration and autism risk: Systematic analysis

This art icle was downloaded by: [ Daina Crafa] On: 15 May 2015, At : 09: 02 Publisher: Taylor & Francis I nform a Lt d Regist ered in England and Wales Regist ered Num ber: 1072954 Regist ered office: Mort im er House, 37- 41 Mort im er St reet , London W1T 3JH, UK International Review of Psychiatry Publicat ion det ails, including inst ruct ions f or aut hors and subscript ion inf ormat ion: ht t p: / / www. t andf online. com/ loi/ iirp20 Maternal migration and autism risk: Systematic analysis a Daina Craf a & Nasir Warf a b a Int egrat ed Program in Neuroscience, Douglas Ment al Healt h Universit y Hospit al, McGill Universit y, Mont real, Quebec, Canada b Wolf son Inst it ut e of Prevent at ive Medicine, Queen Mary Universit y of London, Bart s and The London School of Medicine and Dent ist ry, London, UK Published online: 15 May 2015. To cite this article: Daina Craf a & Nasir Warf a (2015) Mat ernal migrat ion and aut ism risk: Syst emat ic analysis, Int ernat ional Review of Psychiat ry, 27: 1, 64-71 To link to this article: ht t p: / / dx. doi. org/ 10. 3109/ 09540261. 2014. 995601 PLEASE SCROLL DOWN FOR ARTI CLE Taylor & Francis m akes every effort t o ensure t he accuracy of all t he inform at ion ( t he “ Cont ent ” ) cont ained in t he publicat ions on our plat form . However, Taylor & Francis, our agent s, and our licensors m ake no represent at ions or warrant ies what soever as t o t he accuracy, com plet eness, or suit abilit y for any purpose of t he Cont ent . Any opinions and views expressed in t his publicat ion are t he opinions and views of t he aut hors, and are not t he views of or endorsed by Taylor & Francis. The accuracy of t he Cont ent should not be relied upon and should be independent ly verified wit h prim ary sources of inform at ion. 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Term s & Condit ions of access and use can be found at ht t p: / / www.t andfonline.com / page/ t erm s- and- condit ions International Review of Psychiatry, February 2015; 27(1): 64–71 Maternal migration and autism risk: Systematic analysis DAINA CRAFA1 & NASIR WARFA2 1Integrated Downloaded by [Daina Crafa] at 09:02 15 May 2015 Program in Neuroscience, Douglas Mental Health University Hospital, McGill University, Montreal, Quebec, Canada, and 2Wolfson Institute of Preventative Medicine, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK Abstract Autism (AUT) is one of the most prevalent developmental disorders emerging during childhood, and can be amongst the most incapacitating mental disorders. Some individuals with AUT require a lifetime of supervised care. Autism Speaks reported estimated costs for 2012 at £34 billion in the UK; and $3.2 million-$126 billion in the US, Australia and Canada. Ethnicity and migration experiences appear to increase risks of AUT and relate to underlying biological risk factors. Sociobiological stress factors can affect the uterine environment, or relate to stress-induced epigenetic changes during pregnancy and delivery. Epigenetic risk factors associated with AUT also include poor pregnancy conditions, low birth weight, and congenital malformation. Recent studies report that children from migrant communities are at higher risk of AUT than children born to non-migrant mothers, with the exception of Hispanic children. This paper provides the first systematic review into prevalence and predictors of AUT with a particular focus on maternal migration stressors and epigenetic risk factors. AUT rates appear higher in certain migrant communities, potentially relating to epigenetic changes after stressful experiences. Although AUT remains a rare disorder, failures to recognize its public health urgency and local community needs continue to leave certain cultural groups at a disadvantage. Background AUT is a spectrum disorder, and people with AUT may exhibit different combinations of symptoms with different degrees of severity. As such, it is heterogeneous in nature, and diagnosis can initially be difficult (Constantino, 2011). To diagnose AUT, patients are assessed for abnormal behaviours in the following three areas: social skills, language and communication, and stereotypic behaviours. Social deficits are well-known symptoms of AUT. They include avoidance of social interaction, failure to make eye contact, and inability to empathize with another person (Chevallier et al., 2012; Green et al., 2000). Even when AUT is mild to moderate, the disorder can cause significant distress for patients and their families. It can prevent bonding, act as an impediment to learning, and substantially delay the child’s development (Dunst et al., 2011; Schipul et al., 2011). Symptoms of AUT emerge before the child is two years of age, and repeated failure to make eye contact or to respond when called by name are among the earliest indicators (American Psychiatric Association, 2013). These deficits are biopsychosocial in nature and can prevent the patient from forming, or sustaining, meaningful relationships, which can cause problems when seeking jobs or medical care in adulthood (Grant et al., 2001; Green et al., 2000). Other symptoms of AUT include language and communication deficits. Severe language disability frequently co-occurs with the disorder, affecting approximately 38% of all children with AUT (Centers for Disease Control and Prevention, 2014). In some cases, children with AUT may be unable to speak or even communicate non-verbally (American Psychiatric Association, 2013). Moreover, unless treated very early in life, patients are unlikely to learn to speak or effectively communicate (Virués-Ortega, 2010). Stereotypy, a third symptom of AUT, describes repetitive behaviours frequently exhibited by patients, such as mirror gazing or rocking, that provide solitary self-stimulation and may be repeated for long periods of time (Goldman et al., 2009; Matson et al., 2009a). Moreover, the severity of an individual case of AUT is generally described as either ‘high functioning’ or ‘low functioning’, with children with intellectual disability (ID) falling into the latter category. High functioning AUT is generally associated with intelligence quotient (IQ) scores higher than 70 Correspondence: Daina Crafa, MSc, Integrated Program in Neuroscience, Douglas Mental Health Institute, McGill University, Frank B. Common Pavilion, 6875 Boulevard LaSalle, Room F-1145, Montreal, Quebec, Canada, H4H 1R3. Tel: ⫹ 001 514-761-6131. Fax: ⫹ 001 514-888-4064. E-mail: daina.crafa@ mail.mcgill.ca (Received 22 August 2014 ; accepted 25 November 2014 ) ISSN 0954–0261 print/ISSN 1369–1627 online © 2015 Institute of Psychiatry DOI: 10.3109/09540261.2014.995601 Maternal migration and autism risk (e.g. Centers for Disease Control and Prevention, 2014; Gillberg & Billstedt, 2000; Hallett et al., forthcoming; Matson et al., 2009b; Mazurek & Kanne, 2010; Sukhodolsky et al., 2008; Weisbrot et al., 2005). Low functioning AUT is associated with IQ scores below 70, and impairments in speech or daily living skills are most often observed in this group (American Psychiatric Association, 2000). The severity of behavioural problems in the three diagnostic domains (i.e. social, communication, and stereotypy) have been shown to correlate with low IQ, and it has been proposed that children with normal or high IQs are better able to develop compensatory mechanisms to overcome their deficits (Fein et al., 2013). 65 et al., 2009; Gillberg, & Gillberg, 1983, 1996; Keen et al., 2010). Although a few studies show equal or lower rates of AUT in migrant communities (Croen et al., 2002; Dealberto, 2011; Schieve et al., 2012), these studies have generally focused on specific ethnic groups. A systematic review of the literature is necessary to examine global trends and their implications. This comprehensive analysis is aimed to update the current literature on the prevalence and predictors of AUT, particularly focusing on the associations between maternal migration stressors, epigenetic changes and increased rates of AUT in migrant communities. Downloaded by [Daina Crafa] at 09:02 15 May 2015 Risk factors for AUT Several environmental and biological risk factors have been associated with AUT (Croen et al., 2002; Haglund & Källén, 2011; Hultman et al., 2002; Williams et al., 2008). Suboptimal birth or poor pregnancy conditions increase risk for AUT. Low Apgar score, low birth weight, caesarean section, premature birth, congenial malformation, and multiple births have also been linked with the development of AUT (ibid.). Higher parental age (both paternal and maternal age) was reported as a key indicator of risk (Lauritsen et al., 2005; Magnusson et al., 2012; Williams et al., 2008). In both cases, increased age is related to degradation of reproductive cells resulting in suboptimal pregnancy conditions and potential epigenetic changes, causing AUT (Durkin et al., 2008). While genetic sequences remain stable across the lifespan, epigenetic changes are alterable and often heritable modifications that are made to DNA processes, including methylation and histone deacetylation; such modifications may alter the expression of a gene. Numerous studies have linked epigenetic changes to social or environmental causes, including migration, and demonstrated that they may be passed down to later generations (e.g. Dealberto, 2007; Furrow et al., 2011; McEwen et al., 2012; Tahira & Agius, 2012; Uddin et al., 2010). Epigenetic mutations have recently been identified as causing poor birth conditions linked with AUT (Schanen, 2006; Walker et al., 2013), and it is hypothesized that increased risk of autism may be related to epigenetic changes in some communities. Some studies suggest that the stress from maternal migration could potentially initiate such epigenetic changes – sometimes termed the ‘migration theory of autism’ (Gardener et al., 2009; Keen et al., 2010; Kinney et al., 2008; Magnusson et al., 2012). Many studies have reported that children in migrant communities are at higher risk for autism, and it has been theorized that maternal migration prior to giving birth may further increase this risk (Gardener Methods We carried out a systematic review into the world literature examining migration as a risk factor for AUT. We used several databases including PubMed, PyscINFO, Google Scholar and Embase to search for articles that met our inclusion criteria. Papers were eligible for inclusion if they had peer-reviewed population data on AUT and maternal migration. We excluded papers if maternal migration status was not clearly defined (e.g. studies using vague terms such as: ‘one parent’ migrated). Studies of mothers with both pre- and post-pregnancy migration statuses were included in the review. We used comprehensive search terms to identify relevant papers. These included migration, autism, autism migrant, migration and autism, and maternal migration and autism (see Appendix 1 for more search terms). All papers published in English which met the initial inclusion criteria were included in the final analysis (see Table 1). We selected articles if they had a clearly defined method of data collection, analysis and reporting. Studies without clearly tested validity and reliability constructs were excluded from the review. AUT is defined in accordance with the DSM-IV and ICD-10 diagnostic criteria for ‘Autistic disorder’, which is traditionally defined as Kanner-type autism and less subject to heterogeneity across diagnostic manuals. Studies of Asperger syndrome, pervasive developmental disorder – not otherwise specified (PDD-NOS), or other disorders on the AUT spectrum (e.g. Rett syndrome) were excluded. Articles were only considered for inclusion if they reported data for these disorders separately. Since some data collection occurred during earlier versions of the DSM manual, definitions of AUT from the DSM-III (American Psychiatric Association, 1980) and ICD-8 (World Health Organization, 1968), as well as later editions (e.g. DSM-5, American Psychiatric Association, 2013), were considered valid for this study. 66 D. Crafa & N. Warfa Downloaded by [Daina Crafa] at 09:02 15 May 2015 Table 1. Studies that met inclusion criteria and were selected for the final review. Study Country of migration Diagnostic manual Williams et al., 2007 Australia DSM-IV Population registry linked with medical records Lauritsen et al., 2005 Denmark ICD-8, ICD-10 Danish civil registration system Van der Ven et al., 2012 Netherlands DSM-IV Population registry linked with psychiatry case register Haglund, 2011 Sweden DSM-III, DSM-IV, ICD-10 Hultman, 2002 Sweden ICD-9 Magnusson et al., 2013 Sweden DSM-IV Swedish medical birth registry linked with child and youth centre registry Swedish medical birth registry linked with the Swedish inpatient registry Stockholm youth cohort linked with official registries Hassan et al., 2012 UK ICD-10 Keen et al., 2010 UK ICD-10 Croen et al., 2002 USA DSM-III-R ICD-9-CM Schieve et al., 2012 USA Parent-reported DSM diagnosis Data source Sample All children born in New South Wales during the years of data collection All children born in Denmark under 10 years of age during the years of data collection All children born in the urban and sub-rural areas surrounding Utrecht during the years of data collection All children born in Malmö during the years of data collection All children born in Sweden during the years of data collection All children living in Stockholm County ages 0–17 years during the years of data collection All children born in the UK who were also registered in the source databases Autism Service databases were compared with local public health demographic data and population reports projections Wandsworth and Lambeth paediatric child development service records California Department of Developmental Services linked with California live birth certificate files National survey of legal guardians We analysed AUT rates from all of the samples reported by the papers reviewed (Table 2). For easy comparison, rates higher than 1% of the total sample (e.g. higher than the current global average) were classified as high, while rates lower than 1% were All children born in the UK during the years of data collection whose records were on file in data sources All children born in California during the years of data collection All children born in the USA aged 3-17 who were randomly selected to participate in the 2007 National Survey of Children’s Health classified as low. Relative rates of children with AUT born to migrant and non-migrant mothers were compared in the following ways. First, we calculated a sum total of combined rates across all articles, and then the total values of maternal migration status Table 2. Rates of AUT based on the reported findings from each study. Each rate represents the AUT N-value relative to the total study population (AUT⫹ controls). Country First author AUT population N-value All studies Australia Denmark Netherlands Sweden Sweden Sweden UK UK USA USA – Williams Lauritsen Van der Ven Haglund Hultman Magnusson Hassan Keen Croen Schieve 11,185 182 796 137 157 403 3,918 356 388 4,356 493 Control population N-value 4,051,581 85,503 76,399 160,009 68,807 2,020 40,034 61,417 23,825 3,493,514 40,052 AUT (%) 0.28 0.21 1.03 0.09 0.23 16.63 8.91 0.58 1.60 0.12 1.21 AUT (high/low) low low average low low high high low high low high Maternal migration and autism risk (children of migrant mothers versus children of nonmigrant mothers). For each study we also calculated the rate of AUT per 100,000 so that no single study inflated results from across maternal migration status and ethnic groups. Results Downloaded by [Daina Crafa] at 09:02 15 May 2015 Sample and demography Ten large-scale population studies with high N-values conducted in six countries met our inclusion criteria. These studies had high statistical power: N ⫽ 4,062,766 (AUT⫹ control), N ⫽ 11,185 (AUT). Nearly all of these studies used data from birth registries and medical records (Croen et al., 2002; Haglund & Källén, 2011; Hassan, 2012; Hultman et al., 2002; Keen et al., 2010; Lauritsen et al., 2005; Magnusson et al., 2012; Schieve et al., 2012; Van der Ven et al., 2013; Williams et al., 2008). With the exception of one study conducted in Australia, all populations lived in Western Europe (N ⫽ 8) and the USA (N ⫽ 2). The total rate of AUT, which represents the summed total of all studies included, was 0.28%. The rates of AUT for each sample ranged from 0.09– 16.67% (SD ⫽ 5.46), based on the populations reported by each article. Studies with high rates of AUT had a mean of 7.09 (N ⫽ 4, SD ⫽ 7.28); studies reporting low rates of AUT had a mean of 0.25 (N ⫽ 5, SD ⫽ 0.19). The variations between the studies reporting high and low rates were not explained by differences in sample size, data collection methods and country of origin. We compared the rate of AUT for children born to non-migrant mothers with that of children born to migrant mothers (Table 3). Three of the four studies reporting high rates of AUT at population level also reported similar high rates for children born to both migrant- and non-migrant mothers. A fourth study found higher rates for the total AUT population; and the same higher rates for children born to native mothers, but reported lower AUT rate for children born to migrant mothers. On average, studies reported approximately equal rates of AUT for children with maternal and non-maternal migration status (0.1% to 0.2% respectively). Half of the studies showed no significant differences between AUT rates in children born to migrant and non-migrant mothers (Croen et al., 2002; Hassan, 2012; Magnusson et al., 2012; Van der Ven et al., 2013; Williams et al., 2008). Of the remaining studies, two reported higher rates of AUT for children born to non-migrant mothers (Lauritsen et al., 2005; Schieve et al., 2012), and three reported higher rates for children of migrant-born mothers (Haglund & Källén, 2011; Hultman et al., 2002; Keen et al., 2010). We calculated the reported N-values from each study and adjusted the rate of AUT per 100,000 children and therefore controlled for the effects of different sample sizes and ethnic backgrounds. The results showed higher rates of AUT if children had migrant mothers (2.69%) compared with children of non-migrant mothers (0.91%). Six out of ten studies found that giving birth post-maternal migration significantly raised risks of AUT (Haglund & Källén, 2011; Hultman et al., 2002; Keen et al., 2010; Lauritsen et al., 2005; Schieve et al., 2012; Williams et al., 2008), with the exception of children born to Hispanic migrant mothers who had lower rates of AUT (compared to all other migrant groups). Discussion This study reviewed the prevalence and predictors of AUT in children born to migrant and non-migrant mothers in the international literature to clarify global trends. The results indicated maternal migration status as a strong predictor of AUT for children Table 3. Rates of AUT maternal migration status. Rates represent AUT N-value relative to the total AUT population (AUT⫹ controls). Country of migration All studies Australia Denmark Netherlands Sweden Sweden Sweden UK UK USA USA 67 First author AUT (%) for children of non-migrant-born mothers AUT (high/low) AUT (%) for children of migrant-born mothers AUT (high/low) Williams Lauritsen Van der Ven Haglund Hultman Magnusson Hassan Keen Croen Schieve 0.34 0.19 1.00 0.12 0.31 15.66 9.03 0.63 1.14 0.14 1.25 low low average low low high high low high low high 0.19 0.28 1.23 0.05 0.40 28.57 8.48 0.56 2.73 0.10 0.85 low low high low low high high low high low low Downloaded by [Daina Crafa] at 09:02 15 May 2015 68 D. Crafa & N. Warfa of migrant communities (see Table 4). At times, migration status comes across as a proxy for ethnicity. Ethnicity was a strong confounder. However, when we controlled for ethnic status, we observed higher rates of AUT among children with migrant mothers (2.69% versus 0.91%), with the exception of children born to Hispanic migrant mothers who consistently showed lower AUT rates against all other ethnic groups; perhaps showing the differential effects of maternal migration on AUT. In other words, ethnicity and biological risk factors alone cannot account for the differential rates of AUT found in children born to migrant mothers. Several previous studies link maternal migration stressors with obstetric complications during pregnancy and labour (Binder et al., 2012a, 2012b, 2013; Essen et al., 2011). These include stressors linked with sociocultural conditions, beliefs and practices (Magnusson et al., 2012; Van der Ven et al., 2013), for example psychological and medical distress that can accompany common experiences, such as targeted discrimination, or culturally specific experiences, such as forced female circumcision. Mismatch expectations between migrant groups and healthcare providers (Warfa et al., 2006, 2012), cultural or community misunderstandings of care procedures, inaccessible healthcare services, language and communication barriers (Bhui et al. , 2003, 2007; Warfa et al., 2006), and delayed help-seeking behaviour (Bhui et al., 2003; Binder et al, 2012a, 2012b., 2013; Essen et al., 2011; Warfa et al., 2006, 2012) may all lead to stressors that induce epigenetic changes during pregnancy and delivery; with associated risk of AUT. Sociocultural factors, such as discrimination, have been used to explain the higher maternal morbidity and mortality rates found in migrant communities. For example, a major enquiry into maternal and child health in Sweden reported maternal mortality rate that was six times higher than the general population among migrant groups such as Somali migrants (Binder et al., 2012a, 2012b, 2013; Essen et al., 2011; Warfa et al., 2012). The same mechanisms that link the above socio-economic risk factors with a higher rate of maternal mortality and morbidity in migrant communities can also explain the differential AUT rates in children of migrant mothers. In other words, sociocultural related stressors such as discrimination that occur before or during pregnancy and labour can be hypothesized to explain the higher prevalence rate of AUT in immigrant populations. In contrast, nurturing sociocultural conditions may potentially have protective effects on AUT rates. A number of studies report that Hispanic women are significantly less likely to have a baby with low birth weight compared with other ethnic groups (AcevedoGarcia et al., 2005; Collins & Shay, 1994; FuentesAfflick & Lurie, 1997). Sometimes called the Latina or Hispanic paradox, this trend has been observed even when the mother has migrated from stressful conditions such as from a developing country or one with a low human development index. The Latina paradox is frequently observed in Hispanic women moving from Mexico to the USA, and multiple researchers attribute it to the relief of moving from a stressful sociopolitical situation to the close-knit Hispanic communities typical in the USA. This phenomenon appears to occur despite the high rates of unemployment and discrimination sometimes faced by these communities, which is generally still less than what they faced in their home country. Low birth-weight neonates may be up to seven times more likely to develop AUT (Movsas et al., 2013). Positive relationships between the large social network sizes characteristic of Hispanic communities and higher birth weights have been observed, as well as inverse relationships between social network size and AUT Table 4. Risk factors for AUT. N studies report risk Maternal migration 7 Ethnic background Suboptimal pregnancy or birth conditions Parental age Caesarean section Low APGAR score Low birth weight Migrating from developing country Premature birth Immediate family member with AUT or related disorder Congenital malformation Maternal education Multiple births Smoking during pregnancy Urbanization 4 4 3 2 2 2 2 2 1 1 1 1 1 1 First author Williams, Lauritsen, Haglund, Hultman, Magnusson, Keen, Schieve Hassan, Keen, Croen, Schieve Haglund, Hultman, Williams, Croen Williams, Lauritsen, Magnusson Haglund, Hultman Haglund, Hultman Haglund, Hultman Van der Ven, Magnusson Williams, Haglund Lauritsen Hultman Croen Croen Hultman Lauritsen Downloaded by [Daina Crafa] at 09:02 15 May 2015 Maternal migration and autism risk rates (Dyer et al., 2011; Palmer et al., 2010). Accordingly, it seems plausible that nurturing sociocultural conditions may protect the reproductive environment and reduce the chances of having a child with AUT after maternal migration. Some studies show a positive relationship between social network size and higher birth weights (Dyer et al., 2011) and an inverse relationship with AUT rates (Palmer et al., 2010). Taken together, social environment may have protective effects against epigenetic changes related to birthing conditions and AUT. Moreover, these findings suggest that the stress response may emerge as a dynamic between the migrating individual and their new community, rather than being restricted to the act of migration. In conclusion, the link between AUT and maternal migration status is inconsistent with AUT’s epigenetic origins and emergence during early childhood. We further propose that maternity migration stressors and poor environments may cause epigenetic changes during pregnancy and delivery that lead to AUT. The caveats are crucial modifications to the epigenetic literature of AUT. The revised hypothesis includes the importance of recognizing adverse effects of sociocultural practices on mental and physical health and the potential benefits of nurturing social communities. Premenopausal migrant women and their families may particularly benefit from public health outreach and AUT awareness campaigns. Such health education programmes can highlight AUT risk after migration and other stressful sociocultural experiences, as well as the benefits of a nurturing community. This can range from displaying multilingual flyers at migration offices to training doctors to talk with migrant mothers about AUT risk factors, benefits of early diagnosis and treatment methods. These efforts can be geared particularly to non-Hispanic migrants, who appear to be at higher risk, as well migrants who are culturally disinclined to seek AUT treatment. They may also be useful for Caucasian migrants, who may not be aware that they may also be at higher risk for having a child with AUT. Early intervention techniques have been developed to teach young children compensatory mechanisms for coping with the disorder (e.g. Dunlap, 1999; Schreibman, 2000). These techniques are the only proven treatment for AUT. They can significantly improve quality of life and, in some cases, can virtually eliminate AUT symptoms when administered early enough in childhood. As such, early diagnosis of the disorder is crucial to children’s improvement and future wellbeing (Ventola et al., 2006). Modest steps such as these have the potential to greatly improve AUT management in general, and particularly among migrant communities. 69 Limitations There are a few limitations to this systematic review. First, the body of literature on migration and AUT is scant. Secondly, the migration theory of autism has gained relative presence in the global mental health literature, and yet this theory is based largely on research coming from studies with methodological limitations and convenient sample sizes. Likewise, the findings of the larger studies reported in this review are not necessarily representative of all migrant communities living in different countries, nor are the host samples necessarily generalizable to other host communities. Moreover, ethnicity may not be the optimal method of group delineation when assessing autism risk. Evaluations of specific sociocultural communities, political climates, or genetic traits may provide more nuanced assessments. The findings should be read with these limitations in mind. Third, diagnostic criteria for autism have changed across diagnostic manuals and may result in some heterogeneity in our sample, despite our best efforts to control for this. Finally, while maternal migration stressors may lead to adverse epigenetic changes, there also appear to be protective mechanisms that prevent this negative effect (i.e. the Hispanic paradox). The Hispanic protective paradox requires further collaborative investigation. Collaborations between life sciences, social sciences and medical humanities While the race for the cure continues, the disadvantages faced by migrant communities can be lessened through improved knowledge, wider knowledge disseminations and effective community engagement. AUT is a rare illness, and yet, failure to recognize its public health urgency will perpetuate further myths and misconceptions of the development and diagnosis of AUT. With previous reports of misguided cause–effect associations between AUT and MMR vaccines, autism mythology already fills in the current scientific gaps. We call for joint collaborative research by life scientists, social scientists and medical humanists. Interdisciplinary research could consider investigating AUT from diverse biological, social, political and cultural perspectives; and the extent to which these bio-sociocultural stressors are capable of triggering adverse epigenetic changes that are linked with AUT risks. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. 70 D. Crafa & N. Warfa Downloaded by [Daina Crafa] at 09:02 15 May 2015 References Acevedo-Garcia, D., Soobader, M.J., & Berkman, L.F. (2005). The differential effect of foreign-born status on low birth weight by race/ethnicity and education. Pediatrics, 115, e20–30. American Psychiatric Association. (2013). The Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Washington, D.C. American Psychiatric Association. (2000). The Diagnostic and Statistical Manual of Mental Disorders (4th ed.). Washington, DC: American Psychiatric Association. 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