**8. Gene-environment interactions**

It is not just that ASD is co-morbid with dyslexia and ADHD. Other studies have noted high comorbidity with other developmental disorders. Dyspraxia and dyscalculia and conditions with shared symptoms such as specific language impairment are frequently comorbid with autism. Also dyslexia and ADHD themselves co-occur Willcutt and colleagues (Willcutt, Doyle, Nigg, Faraone, & Pennington, 2005) showed that 40% of a sample of twins with ei‐ ther dyslexia or ADHD was co-morbid for the other disorder. Reading difficulties were measured with both rating scale and an objective task in a study by Cheung et al. (2012) and correlations were observed among ADHD, reading difficulties and IQ. Over half, (53%-72%) of the overlapping familial influences between ADHD and reading difficulties were not shared with IQ. In a school based study Kadesjö and colleagues found 40% of children with

Overall, the literature suggests, there is good evidence to suggest that some children do suf‐ fer from symptoms of both dyslexia and ASD, although this is not so well established, and

**6. Reasons for co-occurrence of ASD with other developmental disorders**

Several theories have been put forward to explain the shared symptoms of the various de‐ velopmental conditions – in other words why specific learning and language and social dis‐ orders are not specific. It is likely that all the explanations below play a part in cooccurrence; the causality of co-morbidity is most probably due to a complex web of

One of the most persuasive explanations is that a genetic predisposition may lead to abnor‐ mal neurological development, which in turn may manifest in various different aberrant be‐ haviors and developmental delays. As autism, ADHD and dyslexia and other developmental conditions are all highly heritable, so they all have a large genetic compo‐ nent, the theory seems plausible. The same genetic anomaly may lead to several disorders or psychiatric conditions. In other words one genotype may lead to several (related) pheno‐ types. This is known as 'pleiotropy'. Researchers have suggested that co-occurrence of au‐ tism and ADHD (and other developmental disorders) may reflect such common genetic causes (Reierson et al, 2008). In this model, the origins of both sets of difficulties are due to common genetic anomalies that predispose children to delayed or atypical neurological de‐ velopment. Certainly, specific genetic anomalies have been associated with a range of psy‐ chopathologies in adulthood. However, the genetic picture is complex and exact pathways are not established. It is estimated there are more than a thousand gene variations which could disrupt brain development enough to result in social delays (Sanders et al., 2012).

Such a genetic predisposition is almost certainly complex and multi factorial. So far, over 100 candidate genes have been associated with ASD, most of which encode proteins in‐

ADHD showed reading problems and 29% writing problems (2005).

368 Recent Advances in Autism Spectrum Disorders - Volume I

does not occur so frequently as co-morbidity between ADHD and ASD.

interacting factors.

**7. Genetic explanations**

A second theory is that an environmental insult or a stressful event in the life of the fetus or in a young child's life, may trigger a genetic predisposition to be expressed. Thus this consti‐ tutes a gene- environmental interaction theory. An example might be the high testosterone levels in the womb that have been observed in some studies. Baron-Cohen's Cambridge group, for example, has carried out work that has suggested high levels of fetal testosterone may be linked to the development of autistic traits (Ingudomnukul, Baron-Cohen, Wheel‐ wright, & Knickmeyer, 2007). According to the gene-environment explanation, the elevated testosterone might lead to the differential expression of genes controlling the neurological development of the child. Another example that has been quite widely publicized concerns Omega 3 fatty acids. These have been implicated by Richardson (2006), who has argued that attention-deficit/hyperactivity disorder, dyslexia, developmental coordination disorder (dyspraxia) and conditions on the autism spectrum may all share common origins triggered by problems with phospholipid (fatty acid) metabolism. However this is just one genetic / environmental explanation for co-occurrence that vies with several others, and the available evidence is subject to interpretation.

In the majority of cases, the gene-environment hypothesis seems highly plausible. It may be that autism and co-occurring developmental conditions may all be caused by a genet‐ ic predisposition which is triggered by an early environmental influence (Trottier, Srivas‐ tava, & Walker, 1999).

Many environmental factors have been implicated in ASD but the effect of each is poorly established. After the well publicized paper that linked autism to the MMR vaccination, re‐ search has repeatedly refuted a link between the MMR jab and ASD (Rutter, 2005). Deykin and MacMahon (1979) found increased risk due to exposure to, and clinical illness from, common viral illnesses in the first 18 months of life. In this study, mumps, chickenpox, fever of unknown origin, and ear infections were all significantly associated with ASD risk. Epide‐ miological studies have shown there is a higher rate of adverse prenatal and postnatal events in children with ASD than in the general population (Zwaigenbaum et al., 2002). Newschaffer and colleague's (2007) review named associated obstetric conditions that in‐ cluded low birth weight, gestation duration, and caesarean section. It is possible that such an underlying cause partially could explain both autism and the associated conditions (Ko‐ levzon, Gross, & Reichenberg, 2007). There is evidence to suggest adverse prenatal and peri‐ natal events are also associated with ADHD and cognitive development. Some studies have suggested that the risk of autism may be increased with advancing maternal age (Bolton et al., 1997). Paternal age too has frequently (but not always) associated with autism. There are more mutations in the gametes of older men, and this higher rate of mutation in the genetic material from the paternal side may explain the higher levels of neurodevelopmental disa‐ bilities in their offspring. An alternative explanation is that fathers who themselves have au‐ tistic traits are less likely to have children young. Using anticonvulsants during pregnancy also appears to increase the risk of ASD (Moore et al., 2000). These drugs are used to combat epilepsy which is commonly often comorbid with ASD. Parental occupational exposure to chemicals during the preconception period has also been higher in ASD families than con‐ trols in some studies (Felicetti, 1981).

were observed in a study of abandoned Romanian children, conducted by Michael Rutter and colleagues (1999). As well as cases with known genetic causes, in some cases, underly‐ ing social factors may predispose autistic symptoms. In this study, Rutter and colleagues noted a very high instance of autism (6%) in the Romanian baby cohort, which they put down to poor early care. These children exhibited typical symptoms of autism at four years old, but unlike cases of autism without maltreatment, symptoms by age 6 were much mild‐ er. This case is an illustration of how children who share severe autistic symptoms at young ages may have differing developmental trajectories. In this study, the symptoms of autism may have been triggered primarily by the early neglect, rather than by a genetic predisposi‐ tion, for if a genetic predisposition was involved it would effect 6% or more of the babies, a

Co-Occurrence of Developmental Disorders: Children Who Share Symptoms of Autism, Dyslexia and Attention Deficit

Hyperactivity Disorder

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http://dx.doi.org/10.5772/54159

It is not just aetiological environmental factors that seem to lead to increased risks of dis‐ playing autistic behaviours. Aetiological causes can be distinguished from proximate deter‐ minates which occur at the same time as symptoms, for example, social situations or fluorescent lights may exacerbate the expression of ASD symptoms. There are also those in‐ fluences in the environment that are sometimes referred to in psychiatry as maintenance fac‐ tors, including stigmatisation and labelling. Although their influence in perpetuating ASD and other developmental disorders is unclear, an influence in maintaining symptomatic be‐ haviours of autism and co-morbid conditions can not be discounted. Biological causes and

The competing psychological theories that have been put forward concerning the psycho‐ logical mechanisms of ASD include weak central coherence theory, deficits in executive

The extreme male brain theory as developed by Baron-Cohen (2002) suggests that autis‐ tic individuals can systematize—that is, they can develop internal rules of operation but are less effective at empathizing and handling events that are unexpected or social. The theory was developed from the earlier 'theory of mind' (Baron-Cohen, Leslie, & Frith, 1985). This suggested that autistic people lack the ability to understand other peo‐ ples' mental states, put themselves in another person's place or imagine what they might be thinking or experiencing. This lack of mentalising is discussed by Frith and Happé in their discussion of dyslexia, autism and downstream effects of specific impairments (1998). The 'theory of mind' lines up with the 'mirror neuron theory of autism' (Iacoboni & Dapretto, 2006) which was based on the discovery that the macaque monkey brain contained 'mirror neurons' that fired not only when the animal is in action, but also

An alternative psychological theory for autism is provided by Frith whose 'weak central co‐ herence' theory (Frith, 2003; Happé & Frith, 2006) describes the ability to place information in a context in order to give it meaning. Most people pull together numerous stimuli to form

behavioural outcomes are mediated by experiential and environmental factors.

function and the extreme male brain theory, all were reviewed by Happé in 1994.

**10. Cognitive causes and developmental consequences**

when it observes others carrying out the same actions.

very high proportion.

Environmental risk factors have received widespread media coverage within the last few years, perhaps because of the strong degree of public concern (Russell & Kelly, 2011). In most health and disease categories, a secondary function of diagnosis is to group together people who have a common aetiology. However, the specific effects of genetic factors and environmental risk factors that might play a part in abnormal neural development are large‐ ly unresolved. Goodman and Scott (1997) stress that current understanding of aetiology for childhood developmental conditions will probably look ridiculously simplistic or misguid‐ ed in years to come. Despite, or perhaps because of, the uncertainty, there is an underlying concern among people involved with children who are diagnosed with developmental con‐ ditions that environmental influences may be partially to blame for rising incidence. Novel prenatal and perinatal medical practices, changing diet, shifting family structures and child‐ hood social activities have all been the subject of lay theories to explain rising prevalence not just of ASD, but developmental disorders in childhood more generally, including ADHD and dyslexia (Russell & Kelly, 2011).

#### **9. The influence of childcare and the child's environment**

A third possibility is that environmental factors alone may be enough to trigger not just au‐ tistic behaviors, but also other maladaptive behaviors such as inattention. Autistic behaviors were observed in a study of abandoned Romanian children, conducted by Michael Rutter and colleagues (1999). As well as cases with known genetic causes, in some cases, underly‐ ing social factors may predispose autistic symptoms. In this study, Rutter and colleagues noted a very high instance of autism (6%) in the Romanian baby cohort, which they put down to poor early care. These children exhibited typical symptoms of autism at four years old, but unlike cases of autism without maltreatment, symptoms by age 6 were much mild‐ er. This case is an illustration of how children who share severe autistic symptoms at young ages may have differing developmental trajectories. In this study, the symptoms of autism may have been triggered primarily by the early neglect, rather than by a genetic predisposi‐ tion, for if a genetic predisposition was involved it would effect 6% or more of the babies, a very high proportion.

It is not just aetiological environmental factors that seem to lead to increased risks of dis‐ playing autistic behaviours. Aetiological causes can be distinguished from proximate deter‐ minates which occur at the same time as symptoms, for example, social situations or fluorescent lights may exacerbate the expression of ASD symptoms. There are also those in‐ fluences in the environment that are sometimes referred to in psychiatry as maintenance fac‐ tors, including stigmatisation and labelling. Although their influence in perpetuating ASD and other developmental disorders is unclear, an influence in maintaining symptomatic be‐ haviours of autism and co-morbid conditions can not be discounted. Biological causes and behavioural outcomes are mediated by experiential and environmental factors.
