What Causes Autism Spectrum Disorders? (page 4)

History of Attribution of Cause

Autism has long been considered a classification of a mental disorder. Early individuals with moderate to severe delays in language and social skills would have been placed in institutions to be “treated” by the medical establishment of the time. Kanner, a psychiatrist, first wrote about “infantile autism” and the associated symptoms in his paper in 1943. It is likely that individuals with autism who were high functioning were considered odd, loners who were not classified as needing intervention.

In the 1950s psychiatrist Bruno Bettelheim attributed the symptoms of autism to uncaring and detached mothers who did not love their children enough. Treatment consisted of removing the children from these “refrigerator mothers,” offering psychoanalysis or counseling to the mother, and providing play therapy to the child, ideally in Bettleheim’s institute in Chicago. The disorder was thought to occur in middle-class Caucasian families where both parents were educated. During this period of history not only did the mothers of children with autism have to care for a child with challenging and unusual behaviors, they also experienced the added burden of being blamed as the cause.

In 1964, Bernard Rimland published the book Infantile Autism: The Syndrome and Its Implications for a Neural Theory of Behavior, which attributed the cause of autism to biology rather than poor parenting. Rimland dedicated his career to addressing the biological issues that contribute to and result from autism spectrum disorders. He had long hypothesized that there are brain differences in individuals with ASD compared to the brains of typically developing children. Rimland founded the Autism Research Institute (ARI) that supports the project Defeat Autism Now, or DAN. Annual conferences are held where physicians present information on possible metabolic (interrelated chemical interactions that provide the energy and nutrients) contributions to symptoms and suggest diets that can be used to avoid the side effects of toxins for individuals with ASD.

Genetic Influences.

Autism is currently considered a neurological disorder that is influenced by both environmental (including the in-utero environment) and genetic factors (Sigman, Spence, & Wang, 2006). Evidence for a genetic contribution to ASD is found in a series of twin studies conducted across several countries with similar outcomes (Rutter, 2005). When one twin in a monozygotic pair of twins (identical) was diagnosed with autism, there was a high likelihood that the second twin, with the same DNA, also was diagnosed with autism (Cook, 1998). However, in dizygotic twins (fraternal) the concordance for the diagnosis for autism was very low.

Twenty-eight pairs were examined in the United Kingdom, with 60% of the monozygotic twins both being diagnosed with autism and 0% of the dizygotic twins receiving the diagnosis (Bailey et al., 1995). In Scandanavia, 21 pairs were assessed, with a 91% concordance for monozygotic twins and 0% for dizygotic (Steffenburg et al., 1989). In the United States, 61 pairs were assessed, with a concordance rate of 95.7% for monozygotic twins and 0% for dizygotic (Ritvo, Freeman, Mason-Brothers, Mo, & Ritvo, 1985).

In addition to the twin studies it has been found that the reoccurrence risk for siblings (4.5%) is 45 to 90 times greater than the population risk (.05 – .1%) (Cook, 1998). Results of surveys have revealed that relatives have an increased frequency of lesser variants of autism, including social, language, and repetitive behaviors (Rutter, 2005).

In Their Words Author: Laura Wood

Three Children on the Spectrum

My husband and I have three wonderful sons. They are all on the autism spectrum. Our oldest son Alex’s diagnosis at age 2.5 came as a tremendous blow to us, as it does to every family grappling with this disorder. At that time our twins were 5 months old and we were thoroughly overwhelmed by our responsibilities. But we managed to launch a high-quality home intervention program for Alex and felt that we were doing everything we could do for him.

As the shock of Alex’s diagnosis wore off a bit, I did start overanalyzing certain observations of the twins’ behavior. Were they smiling? Paying attention to faces? During their first year of development, despite my hypervigilance, I believed it to be unlikely that they were autistic. I had not yet heard about the increased likelihood of autism in siblings of autistic children, so I told myself I was being unnecessarily paranoid.

But as the months went by and certain developmental milestones were missed or seemed ambiguous, the nagging feeling returned and slowly I realized that the nightmare scenario was coming to pass. The twins were both diagnosed with autism spectrum disorder shortly before their second birthday.

The most obvious impact of having kids “on the spectrum” is the financial commitment required for their home therapy. We are extremely lucky in Seattle to have a wonderful integrated preschool that all three kids attend for specialized instruction; but supplemental home programs are also recommended for two of our children, and the staggering cost of those programs is not covered by health insurance.

In addition, as many parents of children with special needs will tell you, guilt is ever-present. Sometimes the guilt has a specific source (Am I spending enough time encouraging communication and appropriate play? Have we set up enough hours of home therapy?). Other times the guilt is vague, intangible, and inexplicable.

I have times when I feel bitter and isolated. I look at other families with typically developing children with longing or even with anger. They can’t know what it’s like to take their children to countless therapy appointments and spend tens of thousands of dollars on essential therapy. How can I relate to these parents who take for granted their child’s imaginative play skills or brag recklessly about their baby’s first words? And how can they relate to me when I occasionally confess the reason why my kids don’t always respond appropriately to a peer’s invitation to play? Unless autism has touched their lives in some way, a blank look tinged with pity is all those parents can muster.

But in other ways I recognize the gifts sent our way by this unexpected path in life. There are several wonderful teachers and therapists who would never have been in our lives had it not been for the autism in our family. And my children have reminded me that there are different varieties of intelligence beyond what we think of as typical.

My kids are sweet, wonderful rays of sunshine in my life. They give me so much joy that all the worry and guilt and expense are absolutely worthwhile. I have already learned from them, and I’m sure they have more to teach me as we continue through our lives together.

“Autism spans the genome” (Coleman & Betancur, 2005, p. 17), or is likely to be caused by multiple genes on several chromosomes, and is likely to be associated with chromosomal deletions. Our genes are found on 23 pairs of chromosomes numbered from 1 to 22 and an X or Y chromosome. The larger the number of the chromosome, the smaller the size of the chromosome. When using specialized equipment, each chromosome appears in an X shape with the top arms, or p part, shorter than the lower and longer q portion.

Research indicates that autism spectrum disorder is caused by 2 to 20 susceptible genes across various chromosomes acting in concert (LeCouteur et al., 1996; Minchew, Sweeney, Bauman, & Webb, 2005; Sigman et al., 2006). It is hypothesized that genes on the following chromosomes could contribute to ASD: chromosome 1p, chromosome 2q, chromosome 3, chromosome 5p (Rutter, 2005), chromosome 7q (Buitelaar & Willemsen-Swinkels, 2000; Cook, 2001; Rutter), chromosome 11 that affects the glutamate neurotransmitter system, chromosome 13q (Rutter), chromosome 15q11-q13, or the same region that is missing in Prader-Willi and Angelmann syndrome (Cook; Rutter), chromosome 16 (Rutter), chromosome 17 that has a serotonin transporter gene (Cook), chromosome 19p and 19q (Rutter), chromosome 22q11.2 (Fine et al., 2005), and the X chromosome (Coleman & Betancur, 2005; Rutter). Autism resulting from chromosome 15 is likely due to chromosomal duplication (Coleman & Betancur; Rutter). Chromosome X is of particular interest due to the higher ratio of males to females with the disorder and because of fragile X syndrome, which results in similar symptoms (Coleman & Betancur; Rutter).

It is likely that autism is a syndrome with a common phenotype (visible characteristics) expressed by many different underlying diseases (Coleman & Betancur, 2005). There have been at least 60 different disease entities in individuals that meet the standardized criteria for autism (Coleman & Betancur). There is also mounting evidence that for a significant number of children with ASD, their symptoms may arise from disease of the mitochondria. Mitochondria are rod-shaped bodies found in most cells that produce enzymes for the metabolic conversion of food to energy. Mitochondria cells contain their own DNA that differs from the DNA found in the cell nucleus, and most of the chemical energy in the brain is produced by the mitochondria (Coleman & Betancur).

It is hypothesized that each of the disease entities underlying autistic syndromes will eventually be identified and found to have its own distinctive variation of clinical symptoms and its own specific neuropathology. (Coleman, 2005, p. 63)

When Do the Impairments Occur?

There is evidence of the process resulting in ASD being initiated in all three trimesters of pregnancy as well as some postnatal evidence (Coleman & Betancur, 2005). The first trimester, when the face is formed, is the period when children with autism have stigmata or atypical facial features and are more likely to have more than one syndrome, such as ASD with mental retardation, tuberous sclerosis complex, or a related disorder such as Rett or Angelman syndrome (Coleman & Betancur). It may be that for some disorders—such as tuberous sclerosis, where 43 to 86% of individuals have a PDD—there is an underlying disease process that results in autistic symptoms. However, it also may be that a susceptible gene for autism lies in close proximity to a tuberous sclerosis gene and is triggered along with tuberous schlerosis (Rutter, 2005).

It is the second trimester, or the period of time most associated with brain development, that is associated with the neurodevelopmental errors leading to autism expressed without a similar pattern in physical characteristics (Coleman & Betancur, 2005). Minor anomalies such as low seating of the ears may be present. The onset of the neurodevelopmental events occurs no later than 28 to 30 weeks (Minchew et al., 2005). Relatively few individuals with ASD have issues with the development of the central nervous system that occurs during the third trimester, and children who do are likely to have been exposed to infections (Coleman & Betancur). It is important to note that “most of the developmental neurobiology of autism remains speculative and unconfirmed” (Minchew et al., p. 473).

Differences in Structure and Function of the Brain

Autism does not result from a problem with one location in the brain but from abnormalities within one or multiple neural systems (Akshoomoff, Pierce, & Courchesne, 2002; Coleman, 2005). It is likely that the nerve dysfunctions in people with autism reflect an early brain abnormality that not only affects the cranial nerves but also has secondary effects on later brain development (Rodier, 2000). Autism could be caused by a problem in the neural networking of the brain in which too many connections are established during development due to inadequate pruning of irrelevant connections (Coleman, 2005). It is also hypothesized that there is premature overgrowth in some structures (cerebral volumes, number of neurons) and reduced growth or excessive cell loss in other structures (limbic and cerebellum volumes; (Akshoomoff, 2000).

There is evidence that the brains of children with autism grow at a different rate than those of typical peers, possibly reflecting a lack of neural pruning in early years (Courchesne et al., 2001). It may be that autism is a disorder of growth regulation (Akshoomoff et al., 2002). In Kanner’s original description of autism he noted that 5 of the 11 children had large heads (Minchew et al., 2005). The increase in head circumference in children with autism corresponds to an increase in brain volume that normalizes by adolescence; however, head circumference remains enlarged (Minchew et al.).

Autopsy studies have shown abnormalities in the cerebellum, brain stem, and temporal lobes, and the amygdala in particular (Peeters & Gillberg, 1999; Schultz & Robins, 2005). The frontal lobes are considered to play a role in memory formation and emotional expression, and patients with frontal lobe damage demonstrate a decreased ability to respond to stimuli in the environment (Reichler & Lee, 1989). For this reason researchers are exploring the frontal lobes for a possible link to autism spectrum disorders (Ozonoff, South, & Provencal, 2005). The frontal lobes are the part of the brain where planning, organizing, self-monitoring, inhibition, flexibility, and working memory, or the cognitive construct of executive functioning, is considered to occur (Ozonoff et al.). Due to findings of deficits in these skills in older children and young adults with autism, there is speculation that some turning point is missed during the late preschool period; however, further research is needed to substantiate this theory (Ozonoff et al.).

Imaging studies using magnetic resonance imaging (MRI) technology have demonstrated a reduction in neural activity between brain regions when individuals with ASD are given challenging tasks (Minchew et al., 2005). Neuroimaging studies that access areas of the brain reacting during different tasks, or functional MRIs, have revealed that regions associated with object perception are more active during tests requiring the identification of embedded figures given to subjects with ASD compared with prefrontal regions more active in typical subjects (Ring, 1999). There is also a reported inability to accurately and rapidly shift attention between sensory modalities measured in reaction times to the random presentation of visual and auditory stimuli (Courchesne et al., 1994).

Neuroimaging studies also provide evidence for abnormalities in the systems that underlie face and voice processing (Sigman et al., 2006). Hypoactivity of the fusiform face area (a small region on the underside of the temporal lobe) has been replicated in functional neuroimaging studies (Schultz & Robins, 2005). Hypoactivation has also been found in the amygdala during certain tasks that may reflect less interest or reduced emotional arousal during the task (Schultz & Robins).

Although much progress has been made in the autism research over the past 20 years, many questions remain before we can truly understand the neural mechanisms that result in the clinical features of autism. (Minchew et al., 2005, p. 490)