On Saturday, the Stanford Autism Center at Packard Children’s Hospital will host its sixth annual Autism Spectrum Disorders Update. During the day-long symposium, parents and caregivers will have an opportunity to discuss new autism research and interventions with physicians, as well as learn about the center’s clinical services and ongoing autism studies at the School of Medicine.
In anticipation of the event, we asked Carl Feinstein, MD, director of the center, to respond to your questions about issues related to autism spectrum disorders (ASDs) and to highlight how research is transforming therapies for the condition. Below he addresses a range of topics, including early diagnosis and intervention in infants and the role of environmental factors and genetics in contributing to autism.
AnneMarie asks: How meaningful are environmental factors, such as nutrition and exposure to toxins during pregnancy, in terms of autism risk?
During pregnancy, proper nutrition and taking reasonable measures to avoid exposure to known environmental toxins are basic steps an expectant mother, and family, can take to promote a baby's health and minimize risks of medical problems for the newborn. This principle certainly applies to giving birth to a baby with a healthy brain and nervous system, and pregnant women should consume proper nutrients to support brain development. There are a number of known toxins, including lead, alcohol, mercury, tobacco, various insecticides, petrochemical products and some medicines that are harmful to fetal development. An important area of concern is our current environment and findings showing that food and water sources, and other common materials, can contain man-made chemicals.
A great deal of scientific attention is now being focused on the potential consequences of some of these chemicals on the bodily organs, including the brain, as well as possible mutagenic or harmful effects on the reproductive organs and human genes. There is a very real basis for concern that environmental toxins play a direct causative role or increase the risk for neurodevelopmental disorders, including ASDs. There is now much research underway to discover what types of chemicals present in the environment might be causatively implicated in ASDs.
S. Heller asks: What role do genetics play in autism and is there strong evidence suggesting a single gene or, specific group of genes, is causing the condition?
There is an ongoing debate about how much of the currently recognized prevalence of mild ASDs reflects an actual increase, involving both males and females, and how much is due to increased recognition of milder behavioral traits that were previously undetected or called something else. However, it is well-established that genes and heredity play an important causative role in the condition. This remains the case, even though it has recently been established that environmental causes have been underestimated. There are several hundred known gene abnormalities of differing types that are causally related to ASDs. More continue to be discovered all the time. A relatively small number of these gene abnormalities, if present in a developing child, incur great risk for the condition. Many others, some quite common, present as relatively low “risk factors” for ASDs.
When ASDs result in these individuals, it may be because numerous low-risk genes occurred together, or because a low-risk factor has combined with an environmental factor. There is an important distinction to be made between hereditary (familial genetic factors) that increase the risk of ASDs and non-hereditary genetic causes of the condition, which stem from “copying” mistakes that occur when the reproductive cells are being formed or duplicating in embryogenesis. The latter can result in a child being born with ASDs in a family that appears to have no special hereditary predisposition to the condition.
The Diagnostic and Statistical Manual of Mental Disorders (DSM) is a lengthy document used by doctors to list the current, consensus-driven criteria for what are considered abnormal patterns of behavior, cognition and affect. You are correct in pointing out that autism is a neurodevelopmental disorder, so it makes sense to wonder why it is lumped together with so-called “mental” disorders in the DSM.
My view, which is shared with many colleagues in psychiatry and clinical neuroscience, is that it would have been far more straightforward if the DSM hadn’t chosen the term “mental disorders,” but rather had selected something like brain disorders of thinking, feeling and behavior. “Mental” is a term that has served as a kind of shorthand means to discuss thought processes, but its application to describe the conditions listed in the DSM can be confusing and has resulted in highly unfortunate stigmatizing overtones.
All behaviors, adaptive and maladaptive, are the product of brain functioning, in complex interactions with the social and physical environments. Seen this way, all “mental disorders” are basically disorders of brain functioning. While it was a correct decision by the formulators of the DSM to identify conditions, such as intellectual disability, autism, ADHD and language disorders as neurodevelopmental disorders, the true mistake made was to label the rest of the disorders as “mental”. The explanation for this distinction provided by the DSM is that the term “neurodevelopmental” refers only to conditions that are obvious in earliest childhood. The fact is that many (likely most) of the other major brain disorders in the DSM, such as schizophrenia and bipolar disorder, have long been proven to be neurodevelopmental disorders. The conditions differ only that they begin in childhood and don't fully manifest until the period between late childhood and young adulthood.
Lisa K. asks: A study published earlier this year shows that early signs of autism can be detected in infants as young as 6 months old. How early should parents, or medical professionals, be looking for symptoms of autism?
One of the most exciting research developments of the past five years has been the increasing ability of clinical researchers and cognitive neuroscientists to identify the early symptoms of autism in children between the ages of 6-12 months — both by children's reduced attention to social stimuli and the activities and structure of the brain networks that underlie the very early stages of social attention and perception. The way this has been accomplished has been to focus attention on high-risk infants, those who have an older sibling with autism, and studying very closely and repeatedly their development over the first few years of life. While many of the younger siblings of children with ASDs have normal development, it turns out that about 20 percent have at least some symptoms of ASDs. The first distinctive behavioral manifestations of ASDs in high-risk infants, turns out to be in their social attention. This is not surprising since from the very earliest recognition of autism, social deficit has been its most defining feature. Because of these findings various pediatric sub-specialties have promulgated guidelines stating that careful attention should be paid to the social communicative development of babies who have an older sibling with autism.
It has furthermore been demonstrated, likely because of observations made by parents with an older autistic child, that by 12 months of age (but probably not much before) parents of high-risk infants can reliably detect whether that child is showing symptoms of autism. It is certainly appropriate to begin early intervention to enhance social and communicative development in these babies, when delays are detected. However, it is not clear whether parents who haven’t already had a child with ASDs are reliable detectors in their children of 12 months. For this reason, most pediatricians are concerned that referring babies for an autism evaluation when there is no family history of ASDs could cause unnecessary worry. There is still more much more work to be done to reliably identify babies with ASDs in the first year of life.
There is a concerted and shared effort that has been picking up momentum in the past two decades among both parents of autistic children and clinical researchers to look for environmental toxins that might cause ASDs. It is obviously of the highest priority to identify these environmental toxins. Doing so could identify a primary prevention strategy for ASDs. Furthermore, if researchers can identify the biological mechanisms by which these environmental chemicals cause brain abnormalities associated with ASDs, then closer examination might elucidate neurobiological “targets” for treatment interventions.
Childhood vaccines were one of the first chemicals of suspicion in the search for environmental causes of ASDs. Particularly since a compound with mercury, a known neurotoxin, was widely (but no longer!) used as
an adjuvanta preservative in some vaccine preparations. Use of the mercury-containing compound, Thimerosal, as a vaccine adjuvantpreservative spurred much hypothesizing, and ultimately a significant amount of research, seeking a causal tie to ASDs. However, despite a great deal of elaborate and expensive scientific studies using many types of research strategies, it has been impossible for researchers to demonstrate that this is the case, even though it has been studied in many large population samples.
At present, it appears very unlikely that vaccines of any type are a meaningful causal factor in the vast majority of cases of ASDs. However, many parents haven’t abandoned this belief and have become alienated from, or suspicious of, medical research. As a result, many have decided not to have their children vaccinated and advocate for others to do the same. Unfortunately, large scale refusals by parents to vaccinate their children is presenting a secondary health risk and putting other children at risk of serious illness from infectious diseases.
Previously: Ask Stanford Med: Director of Stanford Autism Center taking questions on research and treatment, New public brain-scan database opens autism research frontiers, New autism treatment shows promising results in pilot study, Study shows gene mutation in brain cell channel may cause autism-like syndrome, New imaging analysis reveals distinct features of the autistic brain and It’s over: No MMR vaccine-autism connection
Photo by Josh Ward