Premature testification is not a laughing matter

All opinions are my own and do not necessarily reflect those of Novo Nordisk.

“These studies, once validated, open an opportunity for creating tests that an expectant mother can take to see if she is producing these autoantibodies. ”

I wrote this statement back in July as part of a post describing the report that maternal autoantibodies to specific neural proteins correlated with the appearance of autism symptoms in the children of those mothers.  Little did I suspect that plans to create a test were already in the works.  Science recently reported (paywall) that researchers behind this study are teaming up with a testing company to develop and market a diagnostic test for maternal autoantibodies.

On the one hand I am much in favor of prognostic tests that will help us anticipate health problems.  I believe in many cases early knowledge and interventions can be helpful, even when there is no “cure.”  One of the hopes for the wave of genomic biomedical research going on now is that it will allow us to better estimate who will and will not come down with specific diseases based on clues in individuals’ DNA.  But on the other hand, it can be problematic when tests are created and released before the underlying biomedical hypothesis has been strongly vetted and supported. Continue reading

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Hanging with the herd, for the immunity of it all

All opinions are my own and do not necessarily reflect those of Novo Nordisk.

When I hear about events such as the recent outbreak of measles among a small group in Texas, I am reminded of how complex, complicated and difficult public health efforts can be. In the US, for example, there are conflicting imperatives:  the rights of people to practice their beliefs versus the right of the community to be protected against preventable health threats.  This particular situation involved members of a church congregation, many of whom had not gotten vaccinated for measles due to worries about a link between autism and the Measles-Mumps-Rubella (MMR) vaccine.  While no scientific evidence has been found to support any such link, many had chosen not to be vaccinated “just in case.”

One day I hope to write about the link between the phenomenon of science denial and personal identity (one perspective can be seen here), but for now I just want to point out how this event and a recent publication by the Centers for Disease Control (CDC) on rotavirus vaccines demonstrate nicely the concept of herd immunity (article behind paywall, but writeup here).  There are different usage patterns for the term, so I’ll say up front I am using “herd immunity” to describe not just the proportion of individuals within a population who are immunized to a given pathogen but also the indirect effects for non-immunized individuals.  The term was first used in a publication in 1923, by Topley and Wilson, in the context of how to describe the host side of their studies in bacterial infection among mice.  The concept later gained mathematical underpinnings, including formulas describing how the different ratios of vaccinated to nonvaccinated individuals defines the degree of herd immunity depending upon how infectious a disease agent is. Continue reading

Maternal versus paternal effects on autism

All opinions my own and do not necessarily reflect those of Novo Nordisk

A report just out in JAMA Pediatrics (behind a paywall, but you can see the abstract at the link) reports the intriguing finding (by the way, just for the record, in blogging I’m finding it hard to find synonyms for “interesting.”  Please bear with me) that the recurrence risk for siblings of children with autism is seen even with half-siblings, albeit at a lower rate.  And more intriguing, the risk for sequential half-siblings is higher when the siblings share a mother than when they share a father.

This strikes a chord to me because it is consistent with other recent research I’ve described before, in which the presence of maternal autoantibodies to certain sets of neural proteins was predictive for development of autism.  As the abstract for the current work says, “the significant recurrence risk in maternal half-siblings may support the role of factors associated with pregnancy and the maternal intrauterine environment in ASDs.”  Whether maternal autoantibodies are associated with recurrence risk in this cohort is unknown.  The earlier study was at UC Davis; this one is from Denmark.  I’m generally of the mind that autism is an extremely complex collection of related syndromes, with many different contributing factors (but not vaccines!), so I think it’s best to just do the experiment and test for autoantibodies in the mothers of recurrent siblings.

And the nice thing about a country like Denmark is that this is probably feasible.  Unlike some other nations with extremely fragmented and incomplete health care systems (*cough*United States*cough*), Denmark has very good, integrated medical records.  Denmark also has very high standards for ethics and consent.  So finding a reasonable cohort of mothers and recontacting them may allow a test of whether an association to autoantibodies can be found here as well.  All towards figuring things out, all good.

I wrote to the authors of the study to ask about their work and how it might relate to the autoantibody studies and received the following email response from Dr. Diana E. Schendel of the CDC, via Therese Grønborg:

“Since our paper supports a role for maternal intrauterine effects in ASD, in addition to familial factors, our results are consistent with findings such as the (sic) UC Davis of maternal-derived factors that put the fetus at risk for ASD in pregnancy. One of the pregnancy related factors investigated in ASD etiology concerns abnormal immune system function – perhaps in the mother or perhaps in the fetus – that could impact brain development.

It is important to note that ASD has many potential causes and our study supports the notion of many etiologic pathways – both through family history and prenatal fetal  environments.”

This is a great statement as it jibes with my own views on diseases like autism–that we’re still very early in our understanding of what creates the presentation of a complex phenotype like autistic behavior, and that we need to keep looking and certainly not expecting simple explanations.  Finding explanations is not going to lead directly to new drugs, but greater understanding and a more personalized and nuanced view of each child’s challenges will help maximize their chances of finding success in life.

More developments in autism prediction

All opinions are my own and do not necessarily reflect those of Novo Nordisk

A recent publication about efforts to find early indicators for autism recently came out in the journal Brain and reports an intriguing observation about brain size.  The researchers sought to identify whether Magnetic Resonance Imaging (MRI) of the brains of infants and very young children could help to predict which children would go on to develop autism.  Like many pilot studies of this sort, the experiment was done simply by looking.  The researchers identified a cohort of newborn siblings of autistic children and also a control cohort without that risk factor and began taking MRI images of their brains at the age of between 6-9 months, and again at 12-15 months and 18-24 months.  Prior research has shown that having a sibling with autism greatly increases the probability that a child will also develop autism, so in this situation the expectation was that some of the sibling group would develop autism and researchers would retrospectively be able to look at the data collected during the study and identify MRI features that correlated with development of disease, should any exist.

The impetus behind this is that previous research has not shown any definitive behavioral clues in infants (6 months or younger) that predict the development of autism.  However, the earlier a child is diagnosed, the earlier behavioral interventions can be applied to help that child and his or her family cope with future challenges. Continue reading

Maternal immune systems, autism and the value of prediction

All opinions are my own and do not necessarily reflect those of Novo Nordisk

Following on these two papers (1, 2) published in Translational Psychiatry.

When I wrote about Gene by Environment (GxE) interactions and the possible health of children, I was describing how changes in maternal health might have an effect on child health at the level of what genes are turned on and off.  In that situation, there may be the possibility that actions by potential mothers before conceiving could positively impact child health.  In many other cases, though, the actions for predicted problems can only take place after birth.  Key point: in many cases these interventions are best done early, which is why states have newborn screening programs (although surprisingly the number of tested conditions varies from state to state).  In the context it’s interesting that a couple of recent papers have identified what may be a way to predict the development of autism in children.

The papers describe findings that may, if corroborated, have a large impact on autism prediction and, eventually, possible treatment and prevention for a subset of patients.  First, the team demonstrated through study of non-human primates that these human autoantibodies, when given to pregnant rhesus monkeys, led to significant changes in both maternal and infant monkey behavior.  Mothers in the experimental group showed more protective behavior toward their infants, and those offspring more frequently approached known and unknown monkeys despite not receiving commensurate social responses.  Male offspring also showed measurable increases in brain volume.  Second, the research team discovered that autoantibodies  to combinations of fetal brain proteins are found in a significant fraction of mothers who have Autism Spectrum Disorder (ASD) children, while mothers from the control group rarely have such autoantibodies to so many of these proteins. Continue reading