The recent emergence in the scientific literature
of ‘gene expression’ as a frequent keyword has suddenly
assigned an unexpected new function to our database.
Apart from purely genetic diseases such as Down
syndrome, cystic fibrosis, colour blindness, haemophilia, phenylketonuria,
Huntington’s chorea, sickle-cell disease, or Turner syndrome,
it is now well-accepted that both genetic and environmental factors
are at the origin of most pathological conditions and personality
traits.
Until recently, it was commonplace to contrast
genetic and environmental factors. There have been endless discussions
about the relative contributions of these two factors. Such discussions
led in particular to twin and adoption studies, in order to disentangle
the effects of genes versus environment. Today many geneticists
aim to identify genes involved in the predisposition towards specific
diseases while epidemiologists look for environmental risk factors.
The dialogue has always been difficult between those who tend
to exaggerate the genetic factors and those who tend to minimize
them. We are still under the indirect influence of the obsolete
Nature versus Culture debates based on narrow preconceived ideas.
The view that humans acquire all, or almost all, their traits
from "nurture" was known as tabula rasa. The opposite
view was the basis for philosophical movements such as ‘Nativism’
and ‘Innatism’.
Today the concept of ‘gene expression’
is a turning point regarding our understanding of the origin of
pathological conditions and personality traits. We are now in
a position to explain that some of our genes express themselves,
while others become silenced; of course they still exist and they
will reappear within the next generation. Gene expression is the
process by which inheritable information from a gene, such as
a DNA sequence, is made into a functional gene product, such as
a protein or RNA. It has been demonstrated that methylation of
DNA is a common method of gene silencing.
An example
In order to illustrate this new role of the primal health
research database, we’ll explore the possible links between
autism and anorexia nervosa, two conditions that, according
to the data we have at our disposal, are to a great extent determined
during the perinatal period. The mysterious increased prevalence
of both diseases, concomitantly, is one of the reasons why we
choose this example. It is well-accepted today that the increased
prevalence in these two conditions is not simply resulting from
improved diagnostic and greater public awareness.
Among the three recent large and authoritative studies of
autism from a Primal Health Research perspective, the Australian
study will convince anyone that the main risk factors occur
in the perinatal period.(1) The 465 subjects born in Western
Australia between 1980 and 1995 and diagnosed with an autism
spectrum disorder by 1999 were compared with the birth records
of 481 siblings of the cases, and with1313 controls. No differences
in gestational age at birth (including premature infants), weight
for gestational age, head circumference, or length were observed
between cases and control subjects. Pre-eclampsia did not appear
as a risk factor. These negative findings lend more credence
to perinatal factors. Compared with their siblings, autism cases
were more likely to have been induced, to have experienced fetal
distress, and to be born with a low Apgar score. Compared with
control subjects, they were more likely to be born after induction
and to be born by elective or emergency c-section.
Similar conclusions can be drawn from a study involving all
Swedish children born from 1974 to 1993. No association was
found between autism and head circumference, maternal diabetes,
being a twin, or season of birth, while c-section appeared to
be a risk factor.(2) This study could not consider labour induction
as a possible risk factor, since this term did not appear in
the Swedish birth registers until 1991. A recent report from
Israel also found no prenatal differences between autistic children
and controls, but the rates of birth complications were higher
among the autistic population.(3)
We must add to these negative findings a series of studies
exploring the possible links with different types of vaccinations
in infancy. These, too, indirectly give weight to the perinatal
factors. All epidemiological studies included in our database
confirm that the risks of autism seem to be the same among children
who did or did not receive MMR.(4,5,6,7) They also seem to be
the same among children who had or had not received a vaccine
containing a mercury derivative.(8) If we take into account
that the risk of autism is not related to the mode of infant
feeding (breast or bottle) we must conclude that the significant
risk factors precede infancy.
We can draw similar conclusions from a large and authoritative
Swedish study of risk factors for anorexia nervosa. The researchers
had access to the birth records of all girls born in Sweden
from 1973 to 1984,(9) and of the 781 girls who had stayed in
a Swedish hospital due to anorexia nervosa between age 10 and
age 21. For each anorexic girl there were five controls (non-anorexic
girls born in the same hospital during the same year). Apart
from being born before 32 weeks gestation, the most significant
risk factor for anorexia nervosa was a cephalohematoma at birth.
Forceps and ventouse deliveries were also risk factors. An Italian
retrospective study of subjects with eating disorders found
that the risk of developing anorexia nervosa increased with
the total number of obstetric complications. In addition, an
increasing number of complications significantly anticipated
the age of onset of anorexia nervosa.(10)
It appears from this Italian study that being shorter for
gestational age significantly differentiates subjects with bulimia
nervosa from those with anorexia nervosa. A study of smoking
in pregnancy as a risk factor for bulimia nervosa also suggests
that the concept of ‘eating disorder’ should be
dismantled. Anorexia nervosa and bulimia nervosa should be studied
separately. Not only can Primal Health Research establish links
between pathological entities, but it can also dismantle of
pre-existing entities.
The contribution of other perspectives
The links suggested by the primal health research perspective
between anorexia and bulimia prompt us to wonder what we can
learn from other perspectives. This question inevitably leads
to refer to clinical considerations mentioned by several teams
of psychiatrists. Janet Treasure et al of the Institute of Psychiatry
of King’s College hospital, in London, have emphasized
the importance of autistic traits in anorexia nervosa.(11) People
with anorexia nervosa find it difficult to change self-set rules;
they see the world in close-up detail, as if they were looking
through a zoom lens, and risk getting constantly lost in the
details.(12) Christopher Gillbert and the team of the Department
of Child and Adolescent Psychiatry at Goteborg University in
Sweden, found that 23% of female patients with severe eating
disorders had symptoms of the autism spectrum.(13)
The oxytocin system in both conditions offers another promising
avenue of research. The first clues came from a study of midday
blood samples from 29 autistic and 30 age-matched normal children.(14)
The autistic group had significantly lower blood oxytocin levels
than the normal group. Oxytocin increased with age in the normal
but not the autistic children. These results inspired an in-depth
inquiry into the oxytocin system of autistic children. In recent
years it has become clear that oxytocin can appear in the brain
in several forms. There is the nonapeptide oxytocin (OT) and
the ‘C-terminal extended peptides’, which are described
together as OT-X. The OT-X represent intermediates of oxytocin
synthesis that accumulate due to incomplete processing. Twenty-eight
male children diagnosed with autistic disorder were compared
with 31 age-matched non-psychiatric control children: there
was a decrease in blood OT, an increase in OT-X and an increase
in the ratio of OT-X/OT in the autistic sample, compared with
control subjects.(15) In other words, autistic children show
deficits in the processing of oxytocin.
There have not been such in-depth inquiries into the oxytocin
system of anorexic patients. However, it has been reported that
the level of oxytocin in the cerebrospinal fluid of women with
‘restricting anorexia’ is significantly lower than
the level of oxytocin in bulimic and control subjects.(16) Such
studies of the oxytocin system provide new reasons to dismantle
the framework of ‘eating disorders’ while reinforcing
the links between anorexia and autism. They offer interpretations
of the perinatal period as critical in the origin of both conditions,
since it is a time when the oxytocin system is highly-challenged,
with a deep redistribution of the specific neuroreceptors. These
are important considerations when the physiological processes
in the perinatal period are routinely disturbed as happens these
days.
Towards a new phase in the history of nosology?
Until now nosology – the naming and classification of
diseases – was mostly based on descriptions of symptoms
(e.g. scarlet fever), on altered functions (e.g., hyperthyroidism)
or on altered organs (e.g., myocardial infarction). Today, the
Primal Health Research Database makes possible a classification
according to critical periods for genes-environment interaction.
After studying in parallel anorexia nervosa and autism, one
can reinforce the suggestions expressed by some psychiatrists
that anorexia nervosa might be considered a female variant of
the autistic spectrum. A plausible interpretation of why it
is undoubtedly more female is that prenatal exposure to male
hormones might protect against the expression of anorexia nervosa.
Such an interpretation is suggested by a study of twins.(17)
Girls who have a twin brother were at low risk of anorexia nervosa,
compared with girls who had a twin sister and with controls.
This interpretation is reinforced by the negative results of
genetic linkage analyses that could not detect any change on
the X chromosome.(18)
With the fast development of primal health research we can
anticipate that new nosological entities will appear while others
will more or less fall away.
Michel Odent
References:
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and the development of autism. Arch Gen Psychiatry 2004; 61:
618-27.
2 -Hultman C, Sparen P, Cnattingius S. Perinatal risk factors
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in individuals diagnosed with autism and in healthy controls.
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rubella vaccine: no epidemiological evidence for a causal association.
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