A Possible Explanation of Autism based on Elevated Maternal Testosterone: A Mechanism that may Explain Differential Growth and Development
(Propranolol and Autism, new, 2013)
New Research, May, 2015, may Prove my Explanation of Autism (Abstract at very bottom of this page.) Also, 2016 High Folic Acid and Increased Autism and Increased homocysteine and glutamate in Autism at bottom of page.
Copyright 2013, James
Michael Howard, Fayetteville, Arkansas, U.S.A.
(My
principal hypothesis may possible be applied to a number of
explanations of human ontogeny, phylogeny, and pathologies. This is
the most compact explanation applicable to this article. It is my
hypothesis that evolution selected increased testosterone during
evolution of primates and humans. ("Androgens in Human
Evolution," Rivista di Biologia / Biology Forum 2001; 94:
345-362) This occurred because testosterone increases androgen
receptor production which increases absorption and use of
dehydroepiandrosterone (DHEA). (Mammals evolved because of selection
for DHEA: "Hormones in Mammalian Evolution," Rivista di
Biologia / Biology Forum 2001; 94: 177-184.) The effect of increased
testosterone in primates / humans occurred because of increased
maternal testosterone. This increased androgen receptors within fetal
brains which increased growth and development, hence, bigger brains.
This reached a maximum in humans with the selection by evolution of
females of very high testosterone. (Human male and female
testosterone is higher than chimpanzee male and females; human and
chimpanzee estrogen are approximately equivalent.) I have had reason
lately, January, 2013, to apply this to autism. (The information just
below should present my connection with this mechanism as it applies
to autism during the past years.) If you read beyond this point, my
hypothesis regarding the connection of DHEA and androgen receptors
stimulated by testosterone may explain the increased size of both
cerebral hemispheres, as a result of the lack of pruning of neurons,
and the increased, localized connectivity with autistic brains.
The
extra use of DHEA by our bigger brains changes the use of our DHEA by
our bodies. Bigger brains produced the changes in our bodies that
differentiate us from the other primates because of competition
between the brain and other tissues for DHEA.
A connection
of prenatal testosterone and autism was suggested around 1987 and
continues in 2012 (Molecular Autism 2012; 3: 17). This, current,
paper concludes: "These preliminary findings are consistent with
the hypothesis that prenatal (but not postnatal) androgen exposure,
coinciding with the critical period for sexual differentiation of the
brain, is associated with the development of autistic traits in 18 to
24 month old toddlers. However, it is recognized that further work
with a larger sample population is needed before the effects of
postnatal androgen exposure on autistic traits can be ruled out.
These results are also in line with the fetal androgen theory of
autism, which suggests that prenatal, organizational effects of
androgen hormones influence the development of autistic traits in
later life."
My first published (journal) application
of my work to autism and maternal testosterone deals with why a
connection exists between maternal testosterone and autism and why
autism may be increasing as a result in Archives of Disease in
Childhood 2006; 91 (7): 622.
"It is my hypothesis
that the “secular trend”, the increase in size and
earlier puberty of children, is caused by an increase in the
percentage of women of higher testosterone within the population with
time. Maternal testosterone has been connected with autism. I suggest
the increase in autism, and other increasing disorders, that are
occurring is due to the secular trend; I suggest increasing exposure
of fetuses to increasing maternal testosterone is increasing autism
(http://www.anthropogeny.com/increase
in autism.htm).
This increase in maternal testosterone
occurs in different groups of women of differing levels of
testosterone. Therefore, the consequences of this fetal exposure will
manifest as increases in different ways. For example, I suggest
obesity, diabetes, and breast cancer are increasing because of this
exposure in different women.
Dr Baron‐Cohen has
demonstrated “mothers of autistic children often show patterns
of brain activity more associated with men” (BBC comments on
the internet). I suggest the connection of these types of mothers is
that they may produce increased levels of testosterone."
A
connection of prenatal / maternal testosterone has received
considerable attention in the literature without a consensus and,
especially, without a mechanism. I intend to suggest a mechanism of
how excessive maternal testosterone can cause autism. This will rely
on my "The Increase in Autism in California (which is also
occurring in other areas)" at:
http://anthropogeny.com/increase%20in%20autism.htm
, "The Mechanism of “Pruning” in the Human Brain"
at: http://anthropogeny.com/Pruning.htm
, and "DHEA, Estradiol, Testosterone, and the Relevance of Their
Ratio …The Androgen Receptor …and the Secular Trend"
at:
http://anthropogeny.com/Androgen%20Receptor%20and%20Secular%20Trend.htm
.
Furthermore, I posted a composite of this mechanism at
"POLS / Biology" in 2011. Here is the link:
http://www.plosbiology.org/annotation/listThread.action;jsessionid=3CAE279EF06459EBF41207BE2FC01F2F?root=11831
. "
How Increased Testosterone May Cause Autism
Posted
by jamesmhoward on 10 Nov 2011 at 21:58 GMT
Regarding JAMA
2011 Nov 9;306(18):2001-10 "Neuron number and size in prefrontal
cortex of children with autism"
I suggest the
increase in prefrontal neuron number and size in autistic children
are the effects of maternal testosterone. High maternal testosterone
has been connected with autism in the literature.
It is my
hypothesis that human evolution resulted from selection for
testosterone: "Androgens in Human Evolution," Rivista di
Biologia / Biology Forum 2001; 94: 345-362. (If your library does not
subscribe to "Rivista ... ," you may read this at:
http://anthropogeny.com/Androgens
in Human Evolution.htm . If you do not want to bother to visit
this website, please, at least, note the chart from "General and
Comparative Endocrinology" of 2003 which directly supports my
explanation of human evolution. You may see the chart by going to the
link above.)
The prefrontal cortex is larger in humans
compared to the great apes. I suggest this is the primary result of
the selection of higher testosterone in human females. That is, the
increased maternal testosterone is the basis for our larger brains
and its effects on subcranial differences between humans and the
great apes. One aspect is increased prefrontal areas.
If
maternal testosterone is high or high at inappropriate times, then,
according to my explanation of human evolution, androgen receptors
would increase in the fetal brain. Excess androgen receptors in the
prefrontal cortex would increase the cell number and size.
My
explanation of human evolution suggests that increased brain size
causes a competition between the brain and the subcranial structures
(body). Hence, as our brains increased in size, out bodies also
started to differ from the great apes. Growth of the brain affects
body growth.
If I am correct, then one should see
competition within the brains of autistic individuals as a result of
this competition. Problems with cerebellum formation and activity
occur frequently within autistic individuals. I suggest this is due
to increased androgen receptors within the prefrontal areas of the
autistic brain which cause increased neuron number and size at the
expense of the cerebellum. Growth of parts of the brain will affect
other parts.
My work suggests that maternal testosterone
periodically increases within the human population and, subsequently,
creates problems. This is occurring at the present time. It is well
known that autism is increasing, along with many other problems,
simultaneously. A well known example is female breast cancer.
I
suggest the foregoing explanation may explain the findings reported
in JAMA. 2011 Nov 9;306(18):2001-10 "Neuron number and size in
prefrontal cortex of children with autism." "
The
foregoing suggests that increased maternal testosterone increases
androgen receptors within the fetal brain. Androgen receptors have
been examined in autism with the idea of finding gene mutations but
none have been found, nor have excessive androgen receptors been
found in autism.
I suggest androgen receptors within the
brain are increased by exposure to increased maternal testosterone.
This would increase absorption of DHEA by these structures. Increased
DHEA would increase growth and size of affected neurons. The result
would be larger cells / larger brain size resulting from increased
testosterone and DHEA. These increased structures might also exhibit
increased connectivity, that is, strong growth. These increased
results of growth
Increased size is often characteristic
of autism as well as strong, local connectivity. I think all tissues
compete for available DHEA. Therefore, these brain structures do not
continue to grow as the body starts using DHEA for growth and
development. During the first year, following the "pruning"
period, extra DHEA becomes available and the growth continues until
the brain and body competition reduces further growth.
The
excessive growth and connectivity would allow, in some cases,
exaggerated function in some parts of the brain at the expense of
other parts. Hence, some autistics become "savants." This
would also apply to growth and development of different parts of the
brain in different hemispheres.
Synaptic Defect in
Autism
A researcher in autism responded to the
foregoing information with some questions including the connection of
autism and synapses defects. I sent the following to
him:
Autism / ASD exhibits increased dendritic spines on
cortical phyramidal cells. A research team from Taiwan recently
published a paper which supports increases in dendritic spines in
cortical pyramidal neurons (Brain Struct Funct 2013: "Testosterone
modulation of dendritic spines of somatosensory cortical pyramidal
neurons," Chen, et al.,) Testosterone varies in pregnant
women because of differences in race and differences in women from
the same group. ...evolution: women of higher testosterone
should increase in percentage within a population with time.
(Please see my "Secular Trend" on the right side of my
website, http://anthropogeny.com
.) Also, this increase in women of higher testosterone,
according to my work, should be the main source of autism resulting
from high, maternal testosterone and should increase rapidly within
the population. Therefore, one need not necessarily find a
mutant gene within the mother or the child when there is a natural
method of evolution for increasing the percentage of these women.
Also, I suggest increased testosterone may be
higher in the lower socioeconomic levels. Increased
testosterone has been connected with reduced learning ability,
reduced impulse control, and sexuality. All of these reduce the
ability to obtain gainful employment and participation in a
society
increasingly dependent upon advanced educational
achievement and personal control. This would concentrate this
type of individual within these levels. It has been determined
that "Lower, not higher, socioeconomic status was associated
with an increased risk of ASD. Studies finding the opposite may be
underestimating the burden of ASD in lower SES groups." (J Am
Acad Child Adolesc Psychiatry. 2012 May;51(5):467-476.)
Possible New Proof, May, 2015
Neurochemistry International. 2015 May 4. pii: S0197-0186(15)00069-8. doi: 10.1016/j.neuint.2015.04.008. [Epub ahead of print]
Abnormal instability, excess density, and aberrant morphology of dendritic spines in prenatally testosterone-exposed mice.
Hatanaka Y, Wada K, Kabuta T.
Abstract
Fetal brain development is programmed by the maternal intrauterine environment, and disturbance of the in utero environment leads to persisting deficits in brain functions of the offspring. Testosterone is an intrauterine environmental factor, and plays significant roles in fetal development. From human and animal model studies, it has been suggested that increased intrauterine testosterone concentration triggers subsequent autistic-like behavior of the offspring; however, the effects of maternal excess testosterone on synaptic development of the offspring remain unknown. In the present study, we employed prenatally testosterone-exposed mice, and by using in vivo two-photon imaging, we analyzed the dynamics, density, and morphology of the dendritic spine, an excitatory postsynaptic structure. We found that the offspring from testosterone-treated dams showed abnormal synaptic instability persisting into young adulthood, whereas dendritic spines in control mice became stabilized with normal synaptic maturation. In prenatally testosterone-exposed mice, the density of dendritic spines was excessively increased, and their morphology was abnormal. These results suggest that prenatally testosterone-exposed mice may have deficits in synaptic development, and furthermore that the observed pathological features of their dendritic spines may be the cause of the synaptic pathogenesis in prenatally testosterone-exposed mice.
Copyright © 2015. Published by Elsevier Ltd.
Why Excess Folic Acid in Pregnant Women My Increase Autism, 2016
I suggest the basis of this finding is reduced cortisol.
It is my hypothesis that autism results from increased growth and development of parts of the brain caused by increased use of dehydroepiandrosterone (DHEA) which is increased by high maternal testosterone.
It is also my hypothesis that cortisol evolved to counteract the effects of DHEA and is the basis of the "fight or flight" mechanism. ("A Theory of the Control of the Ontogeny and Phylogeny of Homo sapiens by the Interaction of Dehydroepiandrosterone and the Amygdala," Copyright 1985, James Michael Howard, Fayetteville, Arkansas, U.S.A. (Registered Copyright TXu220580).) The "cortisol to DHEA ratio" appears numerous times in the medical literature; it is becoming an important mechanism.
Folic acid reduces cortisol. Therefore, by reducing cortisol, folic acid may magnify the growth and development caused by increased DHEA in the fetal brains exposed to increased testosterone. This would increase the percentage of these children identified by diagnoses. This may sound contradictory in that DHEA is low in children with autism; as the testosterone-affected structures “come online” in these children, these structures use so much DHEA that measurable DHEA declines.
Regarding Homocysteine and Glutamte
Glutamate and homocysteine are elevated in autism. I suggest this is a side-effect of their low DHEA. Regarding elevated homocysteine, I have explained this condition in schizophrenia: “DHEA and Increased Homocysteine in Schizophrenia and Other Mental Disorders and Declines,” at: http://anthropogeny.com/Homocysteine.htm . Low DHEA allows increased homocysteine and homocysteine is elevated in autism (Psychiatry Res. 2015 Oct 30;229(3):1031-7). It is known that DHEA inhibits glutamate release (Neurochem Res. 2004 Feb;29(2):335-9) and that glutamate is increased in autism (Neuroreport. 2016 Mar 2;27(4):272-6).