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.


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).