Saturday, May 5, 2007

Evolution of ASDs as invoking tool using phenotype

A major implication of the low NO hypothesis of ASDs is that ASDs are actually evolved adaptive features of human physiology, that ASDs are a fundamental “stress response”, arising from maternal stress in utero and that the characteristic features of ASDs are invoked due to maternal stress. The function of these ASD characteristics is to invoke the “tool making”, and “tool using” phenotype, most characteristically expressed by individuals with Asperger’s, such as Newton, Einstein, and many other great scientists, engineers, and artists. It is well known that many organs are epigenetically programmed by stress in utero [1]. It would be surprising if the most important organ, the brain, were not.

Review of evolution

How does any trait evolve? DNA mutates, acquires new function(s), confers reproductive advantage(s), and is selected for. Evolution selects against non-reproduction from all causes simultaneously. If a trait increases survival/reproduction, evolution will increase that trait until more decreases survival/reproduction (i.e. causes death). There are no other evolutionary endpoints. All “well evolved” traits will prevent death in some circumstances and cause death in others. An overly exuberant immune response (anaphylaxis) can cause death. Anaphylaxis is complex, and exhibits complex genetics. It is not considered a complex disease because an exuberant immune response has understood benefits. Evolution has configured the immune system to minimize the sum of deaths from infection and from anaphylaxis. It is not that anaphylaxis is a “benefit”; rather an immune system capable of anaphylaxis is superior to one that is not. Stress responses are among the most conserved pathways [2]. Many of them date to billions of years ago, long before there were multi-celled organisms, long before there were mitochondria and eukaryotes. Presumably because they are ancient, they are “well evolved”, and when activated too exuberantly each stress response can and will cause death. Whether we call such a trait a “feature” or a “disorder” depends only on the circumstances.

How does a trait that is an emergent property of >100 genes evolve? Genes mutates, mutant genes confer advantageous traits, over evolutionary time organisms with those mutated genes survive/reproduce more and the mutant genes become common in the gene pool. Interactions between different genes enhance survival and advantages from different combinations increase the frequency of those combinations in the gene pool. But that is for advantageous traits. How does a disadvantageous trait evolve? It can only evolve if it is coupled to an advantageous trait that more than compensates for the disadvantage, as in sickle cell trait (which protects against malaria when heterozygous and can causes sickle cell disease when homozygous). Perhaps a negative trait could appear via a novel combination of genes. That would be a rare stochastic occurrence and could not be a cause of common disorders. A novel combination should have novel effects.

The traits of ASDs are not novel, they are characteristic of many people, with autism now having a prevalence of ~5.5-5.7 per 1,000 births [3]. ASDs present on a spectrum with variable severity even in monozygous twins. In some ASD families, all siblings are affected, and affected seriously enough that survival in the “wild” (>100k years ago) would be questionable. ASD occurs in children, long before there is the possibility of reproduction. ASD traits of sub diagnostic severity are not uncommon [4]. I suggest that all humans have some traits of ASD. It is only when those traits reach clinical diagnostic thresholds is someone said to have an ASD, and when severe, to have autism. These distinctions are purely arbitrary, much like the difference between being short and tall, but vastly more complicated.

Humans are unique for their brains and ability to use tools. Humans evolved large and complex brains only because such brains conferred survival and reproductive benefits. Human evolution was shaped mostly by events 100k or more years ago. Humans are the only extant hominin that manufactures and uses tools. The first instances of manufactured stone tools date to about 2.5 to 2.7 MYA (million years ago), and was near universal by 2 MYA [5]. Tools of perishable materials perhaps were earlier. Modern humans are good at tool manufacture and tool use. Tool use has profoundly shaped human evolution and those parts of the human genome that affect brain structures important for tool creation and use. The major structures of the brain are formed in utero and early childhood, and are then largely fixed throughout adult life. It is only in utero and early childhood that major structural changes in the brain, such as are characteristic of ASDs can develop, including larger numbers of neurons[6 ], larger brains, and increased asymmetries [7 ].
Which individuals are most adept at tool use today? It is people with Asperger’s, people with ASD. Many scientists and engineers have Asperger’s, and it is suggested that Einstein, Newton, and many brilliant scientists had Asperger’s [8]. Asperger even said “It seems that for success in science or art a dash of autism is essential.”[9] The stereotypical nerd is someone with facility at math, science and with characteristically poor social skills [10]. The mirror neuron system[11] (responsible for understanding the actions of other individuals) exhibits dysfunction proportional to ASD severity [12].
The major barrier to revolutionary scientific innovation is conventional thinking and existing paradigms [13]. What Kuhn calls “normal science”. Ideas transmitted culturally are difficult to displace even when wrong. It is nearly 150 years since Darwin’s “Origin of Species”, with overwhelming data supporting and no datum inconsistent with evolution, yet in the USA, 40% of the population believes evolution is false [14]. Some on the Nobel Committee were unable to accept relativity as valid and so Einstein received the Nobel Prize for the photoelectric effect, not relativity [15].
Cultural notions of what is appropriate affect abilities (i.e. what people think they or anyone can do). Women exposed to a hypothesis wrongly attributing mathematical ability to genes on the Y chromosome have impaired mathematics performance [16]. A degree of social isolation from disrupted mirror neurons may insulate ASD individuals from incorrect paradigms of science, technology and the peer pressure associated with cultural practices which must be abandoned to overcome the current hard times. No doubt 2.8 MYA everyone “knew” stones didn’t make good tools.
The first stone tools were not developed after committees of peers reviewed proposals and selected the highest scoring for implementation; they were developed by the “Einsteins” of the time working alone. Acquisition of nut cracking skill by capuchin monkeys (Cebus apella) using stones as hammer and anvil takes about 2 years and requires considerable repetitive nonproductive effort while watching proficient individuals [17]. No doubt repetitive trial and error was needed to acquire de novo skill(s) to manufacture stone tools 2 MYA, and such individuals were thought bizarre for “uselessly” banging stones together.

Evolutionary selection exerts its greatest effects not when times are easy, but when times are hard. It is when times are hard, that greater facility with tool creation and use would have its greatest effects on human evolution and be most positively selected for. What were “hard” times 1, 2, 3 MYA? Likely much the same as today, famine, disease, migration, and war. These all cause “stress”. Stress is a low NO state.
I propose that exposure to lowered basal NO in utero due to maternal stress (or other causes) at specific times of fetal neuronal development may produce the characteristic hyperplasia of neural structures associated with Asperger’s and other ASDs. Low NO is suggested to cause the characteristic minicolumn structure associated with autism [18] and the timing of stressors may be crucial to the development of the autism phenotype [19]. In guinea pigs, brief prenatal stress increases brain/body mass ratio, and changes adult behavior [20]. Prenatal stress increases learning ability in rats.[21] Prenatal stress does program hypothalamo-pituitary-adrenal function [22]. Low NO does cause neuronal hyperplasia [23]. The patterning of many neural structures is determined in part by gradients in NO mediating proliferation, differentiation, or apoptosis [24]. Stress in utero causes adaptive changes in the adult physiology of multiple organs. It would be surprising if it did not exert adaptive influences on the most important organ, the brain.

Table 1. lists a few pathways involving NO important in development. The list is incomplete, and is only to illustrate that the numbers of pathways involving NO as a regulatory signal is not small, numbering in the thousands, more than enough degrees of freedom to elicit many extremely complex responses, far beyond our ability to predict a priori, or even to model once completely known in complete and precise detail.

There are multiple families of pathways where NO actively modulates the development of specific brain structure via transcription, DNA methylation, the cell cycle, proliferation, differentiation, apoptosis, growth factor, and receptor mediated effects, all of which are coupled, all of which are nonlinear, and none of which are fully understood. Because these pathways are already regulated by NO, any change in the basal level will change the outcome.
Nonlinear coupled systems of even a few variables are completely intractable to understand and model. We should not be surprised to see complex effects when NO physiology is perturbed even slightly. Monoamniotic twins can be discordant for anencephaly [25] and monozygous twins can be discordant for ASDs, demonstrating the cause(s) of these are not solely genetic, and that large effects can derive from very slightly different environments in utero. The NO exposure history may be identical, but because the development is not exactly synchronous, the outcome can be completely different, as is the characteristic chaotic behavior of coupled non-linear systems.

The way that people with ASDs are treated, being bullied, is characteristic. Children with special needs are bullied more than normal children.[26] Exposure to violence and victimization by bullies does lead to increased aggression and violent behavior, [27]
Table 1. NO pathways

called the “cycle of violence” [43]. It is unlikely that bullies 2 MYA were gentler. There are reports of teenage boys being bullied, acquiring weapons and planning or committing massacres as at Columbine. In more than two thirds of cases there was clear and obvious bullying [44]. In Green Bay Wisconsin, three boys were bullied, developed and implemented a plan to fight back, with guns, bombs and home-made napalm [45, 46]. No doubt young men 2 MYA made similar plans when they were bullied. Adults bully [47] as do academics [48] as do teachers [49].

I speculate that when times got hard; people with ASDs were born, were bullied as children, left as teenagers, developed new weapons technology, came back, killed the alpha male bullies and got the females. A scenario that may have played out millions of times. Because all members of a tribe were likely related, a bully may reproductively benefit through his sister, daughter, or cousin even if he is killed. The new technology may be adopted by the tribe and benefit the inventors’ siblings even if the inventors were killed. As Max Planck said: “A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die, and a new generation grow up that is familiar with it.” Once new technology is developed, be it fire, weapons, agriculture, or clothing, things get easier, stress goes down, children are born with less ASDs, until times get hard again. It is important to remember, that evolution has configured neurodevelopment to minimize death/non-reproduction from all causes simultaneously. That includes death due to inability to develop new technology from not enough ASD traits being balanced by non-reproduction from being "too geeky" from too much.

Violence against women, pregnant women and the cycle of violence

Inducing stress on pregnant women via any mechanism should have similar effects. There is an increased incidence of autism among first born. Whether that is due to first pregnancy anxiety, or stoppage, or other factor(s) remains unknown. Humans are unique among mammals for a high level of preeclampsia and miscarriage which also occurs in contemporaneous hunter gatherer societies suggesting modern environmental effects are not the cause [50]. Preeclampsia exhibits complex genetics [51]. Preeclampsia is a state of oxidative stress [52] and so is a low NO state. Eclampsia and preeclampsia may be dysfunctional extreme forms of a “feature” that induces a degree of neuronal hyperplasia in the developing fetus by inducing low NO.

Intuitively, we would expect strong evolutionary pressure against males abusing females pregnant with their fetus (were such abuse to be solely negative). I was unable to find studies documenting such behavior in non-humans. Physical and emotional abuse of pregnant women is not unknown, or even rare [53], approaching 10% of women in many populations [54]. In regions where “honor killings” occur, assault of women by their partners can exceed 50% [55] . Violence against women might be an evolved mechanism for “programming” the brain of the fetus in utero by changing the in utero environment, providing a rationale for violence against pregnant women by the father of the fetus, or by females’ relatives.

Abuse is considered to be solely detrimental, but in the “wild”, some effects of abuse could be “features”. Low birth weight is a serious problem and abuse is associated with lower birth weight [56]. Babies too large to be born vaginally can now be delivered by caesarian section, an option not available 100k year ago when a baby too large for vaginal birth would certainly die, likely killing the mother. Abuse might induce a degree of ASD, improve facility in tool use, and might foster other behaviors in anticipation of stress. The cycle of violence may be the epigenetic implementation of the adage “the best defense is a good offense”. When times are hard, rapid escalation to violence may be advantageous. Violence against women is most frequent during that couple’s hard times. So called “honor killings” of women are most frequent in regions where the cycle of violence and blood feuds are particularly strong.
This is not to suggest or imply that violence against women is acceptable. If this hypothesis is correct, it is an unfortunate circumstance of human evolution that such violence resulted in survival and reproductive benefits and so may have been selected for enough so that DNA supporting those traits has become a part of the human genome. However that benefit may only pertains in the “wild”, where death from abuse balanced survival from cephalopelvic disproportion.

Just as rape, infanticide and murder of romantic rivals can be successful reproductive strategies for males, so too may pregnant female abuse. It may be a successful strategy for females as well. A strategy some females may unconsciously use in selecting mates or in behaving toward them while pregnant. This is not to excuse or condone such violence but may explain some of the difficulty social policy has in dealing with it. These characteristics are from deep evolutionary time, and likely predate Homo sapiens (as does alpha male infanticide).

Alpha male infanticide is not unknown in current human behavior, is common in recorded history, and was once mandated by major religious traditions.[57] All humans are descended from individuals who reproduced using these strategies. No doubt under the right kind of stress, any human will have these characteristics and behaviors. The behaviors are not “genetic”, they are epigenetic. It is not that alpha male infanticide is "always" a reproductive benefit, rather a developmental program that can generate males capable of infanticide (under the "proper" circumstances) is "superior" (i.e. has greater reproductive benefit) than one that cannot. The development programs written in our genome supports these and other developmental outcomes. To prevent these developmental outcomes, we need to prevent the "proper" circumstances (where such behaviors do provide reproductive benefits) from occurring. If this hypothesis is correct, bullying will not deter such behaviors, it will make them worse. The way to prevent violent adults is to “coddle” them in utero and as children. But that is not a surprise to anyone who understands human behavior. It is surprising that it takes someone with Asperger's to appreciate it.

1 Jeffrey Schwartz and Janna L. Morrison. Impact and mechanisms of fetal physiological
programming. Am J Physiol Regulatory Integrative Comp Physiol 288:11-15, 2005.

2 Kultz D. Evolution of the cellular stress proteome: from monophyletic origin to ubiquitous function. Exp Biol. 2003 Sep;206(Pt 18):3119-24.

3 Centers for Disease Control and Prevention (CDC). Mental health in the United States: parental report of diagnosed autism in children aged 4-17 years--United States, 2003-2004. MMWR Morb Mortal Wkly Rep. 2006 May 5;55(17):481-6

4 Constantino JN, Todd RD. Autistic traits in the general population: a twin study. Arch Gen Psychiatry. 2003 May;60(5):524-30.

5 Susman RL. Fossil Evidence for Early Hominid Tool Use. Science. 1994 Sep 9;265(5178):1570-3.

6 Courchesne E, Karns CM, Davis HR, Ziccardi R, Carper RA, Tigue ZD, Chisum HJ, Moses P, Pierce K, Lord C, Lincoln AJ, Pizzo S, Schreibman L, Haas RH, Akshoomoff NA, Courchesne RY. Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study. Neurology. 2001 Jul 24;57(2):245-54.

7 Herbert MR, Ziegler DA, Deutsch CK, O'Brien LM, Kennedy DN, Filipek PA, Bakardjiev AI, Hodgson J, Takeoka M, Makris N, Caviness VS Jr. Brain asymmetries in autism and developmental language disorder: a nested whole-brain analysis. Brain. 2005 Jan;128(Pt 1):213-26.

8 James I Singular scientists. J R Soc Med. 2003 Jan;96(1):36-9.

9 quoted in 8.
10 Al Yankovic. White & Nerdy. Music video by "Weird Al" Yankovic from the album "Straight Outta Lynwood" Volcano records. http://www.youtube.com/watch?v=-xEzGIuY7kw (accessed 12/25/2006)

11 Rizzolatti G, Craighero L. The mirror-neuron system. Annu Rev Neurosci. 2004;27:169-92.

12 Dapretto M, Davies MS, Pfeifer JH, Scott AA, Sigman M, Bookheimer SY, Iacoboni M. Understanding emotions in others: mirror neuron dysfunction in children with autism spectrum disorders. Nat Neurosci. 2006 Jan;9(1):28-30.

13 Thomas S. Kuhn. The Structure of Scientific Revolutions. 3d edition. University of Chicago Press, 1996.

14 Miller JD, Scott EC, Okamoto S. Public Acceptance of Evolution. Science. 2006 Aug 11;313(5788):765-6.

15 Friedman RM. Einstein and the Nobel Committee: Authority vs. Expertise. europhysics news July/August 2005 129-133.

16 Dar-Nimrod I, Heine SJ. Exposure to Scientific Theories Affects Women’s Math Performance. Science. 2006 Oct 20;314(5798):435.

17 Ottoni EB, de Resende BD, Izar P. Watching the best nutcrackers: what capuchin monkeys (Cebus apella) know about others' tool-using skills. Anim Cogn. 2005 Oct;8(4):215-9.

18 Gustafsson L. Comment on "Disruption in the inhibitory architecture of the cell minicolumn: implications for autism". Neuroscientist. 2004 Jun;10(3):189-91.

19 Beversdorf DQ, Manning SE, Hillier A, Anderson SL, Nordgren RE, Walters SE, Nagaraja HN, Cooley WC, Gaelic SE, Bauman ML. Timing of prenatal stressors and autism. J Autism Dev Disord. 2005 Aug;35(4):471-8.

20 Kapoor A, Matthews SG. Short periods of prenatal stress affect growth, behaviour and hypothalamo–pituitary–adrenal axis activity in male guinea pig offspring. J Physiol. 2005 Aug 1;566(Pt 3):967-77.

21 Cannizzaro C, Plescia F, Martire M, Gagliano M, Cannizzaro G, Mantia G, Cannizzaro E. Single, intense prenatal stress decreases emotionality and enhances learning performance in the adolescent rat offspring: interaction with a brief, daily maternal separation. Behav Brain Res. 2006 Apr 25;169(1):128-36.

22 Kapoor A, Dunn E, Kostaki A, Andrews MH, Matthews SG. Fetal programming of hypothalamo-pituitary-adrenal function: prenatal stress and glucocorticoids. J Physiol. 2006 Apr 1;572(Pt 1):31-44.
23 Peunova N, Scheinker V, Cline H, Enikolopov G. Nitric oxide is an essential negative regulator of cell proliferation in Xenopus brain. J Neurosci. 2001 Nov 15;21(22):8809-18.

24 Contestabile A, Ciani E. R Role of nitric oxide in the regulation of neuronal proliferation, survival and differentiation. Neurochem Int. 2004 Nov;45(6):903-14.

25 Lim KI, Dy C, Pugash D, Williams KP. Monoamniotic twins discordant for anencephaly managed conservatively with good outcomes: two case reports and a review of the literature. Ultrasound Obstet Gynecol. 2005 Aug;26(2):188-93.

26 Van Cleave J, Davis MM. Bullying and peer victimization among children with special health care needs. Pediatrics. 2006 Oct;118(4):e1212-9.

27 Johnson RM, Kotch JB, Catellier DJ, Winsor JR, Dufort V, Hunter W, Amaya-Jackson L. Adverse behavioral and emotional outcomes from child abuse and witnessed violence. Child Maltreat. 2002 Aug;7(3):179-86.

28 St Croix CM, Wasserloos KJ, Dineley KE, Reynolds IJ, Levitan ES, Pitt BR. Nitric oxide-induced changes in intracellular zinc homeostasis are mediated by metallothionein/thionein. Am J Physiol Lung Cell Mol Physiol. 2002 Feb;282(2):L185-92.

29 Tupler R, Perini G, Green MR. Expressing the human genome. Nature. 2001 Feb 15;409(6822):832-3.

30 Hemish J, Nakaya N, Mittal V, Enikolopov G. Nitric Oxide Activates Diverse Signaling Pathways to Regulate Gene Expression. J Biol Chem. 2003 Oct 24;278(43):42321-9.

31 Danishpajooh IO, Gudi T, Chen Y, Kharitonov VG, Sharma VS, Boss GR. Nitric Oxide Inhibits Methionine Synthase Activity in Vivo and Disrupts Carbon Flow through the Folate Pathway. J Biol Chem. 2001 Jul 20;276(29):27296-303.

32 Nisoli E, Clementi E, Paolucci C, Cozzi V, Tonello C, Sciorati C, Bracale R, Valerio A, Francolini M, Moncada S, Carruba MO. Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide. Science. 2003 Feb 7;299(5608):896-9.

33 Nisoli E, Falcone S, Tonello C, Cozzi V, Palomba L, Fiorani M, Pisconti A, Brunelli S, Cardile A, Francolini M, Cantoni O, Carruba MO, Moncada S, Clementi E. Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals. Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16507-12.

34 Ruiz-Stewart I, Tiyyagura SR, Lin JE, Kazerounian S, Pitari GM, Schulz S, Martin E, Murad F, Waldman SA. Guanylyl cyclase is an ATP sensor coupling nitric oxide signaling to cell metabolism. Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):37-42.
35 Morgan ET, Ullrich V, Daiber A, Schmidt P, Takaya N, Shoun H, McGiff JC, Oyekan A, Hanke CJ, Campbell WB, Park CS, Kang JS, Yi HG, Cha YN, Mansuy D, Boucher JL. Cytochromes P450 and flavin monooxygenases--targets and sources of nitric oxide. Drug Metab Dispos. 2001 Nov;29(11):1366-76.

36 Muldowney JA 3rd, Davis SN, Vaughan DE, Brown NJ. NO Synthase Inhibition Increases Aldosterone in Humans. Hypertension. 2004 Nov;44(5):739-45.

37 Mollace V, Muscoli C, Masini E, Cuzzocrea S, Salvemini D. Modulation of prostaglandin biosynthesis by nitric oxide and nitric oxide donors. Pharmacol Rev. 2005 Jun;57(2):217-52.

38 Falcone S, Mauro L, de Rose G, Paolucci C, Sciorati C, Ando S, Clementi E. Nitric oxide regulates oestrogen-activated signalling pathways at multiple levels through cyclic GMP-dependent recruitment of insulin receptor substrate 1. Biochem J. 2002 Aug 15;366(Pt 1):165-73.

39 Ji JY, Diamond SL. Exogenous nitric oxide activates the endothelial glucocorticoid receptor. Biochem Biophys Res Commun. 2004 May 21;318(1):192-7.

40 Murphy PR, Limoges M, Dodd F, Boudreau RT, Too CK. Fibroblast growth factor-2 stimulates endothelial nitric oxide synthase expression and inhibits apoptosis by a nitric oxide-dependent pathway in Nb2 lymphoma cells. Endocrinology. 2001 Jan;142(1):81-8.

41 Canossa M, Giordano E, Cappello S, Guarnieri C, Ferri S. Nitric oxide down-regulates brain-derived neurotrophic factor secretion in cultured hippocampal neurons. Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3282-7.

42 Traister A, Abashidze S, Gold V, Yairi R, Michael E, Plachta N, McKinnell I, Patel K, Fainsod A, Weil M. BMP controls nitric oxide-mediated regulation of cell numbers in the developing neural tube. Cell Death Differ. 2004 Aug;11(8):832-41.

43 Dodge KA, Bates JE, Pettit GS. Mechanisms in the cycle of violence. Science. 1990 Dec 21;250(4988):1678-83.

44 Twemlow SW, Fonagy P, Sacco FC, Otoole ME, Vernberg E. Premeditated mass shootings in schools: threat assessment. J Am Acad Child Adolesc Psychiatry. 2002 Apr;41(4):475-7.

45 http://www.jsonline.com/story/index.aspx?id=498353 (accessed 12/25/06)

46 http://www.jsonline.com/story/index.aspx?id=498527 (accessed 12/25/06)

47 Tracy SJ, Lutgen-Sandvik P, Alberts JK. Nightmares, Demons, and Slaves Exploring the Painful Metaphors of Workplace Bullying. Management Communication Quarterly Volume 20 Number 2 November 2006 148-185.
48 D. Nelson ED, Lambert RD. Sticks, Stones and Semantics: The Ivory Tower Bully’s Vocabulary of Motives. Qualitative Sociology, Vol. 24, No. 1, 2001. 83-106.

49 Twemlow SW, Fonagy P. The prevalence of teachers who bully students in schools with differing levels of behavioral problems. Am J Psychiatry. 2005 Dec;162(12):2387-9.

50 Jauniaux E, Poston L, Burton GJ. Placental-related diseases of pregnancy: Involvement of oxidative stress and implications in human evolution. Hum Reprod Update. 2006 Nov-Dec;12(6):747-55.

51 Reimer T, Koczan D, Gerber B, Richter D, Thiesen HJ, Friese K. Microarray analysis of differentially expressed genes in placental tissue of pre-eclampsia: up-regulation of obesity-related genes. Mol Hum Reprod. 2002 Jul;8(7):674-80.

52 Hubel CA. Oxidative stress in the pathogenesis of preeclampsia. Proc Soc Exp Biol Med. 1999 Dec;222(3):222-35.

53 Bowen E, Heron J, Waylen A, Wolke D; ALSPAC Study Team. Domestic violence risk during and after pregnancy: findings from a British longitudinal study. BJOG. 2005 Aug;112(8):1083-9.

54 Cohen MM, Maclean H. Violence against Canadian Women. BMC Womens Health. 2004 Aug 25;4 Suppl 1:S22.

55 Bott S, Morrison A, Ellsberg M. Preventing and responding to gender-based violence in middle and low-income countries: a global review and analysis. World Bank Policy Research Working Paper 3618, June 2005. http://www-wds.worldbank.org/external/default/WDSContentServer/WDSP/IB/2005/06/28/000112742_20050628084339/Rendered/PDF/wps3618.pdf (accessed 01/07/07).

56 Murphy CC, Schei B, Myhr TL, Du Mont J. Abuse: a risk factor for low birth weight? A systematic review and meta-analysis. CMAJ. 2001 May 29;164(11):1567-72.

57 Bible, Numbers 31:17-18.

7 comments:

Unknown said...
This comment has been removed by a blog administrator.
Anonymous said...

Hi quick heads up on forthcoming article by Crespi et al.

Genomic sister-disorders of neurodevelopment: an evolutionary approach.
Bernard Crespi, Kyle Summers, Steve Dorus

http://www3.interscience.wiley.com/journal/120126559/issue

/S

daedalus2u said...

Thanks, that is interesting. You might want to look at this.

http://www.sfu.ca/biology/faculty/crespi/pdfs/115-Crespi&Badcock2008.pdf

“Psychosis and Autism as Diametrical Disorders of the Social Brain”
by Bernard Crespi and Christopher Badcock
BEHAVIORAL AND BRAIN SCIENCES (2008) 31, 241–320

In looking at the spectrum of symptoms associated with the psychotic spectrum, they do (somewhat) tend to associate with high NO, where the autism spectrum associate with low NO; brain size, birth weight, growth rate.

I saw a very interesting talk by Judith Miles

http://web.mit.edu/autism/miles.html

Where she talked about the association of dysmorphic features with autism and that autism without dysmorphic features (what she calls essential autism) was quite different than autism with dysmorphic features (what she calls complex autism).

http://www3.interscience.wiley.com/journal/117949828/abstract

http://www3.interscience.wiley.com/journal/110491777/abstract

(I have only seen the abstracts of these).

My guess is that complex autism is more of a side effect of what ever caused the dysmorphic features and that essential autism is more related to the ToM vs. ToR trade-off.

I recently realized that ketosis raises NO levels so as to increase mitochondria number in most/all tissues. I think that increased NO level is why a ketogenic diet helps with epilepsy. I think the increased mitochondria number is so that cells can use ketone bodies for ATP production and not glycolysis. During ketosis, the only way to make glucose is from 3 carbon precursors, from the glycerol of fatty acids or from proteins. Better to save glucose for things that really need it, and switch as much as possible over to ketone bodies (which require mitochondria).

Anonymous said...

Interesting that it's low NO. Apparently women with CFS are a lot more likely to have autistic children, but in CFS, NO is high.
http://www.ahmf.org/05currentper.htm
CFS also long associated with mitochondrial problems.
Although looking at that diagnostic diagram here http://www.ahmf.org/05currentper.htm it does show NO to be low in one subset of CFS, the MS-like subset. (I come from a family with CFS, MS, and Aspergers.)

daedalus2u said...

anon 8:38, sorry it has taken me a while to respond.

It is not correct that NO is elevated in CFS. CFS is caused by low NO (my hypothesis).

I am in a gigantic time crunch right now. For more on how low NO causes CFS check out this.

http://www.chronicfatiguetreatments.com/wordpress/treatments/chronic-fatigue-syndrome-nitric-oxide/

Theresa said...

This is awesome!

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