Hormonal Changes in Autism |
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Standard findingsChildren with autism are not sterile, go through puberty at the same time, are the same size and strength and will show other hormonal factors similarly to controls. However, many investigations of hormones in autistic children have shown differences when measuring the actual levels. Section Heading Goes HereThe quick brown fox jumps over the lazy dog. The quick brown fox jumps over the lazy dog. The quick brown fox jumps over the lazy dog. The quick brown fox jumps over the lazy dog. The quick brown fox jumps over the lazy dog.
Section Heading Goes HereThe quick brown fox jumps over the lazy dog. The quick brown fox jumps over the lazy dog. The quick brown fox jumps over the lazy dog. The quick brown fox jumps over the lazy dog. The quick brown fox jumps over the lazy dog. |
Production of
melatonin |
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Melatonin
A simple
compound produced in the pineal gland in the brain by biochemistry from tryptophan. It is
not essential but changes according to the light cycle of the day and can be
used to alter this and avoid ‘jet lag’.
Edward R. Ritvo, Riva Ritvo,
Arthur Yuwiler, Anne Brothers,
B. J. Freeman and
Nir I, Meir D, Zilber N, Knobler H, Hadjez J, Lerner Y. Brief report:
circadian melatonin, thyroid-stimulating hormone, prolactin and cortisol levels in serum of young adults
with autism. J Autism Dev Disord
1995;25(6):641-54. Showed loss of
circadian rhythms chemically with melatonin and cortisol
testing. This in some degree is similar
to the findings of the loss of the changes seen throughout the day in cortisol.
Konturek SJ, Konturek PC, Brzozowska I, Pawlik M, Sliwowski Z, Cześnikiewicz-Guzik M, Kwiecień S, Brzozowski T, Bubenik GA, Pawlik WW. Localization and biological activities of melatonin in intact and diseased gastrointestinal tract (GIT). J Physiol Pharmacol. 2007 Sep;58(3):381-405. Review (This review focuses on the localization, production, metabolism and the functions of MT in GIT and the duodenal unit (liver, biliary routes and pancreas), where multi-step biosynthetic pathways of this indole, similar to those in pinealocytes, have been identified. Interesting to read about the involvement of the cells of the gut in its production and significance)
Ishizaki A, Sugama M, Takeuchi N [Usefulness of melatonin for developmental sleep and emotional/behavior disorders--studies of melatonin trial on 50 patients with developmental disorders] No To Hattatsu. 1999 Sep;31(5):428-37.[Article in Japanese] (they found melatonin to be useful in 35 of 50 patients)
Nocturnal excretion of 6-sulphatoxymelatonin in children and adolescents with autistic disorder.Tordjman S, Anderson GM, Pichard N, Charbuy H, Touitou Y. Biol Psychiatry. 2005 Jan 15;57(2):134-8. They found dramatically lower levels (than controls) of melatonin products excreted in the urine at night.
Abnormal melatonin synthesis in autism spectrum disorders. Melke J, Goubran Botros H, Chaste P, Betancur C, Nygren G, Anckarsäter H, Rastam M, Ståhlberg O, Gillberg IC, Delorme R, Chabane N, Mouren-Simeoni MC, Fauchereau F, Durand CM, Chevalier F, Drouot X, Collet C, Launay JM, Leboyer M, Gillberg C, Bourgeron T. Mol Psychiatry. 2008 Jan;13(1):90-8. A low melatonin level has been reported in individuals with autism spectrum disorders (ASD), but the underlying cause of this deficit was unknown. They are saying that there is a poor connection between daytime and night time vs the production of melanin in autistic children. Also they follow the gene that produces it and suggest that this may be involved.
Jan JE, O'Donnell ME. Use of melatonin in the treatment of paediatric sleep disorders. J Pineal Res. 1996 Nov;21(4):193-9. Review
Giannotti F, Cortesi F, Cerquiglini A, Bernabei P. An open-label study of controlled-release melatonin in treatment of sleep disorders in children with autism. J Autism Dev Disord. 2006 Aug;36(6):741-52. (25 children, aged 2.6-9.6 years with autism without other coexistent pathologies was evaluated openly. During treatment sleep patterns of all children improved. After discontinuation 16 children returned to pre-treatment score, readministration of melatonin was again effective. They had no side effects reported. This is a very encouraging study)
Melatonin in treatment of chronic sleep disorders in
adults with autism: a retrospective study. Galli-Carminati
G, Deriaz N, Bertschy G. Swiss Med Wkly. 2009 May 16;139(19-20):293-6. This
study presents the use of melatonin to treat severe circadian sleep-wake
disturbances in 6 adults with autism. Melatonin was initiated at a daily dose
of 3 mg at nocturnal bedtime. If this proved ineffective, the melatonin dose
was titrated over the following 4 weeks at increments of 3 mg/2 weeks up to a
maximum of 9 mg, unless it was tolerated.
Melatonin administered in the evening dramatically improved the
sleep-wake pattern in all patients. Melatonin appears to be effective in
reducing sleep onset latency and is probably effective in improving nocturnal
awakenings and total sleep time in adults with autism. Its effectiveness
remained stable for the 6-month period of administration.
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These are adrenaline, noradrenaline, dopamine, and their breakdown products e.g. homovanillic acid (HVA) found in the urine. They are used for a nerve to stimulate another. The actual reason for the increased level of the HVA and other breakdown products is not at all clear in that large amounts of the compounds are used in the gut and elsewhere. The raised levels of the catecholamines in blood have the same problem in that their source is still unclear. Also changes in these levels as a result of drug treatment does also not seem to have been followed.
C. Barthelemy, N. Bruneau,
J. M. Cottet-Eymard, J. Domenech-Jouve, B. Garreau,
G. Lelord, J. P. Muh
and L. Peyrin. Journal
of Autism and Developmental Disorders Volume
18, Number 4 / December, 1988 Urinary catecholamines
(dopamine,DA, norepinephrine
NE, epinephrine E) and their main metabolites (HVA, DOPAC, MHPG) were made both
as free and conjugates in eight children diagnosed as autistic according to
DSM-III criteria and eight normal children. Significant differences appeared
for the urinary excretion of both DA and NE and their respective metabolites:
Autistic children showed low DA, high HVA, high NE, low MHPG urinary levels.
These results are consistent with previous findings on altered catecholamine
metabolism in autistic children. They suggest that autistic behaviour might be
related to an abnormal functional imbalance among monoamines either at a
molecular level or at a system level. Furthermore, they emphasize the special
interest of urinary assays in pediatric research.
Garreau B, Barthélémy C, Jouve J, Bruneau N, Muh JP, Lelord G. Urinary homovanillic acid levels of autistic children. Dev Med Child Neurol. 1988 Feb;30(1):93-8. (increased levels in urine suggested by authors to be due to dopamine turnover)
Barthelemy C, Bruneau N, Cottet-Eymard JM, Domenech-Jouve J, Garreau B, Lelord G, Muh JP, Peyrin L. Urinary free and conjugated catecholamines and metabolites in autistic children. J Autism Dev Disord. 1988 Dec;18(4):583-91. (increased levels found of the free form)
Martineau J, Barthélémy C, Jouve J, Muh JP, Lelord G. Monoamines (serotonin and catecholamines) and their derivatives in infantile autism: age-related changes and drug effects. Dev Med Child Neurol. 1992 Jul;34(7):593-603. 156 autistic children aged two to 12 years 6 months, compared with matched mentally retarded and normal controls. Very significant group and age effects were found for dopamine (DA), Homovanillinic acid (HVA), 3methoxy-tryptamine (3MT), norepinephrine and epinephrine (NE + E) and serotonin (5HT). High HVA, 3MT, NE + E and 5HT levels were found in autistic and non-autistic children. The DA, HVA, 3MT, NE + E, 5HT and its metabolite 5HIAA levels decreased significantly with age in the three groups. Significantly decreased levels of DA and HVA were observed in autistic children on haloperidol)
Israngkun PP,
Newman HA, Patel ST, Duruibe VA,
Abou-Issa H.
Potential biochemical markers for infantile autism. Neurochem Pathol. 1986
Aug;5(1):51-70. (raised epinephrine, norepinephrine, serotonin in blood)
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Secretin
The importance of secretin in autism came about after the small publication of Horvath in 1998. The finding was that some of the children responded dramatically. It was followed by a huge demand for initially porcine then artificial human secretin and extended studies were carried out as to whether there was good evidence as to whether it did the children any advantage. The best result from this is from the Cochrane Database below, which simply says that secretin could not be stated as an advantage to autistic children. However, various parents swear by it and in the various studies there does appear to be some uncommon cases that may improve.
Secretin is a hormone produced by the Langhans cells of the pancreas and other similar cells in the upper part of the small bowel. Its main activity is to cause the gut to produce and release enzymes for the breakdown of foods. It does appear to have activity in causing the growth of the gut, and the induction of the enzyme genes in very young animals.
Roberts W, Weaver L, Brian J, Bryson S, Emelianova S, Griffiths AM, MacKinnon B, Yim C, Wolpin J, Koren G. Repeated doses of porcine secretin in the treatment of autism: a permutation, placebo-controlled trial. Pediatrics. 2001 May;107(5):E71. (minimal effect seen except in an occasional i.e. not statistical case)
Horvath K, Stefanatos G, Sokolski K, et al.
Improved social and language skills after secretin
administration in patients with autistic spectrum disorders. J Assoc Acad Minor Phys. 1998;9:9–15 (the first three given secretin)
Esch BE, Carr JE. Secretin as a treatment for autism: a review of the evidence. J Autism Dev Disord. 2004 Oct;34(5):543-56. (clinical review of 13 studies showing that 12 showed no advantage)
Sandler
A, Sutton K, DeWeese J, et al. Lack of benefit of a
single dose of synthetic human secretin in
the treatment of autism and pervasive developmental disorder. N Engl J Med. 1999;341:1801–1806
Chez MG, Buchanan CP, Bagan BT, et al. Secretin and autism: a two part clinical investigation. J
Autism Dev Disord. 2000;30:87–94
Owley T, Steele E, Corsello C, et al. A double-blind, placebo-controlled trial of secretin for the treatment of autistic disorder. MedGenMed. October 6, 1999
Williams KW, Wray JJ, Wheeler DM. Intravenous secretin for autism spectrum disorder. Cochrane Database Syst Rev. 2005 July 20;(3):CD003495. (Review showing that secretin injections cannot be advised currently as, even the advances seen in occasional patients as the likelihood must be very low)
Pollack PF, Wood
JG, Solomon
T. Effect of secretin on growth of
stomach, small intestine, and pancreas of developing rats. Dig Dis Sci. 1990 Jun;35(6):749-58.
(caused the development of the intestine and organs)
Harada
E, Syuto B.
Secretin induces precocious cessation of
intestinal macromolecular transmission and maltase development in the suckling
rat. Biol
Neonate. 1993;63(1):52-60. (causes the intestine
to stop absorbing molecules that previously came in from the gut e.g. neonatal
milk).
Molloy CA, Manning-Courtney P, Swayne S, Bean J, Brown JM, Murray DS, Kinsman AM, Brasington M, Ulrich CD 2nd. Lack of benefit of intravenous synthetic human secretin in the treatment of autism. J Autism Dev Disord. 2002 Dec;32(6):545-51. (this is just one of the studies that found this. Originally Horvath’s 3 cases to which he gave secretin have been interesting and certainly specific cases claim great improvements but the statistics will not stand up over larger studies)
Connors
SL, Crowell
DE. Secretin
and autism: the role of cysteine. J Am Acad
Child Adolesc Psychiatry. 1999 Jul;38(7):795-6 (no further data)
Secretin as a neuropeptide: Also see discussions on brain biochemistry
Ng SS, Yung WH, Chow BK. Secretin as a neuropeptide.
Mol Neurobiol. 2002 Aug;26(1):97-107. (a review of the action
of secretin neuropeptide:
realising that there is a complex activity of secretin)
Banks WA, Goulet M, Rusche JR, Niehoff ML, Boismenu R. Differential transport of a secretin analog across the blood-brain and blood-cerebrospinal fluid barriers of the mouse. J Pharmacol Exp Ther. 2002 Sep;302(3):1062-9. (shows how the drug is passed across into the brain from the blood system)
Toda
Y, Mori K, Hashimoto T, Miyazaki M, Nozaki S, Watanabe Y, Kuroda Y, Kagami S. Administration of secretin
for autism alters dopamine metabolism in the central nervous system. Brain Dev.
2006 Mar;28(2):99-103. (a complex
study in which they gave 12 autistic children some i.v.
secretin and looked for improvements in biopterin, 5HIAA, and homovanillinic
acid –taken as signs of irritation, serotonin turnover and dopamine turnover-
these were found in 7 but all of those with raised biopterin
results initially)
Welch MG, Keune JD, Welch-Horan TB, Anwar N, Anwar M, Ludwig RJ, Ruggiero DA. Secretin: hypothalamic distribution and hypothesized neuroregulatory role in autism. Cell Mol Neurobiol. 2004 Apr;24(2):219-41.
Welch MG, Keune JD, Welch-Horan TB, Anwar N, Anwar M, Ruggiero DA. Secretin activates visceral brain regions in the rat including areas abnormal in autism. Cell Mol Neurobiol. 2003 Oct;23(4-5):817-37 (they are working their way through specific brain regions and staining sites that secretin will interact with and showing using immunostaining the secretin itself, they also stained for secretin-activated regions by looking for c-fos gene expression).
Nishijima I, Yamagata
T, Spencer
CM, Weeber EJ, Alekseyenko O, Sweatt JD, Momoi MY, Ito
M, Armstrong
DL, Nelson
DL, Paylor R, Bradley
A. Secretin receptor-deficient mice exhibit
impaired synaptic plasticity and social behavior. Hum
Mol Genet. 2006 Nov 1;15(21):3241-50.
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Oxytocin
Like secretin this is a hormone and a neuropeptide. Levels
in the brain have not been measured in autism properly but they have been shown
to be raised in the blood. It is well
known in the body for the stimulation of certain muscular tissues in the body
(e.g. the uterus during giving birth, and gut). The oxytocin receptor gene
(OXTR) has been studied in autism because of the role of oxytocin
(OT) in social cognition. Linkage has also been demonstrated to the region of
OXTR in a large sample.
Modahl C, Fein D, Waterhouse L, Newton
N. Does oxytocin deficiency mediate social deficits in autism? J
Autism Dev Disord. 1992 Sep;22(3):449-51.
(suggest
that if there is low levels then it may cause autistic symptoms)
Modahl C, Green L, Fein D, Morris M, Waterhouse L,
Feinstein C, Levin H. Plasma
oxytocin levels in autistic children.
Biol Psychiatry. 1998 Feb 15;43(4):270-7. (they found
specifically lower levels of oxytocin in the blood of
the autistic children and did not show the normal increase with age)
Panksepp J. Commentary on
the possible role of oxytocin in autism. J
Autism Dev Disord. 1993 Sep;23(3):567-9.
(suggest that excess may cause
autism)
Winslow J, Insel T. The social
deficits of the oxytocin knockout mouse. Neuropeptides
2002;36:221-9. A difficult but helpful
indicator if it is involved in autism.
Welch MG, Ruggiero DA. Predicted role of secretin and oxytocin in the treatment of behavioral and developmental disorders: implications for autism. Int Rev Neurobiol. 2005;71:273-315.
Green L, Fein D, Modahl C, Feinstein C, Waterhouse L, Morris M. Oxytocin (OT) and autistic disorder: alterations in peptide forms (OT-X). Biol Psychiatry. 2001 Oct 15;50(8):609-13 (T tests showed that there was a decrease in plasma OT (t = 4.4, p <.0001), an increase in OT-X (t = 2.3, p <.03) and an increase in the ratio of OT-X/OT (t = 4.5, p <.0001) in the autistic sample, compared with control subjects. CONCLUSIONS: The results suggest that children with autistic disorder show alterations in the endocrine OT system. Deficits in OT peptide processing in children with autism may be important in the development of this syndrome. In other words the method of measuring the oxytocin may be picking up the OT-X and not the OT)
Hollander E, Bartz J, Chaplin W, Phillips A, Sumner J, Soorya L, Anagnostou E, Wasserman S. Oxytocin increases retention of social cognition in autism. Biol Psychiatry. 2007 Feb 15;61(4):498-503. (All subjects showed improvements in affective speech comprehension from pre- to post-infusion; however, whereas those who received placebo first tended to revert to baseline after a delay, those who received oxytocin first retained the ability to accurately assign emotional significance to speech intonation on the speech comprehension task.)
Kirsch P, Esslinger C, Chen Q, Mier D, Lis S, Siddhanti S, Gruppe H, Mattay VS, Gallhofer B, Meyer-Lindenberg A. Oxytocin modulates neural circuitry for social cognition and fear in humans. J Neurosci. 2005 Dec 7;25(49):11489-93. We used functional magnetic resonance imaging to image amygdala activation by fear-inducing visual stimuli in 15 healthy males after double-blind crossover intranasal application of placebo or oxytocin. The author considered that this may be involved with autism
Wu S, Jia M, Ruan Y, Liu J, Guo Y, Shuang M, Gong X, Zhang Y, Yang X, Zhang D. Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population. Biol Psychiatry. 2005 Jul 1;58(1):74-7.
Bartz JA, Hollander E.
Oxytocin and experimental therapeutics in
autism spectrum disorders. Prog Brain Res.
2008;170:451-62 (a review for
2008). Given that OXT is involved in the regulation of
repetitive and affiliative behaviours, and that these
are key features of autism, it is believed that OXT may play a role in autism
and that OXT may be an effective treatment for these two core symptom
domains. They attempt to review the data
already available.
Heinrichs M, Domes G. Neuropeptides and social behaviour: effects of oxytocin and vasopressin in humans. Prog Brain Res. 2008;170:337-50. (there is another article on a very similar subject by these authors)
Molecular genetic studies of the arginine
vasopressin 1a receptor (AVPR1a) and the oxytocin
receptor (OXTR) in human behaviour: from autism to altruism with some notes in
between. Israel S, Lerer E, Shalev I, Uzefovsky F, Reibold M, Bachner-Melman R, Granot R, Bornstein G, Knafo A, Yirmiya N, Ebstein RP. Prog
Brain Res. 2008;170:435-49. Review. Converging evidence from both human and
animal studies has highlighted the pervasive role of two neuropeptides,
oxytocin (OXT) and arginine
vasopressin (AVP), in mammalian social behaviours. Recent molecular genetic
studies of the human arginine vasopressin 1a (AVPR1a)
and oxytocin (OXTR) receptors have strengthened the
evidence regarding the role of these two neuropeptides
in a range of normal and pathological behaviours. Significant association
between both AVPR1a repeat regions and OXTR single nucleotide polymorphisms (SNPs) with risk for autism has been provisionally shown
which was mediated by socialization skills in our study. This is specifically looking on oxytocin as a neuropeptide rather
than a hormone per se.
Association between the oxytocin
receptor (OXTR) gene and autism: relationship to Vineland Adaptive Behavior Scales and cognition. Lerer E, Levi S, Salomon S, Darvasi
A, Yirmiya N, Ebstein RP. Mol Psychiatry. 2008 Oct;13(10):980-8. Evidence
both from animal and human studies suggests that common polymorphisms in the oxytocin receptor (OXTR) gene are likely candidates to
confer risk for autism spectrum disorders (ASD). In lower mammals, oxytocin is important in a wide range of social behaviors, and recent human studies have shown that
administration of oxytocin modulates behavior in both clinical and non-clinical groups.
Additionally, two linkage studies and two recent association investigations
also underscore a possible role for the OXTR gene in predisposing to ASD. Significant association with single SNPs and haplotypes (global
P-values <0.05, following permutation test adjustment) were observed with
ASD. Association was also observed with IQ and the Vineland Adaptive Behavior Scales (VABS). In particular, a five-locus haplotype block
(rs237897-rs13316193-rs237889-rs2254298-rs2268494) was significantly associated
with ASD (nominal global P=0.000019; adjusted global P=0.009) and a single haplotype (carried by 7% of the population) within that
block showed highly significant association (P=0.00005)
Regardless of genotype, offspring of VIP-deficient female
mice exhibit developmental delays and deficits in social behavior. Lim MA, Stack CM, Cuasay
K, Stone MM, McFarlane HG, Waschek JA, Hill JM. Int
J Dev Neurosci. 2008 Aug;26(5):423-34.
An interesting finding in that it is clear that the gene in the mother had an
effect on the offspring’s ongoing brain construction.
Variation of the oxytocin/neurophysin
I (OXT) gene in four human populations. Xu
Y, Xue Y, Asan, Daly A, Wu
L, Tyler-Smith C. J
Hum Genet. 2008;53(7):637-43. Oxytocin is a short peptide with multiple functions in
human biology and has been implicated in autism. We aimed to determine the
normal pattern of variation around the oxytocin gene
and resequenced it and its flanking regions in 91
individuals from four HapMap populations and one
chimpanzee. We identified 14 single nucleotide polymorphisms (SNPs), all noncoding, including
eight that were novel
Association of the oxytocin
receptor gene (OXTR) in Caucasian children and adolescents with autism.
Jacob S, Brune CW, Carter CS, Leventhal
BL, Lord C, Cook EH Jr. Neurosci Lett. 2007 Apr 24;417(1):6-9. Two
single nucleotide polymorphisms (SNPs) and a haplotype constructed from them in OXTR have been
associated with autism in the Chinese Han population…although there is argument
about this. They find that there is
indeed argument and it is difficult to be certain but the same effect seems to
appear in the Caucasian population.
Receptor and behavioral
pharmacology of WAY-267464, a non-peptide oxytocin
receptor agonist. Ring RH, Schechter
LE, Leonard SK, Dwyer JM, Platt BJ, Graf R, Grauer S,
Pulicicchio C, Resnick L, Rahman Z, Sukoff Rizzo SJ, Luo B, Beyer CE, Logue SF, Marquis KL, Hughes ZA, Rosenzweig-Lipson S. Neuropharmacology. 2009. This merely goes through the action of the
drug, which can be given orally, and how it interacts with the receptor
protein to cause the same effect as oxytocin would
have. It then mentions the possibility
of using the drug in autism.
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Growth
hormone
A peptide hormone that is released by the pituitary gland in the
brain. The studies done here are
interesting in that they have tried to see if the growth hormone release will
change according to certain drugs that the patient is receiving. Its specific aim is to cause the growth of
the body as a whole according to a specific rate and plan. It is, however, much more complex than this
simple idea and so when elevated levels of GH related hormones were found in
the blood of autism it was difficult to interpret.
Deutsch SI, Campbell M, Sachar EJ, Green WH, David R. Plasma growth hormone response to L-DOPA in infantile autism. J Autism Dev Disord 1985;15:205-12.
Realmuto GM, Jensen JB, Reeve E, Garfinkel BD. Growth hormone response in
autistic children to DA and NE agonists. In: Proceedings
of the
Mills JL, Hediger ML, Molloy CA, Chrousos GP, Manning-Courtney P, Yu KF, Brasington M, England LJ. Elevated levels of growth-related hormones in autism and autism spectrum disorder. Clin Endocrinol (Oxf). 2007 Aug;67(2):230-7. Epub 2007 Jun 4. (Children with autism/ASD had significantly higher levels of many growth-related hormones: IGF-1, IGF-2, IGFBP-3 and GHBP. The IGFs are the peptide insulin-like growth related factors and the GHBP is the Growth Hormone Binding Protein. They also looked for androgens and found no increased level.)
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Cortisol
(look at these
findings along with ACTH below)
This is an adrenal hormone that is released into the blood and will change many factors throughout
the body in terms of the usage of glucose to the immunity of the body. The finding of low levels of cortisol in autism and high levels of adrenocortitrophic
hormone (ACTH), which causes cortisol’s production
and release suggests that the adrenal gland has just decided not to make it at
the level that the brain (which produces the ACTH) would want. Also the non-suspression
of cortisol by dexamethasone
(which causes the decrease in level of ACTH), and its level not changing during
the circadian rhythm are exceptionally significant. Also, as a neurosteroid, it is found to be low.
Jensen JB, Realmuto GM, Garfinkel BD. The dexamethasone suppression test in infantile autism. J Am Acad Child Psychiatry 1985;24:263-5.
Marinović-Ćurin J, Marinović-Terzić I, Bujas-Petković Z, Zekan L, Skrabić V, Dogaš Z, Terzić J. Slower cortisol response during ACTH stimulation test in autistic children. Eur Child Adolesc Psychiatry. 2007 Sep 14;
Corbett BA, Mendoza S, Abdullah M, Wegelin JA, Levine S. Cortisol circadian rhythms and response to stress in children with autism. Psychoneuroendocrinology. 2006 Jan;31(1):59-68. (The results suggest that children with autism process and respond idiosyncratically to novel and threatening events resulting in an exaggerated cortisol response.)
Strous RD, Golubchik P, Maayan R, Mozes T, Tuati-Werner D, Weizman A, Spivak B. Lowered DHEA-S plasma levels in adult individuals with autistic disorder. Eur Neuropsychopharmacol. 2005 May;15(3):305-9.
Richdale AL, Prior MR. Urinary cortisol circadian rhythm in a group of high-functioning children with autism. J Autism Dev Disord. 1992 Sep;22(3):433-47. (They found that there was not a great difference between the ASD group and the controls except as a response)
Hoshino
Y, Yokoyama F, Watanabe M, Murata S, Kaneko M, Kumashiro
H. The diurnal variation and response to dexamethasone
suppression test of saliva cortisol level in autistic
children. Jpn J Psychiatry Neurol.
1987 Jun;41(2):227-35. Some ASD children
showed a poor diurnal variation.
Hoshino Y, Ohno Y, Murata S, Yokoyama F, Kaneko M, Kumashiro H. Dexamethasone suppression test in autistic children. Folia Psychiatr Neurol Jpn. 1984;38(4):445-9. Not great but minor results suggesting an alteration in the hypothalamo-pituitary axis. It needed to be restudied.
Corbett BA, Mendoza S, Wegelin JA, Carmean V, Levine S. Variable cortisol circadian rhythms in children with autism and anticipatory stress. J Psychiatry Neurosci. 2008 May;33(3):227-34. (this is not a new finding but the article is fully available on the internet)
Gene expression
profiling of lymphoblasts from autistic and nonaffected sib pairs: altered pathways in neuronal
development and steroid biosynthesis. Hu VW, Nguyen A, Kim KS, Steinberg ME,
Sarachana T, Scully MA, Soldin
SJ, Luu T, Lee NH. PLoS One. 2009 Jun 3;4(6):e5775. The way this is done is to look and see which
genes on the lymphocytic population of autistic
children are expressed as proteins, and compare this with the ones in a control
group. They found several genes being
used involve 1. Steroid biochemical
formation pathway (including testerone and female
hormones), 2 cholesterol importation
into the cell (SCARB1 and SRD5A1 genes),
plus a list more. What does not
come out is a gene that is a reliable diagnostic, but it does give an insight
into the reasons why other biochemical changes are seen in the body and
brain. They are going particularly into
the effect of the genes, the proteins, and hence the formation of hormones that
is involved. This is a complex
article.
ACTH raised
Tordjman S, Anderson GM, McBride PA, Hertzig ME, Snow ME, Hall LM, Thompson SM, Ferrari P, Cohen DJ. Plasma beta-endorphin, adrenocorticotropin hormone, and cortisol in autism. J Child Psychol Psychiatry. 1997 Sep;38(6):705-15. Higher serum endorphin and ACTH taken by authors to be due to stress responses. Comparison of log transformed data from the three groups revealed that levels of BE and ACTH were significantly higher (p < .05) in the autistic individuals than in normal control
Tani P, Lindberg N, Matto V, Appelberg B, Nieminen-von Wendt T, von Wendt L, Porkka-Heiskanen T. Higher plasma ACTH levels in adults with Asperger syndrome. J Psychosom Res. 2005 Jun;58(6):533-6.
Curin JM, Terzić J, Petković ZB, Zekan L, Terzić IM, Susnjara IM. Lower cortisol and higher ACTH levels in individuals with autism. J Autism Dev Disord. 2003 Aug;33(4):443-8. (also prolactin concentrations in autistic patients with epilepsy were significantly higher when compared with normal subjects). This suggests that the ACTH was unable to cause a specific rise in cortisol and the feedback had been lost.
Slower cortisol response during ACTH stimulation test in autistic children. Marinović-Curin J, Marinović-Terzić I, Bujas-Petković Z, Zekan L, Skrabić V, Dogas Z, Terzić J. Eur Child Adolesc Psychiatry. 2008 Feb;17(1):39-43.
Autonomic and neuroendocrine responses to a psychosocial stressor in adults with autistic spectrum disorder. Jansen LM, Gispen-de Wied CC, Wiegant VM, Westenberg HG, Lahuis BE, van Engeland H. J Autism Dev Disord. 2006 Oct;36(7):891-9. Ten autistic spectrum disorder (ASD) adults were compared to 14 healthy controls in their response to a psychosocial stressor (public speaking). ASD patients showed decreased heart rate, but normal cortisol responses, consistent with our prior findings in children (and hence ACTH)
e.g. Cytokines acting as hormones
Suzuki K, Hashimoto K, Iwata Y, Nakamura K, Tsujii M, Tsuchiya KJ, Sekine Y, Suda S, Sugihara G, Matsuzaki H, Sugiyama T, Kawai M, Minabe Y, Takei N, Mori N. Decreased serum levels of epidermal growth factor in adult subjects with high-functioning autism. Biol Psychiatry. 2007 Aug 1;62(3):267-9. Epub 2006 Nov 21. (the importance of this type of finding is that due to the presence of certain growth factors there might be a change in the formation of the brain early in its development)
Sugihara
G, Hashimoto
K, Iwata
Y, Nakamura
K, Tsujii M, Tsuchiya
KJ, Sekine Y, Suzuki
K, Suda S, Matsuzaki H, Kawai
M, Minabe Y, Yagi A, Takei
N, Sugiyama
T, Mori
N. Decreased serum levels of hepatocyte growth factor in male adults with
high-functioning autism. Prog Neuropsychopharmacol Biol
Psychiatry. 2007 Mar 30;31(2):412-5.
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