Rapid Responses to:
|
|
Rapid Responses: Rapid Responses published:
-
![[Read Rapid Response]](/icons/misc/sectionDOWN.gif)
This could be due to low DHEA...
- James M. Howard (24 October 2004)
-
Mistheory? Re: This could be due to low DHEA...
- Adrian S. Blaj (25 October 2004)
-
Yin, yang and yin-yang.
- Richard G Fiddian-Green (25 October 2004)
-
Re: Mistheory? Re: This could be due to low DHEA...
- James M. Howard (25 October 2004)
-
It is my hypothesis that...
- Adrian S. Blaj (26 October 2004)
-
One swallow does not make a summer
- Marco Procopio (2 November 2004)
|
|
|||
|
James M. Howard, independent biologist 1037 North Woolsey Avenue, Fayetteville, Arkansas 72701-2046, U.S.A.
Send response to journal:
|
It is my hypothesis schizophrenia results from under-development of the brain in utero / neonatally due to low DHEA. Later in life, DHEA availability is adversely affected by cortisol (stressful event) and testosterone (puberty) around the time DHEA naturally begins to decline around age twenty to twenty-five. At this time, low DHEA availability results in decline of these under-developed structures and failure of function. (It is known that schizophrenics, on average, exhibit less DHEA than normals.) It is been "unequivocally proven" that paternal, mitochondria does enter, and become part of the mitochondria of, zygotes, later contributing to adult mitochondria (Biochem Biophys Res Commun. 2003 Oct 17;310(2):247- 51). DHEA has been connected with "protection" of mitochondria in at least one manner, that is, protection from calcium overload (J Steroid Biochem Mol Biol. 2003 Oct;87(1):97-103). Older, paternal, damaged mitochondria may be entering and affecting growth and development of the zygote and fetus. I suggest the increased incidence of schizophrenia attributed to older fathers results from a combination of factors connected with low DHEA. That is, the combination of low maternal DHEA, low DHEA in the affected individual, in combination with damaged paternal mitochondria resulting age-reduced DHEA all combine to increase the probability of schizophrenia. Competing interests: None declared |
|||
|
|
|||
|
Adrian S. Blaj, Psychiatrist London, England
Send response to journal:
|
Madam: James M. Howard writes - 'It is been "unequivocally proven" that paternal, mitochondria does enter, and become part of the mitochondria of, zygotes, later contributing to adult mitochondria (Biochem Biophys Res Commun. 2003 Oct 17;310(2):247- 51)' As I have been
under the impression that mitochondria is inherited solely from the
mother, I tried to get to the reference given above - unfortunately I
found a very large number of links and I simply did not want to waste my
time. If one searches under the string Competing interests:
None declared |
|||
|
|
|||
|
Richard G Fiddian-Green, FRCS, FACS c/' Herhold, Maitland and Co, 44 Dover Street, London W1
Send response to journal:
|
"It is generally believed that certain organelles of the eukaryotic cell, especially mitochondria and chloroplasts, originated as bacterial endosymbionts. This theory is known as the endosymbiotic theory. . An endosymbiont (also known as intracellular symbiont) is any organism that lives within cells of another organism, i.e. forming an endosymbiosis... Several insect species contain obligate bacterial endosymbionts"(1). In the absence of mitochondria in human cells ATP resynthesis must be is exclusively anaerobic. If mitochondria are endosymbionts then they provided, therefore, human cells with the capacity to replenish ATP resynthesis by oxidative phosphorylation. In so doing might they also have also transformed human cells from being poikilothermic into being homeothermic? If they did then the capacity to regulate heat must reside within mitochondria and possibly be a function of pH which rises when the temperature falls and falls whe it rises (2). In a sense, therefore, female (yin) mitochondrial endosymbionts were the evolutionary origin of the yin/yang concept in eastern philosophy and medicine. If mood and behavioural disorders are the product of an impairment of temperature regultion (4), and the aging of paternal mitochondria is a contributing factor as James Howard suggests, perhaps powdered rhinoscerous horn is a remedy for aging being reputedly a supply of yang and therefore an aphrodisiac and supposedly the origin of the term horny(4). It might even exert a psychotropic effect by decreasing the amplitude of the diurnal and monthly and seasonal variations in body temperature (5). But James Howard claims, "It is been "unequivocally proven" that paternal, mitochondria does enter, and become part of the mitochondria of, zygotes, later contributing to adult mitochondria (Biochem Biophys Res Commun. 2003 Oct 17;310(2):247- 51)" (6). What then of the origin of mitocondria? Yin, yang or yin-yang? 1. Definition of Endosymbiont. www.wordiq.com/definition/Endosymbiont 2. Severinghaus JW, Astrup P, Murray JF. Blood gas analysis and critical care medicine. Am J Respir Crit Care Med. 1998 Apr;157(4 Pt 2):S114-22. 3. The Madness of Adam and Eve: how schizophrenia shaped humanity. by Dr David Horrobin DPhil, MA, BM, BCh. Published by Bantam Press. 2001. 4. The Truth about Aphrodisiacs. www.umkc.edu/sites/hsw/aphro 5. Oxygen supply dependency: has it any clinical relevance? Richard G Fiddian-Green (8 September 2004) eLetter re: HJ Silverman, J Abrams, and LJ Rubin Effects of interleukin-2 on oxygen delivery and consumption in patients with advanced malignancy Chest 1988; 94: 816-821 6. This could be due to low DHEA... James M. Howard (24 October 2004) eLetter re: Attila Sipos, Finn Rasmussen, Glynn Harrison, Per Tynelius, Glyn Lewis, David A Leon, and David Gunnell Paternal age and schizophrenia: a population based cohort study BMJ 2004; 0: bmj.38243.672396.55v1-0 Competing interests: None declared |
|||
|
|
|||
|
James M. Howard, independent biologist see my original remark for my address
Send response to journal:
|
You should have used MEDLINE. I, also, was "under the impression that mitochondria is [sic] interited solely from the mother." However, it is apparent that, though rare, our "impressions" were wrong. (See abstract below.)My understanding of "rare" is that the term allows for phenomena to occasionally occur. Therefore, in the case of older paternal effects on subsequent schizophrenia in the offspring, my hypothesis cannot be discounted by your line of "reasoning." Also, I am including a paragraph from your reference: "The researchers think inheritance of paternal mitochondrial DNA is probably very rare. But the findings will have implications for a number of branches of biology. Evolutionary biologists often date the divergence of species by the differences in genetic sequences in mitochondrial DNA. Even if paternal DNA is inherited very rarely, it could invalidate many of their findings. It will also have implications for scientists investigating inherited metabolic diseases." This implies that this phenomenon is real and will have to be taken seriously. Why don't you correct my hypothesis? Biochem Biophys Res Commun. 2003 Oct 17;310(2):247-51. Related Articles, Links New patterns of inheritance in mitochondrial disease. Schwartz M, Vissing J. Department of Clinical Genetics, National University Hospital, Rigshospitalet, Copenhagen, Denmark. With the identification of a patient with mutated mitochondrial DNA (mtDNA) of paternal origin, it has been unequivocally proven that not only does paternal mtDNA survive in the zygote, but it can also contribute substantially to the mtDNA pool of adult, human skeletal muscle. The questions are: how often does paternal mtDNA inheritance occur and what mechanisms are involved? In this paper, we will review current knowledge on the fate of sperm mitochondria after fertilization and discuss the impact paternal inheritance may have on our understanding of mitochondrial biology. Competing interests: None declared |
|||
|
|
|||
|
Adrian S. Blaj, Psychiatrist London, England.
Send response to journal:
|
Dear Mr Howard, I have undertaken a BMJ search and found 67 of your rapid responses which interestingly enough invariably begin with 'it is my hypothesis that...' As it appears that you explain everything in terms of testosterone, DHEA, etc, I have naturally concluded that your hypothesis is correct: the current polemic in the BMJ is also due to an increase of testosterone level in our brave gladiators. Friendly yours, Adrian Competing interests: testosterone producer |
|||
|
|
|||
|
Marco Procopio, Consultant Psychiatrist The Priory Hospital Hove, 14-18 New Church Road, Hove, East Sussex, BN3 4FH
Send response to journal:
|
Editor-Sipos et al (1) set themselves the task of demonstrating the presence of a higher than average paternal age in schizophrenia and that this phenomenon is restricted only to cases with a low family history for the disease. Both hypotheses are confirmed with statistical significance in their study. This is interesting, but the sample studied is biased and this casts serious doubts on the validity of the results. The study in fact includes only subjects with an age at onset between 16 and 38. The literature in schizophrenia demonstrates that it is dangerous to generalise the results obtained from a limited age sample. Often, in fact, differences that appear highly significant in aged biased samples do even up when the cohorts are followed up throughout their lifetime. The aetiological factors involved in schizophrenia are in fact probably the same at all ages from the qualitative point of view, but seem to vary greatly from the quantitative point of view (2). A cautionary tale is represented by the male/female ratio in the incidence and prevalence of schizophrenia. The incidence is significantly higher in men than women in age groups up to the mid 30s, but the ratio between men and women becomes inverted with age, reaching 1:2 for onsets after 40 years of age and 1:6 after 60. Eventually the lifetime morbid risk is the same in both sexes (3). The results of the study by Sipos et al are therefore intriguing, but must be interpreted very cautiously. No stratification can correct the above bias and only the follow up of this cohort for at least further 15 years can offer reliable results. 1. Sipos A, Rasmussen F, Harrison G, Tynelius P, Lewis G, Leon DA, Gunnell D. Paternal age and schizophrenia: a population based cohort study. BMJ; doi: 10.1136/bmj.38243.672396.55 (published 22 October 2004). 2. Kendler KS, Karkowski-Shuman L, Walsh D. Age at onset in schizophrenia and risk of illness in relatives. Br J Psychiatry 1996; 169: 213-218. 3. Jablenski A, Sartorius N, Ernberg G, Anker M, Korten A, Cooper JE et al. Schizophrenia: manifestations, incidence and course in different cultures. A World Health Organisation 10-Country Study. Psychol Med- Monograph Supplement 1992; 20: 1-97. Competing interests: None declared |
|||