Anorexia, Greater Maternal and Paternal Age at the Time of Birth

Psychosomatic Medicine Vol. 36, No. 1 (Jan.-Feb. 1974)
Anorexia Nervosa:
Demographic and Clinical Features in 94 Cases
KATHERINE A. HALMI, MD
A comprehensive chart study was made of numerous clinical and demographic features in 94
patients with anorexia nervosa. Unlike other large series, this survey included the pediatric age
group. A significantly greater maternal and paternal age at time of the patient's birth and a
greater incidence of both low and high birth weights compared with the general population was
found. A relatively high occurrence of premorbid feeding problems was present. Anxiety and
obsessive-compulsive traits were frequent premorbid symptoms. Precipitating events were
identified more frequently in patients with a greater age at onset of illness. Characteristic
behavior noted during the course of this illness is described.




The mothers' age at time of the patients'
birth was significantly greater (p < .001,
Kolmogorov-Smirnov goodness fit test)
than that for national control mothers (14)
or Iowa control mothers2 (Fig. 1). Also,
the fathers' age at the time of the patients'
birth was significantly greater (p < .05,
Kolmogorov-Smirnov goodness-of-fit test)
than that of national control fathers (15)
(Fig. 2). A significantly higher mothers'
age at the time of probands' birth compared
to that of Swedish control mothers
was also reported by Theander (1). Kay
and Leigh (11) did not analyze their data
statistically, but nonetheless stated that
youthfulness or advanced age of mothers
at the patients' birth appeared unimportant.


SUMMARY
Significant demographic characteristics
found in this survey of the hospital
records of 94 anorexia patients include a
greater maternal and paternal age at time
of the probands' birth and a greater
incidence of both low and high birth
weights than in the general population.
Unlike other large series of anorexia
nervosa patients, this survey included the
pediatric age group. This would explain
the relatively high incidence, 8%, of onset
of illness prior to age 10.

STEEP INCREASE IN DIABETES TYPE 1 INCIDENCE IN AUSTRIA SINCE 1999 in a prior study in Austria Fathers of diabetic children were significantly older

1: Eur J Pediatr. 2007 Apr 24; [Epub ahead of print] Links
Steep increase of incidence of childhood diabetes since 1999 in Austria. Time trend analysis 1979-2005. A nationwide study.Schober E, Rami B, Waldhoer T; Austrian Diabetes Incidence Study Group.
Department of Paediatrics, Medical University of Vienna, Vienna, Austria.

In a prospective population-based incidence study all newly diagnosed type 1 diabetic patients 0-<15 years of age were registered by the Austrian Diabetes Incidence Study Group. The nationwide incidence of type 1 diabetes between 2000-2005 was compared with the previously published incidence rates. Long-term trends as well as seasonal trends were estimated by Poisson regression models. A total of 3,599 incident cases (1,908 boys; 1,691 girls) were identified. Case ascertainment was >92%. The overall incidence rate doubled from 7.3 (95% CI; 6.8-7.9)/100,000 in the period 1979-84 to 14.6 (95% CI, 13.7-15.4)/100,000 in the time period 2000-2005. A significant increase during the observation period of 26 years could be demonstrated in all age groups and both sexes (p<0.01), with the steepest increment during the last 5 years. Until 1994 the incidence rate in children 0-<5 years was rather stable, but afterwards increased dramatically with 9.2% (95% CI, 5.2-13.4) annually. Despite this steep increase in time trend, we did not observe a seasonal variation in this age group (0-<5) in contrast to significant seasonal variations in the groups 5-<10 and 10-<15 years of age. Over the past 26 years incidence of type 1 diabetes in childhood increased clearly in Austria. The steepest rise was observed in the last 5 years and in the younger age groups.

PMID: 17453237 [PubMed - as supplied by publisher]

1: Eur J Pediatr. 1999 May;158(5):362-6. Links
Risk factors for type I diabetes mellitus in children in Austria
Rami B, Schneider U, Imhof A, Waldhor T, Schober E.
University Children's Hospital Vienna, Austria.

The aim of this study was to investigate environmental risk factors in the development of type 1 diabetes mellitus in a population-based case-control study. Parents of all patients with manifestation of type 1 diabetes between 1989 and 1994 in Vienna were asked to complete a questionnaire (n = 114). Control children (n = 495), matched for age and sex, were randomly recruited from all schools in Vienna. Fathers of diabetic children were significantly older at the time their children were born than fathers of control children (P = 0.015). Children with diabetes were more likely to be second- or third-born children (P<0.05) and fewer went to kindergarten than the control group children (P = 0.007). No significant difference in duration of gestation, percentage of delivery by caesarean section, birth weight or length was found. Neonatal jaundice was more often observed in the patient group (P = 0.038). Breast feeding was reported by 82.7% of mothers of diabetic children and by 81% of mothers of control children, and the duration of breast feeding was longer in patients than in controls (n.s.). CONCLUSION: In our study, the development of type 1 diabetes mellitus was associated with higher paternal age and neonatal jaundice. No correlation could be found with dietary intake of cow's milk products in early infancy, vaccination and other environmental factors.
PMID: 10333115 [PubMed - indexed for MEDLINE]





ENDOCRINOLOGY
B. Rami á U. Schneider á A. Imhof á T. WaldhoÈ r á E. Schob
Risk factors for type I diabetes mellitus
in children in Austria
Received: 5 May 1998 / Accepted in revised form: 27 August 1998
Eur J Pediatr (1999) 158: 362±366



Fathers of diabetic children were significantly older at the time their children were born than fathers of control children (P = 0.015).




Results
Family/social factors
Fathers of type 1 diabetes cases were signi®cantly older
at the time of birth than fathers of control children
(31.7 ‹ 6.7 vs 30.1 ‹ 6.1 years, P = 0.015). Mothers
of children with diabetes did not di€er signi®cantly in
age at the birth of their children from mothers of con-
trols (27.8 ‹ 5.7 vs 26.9 ‹ 5.1 years, P = 0.13).

Discussion
Previous reports have shown that the risk for type 1
diabetes increases with higher maternal age [3, 6, 24, 30,
33, 40, 41]; only one study group from India reported a
higher risk with lower maternal age [31]. Mothers of
Austrian children with diabetes were older, too, but this
was statistically not signi®cant. In those reports, pater-
nal age as a possible risk factor was not investigated as
much, but either no di€erence was found compared to
controls [3, 5], or fathers of diabetic children were even
younger than fathers of control children [40]. These re-
sults thus contradict our ®ndings. As far as birth order
in our cohort families was concerned, again in contrast
to previous studies [30, 40, 41], the highest risk was
observed in second- or third-born children.

Autism and Childhood Schizophrenia Are Actually One in the Same:We Must Try To Have Men Cryobank Sperm and end natural fathering of babies by 33

From
Blake Fleetwood Huffington Post

04.25.2007
Cho, Autism? This Woman is Going to Kill Herself

By: BwopofProps on April 26, 2007 at 09:44am

Autism and Schizophrenia have many of the same symptoms. In fact, Autism used to be known as "childhood schizophrenia." The major difference is whether or not the person suffers from delusions, or experiences hallucinations. Schizophrenic symptoms may lie dormant, and occur in cyles. Age of onset is usually late teens, early twenties. If the young man was ever out of touch with reality, was paranoid, delusional, or saw, smelled, heard or felt things that were not there, a schizophrenia diagnosis would trump and autism diagnosis.
Both Autistic and Schizophrenic people are usually loners, don't have good social skills and, are often highly intelligent. There is a high comorbidity rate for both diagnoses.
By: BwopofProps on April 26, 2007 at 09:44am

1994: The diagnosis of Asperger’s syndrome was added to the DSM-IV.

A very poignant story about the suffering due most likely to having had an older father when she was conceived?

I lack the planning skills and other means needed courses I took. Although I no longer attend school, I still get
ostracized. Kids in the area make fun of my awkwardness. In every apartment
I lived in,to take my life and am too
afraid of pain to even think of trying, but I spend most of my waking hours
thinking of assisted suicide and wishing it would be legalized where I live.
Isn't it sad that I have to think about such a drastic measure because I
can't get the basic support I need to function and enjoy a decent quality
of life?

Marla Comm
Montreal, Canada

This is a Very Serious Condition and Well Worth Preventing By Earlier Fathering of Babies or Cryobanking Sperm in Ones Mid - Late 20s

What are the father's age of the other school gunman?

Virginia Tech shooter was almost a textbook case of a school gunman
Associated Press
MATT APUZZO and SHARON COHEN
Associated Press Writers

BLACKSBURG, Va. (AP) — Cho Seung-Hui was so reserved, so mysterious, even school bullies couldn’t be bothered to figure him out.
“Go back to China,'’ middle school classmates shouted at the South Korean immigrant, teasing him for his awkward speech.
The shy, quiet boy in that Virginia middle school classroom would grow into the enraged Virginia Tech gunman who lashed out at the world by killing 32 people and himself Monday.
As such details of Cho’s life emerge, and experts pore over his sick and twisted writings and his videotaped rant, it is becoming increasingly clear that he was almost a textbook case of a school shooter: a painfully awkward, picked-on young man who lashed out with methodical fury at a world he believed was out to get him.
“In virtually every regard, Cho is prototypical of mass killers that I’ve studied in the past 25 years,'’ said Northeastern University criminal justice professor James Alan Fox, co-author of 16 books on crime. “That doesn’t mean, however, that one could have predicted his rampage.'’
When criminologists and psychologists look at mass murders, Cho fits the themes they see repeatedly: a friendless figure, someone who has been bullied, someone who blames others and is bent on revenge, a careful planner, a male. And someone who sent up warning signs with his strange behavior long in advance.
Among other things, the 23-year-old was sent to a psychiatric hospital and pronounced an imminent danger to himself. He was accused of stalking two women and photographing female students in class with his cell phone. And his violence-filled writings were so disturbing he was removed from one class, and professors begged him to get counseling. He rarely looked anyone in the eye and did not even talk to his own roommates.
He cast himself in his video diatribe as a persecuted figure like Jesus Christ. Cho, who came to the U.S. at about age 8 in 1992 and whose parents worked at a dry cleaners in suburban Washington, also ranted against rich “brats'’ with Mercedes, gold necklaces, cognac and trust funds.
Classmates in Virginia, where Cho grew up, said he was teased and picked on, apparently because of shyness and his strange, mumbly way of speaking.
Once, in English class at Westfield High School in Chantilly, Va., when the teacher had the students read aloud, Cho looked down when it was his turn, said Chris Davids, a Virginia Tech senior and high school classmate. After the teacher threatened him with an F for participation, Cho began reading in a strange, deep voice that sounded “like he had something in his mouth,'’ Davids said.
“The whole class started laughing and pointing and saying, `Go back to China,”’ Davids said.
Stephanie Roberts, 22, a classmate of Cho’s at Westfield High, said she never witnessed anyone picking on Cho in high school. But she said friends of hers who went to middle school with him told her they recalled him getting bullied there.
“There were just some people who were really mean to him and they would push him down and laugh at him,'’ Roberts said. “He didn’t speak English really well and they would really make fun of him.'’
Cho’s great aunt, who lives in South Korea, said Thursday that because he did not speak much as a child and after the family emigrated to the United States, doctors thought he may be autistic.
“Normally sons and mothers talk. There was none of that for them. He was very cold,'’ Kim Yang-soon said in an interview with AP Television News. “When they went to the United States, they told them it was autism.'’
Neither school officials, who have his educational records, nor police who have his medical records, have mentioned such a diagnosis this week. Autistic individuals often have difficulty communicating, but such a diagnosis would not necessarily explain his violence.
Regan Wilder, 21, who attended Virginia Tech, high school and middle school with Cho, said she was sure Cho probably was picked on in middle school, but so was everyone else. And it didn’t seem as if English was the problem for him, she said. If he didn’t speak English well, there were several other Korean students he could have reached out to for friendship, but he didn’t.
In other developments Thursday:
— Gov. Timothy Kaine appointed an independent panel to look into the tragedy and how authorities handled it. The panel will be led by former Virginia State Police superintendent Gerald Massengill and will include former Homeland Security Secretary Tom Ridge.
— University officials said that all of Cho’s student victims would be awarded degrees posthumously, and officials are outlining a way to let students complete their courses, possibly by allowing their work to this point in the semester count as completed.
— Private funeral ceremonies were held in Blacksburg for two international students killed in the massacre. Egyptian Waleed Mohammed Shaalan and Partahi Mamora Halomoan Lumbantoruan, a civil engineering doctoral student from Indonesia, also will have funerals in their home countries.
— With a backlash developing against the media, and some warning of copycat killers, the major TV networks cut back on showings of Cho’s video rant. “It has value as breaking news,'’ said ABC News spokesman Jeffrey Schneider, “but then becomes practically pornographic as it is just repeated ad nauseam.'’
A 2002 federal study on common characteristics of school shooters found that 71 percent of them “felt bullied, persecuted or injured by others prior to the attack.'’
The report said that “in some of these cases the experience of being bullied seemed to have a significant impact on the attacker and appeared to have been a factor in his decision to mount an attack at the school. In one case, most of the attacker’s schoolmates described the attacker as the kid everyone teased.'’
Cho “would almost be a poster child for the pattern that we saw,'’ said Marisa Randazzo, the former chief research psychologist at the U.S. Secret Service and co-author of the study, conducted jointly with the Education Department.
Among the victims of the Virginia Tech massacre were two other Westfield High graduates, Reema Samaha and Erin Peterson. Both young women graduated from the high school last year. But police said it is not clear whether Cho singled them out.
However, another expert who has worked with mentally disturbed young criminals suggested that Cho’s actions probably had genetic causes.
“This is very different'’ from someone who was bullied to the breaking point — Cho was clearly psychotic and delusional, said Dr. Louis Kraus, chief of child and adolescent psychiatry at Chicago’s Rush University Medical Center.
“This type of mental illness that this poor man had was not something that was likely precipitated by teasing or bullying,'’ he said. More likely, he said, is that Cho had a biological psychiatric disorder that may have worsened in recent years because of the pressures of college life and his leaving the support of his family.
Randazzo said about the only difference between Cho and the killers studied is he hadn’t bragged about the assault in advance, though that may surface later, perhaps in blogs or chat rooms.
Fox, the criminologist, said Cho probably made the decision to go on a killing spree months ago based on his weapon purchase. That would explain why witnesses described him as remarkably calm when he did the shooting.
“There’s a lot of scripting that’s going on in their heads, a lot of planning. Once they’ve decided it, there’s a certain degree of comfort and satisfaction that they’ll be the last to laugh,'’ Fox said.
Fox said there is typically a precipitating event that sets a gunman off. It is not yet known what that was in Cho’s case.
“It may not be huge'’ to normal people, but to Cho “it was the final straw that broke the camel’s back,'’ Fox said.
———
Associated Press writers Sarah Karush and Seth Borenstein in Washington and Lindsey Tanner in Chicago contributed to this report.

HOW ABOUT A PUBLIC HEALTH ANNOUNCEMENT FOR PATERNAL AGE BELOW 33 AND CRYOBANKING SPERM IN ONES 20S

Public release date: 26-Apr-2007

Contact: Karen Peart
karen.peart@yale.edu
203-432-1326
Yale University

The Yale Child Study Center has been awarded the Autism Center of Excellence (ACE) status by the National Institutes of Health. This highly competitive and prestigious award comes with $7.5 million of direct funding over five years to the Autism Program led by Ami Klin.

“This is our largest award to date, and signifies a recognition of the national leadership in research of autism provided by our interdisciplinary group of clinical scientists,” said Klin, the Harris Associate Professor of Child Psychology & Psychiatry in the Child Study Center. “The Yale ACE will further strengthen our commitment to finding the causes of autism and developing more effective treatments.”

Klin’s colleagues on the Yale ACE include Fred Volkmar, Robert Schultz, Warren Jones, Kasia Chawarska, Rhea Paul, Matthew State, Elena Grigorenko and Joseph Chang. The team plans three longitudinal projects focused on infants with autism aged 12 to 24 months. Another project involves neuroimaging studies of a cohort of children evaluated at various stages in their development, first at two years of age, then at four and eight and finally at 10-years-old. The researchers hope to trace underlying mechanisms of brain growth and specialization of individuals with autism. A fifth project focuses on a family of genes and linked proteins found to be associated with forms of autism.

Autism is a complex brain disorder that inhibits a person’s ability to communicate and develop social relationships, and it is often accompanied by extreme behavioral challenges. Autism affects about two million Americans. Autism Spectrum Disorders are diagnosed in one in 150 children in the United States and affects four times as many boys as girls. Researchers do not know how many subtypes of autism exist. There are probably several causes giving rise to this neurodevelopmental syndrome, but researchers have found that it is the most strongly genetic condition among all developmental disorders.

“---------------------------------------------------------------------------------\
Some generalities regarding the genetics and immunology of autism are below:  Autism displays increased frequency of genetic factors for immune responses, e.g., HLA, C4B null allele, extended haplotypes, etc.

 Autism involves a gender factor, i.e., it affects males about four times more than females.

 Autism often occurs in conjunction with a family history of autoimmune diseases, e.g., multiple sclerosis, rheumatoid arthritis, etc.

 Autism also involves hormonal factors, e.g., secretin, beta-endorphin, etc.

 Autism shows an association with infectious agents, in particular viruses.

 Autistic patients have immune abnormalities, especially those that characterize an autoimmune reaction in a disease.

 Autistic patients respond well to immune therapies.



Conclusion

The evidence is rapidly accumulating to suggest that autism is an autoimmune disorder. The autoimmune response is most likely directed against the brain myelin, perhaps secondary to a viral infection. Measles virus is a candidate but other possibilities remain to be explored. More importantly, the patients respond to treatment with immune therapies. Therefore, I conclude that autoimmunity offersstrong prospects for drug discovery and therapy for autism. Naturally, it deserves prompt attention from all those who want to help people with autism.

Selected Reading

Singh, V. K., "Plasma Increase of Interleukin-12 and Interferon-gamma: Pathological Significance in Autism" (Journal of Neuroimmunology, vol. 66, pp. 143-145 [1996]).

Singh, V. K., "Immunotherapy for Brain Diseases and Mental Illnesses," (Progress in Drug Research, vol. 43, pp. 129-146 [1997]).

Singh, V. K., "Serological Association of Measles Virus and Human Herpesvirus-6 With Brain Autoantibodies in Autism" (Clinical Immunology and Immunopathology, vol. 89, pp. 105-108 [1998]).

Singh, V. K., "Autoimmunity and Neurologic Disorders" (Latitudes, vol. 4, pp. 5-11 [1999]).

Dr. Singh received his doctorate from the University of British Columbia, Vancouver, Canada. His post-doctoral fellowship was completed in neurochemistry and neuroimmunology. Spanning over twenty years' experience in neurobiology and immunology research, Dr. Singh studied brain diseases, particularly infantile autism and Alzheimer's disease. Having authored over a hundred scientific publications, he is both a pioneer and an international authority on autoimmunity in autism. Dr. Singh is a member of the American Association for the Advancement of Sciences, the American Association of Immunologists, and the New York Academy of Sciences. He is listed in American Men and Women in Science (United States, R. R. Bowker, publisher) and The International Who's Who of Intellectuals (Cambridge, England, International Biographical Centre).

For further information, please contact Dr. Vijendra Singh, Ph.D., at the Biotechnology Center, Department of Biology, Utah State University, 4700 Old Main Hill, Logan, UT 84322-4700 [E-mail: singhvk@biology.usu.edu].

Reprinted from AAPN, The Autism Autoimmunity Project Newsletter, vol. 1, number 2, December 1999.



Links

"Autoimmunity and Neurological Disorders," interview with V. K. Singh in Latitudes, newsletter of the Association for
Comprehensive NeuroTherapy, http://www.latitudes.org/index.html, vol. 4, no. 2, Spring 1999, by Sheila
Rogers: http://lib.tcu.edu/www/staff/lruede/latitudes

"V. K. Singh: Selected Research on Autism," http://www.gti.net/truegrit/ : Findings in Immunology

"Vijendra K. Singh, Ph.D.: Selected Work on Alzheimer's Disease," (http://lib.tcu.edu/www/staff/lruede/alzheimers)

May 2007 PATERNAL AGE AND AUTISM ARE ASSOCIATED IN A FAMILY-BASED SAMPLE

: Mol Psychiatry. 2007 May;12(5):419-421.Paternal age and autism are associated in a family-based sample.Cantor RM, Yoon JL, Furr J, Lajonchere CM.
[1] 1Department of Human Genetics, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA, USA [2] 2Department of Pediatrics, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA, USA [3] 3AGRE Consortium, Los Angeles, CA, USA.

PMID: 17453057 [PubMed - as supplied by publisher]


The paternal age distribution of the AGRE fathers, whose first child is autistic differs significantly from that of the 'control' sample (P=0.005). A 2 goodness-of-fit test with 2 degrees of freedom was conducted using percents in the 'control' group age categories to calculate the expected values in the AGRE sample. The shift toward higher paternal ages in those with an affected first-born is seen most dramatically in the group of AGRE fathers who are 30–39 years inclusive, which is 54.7% of the distribution compared with the 41.9 % that is expected. We interpret this shifted age distribution to provide support for the recently reported finding by Reichenberg and co-workers that autism risk is associated with advancing paternal age.

PATERNAL AGES BELOW OR ABOVE 35 YEARS OLD ARE ASSOCIATED WITH A DIFFERENT RISK OF SCHIZOPHRENIA

-------------------------------------------------------------------------------------
: Eur Psychiatry. 2007 Jan;22(1):22-6. Epub 2006 Dec 4.Click here to read Links
Paternal ages below or above 35 years old are associated with a different risk of schizophrenia in the offspring.

* Wohl M,
* Gorwood P.

INSERM U675, 16 rue Henri Huchard 75018 Paris, France.






BACKGROUND: A link between older age of fatherhood and an increased risk of schizophrenia was detected in 1958. Since then, 10 studies attempted to replicate this result with different methods, on samples with different origins, using different age classes.

Defining a cut-off at which the risk is significantly increased in the offspring could have an important impact on public health. METHODS: A meta-analysis (Meta Win) was performed, assessing the mean effect size for each age class, taking into account the difference in age class references, and the study design. RESULTS: An increased risk is detected when paternal age is below 20 (compared to 20-24), over 35 (compared to below 35), 39 (compared to less than 30), and 54 years old (compared to less than 25). Interestingly, 35 years appears nevertheless to be the lowest cut-off where the OR is always above 1, whatever the age class reference, and the smallest value where offspring of fathers below or above this age have a significantly different risk of schizophrenia. CONCLUSION: No threshold can be precisely defined, but convergent elements indicate ages below or above 35 years. Using homogeneous age ranges in future studies could help to clarify a precise threshold.

PMID: 17142012 [PubMed - indexed for MEDLINE]

THE AUTISM/EARLY CHILDHOOD SCHIZOPHRENIA EPIDEMIC IS NOT MYSTERIOUS OR UNEXPECTED

How many men in the US have been fathering babies at 33-35 and up? There has been a huge rise in the number of men fathering babies in their mid to late 30s, in their 40s, in their 50s. The epidemics of genetic disorders such as autism are not a surprise and will get worse until we change the age the men father babies and/or cryobank sperm in their mid 20s-30ish.





Paternal age and schizophrenia

Proportional hazards regression analyses, with adjustment for a range of confounding factors described later, showed strong association between risk of schizophrenia and advancing paternal age (3). The hazards ratios were 2.32 (95% CI: 1.56, 3.44) for males and females whose fathers were 35–39 years old at time of conception, 2.08 (95% CI: 1.25, 3.46) for those whose fathers were 40–44 years old, 1.30 (95% CI: 0.56, 3.06) for those whose fathers were 45–49 years old, and 4.62 (95% CI: 2.28; 9.36) for those whose fathers were 50 years old at time of conception. The reference group comprised study subjects whose fathers were 21–24 years old at their conception. Factors taken into account in the analyses were sex, age, maternal age and parity, birth weight, birth length, gestational age, urban vs rural status of place of birth, season of birth, Apgar score at 1 and 5 min after birth, multiple birth, parental death in childhood, family history of schizophrenia, and highest annual income of either parent, highest socioeconomic index of either parent, and highest educational level of either parent.


Paternal age and schizophrenia

Increased paternal age is associated with several diseases possibly due to age-associated increase in sporadic de novo mutations in male germ cells (3). The Swedish study showed a strong positive association of paternal age at conception with risk of schizophrenia in young adulthood (3) and confirms previous smaller studies of schizophrenia (26, 27). The paternal age–schizophrenia association is stronger in those with no family history of schizophrenia, supporting the hypothesis that accumulating de novo mutations in the germ cells of older fathers could play an important role in the etiology of schizophrenia (3).

Genes coding for IGF-I are especially interesting because IGF-I seems to have a role in shaping synaptic connections or myelinization (2, 21, 25).



Footnotes

This paper was presented at the 4th Ferring Pharmaceuticals International Paediatric Endocrinology Symposium, Paris (2006). Ferring Pharmaceuticals has supported the publication of these proceedings


Ferring Pharmaceuticals has products to treat infertility so one cannot believe that they do not know of the association between increasing paternal age and schizophrenia/autism

Sung-Tae Cho, the Killer's Father, "a country bumpkin" and CONSIDERABLY OLDER THAN CHO'S MOTHER

Sung-Tae Cho, the killer's father, came from a poor rural area. He was a "country bumpkin" and considerably older than Cho's mother, Hyang-Im Kim, the daughter of a refugee, said Cho's great-aunt, Kim Yan-Soon. "We practically forced her to get married."

"INCREASED RISK OF SCHIZOPHRENIA WAS ASSOCIATED WITH ADVANCED PATERNAL AGE, PARTICULARY IN FEMALES......."

Are there more females with paternal age derived autism/early childhood schizophrenia than boys? Lisa Croen of Kaiser found more girls. Is that also reflected in the Reichenberg study where the ratio of boys to girls with autism was nearly 1:1?
Do the possibly de novo X-linked mutations in some women cause the some sons of these women to be on autistic spectrum? What happened to the ASD-CARC OLDER DADS AND AUTISM SURVEY data? It had a fabulous response from families. I bet Autism Speaks knows what happened to the data and why it was never published.

Older Dads and Autism Survey
Update: Sept 13 2006
The research study by Reichenberg et al (2006) attracted a lot of attention from both the scientific community and the autism community, with many comments supporting and others criticising the results. Such a reaction is important because it helps us to explore new areas of research and to design better studies.
Our Older Dads and Autism Survey is not a rigorous scientific study. BUT we are trying to see whether there is merit in conducting a more in-depth study. This survey taught us many things - the most important of which is that so many families want to participate in research to find answers. Within one hour and 20 minutes of posting, we had 100 responses! By the end of the first day (only 7 hours), we had 300! The word has spread and you helped make that happen - Thank you. We had more than 1000 responses in only 5 days! We are sharing some of those findings with you now, and the analysis of our results will be posted early next week. Please continue to invite others to participate and we hope that you will come back to participate in other surveys.

If you have not already completed this survey, click here.











July 7, 2003

Parental Age and Risk of Schizophrenia

A Case-control Study

Majella Byrne, MSc, PhD; Esben Agerbo, MSc; Henrik Ewald, MD, DMSc; William W. Eaton, PhD; Preben Bo Mortensen, MD, DMSc

Arch Gen Psychiatry. 2003;60:673-678.

Conclusion Increased risk of schizophrenia was associated with advanced paternal age, particularly in females, lending support to the theory that de novo mutations, possibly X-linked, associated with increased parental age might be responsible for some cases of schizophrenia.



Methods We performed a national population, nested, case-control study based on Danish longitudinal register data. The sample included 7704 patients with an ICD-8 or ICD-10 diagnosis of schizophrenia admitted to a psychiatric facility between 1981 and 1998 in Denmark, and 192 590 individually time-, age-, and sex-matched population controls, their parents, and siblings. The risk of schizophrenia associated with increasing parental age was investigated using conditional logistic regression and controlling for family socioeconomic and demographic factors and family psychiatric history.


Results Advanced paternal and maternal age was associated with increased risk of schizophrenia in univariate analyses. Controlling for socioeconomic factors and family psychiatric history, increased risk of schizophrenia was identified in those with a paternal age of 50 years or older. Sex-specific analyses revealed that the risk of schizophrenia was increased for males with fathers 55 years or older (incidence rate ratio [IRR], 2.10; 95% confidence interval [CI], 1.35-3.28); for females, the risk associated with paternal age was substantial for fathers aged 50 to 54 years (IRR, 2.22; 95% CI, 1.44-3.44) and 55 years or older (IRR, 3.53; 95% CI, 1.82-6.83).

FATHERS AGE RAISED VERY SIGNIFICANTLY IN SCHIZOPHENIA

We have two theories in the paternal age research one is men who wait to father until later in life for the first time and the other road is the last born child. In both cases the rate of schizophrenia is higher; in both cases the man is older. If he has six normal children and the last one (a daughter is schizophrenic) or he never had any children and he is in not 20, not 30, not 40, but 45+++++ and his son/daughter is schizophrenic. It seems that daughters have a higher chance of paternal age autism or schizophrenia at younger paternal ages. Researchers have found the reason for this and it is due to vital genes on the father's X chromosome that mutate and is passed only to daughters.

Seminal findings
We initially examined the relationship between paternal age and the risk for schizophrenia because it is well established that paternal age is the major source of de novo mutations in the human population, and most schizophrenia cases have no family history of psychosis. In 2001, we demonstrated a monotonic increase in the risk of schizophrenia as paternal age advanced in the rich database of the Jerusalem Perinatal Cohort. Compared with the offspring of fathers aged 20-24 years, in well-controlled analyses, each decade of paternal age multiplied the risk for schizophrenia by 1.4 (95 percent confidence interval: 1.2-1.7), so that the relative risk (RR) for offspring of fathers aged 45+ was 3.0 (1.6-5.5), with 1/46 of these offspring developing schizophrenia. There were no comparable maternal age effects (Malaspina et al., 2001).






If we had only considered the risk in the cases with paternal age >30 years, our risk would be equivalent to that reported by Sipos et al. (2004) in the Swedish study (15.5 percent). When paternal ages >25 years are considered, the calculated risk is much higher. Although the increment in risk for fathers age 26 through 30 years is small (~14 percent), this group is very large, which accounts for the magnitude of their contribution to the overall risk. The actual percentage of cases with paternal germ line-derived schizophrenia in a given population will depend on the demographics of paternal childbearing age, among other factors. With an upswing in paternal age, these cases would be expected to become more prevalent.









1979The British Journal of Psychiatry 134: 169-177 (1979)
© 1979 The Royal College of Psychiatrists

Raised parental age in psychiatric patients: evidence for the constitutional hypothesis
EH Hare and PA Moran

In two series of psychiatric patients (numbering about 6,000 and 2,000 respectively), the mean age of the mothers at the time of the patients' birth was found to be very significantly above expectation from the general population, and this was so for each of the major diagnostic groups. In the second series, the age of the fathers was also found to be very significantly above that expected from a sample survey of the general population, and this was so for each diagnostic group. Fathers' age was raised more than mothers', and was highest for schizophrenia. The raised parental age could not be explained in terms of the patient's year of birth or his father's social class. The raised mothers' age could largely be accounted for by regression on the raised fathers' age. The present findings, and those of previous studies, seem best explained on the hypothesis of a constitutional parental trait leading to delayed marriage
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However, we think that approximately one third or one quarter of all schizophrenia cases may be attributable to paternal age. Paternal age is the major source of de novo genetic diseases in the human population, which was first described by Penrose8 in the 1950s. He hypothesized that this was due to copy errors that arose in the male germ line over the many cycles of sperm cell replications. These mutations accumulate as paternal age advances. After the Penrose report, medical researchers identified scores of sporadic diseases in the offspring of older fathers, suggesting that these could occur from gene mutations. Particular attention was paid to conditions in last-born children. In the 1960s, an excess of schizophrenia in last-born children was also reported.


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We sought to investigate whether older paternal age at the time of birth is associated with schizophrenia and other schizophrenia spectrum disorders among the offspring. Several lines of evidence support a relation between older paternal age and schizophrenia spectrum disorders. First, most previous studies that examined this relationship have demonstrated positive associations (1–5), although these studies have been criticized for methodologic limitations. Most recently, Malaspina et al. (1), in a large Israeli birth cohort, demonstrated a robust and "dose-related" effect of paternal age on risk of schizophrenia and related disorders, a finding that was unaltered after adjusting for maternal age.










Malaspina D, Harlap S, Fennig S, Heiman D, Nahon D, Feldman D, Susser ES: Advancing paternal age and the risk of schizophrenia. Arch Gen Psychiatry 2001; 58:361-367[Abstract/Free Full Text]
Hare EH, Moran PA: Raised paternal age in psychiatric patients: evidence for the constitutional hypothesis. Br J Psychiatry 1979; 134:169-177[Abstract]
Gregory I: An analysis of family data on 1000 patients admitted to a Canadian mental hospital. Acta Genet Stat Med 1959; 9:54-96[Medline]
Johanson E: A study of schizophrenia in the male. Acta Psychiatr Scand Suppl 1958; 125
Kinnell HG: Parental age in schizophrenia (letter). Br J Psychiatry 1983; 142:204[Medline]

WHY DOESN'T THE PUBLIC KNOW THAT UP TO AND BY NOW MAYBE MORE THAN 1/3 OF ALL SCHIZOPHRENIA IS CAUSED BY PATERNAL AGE AT CONCEPTION?

Someone recently wrote:


Saying autism is not a mental illness
is functionally incorrect. When the
mental illness schizophrenia is now
determined to be developmental - it
appears in late adolescence as the brain and body mature, while autism manifests itself in childhood - when
autism was once termed “childhood
schizophrenia”, when both illnesses
originate in the brain, when both
conditions share many symptoms, when in
any case it is NOT a disgrace to be called “mentally ill”, you are making
a distinction that is not a distinction.

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: Eur Psychiatry. 2007 Jan;22(1):22-6. Epub 2006 Dec 4.Click here to read Links
Paternal ages below or above 35 years old are associated with a different risk of schizophrenia in the offspring.

* Wohl M,
* Gorwood P.

INSERM U675, 16 rue Henri Huchard 75018 Paris, France.






BACKGROUND: A link between older age of fatherhood and an increased risk of schizophrenia was detected in 1958. Since then, 10 studies attempted to replicate this result with different methods, on samples with different origins, using different age classes.

Defining a cut-off at which the risk is significantly increased in the offspring could have an important impact on public health. METHODS: A meta-analysis (Meta Win) was performed, assessing the mean effect size for each age class, taking into account the difference in age class references, and the study design. RESULTS: An increased risk is detected when paternal age is below 20 (compared to 20-24), over 35 (compared to below 35), 39 (compared to less than 30), and 54 years old (compared to less than 25). Interestingly, 35 years appears nevertheless to be the lowest cut-off where the OR is always above 1, whatever the age class reference, and the smallest value where offspring of fathers below or above this age have a significantly different risk of schizophrenia. CONCLUSION: No threshold can be precisely defined, but convergent elements indicate ages below or above 35 years. Using homogeneous age ranges in future studies could help to clarify a precise threshold.

PMID: 17142012 [PubMed - indexed for MEDLINE]


Schizophrenia Risk and the Paternal Germ Line
By Dolores Malaspina
Paternal age at conception is a robust risk factor for schizophrenia. Possible mechanisms include de novo point mutations or defective epigenetic regulation of paternal genes. The predisposing genetic events appear to occur probabilistically (stochastically) in proportion to advancing paternal age, but might also be induced by toxic exposures, nutritional deficiencies, suboptimal DNA repair enzymes, or other factors that influence the

fidelity of genetic information in the constantly replicating male germ line. We propose that de novo genetic alterations in the paternal germ line cause an independent and common variant of schizophrenia.

Seminal findings
We initially examined the relationship between paternal age and the risk for schizophrenia because it is well established that paternal age is the major source of de novo mutations in the human population, and most schizophrenia cases have no family history of psychosis. In 2001, we demonstrated a monotonic increase in the risk of schizophrenia as paternal age advanced in the rich database of the Jerusalem Perinatal Cohort. Compared with the offspring of fathers aged 20-24 years, in well-controlled analyses, each decade of paternal age multiplied the risk for schizophrenia by 1.4 (95 percent confidence interval: 1.2-1.7), so that the relative risk (RR) for offspring of fathers aged 45+ was 3.0 (1.6-5.5), with 1/46 of these offspring developing schizophrenia. There were no comparable maternal age effects (Malaspina et al., 2001).

Epidemiological evidence
This finding has now been replicated in numerous cohorts from diverse populations (Sipos et al., 2004; El-Saadi et al., 2004; Zammit et al., 2003; Byrne et al., 2003; Dalman and Allenbeck, 2002; Brown et al., 2002; Tsuchiya et al., 2005). By and large, each study shows a tripling of the risk for schizophrenia for the offspring of the oldest group of fathers, in comparison to the risk in a reference group of younger fathers. There is also a "dosage effect" of increasing paternal age; risk is roughly doubled for the offspring of men in their forties and is tripled for paternal age >50 years. These studies are methodologically sound, and most of them have employed prospective exposure data and validated psychiatric diagnoses. Together they demonstrate that the paternal age effect is not explained by other factors, including family history, maternal age, parental education and social ability, family social integration, social class, birth order, birth weight, and birth complications. Furthermore, the paternal age effect is specific for schizophrenia versus other adult onset psychiatric disorders. This is not the case for any other known schizophrenia risk factor, including many of the putative susceptibility genes (Craddock et al., 2006).

There have been no failures to replicate the paternal age effect, nor its approximate magnitude, in any adequately powered study. The data support the hypothesis that paternal age increases schizophrenia risk through a de novo genetic mechanism. The remarkable uniformity of the results across different cultures lends further coherence to the conclusion that this robust relationship is likely to reflect an innate human biological phenomenon that progresses over aging in the male germ line, which is independent of regional environmental, infectious, or other routes.

Indeed, the consistency of these data is unparalleled in schizophrenia research, with the exception of the increase in risk to the relatives of schizophrenia probands (i.e., 10 percent for a sibling). Yet, while having an affected first-degree relative confers a relatively higher risk for illness than having a father >50 years (~10 percent versus ~2 percent), paternal age explains a far greater portion of the population attributable risk for schizophrenia. This is because a family history is infrequent among schizophrenia cases, whereas paternal age explained 26.6 percent of the schizophrenia cases in our Jerusalem cohort. If we had only considered the risk in the cases with paternal age >30 years, our risk would be equivalent to that reported by Sipos et al. (2004) in the Swedish study (15.5 percent). When paternal ages >25 years are considered, the calculated risk is much higher. Although the increment in risk for fathers age 26 through 30 years is small (~14 percent), this group is very large, which accounts for the magnitude of their contribution to the overall risk. The actual percentage of cases with paternal germ line-derived schizophrenia in a given population will depend on the demographics of paternal childbearing age, among other factors. With an upswing in paternal age, these cases would be expected to become more prevalent.

Biological plausibility
We used several approaches to examine the biological plausibility of paternal age as a risk factor for schizophrenia. First, we established a translational animal model using inbred mice. Previously it had been reported that the offspring of aged male rodents had less spontaneous activity and worse learning capacity than those of mature rodents, despite having no noticeable physical anomalies (Auroux et al., 1983). Our model carefully compared behavioral performance between the progeny of 18-24-month-old sires with that of 4-month-old sires. We replicated Auroux's findings, demonstrating significantly decreased learning in an active avoidance test, less exploration in the open field, and a number of other behavioral decrements in the offspring of older sires (Bradley-Moore et al., 2002).

Next, we examined if parental age was related to intelligence in healthy adolescents. We reasoned that if de novo genetic changes can cause schizophrenia, there might be effects of later paternal age on cognitive function, since cognitive problems are intertwined with core aspects of schizophrenia. For this study, we cross-linked data from the Jerusalem birth cohort with the neuropsychological data from the Israeli draft board (Malaspina et al., 2005a). We found that maternal and paternal age had independent effects on IQ scores, each accounting for ~2 percent of the total variance. Older paternal age was exclusively associated with a decrement in nonverbal (performance) intelligence IQ, without effects on verbal ability, suggestive of a specific effect on cognitive processing. In controlled analyses, maternal age showed an inverted U-shaped association with both verbal and performance IQ, suggestive of a generalized effect.

Finally, we examined if paternal age was related to the risk for autism in our cohort. We found very strong effects of advancing paternal age on the risk for autism and related pervasive developmental disorders (Reichenberg et al., in press). Compared to the offspring of fathers aged 30 years or younger, the risk was tripled for offspring of fathers in their forties and was increased fivefold when paternal age was >50 years. Together, these studies provide strong and convergent support for the hypothesis that later paternal age can influence neural functioning. The translational animal model offers the opportunity to identify candidate genes and epigenetic mechanisms that may explain the association of cognitive functioning with advancing paternal age.

Link between older age of fatherhood and an increased risk of schizophrenia was detected in 1958. Since then, 10 studies

We have to mourn all the lost lives from the ramage of Cho Seung-Hui.


What can cause such a being who could take the lives of so many?

What can be done to prevent more school shootings?


It isn't that we don't know, it really isn't such a mystery. For Some reason we are not told and we think that science does not know the answer, but it does know where autism and schizophrenia comes from. WHY WE ARE NOT TOLD IS ANOTHER STORY

Here one of 10 studies that all show the same results.

Am J Psychiatry 159:1528-1533, September 2002
© 2002 American Psychiatric Association

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Alan S. Brown, M.D., Catherine A. Schaefer, Ph.D., Richard J. Wyatt, M.D., Melissa D. Begg, Sc.D., Raymond Goetz, Ph.D., Michaeline A. Bresnahan, Ph.D., Jill Harkavy-Friedman, Ph.D., Jack M. Gorman, M.D., Dolores Malaspina, M.D. and Ezra S. Susser, M.D., Dr.P.H. <
Paternal Age as a Categorical Variable
Having demonstrated a positive association between risk of schizophrenia spectrum disorders and increasing paternal age on a continuous scale, we then examined the effect of paternal age on schizophrenia spectrum disorders risk using the aforementioned 10-year age categories. The unadjusted rate ratios for each of these categories, relative to the 15–24-year age group, are presented in Table 2. There was a steady, monotonic increase in the rate of schizophrenia spectrum disorders with advancing categories of paternal age. The monotonic increase in risk of schizophrenia spectrum disorders with advancing paternal age categories was similar when adjustment was made for maternal age only, and for maternal age, paternal education, paternal race, and parity.Paternal Age as a Categorical Variable
Having demonstrated a positive association between risk of schizophrenia spectrum disorders and increasing paternal age on a continuous scale, we then examined the effect of paternal age on schizophrenia spectrum disorders risk using the aforementioned 10-year age categories. The unadjusted rate ratios for each of these categories, relative to the 15–24-year age group, are presented in Table 2. There was a steady, monotonic increase in the rate of schizophrenia spectrum disorders with advancing categories of paternal age. The monotonic increase in risk of schizophrenia spectrum disorders with advancing paternal age categories was similar when adjustment was made for maternal age only, and for maternal age, paternal education, paternal race, and parity.

We have demonstrated a significant, dose-dependent association between advancing paternal age and risk of schizophrenia and other schizophrenia spectrum disorders in a prospective birth cohort study with several methodologic advantages compared with previous work. The findings persisted after adjustment for maternal age and were present when schizophrenia was examined separately from schizophrenia spectrum disorders. De novo mutations in the male germ cell line may be responsible, at least in part, for the observed association. While further work is necessary to confirm this interpretation, our study nonetheless provides further evidence that advanced paternal age is a risk factor for schizophrenia spectrum disorders. If the de novo mutation hypothesis can be confirmed by future studies, this discovery may lead to the identification of candidate genes for this disorder.

The Autism Market - Let's Learn How to Prevent Autism Instead of Growing a Market for Pharmaceuticals and Genetic Probes

By LIDIA WASOWICZ
UPI Senior Science Writer
SAN FRANCISCO April 20 (UPI) -- An estimated one-third of youngsters with autism are prescribed psychotropic drugs to control their behavior and outlook, scientists report.
The more common pharmaceutical aids include anti-depressants like Prozac for anxiety and depression, stimulants like Ritalin for hyperactivity and impulsivity, anti-convulsants for seizures and anti-psychotic drugs, usually reserved for schizophrenia, for aggression.
In certain cases, these medications can quell such behavioral offshoots of autism as self-injury and severe tantrums, but they do not alter the underlying condition and can wreak havoc with some children's moods and pose other potential risks, doctors say.

"There is no great drug for autism," said Texas psychologist Steven Gutstein, developer of a behavioral treatment called relationship development intervention.

"Children with autism can have other problems that require medication like attentional problems or medical problems," he added. "It's a comorbid disorder, but there's no Ritalin for autism, and there probably never will be because it's a disorder with multiple etiologies."

The drugs that are used are the same as those prescribed for similar symptoms in children without autism, but doctors often find the disorder affects the response, at times making the side effects much more pronounced or the medicine much less effective or both.

Most of these pharmaceuticals are not backed by sufficient science to be approved for such use, and the government acknowledges "much more research is needed" to determine what risks they pose to children and adolescents over the long haul.

Cho Seung-Hui Diagnosed With Autism As A Child

AutismLink Reacts to Diagnosis of Autism in Virginia Tech Shooter



PITTSBURGH, April 19 /PRNewswire-USNewswire/ -- AutismLink and Autism
Center of Pittsburgh Director Cindy Waeltermann today issued a statement
regarding the recent revelation that Virginia Tech shooter Cho Seung-Hui
was diagnosed with autism as a child.
"While the entire autism community in Pittsburgh and across the nation
are devastated by the recent events at Virginia Tech, we would like to
caution the public not to stigmatize children or individuals with autism.
Cho likely did not receive the help and support that he needed early on --
that is why early intervention is so important, and that is why places like
the Autism Center of Pittsburgh exist. The act of one individual should not
reflect upon the entire autistic population.
It is unfair to blame Cho's actions on autism when he was clearly
psychologically impaired and likely had another disorder in addition to his
autism. His psychological evaluations apparently revealed a dark history
that concluded that he was an imminent danger to himself and others and was
also depressed.
This is a wake up call that stresses the importance of early
intervention, research, and appropriate treatment strategies. Many strides
have been made in autism spectrum disorders and research has consistently
shown that when children receive the help that they need early on they are
more likely to become more adept at social and communication skills.
Autism affects 1 in 150 children and is now the most commonly diagnosed
developmental disability in the world. It is time to recognize autism for
the epidemic it is."


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Cho's great-aunt, Kim Yang-soon, said Cho was diagnosed with autism after coming to U.S. in 1992. Speaking from her home in South Korea, she described Cho as "very cold" and said her niece was constantly worried about him.

Prevention Through Earlier Fathering of Babies Will Be Much More Powerful Than Stem Cell Therapies For Disorders

The gene mutations that cause ALS, known as Lou Gehrig's disease cannot easily be fixed by stem cells. Researcher recently found a soluable toxic factor, not yet identified, that appears to be leaching out of disease causing astrocytes,selectively killing off any motor neurons in the area. "The cells that surround the neurons don't sit back and do nothing," Przedborski said in a telephone interview. "You have to take into account the overall situation. There's a neighborhood effect-good guy in a bad neighborhood has a greater chance to turn bad." So it would make no sense to go to the trouble of replacing dead or dying neurons in the nervous system of an ALS patient without first cleaning up the neighborhood. "If you take those healthy stem cells to try to repair the diseased system, you are going to implant those nice cells into diseased environment and they may not survive very well," Przedborski said. SF Chronicle article by Carl Hall April 16, 2007 "How Stem Cell Findings Help Study Disease"

Why the digression to stem cell research? The way to stop ALS is the father your babies before the sperm making cells develop more mutations then you were born with.
FATHERING BABIES BY THE VERY EARLY 30s and CRYOBANKNG SPERM IN YOUR MID 20s WILL DO MUCH MORE THAN STEM CELL RESEARCH FOR ALZHEIMER'S, CANCER, AUTISM, DIABETES, ETC. ETC. ETC.

MUTATIONS ARE VERY OFTEN CAUSED BY ADVANCED PATERNAL AGE AND MUTATIONS IN THE SPERM MAKING CELLS --THE PATERNAL GERM LINE

Mutations in superoxide dismutase-1 (SOD1) cause a form of the fatal paralytic disorder amyotrophic lateral sclerosis (ALS)

ALS is an adult-onset motor neuron disease that can be induced by dominantly inherited mutations in the gene encoding the enzyme SOD1 (refs. 1,2). Mice that are transgenic for the human SOD1 mutations recapitulate the paralytic phenotype...

Nature Neuroscience (15 Apr 2007) Article

Is Autism a Disease? Is it a Disorder due to Various Gene Mutations?

I had asked Dr. Bartzokis why risk of non-familial autism, schizophrenia, MS, and Alzheimer's risk increases with the age of the father at a person's birth.



"The issue is that the older man will have sperm that has undergone more divisions and therefore had more chances to have mutations.
The COMPLEXITY of the myelination process makes it more vulnerable to mutations. I am not talking of one specific mutation. Many things could MANIFEST in the myelination or myelin breakdown process because it is so vulnerable - something going slightly wrong will impact it while it will not impact bone growth or the heart. A good example is ApoE4 - whatever else it may affect, it manifests in the reduced capacity of myelin repair and earlier onset of AD."

THUS, ADVANCING PATERNAL AGE IS CONSISTENTLY ASSOCIATED WITH INCREASED RISK OF AUTISM AND ASDs

Thus, advancing paternal age is consistently associated with increased risk of autism and ASDs.
Advanced paternal age has been associated with several congenital disorders, including Apert syndrome,40 craniosynostosis,41 situs inversus,42 syndactyly,43 cleft lip and/or palate,44-45 hydrocephalus,44 neural tube defects,46 and Down syndrome.47 In addition, advanced paternal age has been associated with schizophrenia15 and decreased intellectual capacities in the offspring.48 The most widely proposed mechanism underlying these congenital anomalies is known as the "copy error" hypothesis, first proposed by Penrose.49 After puberty, spermatocytes divide every 16 days, and by the age of 35 years, approximately 540 cell divisions have occurred. As a result, de novo genetic mutations that result from replication errors and defective DNA repair mechanisms are believed to propagate in successive clones of spermatocytes. These mutations accumulate with advancing paternal age and thus help explain how this disorder, which has a large genetic component, can be maintained in the population despite reduced reproduction in affected individuals.



RESULTS: There was a significant monotonic association between advancing paternal age and risk of ASD. Offspring of men 40 years or older were 5.75 times (95% confidence interval, 2.65-12.46; P<.001) more likely to have ASD compared with offspring of men younger than 30 years, after controlling for year of birth, socioeconomic status, and maternal age. Advancing maternal age showed no association with ASD after adjusting for paternal age. Sensitivity analyses indicated that these findings were not the result of bias due to missing data on maternal age. CONCLUSIONS: Advanced paternal age was associated with increased risk of ASD. Possible biological mechanisms include de novo mutations associated with advancing age or alterations in genetic imprinting.

PMID: 16953005 [PubMed - indexed for MEDLINE]

Tom Harkin, I hope someone gives you this blog to read and ponder

Sen. Tom Harkin (D-Iowa), whose Appropriations subcommittee on the departments of Labor, Education and Health and Human Services held the hearing, said that "millions of families are grappling with the profound difficulties of understanding and coping with this disease."

"We've got to do something about this," Harkin said.

Disorders Linked to Advancing Paternal Age Begin to Increase Rapidly age 33-35

"It makes sense that the mutations causing these diseases would occur more frequently in older men, and indeed that's what we saw for Apert syndrome," says Ethylin Jabs, M.D., director of the Center for Craniofacial Development and Disorders at Johns Hopkins.

Importantly, disorders linked to advancing paternal age begin to increase rapidly at about the same time as maternal risks increase -- age 33 to 35. Until now, the only evidence for paternal age effects has come from determining how many children with these diseases are born to fathers of various ages.

To obtain the first genetic explanation for these effects, the scientists studied sperm from about 60 men of various ages and looked for two genetic changes responsible for 99 percent of the cases of Apert syndrome. They found that men over 50 were, on average, three times as likely as men under 30 to have sperm with at least one of these changes. The mutations were not more common in blood samples as men aged.

The scientists say it's likely that the number of cell divisions that go into making a sperm plays a large role in the link between Apert syndrome and paternal age, and represents a fundamental difference between how aging egg and sperm can impact the health of a child.

"In the men we studied, these mutations had not been inherited, but rather collected over time in the reservoir of primitive cells that become sperm," says first author Rivka Glaser, a graduate student in human genetics at the Johns Hopkins School of Medicine.

Cells that mature into eggs are essentially frozen in time from puberty until the time the egg is signaled to develop. Because of the stage at which they are "frozen," the most likely error in an egg is to have an abnormal partitioning of chromosomes, producing an egg with an extra copy or a missing copy, Glaser says. For example, in Down syndrome, an extra copy of chromosome 21 is inherited from the mother.

Sperm, on the other hand, are continually produced throughout a male's lifetime from a reservoir of primitive cells. These primitive cells, like other kinds of so-called stem cells, can either replicate themselves or take a step closer to becoming a sperm, a process called differentiation. All told, these cells divide every 21 days after puberty, and at each cell division the opportunity exists for an error in copying the DNA.

"Literally hundreds of millions of sperm are made in each batch, so in most cases there are still many normal sperm available," says Jabs, also a professor of pediatrics. Their study showed that "high levels" of mutations among men who had no children with Apert syndrome amounted to roughly 3 sperm with the mutation among 100,000 sperm.

If an error is made in any of the steps toward becoming a sperm, the only cells affected are the resulting sperm for that batch. However, if an error appears in a primitive cell as it replicates itself and the mistake isn't fixed, the mutation will continue to be passed on to all of its progeny, including subsequent primitive cells and other batches of semen.

As men age, more of these primitive cells have collected mutations that cause Apert syndrome, leading to more sperm with the mutations in each batch of semen, the scientists suggest. The risk of having a child with Apert is about six times higher for a man age 52 than for someone who's 27.


Authors on the study are Glaser, Jabs, and Rebecca Schulman, of Johns Hopkins School of Medicine, and Karl Broman, of the Johns Hopkins Bloomberg School of Public Health.


Note: This story has been adapted from a news release issued by Johns Hopkins Medical Institutions.

'THE OPTIMAL TIME FOR A MAN TO FATHER A HEALTHY CHILD IS 25 OR SO THE SAME AS FOR A WOMAN

http://seattletimes.nwsource.com/html/health/2003303295_carnalknowledge15.html

By Faye Flam

By the time I'd reached my early 30s and was still not married, someone offered me this bit of advice: Just pick somebody.

Women are relentlessly reminded of the dreaded biological clock and the risks of having children after 35. But recent science suggests men, too, should be worried.

"The term 'biological clock' has always referred to females, but now there's evidence men are also ticking off some of their healthy children," says Jay Schinfeld, a fertility specialist.

The latest finding, published last month: Older fathers are more likely to have children with autism. Researchers tracked 387,000 people born in Israel and concluded the odds of fathering an autistic child are about 6 in 1,000 for men under 20. When a man reaches 50, those odds shoot up to about 52 in 1,000.
"The optimal time for a man to father a healthy child is the same as for a woman — 25 or so," says Dolores Malaspina, a psychiatry professor at New York University and coauthor of the study.

Malaspina led an earlier study showing a connection between paternal age and schizophrenia. She found children born to fathers over 50 carried about three times the risk of developing schizophrenia as those born to fathers in their 20s.

Autism and schizophrenia both arise from a little-understood combination of genetic and environmental triggers. Both disorders tend to run in families, suggesting that genetic risk factors can be inherited.

But you don't have to carry a genetic disease to pass one on — the trouble can start in your testicles. There, sperm-generating cells divide about 23 times a year, in the process slowly accumulating copying errors.

Older fathers are more likely to have children with achondroplasia (dwarfism) and several other conditions caused by spelling errors in the DNA. So for a man, the older you get, the less your child's genetic endowment will resemble your own.

For women, aging isn't as likely to lead to spelling errors because we make no new eggs after we're born. But that leads to other problems. The million or so we begin life with die at a rate of about 30 a day, and as the remaining eggs age, they get less adept at one of their critical jobs — dividing their 46 chromosomes in half. Eggs don't do this until after they're penetrated by a sperm.

If they get it wrong, some will get extra chromosomes, others will miss one, leading to Down syndrome (an extra chromosome 21), Turner's syndrome (a missing X chromosome in a girl), and Klinefelter's syndrome (an extra X chromosome in a boy).

Menopause creates a natural cutoff for women's fertility around 50, while an increasing number of men much older than that are becoming fathers, or trying to, says Abington's Schinfeld. "We get some as old as 70 coming here to try to make babies," he says.

Some get married a second time to a younger woman and others find love late in life. Schinfeld said one of his patients, a Vietnam veteran in his 60s, came to him with a wife in her 30s. The man explained that during the war he'd rescued a group of villagers, including a little girl, and that girl tracked him down after she grew up. Despite the age difference, they fell in love and got married.

It's hard to say whether men will now be subject to pressure the way women are, or accused of "wanting it all."

THEY ARE NOT COMBATING AUTISM UNLESS THEY SHOW HOW INCREASING PATERNAL AGE AND AUTISM GO HAND IN HAND

NO ONE AT THE CDC IS INTERESTED IN COMBATING/PREVENTING AUTISM


FATHERING BABIES BEFORE 35 WOULD CUT THE RATE OF SPORADIC AUTISM WAY DOWN WHY DOESN'T THE CDC MENTION PATERNAL AGE?

THE MEETING IS FOR THOSE WHO PROFIT FROM AUTISM - NO ONE IS TRYING TO PREVENT AUTISM



Surprise Senate Hearing on Combating Autism - Community Not Notified

We learned for the first time Thursday that the Senate has scheduled a hearing Tuesday, April 17, 2007 entitled "Combating Autism: Undertaking a Coordinated Response". There was no notice of this hearing to the many autism organizations other than Autism Speaks and possibly ASA. We learned of it only because one of our CAA Watch A-CHAMP District Leaders inadvertently heard of the hearing from a highly placed source.

Many of us have placed calls to Subcommittee Chair Sen. Harkin's staff, including members of our strong Iowa contingent. None of us have had the courtesy of a return phone call.

The list of witnesses is pasted below.

On the second panel are two representatives of Autism Speaks and Dr. Judy Favell, former President of the American Psychological Association, Division 33. Dr. Favell is a behaviorist who received a large Dept of Education grant to research the provision of services to children with autism by interactive video. The program, called "telehealth" involves installing a video camera in one's home so that families may engage in therapy sessions at long distrance by video.

Dr. Favell appears to be closely associated with three for-profit ventures. One is Advoserv (www.advoserv.com), a Florida corporation that provides residential and other services in Florida, Delaware, Maryland and New Jersey. The second is Cnow, billed as committed to being the "nation's premier telehealth solutions provider." (http://www.cnowinc.com/) The third venture is the National Institute of Telehealth, which develops the behavioral treatment plan that is implemented via video. Telehealth and telemedicine research is being funded by NIMH, headed by Dr. Insel, one of the witnesses at the hearing. (http://tinyurl.com/2uzyje)



No stakeholders are participating in this hearing.
Welcome to the BRAVE NEW WORLD of autism.

Senate Committee on Appropriations
Hearing Schedule for the Week of April 13, 2007

For more information, media should contact (202) 224-3904.

Tuesday April 17, 2007
2:00 p.m. Labor, Health and Human Services, and Education SD-124
Agenda: Combating Autism: Undertaking a Coordinated Response

Witnesses: Panel I:
Dr. Julie Gerberding, Director
Centers for Disease Control and Prevention
Atlanta, Georgia
Dr. Thomas R. Insel, Director
National Institute of Mental Health
Bethesda, Maryland

Panel II:
Robert C. Wright
Vice Chairman and Executive Officer
General Electric Foundation
Fairfield, Connecticut
Dr. Judith E. Favell
Chief Executive Officer, AdvoServ
Executive Director, The Celeste Foundation
Mount Dora, Florida
Bradley Whitford
Volunteer Spokesperson
for Autism Speaks Organization
New York, New York



Is Thomas Insel serious that he doesn't know that advancing paternal age causes autism and so does a mother with an older father at her birth? Thomas Insel doesn't know that a family history of autoimmume disorders such as type 1 diabetes and Hashimoto's thyroiditis is a major risk factor for having a child with autism. Does Thomas Insel not know that childhood schizophrenia and autism are associated with older and especially older fathers? This is not credible. Does Thomas Insel not know that a public health warning on paternal age over 33 would greatly reduce sporadic autism? I am sure he knows.




Keynote Address #1
Autism: What do we know? What do we need?
Thomas Insel, NIMH/NIH
Since the first IMFAR meeting in 2001, autism has received increased commitment from the
research community, increased cooperation among advocacy groups, and increased awareness in
the public. Nevertheless, we still know very little about the pathophysiology of this illness. Autism
is a developmental brain disease, but we do not know what the ‘lesion’ looks like. Autism is a
genetic disorder, but we have not identified genes of major effect nor have we found many of the
associated alleles. Recent reports document increased prevalence (not incidence) for autism, but
we have yet to identify a single environmental risk factor to explain this increase. And finally,
autism is considered by many experts to be a cluster of disorders, but we have no consistent
approach for sub-typing the various ‘autisms’ into valid syndromes.
While advances are being made on all of these fronts, to maximize progress we will need a
coordinated, strategic effort. In spite of flat budgets at NIH, the research community will need (a)
to expand to include developmental neurobiologists and others who can bring powerful new tools
to autism research, (b) to build cooperative research networks that can share protocols and data
across labs via a common database, and (c) to partner with advocacy groups and families to ensure
that research is relevant and results are disseminated. We There is also an urgent need for studies
to delineate the biological and behavioral subtypes of this complicated disorder so that we can
identify the genetic, environmental, and interactive etiologies of autism, and develop new
treatments and preventive strategies.

WHAT CAUSES DE NOVO AUTISM? The father's increasing age is the major cause of de novo mutations in the population.

- Despite its reputation as the most highly heritable of all neuro-psychiatric diseases, autism appears in families with no history of the disorder. A new study led by Michael Wigler and Jonathan Sebat at Cold Spring Harbor Laboratory provides evidence that the sporadic, non-inherited form of autism may be genetically distinct from heritable autism. Published in “Science Express,” these findings may influence future autism research and diagnostic testing.

Using new high resolution array technology to detect mutations, Sebat and colleagues found that spontaneous deletions and duplications of genetic material, so-called copy number variation, were ten times more prevalent in sporadic cases of autism spectrum disorders than in healthy control subjects They found the spontaneous mutations in 14 of 195 people with autism spectrum disorders compared to two of 196 unaffected individuals. The results also implicate the anomalies as primary, rather than just contributory, causes of the disorder in most cases when they are present, according to the researchers.


"Our results show conclusively that these tiny glitches are frequent in autism, occurring in at least ten percent of cases, and primarily in the sporadic form of the disease, which accounts for 90 percent of affected individuals," said study co-author Jonathan Sebat. " But since each mutation is individually rare–few were seen more than once–the results suggest that many different sites in the genome likely contribute to autism. Therefore, although the presentation of various forms of autism may be similar, any combination of variations of 100 or more genes may be responsible.

DOLORES MALASPINA INVESTIGATES CAN DE NOVO MUTATIONS CAUSE SCHIZOPHRENIA

Dolores Malaspina, M.D., M.S.P.H. (Independent Investigator 2001) of New York State Psychiatric Institute, will examine the novel hypothesis that new genetic mutations can cause schizophrenia, and will attempt to define the clinical profile (phenotype) of this type of schizophrenia, known as sporadic schizophrenia (the birth of an affected individual into an unaffected family). This type of schizophrenia has previously been thought to originate from environmental factors that either act independently or interact with latent genes. Dr. Malaspina has conducted two preliminary studies which support the new mutations hypothesis. As a major influence on new mutations in the human gene pool is related to the advancing age of fathers, Dr. Malaspina first examined the relationship of schizophrenia and paternal age. Data showed a strong escalation in schizophrenia risk as the age of the father increased, accounting for over a quarter of the schizophrenia cases. Another of her studies found that fathers of sporadic schizophrenia cases were 5 years older than familial case fathers. If sporadic schizophrenia can originate from new mutations, then neurodevelopmental genes are reasonable candidates. Her study will examine if patients with sporadic schizophrenia, particularly those with fathers older than 35 at birth, show features found in other neurodevelopmental diseases that correlate with paternal age, such as craniofacial abnormalities, nonspecific cognitive deficits and delayed developmental milestones. However, if genes that arise from mutations are inherited by later generations, then some familial cases with a similar illness would not have a paternal age effect. Dr. Malaspina plans to define the clinical profile in sporadic patients associated with paternal age through group comparisons and cluster analysis. If the study is successful, this illness pattern may be useful in gene identification for schizophrenia.

Autism Speaks Has An Agenda and It is Not About Preventing Autism

"The question that needs to be answered at this point is: What is really happening as the parent ages?" Andy Shih, Chief Scientific Officer of Autism Speaks, former Industry Consultant. What Industry was Andy Shih a consultant for? Prior to joining NAAR, Andy had served as an industry consultant.

Do the any of the directors or officers of Autism Speak care about the answer to this question? No way.

Autism does not need biomedical research it needs to be prevented. That can be done through earlier fathering of babies, cryopreserving semen in cryobanks in ones mid 20s and through understanding the relationship of autoimmune disorders in the family to the risk of having autistic children.

Familial autism is probably partly an X-linked disorder. Also some autism is thought to be autosomal recessive. There is information on the heterogenicity of autism in some of the prior postings.

"New Point Mutations in Humans Are Introduced Through The Male Line" This Has Been Known Since the 1950s", "What is Intriguing is why society chooses

TO IGNORE THIS" said Malaspina.


But now it is becoming increasingly clear that the biological clock ticks
for men as well as women, as researchers turn up evidence that as would-be
fathers get older, they have an increased chance of passing on genetic
defects to their children.

"New point mutations in humans are introduced through the male line," says
Dolores Malaspina, MD, professor of clinical psychiatry at Columbia
University and the New York State Psychiatric Institute. Furthermore, she
adds, the number of mutations in sperm increases as men age.

"This has been known since the 50s," said Malaspina. "What is intriguing is
why society chooses to ignore this."




CULTURAL RESISTANCE
There are many reason why paternal contribution to birth defects has a low
profile. James F. Crow, PhD, emeritus professor of genetics and medical
genetics at the University of Wisconsin in Madison, mentions that most of
these defects occur at low levels, on the order of 1 in tens of thousands.
In contrast, the odds of having a child with Down syndrome are about 1 in
350 when the mother is age 35 years and 1 in 100 at age 40 years. However,
some scientists hint that society may not be ready to hear that older men,
like older women, run the risk of passing on birth defects.

But the risk of having a child who later develops schizophrenia, Malaspina
notes, is about 1 in 110 when the father is age 40-similar to a 40-year-old
woman's risk of having a child with Down syndrome.

Malaspina says she believes her findings met resistance because of a
reluctance by men to accept that fathering children later in life poses
increased health risks to their children.

"Despite the fact that our paper received excellent reviews it was rejected
by two medical journals," she said, noting that the study results now have
been replicated five times with similar results. "And these biases really
hold us back from scientific advances."






from an article by Paul D. Thacker:

Biological Clock Ticks for Men, Too
Genetic Defects Linked to Sperm of Older Fathers
Paul D. Thacker

JAMA. 2004;291:1683-1685.



[mnchp-l] Genetic Defects Linked to Sperm of Older Fathers
McGillivray, Katrina katrina at beststart.org
Wed Apr 14 10:00:40 EDT 2004

Healthier Babies - Damage to fathers' germ cells, or mutations, are responsible for some part of such unfavourable outcomes of pregnancy.

The publications on this website were written by Margaret and Arthur Wynn,

THE AGEING OF FATHERS
In the 1950s Penrose of University College, London (1955), studied the ages of the parents of babies with birth defects believed to have been caused by gene mutations. He concluded:

"The influence of the father's age is shown to he of critical significance. When the effect of the father's age on incidence is appreciable, as in achondroplasia, the hypothesis of fresh gene mutation as the cause is strengthened."

9. Conclusions


THE IMPORTANCE OF THE PROSPECTIVE FATHER

1. The time is ripe for greater attention to fathers' contribution to the outcome of pregnancy. This study suggests that fathers share responsibility with mothers for miscarriage, perinatal death and congenital malformations. Damage to fathers' germ cells, or mutations, are responsible for some part of such unfavourable outcomes of pregnancy.

Is Autism the Ultimate "Autoimmune" Disorder Related to Even More Spontaneous Mutations in the Next Generation with Age and Toxins Affecting Sperm?

Are we seeing an accumulation of DNA mutations in sperm over generations of men fathering children at advanced paternal ages (over 32). Also are we seeing more autism because men are fathering so late in life without a prior history of autoimmune disorders? Is the last born daughter often ill? Is the first born son autistic in families in which the mother has had an older father? What are the various routes to autism, schizphrenia, diabetes type 1, MS, lupus-SLE, rheumatoid arthritis, Hashimoto's Thyroiditis.

Please comment if you have autism in your family. Maybe we can learn together what is causing so much more autism. Granted all severely autistic children will react poorly to vaccinations.

THE MUTATION RATE INCREASES WITH AGE AND AT A RATE MUCH FASTER THAN LINEAR : THE GREATEST MUTATIONAL HAZARD IS FERTILE OLD MALES.

James F. Crow studied the dominant large gene mutations and the X-linked mutations. Not the tiny Copy number variations in multigenetic disorders such as schizophrenia, autism and autoimmune disorders.

Paternal Age Effect

How can we account for a higher mutation rate in males than in females? The most obvious explanation lies in the much greater number of cell divisions in the male germ line than in the female germ line. In the female the germ cell divisions stop by the time of birth and meiosis is completed only when an egg matures. In the male, cell divisions are continuous and many divisions have occurred before a sperm is produced. If mutation is associated with cell division, as if mutations were replication errors, we should expect a much higher mutation rate in males than in females.

This makes the strong prediction that the mutation rate should increase with the age of the father, since the older the man, the more cell divisions have occurred. On the other hand, there should be no age effect in females.



I conclude that for a number of diseases the mutation rate increases with age and at a rate much faster than linear. This suggests that the greatest mutational health hazard in the human population at present is fertile old males.

IS SEVERE AUTISM RELATED TO EARLY CHILDHOOD SCHIZOPHRENIA?

OBJECTIVE: Individuals with schizophrenia and their relatives tend to have either higher or lower than expected prevalences of autoimmune disorders, especially rheumatoid arthritis, celiac disease, autoimmune thyroid diseases, and type 1 diabetes. The purpose of the study was to estimate the association of schizophrenia with these disorders as well as a range of other autoimmune diseases in a single large epidemiologic study. METHOD: The Danish Psychiatric Register, the National Patient Register, and a register with socioeconomic information were linked to form a data file that included all 7,704 persons in Denmark diagnosed with schizophrenia from 1981 to 1998 and their parents along with a sample of matched comparison subjects and their parents. The data linkage required that the autoimmune disease occur before the diagnosis of schizophrenia. RESULTS: A history of any autoimmune disease was associated with a 45% increase in risk for schizophrenia. Nine autoimmune disorders had higher prevalence rates among patients with schizophrenia than among comparison subjects (crude incidence rate ratios ranging from 1.9 to 12.5), and 12 autoimmune diseases had higher prevalence rates among parents of schizophrenia patients than among parents of comparison subjects (adjusted incidence rate ratios ranging from 1.3 to 3.8). Thyrotoxicosis, celiac disease, acquired hemolytic anemia, interstitial cystitis, and Sjögren’s syndrome had higher prevalence rates among patients with schizophrenia than among comparison subjects and also among family members of schizophrenia patients than among family members of comparison subjects. CONCLUSIONS: Schizophrenia is associated with a larger range of autoimmune diseases than heretofore suspected. Future research on comorbidity has the potential to advance understanding of pathogenesis of both psychiatric and autoimmune disorders.

"WE THINK THAT APPROXIMATELY ONE THIRD OR ONE QUARTER OF ALL SCHIZOPHRENIA CASES MAY BE ATTRIBUTALBLE TO PATERNAL AGE"

In Session with Dolores Malaspina, MD, MSPH: Impact of Childhood Trauma on Psychiatric Illness
Dolores Malaspina, MD, MSPH, interviewed by Norman Sussman, MD



Primary Psychiatry. 2006;13(7):33-36






What is the most irrefutable finding that you and your colleagues have made?
The most irrefutable finding is our demonstration that a father’s age is a major risk factor for schizophrenia. We were the first group to show that schizophrenia is linearly related to paternal age and that the risk is tripled for the offspring of the oldest groups of fathers.7 This finding has been born out in every single cohort study that has looked at paternal age and the risk for schizophrenia. The only other finding that has been as consistently replicated in schizophrenia research is that there is an increased risk associated with a family history of schizophrenia. Since only 10% to 15% of schizophrenia cases have a family history, family history does not explain much of the population risk for schizophrenia. However, we think that approximately one third or one quarter of all schizophrenia cases may be attributable to paternal age. Paternal age is the major source of de novo genetic diseases in the human population, which was first described by Penrose8 in the 1950s. He hypothesized that this was due to copy errors that arose in the male germ line over the many cycles of sperm cell replications. These mutations accumulate as paternal age advances. After the Penrose report, medical researchers identified scores of sporadic diseases in the offspring of older fathers, suggesting that these could occur from gene mutations. Particular attention was paid to conditions in last-born children.

AUTISM AND OLDER PARENTS GO TOGETHER IN WESTERN AUSTRALIA

--------------------------------------------------------------------------------
ARCHIVES OF GENERAL PSYCHIATRY

Vol. 61 No. 6, June 2004

Perinatal Factors and the Development of Autism
A Population Study

Emma J. Glasson, BPsych, BSc (Hons), PhD; Carol Bower, MBBS, MSc, PhD, FAFPHM, DLSHTM; Beverly Petterson, MSc, PhD; Nick de Klerk, BSc, MSc, PhD; Gervase Chaney, MBBS, FRACP; Joachim F. Hallmayer, MD


Arch Gen Psychiatry. 2004;61:618-627.


Objective To examine the association of obstetric factors with autism spectrum disorders for a cohort of children, using obstetric data contained in a statutory database collected at the time of birth.

Design Subjects born in Western Australia between 1980 and 1995 and diagnosed with an autism spectrum disorder by 1999 were included as cases (n = 465). Siblings of the cases (n = 481) and a random population-based control group (n = 1313) were compared with the cases on obstetric information contained in the Maternal and Child Health Research Database of Western Australia.

Results Compared with control subjects, cases had significantly older parents and were more likely to be firstborn. Case mothers had greater frequencies of threatened abortion, epidural caudal anesthesia use, labor induction, and a labor duration of less than 1 hour. Cases were more likely to have experienced fetal distress, been delivered by an elective or emergency cesarean section, and had an Apgar score of less than 6 at 1 minute. Cases with a diagnosis of autism had more complications than those with pervasive developmental disorder not otherwise specified or Asperger syndrome. Nonaffected siblings of cases were more similar to cases than control subjects in their profile of complications.

"ADVANCED PATERNAL AGE IS CONSISTENTLY ASSOCIATED WITH INCREASED RISK OF AUTISM AND ASDS"

The results of this review show that 3 of the 4 population-based studies28-29,32 to examine paternal age reported a significant association with risk of autism and ASDs. The fourth study31 also found that paternal age was older in fathers of case patients with autism compared with fathers of controls, although this relationship was statistically weaker in the adjusted analysis. Thus, advancing paternal age is consistently associated with increased risk of autism and ASDs.
Advanced paternal age has been associated with several congenital disorders, including Apert syndrome,40 craniosynostosis,41 situs inversus,42 syndactyly,43 cleft lip and/or palate,44-45 hydrocephalus,44 neural tube defects,46 and Down syndrome.47 In addition, advanced paternal age has been associated with schizophrenia15 and decreased intellectual capacities in the offspring.48 The most widely proposed mechanism underlying these congenital anomalies is known as the "copy error" hypothesis, first proposed by Penrose.49 After puberty, spermatocytes divide every 16 days, and by the age of 35 years, approximately 540 cell divisions have occurred. As a result, de novo genetic mutations that result from replication errors and defective DNA repair mechanisms are believed to propagate in successive clones of spermatocytes. These mutations accumulate with advancing paternal age and thus help explain how this disorder, which has a large genetic component, can be maintained in the population despite reduced reproduction in affected individuals.

OLDER THAN AVERAGE FATHERS(34 mean average age) 1975 SWEDEN AUTISM SPEAKS TRIES TO MINIMIZE THE PATERNAL AGE ISSUE WITH A VENGENCE

: Acta Psychiatr Scand. 1982 Dec;66(6):471-8. Related Articles,


Parental age in child psychiatric clinic attenders.

Gillberg C.

Parental age was detailed from medical records of all children treated or observed as inpatients at the Child and Youth Psychiatric University Clinic of Gothenburg, Sweden, in 1975, and compared with corresponding figures for parental age of children in the general population. Psychotic children and psychotic adolescents tended to have mothers (and fathers) who were older than average. Sixty per cent of child compared with 27% of children in the general population. Children with mothers of psychotic children were 30 years or older at the time of birth of the emotional disorders showed the same mean maternal age as average children in the population. It is suggested that children and adolescents with psychotic disorders have a higher level of "organic" background factors than children with other kinds of child psychiatric disorders.

PMID: 7180566 [PubMed - indexed for MEDLINE]