Correction Dr. Wigler's PNAS Paper Did NOT Attribute Autism to Older Mothers, "Nature" and the Dallas Morning News Reported it Though
. The paper Dr. Wigler wrote and the press release from CSHL did not contain this assertion at all. Nature and The Dallas Morning News contain quotes from Dr. Wigler attributing sporadic autism to older mothers. This assertion of Dr. Wigler's distort the 50 years plus of studies that show that older paternal age is the cause of sporadic genetic disorders because sperm divide hundreds and hundreds and hundreds of time with the age of the man and errors multiply in the sperm precursor cells and sperm. Dr. Wigler knows the public is unaware of this but scientists are not unaware. His paper does not point the finger at the mother's age, but his comments to NATURE and the press do.
Why is Dr.Wigler talking about old eggs when it is clear that older men's sperm stem cells and sperm carry de novo DNA mutations, i.e. probably copy number variations and definitely deletions? There is no evidence that older ovum cause autism. Yes, genetic mutations can be carried in an unaffected female who had an older father or by women who have autistic brothers or relatives. Paternal age derived autism is caused by germ line mutations in the father's sperm and 1:1 male to female. Plenty of males with autism or Asperger's have had older fathers.
Michael Wigler's assertions NOT IN HIS paper because scientists would not buy the assertion to blame sporadic autism on the mother's age. The public however does think that the age of the mother is important and these quotes reinforce this misinformation:
"Older mothers, who are more likely to have autistic children, could fall into this class, notes Wigler. Such mothers' eggs have had more time to accumulate mutations."
"The older the mother, the more likely she has acquired spontaneous mutations" in her chromosomes, and will transmit them at conception, Dr. Wigler said. Less frequently, but just as likely, Dr. Wigler said, fathers can transmit autism traits as well. Why mix up Down syndrome and CNVs in autis? 50% of Down Syndrome is due to an older father.
What about the information in this study of grandparents age and autism, especially the maternal grandfather age at the mother birth?
Why does this paper ignore Burd, ignore Gillberg, ignore Reichenberg, Gross, Croen, Cantor, Lauritsen, Malaspinia, Harlap, Crow, Gorwood, Rasmussen, Sipos, Brown, etc. Do you just change the definition of autism in 1994 and ignore paternal age as the major cause of some of the conditions that you now call autism? Japan has found older fathers and PDD and schizophrenia so has Australia, Denmark any country that has looked has found it. Wigler blames the old eggs.
One scientist wrote:
"Autism is a genetically heterogeneous entity. Although numerous studies have demonstrated a strong genetic basis, no clear etiology has been identified to date. Recently, two studies have demonstrated an increased risk of autism in children born to fathers over the age of 40. However, given the large male-to-female predominance of autism, it is likely that new mutations on the X chromosome account for a significant number of affected cases. Due to the maternal origin of the X chromosome in males, we hypothesize that advanced maternal-grandpaternal age may also be a risk factor for autism. Precedence for this theory exists with other X-linked disorders such as Duchenne muscular dystrophy and Rett syndrome. Additionally, it has been demonstrated that maternal psychiatric illness, but not paternal psychiatric illness, is more prevalent among parents of children with autism. Using anonymous surveys of families with autistic children, we seek to identify the ages of grandparents at the time the parents were born in order to determine if advanced maternal-grandpaternal age is associated with an increased risk for autism when adjusted for advanced maternal and paternal age. Additionally, we will seek out sister-pairs in order to identify any statistical significance between the ages of the maternal grandfather at delivery of each sister. If advanced maternal-grandpaternal age is, in fact, a risk factor, it would help direct molecular researchers towards genes on the X chromosome as potential etiologies for autism. Also, further study of potential mutagenic exposures in the environment of grandparents may help elucidate the reason for the increasing incidence of autism in recent decades."
older papers discussing paternal age etc.:
Anorexia, Greater Maternal and Paternal Age at the Time of Birth
Psychosomatic Medicine Vol. 36, No. 1 (Jan.-Feb. 1974)
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. Labels: Anorexia and advanced paternal and maternal age 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) p =" 0.007)." p =" 0.038)." p =" 0.015)." p =" 0.015)." p =" 0.13)." p="0.005).">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
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.
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]
Labels: age of the fathers raised very significantly in schizophrenia 1979
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.
: 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.
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).
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.
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.
Labels: why doesn't everybody in this country know that up to 1/3 or more of schizphrenia is caused by older paternal age?
Link between older age of fatherhood and an increased risk of schizophrenia was detected in 1958. Since then, 10 studies
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
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. < n =" 465)." n =" 481)" n =" 1313)">/=50 years old and at time of conception than in subjects whose fathers were 21-24 years old. Growth and development in fetal life and childhood are influencing the risk of schizophrenia in adulthood, but the underlying causal pathways are still unknown. De novo mutations in the germ cells of older fathers may play a causal role in the etiology of some cases of schizophrenia.
Labels: advancing paternal age, de novo mutations, mutations in the germ cells of older fathers may play a causal role, neurodevelopmental disorder, schizophrenia
posted by concerned heart @ 7:40 PM 0 comments
"Increasing father's age was associated with increased risk for autism"
BURD 1999 North Dakota
1: J Perinat Med. 1999;27(6):441-50. Links
Prenatal and perinatal risk factors for autism.Burd L, Severud R, Kerbeshian J, Klug MG. University of North Dakota School of Medicine and Health Sciences, North Dakota Fetal Alcohol Syndrome Center, Grand Forks, USA. email@example.com
AIM: To identify pre- and perinatal risk factors for autism. METHOD: Case control study. We matched names of patients from North Dakota who met DSM criteria for autism, a pervasive developmental disorder, and autistic disorder with their birth certificates. Five matched controls were selected for each case. RESULTS: Univariate analysis of the 78 cases and 390 controls identified seven risk factors. Logistic modeling to control for confounding produced a five variable model. The model parameters were chi 2 = 36.6 and p < p="0.0003)." p =" 0.013)." n =" 114)." n =" 495)," p =" 0.015)." p =" 0.007)." p =" 0.038).">50 years. Together, these studies provide strong and convergent support for the hypothesis that later paternal age can influence neural functioning.
Maternal and Paternal Age and Risk of Autism Spectrum Disorders
Lisa A. Croen, PhD; Daniel V. Najjar, MS; Bruce Fireman, MA; Judith K. Grether, PhD
Arch Pediatr Adolesc Med. 2007;161:334-340.
Objective To explore the association between maternal and paternal age and risk of autism spectrum disorders (ASDs) in offspring.
Results Risk of ASDs increased significantly with each 10-year increase in maternal age (adjusted RR, 1.31; 95% confidence interval [CI], 1.07-1.62) and paternal age (RR, 1.28; 95% CI, 1.09-1.51). Adjusted RRs for both maternal and paternal age were elevated for children with autistic disorder (maternal age: RR, 1.18; 95% CI, 0.87-1.60; paternal age: RR, 1.34; 95% CI, 1.06-1.69) and children with Asperger disorder or pervasive developmental disorder not otherwise specified (maternal age: RR, 1.45; 95% CI, 1.09-1.93; paternal age: RR, 1.24; 95% CI, 0.99-1.55). Associations with parental age were somewhat stronger for girls than for boys, although sex differences were not statistically significant.
Conclusion Advanced maternal and paternal ages are independently associated with ASD risk.
Labels: advancing paternal age, autism, Oprah, paternal and maternal age
Tuesday, April 03, 2007
DE NOVO GERMLINE MUTATIONS AND AUTISM
This is the abstract of the groundbreaking research showing germline copy number variations in some people who are autistic.
1: Science. 2007 Mar 15; [Epub ahead of print] Links
Strong Association of De Novo Copy Number Mutations with Autism.Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T, Yamrom B, Yamrom B, Yoon S, Krasnitz A, Kendall J, Leotta A, Pai D, Zhang R, Lee YH, Hicks J, Spence SJ, Lee AT, Puura K, Lehtimaki T, Ledbetter D, Gregersen PK, Bregman J, Sutcliffe JS, Jobanputra V, Chung W, Warburton D, King MC, Skuse D, Geschwind DH, Gilliam TC, Ye K, Wigler M.
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
We tested the hypothesis that de novo copy number variation (CNV) is associated with autism spectrum disorders (ASDs). We performed comparative genomic hybridization (CGH) on the genomic DNA of patients and unaffected subjects to detect copy number variants not present in their respective parents. Candidate genomic regions were validated by higher-resolution CGH, paternity testing, cytogenetics, fluorescence in situ hybridization, and microsatellite genotyping. Confirmed de novo CNVs were significantly associated with autism (P = 0.0005). Such CNVs were identified in 12 out of 118 (10%) of patients with sporadic autism, in 2 out of 77 (2%) of patients with an affected first-degree relative, and in 2 out of 196 (1.0%) of controls. Most de novo CNVs were smaller than microscopic resolution. Affected genomic regions were highly heterogeneous and included mutations of single genes. These findings establish de novo germline mutation as a more significant risk factor for ASD than previously recognized.
Labels: de novo copy number variations in some autistic children, germline mutations
Low Birthweight and Advancing Paternal Age
Research and Practice
Paternal Age as a Risk Factor for Low Birthweight
Nancy E. Reichman 1* Julien O. Teitler 2
AJPH First Look, published online ahead of print March 29, 2006
American Journal of Public Health, 10.2105/AJPH.2005.066324
1 Robert Wood Johnson Medical School
2 Columbia University
Objectives. We examined associations between paternal age and low birthweight in the US urban population.
Methods. Using a population-based sample of 4621 births, we used multiple logistic regression analysis to estimate associations between paternal age and low birthweight, controlling for maternal age, other demographic factors, and the child's gender.
Results. When the child’s gender and the mother's race/ethnicity, birthplace, parity, marital status, and health insurance type were controlled, teenaged fathers were 20% less likely and fathers older than 34 years were 90% more likely than fathers aged 20 to 34 years to have low-birthweight babies. The associations were significant when maternal age was also controlled. No racial/ethnic differences in associations between paternal age and low birthweight were found.
Conclusions. We identified paternal age as an independent risk factor for low birthweight in the US urban population, suggesting that more attention needs to be paid to paternal influences on birth outcomes and to the interactive effects of urban environments and individual risk factors on health.
Key Words: Birth Outcomes, Socioeconomic Factors
Labels: advancing paternal age, autism, low birth weight, schizophrenia
Paternal Age A Major Path To Autism
PRENATAL AND PERINATAL RISK FACTORS FOR AUTISM
A REVIEW and INTEGRATION OF FINDINGS
Alexander Kolevzon, MD; Raz Gross, MD, MPH; Abraham Reichenberg, PhD
Arch Pediatr Adolesc Med. 2007;161:326-333.
Objective To review the evidence for the presence of prenatal and perinatal factors that affect the risk of autism and autism spectrum disorders.
Data Sources Relevant articles were identified by searching MEDLINE, screening reference lists of original studies, and searching major journals likely to publish epidemiological studies on the topic.
Main Exposures Parental characteristics and obstetric complications.
Main Outcome Measures Rates of autism and autism spectrum disorders.
Results Seven epidemiological studies were identified that fulfilled inclusion criteria. The parental characteristics associated with an increased risk of autism and autism spectrum disorders included advanced maternal age, advanced paternal age, and maternal place of birth outside Europe or North America. The obstetric conditions that emerged as significant fell into 2 categories: (1) birth weight and duration of gestation and (2) intrapartum hypoxia.
Conclusions Evidence to suggest that parental age and obstetric conditions are associated with an increased risk of autism and autism spectrum disorders is accumulating. Although not proven as independent risk factors for autism, these variables should be examined in future studies that use large, population-based birth cohorts with precise assessments of exposures and potential confounders.
Author Affiliations: Department of Psychiatry, Mount Sinai School of Medicine (Drs Kolevzon and Reichenberg), Department of Epidemiology, Mailman School of Public Health, Columbia University (Dr Gross), and Department of Psychiatry, College of Physicians and Surgeons, Columbia University (Dr Gross), New York, NY; Unit of Mental Health Epidemiology, The Gertner Institute of Epidemiology and Health Policy Research, Tel Hashomer, Israel (Dr Gross); and Department of Psychological Medicine, Institute of Psychiatry, King's College, London, England (Dr Reichenberg).
This study does not differeniate between familial and non-familial autism.
Low Birthweight and advancing paternal age have been found to go together.
Labels: advancing paternal age, birth weight, maternal age
posted by concerned heart @ 10:10 AM 0 comments
Monday, April 02, 2007
KAISER PERMANENTE STUDY AUTISM RISES WITH ADVANCED MATERNAL AND PATERNAL AGE
Risk of Autism Rises With Age of Moms, Dads
Kaiser Permanente study of more than 132,000 children suggests link between
chronic, life-long condition and advanced maternal and paternal age
OAKLAND, Calif., April 2 /PRNewswire/ -- Men and women who wait to have
babies later in life may increase their children's risk for autism,
according to a Kaiser Permanente study featured in the April issue of
Archives of Pediatrics & Adolescent Medicine, one of the JAMA/Archives
The study investigated 132,844 children born at Kaiser Permanente
hospitals in its Northern California region over a five-year period
(1995-1999) and identified 593 children who had been diagnosed with an
autism spectrum disorder (ASD).
Study results show that a mother's and father's risk of delivering a
child with autism steadily increases as they get older. Women ages 40 and
older showed a 30 percent increase in risk for having a child with autism
(1 in 123), when compared to moms between the ages of 25 and 29 (1 in 156).
Men ages 40 and older had up to a 50 percent increased risk of having a
Labels: autism and advanced maternal and paternal age
posted by concerned heart @ 2:24 PM 0 comments
OLDER FATHERS RISK TRANSMITTING GERM-LINE MUTATIONS
1: Hum Reprod. 2007 Jan;22(1):180-7. Epub 2006 Oct 19
The effects of male age on sperm DNA damage in healthy non-smokers.Schmid TE, Eskenazi B, Baumgartner A, Marchetti F, Young S, Weldon R, Anderson D, Wyrobek AJ.
Lawrence Livermore National Laboratory, Livermore, CA, USA.
BACKGROUND: The trend for men to have children at older age raises concerns that advancing age may increase the production of genetically defective sperm, increasing the risks of transmitting germ-line mutations. METHODS: We investigated the associations between male age and sperm DNA damage and the influence of several lifestyle factors in a healthy non-clinical group of 80 non-smokers (mean age: 46.4 years, range: 22-80 years) with no known fertility problems using the sperm Comet analyses. RESULTS: The average percentage of DNA that migrated out of the sperm nucleus under alkaline electrophoresis increased with age (0.18% per year, P = 0.006), but there was no age association for damage measured under neutral conditions (P = 0.7). Men who consumed >3 cups coffee per day had approximately 20% higher percentage tail DNA under neutral but not alkaline conditions compared with men who consumed no caffeine (P = 0.005). CONCLUSIONS: Our findings indicate that (i) older men have increased sperm DNA damage associated with alkali-labile sites or single-strand DNA breaks and (ii) independent of age, men with substantial daily caffeine consumption have increased sperm DNA damage associated with double-strand DNA breaks. DNA damage in sperm can be converted to chromosomal aberrations and gene mutations after fertilization, increasing the risks of developmental defects and genetic diseases among offspring.
Labels: alkali-labile sites, caffeine, coffee, DNA, dna damaged, double-strand breaks in dna, germ-line mutations, older fathers, single-strand breaks in dna, sperm
posted by concerned heart @ 9:31 AM 0 comments
EFFECTS OF MALE AGE ON THE FREQUENCY OF GERMINAL AND HERITABLE CHROMOSOMAL ABNORMALITIES IN HUMANS AND IN RODENTS
: Fertil Steril. 2004 Apr;81(4):925-43. Links
Effects of male age on the frequencies of germinal and heritable chromosomal abnormalities in humans and rodents.Sloter E, Nath J, Eskenazi B, Wyrobek AJ.
Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, California 94550, USA.
OBJECTIVE: To review evidence regarding the effects of male age on germinal and heritable chromosomal abnormalities using available human and rodent studies and to evaluate possible underlying mechanisms. CONCLUSION(S): The weight of evidence suggests that the increasing trend toward fathering at older ages may have significant effects on the viability and genetic health of human pregnancies and offspring, primarily as a result of structural chromosomal aberrations in sperm.
PMID: 15066442 [PubMed - indexed for MEDLINE]
Labels: genetic health, older fathers, structural chromosomal aberrations in sperm
Sunday, April 01, 2007
Why No Results? More Results Were Due Sept 20?
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.
Labels: What happened to the results?
Minding Your Mind
New Key to Autism
September 25, 2006
By Michael Craig Miller, M.D.Harvard Medical School
What Causes These Genetic Errors?
Should Older Men Stop Fathering Babies?
A study published in the September, 2006 issue of the Archives of General Psychiatry may give older prospective fathers pause before plunging into biological parenthood. The authors found a significant increase in the risk of autism and similar disorders as fathers got older.
What Is Autism?
Autism is a profoundly disabling disorder that starts in early childhood. The key features are:
Abnormal social development – little or no eye contact, prefers to be alone
Difficulty communicating – impaired language ability, uses gestures or pointing rather than words
Unusual behavior – spins objects, doesn't like being cuddled
Evidence of strong abilities sometimes in non-verbal areas, such as math or music
Older people with autism may have some ability to interact with people, but about two-thirds are mentally retarded and most cannot live on their own
Unfortunately, the incidence of this illness appears to be on the rise. Some experts think autism is diagnosed more often simply because more people are aware of it. But that's probably not the whole explanation.
Genetic factors almost certainly play a big role. So autism researchers are eager to discover anything that might increase a person's genetic vulnerability, such as delaying parenthood until age 40 or beyond.
The risk was smallest for children of fathers younger than 20 and greatest for children of fathers older than 50. A man in his 40s, for example, was almost 6 times as likely to have an autistic child as a man age 20. This relationship held even after researchers adjusted the results for the year of the person's birth, their socioeconomic status, or the mother’s age.
This is not the first discovery of its type. Healthcare professionals have long known that as parents age, the risk of giving birth to a child with certain illnesses goes up. Older mothers, for example, are more likely to have a child with Down syndrome. In recent years, studies have revealed a link between aging fathers and schizophrenia.
The Archives study took advantage of the extraordinarily complete health records of over 300,000 Israeli men and women who underwent a complete health assessment when they were 17-year olds — draft age. This gave researchers a good way to determine the incidence of autism in the population. The researchers had access to intellectual, medical and psychiatric evaluations of almost all Israeli boys and three-quarters of girls. (Their identities were kept secret, however.) For most individuals, the father’s age at birth was known.
Although boys were more likely to develop autism than girls, the risk for girls also increased as fathers got older. When fathers were young, about 1 in 6 children with autism were girls. After fathers passed the 40 year-old mark, the proportion of girls with autism rose to about 1 in 3. This suggests that the genetic factors in play for offspring of older fathers are different from those for offspring of younger fathers.
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What Causes These Genetic Errors?
All children inherit genetic material in equal amounts from both parents. In the case of autism, scientists think that the genetic material in the sperm of these older fathers has somehow become altered in harmful ways. These flaws make the child more vulnerable to developing the disease.
According to one theory, mutations (changes) are more likely to develop as men get older. Germ cells give rise to sperm throughout a man's life. These cells make copies of themselves and after several decades, the germ cells are copies of copies of copies. A second theory suggests that the offending genes passed down by older men are not properly marked or "imprinted." Accurate marking — which establishes whether a gene is from the father or the mother — determines if it will be active or not. If there is an error, the gene may function abnormally.
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Should Older Men Stop Fathering Babies?
It's true that medical technology and general improvements in health have made life much more enjoyable for people in middle to late life. Maybe 50 is the new 30 when it comes to some aspects of aging. But a healthy and active lifestyle does not make 50-year-old sperm the new 30-year-old sperm.
The increased risk of passing on any genetic vulnerability to a child is significant when you are older. When it comes to autism, however, the numbers are sobering. A man younger than 30 has no more than a 1 in 1,000 chance of fathering a child with autism. But the risk bumps up to approximately 3 in 1,000 for a man in his 40s and 5 in 1,000 above age 50. If a father in his fifties has a son, the risk of autism may approach 1 in 100.
Table II. Long-term effects of paternal ageing on offspring from table on page 2373 of Long –term effects of delayed parenthood by J.J. Tarin, J. Brines, and A. Cano
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