Tuesday, September 30, 2008

Advanced paternal age is associated with an increased risk for high-functioning autistic-spectrum disorder.

The British Journal of Psychiatry (2008) 193: 316-321. doi: 10.1192/bjp.bp.107.045120
© 2008 The Royal College of Psychiatrists
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Paternal age at birth and high-functioning autistic-spectrum disorder in offspring
Kenji J. Tsuchiya, MD, PhD
Osaka Hamamatsu Joint Research Center for Child Mental Development, and Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan

Kaori Matsumoto, MA and Taishi Miyachi, MD, PhD

Osaka Hamamatsu Joint Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan

Masatsugu Tsujii, PhD

Osaka Hamamatsu Joint Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, and Faculty of Sociology, Chukyo University, Nagoya, Japan

Kazuhiko Nakamura, MD, PhD, Shu Takagai, MD, PhD, Masayoshi Kawai, MD, PhD, Atsuko Yagi, MD, PhD, Kimie Iwaki, MD and Shiro Suda, MD, PhD

Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan

Genichi Sugihara, MD, PhD

Osaka Hamamatsu Joint Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan

Yasuhide Iwata, MD, PhD

Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan

Hideo Matsuzaki, MD, PhD

Osaka Hamamatsu Joint Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan

Yoshimoto Sekine, MD, PhD and Katsuaki Suzuki, MD, PhD

Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan

Toshirou Sugiyama, MD, PhD

Aichi Children's Health and Medical Center, Obu, Japan

Norio Mori, MD, PhD

Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan

Nori Takei, MD, PhD, MSc

Osaka Hamamatsu Joint Research Center for Child Mental Development and Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan, and Division of Psychological Medicine, Institute of Psychiatry, London, UK

Correspondence: Nori Takei, Osaka Hamamatsu Joint Research Center for Child Mental Development (OHJRC–CMD), Hamamatsu University School of Medicine, Handayama 1 Higashiku, Hamamatsu 431-3192, Japan. Email: ntakei@hama-med.ac.jp

Declaration of interest

None. Funding detailed in Acknowledgements.

Background

Previous studies have reported the association between advanced paternal age at birth and the risk of autistic-spectrum disorder in offspring, including offspring with intellectual disability.

Aims

To test whether an association between advanced paternal age at birth is found in offspring with high-functioning autistic-spectrum disorder (i.e. offspring without intellectual disability).

Method

A case–control study was conducted in Japan. The participants consisted of individuals with full-scale IQ70, with a DSM–IV autistic disorder or related diagnosis. Unrelated healthy volunteers were recruited as controls. Parental ages were divided into tertiles (i.e. three age classes). Odds ratios and 95% confidence intervals were estimated using logistic regression analyses, with an adjustment for age, gender and birth order.

Results

Eighty-four individuals with autistic-spectrum disorder but without intellectual disability and 208 healthy controls were enrolled. Increased paternal, but not maternal, age was associated with an elevated risk of high-functioning autistic-spectrum disorder. A one-level advance in paternal age class corresponded to a 1.8-fold increase in risk, after adjustment for covariates.

Conclusions

Advanced paternal age is associated with an increased risk for high-functioning autistic-spectrum disorder.




Related articles in BJP:


Highlights of this issue
Kimberlie Dean
BJP 2008 193: A14. [Full Text]

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Father age link to autism in children

Father age link to autism in children
Older fathers are almost twice as likely to have autistic children as younger men, research has found.

By Rebecca Smith, Medical Editor
Last Updated: 12:31AM BST 01 Oct 2008

A small study of children with autism spectrum disorder, the umbrella term for a range of similar conditions, found they were more likely to have been fathered by men over the age of 33.
There was no link with the condition and the mother's age, the Japanese study found.

The research involved 84 children with high-functioning autism spectrum disorders, meaning they had the social impairments of the condition but had normal intelligence, and 208 children without the disorder.

Children whose fathers were over 33 were 1.8 times more likely to have autism than those fathers were under 29. Men who fathered children between the age of 29 and 32 were 30 per cent more likely to have an autistic child.

The research is published in the British Journal of Psychiatry.

This is the first study to explore the effect of paternal age on the risk of high-functioning autistic spectrum disorder. Its findings correspond with previous studies which have shown a link between older fathers and a low IQ in children.

Benet Middleton, director of communications at The National Autistic Society, said: "The causes of autism are still being investigated. Many experts believe that the pattern of behaviour from which autism is diagnosed may not result from a single cause. Autism affects around one in 100 people in the UK and does not solely affect children of older parents.

"Members of the NAS are made up of parents of children from a variety of ages and backgrounds; in addition there is evidence to suggest that complex genetic factors are responsible for some forms of autism."

Some experts have argued that the measles, mumps and rubella vaccination is linked to the development of autism but this has been widely discredited and other studies have failed to find any link.

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Friday, September 26, 2008

The Male Biological Clock - Does It Exist?

However, Dr Fisch presented data indicating the decline in male fertility is associated with age. Dr Fisch presented his data on the impact of paternal age on Down syndrome (Fisch et al., "The Influence of Paternal Age on Down Syndrome". J.Urol 2003) There are a large number of entities that have been reported to be associated with advanced paternal age. One potential explanation for the increased incidence of some of these entities may be a recognized increase in sperm acneuploidy with increasing age.

The incidence of schizophrenia has also been reported as having a correlation to increasing paternal age ("Advancing Paternal Age and the Risk of Schizophrenia," D. Malaspina, et al., Arch Gen Psychiatry.158:758, 2001).

The potential public health consequences of delayed parenting were emphasized.

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Sunday, September 14, 2008

Tick tock, you don't stop: Men have a biological clock too

Healthy Living
Sunday, September 14, 2008

Tick tock, you don't stop: Men have a biological clock too

by Jessica Ashley, Shine staff, on Thu Sep 11, 2008 3:02pm PDT

Just about the time I think I'm happy not to even think about being pregnant for the next few years and that it's just fine to push snooze on my biological clock, I see one of those apple-cheeked babies peeking out from a thousand dollar stroller at Starbucks. And sigh...my heart melts, my ovaries flip and the inevitable tick-tick-tick drowns out the conversation and coffee-whirring around me.Ladies, I know many of you get this. And gentlemen, it seems your biological clocks may be just as wound up as mine.Research is increasingly showing that fertility is impacted by a man's age, not just a woman's age, eggs and body. If you are a woman with the big red "OVER 35" flag on your ob/gyn chart, you know that you've been well-warned and tested for your risk of conceiving a child with Down syndrome and other developmental issues. Studies of autism, schizophrenia, bipolar disorder and Down syndrome now show that older fathers also carry that red flag of higher risk.This understanding is radical because it shifts the focus (and sometimes, the blame) of fertility. Because females are born with all the eggs they will have in their lifetime and men produce sperm every 90 days, the formula's told us that women's fertility is ever-decreasing while men's is always rejuvenating. Not so, science now says. In fact, the quantity sperm may be produced every three months but the quality of the sperm does go down as men get older. While there are certainly elderly men actively making babies, some studies have shown that it takes 8% of couples more than a year to conceive when the father is 25 or younger, but 15% of couples (almost double the rate of infertility challenge) when the father is 35 or older.I was also fascinated to read that one French study reports that, among couples seeking fertility treatment, each parent's age has equal impact on pregnancy and miscarriage. This means that the older the parent -- male or female -- the lower the chances of getting pregnant at all and the higher the likelihood the woman will miscarry. A final note on this new information on men's fertility: It seems your clocks have less hours in the day than ours. Men's fertility, it is now known, sharply decreases at the age of 24. That's six years before women's fertility declines.Will this change how men and women make decisions about when to parent? Will men's attitudes align with science so that they feel free to acknowledge their own flippy urges to reproduce more freely? Perhaps only time -- and more studies -- will tell.Are you worried about your man's fertility? Do these new studies take the pressure off you or just complicate conception even more?

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Increasing paternal age is a major cause of new genetic disorders in a family

Am J Med Genet A. 2008 Sep 15;146A(18):2385-9. Links
The population-based prevalence of achondroplasia and thanatophoric dysplasia in selected regions of the US.Waller DK, Correa A, Vo TM, Wang Y, Hobbs C, Langlois PH, Pearson K, Romitti PA, Shaw GM, Hecht JT.
Houston Health Science Center, The University of Texas, Houston, Texas 77030, USA. kim.waller@uth.tmc.edu

There have been no large population-based studies of the prevalence of achondroplasia and thanatophroic dysplasia in the United States. This study compared data from seven population-based birth defects monitoring programs in the United States. We also present data on the association between older paternal age and these birth defects, which has been described in earlier studies. The prevalence of achondroplasia ranged from 0.36 to 0.60 per 10,000 livebirths (1/27,780-1/16,670 livebirths). The prevalence of thanatophoric dysplasia ranged from 0.21 to 0.30 per 10,000 livebirths (1/33,330-1/47,620 livebirths). In Texas, fathers that were 25-29, 30-34, 35-39, and > or =40 years of age had significantly increased rates of de novo achondroplasia among their offspring compared with younger fathers. The adjusted prevalence odds ratios were 2.8 (95% CI; 1.2, 6.7), 2.8 (95% CI; 1.0, 7.6), 4.9 (95% CI; 1.7, 14.3), and 5.0 (95% CI; 1.5, 16.1), respectively. Using the same age categories, the crude prevalence odds ratios for de novo cases of thanatophoric dysplasia in Texas were 5.8 (95% CI; 1.7, 9.8), 3.9 (95% CI; 1.1, 6.7), 6.1 (95% CI; 1.6, 10.6), and 10.2 (95% CI; 2.6, 17.8), respectively. These data suggest that thanatophoric dysplasia is one-third to one-half as frequent as achondroplasia. The differences in the prevalence of these conditions across monitoring programs were consistent with random fluctuation. Birth defects monitoring programs may be a good source of ascertainment for population-based studies of achondroplasia and thanatophoric dysplasia, provided that diagnoses are confirmed by review of medical records. Copyright 2008 Wiley-Liss, Inc.

PMID: 18698630 [PubMed - indexed for MEDLINE]

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The Link Between Paternal Age and Genetic Disorders Shows up by 33,34,35

1: Am J Med Genet A. 2008 Sep 15;146A(18):2385-9. Links
The population-based prevalence of achondroplasia and thanatophoric dysplasia in selected regions of the US.Waller DK, Correa A, Vo TM, Wang Y, Hobbs C, Langlois PH, Pearson K, Romitti PA, Shaw GM, Hecht JT.
Houston Health Science Center, The University of Texas, Houston, Texas 77030, USA. kim.waller@uth.tmc.edu

There have been no large population-based studies of the prevalence of achondroplasia and thanatophroic dysplasia in the United States. This study compared data from seven population-based birth defects monitoring programs in the United States. We also present data on the association between older paternal age and these birth defects, which has been described in earlier studies. The prevalence of achondroplasia ranged from 0.36 to 0.60 per 10,000 livebirths (1/27,780-1/16,670 livebirths). The prevalence of thanatophoric dysplasia ranged from 0.21 to 0.30 per 10,000 livebirths (1/33,330-1/47,620 livebirths). In Texas, fathers that were 25-29, 30-34, 35-39, and > or =40 years of age had significantly increased rates of de novo achondroplasia among their offspring compared with younger fathers. The adjusted prevalence odds ratios were 2.8 (95% CI; 1.2, 6.7), 2.8 (95% CI; 1.0, 7.6), 4.9 (95% CI; 1.7, 14.3), and 5.0 (95% CI; 1.5, 16.1), respectively. Using the same age categories, the crude prevalence odds ratios for de novo cases of thanatophoric dysplasia in Texas were 5.8 (95% CI; 1.7, 9.8), 3.9 (95% CI; 1.1, 6.7), 6.1 (95% CI; 1.6, 10.6), and 10.2 (95% CI; 2.6, 17.8), respectively. These data suggest that thanatophoric dysplasia is one-third to one-half as frequent as achondroplasia. The differences in the prevalence of these conditions across monitoring programs were consistent with random fluctuation. Birth defects monitoring programs may be a good source of ascertainment for population-based studies of achondroplasia and thanatophoric dysplasia, provided that diagnoses are confirmed by review of medical records. Copyright 2008 Wiley-Liss, Inc.

PMID: 18698630 [PubMed - indexed for MEDLINE]

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Friday, September 12, 2008

Defining a cut-off at which the risk is significantly increased in the offspring could have an important impact on public health.


1: Eur Psychiatry. 2007 Jan;22(1):22-6. Epub 2006 Dec 4.
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]

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the potential that a direct campaign for fathers to complete their families before age 35 years

Prevalence of dominant mutations in Spain: effect of changes in maternal age distribution.
Martínez-Frías ML, Herranz I, Salvador J, Prieto L, Ramos-Arroyo MA, Rodríguez-Pinilla E, Cordero JF.
Estudio Colaborativo Español de Malformaciones Congénitas (ECEMC), Facultad de Medicina, Universidad Complutense, Madrid, Spain.
We studied the birth prevalence of autosomal dominant mutations in Spain and estimated how a decrease in maternal age distribution may lead to reduction in dominant mutations. The data were collected by the Estudio Colaborativo Español de Malformaciones Congénitas from April, 1976, to December, 1985. Among 553,270 liveborn infants monitored during the period, 66 infants with autosomal dominant conditions were identified. These included Apert, Crouzon, Hay-Wells, Treacher-Collins, Robinow, Stickler, Adams-Oliver, and the blepharophimosis syndromes, achondroplasia, cleidocranial dysostosis, and thanatophoric dysplasia. The overall rate of autosomal dominant conditions was 1.2 per 10,000 liveborn infants. Thirteen (20%) had an affected relative, and 52 (79%) had a negative family history. One case was excluded because of insufficient family data. The rate of autosomal dominant mutations was 0.9 per 10,000 liveborn infants, or 47 per 1 million gametes. A reduction in the maternal age distribution of mothers age 35 years and older from the current 10.8% to 4.9%, as in Atlanta, Georgia, would reduce the rate of Down syndrome in Spain by 33% and through a change in parternal age distribution may lead to a reduction in dominant mutations of about 9.6%. This suggests that a public health campaign to reduce older maternal age distribution in Spain may also lead to a reduction in dominant mutations and emphasizes the potential that a direct campaign for fathers to complete their families before age 35 years may have a small, but measurable, effect in the primary prevention of dominant mutations.
PMID: 3239577 [PubMed - indexed for MEDLINE]

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Tuesday, September 09, 2008

A Biological Clock for Dads Too --TIME CNN Tuesday, Sep. 09, 2008 By ELIZABETH HOWTON

A Biological Clock for Dads Too Turns out women aren't the only ones with an expiration date on their fertility. An emerging body of research is showing that men, too, have a "biological clock."


Not only do men become less fecund as they age, but their fertility begins to decline relatively early — around age 24, six years or so before women's. Historically, infertility has been seen as a female issue, as has the increased risk of Down syndrome and other birth defects, but studies now also link higher rates of autism, schizophrenia and Down syndrome in children born to older fathers. A recent paper by researchers at Sweden's Karolinska Institute found that the risk of bipolar disorder in children increased with paternal age, particularly in children born to men age 55 or older.

It used to be that "if you had hair on your chest, it was your wife's problem," says Barry Behr, an associate professor of obstetrics and gynecology at the Stanford Medical School and director of Stanford's in vitro fertilization laboratory. Even now, he said, though about half of infertility cases are caused by male factors, such as low sperm count or motility, there are many more tests to evaluate a woman's fertility than a man's.

To some degree, that bias is rooted in biology. Women are born with as many eggs as they'll ever have — about a million. That number steadily diminishes, and "the best eggs are ovulated first," Behr says. The ones that remain — after age 35 or so, on average — are vulnerable to toxins, radiation and other insults that may degrade their quality and viability.

By contrast, men make new sperm about every 90 days, Behr says, so the logic has been that there should not be that much difference between a young man's sperm and an old man's. Indeed, men as old as 94 have been known to father children.

Still, the research suggests it gets harder with age. A French study published in the current issue of Reproductive BioMedicine Online found that in couples undergoing infertility treatment, the father's age had as much effect as the mother's on rates of pregnancy and miscarriage — the older either parent was, the less likely they were to get pregnant, and the more likely to miscarry. Other studies have found similar trends: on average, it will take longer than a year to conceive for 8% of couples in which the man is younger than 25; that percentage nearly doubles, to 15%, in couples with men 35 or older. Data have also suggested that couples whose partners are the same age, or in which the man is younger than the woman, are more likely to conceive within a year, compared with couples in which men are at least five years older than their partners.

There are many possible explanations for the decline in male fertility, from a decrease in the number of sperm and their motility, to lower testosterone levels, to the effects of other age-related diseases such as diabetes, which is associated with erectile dysfunction and lower levels of testosterone. But researchers think that genetic factors may be behind the link between paternal age and risk of bipolar disorder and other psychiatric disorders, like autism and schizophrenia, whose origins are increasingly being attributed to DNA. Although sperm may be no more than 90 days old, the cells that make sperm may be subject to increasing DNA mutations as men age, affecting the quality of the sperm they produce.

In the Swedish study, published Sept. 1 in the Archives of General Psychiatry, researchers found that risk of developing bipolar disorder began to increase in children born to fathers around age 40. The highest risk, however, occurred in men 55 and older; their offspring were 37% more likely to develop the disorder than children born to men in their 20s. Children of older men were also twice as likely to develop early-onset disease — before age 20 — which studies suggest has a strong genetic component.

What does all this mean for would-be older dads? While women are used to seeing grim statistics about their decreasing chances of achieving pregnancy and the increasing risks of Down syndrome as they age, men have typically believed they had all the time in the world. Perhaps now, men in the mid-30s will start sharing the same "now or never" pressure to conceive that women have long endured.

When older men father children, Behr says, the traditional response has been to "pat them on the back and buy them a beer." He has seen patients that he felt were too old to become fathers, but "plenty of people make decisions about parenthood that I wouldn't," he says. "Our responsibility is to educate patients with the facts, and they decide."

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Monday, September 08, 2008

Bipolar Disorder Tied to Age of Fathers (This is where new autism, bipolar, and schizophrenia comes from)

Bipolar Disorder Tied to Age of Fathers
By NICHOLAS BAKALAR
Published: September 8, 2008
The older a man is, the more likely he is to father children who develop bipolar disorder as adults, a large Swedish study reports.


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Get Health News From The New York Times » Previous studies have found an association between paternal age and both autism and schizophrenia, but this is the first time a connection with bipolar illness has been suggested. The study appears in the September issue of The Archives of General Psychiatry.

The researchers examined highly accurate Swedish government health records of more than seven million people with known biological parents to find 13,428 with bipolar disorder diagnosed at two or more separate hospital admissions. They matched each case with five controls, people of the same age and sex but without bipolar illness. They divided the fathers into five-year age categories beginning at 20.

After statistically adjusting for the age of the mother, family history of psychotic disorders, education level and other factors, they found consistently increasing risk as fathers aged. The highest risk was in fathers 55 and older. For mothers, after adjusting for the father’s age, they found a statistically significant increase in only the 35 to 39 age group.

“It’s a strong study from a methodological standpoint,” said Dr. Alan Brown, an associate professor of psychiatry at Columbia who was not involved in the study. “National registries are very important because you’re less likely to get bias and you can generalize findings across a whole country.”

David Glahn, an associate professor of psychiatry at Yale, also uninvolved in the work, agreed. “The methodology is very strong,” he said. “The statistics done here are all first-rate.”

There is a possible biological explanation for the phenomenon, the authors write. The older a man is, the more often his sperm cells have replicated, and the more replications, the greater the chance for DNA copying errors. These are random changes, called de novo mutations, that are not inherited. Women are born with a complete supply of eggs that do not replicate as they age. The finding of only a small effect of mother’s age on the incidence of bipolar illness in the offspring is consistent with this idea.

Emma M. Frans, a doctoral student in epidemiology at the Karolinska Institute and the lead author of the study, said in a phone interview that the findings applied to adult offspring only, not children. Bipolar illness is a rare disease in any age group; in community samples the prevalence varies from 0.4 percent to 1.6 percent of the population. Still, the risk of bipolar disease in the offspring of the oldest fathers was 35 percent higher than for those of the youngest, and the association was even stronger in the small number of cases in the study diagnosed before age 20.

Dr. Dolores Malaspina, a professor of psychiatry at New York University who has studied schizophrenia in the offspring of older fathers, called the new study “very important,” but added: “The vast majority of children of any fathers will not get bipolar illness. At the level of the whole population, it may be important, but for the individual father it’s a small risk.”

The Well column returns next week. Tara Parker-Pope’s blog is online: nytimes.com/well.

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Friday, September 05, 2008

Older dads beget more bipolar kids

Older dads beget more bipolar kids
By Tom Avril

Inquirer Staff Writer

A warning for the older man who seeks fatherhood: the child may be more likely to develop bipolar disorder when grown up.

Researchers analyzed the records of 13,428 patients in Sweden who had the severe mood disorder, comparing each case with five control patients who did not have the disease.

People who had been born to fathers 55 or older were 37 percent more likely to be diagnosed with bipolar disorder than were the offspring of fathers who were 20 to 24 years at the time of birth. For early-onset cases, defined as those in which the disorder manifests before age 20, the effect was stronger.

Children born to fathers 50 and older were 2.63 times as likely to suffer from an early-onset case, according to results described in the current issue of Archives of General Psychiatry.

Advanced paternal age had already been linked with schizophrenia and autism in the offspring.

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Wednesday, September 03, 2008

Advancing paternal age and bipolar disorder.

1: Arch Gen Psychiatry. 2008 Sep;65(9):1034-40.
Advancing paternal age and bipolar disorder.Frans EM, Sandin S, Reichenberg A, Lichtenstein P, Långström N, Hultman CM.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-171 77 Stockholm, Sweden. Emma.Frans@ki.se

CONTEXT: Advancing paternal age has been reported as a risk factor for neurodevelopmental disorders. OBJECTIVES: To determine whether advanced paternal age is associated with an increased risk of BPD in the offspring and to assess if there was any difference in risk when analyzing patients with early-onset BPD separately. DESIGN: A nationwide nested case-control study based on Swedish registers was performed. Risk for BPD in the offspring of older fathers was estimated using conditional logistic regression analysis controlling for potential confounding of parity, maternal age, socioeconomic status, and parental family history of psychotic disorders. SETTING: Identification of 7,328,100 individuals and their biological parents by linking the nationwide Multigeneration Register and the Hospital Discharge Register. PARTICIPANTS: A total of 13,428 patients with a BPD diagnosis on at least 2 separate hospital admissions was identified. Five healthy control subjects matched for sex and year of birth were randomized to each case. Main Outcome Measure Bipolar disorder based on ICD codes at discharge from hospital treatment. RESULTS: An association between paternal age and risk for BPD in the offspring of older men was noted. The risk increased with advancing paternal age. After controlling for parity, maternal age, socioeconomic status, and family history of psychotic disorders, the offspring of men 55 years and older were 1.37 (95% confidence interval [CI], 1.02-1.84) times more likely to be diagnosed as having BPD than the offspring of men aged 20 to 24 years. The maternal age effect was less pronounced. For early-onset (<20 years) cases, the effect of paternal age was much stronger (odds ratio, 2.63; 95% CI, 1.19-5.81), whereas no statistically significant maternal age effect was found. CONCLUSIONS: Advanced paternal age is a risk factor for BPD in the offspring. The results are consistent with the hypothesis that advancing paternal age increases the risk for de novo mutations in susceptibility genes for neurodevelopmental disorders.

PMID: 18762589 [PubMed - in process]

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Francis Collins Could Have Warned About Increasing Paternal Age and Genetic Disease But Did Not

So Much For Taking Some Time Off
September 3, 2008

Fresh out of his post as director of NHGRI, Francis Collins will be spending the coming months working on a book on personalized medicine. "Arguably the nation's leading geneticist," says a Yahoo news article, Collins is penning "Body Language: How Personalized Medicine Will Change Your Life," slated to appear on shelves in Fall 2009.

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Tuesday, September 02, 2008

Bipolar Risk for Kids Born to Older Dads

Bipolar Risk for Kids Born to Older Dads
Study Shows Age of Dad Is a Factor in Risk of Child Developing Bipolar Disorder
By Salynn Boyles
WebMD Health NewsReviewed by Louise Chang, MDSept. 2, 2008 -- A new study suggests that children born from older fathers are at increased risk of developing bipolar disorder.

Earlier research has shown a link between older paternal age and risk for autism and schizophrenia. The new findings appear in the September issue of Archives of Psychiatry.

Overall, children born to fathers in their mid-50s and older were found to have a 37% higher risk for bipolar disorder than children born to dads in their early 20s.

The risk of developing the mood disorder before the age of 20 was roughly 2.5-times greater for children born to men age 50 and older than for children born to men between the ages of 20 and 24.

While characterizing this increase in risk as "quite strong," researcher Emma M. Frans, MmedSc, of Stockholm's Karolinska Institute tells WebMD that the relative risk at the individual level is still very small.

"There are very few men having children at this age, and most of the children born to these men will be healthy," she says.

Not Much Known About Bipolar Causes
According to the National Institute of Mental Health, about 5.7 million American adults have bipolar disorder, a serious mental illness characterized by dramatic, episodic mood swings.

While the mood disorder tends to run in families, suggesting a genetic link, little else is known about the causes of bipolar disorder.

Because older paternal age has been found to be a risk factor for other genetically influenced mental illnesses, such as schizophrenia, Frans and colleagues explored its role in bipolar disorder.

Using data from a nationwide Swedish health registry, they identified close to 13,500 people with a diagnosis of bipolar disorder. Each was randomly matched to five people without the disorder who were the same sex and born in the same year for comparison.

After taking into account maternal age and several other potential influences on risk, the researchers concluded that the offspring of men 55 years of age and older were 1.37 times more likely to have a diagnosis of bipolar disorder than the offspring of men between the ages of 20 and 24.

Older maternal age was associated with a slight, but nonsignificant, overall increase in risk, but no association was seen between maternal age and the risk for a bipolar diagnosis before age 20.

Greater Age Means More Mutations
The fact that paternal age appears to be a more important risk factor for bipolar disorder than maternal age suggests that genetic mutations in sperm may be to blame, Frans says.

Men add more mutations to the gene pool than women because their reproductive cells continue to divide throughout their lives. Women have only about 23 divisions in the cells that produce their eggs, and these divisions occur before birth, the researchers note.

Greater Age Means More Mutations continued...
More divisions mean more potential mutations or DNA damage that could be driving the increased risk for bipolar disorder and other genetically influenced mental disorders.

According to one analysis cited by the researchers, by the time a man reaches the age of 20 the cells that create sperm will have passed through 200 divisions. By age 40, about 660 divisions have occurred.

Male fertility expert Harry Fisch, MD, tells WebMD that researchers are only just beginning to understand the impact of paternal age on child health.

Fisch directs the Male Reproductive Center at New York-Presbyterian Hospital/Columbia University Medical Center. He is also the author of the book The Male Biological Clock.

"What we know probably represents just the tip of the iceberg," he says. "Until just a few years ago, there was not much research in this area. But it is important that we understand this because so many more men are having children later in life."

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Mental Illness Linked to Age of the Father

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Monday, September 01, 2008



Older fathers linked with bipolar

Sperm can carry genetic errors
Older fathers are more likely to have children with bipolar disorder, research suggests.
The risk goes up when men are older than 29 before they start their family, and is highest if they are over 55.
Increasing paternal age has already been linked with schizophrenia and autism, but not bipolar disorder, formerly known as manic depression.
The Swedish study, in Archives of Psychiatry, suggests the risk may, in part, be explained by ageing sperm.
DNA errors
Unlike women who are born with all their eggs, men make new sperm throughout their adult life.
The process of making sperm involves copying DNA, and this prone to error, particularly as men age, say the Karolinska Institute researchers.
Bipolar disorder
People with bipolar disorder fluctuate between intense depression and mania, interspersed by periods of relative calm
The exact causes of bipolar disorder aren't known, but it appears to run in families
About 1 in every 100 people develop bipolar disorder in their lifetime
Lead researcher Emma Frans explained: "Women are born with their full supply of eggs. Therefore, DNA copy errors should not increase in number with maternal age."
Consistent with this notion, they found smaller effects of increased maternal age on the risk of bipolar disorder in the families they studied.
For the study, they identified 13,428 patients in Swedish registers with a diagnosis of bipolar disorder.
For each one they randomly selected from the registers five controls who were the same sex and age but did not have bipolar disorder.
Older dads
After controlling for other factors like age of the individual's mother, number of siblings and family history of mental health problems, they found a clear link between risk of bipolar disorder and father's age.
The older an individual's father, the more likely he or she was to have bipolar disorder.
The children of men 55 years and older were 1.37 times more likely to go on to be diagnosed with bipolar disorder than those of men aged 20 to 24.
Marjorie Wallace, chief executive of the mental health charity SANE, said: "Bipolar disorder is a cruel affliction carrying a high risk of suicide and SANE welcomes this contribution to our understanding of this condition.
"There are, however, a complex range of factors that make people more or less prone to illnesses such as this, so a great deal of work still needs to be done if we are to develop better treatments and raise hope for the future."
Neil Tinning, patron of MDF The Bi-Polar Organisation, said: "From the point of view of a bipolar sufferer, this study demonstrates we need more investment, more education and more representative research into this debilitating and life threatening illness."
Bipolar disorder affects half a million people in the UK. Other than a family history of psychotic disorders, few risk factors for the condition have been identified.

Bipolar risk rises with father's age

Bipolar risk rises with father's age

Adam Cresswell, Health editor September 02, 2008
CHILDREN of older fathers are more likely to have bipolar disorder - a discovery that could explain the increasing numbers of people diagnosed with the condition.
Compared with the offspring of fathers aged 20 to 24, people whose fathers were aged 55 or over at the time of their birth are 37 per cent more likely to be diagnosed with bipolar disorder.
Children of fathers aged 30-34 had an 11 per cent increased risk of bipolar, while children of fathers aged 40-44 had a 15 per cent increased risk.
Having an older mother also increased the risk, but the effect was far less pronounced.
The research is based on nearly 13,500 Swedish people with bipolar disorder, a severe mood disorder that causes repeated peaks of euphoria and hyperactivity followed by troughs of depression.
The authors of the study, published in the US journal Archives of General Psychiatry, said paternal age was already known to be linked to other developmental disorders such as schizophrenia and autism. They suggested the findings might reflect the increased risk of DNA mutations in sperm cells, which, unlike a woman's eggs, undergo hundreds of replication cycles in which errors can occur.
Australian psychiatrist Gordon Parker, executive director of the Black Dog Institute, said the findings were important, and might explain why diagnoses of bipolar disorder had been rising.
In 1992, according to the Australian Bureau of Statistics, 35 per cent of fathers of children aged 0-14 were under 35. This fell to 26 per cent by 2003. The proportion of fathers aged 45 and over rose from 19 per cent in 1992 to 25 per cent in 2003.
However, Professor Parker said as the existing risk of bipolar disorder was thought to be between 4 and 6 per cent, the effect of the increases remained slight.
"I would hate to see any concern in the community that people shouldn't have babies because they have bipolar disorder in their family," he said.

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