First-born children of older parents were three times more likely to develop autism than later children of younger parents, researchers found.

First-born children of older parents are more likely to be autistic
A major US study has provided the strongest evidence yet that older mothers and fathers are more likely to have a child with autism.

By Roger Dobson
Last Updated: 7:48PM BST 25 Oct 2008

First-born children of older parents were three times more likely to develop autism than later children of younger parents, researchers found.

"The results provide the most compelling evidence to date that autism risk increases with both maternal and paternal age, and decreases with birth order," according to the research team, whose study was funded by the US Centers for Disease Control and Prevention.

The findings could help to provide an explanation for the recent increase in the number of children diagnosed with autism, which has coincided with a trend towards parents having children at an older age, and to smaller family sizes.

The researchers say in their paper, reported in the American Journal of Epidemiology: "The increase in autism risk with both maternal and paternal age has potential implications for public health planning and investigations of autism."

In the study, the researchers examined records of 240,000 children born in 1994, and identified 1,251 as having autism. After taking into account a range of factors, both maternal and paternal age were found to be independently associated with autism.

For mothers aged 35 or over, the risk of having an autistic child was 30 per cent higher than for mothers aged 25 to 29. Mothers under 20 had a 30 per cent lower risk than those aged 35 to 29. Fathers aged 40 or over had a 40 per cent higher risk of having an autistic child than fathers aged 25 to 29.

Many western countries have seen a trend for women to have their first child later in life, while the decline in average family size means that a higher proportion of today's children are first-born.

There is no clear explanation for why parental age increases the risk of having an autistic child. The researchers speculate that older fathers could be more likely to pass on gene mutations, while older mothers may be more prone to age-related chromasome changes or pregnancy complications. Older parents are also more likely to have undergone fertility treatment.

Another theory is that older parents may be more aware of developmental abnormalities, and therefore more likely to seek treatment and have their child diagnosed with disorders such as autism.

Firstborn children are also more prone to suffer from other childhood disorders, including type I diabetes. One possible explanation is the so-called "hygiene hypothesis", which suggests that firstborns are exposed to fewer infections from other children early in childhood and as a result are more likely to develop autoimmune diseases.

Advanced Parental Age and the Risk of Autism Spectrum Disorder

Oxford Journals Medicine American Journal of Epidemiology American Journal of Epidemiology Advance Access 10.1093/aje/kwn250


American Journal of Epidemiology Advance Access published online on October 21, 2008
American Journal of Epidemiology, doi:10.1093/aje/kwn250
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American Journal of Epidemiology © 2008 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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ORIGINAL CONTRIBUTION


Advanced Parental Age and the Risk of Autism Spectrum Disorder
Maureen S. Durkin, Matthew J. Maenner, Craig J. Newschaffer, Li-Ching Lee, Christopher M. Cunniff, Julie L. Daniels, Russell S. Kirby, Lewis Leavitt, Lisa Miller, Walter Zahorodny and Laura A. Schieve
Correspondence to Dr. Maureen Durkin, Waisman Center and Departments of Population Health Sciences and Pediatrics, University of Wisconsin School of Medicine and Public Health, 789 WARF, 610 Walnut Street, Madison, WI 53726 (e-mail: mdurkin@wisc.edu).

Received for publication March 21, 2008. Accepted for publication July 16, 2008.


ABSTRACT
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
References


This study evaluated independent effects of maternal and paternal age on risk of autism spectrum disorder. A case-cohort design was implemented using data from 10 US study sites participating in the Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network. The 1994 birth cohort included 253,347 study-site births with complete parental age information. Cases included 1,251 children aged 8 years with complete parental age information from the same birth cohort and identified as having an autism spectrum disorder based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. After adjustment for the other parent's age, birth order, maternal education, and other covariates, both maternal and paternal age were independently associated with autism (adjusted odds ratio for maternal age 35 vs. 25–29 years = 1.3, 95% confidence interval: 1.1, 1.6; adjusted odds ratio for paternal age 40 years vs. 25–29 years = 1.4, 95% confidence interval: 1.1, 1.8). Firstborn offspring of 2 older parents were 3 times more likely to develop autism than were third- or later-born offspring of mothers aged 20–34 years and fathers aged <40 years (odds ratio = 3.1, 95% confidence interval: 2.0, 4.7). The increase in autism risk with both maternal and paternal age has potential implications for public health planning and investigations of autism etiology.


autistic disorder; birth order; maternal age; paternal age


Abbreviations: ASD, autism spectrum disorder; PDD-NOS, pervasive developmental disorders-not otherwise specified


INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
References


This paper examines the relation between parental age at delivery and the prevalence of autism spectrum disorder (ASD). The possibility that autism is more common in offspring of older parents has generated considerable interest (1–6). Confirmation of such an association could have important public health implications in light of increasing trends in recent decades regarding both maternal and paternal age (7). In addition, evidence of paternal and maternal age effects on autism risk may provide clues to the etiology of a class of neurodevelopmental disorder that is still poorly understood and thought to be complex and multifactoral.

In evaluating the association between parental age and autism risk, it is important to account for other variables related to both parental age and autism or that may modify the association. Birth order is a potentially confounding factor because it is positively associated with parental age and has been reported in some studies to be associated with autism risk, with at least 3 studies reporting firstborn children to be at increased risk of autism (1, 2, 4). The goal of this study was to determine, in a large, population-based cohort of US children, whether advancing maternal and paternal age each independently increase a child's risk of developing autism after controlling for the other parent's age, birth order, and other risk factors.


MATERIALS AND METHODS
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
References


Study design and sample
We implemented a population-based, case-cohort design in which the comparison group was a cohort of all livebirths in 1994 in 10 geographically defined study areas participating in the Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network (8). The 10 areas are all sites with deidentified birth certificate information on parental age and other relevant variables included in the Network database and include sites in Alabama, Arizona, Arkansas, Colorado, Georgia, Maryland, Missouri, New Jersey, North Carolina, and Wisconsin.

The cohort serving as the comparison group includes all livebirths to mothers residing in any 1 of the study areas in 1994, with complete information available from birth certificates on maternal and paternal age, birth order, and other variables. We used 2 data sources to construct the cohort: 1994 deidentified birth records for the Wisconsin study area provided by the Wisconsin Department of Health and Family Services and, for the remaining sites, the National Center for Health Statistics public use natality data files (9). The public use file includes county of residence for births in densely populated counties, which enabled us to ascertain deidentified birth information for all births in most of the counties. We were unable to precisely obtain counts of births occurring in sparsely populated counties in which 13,043 (4.1%) of the study-area births occurred in 1994. For these counties, we obtained county-level aggregate information on the total number of births in 1994 and their distribution by variables such as maternal marital status, ethnicity, and age and selected a stratified random sample of deidentified birth records (equal in number and similar in distribution by maternal marital status, ethnicity, and age to all livebirths occurring in the respective counties in 1994) from sparsely populated counties of the state in which the study area was located. The full cohort included 326,785 livebirths, of which 73,438 (22.5%) were excluded because of missing paternal age. The cohort serving as the comparison group thus included the 253,347 livebirths with complete information on parental age and other key variables (Table 1).




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Table 1. Characteristics of the 1994 Birth Cohort and ASD Cases, 10 Study Sites From the US Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network




The total number of children aged 8 years residing in the study areas in 2002 determined by the Autism and Developmental Disabilities Monitoring Network surveillance system to have an ASD was 2,142. Birth certificate information was available for 1,517 (70.8%) of these children, who were born in the same state as their state of residence in 2002. The remaining 29.2% of cases were excluded from this analysis because of missing birth certificate information. The case group for the present analysis was further restricted to the 1,251 children (58.4% of the total ASD case group) for whom information on both parents' age as well as birth order and gestational age was available. Our final sample was comparable to the total population of ASD cases regarding demographic factors and ASD case characteristics (Table 1).
Case definition
ASDs include behaviorally defined neurodevelopmental disorders diagnosed through clinical observation, and they encompass impairments in social, communicative, and behavioral development, often accompanied by abnormalities in intellectual functioning, learning, attention, and sensory processing. For this study, children with ASD included members of the birth cohort residing in the study area in 2002 who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for autistic disorder; pervasive developmental disorders-not otherwise specified (PDD-NOS (http://www.cdc.gov/ncbddd/autism/overview_diagnostic_criteria.htm), including atypical autism); or Asperger's disorder (10) based on a comprehensive review of educational and clinical records by trained clinicians. Children were classified by clinician reviewers as having an ASD if they had either a documented previous classification of ASD (65%) or an evaluation record from an educational or medical setting indicating unusual behaviors consistent with ASD (35%). For children previously identified as having an ASD, case status was confirmed on the basis of evaluation records. For children without a documented ASD classification, data were abstracted on all relevant ASD and developmental behaviors from education or medical evaluations to determine whether behaviors described in the evaluations by clinical reviewers were consistent with the diagnostic criteria. Because case status was determined solely on the basis of information contained in evaluation records, and because Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria are less well defined for PDD-NOS than for autistic disorder, the surveillance protocol for determining whether a child could be classified as having PDD-NOS required documentation of at least 1 behavior considered to be an ASD discriminator, such as being oblivious to others when there is a clear social opportunity or demonstrating atypical and persistent focus on sensory input (11).

Of the 1,251 ASD cases, 80.7% were determined to meet criteria for autistic disorder, while there was insufficient information for those remaining to distinguish between autistic disorder, Asperger's disorder, or PDD-NOS. Information from standardized intelligence tests was available for approximately 75% of the ASD cases. On the basis of this information, children with ASD were classified as having intellectual impairment (an IQ of <70) versus normal intelligence. Further details regarding the 2002 Autism and Developmental Disabilities Monitoring Network sample and methodology have been reported previously (8, 11).

Analytic strategy and statistical methods
Potential for confounding effects of birth order, gender, and other variables was evaluated by first examining unadjusted associations between each potential confounder and the independent variables of maternal and paternal age as well as the dependent variable, ASD case status. Variables were considered to be potentially confounding factors if they were associated with both parental age and ASD. Unadjusted odds ratios with confidence intervals were computed to evaluate the magnitude of these associations, and unconditional logistic regression models were fit to estimate adjusted odds ratios and 95% confidence intervals. Statistical significance was evaluated by using chi-square tests for categorical variables and analysis of variance for continuous variables.

To enhance the comparability of our findings with those from other studies, we fit 2 types of models, 1 with parental ages categorized into 6 categories: <20, 20–24, 25–29, 30–34, 35–39, 40 years; and the other with parental age as a continuous variable with the odds ratio scaled to reflect a 10-year difference in age (4). Although we found the association between parental age and autism risk to be similar across the 10 sites, to adjust for potential site-to-site variability we included site dummy variables in all multivariable models. To evaluate interaction or modifying effects of each covariate and of ASD subtypes on the associations between parental age and ASD, we performed stratified analyses. We also tested interaction terms for maternal age by paternal age and 2-way and 3-way interaction terms for each parent's age by the other covariates in the regression models, but we identified no significant interactions. SAS version 9.1.3 software (SAS Institute, Inc., Cary, North Carolina) was used for all statistical analyses.

This research involved secondary analysis of deidentified data and was approved by the University of Wisconsin Institutional Review Board.


RESULTS
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ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
References


In unadjusted analyses, both mean maternal age and mean paternal age were significantly higher for ASD cases than for the birth cohort as a whole (Table 2). Table 2 also shows that mean parental ages differed significantly in unadjusted analyses across categories of birth order, maternal education, ethnicity, multiple birth, gestational age, and birth weight for gestational age, but not for gender. With parental age 25–29 years as the reference group, the odds of developing ASD was significantly reduced for parental age <20 years and increased for maternal age 35 and paternal age 40 years (Table 3, unadjusted odds ratios). We therefore used these age cutoffs (maternal age 35, paternal age 40 years) to classify each parent's age as "older" versus "younger." Other significant predictors of ASD in unadjusted analyses included low birth order, male gender, advanced maternal education, and preterm birth (Table 3).




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Table 2. Unadjusted Mean Maternal and Paternal Ages at Delivery for ASD Cases Compared With the Cohort as a Whole, and in the Cohort as a Whole Stratified by Covariate Categories, 1994 Birth Cohort From 10 Study Sites From the US Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network






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Table 3. Distribution of ASD Cases and Birth Cohort Comparison Group by Parental Age Categories and Other Independent Variables, and Unadjusted and Adjusted Odds Ratios With 95% Confidence Intervals, 1994 Birth Cohort From 10 Study Sites From the US Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network




Multivariable analysis of parental ages modeled as categorical variables
After we adjusted for the other parent's age and other covariates, the increases in ASD risk associated with maternal age 35 years and paternal age 40 years (relative to age 25–29 years) were slightly reduced compared with the unadjusted analysis (Table 3). In contrast, the results for birth order suggest that the decline in ASD risk associated with increasing birth order is somewhat stronger in the adjusted analysis than in the unadjusted analysis (Table 3). In addition, the apparent increase in ASD risk associated with higher levels of maternal education in the unadjusted analysis is no longer evident in the adjusted model, suggesting that the apparent maternal education effect is due to its association with parental age (Table 3).
Parental ages modeled as continuous variables
In unadjusted analyses, the risk of developing ASD increased significantly with each 10-year increase in both maternal age and paternal age. After adjustment for age of the other parent and other covariates, each 10-year increase in maternal age was associated with a 20% increase in ASD risk (odds ratio = 1.2, 95% confidence interval: 1.1, 1.4) while each 10-year increase in paternal age was associated with a 30% increase in ASD risk (odds ratio = 1.3, 95% confidence interval: 1.1, 1.5).

Combined effects of parental age and birth order
The risk of ASD within each of 3 parental age categories (both parents "younger," 1 parent "older," and both parents "older") was highest among firstborn children and declined with increasing birth order (Table 4). Considering the combined effects of parental age and birth order, we excluded from the analysis births to mothers aged <20 years and found the lowest risk group to be third- or later-born offspring of mothers aged 20–34 years and fathers aged <40 years. Compared with that for this group, the risk of ASD increased with both declining birth order and increasing number of older parents. The highest risk group included firstborn offspring of mothers aged 35 years and fathers aged 40 years, with a risk 3 times that of the reference group (Table 4).




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Table 4. Adjusted Odds Ratiosa With 95% Confidence Intervals Indicating Increasing Risk of ASD With Parental Ageb and Decreasing Risk With Birth Order, 1994 Birth Cohort From 10 Study Sites From the US Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network





DISCUSSION
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
References


Our findings are consistent with those recently reported from a large study of members of a California health maintenance organization (4) that found the risk of ASD to be positively and independently associated with both maternal and paternal age, with adjusted odds ratios nearly identical to those reported here. These findings contrast somewhat with 5 other recent epidemiologic studies that found only 1 or neither parent's age to be associated with ASD risk after controlling for the other parent's age (2, 3, 12–14).
The lack of consistency across studies could be due to limitations of sample size and of population representation of previous studies as well as other methodological differences, including autism case definitions and inclusion criteria and the ability to control for important variables. The present study included a large sample of children with sufficient information to enable evaluation of separate and combined effects of each parent's age as well as birth order and other variables. With more than 1,200 cases, it included over 50% more cases and thus more statistical power than any of the previous studies examining independent effects of maternal and paternal age on ASD risk.

Another advantage of this study is the population-based nature and diversity of the cohort, allowing control for factors that may confound the association between parental age and ASD. Maternal education is 1 variable we considered to be a potentially confounding factor because it is associated with maternal age and has been observed to be related to ASD risk (15). Our results, however, suggest that the association between advanced maternal education and ASD risk observed in unadjusted analysis may be spurious and due to confounding by parental age.

The results of this study also demonstrate the importance of controlling for birth order in evaluating independent effects of parental age on ASD risk. Because birth order increases with parental age and, in this and other studies, has been found to be negatively associated with ASD risk, failure to control for birth order may mask a positive association between parental age and ASD risk. Two of the previous studies reporting an association between advancing maternal age and ASD (2, 4) also had adjusted for birth order and, similar to the present study, found birth order to be negatively associated with ASD.

An additional advantage of this study is its restriction to a single birth year, thereby controlling for temporal trends in recent decades in both ASD prevalence and parental ages at the birth of their children. This feature of the study allows estimation of the association between parental age and ASD risk independently of temporal trends in diagnostic practices or other factors.

Public health implications
The strength of the independent associations between maternal and paternal age and ASD risk, as indicated by the odds ratios in the range of 1.2–1.4 reported here, is modest. However, the observation that these effects are independent of each other and of low birth order raises the likelihood that the combined effects of parental age and birth order may have important public health implications. Mean maternal age in the United States has increased steadily since the 1970s, particularly for firstborn children, for whom mean maternal age at delivery increased by 3.8 years between 1970 and 2004 (16). In addition, the proportion of births to women aged 35 years began increasing in the United States after 1980, when it was 5%; by 2004, it had increased to 14.2% (17, 18). During this same period, fertility rates for men aged 40 years also increased each year, while fertility among men aged <30 years declined (16). With the decline in average family size in recent decades, we would also expect the proportion of children who are firstborn to have increased. Similar trends are occurring in other developed countries (7). The results of this study raise the question of whether some portion of the recent rise in ASD prevalence (19) may be linked to recent trends in parental age and family size. A further question is whether a modest increase in prevalence associated with advancing parental age and low birth order may have contributed to a greater awareness of ASD and, in turn, increases in measured prevalence. The tendency for older parents of firstborn children to have higher levels of educational achievement and resources than other parents could further contribute to increased awareness and an expansion of the diagnosis of ASD.

Potential etiologic implications of parental age effects
Because we observed independent effects of the age of each parent on ASD risk, the possible mechanisms for these effects could include a broad range of processes associated with either or both maternal and paternal age. The observed paternal age effect independent of maternal age could point to a causal role of gene mutations in male germ cells, because the probability or selection of these mutations increases as men age (20, 21). The independent effect of maternal age, on the other hand, may point to age-related chromosome changes, pregnancy complications, or environmental exposures during pregnancy. Independent effects of 1 or both parents' ages also could point to a role of accumulated environmental exposures that may have mutagenic effects on gametes or could result from a combination of mechanisms (21, 22).

The association between advanced maternal and paternal age and ASD is also consistent with a potential role of infertility treatments or assisted reproductive technologies, the uses of which have increased in the past decade, especially by women and men of advanced reproductive age (23). Numerous studies have found associations between these technologies and adverse pregnancy outcomes, including those due to epigenetic effects (24–27), although a recent review found no evidence of elevated rates of autism among children born after in vitro fertilization techniques (28). Even though we have no information about exposure to these treatments in our cohort, the observation that firstborn children of older parents had the highest ASD risk is consistent with a possible infertility treatment effect because women who give birth after infertility treatment are more likely to be primiparous than those represented in the general birth cohort. However, the association between multiple birth and ASD in this study was weak and not statistically significant (Table 3, unadjusted odds ratio), whereas assisted reproduction technologies are strongly associated with multiple birth (23).

Another unmeasured factor in the present study potentially associated with both advanced parental age and ASD risk in offspring is psychopathology or behavioral traits of parents that may result in both delayed parenthood and genetic susceptibility to autism in offspring (14).

Birth-order effects
The observation in this and at least 2 previous studies (2, 4) that the risk of developing ASD was highest for firstborn children and declined with increasing birth order is a pattern also observed for other childhood disorders, including type I diabetes and atopy, and is cited as support for the "hygiene hypothesis." According to this hypothesis, firstborn children are exposed to fewer infections from other children early in childhood and, because of delayed immunologic challenge, may be more likely to develop autoimmune responses including those that may adversely affect neurodevelopment (29). Another possible factor that could lead to the observed birth-order effect is exposure to potentially neurotoxic, fat-soluble chemicals accumulated in maternal tissue that have been passed to offspring transplacentally or through breast milk (30). Because of accumulation over a lifetime, the load of such neurotoxins transmitted might be expected to be highest for firstborn children, particularly when combined with advanced maternal age. Another possible explanation for the observed birth order effect is "stoppage" or a tendency for parents of 1 child with ASD not to have subsequent children because of the demands of parenting a child with a disability or concerns about genetic susceptibility (31), thus increasing the likelihood in the cohort as a whole that a child with ASD will have a low birth order. Information available for the present study did not allow examination of these hypotheses.

Another important limitation of this study is that the cohort available for analysis excludes births with missing paternal age information. Because this exclusion applied to both the ASD cases and the comparison group (Table 1), we would not expect it to have resulted in biased estimates of the association between ASD and parental age. In a separate analysis, we examined the association between maternal age and ASD without adjusting for paternal age and including the full birth cohort, and we found the association between maternal age and ASD to be the same as that observed in the subcohort with paternal age.

Another limitation is that the birth cohort comparison group includes about 1% of births of children who died postnatally in addition to an undetermined number who moved out of the study area between birth and the age of 8 years, whereas children who died postnatally and those moving out of the study area after birth are excluded from the case group. Because of this limitation, we could not estimate cumulative incidence of ASD. Nonetheless, this limitation is unlikely to have biased the estimated odds ratios reported in this study, particularly those adjusted for factors such as gestational age and birth weight for gestational age, which are strongly associated with postnatal mortality. Another possible explanation for the increase in ASD among offspring of older parents, but one we cannot evaluate with the data available, is that, compared with younger parents, older parents may be more aware of developmental abnormalities and better able to access diagnostic and special educational services. Other limitations are that parity pertains to only mothers and does not take into account the number of previous births fathered by the fathers represented in the cohort, potential for residual confounding by factors not measured in the present study, possible misclassification of ASD case status, and missing information on paternal education.

Conclusion
The results of this study provide the most compelling evidence to date that ASD risk increases with both maternal and paternal age and decreases with birth order. Further research involving large, well-characterized birth cohorts followed longitudinally will be required to confirm these findings and adequately evaluate the range of alternative genetic and environmental hypotheses that this and other studies raise regarding parental age and birth-order effects on ASD risk. Smaller, focused studies may also be useful, such as Crow's idea to look for mutations responsible for complex disorders of unknown etiology and with parental age effects by studying affected families with older parents (20).






ACKNOWLEDGMENTS

Author affiliations: Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (Maureen S. Durkin, Matthew J. Maenner); Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (Maureen S. Durkin, Lewis Leavitt); Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin (Maureen S. Durkin, Matthew J. Maenner, Lewis Leavitt); Department of Epidemiology, Drexel University, Philadelphia, Pennsylvania (Craig J. Newschaffer); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (Li-Ching Lee); Department of Pediatrics, University of Arizona College of Medicine, Tucson, Arizona (Christopher M. Cunniff); Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (Julie L. Daniels); Department of Maternal and Child Health, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama (Russell S. Kirby); Department of Public Health and Environment, State of Colorado, Denver, Colorado (Lisa Miller); Department of Pediatrics, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Trenton, New Jersey (Walter Zahorodny); and National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia (Laura A. Schieve).

This work was funded by the Centers for Disease Control and Prevention, Cooperative Agreements UR3/CCU523235 and UR3/DD000078. Additional funding for graduate student support for data analysis was provided by the University of Wisconsin.

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

Conflict of interest: none declared.


References
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ABSTRACT
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MATERIALS AND METHODS
RESULTS
DISCUSSION
References




Tsai LY, Stewart MA. Etiological implication of maternal age and birth order in infantile autism. J Autism Dev Disord (1983) 13(1):57–65.[CrossRef][ISI][Medline]
Glasson EJ, Bower C, Petterson B, et al. Perinatal factors and the development of autism. Arch Gen Psychiatry (2004) 61(6):618–627.[Abstract/Free Full Text]
Reichenberg A, Gross R, Weiser M, et al. Advancing paternal age and autism. Arch Gen Psychiatry (2006) 63(9):1026–1032.[Abstract/Free Full Text]
Croen LA, Najjar DV, Fireman B, et al. Maternal and paternal age and risk of autism spectrum disorder. Arch Pediatr Adolesc Med. (2007) 161(4):334–340.[Abstract/Free Full Text]
Cantor RM, Yoon JL, Furr J, et al. Paternal age and autism are associated in a family-based sample. Mol Psychiatry (2007) 12(5):419–421.[CrossRef][ISI][Medline]
Koyama T, Miyake Y, Kurita H. Parental ages at birth of children with pervasive developmental disorders are higher than those of children in the general population. Psychiatry Clin Neurosci. (2007) 61(2):200–202.[Medline]
Bray I, Gunnell D, Davey Smith G. Advanced paternal age: how old is too old? J Epidemiol Community Health (2006) 60(10):851–853.[Abstract/Free Full Text]
Autism and Developmental Disabilities Monitoring Network Surveillance Year 2002 Principal Investigators; Centers for Disease Control and Prevention. 14 sites, United States, 2002. MMWR Surveill Summ. (2007) 56(1):12–28.[Medline]
National Center for Health Statistics, natality data, public-use data files. (http://www.cdc.gov/nchs/products/elec_prods/subject/natality.htm) (Accessed November 2007).
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR. Fourth Edition, Text Revision (2000) Arlington, VA: American Psychiatric Association.
Rice CE, Baio JL, Van Naarden Braun K, et al. A public health collaboration for the surveillance of autism spectrum disorders. Paediatr Perinat Epidemiol. (2007) 21(2):179–190.[CrossRef][ISI][Medline]
Lauritsen MB, Pedersen CB, Mortensen PB. Effects of familial risk factors and place of birth on the risk of autism: a nationwide register-based study. J Child Psychol Psychiatry (2005) 46(9):963–971.[CrossRef][ISI][Medline]
Maimburg RD, Vaeth M. Perinatal risk factors for infantile autism. Acta Psychiatr Scand. (2006) 114(4):257–264.[CrossRef][ISI][Medline]
Larsson HJ, Eaton WW, Madsen KM, et al. Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status. Am J Epidemiol. (2005) 161(10):916–925.[Abstract/Free Full Text]
Treffert DA. Epidemiology of infantile autism. Arch Gen Psychiatry (1970) 22(5):431–438.[ISI][Medline]
Martin JA, Hamilton BE, Sutton PD. Births: final data for 2004. Natl Vital Stat Rep. (2006) 55(1):1–102.[Medline]
Mathews TJ, Hamilton BE. Mean age of mother, 1970–2000. Natl Vital Stat Rep. (2002) 51(1):1–14.[Medline]
CDC. National Vital Statistics System. (http://www.cdc.gov/nchs/births.htm#Tabulated) (Accessed September 11, 2008).
Yeargin-Allsopp M, Rice C, Karapurkar T, et al. Prevalence of autism in a US metropolitan area. JAMA (2003) 289(1):49–55.[Abstract/Free Full Text]
Crow JF. The high spontaneous mutation rate: is it a health risk? Proc Natl Acad Sci U S A (1997) 94(16):8380–8386.[Abstract/Free Full Text]
Crow JF. Age and sex effects on new mutation rates: an old problem with new complexities. J Radiat Res (Tokyo) (2006) 47(suppl_B):B75–B82.[CrossRef][Medline]
Penrose LS. Parental age and mutation. Lancet (1955) 269(6885):312–313.[CrossRef][Medline]
Wright VC, Chang J, Jeng G, et al. Assisted reproductive technology surveillance—United States, 2004. MMWR Surveill Summ. (2007) 56(6):1–22.[Medline]
Ombelet W, Martens G, De Sutter P, et al. Perinatal outcome of 12,021 singleton and 3108 twin births after non-IVF-assisted reproduction: a cohort study. Hum Reprod. (2006) 21(4):1025–1032.[Abstract/Free Full Text]
Schieve LA, Rasmussen SA, Reefhuis J. Risk of birth defects among children conceived with assisted reproductive technology: providing an epidemiologic context to the data. Fertil Steril. (2005) 84(5):1320–1324.[CrossRef][ISI][Medline]
DeBaun MR, Niemitz EL, Feinberg AP. Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19. Am J Hum Genet. (2003) 72(1):156–160.[CrossRef][ISI][Medline]
Sato A, Otsu E, Negishi H, et al. Aberrant DNA methylation of imprinted loci in superovulated oocytes. Hum Reprod. (2007) 22(1):26–35.[Abstract/Free Full Text]
Newschaffer CJ, Croen LA, Daniels J, et al. The epidemiology of autism spectrum disorders. Annu Rev Public Health (2007) 28:235–258.[CrossRef][ISI][Medline]
Rook GA. The hygiene hypothesis and the increasing prevalence of chronic inflammatory disorders. Trans R Soc Trop Med Hyg. (2007) 101(11):1072–1074.[CrossRef][ISI][Medline]
Iida T, Hirakawa H, Matsueda T, et al. Polychlorinated dibenzo-P-dioxins and related compounds in breast milk of Japanese primiparas and multiparas. Chemosphere (1999) 38(11):2461–2466.[Medline]
Jones MB, Szatmari P. Stoppage rules and genetic studies of autism. J Autism Dev Disord (1988) 18(1):31–40.[CrossRef][ISI][Medline]

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Advanced Parental Age and the Risk of Autism Spectrum Disorder

1: Am J Epidemiol. 2008 Oct 21. [Epub ahead of print]
Advanced Parental Age and the Risk of Autism Spectrum Disorder.Durkin MS, Maenner MJ, Newschaffer CJ, Lee LC, Cunniff CM, Daniels JL, Kirby RS, Leavitt L, Miller L, Zahorodny W, Schieve LA.
This study evaluated independent effects of maternal and paternal age on risk of autism spectrum disorder. A case-cohort design was implemented using data from 10 US study sites participating in the Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network. The 1994 birth cohort included 253,347 study-site births with complete parental age information. Cases included 1,251 children aged 8 years with complete parental age information from the same birth cohort and identified as having an autism spectrum disorder based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. After adjustment for the other parent's age, birth order, maternal education, and other covariates, both maternal and paternal age were independently associated with autism (adjusted odds ratio for maternal age >/=35 vs. 25-29 years = 1.3, 95% confidence interval: 1.1, 1.6; adjusted odds ratio for paternal age >/=40 years vs. 25-29 years = 1.4, 95% confidence interval: 1.1, 1.8). Firstborn offspring of 2 older parents were 3 times more likely to develop autism than were third- or later-born offspring of mothers aged 20-34 years and fathers aged <40 years (odds ratio = 3.1, 95% confidence interval: 2.0, 4.7). The increase in autism risk with both maternal and paternal age has potential implications for public health planning and investigations of autism etiology.

PMID: 18945690 [PubMed - as supplied by publisher]

The report said there was significant DNA damage to sperm in samples from men over the age of 35.

Oct
23
2008
Men have their own biological clock
Published by Times of the Internet at 3:34 am under Top News

SYDNEY, Oct. 22 (UPI) —


An Australian study suggests men have a biological clock that signals a drop in fertility after the age of 35.



Researchers at Sydney IVF said sperm and DNA samples from more than 3,000 men shows DNA fragmentation of sperm increased with age, the Australian Broadcasting Corp. reported Wednesday.



The report said there was significant DNA damage to sperm in samples from men over the age of 35.



They cannot take fertility absolutely for granted, there is also an impact of male age on fertility, Mark Bowman of Sydney IVF said.



Copyright 2008 by United Press International
All Rights Reserved.

Study Backs Link Between Father’s Age, Schizophrenia

Study Backs Link Between Father’s Age, Schizophrenia
ISLAMABAD: Children born to older fathers have a higher than normal risk of developing schizophrenia later in life, Swedish scientists said on Friday.
They suspect that accumulating mutations in the sperm of older men add to the risk of their children suffering from the psychotic disorder.
"There is an association between paternal age and the risk of schizophrenia in the offspring," Professor Finn Rasmussen, of the Karolinska Institute in Stockholm, told.
Other researchers have suggested such a link before but Rasmussen said his study of 700,000 people in Sweden is the largest and most significant.
"On a population level this is important because of the increasing paternal age of the population," he added.
Career demands and other factors have resulted in couples postponing having children. In England and Wales the average paternal age has increased from 29.2 in 1980 to 32.1 in 2002.
Rasmussen and his team, who reported their research in the British Medical Journal, estimated that the three-year age increase in the last 20 years could result in 12-15 percent more cases of schizophrenia.
The causes of schizophrenia are unknown. Scientists believe it affects chemicals in the brain and that there is a biological link which can predispose a person to the disease.
It affects about 24 million people worldwide, mostly in the 15-35 age group. Although it is a treatable illness, more than 50 percent of sufferers do not receive appropriate care, according to the World Health Organization.
Schizophrenia usually begins in the late teens and early 20s and is characterized by hallucinations, delusions, hearing voices and changes in behavior.
In their study of people born between 1973 and 1980, Rasmussen and his colleagues analyzed hospital admissions for schizophrenia and other disorders between 1989 and 2001.
They calculated that, overall, 15.5 percent of schizophrenia cases in the study group may have been due to the patient having a father who was over 30 years at the birth.
The risk increases with age, so a child born to a man of 50 could have a higher risk than one whose father was 30.
"The occurrence of mutation in sperm increases with age," Rasmussen added.

The Man's Biological Clock is Ticking for the Health of the Offspring too

Biological clock ticking for men too
By medical reporter Sophie Scott

Posted 4 hours 42 minutes ago

Video: Male biological clock ticking too (ABC News) Map: Sydney 2000
The drop off in fertility for women after the age of 35 is well known. Now Australian researchers have found that men face a similar decline at the same age.

Sydney IVF researchers took sperm samples from more than 3,000 men and their DNA or genetic make-up was examined.

Mark Bowman from Sydney IVF says they found older men had less chance of fathering a child.

"They cannot take fertility absolutely for granted, there is also an impact of male age on fertility," he said.

Dr Kylie de Boer says the samples showed that as men age their sperm starts to fragment or break down, which makes the sperm less viable for fertilising the egg.

The older the man, the more damage, researchers found.

"The rate of DNA fragmentation of sperm increased with age and there was a significant DNA damage to sperm when the man was above the age of 35," Mr Bowman said.

And while the Rupert Murdochs of this world have fathered children later in life, the new research suggests they are the exception, not the rule.

One in six Australian couples end up seeking medical treatment because they cannot conceive and in almost half of those cases it is due to male infertility.

Mr Bowman says a healthy lifestyle is one way of holding back the years.

"The messages would be limit alcohol, don't smoke, eat a healthy diet, take anti-oxidants and probably spend more time with your partner," he said.


Tags: health, mens-health, reproduction-and-contraception,

Long-term effects of delayed fatherhood in mice on postnatal development and behavioral traits of offspring

Long-term effects of delayed fatherhood in mice on postnatal
development and behavioral traits of offspring1
Short title: Long-term effects of paternal age on offspring
Summary sentence: Delayed fatherhood has long-term effects on preweaning development,
spontaneous motor activity and passive-avoidance learning capacity of offspring in the mouse
model
Key words: delayed fatherhood long-term effects offspring
Silvia García-Palomares3, José F. Pertusa3, José Miñarro4, Miguel A. García-Pérez5,6,
Carlos Hermenegildo5,7, Francisco Rausell3, Antonio Cano8 and Juan J. Tarín2,3
1Supported by grant BFI2003-04761 from “Ministerio de Ciencia y Tecnología”, cofinanced by
the “Fondo Europeo de Desarrollo Regional (FEDER); grant ISCIII2006-PI0405 from “Instituto
de Salud Carlos III, Fondo de Investigación Sanitaria, Ministerio de Sanidad y Consumo”,
cofinanced by the FEDER; and grants GV2004-B-206 and AE/2007/001 from “Generalitat
Valenciana, Conselleria d’Émpresa, Universitat i Ciencia”.
2Correspondence: Juan J. Tarín, Department of Functional Biology and Physical Anthropology,
Faculty of Biological Sciences, University of Valencia, Dr. Moliner 50, 46100 Burjassot,
Valencia, Spain; Tel. 34-96-354 3221; E-mail: tarinjj@uv.es
3Department of Functional Biology and Physical Anthropology, Faculty of Biological Sciences,
University of Valencia, Burjassot, 46100 Valencia, Spain
BOR

delayed fatherhood long-term effects offspring

Delayed fatherhood in mice decreases reproductive fitness
and longevity of offspring1
Short title: Long-term effects of paternal age on offspring
Summary sentence: Delayed fatherhood decreases reproductive fitness and longevity of
offspring in the mouse model
Key words: delayed fatherhood long-term effects offspring
Silvia García-Palomares3, Samuel Navarro4, José F. Pertusa3, Carlos Hermenegildo5,6,
Miguel A. García-Pérez5,7, Francisco Rausell3, Antonio Cano8 and Juan J. Tarín2,3
1Supported by grant BFI2003-04761 from “Ministerio de Ciencia y Tecnología”, cofinanced by
the “Fondo Europeo de Desarrollo Regional (FEDER); grant ISCIII2006-PI0405 from “Instituto
de Salud Carlos III, Fondo de Investigación Sanitaria, Ministerio de Sanidad y Consumo”,
cofinanced by the FEDER; and grants GV2004-B-206 and AE/2007/001 from “Generalitat
Valenciana, Conselleria d’Émpresa, Universitat i Ciencia”.
2Correspondence: Juan J. Tarín, Department of Functional Biology and Physical Anthropology,
Faculty of Biological Sciences, University of Valencia, Dr. Moliner 50, 46100 Burjassot,
Valencia, Spain; Tel. 34-96-354 3221; E-mail: tarinjj@uv.es
3Department of Functional Biology and Physical Anthropology, Faculty of Biological Sciences,
University of Valencia, Burjassot, 46100 Valencia, Spain
4Department of Pathology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain
5Research Unit, Hospital Clínico de Valencia, 46010 Valencia, Spain

Does a dad's age effect a child's mental health? (sperm DNA)

Research is increasingly showing that fertility is impacted by aman's age, not just a woman's age, eggs and body. If you are awoman with the big red “OVER 35″ flag on your ob/gyn chart, youknow that you've been well-warned and tested for your risk ofconceiving a child with Down syndrome and other developmentalissues. Studies of autism, schizophrenia, bipolar disorder and Down syndrome now show that olderfathers also carry that red flag of higher risk.
This understanding is radical because it shifts the focus (andsometimes, the blame) of fertility. Because females are born withall the eggs they will have in their lifetime and men produce spermevery 90 days, the formula's told us that women's fertility isever-decreasing while men's is always rejuvenating. Not so, sciencenow says. In fact, the quantity sperm may be produced every threemonths but the quality of the sperm does go down as men get older.While there are certainly elderly men actively making babies, somestudies have shown that it takes 8% of couples more than a year toconceive when the father is 25 or younger, but 15% of couples(almost double the rate of infertility challenge) when the fatheris 35 or older.
I was also fascinated to read that one French study reports that,among couples seeking fertility treatment, each parent's age hasequal impact on pregnancy and miscarriage. This means that theolder the parent — male or female — the lower thechances of getting pregnant at all and the higher the likelihoodthe woman will miscarry.
A final note on this new information on men's fertility: It seemsyour 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 sixyears before women's fertility declines.
Will this change how men and women make decisions about when toparent? Will men's attitudes align with science so that they feelfree to acknowledge their own flippy urges to reproduce morefreely? Perhaps only time — and more studies — will tell.
Are you worried about your man's fertility? Do thesenew studies take the pressure off you or just complicate conceptioneven more?Read more:
Does a dad's age effect a child's mental health?
If your man's biological clock is ticking, for zygote's sake, don'tlet him turn on the seat heaters!

Advanced Parental Age at Birth Is Associated With Poorer Social Functioning in Adolescent Males: Shedding Light on a Core Symptom of Schizophrenia and

Autism

Schizophrenia Bulletin Advance Access originally published online on September 15, 2008
Schizophrenia Bulletin 2008 34(6):1042-1046; doi:10.1093/schbul/sbn109


© The Author 2008. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.


Advanced Parental Age at Birth Is Associated With Poorer Social Functioning in Adolescent Males: Shedding Light on a Core Symptom of Schizophrenia and Autism
Mark Weiser14, Abraham Reichenberg5, Nomi Werbeloff2, Karine Kleinhaus6, Gad Lubin3, Moti Shmushkevitch3, Asaf Caspi2,4, Dolores Malaspina7 and Michael Davidson2,4
2 Department of Psychiatry, Sheba Medical Center, Tel-Hashomer, Ramat Gan 52621, Israel
3 IDF, Division of Mental Health, Israel
4 Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel
5 Institute of Psychiatry, London, UK
6 Department of Psychiatry, Colombia University, NY
7 Department of Psychiatry, New York University, NY

1 To whom correspondence should be addressed; tel: +972-52-666-6575, fax: +972-3-6358599, e-mail: mweiser@netvision.net.il.

Background: Evidence indicates an association between older parents at birth and increased risk for schizophrenia and autism. Patients with schizophrenia and autism and their first-degree relatives have impaired social functioning; hence, impaired social functioning is probably an intermediate phenotype of the illness. This study tested the hypothesis that advanced father's age at birth would be associated with poorer social functioning in the general population. To test this hypothesis, we examined the association between parental age at birth and the social functioning of their adolescent male offspring in a population-based study. Methods: Subjects were 403 486, 16- to 17-year-old Israeli-born male adolescents assessed by the Israeli Draft Board. The effect of parental age on social functioning was assessed in analyses controlling for cognitive functioning, the other parent's age, parental socioeconomic status, birth order, and year of draft board assessment. Results: Compared with offspring of parents aged 25–29 years, the prevalence of poor social functioning was increased both in offspring of fathers younger than 20 years (odds ratio [OR] = 1.27, 95% confidence interval [CI] = 1.08–1.49) and in offspring of fathers 45 years old (OR = 1.52, 95% CI = 1.43–1.61). Male adolescent children of mothers aged 40 years and above were 1.15 (95% CI = 1.07–1.24) times more likely to have poor social functioning. Conclusions: These modest associations between parental age and poor social functioning in the general population parallel the associations between parental age and risk for schizophrenia and autism and suggest that the risk pathways between advanced parental age and schizophrenia and autism might, at least partially, include mildly deleterious effects on social functioning.


Keywords: schizophrenia / social functioning / parental age

Father's Age Linked to Risk of Schizophrenia

April 12, 2001


Father's Age Linked to Risk of Schizophrenia

By ERICA GOODE





Expanded Coverage

Health: Psychology





Join a Discussion on Mental Health and Treatment





he risk of having a child with schizophrenia may increase with a father's advancing age, researchers reported yesterday.

The researchers, who examined the relationship between the fathers' ages and schizophrenia among 87,907 Israelis born from 1964 through 1976, found that the older the father, the more likely he was to have a child who suffered from schizophrenia, a devastating mental illness.

Men who were 45 through 49, for example, were twice as likely to have offspring with schizophrenia or a related disorder as were men under 25, the researchers found. The overall risk of having a child with the illness, however, remained small.

"The finding is a very strong association of schizophrenia risk and father's age," said Dr. Delores Malaspina, an associate professor of clinical psychiatry at the Columbia University College of Physicians and Surgeons and the lead author of the report, which appears in this month's issue of the journal Archives of General Psychiatry.

Other scientists were more skeptical. They noted that confirmation through other studies was needed before such a link could be said to be established, and they cautioned that in the history of schizophrenia research, many apparent associations had eventually proved spurious or impossible to replicate.

If the results of the study hold up to scrutiny, Dr. Malaspina said, "The next question is, `What might explain that finding?' " One possibility, the researchers argue in their report, is that some cases of schizophrenia are a result of genetic abnormalities in sperm cells that become more likely as a man ages.

Stem cells in the testicles divide throughout a man's life in a process that leads to the production of sperm. Each cell division carries the chance for copying errors in reproducing the DNA. By the age of 40, research suggests, about 660 such divisions have taken place. Genetic mutations can also occur from exposure to radiation or chemicals over a man's life.

In contrast, the divisions of cells that produce a woman's eggs occur only before birth.

A number of physical illnesses and birth defects have been linked to genetic mutations during sperm production in older fathers, including Apert syndrome, a rare congenital deformity of the skull, fingers and toes, and achondroplasia, the most common form of dwarfism.

Some cases of schizophrenia, the researchers suggested, might be associated with similar mutations.

The illness runs in families, and is known to have a strong genetic component, though efforts to identify the specific gene or genes that predispose a person to schizophrenia have so far been inconclusive. The disease affects 1 of every 100 Americans and is more common in men. Full-blown symptoms often first appear in late adolescence or early adulthood.

In some cases, people who do not have a family history of schizophrenia also develop the illness. Dr. Malaspina said that the findings of her study "suggest that relevant mutations are there" in such sporadic cases "as well as in familial cases."

Dr. James F. Crow, a professor emeritus of genetics at the University of Wisconsin, said, "I think this is very strong evidence for a mutation component to schizophrenia, but it's quite an open question as to how much of a component."

But other scientists cautioned that other explanations beside spontaneous genetic mutation could also account for the study's results.

For example, said Dr. Ann Pulver, director of the epidemiology and genetics program in psychiatry at Johns Hopkins University, "It may be that the fathers of schizophrenics have unusual characteristics that delay reproduction."

"I think this is an interesting contribution to the epidemiological literature, that paternal age may be a risk factor for a subgroup of schizophrenic patients," Dr. Pulver said. "And it may be that advanced paternal age is associated with a mutation. But that is a hypothesis and one would need to test it.

In the study, Dr. Malaspina and her colleagues took advantage of the Jerusalem Perinatal Study, a research archive that includes information about all births in one area of Jerusalem. Records from the study were correlated with those of a national registry of psychiatric illness kept by the Israeli government.

The researchers found that in 1,337 people admitted to psychiatric hospitals before 1998, the fathers' ages were strongly associated with a diagnosis of schizophrenia or a related disorder. The risk of schizophrenia increased steadily with the father's increasing age. Advancing age of the fathers, the investigators reported, accounted for 26 percent of the cases of schizophrenia in the study; for fathers over 50, two out of every three cases of the illness could be attributed to the father's age.

Whose biological clock is ticking? Harry Fisch

Whose biological clock is ticking?
Submitted by David on Sun, 2008-10-05 22:08
"Everybody was familiar with the concept of women's biological clock, but when we introduced 'male' to the equation, the reaction was 'What are you talking about? Men can have children at any age,'" recalls urologist Harry Fisch, director of the Male Reproductive Center at Columbia Presbyterian Hospital in New York City and author of The Male Biological Clock. "It became a social issue. Men do not like to be told they have a problem."

Nonetheless, a virtual tidal wave of recent research has made it irrefutable: Not only does male fertility decrease decade by decade, especially after age 35, but aging sperm can be a significant and sometimes the only cause of severe health and developmental problems in offspring...

(excerpted from Psychology Today) » Add new comment

Overlap Found Between Autism, Schizophrenia-Spectrum Disorders

Psychiatr News October 3, 2008
Volume 43, Number 19, page 20
© 2008 American Psychiatric Association

Overlap Found Between Autism, Schizophrenia-Spectrum Disorders
Joan Arehart-Treichel
Some patients may have traits of both autism and schizophrenia because the autism-spectrum and schizophrenia-spectrum disorders share some of the same susceptibility genes.

Although autism and schizophrenia are now generally recognized as two separate illnesses, there is reason to believe that autistic traits and schizophrenia traits co-occur in some individuals.

For instance, some children with autism disorder have been found to develop schizophrenia later in life, the negative symptoms of schizophrenia have been found to co-vary with autistic traits in certain schizophrenia subjects, and a link between autistic traits and schizophrenia traits was found in a sample of college students.

Now certain individuals with schizotypal personality disorder—considered the mildest schizophrenia-spectrum illness—have been found to possess an unusual preponderance of autistic traits. The results of the study, which was led by Michelle Esterberg, M.P.H., of Emory University, were published in the September Schizophrenia Research.

The study included 121 adolescent subjects—35 with schizotypal personality disorder; 38 with other types of personality disorders (antisocial, avoidant, borderline, narcissistic, obsessive-compulsive, paranoid, or schizoid); and 48 with no personality disorders. The subjects were evaluated for various autistic characteristics, and the results for each group were then compared.

The schizotypal group scored significantly higher than the other two groups on a number of autistic traits. They included being socially anxious, having no close friends, using a limited number of facial expressions, not showing affection, being unaware of social cues, having circumscribed or unusual interests, and being resistant to change. Furthermore, the schizotypal group scored especially high on deficits in the social-functioning domain.

"The present findings indicate significant ... overlap between autism-spectrum and schizophrenia-spectrum disorders," Esterberg and her colleagues concluded.

Why might autistic traits and schizophrenia traits coexist in certain persons? Esterberg and her group suspect that it is because the autism-spectrum disorders and the schizophrenia-spectrum disorders share some of the same susceptibility genes or because some of the susceptibility genes contributing to each spectrum are occasionally inherited together.

For instance, individuals who lack genes on a particular stretch of chromosome 22—called the 22q11 chromosomal deletion—are known to be at heightened risk for both the autistic-spectrum and schizophrenia-spectrum disorders, they pointed out, suggesting that some genes located in this stretch are complicit in both disorders (Psychiatric News, September 19).

But one point they are quite sure about, as are many other investigators, is that autism and schizophrenia are not identical illnesses. One reason is because 10 of their schizotypal subjects, as well as two other subjects from the "other personality disorder" category, developed schizophrenia during a three-year follow-up period. Yet the researchers could find no link between having autistic traits and subsequently developing schizophrenia.

The study was funded by the National Institute of Mental Health.

An abstract of "Childhood and Current Autistic Features in Adolescents With Schizotypal Personality Disorder" can be accessed at by clicking on "Browse A-Z," "S," and then "Schizophrenia Research."