Unexpected Associations between the Number of FRAXE Repeats in Boys and Evidence of Diabetes in Their Mothers and Maternal Grandmothers

The FRAXE section of the FMR2 gene, located on the X chromosome, contains varying numbers of trinucleotide repeats; boys with over 200 repeats tend to have mild cognitive impairments, though this is rare. Little is known, however, concerning the phenotypes of individuals with smaller numbers of repeats. Here we answer the research question as to whether the health of ancestors of boys from whom the relevant X chromosome was inherited differed in any way according to the number of FRAXE repeats. Numbers of FRAXE repeats in 5057 boys from the Avon Longitudinal Study of Parents and Children (ALSPAC) were assessed. The distribution was bimodal, with the second smaller distribution starting at 22 repeats. We tested whether possession of 22+ repeats was associated with differences in the health of mothers (who share the X chromosome) and maternal grandmothers (half of whom share it). Female ancestors of boys with >21 repeats compared with <22 showed that maternal grandmothers (MGM) and mothers (M) had an increased risk of diabetes: MGM Type I odds ratio (OR) 2.40 [95%CI: 1.07,5.38]; MGM Type II OR 1.61 [0.96,2.70]; M OR 1.95 [0.96,3.94] using self-reported questionnaire measures. These results were confirmed from maternal medical records which revealed an increased level of diabetes [OR 2.40 (1.16,4.96)] and an increased risk of repeated glycosuria during pregnancy [OR 1.60 (1.08,2.36)]. We tested numbers of FRAXA repeats and showed no such associations, indicating that the findings were not associated with triploid repeats in general. If these findings are replicated elsewhere, there are at least three possible interpretations: (i) maternal diabetes/prediabetes results in an increased number of FRAXE repeats; (ii) women with high numbers of FRAXE repeats are at increased risk of diabetes; or (iii) some common factor, e.g. genomic instability, results in both diabetes and increased repeats.

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Timing of menarche and depressive symptoms in adolescent girls from a UK cohort

The British Journal of Psychiatry ◽

10.1192/bjp.bp.110.080861 ◽

2011 ◽

Vol 198 (1) ◽

pp. 17-23 ◽

Cited By ~ 63

Author(s):

Carol Joinson ◽

Jon Heron ◽

Glyn Lewis ◽

Tim Croudace ◽

Ricardo Araya

Keyword(s):

Depressive Symptoms ◽

Adolescent Girls ◽

Structural Equation ◽

Equation Model ◽

Late Childhood ◽

Parents And Children ◽

Increased Risk ◽

Early Maturing ◽

Timing Of Menarche ◽

Avon Longitudinal Study

BackgroundA growing number of studies suggest a link between timing of menarche and risk of depressive symptoms in adolescence, but few have prospectively examined the emergence of depressive symptoms from late childhood into adolescence.AimsTo examine whether girls who experience earlier menarche than their peers have higher levels of depressive symptoms in adolescence.MethodThe study sample comprised 2184 girls from the Avon Longitudinal Study of Parents and Children. The association between timing of menarche and depressive symptoms at 10.5, 13 and 14 years was examined within a structural equation model.ResultsGirls with early menarche (<11.5 years) had the highest level of depressive symptoms at 13 (P = 0.007) and 14 years (P<0.001) compared with those with normative and late timing of menarche.ConclusionsEarly maturing girls are at increased risk of depressive symptoms in adolescence and could be targeted by programmes aimed at early intervention and prevention.

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The association between maternal postnatal depressive symptoms and offspring sleep problems in adolescence

Psychological Medicine ◽

10.1017/s0033291716002427 ◽

2016 ◽

Vol 47 (3) ◽

pp. 451-459 ◽

Cited By ~ 9

Author(s):

A. K. Taylor ◽

E. Netsi ◽

H. O'Mahen ◽

A. Stein ◽

J. Evans ◽

...

Keyword(s):

Sleep Problems ◽

Health Impact ◽

Antenatal Depression ◽

Adolescent Offspring ◽

Postnatal Depressive Symptoms ◽

Parents And Children ◽

Increased Risk ◽

Confounding Variables ◽

Sleep Screening ◽

Avon Longitudinal Study

BackgroundSleep problems are associated with increased risk of physical and mental illness. Identifying risk factors is an important method of reducing public health impact. We examined the association between maternal postnatal depression (PND) and offspring adolescent sleep problems.MethodThe sample was derived from Avon Longitudinal Study of Parents and Children (ALSPAC) participants. A sample with complete data across all variables was used, with four outcome variables. A sensitivity analysis imputing for missing data was conducted (n = 9633).ResultsPND was associated with increased risk of sleep problems in offspring at ages 16 and 18 years. The most robust effects were sleep problems at 18 years [adjusted odds ratio (OR) for a 1 s.d. increase in PND, 1.26, 95% confidence interval (CI) 1.15–1.39, p < 0.001] and waking more often (adjusted OR 1.14, 95% CI 1.05–1.25, p = 0.003). This remained after controlling for confounding variables including antenatal depression and early sleep problems in infancy.ConclusionsPND is associated with adolescent offspring sleep problems. Maternal interventions should consider the child's increased risk. Early sleep screening and interventions could be introduced within this group.

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Curiosity killed the cat: no evidence of an association between cat ownership and psychotic symptoms at ages 13 and 18 years in a UK general population cohort

Psychological Medicine ◽

10.1017/s0033291717000125 ◽

2017 ◽

Vol 47 (9) ◽

pp. 1659-1667 ◽

Cited By ~ 10

Author(s):

F. Solmi ◽

J. F. Hayes ◽

G. Lewis ◽

J. B. Kirkbride

Keyword(s):

Psychotic Symptoms ◽

Early Age ◽

Structured Interviews ◽

Dog Ownership ◽

Parents And Children ◽

Increased Risk ◽

General Population Cohort ◽

Avon Longitudinal Study ◽

Multivariable Adjustment ◽

In Pregnancy

BackgroundCongenital or early life infection with Toxoplasma gondii has been implicated in schizophrenia aetiology. Childhood cat ownership has been hypothesized as an intermediary marker of T. gondii infection and, by proxy, as a risk factor for later psychosis. Evidence supporting this hypothesis is, however, limited.MethodWe used birth cohort data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to investigate whether cat ownership in pregnancy and childhood (ages 4 and 10 years) was associated with psychotic experiences (PEs) in early (age 13, N = 6705) and late (age 18, N = 4676) adolescence, rated from semi-structured interviews. We used logistic regression to examine associations between cat ownership and PEs, adjusting for several sociodemographic and socioeconomic factors, household characteristics and dog ownership. Missing data were handled via multiple imputation.ResultsCat ownership during pregnancy was not associated with PEs at age 13 years [adjusted odds ratio (OR) 1.15, 95% confidence interval (CI) 0.97–1.35] or 18 years (OR 1.08, 95% CI 0.86–1.35). Initial univariable evidence that cat ownership at ages 4 and 10 years was associated with PEs at age 13 years did not persist after multivariable adjustment (4 years: OR 1.18, 95% CI 0.94–1.48; 10 years: OR 1.12, 95% CI 0.92–1.36). There was no evidence that childhood cat ownership was associated with PEs at age 18 years.ConclusionsWhile pregnant women should continue to avoid handling soiled cat litter, given possible T. gondii exposure, our study strongly indicates that cat ownership in pregnancy or early childhood does not confer an increased risk of later adolescent PEs.

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Childhood dietary patterns and cardiovascular risk factors in adolescence: results from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort

Public Health Nutrition ◽

10.1017/s1368980016001592 ◽

2016 ◽

Vol 19 (18) ◽

pp. 3369-3377 ◽

Cited By ~ 5

Author(s):

Caroline J Bull ◽

Kate Northstone

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Longitudinal Study ◽

Cardiovascular Risk Factors ◽

Dietary Patterns ◽

Dietary Pattern ◽

Cvd Risk ◽

Parents And Children ◽

Increased Risk ◽

Avon Longitudinal Study

AbstractObjectiveTo investigate the prospective associations between dietary patterns in childhood and CVD risk in adolescence.DesignProspective cohort study. Exposures were dietary patterns at age 7, 10 and 13 years derived by cluster analysis. Outcomes were physiological and biochemical cardiovascular risk markers.SettingAvon Longitudinal Study of Parents and Children (ALSPAC), UK.SubjectsChildren (n2311, 44.1 % male) with complete data available.ResultsAfter adjustment for known confounders, we observed an association between being in the ‘Processed’ and ‘Packed lunch’ dietary pattern clusters at age 7 and BMI at age 17. Compared with the ‘healthy’ cluster, the OR (95 % CI) for being in the top 10 % for BMI was 1·60 (1·01, 2·55;P=0·05) for the ‘Processed’ cluster and 1·96 (1·22, 3·13;P=0·005) for the ‘Packed lunch’ cluster. However, no association was observed between BMI and dietary patterns at age 10 and 13. Longitudinal analyses showed that being in either the ‘Processed’ or ‘Packed lunch’ cluster at age 7 was associated with increased risk of being in the top 10 % for BMI regardless of subsequent cluster membership. No associations between other cardiovascular risk measures and dietary patterns were robust to adjustment for confounders.ConclusionsWe did not find any consistent evidence to support an association between dietary patterns in childhood and cardiovascular risk factors in adolescence, with the exception of BMI and dietary pattern at age 7 only. However, the importance of dietary intake in childhood upon health later in life requires further investigation and we would encourage the adoption of a healthy diet as early in life as possible.

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Symptoms of generalized anxiety disorder but not panic disorder at age 15 years increase the risk of depression at 18 years in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort study

Psychological Medicine ◽

10.1017/s003329171500149x ◽

2015 ◽

Vol 46 (1) ◽

pp. 73-85 ◽

Cited By ~ 12

Author(s):

S. J. C. Davies ◽

R. M. Pearson ◽

L. Stapinski ◽

H. Bould ◽

D. M. Christmas ◽

...

Keyword(s):

Longitudinal Study ◽

Missing Data ◽

Anxiety Disorder ◽

Panic Disorder ◽

Generalized Anxiety Disorder ◽

Well Being ◽

Generalized Anxiety ◽

Parents And Children ◽

Increased Risk ◽

Avon Longitudinal Study

Background.Generalized anxiety disorder (GAD) and panic disorder (PD) differ in their biology and co-morbidities. We hypothesized that GAD but not PD symptoms at the age of 15 years are associated with depression diagnosis at 18 years.Method.Using longitudinal data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort we examined relationships of GAD and PD symptoms (measured by the Development and Well-Being Assessment) at 15 years with depression at 18 years (by the Clinical Interview Schedule – Revised) using logistic regression. We excluded adolescents already depressed at 15 years and adjusted for social class, maternal education, birth order, gender, alcohol intake and smoking. We repeated these analyses following multiple imputation for missing data.Results.In the sample with complete data (n= 2835), high and moderate GAD symptoms in adolescents not depressed at 15 years were associated with increased risk of depression at 18 years both in unadjusted analyses and adjusting for PD symptoms at 15 years and the above potential confounders. The adjusted odds ratio (OR) for depression at 18 years in adolescents with high relative to low GAD scores was 5.2 [95% confidence interval (CI) 3.0–9.1, overallp< 0.0001]. There were no associations between PD symptoms and depression at 18 years in any model (high relative to low PD scores, adjusted OR = 1.3, 95% CI 0.3–4.8, overallp= 0.737). Missing data imputation strengthened the relationship of GAD symptoms with depression (high relative to low GAD scores, OR = 6.2, 95% CI 3.9–9.9) but those for PD became weaker.Conclusions.Symptoms of GAD but not PD at 15 years are associated with depression at 18 years. Clinicians should be aware that adolescents with GAD symptoms may develop depression.

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Peripubertal Anti-Mullerian Hormone Levels Are Associated With Hyperandrogenemia During Adolescence: The Avon Longitudinal Study of Parents and Children

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1476 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A725-A726

Author(s):

Abigayil Dieguez ◽

Chen Yeh ◽

Laura Rasmussen-Torvik ◽

Laura Christine Torchen

Keyword(s):

Longitudinal Study ◽

Polycystic Ovary ◽

Endocrine Disorders ◽

Fasting Insulin ◽

Reproductive Maturity ◽

Metabolic Phenotypes ◽

Testosterone Levels ◽

Parents And Children ◽

Increased Risk ◽

Avon Longitudinal Study

Abstract Polycystic ovary syndrome (PCOS) is among the most common endocrine disorders in women and is associated with negative reproductive and metabolic outcomes including subfertility, pregnancy complications, metabolic syndrome, and type 2 diabetes. The diagnosis of PCOS cannot be made until reproductive maturity, when the diagnostic criteria of hyperandrogenemia and oligomenorrhea develop. However, studies have described early metabolic and reproductive characteristics of the disorder in girls at increased risk, suggesting the pathogenesis starts much earlier. Indeed, studies in animal models suggest that exposure to excessive androgen or anti-Mullerian hormone (AMH) levels during critical developmental periods can program the offspring to develop the metabolic and reproductive features of PCOS during reproductive maturity. We investigated early maternal or peripubertal factors associated with hyperandrogenemia during adolescence using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a United Kingdom birth cohort which has been ongoing since 1991. We performed linear regression to test for an association of testosterone levels at 15 years with peripubertal reproductive and metabolic phenotypes and with maternal measures of insulin sensitivity. Peripubertal phenotypes included AMH levels at 7, 9, and 11 years, and androstenedione, DHEAS, SHBG, IGF-1, fasting insulin, QUICKI, post-glucose insulin, leptin and adiponectin at age 8 years. Maternal phenotypes included fasting insulin levels and QUICKI at a post-partum visit. Unadjusted and adjusted analyses including the covariates pubertal stage, ethnicity, maternal and daughter BMI were performed. Testosterone levels at age 15 years were significantly positively associated with AMH levels at ages 7(N=299), 9(N=295), and 11(N=300) years in both the adjusted and unadjusted models (Age 7 unadjusted P<0.0001, adjusted P=0.01; Age 9 unadjusted P<0.0001, adjusted P=0.003; Age 11 unadjusted P<0.0001, adjusted P=0.02). Testosterone at age 15 years was also associated with DHEAS at age 8 years using the unadjusted (P<0.0001) but not the adjusted model. There was no significant association between any of the other peripubertal metabolic and reproductive phenotypes or the maternal metabolic phenotypes of fasting insulin and QUICKI with testosterone level at age 15 years. We have found a persistent and significant positive association of AMH levels at pre- or peri-pubertal ages with testosterone levels during adolescence, a developmental stage at which a clinical diagnosis of PCOS can be made. It remains unclear if this early elevation in AMH contributes to the pathogenesis of hyperandrogenemia or is an early marker of PCOS. Nonetheless, these findings suggest there are early differences in the reproductive phenotype in girls with hyperandrogenemia, even before the onset of puberty.

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The ALSPAC fetal and neonatal resource: detailed data abstracted from the clinical records of the new-born

Wellcome Open Research ◽

10.12688/wellcomeopenres.17214.1 ◽

2021 ◽

Vol 6 ◽

pp. 298

Author(s):

Karen Birmingham ◽

Yasmin Iles-Caven ◽

Kate Northstone ◽

Jean Golding

Keyword(s):

Longitudinal Study ◽

Medical Records ◽

Fetal Monitoring ◽

Detailed Data ◽

New Born ◽

Parents And Children ◽

The Status ◽

Clinical Records ◽

Fetus And Neonate ◽

Avon Longitudinal Study

In a previous Data Note, we outlined the data obtained from clinical obstetric records concerning many details of the pregnancies resulting in the births of the children in the Avon Longitudinal Study of Parents and Children (ALSPAC). Here we describe the data that have been abstracted from medical records concerning the fetus and neonate. Full details concerning the selection biases regarding the data abstracted are outlined in the previous Data Note. The records that have been abstracted, and described in this Data Note, concern the health of the fetus (measured in relation to the results of fetal monitoring, presentation at various stages of pregnancy, and the method of delivery) as well as the status of the newborn immediately post-delivery. Details of signs, symptoms and treatments of this population of new-born babies, as recorded in the clinical records, are described for the time during which they were in hospital or under the care of a designated midwife. These data add depth to the information collected from elsewhere concerning this period of the child’s life: from the questionnaires completed at the time by the mother; and clinical details from neonatal intensive or special care units which will be detailed in a further Data Note.

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Hypertensive disorders of pregnancy and the risk of offspring depression in childhood: Findings from the Avon Longitudinal Study of Parents and Children

Development and Psychopathology ◽

10.1017/s0954579419000944 ◽

2019 ◽

Vol 32 (3) ◽

pp. 845-851 ◽

Cited By ~ 2

Author(s):

Berihun Assefa Dachew ◽

James G. Scott ◽

Kim Betts ◽

Abdullah Mamun ◽

Rosa Alati

Keyword(s):

Longitudinal Study ◽

Birth Weight ◽

Low Birth Weight ◽

Mental Health Problems ◽

Well Being ◽

Hypertensive Disorders Of Pregnancy ◽

Hypertensive Disorders ◽

Parents And Children ◽

Increased Risk ◽

Avon Longitudinal Study

AbstractHypertensive disorders of pregnancy (HDP) may increase the risk of offspring depression in childhood. Low birth weight is also associated with increased risk of mental health problems, including depression. This study sought to investigate (a) whether there is an association between HDP and the risk of depression in childhood and (b) whether low birth weight mediates this association. The current study is based on the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective, population-based study that has followed a cohort of offspring since their mothers were pregnant (n = 6,739). Depression at the age of 7 years was diagnosed using parent reports via the Development and Well-Being Assessment (DAWBA). Log-binomial regression and mediation analyses were used. Children exposed to HDP were 2.3 times more likely to have a depression diagnosis compared with nonexposed children, adjusted Risk Ratio [RR], 2.31; 95% CI, [1.20, 4.47]. Low birth weight was a weak mediator of this association. Results were adjusted for confounding variables including antenatal depression and anxiety during pregnancy.This study suggests that fetal exposure to maternal hypertensive disorders of pregnancy increased the risk of childhood depression. The study adds to the evidence suggesting that the uterine environment is a critical determinant of neurodevelopmental and psychiatric outcomes.

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Associations of Existing Diabetes, Gestational Diabetes, and Glycosuria with Offspring IQ and Educational Attainment: The Avon Longitudinal Study of Parents and Children

Experimental Diabetes Research ◽

10.1155/2012/963735 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 50

Author(s):

Abigail Fraser ◽

Scott M. Nelson ◽

Corrie Macdonald-Wallis ◽

Debbie A. Lawlor

Keyword(s):

Longitudinal Study ◽

Gestational Diabetes ◽

Educational Attainment ◽

Maternal Education ◽

Maternal Diabetes ◽

Diabetes In Pregnancy ◽

Parents And Children ◽

Diabetes Gestational ◽

Avon Longitudinal Study ◽

In Pregnancy

Introduction. Results from studies examining associations of maternal diabetes in pregnancy with offspring cognitive outcomes have been inconclusive.Methods. We used data from the Avon Longitudinal Study of Parents and Children, a UK prospective pregnancy cohort. Outcomes were School Entry Assessment (SEA) scores (age 4,N=6,032) and WISC-III IQ (age 8,N=5,282–5,307) and General Certificate of Secondary Education (GCSE) results (age 16,N=7,615).Results. Existing diabetes, gestational diabetes, and, to a lesser extent, glycosuria were associated with lower offspring SEA scores (age 4), IQ (age 8), and GCSE results (age 16) even when adjusting for offspring sex, maternal age, prepregnancy BMI, smoking in pregnancy, parity, caesarean section, maternal education, and occupational social class. Offspring of mothers with existing diabetes had a threefold risk of achieving no GCSEs graded A*-C, whilst offspring of women with gestational diabetes had, on average, a five point lower IQ compared to offspring of women with no diabetes or glycosuria.Conclusions. Maternal diabetes in pregnancy is consistently associated with lower offspring cognition and educational attainment though confidence intervals were wide. The weaker associations with glycosuria suggest a dose-dependent adverse association with IQ.

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Are children of depressed mothers exposed to higher contextual, family and mother-based risks?

European Psychiatry ◽

10.1016/s0924-9338(11)72898-x ◽

2011 ◽

Vol 26 (S2) ◽

pp. 1193-1193

Author(s):

E.D. Barker ◽

W. Copeland ◽

B. Maughan ◽

R. Uher

Keyword(s):

Maternal Depression ◽

Maternal Mental Health ◽

Internalizing Disorders ◽

Beneficial Effects ◽

Parents And Children ◽

Increased Risk ◽

Depressed Mothers ◽

Contextual Family ◽

Avon Longitudinal Study ◽

Child Age

ObjectiveIn general, depressed mothers experience greater environmental and family risks, and lead riskier lifestyles. Whether the exposure of these risks add to child maladjustment, beyond exposure to maternal depression, is an important unanswered question, and is examined in the present study.MethodIn a total of 9,000 mother-offspring pairs in the Avon Longitudinal Study of Parents and Children, we examined (i) if children of depressed mothers had higher risk exposures than children of non-depressed mothers (32 weeks gestation, child age 1.5 years); (ii) whether maternal depression increased risk for diagnoses of externalizing and internalizing disorders (child age 7.5 years); (iii) the decrease in these odds when we controlled for the risk exposures; and (iv) whether risk exposure increased the odds of a diagnosis, above the influence of maternal depression.ResultsChildren of depressed mothers were exposed to higher levels of risks and maternal depression increased the risk for diagnoses of both externalizing and internalizing disorders. The decrease in these odds was between 25–50% when controlling for child risk exposures. At the same time, risk exposures to the child significantly increased the odds of both externalizing and internalizing diagnoses, above the influence of maternal depression.ConclusionsMaladjustment in offspring of depressed mothers is influenced by risk exposures closely associated with maternal mental health, suggesting that these children are “doubly” hit by risk. It is suggested that the present results may aide in interpreting why treating depressed mothers shows certain levels of beneficial effects for children, but not complete remission.

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