1. |
- D'Onofrio, Brian M., et al.
(author)
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Familial confounding of the association between maternal smoking during pregnancy and offspring substance use and problems
- 2012
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In: Archives of General Psychiatry. - Chicago, USA : American Medical Association. - 0003-990X .- 1538-3636. ; 69:11, s. 1140-1150
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Journal article (peer-reviewed)abstract
- Context: Previous epidemiological, animal, and human cognitive neuroscience research suggests that maternal smoking during pregnancy (SDP) causes increased risk of substance use/problems in offspring.Objective: To determine the extent to which the association between SDP and offspring substance use/problems depends on confounded familial background factors by using a quasi-experimental design.Design: We used 2 separate samples from the United States and Sweden. The analyses prospectively predicted multiple indices of substance use and problems while controlling for statistical covariates and comparing differentially exposed siblings to minimize confounding.Setting: Offspring of a representative sample of women in the United States (sample 1) and the total Swedish population born during the period from January 1, 1983, to December 31, 1995 (sample 2).Patients or Other Participants: Adolescent offspring of the women in the National Longitudinal Survey of Youth 1979 (n = 6904) and all offspring born in Sweden during the 13-year period (n = 1,187,360).Main Outcome Measures: Self-reported adolescent alcohol, cigarette, and marijuana use and early onset (before 14 years of age) of each substance (sample 1) and substance-related convictions and hospitalizations for an alcohol- or other drug-related problem (sample 2).Results: The same pattern emerged for each index of substance use/problems across the 2 samples. At the population level, maternal SDP predicted every measure of offspring substance use/problems in both samples, ranging from adolescent alcohol use (hazard ratio [HR](moderate), 1.32 [95% CI, 1.22-1.43]; HR(high), 1.33 [1.17-1.53]) to a narcotics-related conviction (HR(moderate), 2.23 [2.14-2.31]; HR(high), 2.97 [2.86-3.09]). When comparing differentially exposed siblings to minimize genetic and environmental confounds, however, the association between SDP and each measure of substance use/problems was minimal and not statistically significant.Cocnlusions: The association between maternal SDP and offspring substance use/problems is likely due to familial background factors, not a causal influence, because siblings have similar rates of substance use and problems regardless of their specific exposure to SDP.
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2. |
- McCoy, Brittany M., et al.
(author)
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Mediators of the association between parental severe mental illness and offspring neurodevelopmental problems
- 2014
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In: Annals of Epidemiology. - New York, USA : Elsevier. - 1047-2797 .- 1873-2585. ; 24:9, s. 629-634.e1
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Journal article (peer-reviewed)abstract
- Purpose: Parental severe mental illness (SMI) is associated with an increased risk of offspring autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). We conducted a study to examine the extent to which risk of preterm birth, low birth weight, and small for gestational age mediated this association.Methods: We obtained data on offspring born 1992-2001 in Sweden (n = 870,017) through the linkage of multiple population-based registers. We used logistic and Cox regression to assess the associations between parental SMI, adverse pregnancy outcomes, and offspring ASD and ADHD, as well as tested whether adverse pregnancy outcomes served as mediators.Results: After controlling for measured covariates, maternal and paternal SMI were associated with an increased risk for preterm birth, low birth weight, and gestational age, and for offspring ASD and ADHD. These pregnancy outcomes were also associated with an increased risk of ASD and ADHD. We found that pregnancy outcomes did not mediate the association between parental SMI and offspring ASD and ADHD, as there was no substantial change in magnitude of the risk estimates after controlling for pregnancy outcomes.Conclusions: Parental SMI and adverse pregnancy outcomes appear to be independent risk factors for offspring ASD and ADHD.
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3. |
- Narusyte, Jurgita, et al.
(author)
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Parental criticism and externalizing behavior problems in adolescents : the role of environment and genotype-environment correlation
- 2011
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In: Journal of Abnormal Psychology. - : American Psychological Association (APA). - 0021-843X .- 1939-1846. ; 120:2, s. 365-376
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Journal article (peer-reviewed)abstract
- Genetic factors are important for the association between parental negativity and child problem behavior, but it is not clear whether this is due to passive or evocative genotype environment correlation (rGE). In this study, we applied the extended children-of-twins model to directly examine the presence of passive and evocative rGE as well as direct environmental effects in the association between parental criticism and adolescent externalizing problem behavior. The cross-sectional data come from the Twin and Offspring Study in Sweden (N = 909 pairs of adult twins) and from the Twin Study of Child and Adolescent Development (N = 915 pairs of twin children). The results revealed that maternal criticism was primarily due to evocative rGE emanating from their adolescent’s externalizing behavior. On the other hand, fathers’ critical remarks tended to affect adolescent problem behavior in a direct environmental way. This suggests that previously reported differences in caretaking between mothers and fathers also are reflected in differences in why parenting is associated with externalizing behavior in offspring.
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4. |
- Chang, Zheng, et al.
(author)
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Maternal age at childbirth and risk for ADHD in offspring : a population-based cohort study
- 2014
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In: International Journal of Epidemiology. - Oxford, United Kingdom : Oxford University Press. - 0300-5771 .- 1464-3685. ; 43:6, s. 1815-1824
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Journal article (peer-reviewed)abstract
- Background: Women who give birth at younger ages (e.g. teenage mothers) are more likely to have children who exhibit behaviour problems, such as attention-deficit/hyperactivity disorder (ADHD). However, it is not clear whether young maternal age is causally associated with poor offspring outcomes or confounded by familial factors.Methods: The association between early maternal age at childbirth and offspring ADHD was studied using data from Swedish national registers. The sample included all children born in Sweden between 1988 and 2003 (N = 1 495 543), including 30 674 children with ADHD. We used sibling- and cousin-comparisons to control for unmeasured genetic and environmental confounding. Further, we used a children-of-siblings model to quantify the genetic and environmental contribution to the association between maternal age and offspring ADHD.Results: Maternal age at first birth (MAFB) was associated with offspring ADHD. Teenage childbirth (<20 years) was associated with 78% increased risk of ADHD. The association attenuated in cousin-comparison, suggesting unmeasured familial confounding. The children-of-siblings model indicated that the association between MAFB and ADHD was mainly explained by genetic confounding.Conclusions: All children born to mothers who bore their first child early in their reproductive lives were at increased risk of ADHD. The association was mainly explained by genetic factors transmitted from mothers to their offspring that contribute to both age at childbirth and ADHD in offspring. Our results highlight the importance of using family-based designs to understand how early life circumstances affect child development.
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5. |
- Chang, Zheng, et al.
(author)
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Serious transport accidents in adults with attention-deficit/hyperactivity disorder and the effect of medication : a population-based study
- 2014
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In: JAMA psychiatry. - Chicago, USA : American Medical Association. - 2168-6238 .- 2168-622X. ; 71:3, s. 319-325
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Journal article (peer-reviewed)abstract
- Importance: Studies have shown that attention-deficit/hyperactivity disorder (ADHD) is associated with transport accidents, but the magnitude of the association remains unclear. Most important, it is also unclear whether ADHD medication reduces this risk.Objectives: To estimate the association between ADHD and the risk of serious transport accidents and to explore the extent to which ADHD medication influences this risk among patients with ADHD.Design, setting and participants: In total, 17,408 patients with a diagnosis of ADHD were observed from January 1, 2006, through December 31, 2009, for serious transport accidents documented in Swedish national registers. The association between ADHD and accidents was estimated with Cox proportional hazards regression. To study the effect of ADHD medication, we used stratified Cox regression to compare the risk of accidents during the medication period with the risk during the nonmedication period within the same patients.Main outcomes and measures: Serious transport accident, identified as an emergency hospital visit or death due to transport accident.Results: Compared with individuals without ADHD, male patients with ADHD (adjusted hazard ratio, 1.47; 95% CI, 1.32-1.63) and female patients with ADHD (1.45; 1.24-1.71) had an increased risk of serious transport accidents. In male patients with ADHD, medication was associated with a 58% risk reduction (hazard ratio, 0.42; 95% CI, 0.23-0.75), but there was no statistically significant association in female patients. Estimates of the population-attributable fractions suggested that 41% to 49% of the accidents in male patients with ADHD could have been avoided if they had been receiving treatment during the entire follow-up.Conclusions and relevance: Attention-deficit/hyperactivity disorder is associated with an increased risk of serious transport accidents, and this risk seems to be possibly reduced by ADHD medication, at least among male patients. This should lead to increased awareness among clinicians and patients of the association between serious transport accidents and ADHD medication.
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6. |
- Chen, Qi, et al.
(author)
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Drug treatment for attention-deficit/hyperactivity disorder and suicidal behaviour : register based study
- 2014
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In: BMJ-BRITISH MEDICAL JOURNAL. - London, United Kingdom : B M J Group. - 1756-1833. ; 348
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Journal article (peer-reviewed)abstract
- Objective: To investigate the association between drug treatment for attention-deficit/hyperactivity disorder (ADHD) and risk of concomitant suicidal behaviour among patients with ADHD.Design: Register based longitudinal study using within patient design.Setting: Linkage of multiple national registers in Sweden.Participants: 37,936 patients with ADHD born between 1960 and 1996 and followed from 2006 to 2009 for treatment status by ADHD drug treatment and suicide related events (suicide attempt and completed suicide).Main outcome measure: Incidence rate of suicide related events during ADHD drug treatment periods compared with that during non-treatment periods.Results: Among 37,936 patients with ADHD, 7019 suicide related events occurred during 150,721 person years of follow-up. At the population level, drug treatment of ADHD was associated with an increased rate of suicide related events (hazard ratio 1.31, 95% confidence interval 1.19 to 1.44). However, the within patient comparison showed a reverse association between ADHD drug treatment and rate of suicide related events (0.89, 0.79 to 1.00). Among stimulant users, a reduced within patient rate of suicide related events was seen during treatment periods (0.81, 0.70 to 0.94). Among non-stimulant/mixed users, no significantly increased within patient rate of suicide related events during non-stimulant treatment periods was seen (0.96, 0.72 to 1.30).Conclusions: This study found no evidence for a positive association between the use of drug treatments for ADHD and the risk of concomitant suicidal behaviour among patients with ADHD. If anything, the results pointed to a potential protective effect of drugs for ADHD on suicidal behaviour, particularly for stimulant drugs. The study highlights the importance of using within patient designs to control for confounding in future pharmacoepidemiological studies.
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7. |
- Chen, Qi, et al.
(author)
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Maternal pre-pregnancy body mass index and offspring attention deficit hyperactivity disorder : a population-based cohort study using a sibling-comparison design
- 2014
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In: International Journal of Epidemiology. - Oxford, United Kingdom : Oxford University Press. - 0300-5771 .- 1464-3685. ; 43:1, s. 83-90
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Journal article (peer-reviewed)abstract
- Background: High maternal pre-pregnancy body mass index (BMI) is associated with increased risk of offspring attention deficit hyperactivity disorder (ADHD). However, the role of unmeasured familial confounding for this association remains unclear.Methods: We conducted a population-based cohort study via linkage of Swedish national and regional registers to investigate maternal pre-pregnancy BMI (underweight: BMI <18.5; overweight: 25≤ BMI <30; obesity: BMI ≥30) in relation to offspring ADHD. We followed 673 632 individuals born in Sweden between 1992 and 2000, with prospectively collected information on maternal pre-pregnancy BMI, until they received an ADHD diagnosis or ADHD medication, death, emigration or 31 December 2009. Hazard ratios (HRs) were estimated by Cox proportional hazards models. Stratified Cox proportional hazards models were applied to data on full siblings to control for unmeasured familial confounding.Results: At the population level, pre-pregnancy overweight/obesity was associated with increased risk of offspring ADHD (HR(overweight) = 1.23, 95% CI = 1.18-1.27, P = 0.01; HR(obesity) = 1.64, 95% CI = 1.57-1.73, P = 0.01), after adjustment for measured covariates. In full sibling comparisons, however, previously observed associations no longer remained (HR(overweight) = 0.98, 95% CI = 0.83-1.16, P = 0.82; HR(obesity) = 1.15, 95% CI = 0.85-1.56, P = 0.38).Conclusions: The results suggested that the association between maternal pre-pregnancy overweight/obesity and offspring ADHD could be ascribed to unmeasured familial confounding.
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8. |
- Class, Quetzal A., et al.
(author)
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Fetal growth and psychiatric and socioeconomic problems : population-based sibling comparison
- 2014
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In: British Journal of Psychiatry. - London, United Kingdom : Royal College od Psychiatrists. - 0007-1250 .- 1472-1465. ; 205:5, s. 355-361
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Journal article (peer-reviewed)abstract
- Background: It is unclear whether associations between fetal growth and psychiatric and socioeconomic problems are consistent with causal mechanisms.Aims: To estimate the extent to which associations are a result of unmeasured confounding factors using a sibling-comparison approach.Method: We predicted outcomes from continuously measured birth weight in a Swedish population cohort (n = 3 291 773), while controlling for measured and unmeasured confounding.Results: In the population, lower birth weight (⩽ 2500 g) increased the risk of all outcomes. Sibling-comparison models indicated that lower birth weight independently predicted increased risk for autism spectrum disorder (hazard ratio for low birth weight = 2.44, 95% CI 1.99-2.97) and attention-deficit hyperactivity disorder. Although attenuated, associations remained for psychotic or bipolar disorder and educational problems. Associations with suicide attempt, substance use problems and social welfare receipt, however, were fully attenuated in sibling comparisons.Conclusions: Results suggest that fetal growth, and factors that influence it, contribute to psychiatric and socioeconomic problems.
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9. |
- Donahue, Kelly L, et al.
(author)
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Childhood Behavior Problems and Adolescent Sexual Risk Behavior: Familial Confounding in the Child and Adolescent Twin Study in Sweden (CATSS).
- 2013
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In: The Journal of adolescent health : official publication of the Society for Adolescent Medicine. - : Elsevier BV. - 1879-1972. ; 52:5, s. 606-612
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Previous studies have found associations between childhood behavior problems and adolescent sexual risk behavior. Using a quasi-experimental approach, we examined the extent to which this association may be due to between-family differences (i.e., unmeasured familial confounds) not adequately explored in prior research. METHODS: We used data from a longitudinal, population-based cohort of young twins in Sweden (first assessment: age 9 or 12 years; second assessment: age 15; n= 2,388). We explored the nature of the association between symptom scores for attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) at age 9 or 12 and the likelihood of having had sexual intercourse and number of sexual partners by age 15. Two-level mixed-effects models were used to estimate the effect of symptom score on each outcome after controlling for potential unmeasured familial confounds. RESULTS: Higher ADHD, ODD, and CD scores were associated with significantly increased likelihood of sexual intercourse by age 15. Higher ADHD and ODD scores were also associated with increased number of sexual partners. After controlling for unmeasured familial confounds, however, behavior problems were no longer significantly associated with either outcome. CONCLUSION: The association between childhood behavior problems and sexual risk behaviors may be due to characteristics shared within families. Hence, prevention strategies aimed at reducing these behaviors might need to address broader risk factors that contribute to both behavior problems and a greater likelihood of sexual risk behavior.
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10. |
- D'Onofrio, Brian M., et al.
(author)
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Paternal age at childbearing and offspring psychiatric and academic morbidity
- 2014
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In: JAMA psychiatry. - Chicago, United States : American Medical Association. - 2168-6238 .- 2168-622X. ; 71:4, s. 432-438
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Journal article (peer-reviewed)abstract
- Importance: Advancing paternal age is associated with increased genetic mutations during spermatogenesis, which research suggests may cause psychiatric morbidity in the offspring. The effects of advancing paternal age at childbearing on offspring morbidity remain unclear, however, because of inconsistent epidemiologic findings and the inability of previous studies to rigorously rule out confounding factors.Objective: To examine the associations between advancing paternal age at childbearing and numerous indexes of offspring morbidity.Design, setting and participants: We performed a population-based cohort study of all individuals born in Sweden in 1973-2001 (N = 2,615,081), with subsets of the data used to predict childhood or adolescent morbidity. We estimated the risk of psychiatric and academic morbidity associated with advancing paternal age using several quasi-experimental designs, including the comparison of differentially exposed siblings, cousins, and first-born cousins.Exposure: Paternal age at childbearing.Main outcomes and measures: Psychiatric (autism, attention-deficit/hyperactivity disorder, psychosis, bipolar disorder, suicide attempt, and substance use problem) and academic (failing grades and low educational attainment) morbidity.Results: In the study population, advancing paternal age was associated with increased risk of some psychiatric disorders (eg, autism, psychosis, and bipolar disorders) but decreased risk of the other indexes of morbidity. In contrast, the sibling-comparison analyses indicated that advancing paternal age had a dose-response relationship with every index of morbidity, with the magnitude of the associations being as large or larger than the estimates in the entire population. Compared with offspring born to fathers 20 to 24 years old, offspring of fathers 45 years and older were at heightened risk of autism (hazard ratio [HR] = 3.45; 95% CI, 1.62-7.33), attention-deficit/hyperactivity disorder (HR = 13.13; 95% CI, 6.85-25.16), psychosis (HR = 2.07; 95% CI, 1.35-3.20), bipolar disorder (HR = 24.70; 95% CI, 12.12-50.31), suicide attempts (HR = 2.72; 95% CI, 2.08-3.56), substance use problems (HR = 2.44; 95% CI, 1.98-2.99), failing a grade (odds ratio [OR] = 1.59; 95% CI, 1.37-1.85), and low educational attainment (OR = 1.70; 95% CI, 1.50-1.93) in within-sibling comparisons. Additional analyses using several quasi-experimental designs obtained commensurate results, further strengthening the internal and external validity of the findings.Conclusions and relevance: Advancing paternal age is associated with increased risk of psychiatric and academic morbidity, with the magnitude of the risks being as large or larger than previous estimates. These findings are consistent with the hypothesis that new genetic mutations that occur during spermatogenesis are causally related to offspring morbidity.
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