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Background: Externalizing symptoms are associated with risk of future substance use disorder (SUD). Few longitudinal studies exist using general population-based samples which assess the spectrum of attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms., Aims/objectives: We aimed to study the associations between adolescent ADHD symptoms and subsequent SUD and additionally examine whether the risk of SUD is influenced by comorbid oppositional defiant disorder (ODD) symptoms., Methods: The Northern Finland Birth Cohort 1986 was linked to nationwide health care register data for incident SUD diagnoses until age 33 years (n = 6278, 49.5% male). ADHD/ODD-case status at age 16 years was defined using parent-rated ADHD indicated by Strengths and Weaknesses of ADHD symptoms and Normal Behaviors (SWAN) questionnaire with 95% percentile cut-off. To assess the impact of ODD comorbidity on SUD risk, participants were categorized into four groups based on their ADHD/ODD case status. Cox-regression analysis with hazard ratios (HRs) and 95% confidence intervals (CIs) were used to study associations between adolescent ADHD/ODD case statuses and subsequent SUD., Results: In all, 552 participants (8.8%) presented with ADHD case status at the age of 16 years, and 154/6278 (2.5%) were diagnosed with SUD during the follow-up. ADHD case status was associated with SUD during the follow-up (HR = 3.84, 95% CI 2.69-5.50). After adjustments for sex, family structure, and parental psychiatric disorder and early substance use the association with ADHD case status and SUD remained statistically significant (HR = 2.60, 95% CI 1.70-3.98). The risk of SUD remained elevated in individuals with ADHD case status irrespective of ODD symptoms., Conclusions: ADHD in adolescence was associated with incident SUD in those with and without symptoms of ODD. The association of ADHD and SUD persisted even after adjustment for a wide range of potential confounds. This emphasizes the need to identify preventative strategies for adolescents with ADHD so as to improve health outcomes., (© 2023 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Background: Diagnosis of attention deficit hyperactive disorder (ADHD) has been associated with increased risk of mortality in large register samples. However, there is less known about the association between symptoms of ADHD in adolescents and risk of mortality in general population samples., Methods: The Northern Finland Birth Cohort 1986 ( n  = 9432 at recruitment in early pregnancy) linked to nationwide register data for deaths was utilized to study the association between parent-rated ADHD symptoms assessed using Strengths and Weaknesses of ADHD symptoms and Normal Behaviors (SWAN) questionnaire and mortality until age 33 years. Cox-regression analysis with hazard ratios (HRs) and 95% confidence intervals (CIs) was used to study the association between SWAN inattentive, hyperactive, and combined symptom scores and risk of death., Results: Sixty-three (0.9%) of the 6685 participants died during the follow-up. Higher SWAN inattentive (crude HR = 2.30, 95% CI 1.46-3.63), SWAN hyperactive (crude HR = 2.43, 95% CI 1.29-4.56), and SWAN combined (crude HR = 2.69, 95% CI 1.57-4.61) scores were associated with increased risk of death. After adjustments for sex, family structure, and lifetime parental psychiatric disorder, these associations persisted. Further adjustment for frequent alcohol intoxication, cannabis, and other substance use in adolescence attenuated these to below statistical significance., Conclusions: These results extend previous findings on the risk of mortality in adolescents who have symptoms of ADHD. Further research with larger samples are needed to determine whether the association between ADHD symptoms and mortality is independent of adolescent substance use.

Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG < 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation with intelligence, educational attainment, wellbeing, smoking, and body fat (rG > 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits., Competing Interests: The authors have declared that no competing interests exist.

Attention-deficit/hyperactivity disorder (ADHD) often co-occurs with obesity, however, the potential causality between the traits remains unclear. We examined both genetic and prenatal evidence for causality using Mendelian Randomisation (MR) and polygenic risk scores (PRS). We conducted bi-directional MR on ADHD liability and six obesity-related traits using summary statistics from the largest available meta-analyses of genome-wide association studies. We also examined the shared genetic aetiology between ADHD symptoms (inattention and hyperactivity) and body mass index (BMI) by PRS association analysis using longitudinal data from Northern Finland Birth Cohort 1986 (NFBC1986, n = 2984). Lastly, we examined the impact of the prenatal environment by association analysis of maternal pre-pregnancy BMI and offspring ADHD symptoms, adjusted for PRS of both traits, in NFBC1986 dataset. Through MR analyses, we found evidence for bidirectional causality between ADHD liability and obesity-related traits. PRS association analyses showed evidence for genetic overlap between ADHD symptoms and BMI. We found no evidence for a difference between inattention and hyperactivity symptoms, suggesting that neither symptom subtype is driving the association. We found evidence for association between maternal pre-pregnancy BMI and offspring ADHD symptoms after adjusting for both BMI and ADHD PRS (association p-value = 0.027 for inattention, p = 0.008 for hyperactivity). These results are consistent with the hypothesis that the co-occurrence between ADHD and obesity has both genetic and prenatal environmental origins., (© 2021. The Author(s).)

Objective: To prospectively investigate the association and directionality between attention-deficit/hyperactivity disorder (ADHD) symptoms and obesity from childhood to adolescence in the general population. We examined whether obesogenic behaviors, namely, physical inactivity and binge eating, underlie the potential ADHD symptom-obesity association. We explored whether childhood conduct disorder (CD) symptoms are related to adolescent obesity/physical inactivity., Method: At 7 to 8 years (n = 8,106), teachers reported ADHD and CD symptoms, and parents reported body mass index (BMI) and physically active play. At 16 years (n = 6,934), parents reported ADHD symptoms; adolescents reported physical activity (transformed to metabolic equivalent of task [MET] hours per week) and binge eating; BMI and waist-hip ratio (WHR) were measured via clinical examination. Obesity was defined using the International Obesity Task Force (IOTF) cut-offs for BMI and the 95th percentile cut-off for WHR., Results: Childhood ADHD symptoms significantly predicted adolescent obesity, rather than the opposite. Inattention-hyperactivity symptoms at 8 years were associated with indices of obesity at 16 years (obese BMI: odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.10-3.33; 95th percentile WHR: OR = 1.71, 95% CI = 1.05-2.78), adjusted for gender, baseline BMI, physical activity, family structure change, and maternal education. Child CD symptoms associated with indices of adolescent obesity. Reduced physically active play in childhood predicted adolescent inattention (OR = 1.61, 95% CI = 1.16-2.24). Childhood ADHD and CD symptoms were linked with physical inactivity in adolescence (inattention-hyperactivity; OR = 1.60, 95% CI = 1.20-2.13), but not binge eating. Physical inactivity mediated the associations., Conclusions: Children with ADHD or CD symptoms are at increased risk for becoming obese and physically inactive adolescents. Physical activity may be beneficial for both behavior problems and obesity., (Copyright © 2014 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

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.

Objective: In this study, the authors investigated whether ADHD and oppositional defiant disorder (ODD) behaviors share associations with problems in cognitive functioning and/or family risk factors in adolescence. This was done by examining independent as well as specific associations of cognitive functioning and family risk factors with ADHD and ODD behaviors., Method: A sample of 120 adolescents from the general population was assessed on various cognitive tasks. ADHD and ODD behaviors were measured through parental and teacher ratings based on Diagnostic and Statistical Manual of Mental Disorders (4th edition) criteria. Parents and adolescents provided information regarding measures of family risk factors., Results: The results show that only cognitive functioning was associated with ADHD behaviors, and family risk factors were, independent of cognitive functioning, associated with ODD behaviors., Conclusion: These results suggest that cognitive performance bears a specific significance for ADHD behaviors, whereas family risk factors have specific importance for ODD behaviors.

Background: The role of the placenta in fetal programming has been recognized as a highly significant, yet often neglected area of study. We investigated placental size in relation to psychopathology, in particular attention deficit hyperactivity disorder (ADHD) symptoms, in children at 8 years of age, and later as adolescents at 16 years., Methodology/principal Findings: Prospective data were obtained from The Northern Finland Birth Cohort (NFBC) 1986. Placental weight, surface area and birth weight were measured according to standard procedures, within 30 minutes after birth. ADHD symptoms, probable psychiatric disturbance, antisocial disorder and neurotic disorder were assessed at 8 years (n = 8101), and ADHD symptoms were assessed again at 16 years (n = 6607), by teachers and parents respectively. We used logistic regression analyses to investigate the association between placental size and mental health outcomes, and controlled for gestational age, birth weight, socio-demographic factors and medical factors, during gestation. There were significant positive associations between placental size (weight, surface area and placental-to-birth-weight ratio) and mental health problems in boys at 8 and 16 years of age. Increased placental weight was linked with overall probable psychiatric disturbance (at 8 y, OR= 1.14 [95% CI= 1.04-1.25]), antisocial behavior (at 8 y, OR = 1.14 [95% CI= 1.03-1.27]) and ADHD symptoms (inattention-hyperactivity at 16 y, OR= 1.19 [95% CI = 1.02-1.38]). No significant associations were detected among girls., Conclusions/significance: Compensatory placental growth may occur in response to prenatal insults. Such overgrowth may affect fetal development, including brain development, and ultimately contribute to psychopathology.

Objective: This study aimed to replicate and extend previous work showing an association between maternal pre-pregnancy adiposity and risk for attention deficit hyperactivity disorder (ADHD) symptoms in children., Methods: A Swedish population-based prospective pregnancy-offspring cohort was followed up when children were 5 years old (N = 1,714). Mothers and kindergarten teachers rated children's ADHD symptoms, presence and duration of problems, and emotionality. Dichotomized outcomes examined difficulties of clinical relevance (top 15% of the distribution). Analyses adjusted for pregnancy (maternal smoking, depressive symptoms, life events, education, age, family structure), birth outcomes (birth weight, gestational age, infant sex) and concurrent variables (family structure, maternal depressive symptoms, parental ADHD symptoms, and child overweight) in an attempt to rule out confounding., Results: Maternal pre-pregnancy overweight and obesity predicted high inattention symptom scores and obesity was associated with a two-fold increase in risk of difficulties with emotion intensity and emotion regulation according to teacher reports. Means of maternal ratings were unrelated to pre-pregnancy body mass index (BMI). Presence and duration of problems were associated with both maternal over and underweight according to teachers., Conclusions: Despite discrepancies between maternal and teacher reports, these results provide further evidence that maternal pre-pregnancy overweight and obesity are associated with child inattention symptoms and extend previous work by establishing a link between obesity and emotional difficulties. Maternal adiposity at the time of conception may be instrumental in programming child mental health, as prenatal brain development depends on maternal energy supply. Possible mechanisms include disturbed maternal metabolic function. If maternal pre-pregnancy obesity is a causal risk factor, the potential for prevention is great.

Background: Prenatal exposure to smoking has been associated with Attention Deficit Hyperactivity Disorder (ADHD) in a number of epidemiological studies. However, mothers with the ADHD phenotype may 'treat' their problem by smoking and therefore be more likely to smoke even in a society where smoking is not acceptable. This will cause genetic confounding if ADHD has a heritable component, especially in populations with low prevalence rates of smoking since this reason for smoking is expected to be proportionally more frequent in a population with few 'normal' smokers. We compared the association in cohorts with different smoking frequencies., Methods: A total of 20 936 women with singleton pregnancies were identified within three population-based pregnancy cohorts in Northern Finland (1985-1986) and in Denmark (1984-1987 and 1989-1991). We collected self-reported data on their pre-pregnancy and pregnancy smoking habits and followed the children to school age where teachers and parents rated hyperactivity and inattention symptoms., Results: Children, whose mothers smoked during pregnancy, had an increased prevalence of a high hyperactivity-inattention score compared with children of nonsmokers in each of the cohorts after adjustment for confounders but we found no statistical significant difference between the associations across the cohorts., Conclusion: The estimated association was not strongest in the population with the fewest smokers which does not support the hypothesis that the association is entirely due to genetic confounding.

This study examined independent contributions of executive functioning (EF), state regulation (SR), and social risk factors to symptom dimensions of attention deficit hyperactivity disorder (ADHD) in two cohorts, which included 221 Norwegian children and 294 Finnish adolescents. Independent contributions of EF and SR were shown in the Norwegian cohort and EF contributed independently in the Finnish cohort. When controlling for each symptom dimension, cognitive functioning and social risk factors were differentially associated with inattention and hyperactivity/impulsivity symptoms. The results show the need to include both social risk factors and cognitive functioning to obtain a better understanding of ADHD symptoms.

Background: Attention Deficit/Hyperactivity Disorder (ADHD) affects many children, adolescents, and adults and is associated with a number of impairments. Poor academic performance is related to ADHD in clinical samples. However, it is unclear to what extent core ADHD symptoms and scholastic impairment are related in non-referred school-aged children., Methods: Data come from three population-based cohorts from Sweden, Denmark, and Finland, which are part of the Nordic Network on ADHD. The combined sample size was 13,087 children who were studied at ages 7-8 or 10-12 years. Teachers rated children on inattention and hyperactivity symptoms and reported children's scholastic performance on basic skills., Results: There was a significant association in all cohorts between core ADHD symptoms and scholastic impairment in reading, writing, and mathematics. Particularly, inattention was related to a two to tenfold increase in scholastic impairment. Prevalence of hyperactivity symptoms was similar across the three cohorts, but inattention was lowest among children from the Finnish cohort, after stratification on living conditions., Conclusion: These results extend previous reports of scholastic impairment among children with clinically diagnosed ADHD to non-referred population samples from three European countries. Surveillance policies should be implemented in school systems to catch children in need of behavioral or scholastic support early.

Background: There are some indications that maternal lifestyle during pregnancy (smoking and stress) contributes to symptoms of ADHD in children. We prospectively studied whether prenatal exposure to maternal smoking and/or stress is associated with ADHD symptoms and diagnostic criteria (according to DSM-IV) in 7-year-olds., Methods: Nulliparous Scandinavian women were consecutively recruited at their first prenatal health care visit and assessments of smoking and stress were collected at gestational weeks 10, 12, 20, 28, 32, and 36. Children were followed up at 7 years old. We obtained full data for 72% of the sample: ADHD symptoms were rated by 74% of mothers (n=290) and 96% of eligible teachers (n=208). Attrition analyses showed no differences on key variables between participants and non-participants at follow-up., Results: Results of multiple regression analyses showed prenatal exposure to smoking (beta=.16, p<.01) and stress (beta=.18, p<.01) were independently associated with later symptoms of ADHD. Results of logistic regression analyses showed that fulfillment of the diagnostic criteria for ADHD was related to exposure to prenatal stress (beta=.68, p<.01) especially in boys. The results were not confounded by sociodemographic factors or birth outcomes., Conclusions: This study provides evidence that prenatal exposure to stress and smoking is independently associated with later symptoms of ADHD in human children, particularly for boys. Because stress and smoking are relatively common during pregnancy, and yet preventable, these results are of public health significance.

Objective: The purpose of this review was to examine the literature assessing the relationship between prenatal exposure to nicotine, alcohol, caffeine, and psychosocial stress during pregnancy to the risk of developing behavioral problems related to attention deficit hyperactivity disorder (ADHD) in childhood., Method: PubMed, MEDLINE, EMBASE, and PsycINFO were searched systematically. Studies using DSM diagnostic criteria and other validated diagnostic or screening instruments for ADHD and those examining ADHD symptoms were included. A narrative approach was used because the studies differed too much in methods and data sources to permit a quantitative meta-analysis., Results: Twenty-four studies on nicotine (tobacco smoking), nine on alcohol, one on caffeine, and five on psychosocial stress were identified. All were published between 1973 and 2002. In spite of inconsistencies, the studies on nicotine indicated a greater risk of ADHD-related disorders among children whose mothers smoked during pregnancy. Contradictory findings were reported in the alcohol studies, and no conclusion could be reached on the basis of the caffeine study. Results from studies on psychological stress during pregnancy were inconsistent but indicated a possible modest contribution to ADHD symptoms in the offspring. Many studies suffered from methodological shortcomings, such as recall bias, crude or inaccurate exposure assessments, low statistical power, and lack of or insufficient control of confounders. A general lack of information on familial psychopathology also limited the interpretations., Conclusions: Exposure to tobacco smoke in utero is suspected to be associated with ADHD and ADHD symptoms in children. Other maternal lifestyle factors during pregnancy may also be associated with these disorders. Further studies are needed to reach conclusions.