Risk Of Attention Deficit Hyperactivity Disorder Research Articles

Mother's and children's ADHD genetic risk, household chaos and children's ADHD symptoms: A gene-environment correlation study.

Chaotic home environments may contribute to children's attention-deficit hyperactivity disorder (ADHD) symptoms. However, ADHD genetic risk may also influence household chaos. This study investigated whether children in chaotic households had more ADHD symptoms, if mothers and children with higher ADHD genetic risk lived in more chaotic households, and the joint association of genetic risk and household chaos on the longitudinal course of ADHD symptoms across childhood. Participants were mothers and children from the Environmental Risk (E-Risk) Longitudinal Twin Study, a UK population-representative birth cohort of 2,232 twins. Children's ADHD symptoms were assessed at ages 5, 7, 10 and 12 years. Household chaos was rated by research workers at ages 7, 10 and 12, and by mother's and twin's self-report at age 12. Genome-wide ADHD polygenic risk scores (PRS) were calculated for mothers (n = 880) and twins (n = 1,999); of these, n = 871 mothers and n = 1,925 children had information on children's ADHD and household chaos. Children in more chaotic households had higher ADHD symptoms. Mothers and children with higher ADHD PRS lived in more chaotic households. Children's ADHD PRS was associated with household chaos over and above mother's PRS, suggesting evocative gene-environment correlation. Children in more chaotic households had higher baseline ADHD symptoms and a slower rate of decline in symptoms. However, sensitivity analyses estimated that gene-environment correlation accounted for a large proportion of the association of household chaos on ADHD symptoms. Children's ADHD genetic risk was independently associated with higher levels of household chaos, emphasising the active role of children in shaping their home environment. Our findings suggest that household chaos partly reflects children's genetic risk for ADHD, calling into question whether household chaos directly influences children's core ADHD symptoms. Our findings highlight the importance of considering parent and child genetic risk in relation to apparent environmental exposures.

The association between dietary acid load and risk of attention-deficit hyperactivity disorder: a case-control study

ABSTRACT Although previous studies have suggested that dietary acid load may be associated with mental health, the relationship between food-induced acid production and odds of attention-deficit hyperactivity disorder remains (ADHD) unclear. The aim of the present study was to evaluate the relationship between dietary renal acid load and odds of ADHD among children. A case-control study was designed to assess the data of 500 children aged 4 to 12 years (200 children with diagnosed ADHD and 300 control group). Patients were clinically diagnosed according to the Diagnostic and Statistical Manual-5th Edition criteria. Subjects in the control group did not have any history of chronic diseases and they were screened for the absence of ADHD. Dietary intake was assessed by a semi-quantitative food frequency questionnaire. The odds of incident ADHD for each unit increase of potential acid load (PRAL) in the raw model showed ~9.8% (OR = 1.098, 95% CI: 1.072, 1.125, p < .001) higher odds of ADHD. In model 1, where age, gender, Body mass index (BMI), and socio-economic status were adjusted, the odds of ADHD was ~10.7% (OR = 1.107, 95% CI: 1.076, 1.140, p < .001). Also, in model 2 (model 1 in addition to energy) the odds was ~10.8% (OR = 1.108, 95% CI: 1.065, 1.152, p < .001). Findings of the present study suggest a possible relationship between oxidative stresses and odds of development of ADHD. Furthermore, the size of the odds ratio is small. It appears that dietary considerations are warranted in order to ameliorate the impact and/or incidence of ADHD.

Association between cord blood metabolites in tryptophan pathway and childhood risk of autism spectrum disorder and attention-deficit hyperactivity disorder

Alterations in tryptophan and serotonin have been implicated in various mental disorders; but studies are limited on child neurodevelopmental disabilities such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). This prospective cohort study examined the associations between levels of tryptophan and select metabolites (5-methoxytryptophol (5-MTX), 5-hydroxytryptophan (5-HTP), serotonin, N-acetyltrytophan) in cord plasma (collected at birth) and physician-diagnosed ASD, ADHD and other developmental disabilities (DD) in childhood. The study sample (n = 996) derived from the Boston Birth Cohort, which included 326 neurotypical children, 87 ASD, 269 ADHD, and 314 other DD children (mutually exclusive). These participants were enrolled at birth and followed-up prospectively (from October 1, 1998 to June 30, 2018) at the Boston Medical Center. Higher levels of cord 5-MTX was associated with a lower risk of ASD (aOR: 0.56, 95% CI: 0.41, 0.77) and ADHD (aOR: 0.79, 95% CI: 0.65, 0.96) per Z-score increase, after adjusting for potential confounders. Similarly, children with cord 5-MTX ≥ 25th percentile (vs. <25th percentile) had a reduction in ASD (aOR: 0.27, 95% CI: 0.14, 0.49) and ADHD risks (aOR: 0.45, 95% CI: 0.29, 0.70). In contrast, higher levels of cord tryptophan, 5-HTP and N-acetyltryptophan were associated with higher risk of ADHD, with aOR: 1.25, 95% CI: 1.03, 1.51; aOR: 1.32, 95% CI: 1.08, 1.61; and aOR: 1.27, 95% CI: 1.05, 1.53, respectively, but not with ASD and other DD. Cord serotonin was not associated with ASD, ADHD, and other DD. Most findings remained statistically significant in the sensitivity and subgroup analyses.

PM2.5 exposure and incident attention-deficit/hyperactivity disorder during the prenatal and postnatal periods: A birth cohort study

Only a few studies have assessed the effects of fine particulate matter (PM2.5) exposure during the prenatal and postnatal periods on the development of attention-deficit/hyperactivity disorder (ADHD). We investigated the association of exposure to PM2.5 during pregnancy and early life with ADHD. This birth cohort consisted of 425,736 singleton live-term births between 2004 and 2015 in Taiwan. Daily PM2.5 concentrations were derived from a 1-km satellite-based estimation model. A time-dependent Cox model was used to assess the effects of PM2.5 on ADHD during the first, second, and third trimesters and from age 1–5 years after birth. The distributed lag nonlinear model was utilized to explore the dose–response relationship. Total 9,294 children were diagnosed with ADHD during the study period. The hazard ratio (HR) of ADHD was significantly associated with a 10 μg/m3 increase in PM2.5 during the first trimester (HR = 1.26; 95% confidence interval [CI]: 1.13–1.40) and increased at PM2.5 over 16 μg/m3. For postnatal periods, the HR of ADHD was significantly associated with increased PM2.5 at the first to third year of life (HR ranged between 1.40 and 1.87). According to the dose-response relationship of exposure to PM2.5 at the third year of life, the HR of ADHD was significantly associated with PM2.5 above 16 μg/m3 and sharply increased as PM2.5 >50 μg/m3. We did not observe a significant modification of sex on the relation between PM2.5 and ADHD. Exposure of pregnant women to PM2.5 above 16 μg/m3 from conception to the early life of their children may increase the risk of ADHD. The government should improve the criteria for air quality control and meet the WHO air quality guidelines to protect pregnant women and children from developing ADHD in the future.

Genetic Relationships between Attention-Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, and Intelligence

Introduction: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) commonly co-occur; both traits exert an influence on intelligence scores. Genetic relationships between these three traits are far from being clear. Methods: The summary results of genome-wide association studies of ADHD (20,183 cases and 35,191 controls), ASD (18,381 cases and 27,969 controls), and intelligence (269,867 participants) were used for the analyses. Local genetic correlation analysis and polygenic overlap analysis were used to explore the shared genetic components between ADHD, ASD, and intelligence. Mendelian randomization (MR) analysis was used to examine the causal associations between ADHD, ASD, and intelligence. A cross-trait meta-analysis was performed to identify pleiotropic genetic variants across the three traits. Results: Our results showed that intelligence has a positive and negative genetic correlation with ASD and ADHD, respectively, including three hub genomic regions showing correlated genetic effects across the three traits. Polygenic overlap analysis indicated that all the risk variants contributing to ADHD are overlapped with half of those for intelligence, and the majority of the shared variants have opposite effect directions between them. The majority of risk variants (80%) of ASD are overlapped with almost all the risk variants of intelligence (97%). Notably, some ASD/intelligence overlapping variants displayed opposing effects on these two conditions. MR analysis showed that the genetic liability to higher intelligence was associated with an increased risk for ASD (OR = 1.12) and a decreased risk for ADHD (OR = 0.78). Cross-trait meta-analyses identified 170 pleiotropic genomic loci across the three traits, including 12 novel loci. Functional analyses of the novel genes support their potential involvement in neurodevelopment. Conclusion: Our results suggest that ADHD is associated with inheriting a reduced set of low-intelligence alleles, whereas ASD results from incongruous effects from a mixture of high-intelligence and low-intelligence contributing alleles summed up with additional, ASD-specific risk variants not associated with intelligence.

Associations of a family history of lupus with the risks of lupus and major psychiatric disorders in first-degree relatives.

Genetic factors link psychiatric disorders, particularly major depressive disorder (MDD), bipolar disorder, and obsessive-compulsive disorder (OCD), with systemic lupus erythematosus (SLE). Additionally, maternal SLE is a risk factor for long-term developmental problems, particularly learning disabilities, attention disorders, autism spectrum disorder (ASD) and speech disorders, in children. We aimed to determine whether first-degree relatives (FDRs) of patients with SLE have increased risks of SLE and major psychiatric disorders. Using the Taiwan National Health Insurance Research Database, we recruited 40 462 FDRs of patients with SLE as well as 161 848 matched controls. The risks of major psychiatric disorders, including schizophrenia, bipolar disorder, OCD, MDD, ASD and attention-deficit/hyperactivity disorder (ADHD), were assessed. The FDRs of patients with SLE had higher risks of SLE (reported as the adjusted relative risk and 95% confidence interval: 14.54; 12.19-17.34), MDD (1.23; 1.12-1.34), ADHD (1.60; 1.55-1.65), OCD (1.41; 1.14-1.74) and bipolar disorder (1.18; 1.01-1.38) compared with controls. Specifically, male FDRs of patients with SLE had higher risks of SLE and bipolar disorder, whereas female FDRs of patients with SLE had higher risks of MDD and OCD. Differences in the familial relationship (i.e. parents, children, siblings and twins) were consistently associated with higher risks of these disorders compared with controls. The FDRs of patients with SLE had higher risks of SLE, MDD, ADHD, OCD and bipolar disorder than the controls.

The interaction between infant negative emotionality and cognition predicts ADHD-related behaviors in toddlerhood

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent disorder commonly identified in childhood. Affective and cognitive characteristics that are identifiable as early as infancy could be signals of risk for developing ADHD. Specifically, the interplay between emotionality and cognition may be important in predicting early symptoms of ADHD. This study examined the independent and interactive effects of infant negative emotionality and cognition on the development of inattention and hyperactivity/impulsivity in toddlerhood among infants at high and low familial likelihood for ADHD. Participants were 64 infants (M = 8.7, SD = 1.8) at high (n = 32) and low (n = 32) familial likelihood for ADHD, defined as at least one parent with ADHD or two parents without ADHD, respectively. Negative emotionality and cognition in infancy were assessed using the Infant Behavior Questionnaire and the Bayley’s Scales of Infant and Toddler Development, and ADHD symptoms were assessed at toddler follow-up (M= 20.0, SD= 3.2) using the Child Behavior Checklist. Accounting for the quality of parent-child interaction, infants’ negative emotionality (β = .033, p = .938) and cognition (β = .006, p = .884) did not independently predict toddlers’ ADHD-related behaviors, but their interaction did (β = .110, p = .019). For infants with higher levels of cognition (>95th percentile), higher negative emotionality predicted more ADHD-related behaviorss. For infants with lower levels of cognition (<11th percentile), higher negative emotionality predicted fewer ADHD-related behaviors. There may be two affective-cognitive pathways to inattention and hyperactivity/impulsivity in toddlerhood. The combination of higher levels of negative emotionality and cognition may result in greater frustration when goals are blocked, resulting in the expression of dysregulated behaviors (i.e., ADHD symptoms). Alternatively, low levels of negative emotionality and cognition combined may lead to dysregulation that is primarily cognitive in nature (such as the inattention symptoms of ADHD). Investigating affective and cognitive processes simultaneously may be important for increasing understanding of the early signals of ADHD risk.

Migration modulates the prevalence of ASD and ADHD: a systematic review and meta-analysis

BackgroundMigration has been implicated as a risk factor for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), but evidence is still limited and inconsistent. We aim to investigate the relationship between migration status and risk of ASD and ADHD.MethodsElectronic databases including PubMed, EMBASE, Web of Science, and PsychINFO were searched to identify observational studies on this topic, from inception to February 2021. Random-effects meta-analysis models were used to pool the summary odds ratio (OR) and 95% confidence interval (95% CI), and subgroup analyses were conducted to detect possible discrepancies in associations. Certainty of evidence was assessed as per the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines.ResultsA total of 13 studies (6,532,546 participants) for ASD, five studies (2,875,070 participants) for ADHD, and six studies (31,158 participants) for hyperactivity were included. Overall, the pooled results indicated that migration was associated with increased risk of ASD (pooled OR: 1.32; 95% CI: 1.07–1.63; P for Z test = 0.010), but no association was found between migration and ADHD (pooled OR: 0.84; 95% CI: 0.53–1.32; P for Z test = 0.452) or hyperactivity (pooled standardized mean difference: -0.073; 95% CIs: − 0.383–0.236; P for Z test = 0.642). Subgroup analyses further demonstrated that maternal migration was ASD risk factor (pooled OR: 1.49; 95% CI: 1.19–1.87), and migrant children were more likely to develop ASD with comorbid intellectual disability (ID) (pooled OR: 1.21, P for interaction = 0.006) than ASD without ID. After standardized the origin of migrants, European migrant children from Americas were at higher risk of ASD and ADHD (pooled OR were 4.13 and 1.26), and increased ASD risk was also observed in African children (pooled OR: 2.72). The GRADE of evidence was very low.ConclusionsMaternal migration is a risk factor for ASD, and migrant ASD children are more likely comorbid ID. The role of migration on ADHD remains controversial, more studies are needed to assess the association between migration status and ADHD. Health care practitioners should consider screening and providing extra resources for migrant children.

Attention-deficit hyperactivity disorder in children born to mothers with infertility: a population-based cohort study

STUDY QUESTIONIs the risk of attention-deficit hyperactivity disorder (ADHD) increased in children born to mothers with infertility, or after receipt of fertility treatment, compared to mothers with unassisted conception?SUMMARY ANSWERInfertility itself may be associated with ADHD in the offspring, which is not amplified by the use of fertility treatment.WHAT IS KNOWN ALREADYInfertility, and use of fertility treatment, is common. The long-term neurodevelopmental outcome of a child born to a mother with infertility, including the risk of ADHD, remains unclear.STUDY DESIGN, SIZE, DURATIONThis population-based cohort study comprised all singleton and multiple hospital births in Ontario, Canada, 2006–2014. Outcomes were assessed up to June 2020.PARTICIPANTS/MATERIALS, SETTING, METHODSLinked administrative datasets were used to capture all hospital births in Ontario, maternal health and pregnancy measures, fertility treatment and child outcomes. Included were all children born at ≥24 weeks gestation between 2006 and 2014, and who were alive at age 4 years. The main exposure was mode of conception, namely (i) unassisted conception (reference group), (ii) infertility without fertility treatment (history of an infertility consultation with a physician within 2 years prior to conception but no fertility treatment), (iii) ovulation induction (OI) or intrauterine insemination (IUI) and (iv) IVF or intracytoplasmic sperm injection (ICSI). The main outcome was a diagnosis of ADHD after age 4 years and assessed up to June 2020. Hazard ratios (HRs) were adjusted for maternal age, income quintile, rurality, immigration status, smoking, obesity, parity, any drug or alcohol use, maternal history of mental illness including ADHD, pre-pregnancy diabetes mellitus or chronic hypertension and infant sex. In addition, we performed pre-planned stratified analyses by mode of delivery (vaginal or caesarean delivery), infant sex, multiplicity (singleton or multiple), timing of birth (term or preterm <37 weeks) and neonatal adverse morbidity (absent or present).MAIN RESULTS AND THE ROLE OF CHANCEThe study included 925 488 children born to 663 144 mothers, of whom 805 748 (87%) were from an unassisted conception, 94 206 (10.2%) followed infertility but no fertility treatment, 11 777 (1.3%) followed OI/IUI and 13 757 (1.5%) followed IVF/ICSI. Starting at age 4 years, children were followed for a median (interquartile range) of 6 (4–8) years. ADHD occurred among 7.0% of offspring in the unassisted conception group, 7.5% in the infertility without fertility treatment group, 6.8% in the OI/IUI group and 6.3% in the IVF/ICSI group. The incidence rate (per 1000 person-years) of ADHD was 12.0 among children in the unassisted conception group, 12.8 in the infertility without fertility treatment group, 12.9 in the OI/IUI group and 12.2 in the IVF/ICSI group. Relative to the unassisted conception group, the adjusted HR for ADHD was 1.19 (95% CI 1.16–1.22) in the infertility without fertility treatment group, 1.09 (95% CI 1.01–1.17) in the OI/IUI group and 1.12 (95% CI 1.04–1.20) in the IVF/ICSI group. In the stratified analyses, these patterns of risk for ADHD were largely preserved. An exception was seen in the sex-stratified analyses, wherein females had lower absolute rates of ADHD but relatively higher HRs compared with that seen among males.LIMITATIONS, REASONS FOR CAUTIONSome mothers in the isolated infertility group may have received undocumented OI oral therapy, thereby leading to possible misclassification of their exposure status. Parenting behaviour, schooling and paternal mental health measures were not known, leading to potential residual confounding.WIDER IMPLICATIONS OF THE FINDINGSInfertility, even without treatment, is a modest risk factor for the development of ADHD in childhood. The reason underlying this finding warrants further study.STUDY FUNDING/COMPETING INTEREST(s)This study was made possible with funding from the Canadian Institutes of Health Research, Grant number PJT 165840. The authors report no conflict of interest.TRIAL REGISTRATION NUMBERN/A.

Association of Maternal Use of Triptans During Pregnancy With Risk of Attention-Deficit/Hyperactivity Disorder in Offspring

Triptans are commonly used in the treatment of migraine. Prenatal exposure to triptans may be associated with adverse fetal neurodevelopment; however, there is limited information about the long-term safety of triptan use during pregnancy. To examine the association between maternal use of triptans during pregnancy and diagnosis and symptoms of attention-deficit/hyperactivity disorder (ADHD) among offspring. This study used data from the Norwegian Mother, Father and Child Cohort Study (recruitment 1999-2008), linked to national health registries. Live-born singleton children born to women with migraine before or during pregnancy were included. Two analytic samples were defined: one to assess ADHD diagnosis and one to assess ADHD symptoms. Data were analyzed from May 1 to November 30, 2021. Maternal self-report of triptan use during pregnancy. Exposed children were compared with 2 groups of unexposed children whose mothers reported migraine (1) during pregnancy and (2) before pregnancy only. An ADHD diagnosis was defined as diagnosis of hyperkinetic disorder or receipt of dispensed ADHD medication. Symptoms of ADHD at 5 years were measured by the Conners' Parent Rating Scale, where a higher score indicates more symptoms of ADHD. Cox proportional hazards regression models and generalized linear models with inverse probability weights were used to estimate weighted hazard ratios (HRs) and standardized mean differences, respectively, with 95% CIs. The ADHD diagnosis sample comprised 10 167 children (mean [SD] maternal age, 30.2 [4.6] years; 5231 boys [51.5%]), and the ADHD symptoms sample comprised 4367 children (mean [SD] maternal age, 30.6 [4.4] years; 2191 boys [50.2%]). Children were followed up for a mean (SD) of 10.6 (2.2) years. Children with prenatal triptan exposure had no increased risk of ADHD diagnosis compared with unexposed children whose mothers had migraine during pregnancy (weighted HR, 1.16; 95% CI, 0.78-1.74) and compared with unexposed children whose mothers had migraine only before pregnancy (weighted HR, 1.28; 95% CI, 0.84-1.94). There were no differences in ADHD symptom scores between exposed and unexposed children. The findings of this study suggest that there is no increased risk of ADHD among offspring associated with prenatal exposure to triptans.

Sex-different interrelationships of rs945270, cerebral gray matter volumes, and attention deficit hyperactivity disorder: a region-wide study across brain

Previous genome-wide association studies (GWAS) reported that the allele C of rs945270 of the kinectin 1 gene (KTN1) most significantly increased the gray matter volume (GMV) of the putamen and modestly regulated the risk for attention deficit hyperactivity disorder (ADHD). On the other hand, ADHD is known to be associated with a reduction in subcortical and cortical GMVs. Here, we examined the interrelationships of the GMVs, rs945270 alleles, and ADHD symptom scores in the same cohort of children. With data of rs945270 genotypes, GMVs of 118 brain regions, and ADHD symptom scores of 3372 boys and 3129 girls of the Adolescent Brain Cognition Development project, we employed linear regression analyses to examine the pairwise correlations adjusted for the third of the three traits and other relevant covariates, and examine their mediation effects. We found that the major allele C of rs945270 modestly increased risk for ADHD in males only when controlling for the confounding effects of the GMV of any one of the 118 cerebral regions (0.026 ≤ p ≤ 0.059: Top two: left and right putamen). This allele also significantly increased putamen GMV in males alone (left p = 2.8 × 10−5, and right p = 9.4 × 10−5; α = 2.1 × 10−4) and modestly increased other subcortical and cortical GMVs in both sexes (α < p < 0.05), whether or not adjusted for ADHD symptom scores. Both subcortical and cortical GMVs were significantly or suggestively reduced in ADHD when adjusted for rs945270 alleles, each more significantly in females (3.6 × 10−7 ≤ p < α; Top two: left pallidum and putamen) and males (3.5 × 10−6 ≤ p < α), respectively. Finally, the left and right putamen GMVs reduced 14.0% and 11.7% of the risk effects of allele C on ADHD, and allele C strengthened 4.5% (left) and 12.2% (right) of the protective effects of putamen GMVs on ADHD risk, respectively. We concluded that the rs945270-GMVs-ADHD relationships were sex-different. In males, the major allele C of rs945270 increased risk for ADHD, which was compromised by putamen GMVs; this allele also but only significantly increased putamen GMVs that then significantly protected against ADHD risk. In females, the top two GMVs significantly decreasing ADHD risk were left pallidum and putamen GMVs. Basal ganglia the left putamen in particular play the most critical role in the pathogenesis of ADHD.

Effect of Mindfulness Intervention on Inattentive Behaviors in Children at Risk for ADHD: A Single-Subject Study

Mindfulness is the increased awareness that arises when we pay attention on purpose to the present non-judgmentally. To investigate the influence of mindfulness on inattentive behaviors in children at risk for attention deficit hyperactivity disorder (ADHD), a single-subject A-B-A reversal experimental design was adopted in which two children at risk for ADHD received 6-week mindfulness training, with 20-30 minutes per session and 3-4 times per week. The results based on visual analysis, C-statistics, and social validity analysis showed that mindfulness training was effective in reducing the duration of inattentive behaviors in children at risk for ADHD, and that the training could improve the function of the attention network in these children, which could be reflected in the increased efficiency in the vigilance network and the executive function network.

Influence of Maternal Diabetes on the Risk of Neurodevelopmental Disorders in Offspring in the Prenatal and Postnatal Periods.

This study aimed to evaluate the influence of maternal diabetes in the risk of neurodevelopmental disorders in offspring in the prenatal and postnatal periods. This cohort study included singleton gestational diabetes mellitus (GDM) pregnancies >22 weeks' gestation with live newborns between 1991 and 2008. The control group was randomly selected and matched (1:2) for maternal age, weeks of gestation and birth year. Cox regression models estimated the effect of GDM on the risk of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and maternal type 2 diabetes mellitus (T2DM). Moreover, interaction between maternal T2DM and GDM-ADHD relationship was evaluated. Children (n=3,123) were included (1,073 GDM; 2,050 control group). The median follow-up was 18.2 years (interquartile range, 14.2 to 22.3) (n=323 with ADHD, n=36 with ASD, and n=275 from women who developed T2DM). GDM exposure was associated with ADHD (hazard ratio [HR]crude, 1.67; 95% confidence interval [CI], 1.33 to 2.07) (HRadjusted, 1.64; 95% CI, 1.31 to 2.05). This association remained significant regardless of the treatment (diet or insulin) and diagnosis after 26 weeks of gestation. Children of mothers who developed T2DM presented higher rates of ADHD (14.2 vs. 10%, P=0.029). However, no interaction was found when T2DM was included in the GDM and ADHD models (P>0.05). GDM was not associated with an increased risk of ASD (HRadjusted, 1.46; 95% CI, 0.74 to 2.84). Prenatal exposure to GDM increases the risk of ADHD in offspring, regardless of GDM treatment complexity. However, postnatal exposure to maternal T2DM was not related to the development of ADHD.

A nationwide cohort study on the risk of ADHD in children with amblyopia mediated by fine motor skill impairment in East Asia

This national administrative investigation of Republic of Korea compared the risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders(ASD) in preschool amblyopic children and identified factors that possibly mediate this association. After propensity score (PS) matching, 7762 amblyopic children and 31,030 non-amblyopic children were included. Amblyopia was associated with ADHD (aOR:1.687; 95% CI 1.444, 1.970) but not with ASD (aOR: 0.591; 95% CI 0.341, 1.026). Fine motor skill impairment was a mediating factor in association of amblyopia with ADHD, accounting for 4.2% (95% CI 1.7, 8.0). In conclusion, amblyopic children have a greater risk of ADHD, and deficits in fine motor skills mediate this association. We suggest increased attention given to fine motor skill underdevelopment in amblyopic children to prevent the development of ADHD.

Association of Perinatal and Childhood Ischemic Stroke With Attention-Deficit/Hyperactivity Disorder

Early detection of attention-deficit/hyperactivity disorder (ADHD) plays a crucial role in reducing negative effects on everyday life, including academic failure and poor social functioning. Children who survive ischemic strokes risk major disabilities, but their risk of ADHD has not been studied in nationwide cohorts. To assess the risk of ADHD in children after pediatric ischemic stroke. Participants in this Swedish nationwide cohort study included 1320 children diagnosed with ischemic stroke recorded in linked Swedish national registers from January 1, 1969, to December 31, 2016, without prior ADHD diagnosis. Ten matched controls were identified for each index case, and first-degree relatives were identified for index individuals and controls. Analyses were stratified by perinatal and childhood strokes and presence of comorbid adverse motor outcomes and/or epilepsy. End of follow-up was the date of ADHD diagnosis, death, or December 31, 2016, whichever occurred first. Data analyses were performed August 1 to 28, 2021. Pediatric ischemic stroke. Attention-deficit/hyperactivity disorder identified using codes from the International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, and/or prescribed ADHD medication recorded in the Medical Birth Register, National Patient Register, or Prescribed Drug Register after stroke. Cox proportional hazards regression was used to assess adjusted hazard ratios (aHRs) for ADHD after pediatric stroke, adjusting for parental age and ADHD in first-degree relatives. Of 1320 children with stroke included in the analysis (701 boys [53.1%]), 75 (45 boys [60.0%]) were diagnosed with ADHD after stroke compared with 376 (252 boys [67.0%]) among the controls (aHR, 2.00 [95% CI, 1.54-2.60]). The risk was increased after both perinatal (aHR, 2.75 [95% CI ,1.65-4.60]) and childhood (aHR, 1.82 [95% CI, 1.34-2.48]) strokes and were similar if children born preterm or small for gestational age were excluded. Compared with controls, risks of ADHD were higher among children with perinatal stroke and adverse motor outcomes and/or epilepsy (aHR, 6.17 [95% CI, 2.80-13.62]) than among those without these comorbidities (aHR, 1.65 [95% CI, 0.80-3.42]). However, findings were similar in childhood stroke for children with adverse motor outcomes and/or epilepsy (aHR, 1.80 [95% CI, 1.12-2.89]) and among those without these comorbidities (aHR, 1.92 [95% CI, 1.28-2.90]). This cohort study of 1320 children with pediatric ischemic stroke suggests that there is an increased risk of ADHD, particularly in children with adverse motor outcomes and/or epilepsy, compared with controls. The risk increases after childhood strokes regardless of comorbidities.

Clinical and Genetic Correlates of Bipolar Disorder With Childhood-Onset Attention Deficit Disorder.

Background:Bipolar disorder (BD) with co-occurring attention deficit-hyperactivity disorder (ADHD) is associated with an unfavorable course of illness. We aimed to identify potential clinical and genetic correlates of BD with and without ADHD.MethodsAmong patients with BD (N = 2,198) enrolled in the Mayo Clinic Bipolar Biobank we identified those with ADHD diagnosed in childhood (BD+cADHD; N = 350), those with adult-onset attention deficit symptoms (BD+aAD; N = 254), and those without ADHD (N = 1,594). We compared the groups using linear or logistic regression adjusting for age, sex, and recruitment site. For genotyped patients (N = 1,443), logistic regression was used to compare ADHD and BD polygenic risk scores (PRSs) between the BD groups, as well as to non-BD controls (N = 777).ResultsCompared to the non-ADHD BD group, BD+cADHD patients were younger, more often men and had a greater number of co-occurring anxiety and substance use disorders (all p < 0.001). Additionally, BD+cADHD patients had poorer responses to lithium and lamotrigine (p = 0.005 and p = 0.007, respectively). In PRS analyses, all BD patient subsets had greater genetic risk for BD and ADHD when compared to non-BD controls (p < 0.001 in all comparisons). BD+cADHD patients had a higher ADHD-PRS than non-ADHD BD patients (p = 0.012). However, BD+aAD patients showed no evidence of higher ADHD-PRS than non-ADHD BD patients (p = 0.38).ConclusionsBD+cADHD was associated with a greater number of comorbidities and reduced response to mood stabilizing treatments. The higher ADHD PRS for the BD+cADHD group may reflect a greater influence of genetic factors on early presentation of ADHD symptoms.

Prenatal Antidepressant Exposure and the Risk of Attention-deficit/Hyperactivity Disorder in Childhood: A Cohort Study With Triangulation.

Uncontrolled confounding from maternal depression and genetic and environmental factors is expected in studies investigating the effect of prenatal antidepressant exposure on the risk of attention-deficit/hyperactivity disorder (ADHD) in childhood and may explain inconsistencies in the existing evidence. We aimed to assess this effect using triangulation. Using population-based health registries, we conducted a nationwide cohort study of all children born in Denmark between 1997 and 2017 and followed through 2018 for ADHD. We assessed the effect of prenatal antidepressant exposure on the risk of ADHD in childhood by comparing children with and without prenatal antidepressant exposure in terms of adjusted incidence rate ratios (IRRs), adjusted incidence rate differences (IRDs), and adjusted risk differences (RDs) and the associated 95% confidence intervals (CIs). We triangulated results from four different analytic approaches: an overall analysis, a negative control analysis, a sibling analysis, and a former-user analysis. The overall study cohort consisted of 1,253,362 children, among whom 28,910 (2.3%) had prenatal antidepressant exposure. ADHD during follow-up was diagnosed among 1,411 (4.9%) of the exposed and in 37,196 (3.0%) of the unexposed children. Triangulation suggested an IRR of 1.09-1.15; an IRD less than 1 case/1,000 person-years, and an RD of 0.9%-2.2% over an up to 18-year period. Based on triangulation, we estimated a modest effect of prenatal antidepressant exposure on the risk of ADHD in childhood. However, considering the limitations of our approaches, this observed association may be partially due to residual biases. See video abstract at, http://links.lww.com/EDE/B935.

MEF2C gene variations are associated with ADHD in the Chinese Han population: a case-control study.

Myocyte enhancer factor 2C (MEF2C) is associated with hyperactivity and might be a novel risk gene for susceptibility to attention deficit hyperactivity disorder (ADHD). Therefore, this study aimed to explore the association between MEF2C genetic variants and ADHD in the Chinese Han population. A total of 215 patients with ADHD and 233 controls were recruited for this study. The Swanson, Nolan, and Pelham version IV questionnaire was used to evaluate the clinical features of ADHD. In silico analysis was used to annotate the biological functions of the promising single nucleotide polymorphisms. Our findings indicated that MEF2C rs587490 was significantly associated with ADHD in the multiplicative model (OR = 0.640, p = 0.002). Participants with the rs587490 TT allele exhibited less hyperactivity/impulsivity than those with the rs587490 CC allele. Furthermore, the expression quantitative trait loci analysis suggested that rs587490 could regulate the gene expression of MEF2C in the hippocampus, putamen, thalamus, and frontal white matter. Our study concluded that the MEF2C rs587490 T allele is significantly associated with a reduced risk of ADHD in the Chinese Han population, which provides new insight into the genetic etiology of ADHD.

A nationwide study of the risks of major mental disorders among the offspring of parents with rheumatoid arthritis

Rheumatoid arthritis (RA) may share genomic risks with certain mental disorders. This study aimed at investigating associations between parental RA and risks of mental disorders in offspring. Using the National Health Insurance Research Database (2001–2010), we conducted a matched cohort study involving two parent–child cohorts (i.e., RA-parent–child cohort and non-RA-parent–child cohort) between which risks of major mental disorders in offspring were compared. There were 23,981 parent–child pairs in the RA-parent–child cohort and 239,810 in the non-RA-parent–child cohort. Preliminary analysis demonstrated increased risks of autism spectrum disorders (ASDs) [Odds ratio (OR) 1.47; 95% confidence interval (CI) 1.05–2.07], attention-deficit/hyperactivity disorder (ADHD) [OR 1.34; (95% CI 1.17–1.54)], bipolar disorder [OR 1.41 (95% CI 1.17–1.70)], and major depressive disorder [OR 1.20 (95% CI 1.07–1.35)] associated with parental RA. Sub-group analysis further showed higher risks of the four disorders in children of mothers with RA but not those from fathers with RA. Higher risks of ASDs and ADHD were not noted in children of mothers with RA before childbirth. Maternal RA, but not paternal RA or mothers diagnosed with RA before childbirth, was associated with increased risks of multiple mental disorders in their offspring, suggesting potential contributions of maternal genetic factors to ASDs and ADHD development in offspring.

Association between plasma proteome and childhood neurodevelopmental disorders: A two-sample Mendelian randomization analysis.

SummaryBackgroundChildhood neurodevelopmental disorders, including autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and Tourette syndrome (TS), comprise a major cause of health-related disabilities in children. However, biomarkers towards pathogenesis or novel drug targets are still limited. Our study aims to provide a comprehensive investigation of the causal effects of the plasma proteome on ASD, ADHD, and TS using the two-sample Mendelian Randomization (MR) approach.MethodsGenetic associations with 2994 plasma proteins were selected as exposures and genome-wide association data of ASD, ADHD, TS were utilized as outcomes. MR analyses were carried out using the inverse-variance weighted method, and the MR-Egger and weighted median methods were used for sensitivity analysis.FindingsUsing single-nucleotide polymorphisms as instruments, the study suggested increased levels of MAPKAPK3 (OR: 1.09; 95% CI: 1.05–1.13; P = 1.43 × 10−6) and MRPL33 (OR: 1.07; 95% CI: 1.04–1.11; P = 5.37 × 10−6) were causally associated with a higher risk of ASD, and increased MANBA level was associated with a lower risk of ADHD (OR: 0.91; 95% CI: 0.88–0.95; P = 8.97 × 10−6). The causal associations were robust in sensitivity analysis, leave-one-out analysis and Multivariable MR, and no pleiotropy was observed. No significant risk protein was identified for TS.InterpretationThe study findings support the idea that the MAPK/ERK signaling pathway and mitochondrial dysfunction are involved in the pathogenesis of ASD, while a deficiency in beta-mannosidase might play a role in the development of ADHD.