The association between attention deficit hyperactivity disorder and pregnancy, delivery and neonatal outcomes-an evaluation of a population database.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the more common neuropsychiatric disorders in women of reproductive age. Our objective was to compare perinatal outcomes between women with an ADHD diagnosis and those without. METHODS: A retrospective population-based cohort study utilizing the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample (HCUP-NIS) United States database. The study included all women who either delivered or experienced maternal death from 2004 to 2014. Perinatal outcomes were compared between women with an ICD-9 diagnosis of ADHD and those without. RESULTS: Overall, 9,096,788 women met the inclusion criteria. Amongst them, 10,031 women had a diagnosis of ADHD. Women with ADHD, compared to those without, were more likely to be younger than 25 years of age; white; to smoke tobacco during pregnancy; to use illicit drugs; and to suffer from chronic hypertension, thyroid disorders, and obesity (p < 0.001 for all). Women in the ADHD group, compared to those without, had a higher rate of hypertensive disorders of pregnancy (HDP) (aOR 1.36, 95% CI 1.28-1.45, p < 0.001), cesarean delivery (aOR 1.19, 95% CI 1.13-1.25, p < 0.001), chorioamnionitis (aOR 1.34, 95% CI 1.17-1.52, p < 0.001), and maternal infection (aOR 1.33, 95% CI 1.19-1.5, p < 0.001). Regarding neonatal outcomes, patients with ADHD, compared to those without, had a higher rate of small-for-gestational-age neonate (SGA) (aOR 1.3, 95% CI 1.17-1.43, p < 0.001), and congenital anomalies (aOR 2.77, 95% CI 2.36-3.26, p < 0.001). CONCLUSION: Women with a diagnosis of ADHD had a higher incidence of a myriad of maternal and neonatal complications, including cesarean delivery, HDP, and SGA neonates.

Genetic correlation and causal associations between psychiatric disorders and lung cancer risk.

BACKGROUND: Patients with certain psychiatric disorders have increased lung cancer incidence. However, establishing a causal relationship through traditional epidemiological methods poses challenges. METHODS: Available summary statistics of genome-wide association studies of cigarette smoking, lung cancer, and eight psychiatric disorders, including attention deficit/hyperactivity disorder (ADHD), autism, depression, major depressive disorder, bipolar disorder, insomnia, neuroticism, and schizophrenia (range N: 46,350-1,331,010) were leveraged to estimate genetic correlations using Linkage Disequilibrium Score Regression and assess causal effect of each psychiatric disorder on lung cancer using two-sample Mendelian randomization (MR) models, comprising inverse-variance weighted (IVW), weighted median, MR-Egger, pleiotropy residual sum and outlier testing (MR-PRESSO), and a constrained maximum likelihood approach (cML-MR). RESULTS: Significant positive correlations were observed between each psychiatric disorder and both smoking and lung cancer (all FDR < 0.05), except for the correlation between autism and lung cancer. Both univariable and the cML-MA MR analyses demonstrated that liability to schizophrenia, depression, ADHD, or insomnia was associated with an increased risk of overall lung cancer. Genetic liability to insomnia was linked specifically to squamous cell carcinoma (SCC), while genetic liability to ADHD was associated with an elevated risk of both SCC and small cell lung cancer (all P < 0.05). The later was further supported by multivariable MR analyses, which accounted for smoking. LIMITATIONS: Participants were constrained to European ancestry populations. Causal estimates from binary psychiatric disorders may be biased. CONCLUSION: Our findings suggest appropriate management of several psychiatric disorders, particularly ADHD, may potentially reduce the risk of developing lung cancer.

Early childhood exposure to environmental phenols and parabens, phthalates, organophosphate pesticides, and trace elements in association with attention deficit hyperactivity disorder (ADHD) symptoms in the CHARGE study.

BACKGROUND: A growing body of literature investigated childhood exposure to environmental chemicals in association with attention-deficit/hyperactivity disorder (ADHD) symptoms, but limited studies considered urinary mixtures of multiple chemical classes. This study examined associations of concurrent exposure to non-persistent chemicals with ADHD symptoms in children diagnosed with autism spectrum disorder (ASD), developmental delay (DD), and typical development (TD). METHODS: A total of 549 children aged 2-5 years from the Childhood Autism Risks from Genetics and Environment (CHARGE) case-control study were administered the Aberrant Behavior Checklist (ABC). This study focused on the ADHD/noncompliance subscale and its two subdomains (hyperactivity/impulsivity, inattention). Sixty-two chemicals from four classes (phenols/parabens, phthalates, organophosphate pesticides, trace elements) were quantified in child urine samples, and 43 chemicals detected in > 70% samples were used to investigate their associations with ADHD symptoms. Negative binomial regression was used for single-chemical analysis, and weighted quantile sum regression with repeated holdout validation was applied for mixture analysis for each chemical class and all chemicals. The mixture analyses were further stratified by diagnostic group. RESULTS: A phthalate metabolite mixture was associated with higher ADHD/noncompliance scores (median count ratio [CR] = 1.10; 2.5th, 97.5th percentile: 1.00, 1.21), especially hyperactivity/impulsivity (median CR = 1.09; 2.5th, 97.5th percentile: 1.00, 1.25). The possible contributors to these mixture effects were di-2-ethylhexyl phthalate (DEHP) metabolites and mono-2-heptyl phthalate (MHPP). These associations were likely driven by children with ASD as these were observed among children with ASD, but not among TD or those with DD. Additionally, among children with ASD, a mixture of all chemicals was associated with ADHD/noncompliance and hyperactivity/impulsivity, and possible contributors were 3,4-dihydroxy benzoic acid, DEHP metabolites, MHPP, mono-n-butyl phthalate, and cadmium. CONCLUSIONS: Early childhood exposure to a phthalate mixture was associated with ADHD symptoms, particularly among children with ASD. While the diverse diagnostic profiles limited generalizability, our findings suggest a potential link between phthalate exposure and the comorbidity of ASD and ADHD.

Behavioural disorders after prenatal exposure to anaesthesia for maternal surgery.

BACKGROUND: The association between prenatal exposure to general anaesthesia for maternal surgery during pregnancy and subsequent risk of disruptive or internalising behavioural disorder diagnosis in the child has not been well-defined. METHODS: A nationwide sample of pregnant women linked to their liveborn infants was evaluated using the Medicaid Analytic eXtract (MAX, 1999-2013). Multivariate matching was used to match each child prenatally exposed to general anaesthesia owing to maternal appendectomy or cholecystectomy during pregnancy with five unexposed children. The primary outcome was diagnosis of a disruptive or internalising behavioural disorder in children. Secondary outcomes included diagnoses for a range of other neuropsychiatric disorders. RESULTS: We matched 34,271 prenatally exposed children with 171,355 unexposed children in the database. Prenatally exposed children were more likely than unexposed children to receive a diagnosis of a disruptive or internalising behavioural disorder (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.23-1.40). For secondary outcomes, increased hazards of disruptive (HR, 1.32; 95% CI, 1.24-1.41) and internalising (HR, 1.36; 95% CI, 1.20-1.53) behavioural disorders were identified, and also increased hazards of attention-deficit/hyperactivity disorder (HR, 1.32; 95% CI, 1.22-1.43), behavioural disorders (HR, 1.28; 95% CI, 1.14-1.42), developmental speech or language disorders (HR, 1.16; 95% CI, 1.05-1.28), and autism (HR, 1.31; 95% CI, 1.05-1.64). CONCLUSIONS: Prenatal exposure to general anaesthesia is associated with a 31% increased risk for a subsequent diagnosis of a disruptive or internalising behavioural disorder in children. Caution is advised when making any clinical decisions regarding care of pregnant women, as avoidance of necessary surgery during pregnancy can have detrimental effects on mothers and their children.

An Industry-Relevant Metal Mixture, Iron Status, and Reported Attention-Related Behaviors in Italian Adolescents.

BACKGROUND: Exposure to environmental metals has been consistently associated with attention and behavioral deficits in children, and these associations may be modified by coexposure to other metals or iron (Fe) status. However, few studies have investigated Fe status as a modifier of a metal mixture, particularly with respect to attention-related behaviors. METHODS: We used cross-sectional data from the Public Health Impact of Metals Exposure study, which included 707 adolescents (10-14 years of age) from Brescia, Italy. Manganese, chromium, and copper were quantified in hair samples, and lead was quantified in whole blood, using inductively coupled plasma mass spectrometry. Concentrations of Fe status markers (ferritin, hemoglobin, transferrin) were measured using immunoassays or luminescence assays. Attention-related behaviors were assessed using the Conners Rating Scales Self-Report Scale-Long Form, Parent Rating Scales Revised-Short Form, and Teacher Rating Scales Revised-Short Form. We employed Bayesian kernel machine regression to examine associations of the metal mixture with these outcomes and evaluate Fe status as a modifier. RESULTS: Higher concentrations of the metals and ferritin were jointly associated with worse self-reported attention-related behaviors: metals and ferritin set to their 90th percentiles were associated with 3.0% [ß=0.03; 95% credible interval (CrI): -0.01, 0.06], 4.1% (ß=0.04; 95% CrI: 0.00, 0.08), and 4.1% (ß=0.04; 95% CrI: 0.00, 0.08) higher T-scores for self-reported attention deficit/hyperactivity disorder (ADHD) index, inattention, and hyperactivity, respectively, compared with when metals and ferritin were set to their 50th percentiles. These associations were driven by hair manganese, which exhibited nonlinear associations with all self-reported scales. There was no evidence that Fe status modified the neurotoxicity of the metal mixture. The metal mixture was not materially associated with any parent-reported or teacher-reported scale. CONCLUSIONS: The overall metal mixture, driven by manganese, was adversely associated with self-reported attention-related behavior. These findings suggest that exposure to multiple environmental metals impacts adolescent neurodevelopment, which has significant public health implications. https://doi.org/10.1289/EHP12988.

Genetic contribution to the comorbidity between attention-deficit/hyperactivity disorder and substance use disorders.

We characterized the genetic architecture of the attention-deficit hyperactivity disorder-substance use disorder (ADHD-SUD) relationship by investigating genetic correlation, causality, pleiotropy, and common polygenic risk. Summary statistics from genome-wide association studies (GWAS) were used to investigate ADHD (Neff = 51,568), cannabis use disorder (CanUD, Neff = 161,053), opioid use disorder (OUD, Neff = 57,120), problematic alcohol use (PAU, Neff = 502,272), and problematic tobacco use (PTU, Neff = 97,836). ADHD, CanUD, and OUD GWAS meta-analyses included cohorts with case definitions based on different diagnostic criteria. PAU GWAS combined information related to alcohol use disorder, alcohol dependence, and the items related to alcohol problematic consequences assessed by the alcohol use disorders identification test. PTU GWAS was generated a multi-trait analysis including information regarding Fagerström Test for Nicotine Dependence and cigarettes per day. Linkage disequilibrium score regression analyses indicated positive genetic correlation with CanUD, OUD, PAU, and PTU. Genomic structural equation modeling showed that these genetic correlations were related to two latent factors: one including ADHD, CanUD, and PTU and the other with OUD and PAU. The evidence of a causal effect of PAU and PTU on ADHD was stronger than the reverse in the two-sample Mendelian randomization analysis. Conversely, similar strength of evidence was found between ADHD and CanUD. CADM2 rs62250713 was a pleiotropic SNP between ADHD and all SUDs. We found seven, one, and twenty-eight pleiotropic variants between ADHD and CanUD, PAU, and PTU, respectively. Finally, OUD, CanUD, and PAU PRS were associated with increased odds of ADHD. Our findings demonstrated the contribution of multiple pleiotropic mechanisms to the comorbidity between ADHD and SUDs.

Differences in psychiatric comorbidity patterns in patients diagnosed with chronic stress-induced exhaustion disorder and depression - A cohort study in the total population of Region Stockholm.

The high prevalence of stress-related disorders and depression underscores the urgent need to unravel their impact on individual well-being. This study aim to investigate common psychiatric and stress-related diagnoses, along with postviral fatigue, in individuals with prior stress-induced exhaustion disorder (SED) and prior depression compared to those without prior SED or depression, and to study whether the psychiatric comorbidity patterns differ. The study includes individuals in Region Stockholm who, in 2011, did not have a diagnosis of SED or depression. ICD-10 diagnosis of SED, depression, or both, recorded in 2012-2013, were compared to individuals without prior SED or depression in a cohort (n = 1,362,886), aged 18 to 65. Odds ratios (OR) with 99 % confidence intervals, adjusted for age and neighborhood socioeconomic status, were calculated for psychiatric disorders and post-viral fatigue in 2014-2022. Patients with prior SED showed associations primarily with stress related diagnoses, including acute stress reaction, reaction to severe stress, as well as post-COVID-19 and post-viral fatigue syndrome. These ORs were all larger for SED than depression. Depression was primarily associated with post-traumatic stress disorder (PTSD), alcohol related and substance use disorders, schizophrenia, schizotypal disorders, delusional disorders, manic episode, bipolar affective disorder, persistent mood disorder, neurotic disorder, borderline personality disorder, autistic disorder, Asperger's syndrome, attention -deficit hyperactivity disorder, attention-deficit disorders ADHD/ADD), and suicide attempt. These ORs were all higher for depression, although autistic disorders, ADHD/ADD and PTSD were also highly associated with prior SED (OR > 3.5). The divergent psychiatric comorbidity patterns suggest different underlying mechanisms and clinical prognosis.

Stress as a mediator of brain alterations in attention-deficit hyperactivity disorder: A systematic review.

OBJECTIVE: Stress is a known risk factor for numerous psychopathologies, whereas evidence is lacking regarding the specific consequences of stress on the neural basis of attention-deficit hyperactivity disorder (ADHD). A systematic literature review was thus conducted to clarify the role of stress in the association between the resulting alterations of brain structure, connectivity, and function in ADHD. METHODS: The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under identifier CRD42023379809. A systematic search of the PubMed and CINAHL databases was conducted for articles published prior to December 22nd, 2022. Retrieved literature was screened in Rayyan and data extraction was performed with respect to neuroimaging, stress exposure, and ADHD outcomes. The Quality in Prognosis Studies (QUIPS) tool was adapted based on the Conducting Systematic Reviews and Meta-Analyses of Observational Studies of Etiology (COSMOS-E) guidance article to assess risk of bias and quality of studies. Strength of the evidence was assessed under the guidance of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. RESULTS: Screening 25,026 non-duplicate articles yielded 20 eligible studies for inclusion. Exposure to early life trauma, institutionalization, prenatal smoking or alcohol consumption, air pollution, low socioeconomic status, or low birth weight were associated with alterations in brain structure, function, and connectivity in ADHD. However, most studies did not provide strong evidence due to small sample sizes and lack of statistical approaches to determine a direct mediation of the association between stress and ADHD by neural outcomes. CONCLUSION: This systematic review was the first to summarize evidence of structural and functional stress-associated alterations in the brain, which were found to be directly and indirectly associated with ADHD outcomes. Overall, stress requires consideration as a significant determinant of neurodevelopmental outcomes in ADHD. However, extensive further research is warranted due to little available evidence and the difficulty of obtaining clear results. In light of such a complex research question, in order to confirm findings, provide further evidence, and establish causality systematic longitudinal studies would be required. Investigating the topic may provide invaluable information when it comes to tailoring prevention and treatment strategies in ADHD, and should be pursued in order to integrate the factor of stress into a more comprehensive understanding of ADHD.

A systematic review of attention-deficit/hyperactivity disorder in people living with cystic fibrosis.

There is a lack of research that has focused on attention-deficit hyperactivity disorder (ADHD) in people with cystic fibrosis (pwCF). Given ADHD is associated with executive functioning impairments, exploring ADHD in the context of living with cystic fibrosis (CF) is of great importance. The purpose of the current systematic review was to examine ADHD in pwCF across the lifespan in terms of its prevalence, its impact on various health outcomes, and treatments for managing ADHD. This systematic review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Articles reporting studies of any design that focused on ADHD in pwCF were included. Studies were excluded if they did not meet this criterion and if they were written in languages other than English. PsycINFO, MEDLINE, EMBASE, and CINAHL databases were searched. Search items were based on three concepts: (1) terms related to CF, (2) terms related to ADHD, and (3) terms related to age. Ten studies were included in this systematic review. Reported prevalence rates of ADHD in pwCF ranged from 5.26% to 21.9%. The reported relationships between ADHD and CF and other health outcomes is inconsistent. In terms of treatment considerations, pharmacological interventions and behavioural strategies for managing ADHD in the context of living with CF have been reported as being successful. Additional research is needed to further explore ADHD in the CF population and health variables that may be associated with CF prognosis.

Sex, hormones and cerebrovascular function: from development to disorder.

Proper cerebrovascular development and neurogliovascular unit assembly are essential for brain growth and function throughout life, ensuring the continuous supply of nutrients and oxygen. This involves crucial events during pre- and postnatal stages through key pathways, including vascular endothelial growth factor (VEGF) and Wnt signaling. These pathways are pivotal for brain vascular growth, expansion, and blood-brain barrier (BBB) maturation. Interestingly, during fetal and neonatal life, cerebrovascular formation coincides with the early peak activity of the hypothalamic-pituitary-gonadal axis, supporting the idea of sex hormonal influence on cerebrovascular development and barriergenesis.Sex hormonal dysregulation in early development has been implicated in neurodevelopmental disorders with highly sexually dimorphic features, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Both disorders show higher prevalence in men, with varying symptoms between sexes, with boys exhibiting more externalizing behaviors, such as aggressivity or hyperactivity, and girls displaying higher internalizing behaviors, including anxiety, depression, or attention disorders. Indeed, ASD and ADHD are linked to high prenatal testosterone exposure and reduced aromatase expression, potentially explaining sex differences in prevalence and symptomatology. In line with this, high estrogen levels seem to attenuate ADHD symptoms. At the cerebrovascular level, sex- and region-specific variations of cerebral blood flow perfusion have been reported in both conditions, indicating an impact of gonadal hormones on the brain vascular system, disrupting its ability to respond to neuronal demands.This review aims to provide an overview of the existing knowledge concerning the impact of sex hormones on cerebrovascular formation and maturation, as well as the onset of neurodevelopmental disorders. Here, we explore the concept of gonadal hormone interactions with brain vascular and BBB development to function, with a particular focus on the modulation of VEGF and Wnt signaling. We outline how these pathways may be involved in the underpinnings of ASD and ADHD. Outstanding questions and potential avenues for future research are highlighted, as uncovering sex-specific physiological and pathological aspects of brain vascular development might lead to innovative therapeutic approaches in the context of ASD, ADHD and beyond.

Treatment Utilization Pattern of Preschool Children With Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: The aim of this study was to identify patterns of ADHD care, including factors that guide selection and sequencing of treatments in a large nationwide sample of preschool-aged youth over the past 6 years. METHOD: A retrospective cohort study utilizing a large electronic health record (TriNetX) of nearly 24,000 children ages 3 to 6 diagnosed with ADHD. RESULTS: One in three preschoolers with ADHD were prescribed psychotropic medication, most commonly methylphenidate and guanfacine. One in 10 had at least one psychotherapy billing code during the entire assessment with most youth starting medication before psychotherapy. Rates of most treatments, including polypharmacy, increased with comorbid psychiatric disorders or sleep problems and over the course of the coronavirus pandemic. CONCLUSION: Rates of treatment have increased over time but are still largely inconsistent with published care guidelines that advise therapy before medication. Clinicians appear to prioritize psychiatric comorbidity and sleep problems when selecting treatments.

Prevalence and Related Factors of Attention Deficit Hyperactivity Disorder in School-age Children With Atopic Dermatitis.

Context: Atopic dermatitis (AD) is a chronic inflammatory skin disease and commonly affects children. AD is associated with a high incidence of ADHD, the most common psychological and neurobehavioral disorder in children and adolescents. If clinicians don't identify ADHD and intervene early, preschool children can experience adverse effects. Objective: The study intended to investigate the prevalence of attention deficit hyperactivity disorder (ADHD) in preschool children with AD, analyze the associated factors, and provide insights for early identification of risk factors and the development of interventions to reduce the likelihood of ADHD occurrence. Design: The research team performed a prospective, observational, case-control study. Setting: The study took place at the Zhoushan branch of Ruijin Hospital at the Shanghai Jiaotong University School of Medicine in Zhoushan, Zhejiang, China. Participants: Participants were 80 school-aged children diagnosed with AD and admitted to the hospital between May 2019 and May 2023. Groups: Based on the presence or absence of ADHD, the research team divided the children into two groups: (1) the Simple AD group with 71 participants with AD only, and the AD + ADHD group, with 9 participants with AD and ADHD. Outcome Measures: The research team: (1) collected and analyzed participants' demographic and clinical data, including an assessment of the AD severity using the SCORing Atopic Dermatitis (SCORAD) scale and the presence of sleep disorders using the Children's Sleep Habits Questionnaire (CSHQ); (2) assessed the presence of ADHD using the Swanson, Nolan, and Pelham-IV rating scales (SNAP-IV); (3) analyzed the factors influencing the occurrence of ADHD in AD children, using univariate and multivariate logistic regression analysis. Results: Among the 80 school-age children with AD, 9 participants (11.25%) had received a diagnosis of ADHD. The AD + ADHD group's age (P < .001); body mass index (BMI), with P < .001; AD severity (P = .013); rate of sleep disorders (P = .001); and levels of serum interleukin 6 (IL-6), with (P < .001), interleukin 4 (IL-4), with (P < .001), and nerve growth factor (NGF), with (P < .001) were all significantly greater than those of the Simple AD group. The univariate logistic regression analysis indicated that age (P = .014), BMI (P = .024), AD severity (P = .022), sleep disorders (P = .042), and levels of IL-6 (P = .044), IL-4 (P = .045), and NGF (P = .046) were all significantly related to the development of ADHD in school-age children with AD. The multivariate logistic regression analysis revealed that sleep disorders (P = .018) and elevated levels of serum IL-6 (P = .032), IL-4 (P = .021), and NGF (P = .016 ) were independent risk factors for ADHD (OR = 2.651, 3.074, 2.686, 3.340). Conclusions: School-aged children with AD are more likely to develop ADHD, which is mainly associated with sleep disorders and elevated levels of serum IL-6, IL-4, and NGF. Clinicians should give attention to these risk factors and implement early interventions to reduce the risk of children with AD developing ADHD.

Early childhood general anesthesia and risk of Attention Deficit Hyperactivity Disorder.

BACKGROUND: The relationship between early childhood exposure to general anesthesia (GA) and the risk of developing Attention Deficit Hyperactivity Disorder (ADHD) is still uncertain and previous studies have presented conflicting results. This population-based cohort study aimed to investigate the potential relationship between GA exposure and ADHD risk using propensity score matching (PSM) in a large sample size. METHODS: The study included 15,072 children aged 0-3 years who received GA and were hospitalized for more than 1 day in Taiwan from 2004 to 2014. The nonexposed group was randomly selected through 1:1 PSM from the Taiwan Maternal and Child Health Database (TMCHD). The primary objectives of this study were to determine the incidence rates (IR) and incidence rate ratios (IRR) of ADHD in the two cohorts, employing Poisson regression models. RESULTS: The GA group and non-GA group each comprised 7,536 patients. The IR of ADHD was higher in the GA group (122.45 per 10,000 person-years) than in the non-GA group (64.15 per 10,000 person-years), and the IRR of ADHD in the GA group was 1.39 (95% CI: 1.26, 1.55). The study found that the number of times of exposure to GA, duration of exposure, male gender, and central nervous system surgery were significant risk factors for ADHD in the future. CONCLUSIONS: This study's findings suggest that there is a significant correlation between early childhood exposure to GA and the risk of developing ADHD, and GA may be an important risk factor for ADHD in children undergoing surgery. The study also identified several risk factors for ADHD, including the number of times of exposure to GA, duration of exposure, male gender, and central nervous system surgery.

Attention-deficit/hyperactivity disorder and the menstrual cycle: Theory and evidence.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that exhibits striking sex differences in symptoms, prevalence, and associated problems across development. Etiological factors and mechanisms underlying these sex differences remain one of the most understudied aspects of this disorder. The current paper seeks to provide a novel theoretical framework for understanding this phenomenon by reviewing evidence that females with ADHD may experience a "double whammy" of organizational and activational pubertal hormonal effects. We propose a novel theory of activational effects of cyclical circulating ovarian hormones on ADHD with increasing risk at times of rapid declines in estrogen. These declines may decrease executive function and trait control at two points of the cycle characterized by biphasic affective risk: (1) increases in approach/risk-taking behaviors at mid-cycle (periovulatory) and (2) increases in avoidance/negative affect perimenstrually. Low estrogen and control may then interact with increases in positive and negative affect, respectively, to increase hyperactivity-impulsivity symptoms post-ovulation and inattention symptoms perimenstrually. These interactions may be exacerbated by organizational pubertal effects on relatively overdeveloped limbic circuitry and adolescent-specific social pressures magnified in females with ADHD.

Are congenital heart defects connected to more severe attention-deficit/hyperactivity disorder?: A systematic review and meta-analysis.

BACKGROUND: Congenital heart defects (CHDs) are the most common cause of birth defect-related infant morbidity and mortality, affecting 1% of 40,000 births per year in the United States. On the other side, the etiology of attention-deficit/hyperactivity disorder (ADHD) is multifactorial. Multiple studies have found that cardiac surgery patients have higher morbidity of having this disorder. Many studies have investigated the prevalence of ADHD in different subtypes of CHD, but few have focused on the severity of ADHD symptoms. Thus, we conducted this systematic review and meta-analysis to investigate the severity of ADHD symptoms in CHD patients. METHODS: We searched PubMed, Embase, Scopus, and Web of Science were searched from inception to March 6, 2023 without any restrictions. We included observational studies published in English language that evaluated burden of symptom of ADHD in CHD patients. Moreover, the standardized mean difference (SMD) for continuous outcomes with 95% confidence interval (CI) was pooled. P-values <.05 are considered as significant, and we performed all statistical analyses using RevMan software Version 5.4.1. RESULTS: Eight studies were included in our review with a total number of 120,158 patients. CHD was associated with a statistically significant increase in both ADHD index T score and ADHD Hyperactivity-Impulsivity Subscale (informant) with (SMD = 0.65, 95% CI [0.40, 0.90], P < .00001, I2 = 81%) and (SMD = 0.16, 95% CI [0.04, 0.28], P = .008, I2 = 0%). Regarding ADHD Inattention Subscale (informant), the pooled data showed that a significant increase of this score in the CHD group (SMD = 0.25, 95% CI [0.13, 0.37], P < .001, I2 = 0%), and ADHD Combined Score (informant) showed a significant increase of this score in the CHD group (SMD = 0.23, 95% CI [0.11, 0.35], P = .0002, I2 = 0%). CONCLUSION: Our study revealed a strong association between CHD and not only ADHD, but also the severity of ADHD, making early diagnosis of ADHD in children with CHD a mandatory step in the clinical evaluation practice to improve these children on both clinical and psychological aspects.

[Birth conditions and attention deficit/hyperactivity disorders (ADHD) in adults in the Pelotas (Brazil) birth cohorts of 1982 and 1993]. / Condições de nascimento e transtorno do déficit de atenção com hiperatividade (TDAH) em adultos nas coortes de nascimento de Pelotas, Rio Grande do Sul, Brasil, de 1982 e 1993.

This study evaluates the association of birth conditions with attention deficit/hyperactivity disorders (ADHD) in adults using data from two birth cohorts in the city of Pelotas Rio Grande do Sul State, Brazil. In 1982 and 1993 all births in the city were identified and have been prospectively monitored. In the follow-ups at 30 and 22 years of the 1982 (n = 3,574) and 1993 (n = 3,780) cohorts, respectively, participants were examined, and trained psychologists applied the Mini-International Neuropsychiatric Interview (M.I.N.I.). Those individuals who met the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria were defined as positive for ADHD. Poisson regression with robust variance adjustment was used to estimate the prevalence ratio (PR) adjusted for sex, maternal skin color, family income, maternal age, maternal schooling during pregnancy, maternal marital status, parity, and maternal smoking during pregnancy. The prevalence of adult ADHD was 4.4% and 4.5% in the 1982 and 1993 cohorts, respectively. The prevalence of ADHD was higher in those born with lower weight, but no linear trend was observed, and those born with weight between 3,000 and 3,499 grams (PR = 1.40; 95%CI: 1.05-1.86) had the highest risk. For gestational age, we observed an inversely proportional relationship for the presence of ADHD: preterm infants had a 33% higher risk (95%CI: 0.90-1.96) of being considered as having ADHD than those born at 39 or more weeks, but as the confidence interval included nullity, this association may have occurred at random. These results indicate that birth weight and gestational age may be associated with adult ADHD.

Este artigo avaliou a associação das condições de nascimento com o transtorno do déficit de atenção com hiperatividade (TDAH) em adultos utilizando dados de duas coorte de nascimento da cidade de Pelotas, Rio Grande do Sul, Brasil. Em 1982 e 1993, todos os nascimentos ocorridos na cidade foram identificados e prospectivamente acompanhados. Nos acompanhamentos aos 30 e 22 anos das coortes 1982 (n = 3.574) e 1993 (n = 3.780), respectivamente, os participantes foram examinados e psicólogos treinados aplicaram a Mini-International Neuropsychiatric Interview (M.I.N.I.). Aqueles indivíduos que preencheram os critérios diagnósticos do Manual Diagnóstico e Estatístico de Transtornos Mentais (DSM-5) foram definidos como positivos para TDAH. A regressão de Poisson com ajuste robusto da variância foi usada para estimar a razão de prevalência (RP) ajustadas para sexo, cor da pele materna, renda familiar, idade materna, escolaridade materna durante a gestação, estado civil materno, paridade e tabagismo materno durante a gestação. A prevalência do TDAH adulto foi de 4,4% e 4,5% nas coortes de 1982 e 1993, respectivamente. A prevalência de TDAH foi maior naqueles que nasceram com menor peso, mas não foi observada tendencia linear. Além disso, aqueles que nasceram com peso entre 3.000 e 3.499 gramas (g) (RP = 1,40, IC95%: 1,05-1,86) apresentaram maior risco para o transtorno. Para a idade gestacional, observamos uma relação inversamente proporcional acerca da presença de TDAH, os pré-termos apresentaram risco 33% maior (IC95%: 0,90-1,96) de ser considerado com TDAH do que os nascidos com 39 ou mais semanas, mas como o intervalo de confiança incluiu a nulidade, essa associação pode ter ocorrido ao acaso. Tais resultados indicam que o peso ao nascer e a idade gestacional podem estar associados ao TDAH adulto.

El presente estudio evaluó la asociación de las condiciones de nacimiento con el trastorno por déficit de atención con hiperactividad (TDAH) en adultos utilizando datos de dos cohortes de nacimiento de la ciudad de Pelotas. En 1982 y 1993 se identificaron todos los nacimientos de la ciudad y se les ha hecho un seguimiento prospectivo. En los seguimientos a los 30 y 22 años de las cohortes de 1982 (n = 3.574) y 1993 (n = 3.780), respectivamente, los participantes fueron examinados y psicólogos capacitados aplicaron la Mini-International Neuropsychiatric Interview (M.I.N.I.). Aquellas personas que cumplieron con los criterios de diagnóstico del Manual Diagnóstico y Estadístico de los Trastornos Mentales (DSM-5) se definieron como positivos para TDAH. Se utilizó la regresión de Poisson con ajuste robusto de la varianza para estimar la razón de prevalencia (RP) ajustada por sexo, color de piel materna, ingreso familiar, edad materna, educación materna en la gestación, estado civil materno, paridad y tabaquismo materno en la gestación. La prevalencia del TDAH en adultos fue de 4,4% y 4,5 %, en las cohortes de 1982 y 1993, respectivamente. La prevalencia de TDAH fue mayor en aquellos que nacieron con menor peso, pero no se observó una tendencia lineal, y aquellos que nacieron con peso entre 3.000 y 3.499 gramos (RP = 1,40; IC95%: 1,05-1,86) presentaron el mayor riesgo. Para la edad gestacional, se observó una relación inversamente proporcional para la presencia de TDAH, los niños prematuros presentaron un 33 % más de riesgo (IC95 %: 0,90-1,96), de ser considerado como teniendo TDAH que los nacidos con 39 o más semanas, pero como el intervalo de confianza incluyó la nulidad, esa asociación puede haber ocurrido al azar. Tales resultados indican que el peso al nacer y la edad gestacional pueden estar asociados con el TDAH en adultos.

Childhood attention-deficit hyperactivity disorder problems and mid-life cardiovascular risk: prospective population cohort study.

BACKGROUND: It is well-known that childhood attention-deficit hyperactivity disorder (ADHD) is associated with later adverse mental health and social outcomes. Patient-based studies suggest that ADHD may be associated with later cardiovascular disease (CVD) but the focus of preventive interventions is unclear. It is unknown whether ADHD leads to established cardiovascular risk factors because so few cohort studies measure ADHD and also follow up to an age where CVD risk is evident. AIMS: To examine associations between childhood ADHD problems and directly measured CVD risk factors at ages 44/45 years in a UK population-based cohort study (National Child Development Study) of individuals born in 1958. METHOD: Childhood ADHD problems were defined by elevated ratings on both the parent Rutter A scale and a teacher-rated questionnaire at age 7 years. Outcomes were known cardiovascular risk factors (blood pressure, lipid measurements, body mass index and smoking) at the age 44/45 biomedical assessment. RESULTS: Of the 8016 individuals assessed both during childhood and at the biomedical assessment 3.0% were categorised as having childhood ADHD problems. ADHD problems were associated with higher body mass index (B = 0.92 kg/m2, s.d. = 0.27-1.56), systolic (3.5 mmHg, s.d. = 1.4-5.6) and diastolic (2.2 mmHg, s.d. = 0.8-3.6) blood pressure, triglyceride levels (0.24 mol/l, s.d. = 0.02-0.46) and being a current smoker (odds ratio OR = 1.6, s.d. = 1.2-2.1) but not with LDL cholesterol. CONCLUSIONS: Childhood ADHD problems predicted multiple cardiovascular risk factors by mid-life. These findings, when taken together with previously observed associations with cardiovascular disease in registries, suggest that individuals with ADHD could benefit from cardiovascular risk monitoring, given these risk factors are modifiable with timely intervention.

Grazing Is Associated with ADHD Symptoms, Substance Use, and Impulsivity in a Representative Sample of a Large Metropolitan Area in Brazil.

Grazing is a clinically relevant eating behaviour, especially when it presents with a sense of loss of control (compulsive grazing). There is evidence that other disordered eating patterns are associated with problematic substance use and impulsivity-related conditions, such as attention-deficit/hyperactivity disorder (ADHD). This overlap contributes to higher psychopathology and treatment complications. Less is known about grazing, and most information originates in high-income countries. Hence, we sought to investigate relationships between grazing, tobacco and alcohol use, ADHD, and impulsivity in a large representative sample from Brazil. Data were collected by trained interviewers from adults (N = 2297) through an in-person household survey based on a stratified and clustered probability sample. We found significant associations between compulsive grazing and problematic alcohol use (OR = 3.02, 95% CI: 1.65, 5.53), ADHD (OR = 8.94, 95% CI: 5.11, 15.63), and smoking (OR = 1.67, 95% CI: 1.12, 2.47), with impulsivity contributing to the first two relationships. The substantial association with ADHD suggests that other executive functions may promote disordered eating, possibly expressed through difficulties in adhering to regular meals. Clinically, these findings highlight the importance of assessing problematic eating patterns, such as compulsive grazing, in those presenting with difficulties with substance use or impulsivity, and vice versa.