Attention-deficit/hyperactivity Disorder Factors Research Articles

Characterizing the metabolomic signature of attention-deficit hyperactivity disorder in twins

Emerging evidence implicate the gut microbiota as a potential susceptibility factor in attention-deficit hyperactivity disorder (ADHD), a common multifactorial neurodevelopmental condition. However, little is known about the biochemical signature of ADHD, including the metabolic contribution of the microbiota via the gut-brain axis, and the relative contribution of genetics and environmental factors. Here, we perform unbiased metabolomic profiling of urine and fecal samples collected from a well-characterized Swedish twin cohort enriched for ADHD (33 ADHD, 79 non-ADHD), using 1H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. Our results highlight sex-specific patterns in the metabolic phenotype of individuals with ADHD. Specifically, the urine profile of males, but not females, with ADHD was characterized by greater excretion of hippurate, a product of microbial-host co-metabolism that can cross the blood-brain-barrier with bioactivity of potential relevance to ADHD. This trans-genomic metabolite was also negatively correlated with IQ in males and was significantly correlated with fecal metabolites associated with gut microbial metabolism. The fecal profile of ADHD individuals was characterized by increased excretion of stearoyl-linoleoyl-glycerol, 3,7-dimethylurate, and FAD and lower amounts of glycerol 3-phosphate, thymine, 2(1H)-quinolinone, aspartate, xanthine, hypoxanthine, and orotate. These changes were independent of ADHD medication, age, and BMI. Furthermore, our specific twins’ models revealed that many of these gut metabolites had a stronger genetic influence than environmental. These findings suggest that metabolic disturbances in ADHD, involving combined gut microbial and host metabolic processes, may largely derive from gene variants previously linked to behavioral symptoms in this disorder.This article is part of the Special Issue on “Microbiome & the Brain: Mechanisms & Maladies”.

Prevalence and Risk Factors of Attention Deficit-Hyperactivity Disorder in the Saudi Population: A Systematic Review and Meta-analysis.

To determine the prevalence and risk factors of attention deficit hyperactivity disorder (ADHD) in Saudi Arabia. Observational studies (case-control, cohort, and cross-sectional) that reported the prevalence and risk factors of ADHD among Saudis and were published in English were included. In March 2022, a computerized search was conducted on Medline (via PubMed), Web of Science, and Scopus using keywords associated with ADHD and Saudi Arabia. Two-stage screening and data extraction were performed. The National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-sectional studies was used for the quality assessment. A random-effects model was used to estimate the prevalence. The Comprehensive Meta-analysis program was used for the analysis. Fourteen studies (N = 455,334 patients) were included. The pooled prevalence of ADHD in the Saudi population was 12.4% (95% CI: 5.4%-26%). For ADHD-Inattentive and ADHD-Hyperactive presentations, the prevalence was 2.9% (95% CI: 0.3%-23.3%) and 2.5% (95% CI: 0.2%-20.5%), respectively. Regarding the combined AD and HD, the prevalence was 2.5% (95% CI: 0.2%-20.5%). Children of women with psychological disorders during pregnancy (P = 0.043), insufficient vitamin B during pregnancy (P = 0.006), allergic reactions (P = 0.032), and disabling symptoms of muscle pain during pregnancy (P = 0.045) were associated with an increased risk of ADHD. The prevalence of ADHD in the Saudi population is comparable with that in other countries from the Middle East and North Africa region. Careful monitoring of pregnant women, attention to nutritional sufficiency, psychological and emotional support, and avoidance of stressful events may lead to reducing the incidence of ADHD in the offspring. None. PROSPERO (Ref no.: CRD42023390040).

Prenatal, Perinatal, and Other Risk Factors of Attention-Deficit Hyperactivity Disorder in Soerojo Hospital

Prenatal, Perinatal, and Other Risk Factors of Attention-Deficit Hyperactivity Disorder in Soerojo Hospital

Risk of attention-deficit hyperactivity disorder in offspring of mothers with infections during pregnancy.

Maternal infections during pregnancy are common events that have been suggested to be risk factors for Attention-deficit hyperactivity disorder (ADHD) in offspring. Only a few studies have been conducted to date and results are conflicting. The current study investigates the associations between specific groups of prenatal maternal infections and offspring ADHD, considering timing of exposure and the role of fever. We used data from the prospective Norwegian Mother, Father and Child Cohort Study (MoBa), including more than 112,000 pregnancies, linked with data from the Medical Birth Registry of Norway and the Norwegian Patient Registry to estimate odds ratios for the likelihood that children develop ADHD after being exposed to maternal infections during gestation. Children exposed to any maternal infection during pregnancy showed increased risk of receiving an ADHD diagnosis (OR=1.15, CI=1.03-1.27). Specifically, increased ADHD risk was observed after exposure to genitourinary infections in second (OR=1.42, CI=1.06-1.90) or third trimester (OR=2.04, CI=1.19-3.49), and to respiratory infections in second trimester (OR=1.31, CI=1.12-1.54), provided these infections were accompanied by episodes of fever. Increased ADHD risk was also observed after exposure to diarrhea without fever in the third trimester (OR=1.25, CI=1.07-1.46). Overall, our results suggest that prenatal exposure to maternal infections, particularly with co-occurring episodes of fever, are risk factors for ADHD. Fever (or severity of the infection) appears to be more important in mid-pregnancy associations. Our results indicate that type of infection and timing of exposure might influence the associations, but small effect sizes require careful interpretations. The association between infection and ADHD should be estimated using discordant siblings or other negative control designs that give better adjustment for unmeasured familial confounding.

Prevalence and Associated Factors of Attention-Deficit Hyperactivity Disorder among Children Aged 6-17 Years in North Eastern Ethiopia.

Attention-deficit hyperactivity disorder is one of the public neurodevelopmental disorders characterized by impulsivity and restlessness or hyperactivity. This study aimed to assess the prevalence of Attention-deficit hyperactivity disorder and its associated factors among children aged 6 to 17 years in Shewa Robit town, Northeastern Ethiopia, 2020. A community-based cross-sectional study was conducted among 365 children aged 6-17 years from Feb 1-March 30, 2020, at Shewa Robit town. Systematic random sampling was employed to select study participants. Data were collected by interview using structured and pretested questionnaires. Finally, data was entered using Epi-data 4.2 and analyzed using SPSS version 25. Bivariable and multivariable binary logistic regression analysis was conducted to identify associated factors of attention deficit hyperactivity disorder. Odds ratios with 95% CI were calculated, and variables having a p-value < 0.05 were considered statistically significant. The prevalence of ADHD among children aged 6 to 17 years was 13%. Financial crises [AOR 4.76(95% CI 1.51-15.05)], children a previous history of the mental problem [AOR 8.45(95% CI 1.24-57.43)], C/S delivery [AOR 6.38(95% CI 1.26-32.26)] and substance use in life [AOR 2.43(95% CI 1.09-5.43)] were significantly associated with attention deficit hyperactivity disorder. The prevalence of ADHD in children 6 to 17 years old was high (13%). Financial crises, children's history of mental disorders, C/S delivery, and lifetime substance use were significantly associated with attention deficit hyperactivity disorder. Therefore, particular attention should be given to mothers and children with significant factors.

Maternal Thyroid Anomalies and Attention-Deficit Hyperactivity Disorder in Progeny.

Previous epidemiologic investigations suggested that maternal thyroid anomalies are a possible causal factor in attention-deficit hyperactivity disorder (ADHD) in progeny, yet clinical trials indicated that levothyroxine treatment was ineffective in preventing neurodevelopmental impairments. We used an Israeli cohort of 385,542 singleton births from 1999-2012 to explore the interrelated roles of maternal thyroid conditions, laboratory gestational thyroid hormone measurements, use of thyroid medications, and offspring ADHD. Analyses were performed using Cox proportional hazards models. Results indicated that maternal hypothyroidism diagnosis was associated with an elevated progeny ADHD hazard (adjusted hazard ratio= 1.14, 95% confidence interval= 1.10, 1.18). However, this association was unmitigated by gestational use of levothyroxine and was unexplained by maternal gestational thyroid hormone levels. Associations with gestational thyrotropin values and hypothyroxinemia were also observed but were robust only in mothers without other records indicative of a thyroid problem. Results indicated that maternal thyroid hypofunction was associated with progeny ADHD but possibly not due to a direct causal relationship. Instead, maternal thyroid hypofunction may serve as a proxy indicator for other factors that affect neurodevelopment through thyroid hormone independent pathways, which are thus unaffected by pharmaceutical treatments for thyroid hypofunction. Factors known to disrupt thyroid functioning should be examined for their independent ADHD-related effects.

Increased prevalence of inattention-related symptoms in a large cohort of patients with congenital heart disease.

The objective of this study is to assess the prevalence and risk factors for attention-deficit hyperactivity disorder (ADHD) in a large cohort of patients with congenital heart disease (CHD). Patients (n = 695) with CHD who were aged 6-15years and visited the outpatient clinics in our hospital from June 2015 to May 2017 were enrolled. Their medical records were collected, and the Chinese version of the Swanson, Nolan, and Pelham rating scale (SNAP-IVc) and a questionnaire about neuropsychiatric care-seeking behavior were completed by parents and counselors. Of the 695 patients, the overall prevalence of ADHD was 12.4%, including 3.2% for the combined subtype, 6.8% for the inattentive-predominant subtype, and 2.4% for the hyperactivity/impulsive-predominant subtype. Only the inattention-predominant subtype was significantly more prevalent than in the general population. The prevalence of the inattention-predominant subtype was highest in the patients with cyanotic CHD, high severity index, and in those who had received surgery or cardiopulmonary bypass. Multivariate regression analysis indicated that the risk factors for inattention-related symptoms included postoperative seizure and previous cardiopulmonary bypass (odds ratio: 3.22 and 3.82; P = 0.027 and < 0.001, respectively). Only 58.7% of the patients with probable ADHD ever sought neuropsychiatric care, and only 27% regularly attended neuropsychiatric clinics. The inattention-predominant subtype of ADHD was more prevalent in our CHD patients, especially in those with cyanotic CHD, higher disease severity index, and in those who had undergone a surgical intervention. The percentage of patients receiving regular neuropsychiatric clinic follow-up was low.

Exposure to green spaces as a modifiable risk factor in attention-deficit hyperactivity disorder

Exposure to green spaces as a modifiable risk factor in attention-deficit hyperactivity disorder

Nutritional and environmental factors in attention-deficit hyperactivity disorder (ADHD): A cross-sectional study

Objectives: Attention-deficit hyperactivity disorder (ADHD) has been related to nutrient deficiencies and ‘unhealthy’ diets, and to date there is only one study that examined the relationship between the Mediterranean diet and ADHD. The aim was to determine the association between those environmental, nutritional, and body composition factors that may affect the pathogenesis and symptomatology of patients with ADHD in Spain.Methods: A total of 89 children and adolescents (41 with diagnosed ADHD and 48 controls) were studied in an observation case–control study. Anthropometry, nutritional status, adherence to a Mediterranean diet, sedentary behaviour, and sleep were measured.Results: Lower adherence to a Mediterranean diet was associated with ADHD diagnosis. Individuals with ADHD more often missed having a second serving of vegetables daily and showed reduced intakes of fish, pulses, and pasta or rice almost every day when compared with controls. Statistically significant differences (P < 0.05) were found for fish, cereal, no breakfast and commercially baked goods consumption. There were also statistically significant differences between ADHD individuals and controls when analysing sedentary behaviours and BMI (P < 0.05).Conclusion: Low adherence to a Mediterranean diet might play a role in ADHD development. Not only specific nutrients but also the whole diet should be considered in ADHD. No clear association was found for anthropometry and sedentary behaviours.

주의력결핍 과잉행동장애의 산전 및 주산기 위험인자

Objectives : The purpose of this study was to examine the prenatal, perinatal and developmental risk factors of attention-deficit hyperactivity disorder (ADHD), compared to unaffected siblings (SIB), and typically developing children (TC). Methods : Subjects with ADHD, their SIB, and TC were recruited from the child psychiatry outpatient clinic of the Asan Medical Center Children's Hospital. The parents of the children completed questionnaires on perinatal and developmental risk factors. Results : Fifty-eight subjects with ADHD (41 boys, <TEX>$7.7{\pm}1.3years$</TEX>), 21 SIB (8 boys, <TEX>$8.2{\pm}1.8years$</TEX>), and 22 TC (8 boys, <TEX>$8.5{\pm}2.1years$</TEX>) were included. The ADHD group showed higher rates of maternal stress during pregnancy than the SIB group (p=.002), and the ADHD group showed higher rates of familial psychiatric history than the TC (odds ratio, 8.76 ; 95% confidence interval, 1.69 to 45.45). Conclusion : These findings suggest that among perinatal and developmental factors, maternal stress during pregnancy contribute to the development of ADHD. Future prospective studies will be needed in order to determine the causal relationship between perinatal risk factors and development of ADHD.

The influence of low level pre- and perinatal exposure to PCDD/Fs, PCBs, and lead on attention performance and attention-related behavior among German school-aged children: results from the Duisburg Birth Cohort Study.

Prenatal exposure to polychlorinated biphenyls (PCBs) and lead are thought to be risk factors for attention-deficit hyperactivity disorder (ADHD), whereas the prenatal influence of polychlorinated dibenzo-p-dioxins and -furans (PCDD/Fs) on attention performance has been less studied. Within the Duisburg Birth Cohort Study, we investigated low-level exposure to these compounds in relation to children's attention. We measured blood levels of PCDD/Fs, PCBs and lead from pregnant mothers (32(nd) week of pregnancy) and PCDD/Fs and PCBs in breast milk (2 weeks after delivery). The attention of school-aged children (N=117) was investigated with a computer-based test battery of attention performance (KITAP) and a parent rating questionnaire of behaviors related to ADHD (FBB-ADHS). Influences of the exposure on attention were analyzed by multiple regression analyses. Increasing prenatal PCDD/F and PCB concentrations were significantly (p<0.05) associated with a higher number of omission errors in the subtest Divided Attention (47% and 42%; 95% confidence intervals (95%-CI): 1.08-2.00 and 1.07-1.89, respectively). Prenatal lead concentrations had few significant associations with attention performance (e.g., a 23% higher number of omission errors in the subtest Distractibility; 95%-CI: 1.00-1.51), whereas ADHD-related behavior (questionnaire based) was increased with increasing lead exposure (Overall-ADHD: 9%; 95%-CI: 1.01-1.17). ADHD-related behavior was negatively associated with prenatal PCDD/F or PCB exposures (e.g., for PCB exposure: -10%; 95%-CI: 0.82-0.99). Pre- and perinatal PCDD/F and PCB exposure may have subtle influences on attention performance in healthy children at low environmental levels, while behavior changes are negatively associated. Furthermore, we provide additional evidence for the impact of prenatal lead exposure on attention deficits.

구조적 면담으로 ADHD로 진단받은 아동의 주산기 요인 및 발달력상 위험인자

Objectives:The objective of this study was to examine the perinatal and developmental risk factors of attention-deficit hyperactivity disorder (ADHD) diagnosed with a structured interview among Korean children. Methods:The current study included 924 children (6-15 years) recruited from schools in five Korean cities or a child psychiatry outpatient clinic of Seoul National University Children's Hospital. The parents of the children completed the structured diagnostic interview for attention-deficit hyperactivity disorder, as well as questionnaires on perinatal and developmental risk factors. Results:Preterm delivery, severe maternal stress during pregnancy, change in primary care taker during the first three years, postpartum depression, and delayed first sentence showed a significant association with ADHD diagnosis. Conclusion:These findings suggest that perinatal and developmental factors contribute to development of ADHD in Korean children. Conduct of future research using a prospective design is needed in order to identify the causal relationship between observed risk factors and development of ADHD.

The role of iron deficiency in children with attention deficit/hpyperactivity disorder

Objective: Attention Deficit-Hyperactivity Disorder is a common neurobiological syndrome of the childhood. Iron deficiency is suggested to be an etiologic factor of Attention Deficit-Hyperactivity Disorder because of its role in the dopamine metabolism. The objective of this study is to evaluate iron deficiency in patients with Attention Deficit-Hyperactivity Disorder in comparison with healty children and to predict the severity of the symptoms on admission with reference to serum ferritin levels. Methods: Fifty children with Attention DeficitHyperactivity Disorder and fifty age and sex-matched control subjects were evaluated. Ferritin levels in both groups and their relationship with DSM-4 score were investigated. Results: The mean serum ferritin level in the patient group was 27±13.2 ng/ml which was significantly lower than the control group with a mean value of 41±26 ng/ml. In Attention Deficit-Hyperactivity Disorder group, serum ferritin levels did not correlate with the score of the disease described in DSM-4 (r=0.09; p>0.05). Conclusion: In conclusion, iron deficiency is an etiologic factor in Attention DeficitHyperactivity Disorder but the severity of the symptoms on admission did not correlate with serum ferritin levels.

Parental and Family Factors for Attention-deficit Hyperactivity Disorder in Taiwanese Children

The present study aimed to examine the association between attention-deficit-hyperactivity disorder (ADHD) and maternal psychological distress, parenting style and perceived family support, and the child's interaction with parents and behavioural problems at home in Taiwan. The sample included 375 medicated pediatric patients with DSM-IV ADHD, and 750 school controls selected based on the age and gender structures of the ADHD group. Mothers reported on the Chinese Health Questionnaire, the Chinese versions of the Parental Bonding Instrument, the Family Adaptation, Partnership, Growth, Affection, and Resolve, and the Home Behaviours of the Social Adjustment Inventory for Children and Adolescents. Mothers of children with ADHD reported greater psychological distress and perceived less support from their families than did mothers of controls. Moreover, mothers of children with ADHD were less affectionate and more overprotective and controlling toward their children than were mothers of controls. This difference was more apparent in boys than in girls. Children with ADHD were less likely to interact with their parents, yet demonstrated more severe behavioural problems at home. Although the Taiwanese children with ADHD were under treatment with methylphenidate, they and their families still encountered a variety of difficulties in interaction, support, and communication with each other. Therefore, the parental approach should be integrated into the medication treatment for ADHD in Taiwan.

The SNAP25 gene as a susceptibility gene contributing to attention-deficit hyperactivity disorder

The synaptosomal-associated protein of 25 kDa gene (SNAP25) has been suggested as a genetic susceptibility factor in attention-deficit hyperactivity disorder (ADHD) based on the mouse strain coloboma. This strain is hemizygous for the SNAP25 gene and displays hyperactivity that responds to dextroamphetamine, but not to methylphenidate. Previously, we reported association of SNAP25 and ADHD using two polymorphisms. To further investigate this gene, we screened the exons for DNA variation and genotyped ten additional polymorphisms in an expanded sample of families from Toronto and a second sample of families collected in Irvine, CA. Significant results were observed in the Toronto sample for four markers, although not in the Irvine sample. The paper discusses the possible influence of the selection criteria on these differential results. The Irvine sample selected subjects that met the DSM-IV combined subtype diagnosis, whereas the Toronto sample included all subtypes. Analysis of the DSM-IV subtypes in the Toronto sample indicated that the differential results were not attributable to ADHD subtype. Differences in ethnicity, differential medication response, and other clinical characteristics of the samples cannot be ruled out at this time. Quantitative analysis of the dimensions of hyperactivity/impulsivity and inattention in the Toronto sample found that both behavioral traits were associated with SNAP25. Our findings continue to support SNAP25 in the susceptibility to ADHD.

Studying the epidemiology of attention-deficit hyperactivity disorder: screening method and pilot results.

As part of a larger epidemiologic study of risk factors for attention-deficit hyperactivity disorder (ADHD), this pilot study combined parent and teacher information to estimate ADHD prevalence among elementary school children in a North Carolina county. The methods developed for this study and the pitfalls we encountered illustrate the challenges involved in conducting population-based studies of ADHD. We employed 2-stage screening using DSM-IV criteria. Teachers completed behaviour-rating scales for all children. We then administered a structured telephone interview to parents of potential cases. We screened 362 of 424 (85%) children in grades 1 to 5 in 4 schools. According to parent reports, 43 children (12%) had previously been diagnosed with ADHD by a health professional. Thirty-four children (9%) were taking ADHD medication. Forty-six children (12.7%) met study case criteria for ADHD, based on combined teacher and parent reports. Of the 46 cases, 18 (39%) had not been previously identified. Eight previously diagnosed children, however, did not meet case criteria. After we adjusted for nonresponse, the estimated prevalence was 16% (95%CI, 12% to 20%). These data suggest that the DSM-IV prevalence of ADHD has been substantially underestimated, although the true prevalence in this population may be less than the 16% estimated here. Population-based studies of ADHD are feasible and may provide important information about practice and treatment patterns in community settings, as well as a broader understanding of the etiology and life course of this common disorder.

Pregnancy, delivery and infancy complications (PDICs) as risk factors of attention-deficit hyperactivity disorder (ADHD), a specific comparison with child psychiatric controls

Pregnancy, delivery and infancy complications (PDICs) as risk factors of attention-deficit hyperactivity disorder (ADHD), a specific comparison with child psychiatric controls

Not in Their Genes: A Critical View of the Genetics of Attention-Deficit Hyperactivity Disorder

This article examines evidence cited in favor of the operation of genetic factors in attention-deficit hyperactivity disorder (ADHD). Like other psychiatric conditions, a belief in the genetic basis of ADHD is derived from the results of family, twin, and adoption studies. Because family studies are widely believed to be confounded by environmental factors, primary emphasis is placed on twin and adoption studies. ADHD twin studies depend on the validity of the equal environment assumption (EEA), which holds that the environments of identical (MZ) and fraternal (DZ) twins are the same. Here it is argued that however the EEA is defined, it cannot be accepted. Therefore, the greater similarity or concordance of MZ twins when compared to DZ twins is plausibly explained by environmental factors. Adoption studies constitute a third method for investigating the role of genetic factors in ADHD. It is argued that these studies are greatly flawed by factors including non blinded diagnoses and the failure to study the biological relatives of adoptees. After an examination of the total weight of evidence in favor of a genetic basis or predisposition for ADHD, it is concluded that a role for genetic factors is not supported and that future research should be directed toward psychosocial causes

Impact of Adversity on Functioning and Comorbidity in Children with Attention-Deficit Hyperactivity Disorder

Prior research on risk factors for attention-deficit hyperactivity disorder (ADHD) has shown that familial risk factors play a role in the disorder's etiology. This study investigated whether features of the family environment were associated with ADHD. One hundred forty children with ADHD and 120 normal control probands were studied. Subjects were Caucasian, non-Hispanic males between the ages of 6 and 17 years. Exposure to parental psychopathology and exposure to parental conflict were used as indicators of adversity, and their impact on ADHD and ADHD-related psychopathology and dysfunction in children was assessed. Increased levels of environmental adversity were found among ADHD compared with control probands. The analyses showed significant associations between the index of parental conflict and several of the measures of psychopathology and psychosocial functioning in the children. In contrast, the index of exposure to parental psychopathology had a much narrower impact, affecting primarily the child's use of leisure time and externalizing symptoms. A relationship appears to exist between adversity indicators and the risk for ADHD as well as for its associated impairments in multiple domains. These findings confirm previous work and stress the importance of adverse family-environment variables as risk factors for children who have ADHD.

Effects of presentation rate of stimuli on response inhibition in ADHD children with and without tics.

Presentation rate of stimuli is a crucial factor in Attention-deficit Hyperactivity Disorder (ADHD), that is, especially in ADHD children without tics ( n = 24), the ability to inhibit a response decreases in conditions with fast and slow presentation rates of stimuli.