Do maternal anxiety and depressive symptoms predict anxiety in children with and without ADHD at 8 years?

Maternal anxiety and depression during pregnancy and early childhood have been associated with child anxiety and attention-deficit/hyperactivity disorder (ADHD). However, previous studies are limited by their short follow-up, few assessments of maternal symptoms, and by not including maternal and child ADHD. The present study aimed to fill these gaps by investigating whether maternal anxiety and depressive symptoms from pregnancy to child age 5 years increase the risk of child anxiety disorders at age 8 years. This study is part of the population-based Norwegian Mother, Father, and Child Cohort Study. Maternal anxiety and depressive symptoms were assessed by the Hopkins Symptom Checklist (SCL) six times from pregnancy through early childhood, and ADHD symptoms by the Adult Self-Report Scale (ASRS). At age 8 years (n = 781), symptoms of anxiety disorders and ADHD were assessed, and disorders classified by the Child Symptom Inventory-4. Logistic regression models estimated the risk of child anxiety depending on maternal symptoms. The mothers of children classified with an anxiety disorder (n = 91) scored significantly higher on the SCL (at all time points) and ASRS compared with the other mothers. In univariable analyses, maternal anxiety and/or depression and ADHD were associated with increased risk of child anxiety (odds ratios = 2.99 and 3.64, respectively), remaining significant in the multivariable analysis adjusted for covariates. Our findings link maternal anxiety, depression, and ADHD during pregnancy and early childhood to child anxiety at age 8 years.

Executive function in children with disruptive mood dysregulation disorder compared to attention-deficit/hyperactivity disorder and oppositional defiant disorder, and in children with different irritability levels.

Addressing current challenges in research on disruptive mood dysregulation disorder (DMDD), this study aims to compare executive function in children with DMDD, children with attention-deficit/hyperactivity disorder (ADHD), and children with oppositional defiant disorder (ODD). We also explore associations between irritability, a key DMDD characteristic, and executive function in a clinical sample regardless of diagnosis. Our sample include children (6-12 years) referred to child psychiatric clinics. Measures of daily-life (parent-reported questionnaire) and performance-based (neuropsychological tasks) executive function were applied. Identifying diagnoses, clinicians administered a standardized semi-structured diagnostic interview with parents. Irritability was assessed by parent-report. First, we compared executive function in DMDD (without ADHD/ODD), ADHD (without DMDD/ODD), ODD (without DMDD/ADHD) and DMDD + ADHD (without ODD). Second, we analyzed associations between executive function and irritability using the total sample. In daily life, children with DMDD showed clinically elevated and significantly worse emotion control scores compared to children with ADHD, and clinically elevated scores on cognitive flexibility compared to norm scores. Children with DMDD had significantly less working memory problems than those with ADHD. No differences were found between DMDD and ODD. Increased irritability was positively associated with emotional dyscontrol and cognitive inflexibility. For performance-based executive function, no diagnostic differences or associations with irritability were observed. We discuss how, in daily life, children with high irritability-levels get overwhelmed by feelings without accompanying regulatory capacities.

Neuropsychological mechanisms of social difficulties in disruptive mood dysregulation disorder versus oppositional defiant disorder.

Children with Disruptive Mood Dysregulation Disorder (DMDD) or Oppositional Defiant Disorder (ODD) are characterized by irritability and social difficulties. However, the mechanisms underlying these disorders could be different. This study explores differences in social cognition and executive function (EF) across DMDD and ODD and the influence of these factors and their interaction on social problems in both groups. Children with DMDD (n = 53, Mage = 9.3) or ODD (n = 39, Mage = 9.6) completed neuropsychological tasks measuring social cognition (Theory of Mind and Face-Emotion Recognition) and EF (cognitive flexibility, inhibition, and working memory). Parents reported social problems. More than one-third of the children with DMDD and almost two-thirds of those with ODD showed clear difficulties with Theory of Mind. Most children with DMDD (51-64%) or ODD (67-83%) showed difficulties with EF. In children with DMDD, worse EF (ß = -.36) was associated with more social problems, whereas in children with ODD, better EF (ß = .44) was associated with more social problems. In those with ODD, but not in those with DMDD, the interaction between social cognition and EF contributed to the explained variance of social problems (ß = -1.97). Based on the observed interaction pattern, enhanced EF may lead to increased social problems among children with ODD who also exhibit social cognition difficulties. This study suggests the existence of distinct neuropsychological mechanisms underlying the social issues observed in children with DMDD versus those with ODD.

Disruptive Mood Dysregulation Disorder in a Norwegian Clinical Child Population.

BACKGROUND: Disruptive Mood Dysregulation Disorder was included in DSM-5 to accommodate new research addressing aspects of emotional dysregulation in children suffering from disruptive behavior problems. Despite growing interest in Disruptive Mood Dysregulation Disorder, few studies have looked at prevalence rates in European clinical populations. The primary objective of this study was to examine the prevalence and characteristics associated with Disruptive Mood Dysregulation Disorder in a Norwegian clinical sample. METHODS: The present study assessed children 6-12 years of age referred to a mental health clinic for evaluation and treatment (N = 218, Mage = 9.6, 60.4% boys) and compared those who did and did not meet Disruptive Mood Dysregulation Disorder diagnostic criteria. Diagnoses were determined using K-SADS-PL 2013. Associated difficulties at home and in school were measured by Achenbach Systems of Empirically Based Assessment battery. RESULTS: In this clinical sample, 24% met the diagnostic criteria for Disruptive Mood Dysregulation Disorder. Children with Disruptive Mood Dysregulation Disorder were more likely than those without Disruptive Mood Dysregulation Disorder to be male (77% vs. 55%, p = .008), be living in poverty, have multiple mental health diagnoses (79% vs. 53%, p = .001), and have lower global functioning levels as measured by Children's Global Assessment Scale (range 0-100, M = 47, SD = 8.5 vs. M = 57, SD = 11.4, p=<.001). Finally, parents and teachers of children with Disruptive Mood Dysregulation Disorder reported lower overall competence and adaptive functioning, and higher total symptom load than children with other diagnoses. CONCLUSION: Disruptive Mood Dysregulation Disorder is highly prevalent in a Norwegian clinical sample and displays a high symptom load. Our results are in accordance with similar studies. Consistent findings across the world may support Disruptive Mood Dysregulation Disorder as a valid diagnostic category.

Sub-threshold or full-syndrome borderline personality disorder in adolescents with recurrent self-harm - distinctly or dimensionally different?

BACKGROUND: Borderline personality disorder (BPD) is a severe mental disorder frequently seen in individuals with recurrent self-harm behaviour. To what extent there are distinguishing characteristics between self-harming adolescents who meet the criteria for a full diagnosis of BPD, a sub-threshold number of BPD criteria and those who don't have BPD, with respect to clinical characteristics, is still uncertain and could have important clinical implications. METHODS: Data from 103 adolescents with recurrent self-harm behaviour recruited from child and adolescent psychiatric outpatient clinics were collected through clinical interviews and self-reports. Bivariate analyses comparing participants with or without a diagnosis of BPD were performed. Group differences based on the number of BPD criteria fulfilled (few-if-any BPD: 0-2 criteria, sub-threshold BPD: 3-4 criteria, full-syndrome BPD: 5 or more criteria) were tested and regression analyses performed. RESULTS: Adolescents with a diagnosis of BPD (28.2%) had significantly higher numbers of co-morbid DSM-5 disorders, suicide attempts and self-harm methods. They also reported significantly higher levels of suicidal ideation, depression, anxiety and impulsivity, compared with adolescents without BPD. Adolescents with sub-threshold BPD (20.4%) place themselves in the intermediate position between participants with full-syndrome BPD and participants with few-if-any BPD, in terms of these symptoms. Higher levels of emotional regulation difficulties and a lower level of global functioning were significantly associated with fulfilling a higher number of BPD criteria. CONCLUSION: Adolescents with recurrent self-harm who meet diagnostic criteria for a full-syndrome BPD or sub-threshold BPD seem to have difficulties within the same spectrum. They seem dimensionally, but not categorically, different with respect to the severity of their difficulties. These adolescents need interventions aimed at their dysfunctional self-harm behaviour, emotional regulation difficulties and BPD symptoms at an earlier, rather than at a later stage of symptom development.

Anxiety and depression from age 3 to 8 years in children with and without ADHD symptoms.

Childhood anxiety and depressive symptoms may be influenced by symptoms of attention deficit/hyperactivity disorder (ADHD). We investigated whether parent- and teacher-reported anxiety, depressive and ADHD symptoms at age 3 years predicted anxiety disorders and/or depression in children with and without ADHD at age 8 years. This study is part of the longitudinal, population-based Norwegian Mother, Father and Child Cohort Study. Parents of 3-year-olds were interviewed, and preschool teachers rated symptoms of anxiety disorders, depression and ADHD. At age 8 years (n = 783), Child Symptom Inventory-4 was used to identify children who fulfilled the diagnostic criteria for anxiety disorders and/or depression (hereinafter: Anx/Dep), and ADHD. Univariable and multivariable logistic regression analyses were used. In the univariable analyses, parent-reported anxiety, depressive and ADHD symptoms, and teacher-reported anxiety symptoms at age 3 years all significantly predicted subsequent Anx/Dep. In the multivariable analyses, including co-occurring symptoms at age 3 years and ADHD at 8 years, parent-reported anxiety and depressive symptoms remained significant predictors of subsequent Anx/Dep. At age 3 years, regardless of ADHD symptoms being present, asking parents about anxiety and depressive symptoms, and teachers about anxiety symptoms, may be important to identify children at risk for school-age anxiety disorders and/or depression.

Early and repeated screening detects children with persistent attention-deficit/hyperactivity disorder.

Preschool screening of attention-deficit/hyperactivity disorder (ADHD) has been found too inaccurate to be clinically useful. This may be due to the known instability of ADHD symptoms from preschool onwards, and the use of a single screening only. We hypothesized that by identifying a group of children with persistent ADHD from preschool to school age and repeating the screening, the clinical usefulness of screening would increase. This study is part of the prospective longitudinal, population-based Norwegian Mother, Father and Child Cohort Study, with a diagnostic parent interview at 3.5 years and follow-up with parent questionnaires at ages 5 and 8 years (n = 707). We identified a group classified with ADHD at all three time points (persistent ADHD). We then used the Child Behavior Checklist ADHD DSM-oriented scale at ages 3.5 and 5 years to investigate the accuracies of single- and two-stage screening at different thresholds to identify children with persistent ADHD. About 30% of the children were classified with ADHD at least once across time (at ages 3.5, 5, and/or 8 years), but only 4% (n = 30) had persistent ADHD. At all thresholds, the two-stage screening identified children with persistent ADHD more accurately than single screening, mainly due to a substantial reduction in false positives. Only a small group of children were classified with persistent ADHD from preschool to school age, underlining that future screening studies should distinguish this group from those with fluctuating symptoms when estimating screening accuracies. We recommend a two-stage screening process to reduce false positives.

Excessive hair cortisol concentration as an indicator of psychological disorders in children.

Cortisol in hair is a new biomarker assessing long-term hypothalamic-pituitary-adrenal (HPA) axis activity, which is related to emotion regulation. We compare hair cortisol concentrations (HCC), in clinically referred children with disruptive mood dysregulation disorder (DMDD) (n = 19), children with other types of psychological disorders (n = 48), and healthy subjects (n = 36). We also investigate the association between HCC and irritability, age, and sex. Our results show that children with DMDD or other types of psychological disorders have higher HCC than healthy subjects, p < .001, ηp2 = .39. No difference between children with DMDD and those with other types of psychological disorders was found, p = .91, nor an association between HCC and irritability in the clinical sample, p = .32. We found a significant negative correlation between HCC and age in those with DMDD, r = -0.54, p < .05, but not in the normative sample, r = -0.20, p = .25. No differences in HCC between girls and boys were found in the normative sample, p = .49. Children in need of psychological treatment, including those with DMDD, seem to have dysregulated HPA-axis activity over time. Excessive accumulated cortisol concentrations in hair could be an indicator of a psychological disorder in children.

DSM-5 Non-Suicidal Self-Injury Disorder in a Clinical Sample of Adolescents with Recurrent Self-Harm Behavior.

INTRODUCTION: Non-suicidal self-injury disorder (NSSID) is a new diagnosis proposed in DSM-5 with a need of further study, especially in adolescent clinical populations where non-suicidal self-injury (NSSI) is particularly prevalent. We aimed to study characteristics of NSSID and estimate an optimal cutoff frequency level of NSSI behavior. METHODS: Data were collected from 103 outpatient adolescents (ages 12-18) with recurrent self-harm behavior. RESULTS: Adolescents with NSSID reported significantly more frequent NSSI behavior and suicide attempts than adolescents without NSSID. Frequency of NSSI, global functioning, depressive symptoms, number of self-harm methods and anxiety symptoms best discriminated between adolescents with and without NSSID. An optimal cutoff level for a diagnosis of NSSID was found to be ≥15 days with NSSI during the last year, which led to a reduction in the rate of adolescents diagnosed with NSSID from 54% to 46%. CONCLUSION: This study shows that NSSID is a highly impairing disorder characterized by high risk of multiple NSSI and suicide attempts, decreased functioning and other associated psychiatric disorders. Clinical awareness of these risks are important to ensure early detection and treatment. Future prospective longitudinal studies are needed to further validate the characteristics of the NSSID diagnosis and its clinical utility.

Prenatal organophosphate ester exposure and executive function in Norwegian preschoolers.

Organophosphate esters (OPEs) are ubiquitous chemicals, used as flame retardants and plasticizers. OPE usage has increased over time as a substitute for other controlled compounds. This study investigates the impact of prenatal OPE exposure on executive function (EF) in preschoolers. Methods: We selected 340 preschoolers from the Norwegian Mother, Father, and Child Cohort Study. Diphenyl-phosphate (DPhP), di-n-butyl-phosphate (DnBP), bis(2-butoxyethyl) phosphate (BBOEP), and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were measured in maternal urine. EF was measured using the Behavior Rating Inventory of Executive Functioning-Preschool (BRIEF-P) and the Stanford-Binet fifth edition (SB-5). EF scores were scaled so a higher score indicated worse performance. We estimated exposure-outcome associations and evaluated modification by child sex using linear regression. Results: Higher DnBP was associated with lower EF scores across multiple rater-based domains. Higher DPhP and BDCIPP were associated with lower SB-5 verbal working memory (ß = 0.49, 95% CI = 0.12, 0.87; ß = 0.53, 95% CI = 0.08, 1.02), and higher BBOEP was associated with lower teacher-rated inhibition (ß = 0.34, 95% CI = 0.01, 0.63). DPhP was associated with lower parent-reported BRIEF-P measures in boys but not girls [inhibition: boys: 0.37 (95% CI = 0.03, 0.93); girls: -0.48 (95% CI = -1.27, 0.19); emotional control: boys: 0.44 (95% CI = -0.13, 1.26); girls: -0.83 (95% CI = -1.73, -0.00); working memory: boys: 0.49 (95% CI = 0.03, 1.08); girls: -0.40 (95% CI = -1.11, 0.36)]. Fewer sex interactions were observed for DnBP, BBOEP, and BDCIPP, with irregular patterns observed across EF domains. Conclusions: We found some evidence prenatal OPE exposure may impact EF in preschoolers and variation in associations by sex.

Gestational thyroid hormone concentrations and risk of attention-deficit hyperactivity disorder in the Norwegian Mother, Father and Child Cohort Study.

BACKGROUND: Maternal thyroid function plays an important role in foetal brain development; however, little consensus exists regarding the relationship between normal variability in thyroid hormones and common neurodevelopmental disorders, such as attention-deficit hyperactivity disorder (ADHD). OBJECTIVE: We sought to examine the association between mid-pregnancy maternal thyroid function and risk of clinically diagnosed ADHD in offspring. METHODS: We conducted a nested case-control study in the Norwegian Mother, Father and Child Cohort Study. Among children born 2003 or later, we randomly sampled singleton ADHD cases obtained through linkage with the Norwegian Patient Registry (n = 298) and 554 controls. Concentrations of maternal triiodothyronine (T3), thyroxine (T4), T3-Uptake, thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody (TPO-Ab) were measured in maternal plasma, collected at approximately 17 weeks' gestation. Indices of free T4 (FT4i) and free T3 (FT3i) were calculated. We used multivariable adjusted logistic regression to calculate odds ratios and accounted for missing covariate data using multiple imputation. We used restricted cubic splines to assess non-linear trends and provide flexible representations. We examined effect measure modification by dietary iodine and selenium intake. In sensitivity analyses, we excluded women with clinically significant thyroid disorders (n = 73). RESULTS: High maternal T3 was associated with increased risk of ADHD (5th vs 1st quintile odds ratio  2.27, 95% confidence interval 1.21, 4.26). For FT4i, both the lowest and highest quintiles were associated with an approximate 1.6-fold increase in risk of ADHD, with similar trends found for T4. The FT4i association was modified by dietary iodine intake such that the highest risk strata were confined to the low intake group. CONCLUSIONS: Both high and low concentrations of maternal thyroid hormones, although within population reference ranges, increase the risk of ADHD in offspring. Increased susceptibility may be found among women with low dietary intake of iodine and selenium.

Gestational organophosphate ester exposure and preschool attention-deficit/hyperactivity disorder in the Norwegian Mother, Father, and Child cohort study.

BACKGROUND: Attention-deficit/hyperactivity-disorder (ADHD) is a leading neurodevelopmental disorder in children worldwide; however, few modifiable risk factors have been identified. Organophosphate esters (OPEs) are ubiquitous chemical compounds that are increasingly prevalent as a replacement for other regulated chemicals. Current research has linked OPEs to neurodevelopmental deficits. The purpose of this study was to assess gestational OPE exposure on clinically-assessed ADHD in children at age 3 years. METHODS: In this nested case-control study within the Norwegian Mother, Father, and Child Cohort study, we evaluated the impact of OPE exposure at 17 weeks' gestation on preschool-age ADHD. Between 2007 and 2011, 260 ADHD cases were identified using the Preschool Age Psychiatric Assessment and compared to a birth-year-stratified control group of 549 children. We categorized bis(2-butoxyethyl) phosphate (BBOEP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) as values < limit of detection (LOD) (BBOEP N = 386, BDCIPP N = 632), ≥LOD but < limit of quantification (LOQ) (BBOEP N = 413; BDCIPP N = 75), or above LOQ (BBOEP N = 70; BDCIPP N = 102). Diphenyl phosphate (DPhP) and di-n-butyl phosphate (DnBP) were categorized as quartiles and also modeled with a log10 linear term. We estimated multivariable adjusted odds ratios (ORs) using logistic regression and examined modification by sex using an augmented product term approach. RESULTS: Mothers in the 3rd DnBP quartile had 1.71 times the odds of having a child with ADHD compared to the 1st quartile (95%CI: 1.13, 2.58); a similar trend was observed for log10 DnBP and ADHD. Mothers with BDCIPP ≥ LOD but < LOQ had 1.39 times the odds of having a child with ADHD compared to those with BDCIPP < LOD (95%CI: 0.83, 2.31). Girls had lower odds of ADHD with increasing BBOEP exposure (log10 OR: 0.55 (95%CI: 0.37, 0.93), however boys had a weakly increased odds (log10 OR: 1.25 (95%CI: 0.74, 2.11) p-interaction = 0.01]. CONCLUSIONS: We found modest increased odds of preschool ADHD with higher DnBP and BDCIPP exposure.

Attention-deficit/hyperactivity disorder from preschool to school age: change and stability of parent and teacher reports.

Identifying attention-deficit/hyperactivity disorder (ADHD) in pre-schoolers may improve their development if treated, but it is unclear whether ADHD symptoms from this age are stable enough to merit treatment. We aimed to investigate the stability of parent- and teacher-reported ADHD symptoms and ADHD classified above the diagnostic symptom thresholds, including for hyperactivity-impulsivity (HI), inattention and combined presentations from age 3 to 8 years. This study is part of the longitudinal, population-based Norwegian Mother, Father and Child Cohort Study. At child age 3 years, parents were interviewed and teachers rated ADHD symptoms. At age 8 years, parents (n = 783) and teachers (n = 335) reported ADHD symptoms by the Child Symptom Inventory-4. We found a significant reduction in the mean number of parent-reported ADHD and HI symptoms from age 3 to 8 years, but otherwise similar mean numbers. Parent-reported ADHD symptoms were moderately correlated between ages, while correlations were low for teachers. A total of 77/108 (71%) of the children classified with parent-reported HI presentation at age 3 years were no longer classified within any ADHD presentation at age 8 years, the only clear trend across time for either informant. There was a low to moderate parent-teacher-agreement in the number of reported symptoms, and very low informant agreement for the classified ADHD presentations. Overall, clinicians should exercise caution in communicating concern about HI symptoms in preschool children. Age 3 years may be too early to apply the ADHD diagnostic symptom criteria, especially if parents and teachers are required to agree.

Organophosphorus Pesticide Exposure at 17 Weeks' Gestation and Odds of Offspring Attention-Deficit/Hyperactivity Disorder Diagnosis in the Norwegian Mother, Father, and Child Cohort Study.

Prenatal organophosphorus pesticides (OPs) are ubiquitous and have been linked to adverse neurodevelopmental outcomes. However, few studies have examined prenatal OPs in relation to diagnosed attention-deficit/hyperactivity disorder (ADHD), with only two studies exploring this relationship in a population primarily exposed through diet. In this study, we used a nested case-control study to evaluate prenatal OP exposure and ADHD diagnosis in the Norwegian Mother, Father, and Child Cohort Study (MoBa). For births that occurred between 2003 and 2008, ADHD diagnoses were obtained from linkage of MoBa participants with the Norwegian Patient Registry (N = 297), and a reference population was randomly selected from the eligible population (N = 552). Maternal urine samples were collected at 17 weeks' gestation and molar sums of diethyl phosphates (ΣDEP) and dimethyl phosphates metabolites (ΣDMP) were calculated. Multivariable adjusted logistic regression models were used to estimate the association between prenatal OP metabolite exposure and child ADHD diagnosis. Additionally, multiplicative effect measure modification (EMM) by child sex was assessed. In most cases, mothers in the second and third tertiles of ΣDMP and ΣDEP exposure had slightly lower odds of having a child with ADHD, although confidence intervals were wide and included the null. EMM by child sex was not observed for either ΣDMP or ΣDEP. In summary, we did not find evidence that OPs at 17 weeks' gestation increased the odds of ADHD in this nested case-control study of ADHD in MoBa, a population primarily experiencing dietary exposure.

Prenatal Exposure to Organophosphorus Pesticides and Preschool ADHD in the Norwegian Mother, Father and Child Cohort Study.

Prenatal organophosphorus pesticide (OPP) exposure has been associated with child attention-deficit/hyperactivity disorder (ADHD) in agricultural communities and those that are exposed to residentially applied insecticides. To examine this association in populations that are exposed primarily through diet, we estimate the associations between prenatal OPP exposure and preschool ADHD in the Norwegian Mother, Father and Child Cohort Study (MoBa), and describe modification by paraoxonase 1 (PON1) gene variants. We used participants from the MoBa Preschool ADHD Sub-study (n = 259 cases) and a random sample of MoBa sub-cohort participants (n = 547) with birth years from 2004 to 2008. Prenatal urinary dialkylphosphate (DAP) metabolites (total diethylphosphate [∑DEP] and total dimethylphosphate [∑DMP]) were measured by an ultra-performance liquid chromatography-time-of-flight system and summed by molar concentration. Maternal DNA was genotyped for coding variants of PON1 (Q192R and L55M). We used a multivariable logistic regression to calculate the odds ratios (OR) and 95% confidence intervals, adjusted for maternal education, parity, income dependency, age, marital status, ADHD-like symptoms, pesticide use, produce consumption, and season. We found no associations between DAP metabolite concentrations and preschool ADHD. The adjusted ORs for exposure quartiles 2-4 relative to 1 were slightly inverse. No monotonic trends were observed, and the estimates lacked precision, likely due to the small sample size and variation in the population. We found no evidence of modification by PON1 SNP variation or child sex. Maternal urinary DAP concentrations were not associated with preschool ADHD.

Prenatal organophosphorus pesticide exposure and executive function in preschool-aged children in the Norwegian Mother, Father and Child Cohort Study (MoBa).

INTRODUCTION: Prenatal exposure to organophosphorus pesticides (OPPs) has been associated with neurodevelopmental deficits in children, however evidence linking OPPs with specific cognitive mechanisms, such as executive function (EF), is limited. OBJECTIVE: This study aims to evaluate the association between prenatal exposure to OPPs with multiple measures of EF in preschool-aged children, while considering the role of variant alleles in OPP metabolism genes. METHODS: We included 262 children with preschool attention-deficit/hyperactivity disorder (ADHD), and 78 typically developing children, from the Preschool ADHD substudy of the Norwegian, Mother, Father, and Child Cohort Study. Participants who gave birth between 2004 and 2008 were invited to participate in an on-site clinical assessment when the child was approximately 3.5 years; measurements of EF included parent and teacher rating on Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P), and three performance-based assessments. We measured OPP metabolites in maternal urines collected at ∼17 weeks' gestation to calculate total dimethyl- (ΣDMP) and diethyl phosphate (ΣDEP) metabolite concentrations. We estimated multivariable adjusted ß's and 95% confidence intervals (CIs) corresponding to a change in z-score per unit increase in log-ΣDMP/DEP. We further characterized gene-OPP interactions for maternal variants in PON1 (Q192R, M55L), CYP1A2 (1548T > C), CYP1A1 (IntG > A) and CYP2A6 (-47A > C). RESULTS: Prenatal OPP metabolite concentrations were associated with worse parent and teacher ratings of emotional control, inhibition, and working memory. A one log-∑DMP increase was associated with poorer teacher ratings of EF on the BRIEF-P (e.g. emotional control domain: ß = 0.55, 95% CI: 0.35, 0.74), when weighted to account for sampling procedures. We found less consistent associations with performance-based EF assessments. We found some evidence of modification for PON1 Q192R and CYP2A6 -47A > C. Association with other variants were inconsistent. CONCLUSIONS: Biomarkers of prenatal OPP exposure were associated with more adverse teacher and parent ratings of EF in preschool-aged children.

Cognitive, emotional, and social functioning of preschoolers with attention deficit hyperactivity problems.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is associated with deficits in different functional domains. It remains unclear if deficits in different domains are equally strong in early childhood, and which deficits are specific to ADHD. Here, we describe functional domains in preschoolers and assess deficits in children with ADHD problems, by comparing them to preschoolers with other mental health problems or who develop typically. METHODS: The ADHD Study assessed 1195 ca. 3.5 years old preschoolers through a semi-structured parent interview, parent questionnaires, and with neuropsychological tests. We determined functional domains by applying factor analytic methods to a broad set of questionnaire- and test-scales. Using resulting factor scores, we employed a Bayesian hierarchical regression to estimate functional deficits in children with ADHD. RESULTS: We found that preschoolers' functioning could be described along the seven relatively independent dimensions activity level and regulation, executive function, cognition, language, emotion regulation, introversion, and sociability. Compared to typically developing preschoolers, those with ADHD had deficits in all domains except introversion and sociability. Only deficits in activity level regulation and executive functions were larger than 0.5 standardised mean deviations and larger than deficits of children with other mental health problems. CONCLUSIONS: Preschoolers with ADHD have deficits in multiple functional domains, but only impairments in activity level and regulation and executive functions are specific for ADHD and large enough to be clinically significant. Research on functioning in these domains will be important for understanding the development of ADHD, and for improving treatment and prevention approaches.

The effect of special educational assistance in early childhood education and care on psycho-social difficulties in elementary school children.

BACKGROUND: Three to seven percent of pre-schoolers have developmental problems or child psychiatric disorders. Randomized controlled trials (RCTs) indicate that interventions in early childhood education and care (ECEC) improve long-term outcomes of children from disadvantaged backgrounds. It is unknown if such effects generalize beyond the well-structured context of RCTs and to children who may not have a disadvantaged background but have developmental problems or psychiatric disorders. METHODS: We used data from the population-based Norwegian Mother, Father and Child Cohort Study, recruiting pregnant women from 1999 to 2009, with child follow-up from ages 6, 18, and 36 months to ages 5, 7, and 8 years. This sub-study included 2499 children with developmental problems or psychiatric disorders at age five. We investigated the effects of special educational assistance at age five on mother-reported internalizing, externalizing, and communication problems at age eight. We analysed bias due to treatment by indication with directed acyclic graphs, adjusted for treatment predictors to reduce bias, and estimated effects in different patient groups and outcome domains with a hierarchical Bayesian model. RESULTS: In the adjusted analysis, pre-schoolers who received special educational assistance had on average by 0.1 (0.04-0.16) standardised mean deviation fewer psycho-social difficulties in elementary school. CONCLUSION: In a sample of children from mostly higher socioeconomic backgrounds we estimate a positive effects of special educational assistance during the transition from preschool to the school years. It may therefore be considered as an intervention for pre-schoolers with developmental or behaviour problems. More research with improved measurements of treatment and outcomes is needed to solidify the findings and identify success factors for the implementation of special educational assistance in ECEC.

Is age of self-harm onset associated with increased frequency of non-suicidal self-injury and suicide attempts in adolescent outpatients?

BACKGROUND: Self-harm in adolescents is an increasing public health concern and an important risk factor for suicide. We aimed to examine how age of self-harm onset in adolescents was associated with frequency of subsequent suicidal and non-suicidal self-harm (NSSI) episodes, and how age of onset and duration of self-harm may influence the frequency of self-harm. METHODS: Data from 103 adolescents with recurrent self-harm recruited from child and adolescent psychiatric outpatient clinics were collected through clinical interviews and self-reports, and analysed with negative binomial and hurdle models. RESULTS: A lower age of self-harm onset and a longer duration of self-harm were both significantly associated with increased frequency of subsequent episodes of NSSI and risk of a first suicide attempt. There was an increase in repeated suicide attempts when the age of onset of self-harm decreased and the duration increased, and dramatically more for long duration of NSSI before first suicide attempt. CONCLUSION: Initiating self-harm behaviour at the youngest age had the highest risk of increased frequency of NSSI and suicide attempts. Longer duration of self-harm behaviour increased this risk. This underlines the importance of early identification of self-harm behaviour in adolescents, and the use of effective interventions.

Underlying mechanisms of disruptive mood dysregulation disorder in children: A systematic review by means of research domain criteria.

Background: A systematic overview of underlying mechanisms in the new disruptive mood dysregulation disorder (DMDD) diagnosis is needed. The Research Domain Criteria (RDoC) represent a system of six domains of human functioning, which aims to structure the understanding of the nature of mental illnesses. By means of the RDoC framework, the objective of this systematic review is to synthesize available data on children and youths <18 years suffering from DMDD as reported in peer reviewed papers. Methods: A literature search guided by PRISMA was conducted using Medline, PsychInfo, and Embase, while the RDoC domains were employed to systematize research findings. Risk of bias in the included studies was examined. Results: We identified 319 studies. After study selection, we included 29 studies. Twenty-one of these had findings relating to >1 RDoC domain. The risk of bias assessment shows limitations in the research foundation of current knowledge on mechanisms of DMDD. Discussion: Reviewing self-report, behavior and neurocircuit findings by means of RDoC domains, we suggest that DMDD youths have a negative interpretation bias in social processes and valence systems. In occurrence of a negative stimuli interpretation, aberrant cognitive processing may arise. However, current knowledge of DMDD is influenced by lack of sample diversity and open science practices. Conclusion: We found the six RDoC domains useful in structuring current evidence of the underlying mechanisms of DMDD. Important opportunities for future studies in this field of research are suggested. In clinical practice, this comprehensive summary on DMDD mechanisms can be used in psychoeducation and treatment plans.