Category Archives: J Am Acad Child Adolesc Psychiatry

A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts.

A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts.

J Am Acad Child Adolesc Psychiatry. 2016 Oct;55(10):896-905.e6

Authors: Middeldorp CM, Hammerschlag AR, Ouwens KG, Groen-Blokhuis MM, St Pourcain B, Greven CU, Pappa I, Tiesler CM, Ang W, Nolte IM, Vilor-Tejedor N, Bacelis J, Ebejer JL, Zhao H, Davies GE, Ehli EA, Evans DM, Fedko IO, Guxens M, Hottenga JJ, Hudziak JJ, Jugessur A, Kemp JP, Krapohl E, Martin NG, Murcia M, Myhre R, Ormel J, Ring SM, Standl M, Stergiakouli E, Stoltenberg C, Thiering E, Timpson NJ, Trzaskowski M, van der Most PJ, Wang C, EArly Genetics and Lifecourse Epidemiology (EAGLE) Consortium, Psychiatric Genomics Consortium ADHD Working Group, Nyholt DR, Medland SE, Neale B, Jacobsson B, Sunyer J, Hartman CA, Whitehouse AJ, Pennell CE, Heinrich J, Plomin R, Davey Smith G, Tiemeier H, Posthuma D, Boomsma DI

Abstract
OBJECTIVE: The aims of this study were to elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis.
METHOD: Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (<13 years of age) from nine population-based cohorts. SNP-based heritability was estimated in data from the three largest cohorts. Meta-analysis based on genome-wide association (GWA) analyses with SNPs was followed by gene-based association tests, and the overlap in results with a meta-analysis in the Psychiatric Genomics Consortium (PGC) case-control ADHD study was investigated.
RESULTS: SNP-based heritability ranged from 5% to 34%, indicating that variation in common genetic variants influences ADHD symptom scores. The meta-analysis did not detect genome-wide significant SNPs, but three genes, lying close to each other with SNPs in high linkage disequilibrium (LD), showed a gene-wide significant association (p values between 1.46 × 10(-6) and 2.66 × 10(-6)). One gene, WASL, is involved in neuronal development. Both SNP- and gene-based analyses indicated overlap with the PGC meta-analysis results with the genetic correlation estimated at 0.96.
CONCLUSION: The SNP-based heritability for ADHD symptom scores indicates a polygenic architecture, and genes involved in neurite outgrowth are possibly involved. Continuous and dichotomous measures of ADHD appear to assess a genetically common phenotype. A next step is to combine data from population-based and case-control cohorts in genetic association studies to increase sample size and to improve statistical power for identifying genetic variants.

PMID: 27663945 [PubMed – in process]

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Thinner Medial Temporal Cortex in Adolescents With Attention-Deficit/Hyperactivity Disorder and the Effects of Stimulants.

Thinner Medial Temporal Cortex in Adolescents With Attention-Deficit/Hyperactivity Disorder and the Effects of Stimulants.

J Am Acad Child Adolesc Psychiatry. 2015 Aug;54(8):660-667

Authors: Schweren LJ, Hartman CA, Heslenfeld DJ, van der Meer D, Franke B, Oosterlaan J, Buitelaar JK, Faraone SV, Hoekstra PJ

Abstract
OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) has been associated with widespread changes in cortical thickness (CT). Findings have been inconsistent, however, possibly due to age differences between samples. Cortical changes have also been suggested to be reduced or to disappear with stimulant treatment. We investigated differences in CT between adolescents/young adults with and without ADHD in the largest ADHD sample to date, the NeuroIMAGE sample. Second, we investigated how such differences were related to age and stimulant treatment.
METHOD: Participants (participants with ADHD = 306; healthy controls = 184, 61% male, 8-28 years of age, mean age = 17 years) underwent structural magnetic resonance imaging. Participants and pharmacies provided detailed information regarding lifetime stimulant treatment, including cumulative intake and age of treatment initiation and cessation. Vertexwise statistics were performed in Freesurfer, modeling the main effect of diagnosis on CT and its interaction with age. Effects of stimulant treatment parameters on CT were modeled within the sample with ADHD.
RESULTS: After correction for multiple comparisons, participants with ADHD showed decreased medial temporal CT in both left (pCLUSTER = .008) and right (pCLUSTER = .038) hemispheres. These differences were present across different ages and were associated with symptoms of hyperactivity and prosocial behavior. There were no age-by-diagnosis interaction effects. None of the treatment parameters predicted CT within ADHD.
CONCLUSION: Individuals with ADHD showed thinner bilateral medial temporal cortex throughout adolescence and young adulthood compared to healthy controls. We found no association between CT and stimulant treatment. The cross-sectional design of the current study warrants cautious interpretation of the findings.

PMID: 26210335 [PubMed – as supplied by publisher]

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Preschool Attention-Deficit/Hyperactivity and Oppositional Defiant Problems as Antecedents of School Bullying.

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Preschool Attention-Deficit/Hyperactivity and Oppositional Defiant Problems as Antecedents of School Bullying.

J Am Acad Child Adolesc Psychiatry. 2015 Jul;54(7):571-9

Authors: Verlinden M, Jansen PW, Veenstra R, Jaddoe VW, Hofman A, Verhulst FC, Shaw P, Tiemeier H

Abstract
OBJECTIVE: To examine whether early manifestations of attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) increase children’s later risk of bullying or victimization.
METHOD: Using a population-based, prospective cohort, our multi-informant approach comprised reports of parents, teachers, and peers. ADHD and ODD behavioral problems at ages 1.5, 3, and 5 years were determined from parental reports on the Child Behavior Checklist. Later bullying behavior at school was reported by teachers using a questionnaire (n = 3,192, mean age 6.6 years), and by peer/self-reports using peer nominations (n = 1,098, mean age 7.6 years). We examined the following: whether problem behavior scores at age 1.5, 3, or 5 years predicted a risk of bullying involvement; and whether high or increasing behavioral problems throughout ages 1.5 to 5 years were associated with bullying involvement at school. Analyses were adjusted for a range of child and maternal covariates.
RESULTS: Behavioral problems at a young age each predicted later bullying involvement at school. For example, higher ADHD problem scores at age 3 years were associated with the risks of becoming a bully or a bully-victim (ORBULLY = 1.20, 95% CI = 1.07-1.35 [teacher report], ORBULLY-VICTIM = 1.28, 95% CI = 1.14-1.43 [teacher report], and ORBULLY-VICTIM = 1.35, 95% CI = 1.03-1.78 [peer/self-report]). Children whose behavioral problem scores were high or increased over time consistently had elevated risks of becoming a bully or a bully-victim.
CONCLUSION: Behavioral problems at a young age may predispose children to bullying involvement in early elementary school.

PMID: 26088662 [PubMed – in process]

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Clinical Predictors of Response to Cognitive-Behavioral Therapy in Pediatric Anxiety Disorders: The Genes for Treatment (GxT) Study.

Clinical Predictors of Response to Cognitive-Behavioral Therapy in Pediatric Anxiety Disorders: The Genes for Treatment (GxT) Study.

J Am Acad Child Adolesc Psychiatry. 2015 Jun;54(6):454-63

Authors: Hudson JL, Keers R, Roberts S, Coleman JR, Breen G, Arendt K, Bögels S, Cooper P, Creswell C, Hartman C, Heiervang ER, Hötzel K, In-Albon T, Lavallee K, Lyneham HJ, Marin CE, McKinnon A, Meiser-Stedman R, Morris T, Nauta M, Rapee RM, Schneider S, Schneider SC, Silverman WK, Thastum M, Thirlwall K, Waite P, Wergeland GJ, Lester KJ, Eley TC

Abstract
OBJECTIVE: The Genes for Treatment study is an international, multisite collaboration exploring the role of genetic, demographic, and clinical predictors in response to cognitive-behavioral therapy (CBT) in pediatric anxiety disorders. The current article, the first from the study, examined demographic and clinical predictors of response to CBT. We hypothesized that the child’s gender, type of anxiety disorder, initial severity and comorbidity, and parents’ psychopathology would significantly predict outcome.
METHOD: A sample of 1,519 children 5 to 18 years of age with a primary anxiety diagnosis received CBT across 11 sites. Outcome was defined as response (change in diagnostic severity) and remission (absence of the primary diagnosis) at each time point (posttreatment, 3-, 6-, and/or 12-month follow-up) and analyzed using linear and logistic mixed models. Separate analyses were conducted using data from posttreatment and follow-up assessments to explore the relative importance of predictors at these time points.
RESULTS: Individuals with social anxiety disorder (SoAD) had significantly poorer outcomes (poorer response and lower rates of remission) than those with generalized anxiety disorder (GAD). Although individuals with specific phobia (SP) also had poorer outcomes than those with GAD at posttreatment, these differences were not maintained at follow-up. Both comorbid mood and externalizing disorders significantly predicted poorer outcomes at posttreatment and follow-up, whereas self-reported parental psychopathology had little effect on posttreatment outcomes but significantly predicted response (although not remission) at follow-up.
CONCLUSION: SoAD, nonanxiety comorbidity, and parental psychopathology were associated with poorer outcomes after CBT. The results highlight the need for enhanced treatments for children at risk for poorer outcomes.

PMID: 26004660 [PubMed – in process]

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Increased Neural Responses to Reward in Adolescents and Young Adults With Attention-Deficit/Hyperactivity Disorder and Their Unaffected Siblings.

Increased Neural Responses to Reward in Adolescents and Young Adults With Attention-Deficit/Hyperactivity Disorder and Their Unaffected Siblings.

J Am Acad Child Adolesc…

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Attention-deficit/hyperactivity disorder (ADHD) and motor timing in adolescents and their parents: familial characteristics of reaction time variability vary with age.

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Attention-deficit/hyperactivity disorder (ADHD) and motor timing in adolescents and their parents: familial characteristics of reaction time variability vary with age. …

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Different mechanisms of white matter abnormalities in attention-deficit/hyperactivity disorder: a diffusion tensor imaging study.

Different mechanisms of white matter abnormalities in attention-deficit/hyperactivity disorder: a diffusion tensor imaging study.

J Am Acad Child Adolesc Psychiatry. 2014 Jul;53(7):790-799.e3

Authors: van Ewijk H, Heslenfeld DJ, Zwiers MP, Faraone SV, Luman M, Hartman CA, Hoekstra PJ, Franke B, Buitelaar JK, Oosterlaan J

Abstract
OBJECTIVE: Literature regarding white matter (WM) abnormalities in attention-deficit/hyperactivity disorder (ADHD) is sparse and inconsistent. In this article, we shed more light on WM microstructure in ADHD, its association with symptom count, and the familiality of WM abnormalities in ADHD.
METHOD: Diffusion tensor imaging (DTI) was performed in a large sample of individuals with ADHD (n = 170), their unaffected siblings (n = 80), and healthy controls (n = 107), aged 8 to 30 years. Extensive categorical as well as dimensional data regarding ADHD status and symptom count were collected. A whole-brain voxelwise approach was used to investigate associations between ADHD status and symptom count and WM microstructure, as measured by fractional anisotropy (FA) and mean diffusivity (MD).
RESULTS: Individuals with ADHD showed decreased FA and decreased MD in several widespread, non-overlapping brain regions. In contrast, higher ADHD symptom count was consistently associated with increased FA and decreased MD in the ADHD group. Unaffected siblings resembled individuals in the ADHD group with regard to decreased FA but had MD similar to that in healthy controls. Results were not confounded by socioeconomic status, the presence of comorbidities, or a history of medication use.
CONCLUSIONS: Our results indicate widespread disturbances in WM microstructure in ADHD, which seem to be driven by 2 different mechanisms. Decreased FA in ADHD may be due to a familial vulnerability to the disorder, whereas a second mechanism may drive the association between ADHD symptom count and both higher FA and lower MD. Such different mechanisms may play an important role in the inconsistencies found in the current literature.

PMID: 24954828 [PubMed – in process]

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A Follow-Up Study of Maternal Expressed Emotion Toward Children With Attention-Deficit/Hyperactivity Disorder (ADHD): Relation With Severity and Persistence of ADHD and Comorbidity.

A Follow-Up Study of Maternal Expressed Emotion Toward Children With Attention-Deficit/Hyperactivity Disorder (ADHD): Relation With Severity and Persistence of ADHD and Comorbidity.

J Am Acad Child Adolesc Psychiatry. 2014 Mar;53(3):311-319.e1

Authors: Richards JS, Vásquez AA, Rommelse NN, Oosterlaan J, Hoekstra PJ, Franke B, Hartman CA, Buitelaar JK

Abstract
OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is associated with conflicted parent-child relationships. The underlying mechanisms of this association are not yet fully understood. We investigated the cross-sectional and longitudinal relationships between externalizing psychopathology in children with ADHD, and expressed emotion (EE; warmth and criticism) and psychopathology in mothers.
METHOD: In this 6-year follow-up study, 385 children with an ADHD combined subtype were included at baseline (mean, 11.5 years, 83.4% male), of which 285 children (74%) were available at follow-up (mean, 17.5 years, 83.5% male). At both time points, measures of child psychopathology (i.e., ADHD severity, oppositional, and conduct problems), maternal EE, and maternal psychopathology (i.e., ADHD and affective problems) were obtained.
RESULTS: EE was not significantly correlated over time. At baseline, we found a nominally negative association (p ≤ .05) between maternal warmth and child ADHD severity. At follow-up, maternal criticism was significantly associated with child oppositional problems, and nominally with child conduct problems. Maternal warmth was nominally associated with child oppositional and conduct problems. These associations were independent of maternal psychopathology. No longitudinal associations were found between EE at baseline and child psychopathology at follow-up, or child psychopathology at baseline and EE at follow-up.
CONCLUSIONS: The results support previous findings of cross-sectional associations between parental EE and child psychopathology. This, together with the finding that EE was not stable over 6 years, suggests that EE is a momentary state measure varying with contextual and developmental factors. EE does not appear to be a risk factor for later externalizing behavior in children with ADHD.

PMID: 24565358 [PubMed – in process]

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Emotion regulation training for adolescents with borderline personality disorder traits: a randomized controlled trial.

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Emotion regulation training for adolescents with borderline personality disorder traits: a randomized controlled trial.

J Am Acad Child Adolesc Psychiatry. 2012…

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The TRacking Adolescents’ Individual Lives Survey (TRAILS): design, current status, and selected findings.

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The TRacking Adolescents’ Individual Lives Survey (TRAILS): design, current status, and selected findings.

J Am Acad Child Adolesc Psychiatry. 2012…

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A randomized double-blind study of atomoxetine versus placebo for attention-deficit/hyperactivity disorder symptoms in children with autism spectrum disorder.

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A randomized double-blind study of atomoxetine versus placebo for attention-deficit/hyperactivity disorder symptoms in children with autism spectrum disorder.

J Am…

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