Search

Introduction: Maximal grip strength, a measure of how much force a person's hand can generate when squeezing an object, may be an effective method for understanding potential neurobiological differences during motor tasks. Grip strength in autistic individuals may be of particular interest due to its unique developmental trajectory. While autism-specific differences in grip-brain relationships have been found in adult populations, it is possible that such differences in grip-brain relationships may be present at earlier ages when grip strength is behaviorally similar in autistic and non-autistic groups. Further, such neural differences may lead to the later emergence of diagnostic-group grip differences in adolescence. The present study sought to examine this possibility, while also examining if grip strength could elucidate the neuro-motor sources of phenotypic heterogeneity commonly observed within autism. Methods: Using high resolution, multi-shell diffusion, and quantitative R1 relaxometry imaging, this study examined how variations in key sensorimotorrelated white matter pathways of the proprioception input, lateral grasping, cortico-cerebellar, and corticospinal networks were associated with individual variations in grip strength in 68 autistic children and 70 non-autistic (neurotypical) children (6-11 years-old). Results: In both groups, results indicated that stronger grip strength was associated with higher proprioceptive input, lateral grasping, and corticospinal (but not cortico-cerebellar modification) fractional anisotropy and R1, indirect measures concordant with stronger microstructural coherence and increased myelination. Diagnostic group differences in these grip-brain relationships were not observed, but the autistic group exhibited more variability particularly in the cortico-cerebellar modification indices. An examination into the variability within the autistic group revealed that attention-deficit/hyperactivity disorder (ADHD) features moderated the relationships between grip strength and both fractional anisotropy and R1 relaxometry in the premotor-primary motor tract of the lateral grasping network and the cortico-cerebellar network tracts. Specifically, in autistic children with elevated ADHD features (60% of the autistic group) stronger grip strength was related to higher fractional anisotropy and R1 of the cerebellar modification network (stronger microstructural coherence and more myelin), whereas the opposite relationship was observed in autistic children with reduced ADHD features. Discussion: Together, this work suggests that while the foundational elements of grip strength are similar across school-aged autistic and non-autistic children, neural mechanisms of grip strength within autistic children may additionally depend on the presence of ADHD features. Specifically, stronger, more coherent connections of the cerebellar modification network, which is thought to play a role in refining and optimizing motor commands, may lead to stronger grip in children with more ADHD features, weaker grip in children with fewer ADHD features, and no difference in grip in non-autistic children. While future research is needed to understand if these findings extend to other motor tasks beyond grip strength, these results have implications for understanding the biological basis of neuromotor control in autistic children and emphasize the importance of assessing co-occurring conditions when evaluating brain-behavior relationships in autism. [ABSTRACT FROM AUTHOR]

Background: ADHD polygenic scores (PGSs) have been previously shown to predict ADHD outcomes in several studies. However, ADHD PGSs are typically correlated with ADHD but not necessarily reflective of causal mechanisms. More research is needed to elucidate the neurobiological mechanisms underlying ADHD. We leveraged functional annotation information into an ADHD PGS to (1) improve the prediction performance over a non-annotated ADHD PGS and (2) test whether volumetric variation in brain regions putatively associated with ADHD mediate the association between PGSs and ADHD outcomes. Methods: Data were from the Philadelphia Neurodevelopmental Cohort (N = 555). Multiple mediation models were tested to examine the indirect effects of two ADHD PGSs—one using a traditional computation involving clumping and thresholding and another using a functionally annotated approach (i.e., AnnoPred)—on ADHD inattention (IA) and hyperactivity-impulsivity (HI) symptoms, via gray matter volumes in the cingulate gyrus, angular gyrus, caudate, dorsolateral prefrontal cortex (DLPFC), and inferior temporal lobe. Results: A direct effect was detected between the AnnoPred ADHD PGS and IA symptoms in adolescents. No indirect effects via brain volumes were detected for either IA or HI symptoms. However, both ADHD PGSs were negatively associated with the DLPFC. Conclusions: The AnnoPred ADHD PGS was a more developmentally specific predictor of adolescent IA symptoms compared to the traditional ADHD PGS. However, brain volumes did not mediate the effects of either a traditional or AnnoPred ADHD PGS on ADHD symptoms, suggesting that we may still be underpowered in clarifying brain-based biomarkers for ADHD using genetic measures. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Sensorimotor Features and Daily Living Skills in Autistic Children With and Without ADHD" which appeared in the previous issue of the periodical.

Objective: Parenting behavior is a well-established correlate of offspring ADHD. However, little is known about how parenting exerts its effects on offspring ADHD symptomatology. We examined whether prospective associations between positive and negative parenting behaviors and child ADHD symptoms are mediated by deficits in child executive function (EF) and reward responsivity (RR). Method : One hundred and thirty-five children with and without ADHD were assessed across two Waves, when children were mean ages 6 and 8 respectively. Children completed tasks on EF, and parents completed questionnaires about their parenting behaviors and their children's RR and ADHD symptoms. Results : Negative parenting behavior at Wave 1 was indirectly associated with offspring ADHD symptoms at Wave 2 via offspring EF. Conclusion : Individual differences in EF, but not RR, during early childhood may constitute a potential pathway by which negative parenting behaviors exerts its effects on subsequent offspring ADHD symptomatology. Treatment implications are discussed. [ABSTRACT FROM AUTHOR]

This study explored whether maltreatment moderates the association of polygenic risk for ADHD. Because individuals with low polygenic scores (PGS) for ADHD were previously shown to have better than expected functional outcomes (i.e., cognitive, mental health, social-emotional) than individuals with middle or high ADHD PGS, we hypothesized low ADHD PGS may confer a protective effect from maltreatment in the development of ADHD. Data were from participants with phenotypic and genotypic data in the National Longitudinal Study of Adolescent to Adult Health (Add Health; n = 4,722). ADHD PGS were generated from the most recent genome-wide association study on ADHD and categorized into three groups (i.e., low, medium, high) using empirically determined cut-points. A maltreatment factor score was derived from five forms of self-reported maltreatment experiences prior to age 18. ADHD PGS and maltreatment were positively associated with ADHD symptoms, as expected. However, no interaction between ADHD PGS and maltreatment on ADHD symptoms was detected. Despite the increase in predictive power afforded by PGS, the lack of an interaction between ADHD PGS and maltreatment on ADHD symptoms converges with an emerging body of PGS studies that have also failed to detect PGS-environment interplay in mental disorders. We discuss possible reasons for this pattern of results and offer alternative methods for future research in understanding gene-environment interactions. [ABSTRACT FROM AUTHOR]

Background: Polygenic scores (PGS) are widely used to characterize genetic liability for heritable mental disorders, including attention-deficit/hyperactivity disorder (ADHD). However, little is known about the effects of a low burden of genetic liability for ADHD, including whether this functions as a low risk or protective factor for ADHD and related functional outcomes in later life. The current study examines the association of low ADHD PGS and functional outcomes in adulthood. Methods: Participants were from Wave IV of the National Longitudinal Study of Adolescent to Adult Health (Add Health) (N = 7088; mean age = 29, s.d. = 1.74). ADHD PGS was computed from an existing genome-wide association study, and adult functional outcomes, including cognition, educational attainment, mental health, and physical health were assessed during in-home interviews. Results: Individuals at the lowest end of the ADHD PGS distribution (i.e. lowest 20th percentile) had the lowest probabilities of ADHD, exhibiting a 17–19% reduction in risk for ADHD relative to the observed 8.3% prevalence rate of ADHD in Add Health. Furthermore, individuals with low ADHD PGS had higher cognitive performance, greater levels of educational attainment, and lower BMI relative to individuals representing the rest of the ADHD PGS distribution, including those who were in the medium and high-PGS groups. Conclusions: Findings indicate that psychiatric PGS likely capture far more than just the risk and the absence of risk for a psychiatric outcome; where one lies along the PGS distribution may predict diverging functional consequences, for better and for worse. [ABSTRACT FROM AUTHOR]

Background: Children with ADHD frequently engage in higher rates of externalizing behaviors in adulthood relative to children without. However, externalizing behaviors vary across development. Little is known about how this risk unfolds across development. Phenotypic and polygenic models of childhood ADHD were used to predict individual differences in adult externalizing trajectories. Supportive parenting, school connectedness, and peer closeness were then examined as causal mechanisms. Methods: Data were from the National Longitudinal Study of Adolescent to Adult Health (N = 7,674). Externalizing behavior was measured using data from age 18 to 32 and modeled using latent class growth analysis. Child ADHD was measured using retrospective self‐report (phenotypic model) and genome‐wide polygenic risk scores (polygenic model). Multiple mediation models examined the direct and indirect effects of the phenotypic and polygenic models (separately) on externalizing trajectories through the effects of adolescent supportive parenting, school connectedness, and peer closeness. Results: Phenotypic and polygenic models of ADHD were associated with being in the High Decreasing (3.2% of sample) and Moderate (16.1%) adult externalizing trajectories, but not the severe Low Increasing trajectory (2.6%), relative to the Normal trajectory (78.2%). Associations between both models of ADHD on the High Decreasing and Moderate trajectories were partially mediated through the effects of school connectedness, but not supportive parenting or peer closeness. Conclusions: Findings shed light on how childhood ADHD affects downstream psychosocial processes that then predict specific externalizing outcomes in adulthood. They also reinforce the importance of fostering a strong school environment for adolescents with (and without) ADHD, as this context plays a critical role in shaping the development of externalizing behaviors in adulthood. [ABSTRACT FROM AUTHOR]

Inconsistent parental discipline is a robust correlate of child attention-deficit/hyperactivity disorder (ADHD) symptoms, but few studies have considered the role of inconsistent positive parenting on ADHD, as well as the effects of stress on negative and positive parental consistency. This study advanced a novel ecological momentary assessment (EMA) using participant smartphones to measure parental consistency, and examined its associations with family, social, and parenting-related dimensions of stress and child ADHD symptoms. Participants were 184 kindergartners with and without ADHD and their parents. Harsh and warm dimensions of parental behavior were assessed using questionnaires, observations, and an EMA administered through parents' smartphones, which measured parent-child behaviors every day for a period of 1 week. Family, social, and parenting-related stress were assessed from questionnaires, and child ADHD symptoms were assessed from a fully structured diagnostic interview with the parent. Child ADHD symptoms were associated with variability in warm parenting behaviors, and higher levels of parenting-related stress were related to greater variability in harsh parenting behaviors. No significant interactions were detected between parental stress and child ADHD on parental variability. These findings suggest that different factors influence the consistency in parenting behavior, depending on whether positive parenting or negative parenting is assessed. Parent-based treatment programs for children with ADHD should include a stronger focus on reducing stress from parenting (e.g., teaching coping skills for parents), as this may lead to greater consistency in parental behavior more generally, and presumably better child outcomes. [ABSTRACT FROM AUTHOR]

CONTEXT: Although children with attention-deficit/hyperactivity disorder (ADHD) are at elevated risk for comorbid psychopathology, the clinical correlates of ADHD in girls are far less understood relative to boys, despite ADHD being one of the most common childhood disorders in girls. OBJECTIVE: To meta-analytically summarize rates of comorbid internalizing (anxiety, depression) and externalizing (oppositional defiant disorder [ODD], conduct disorder [CD]) psychopathology among girls with and without ADHD. DATA SOURCES: Literature searches (PubMed, Google Scholar) identified published studies examining comorbid psychopathology in girls with and without ADHD. STUDY SELECTION: Eighteen studies (1997 participants) met inclusion criteria and had sufficient data for the meta-analysis. DATA EXTRACTION: Odds ratios for each comorbid disorder were calculated from available data. Demographic (eg, age, race/ethnicity) and study characteristics (eg, referral source, diagnostic method) were also coded. RESULTS: Compared with girls without ADHD, girls with ADHD were significantly more likely to meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for each comorbid disorder assessed. Relative odds were higher for externalizing (ODD: 5.6 x; CD: 9.4x) relative to internalizing disorders (anxiety: 3.2x; depression: 4.2x). Meta-regression revealed larger effect sizes of ADHD on anxiety for studies using multiple diagnostic methods, featuring younger children, and including clinic-referred (versus community-referred) girls; the effect of ADHD on ODD varied based on diagnostic informant. LIMITATIONS: Findings were derived from cross-sectional studies, precluding causal inferences. CONCLUSIONS: Girls with ADHD frequently exhibit comorbid externalizing and internalizing disorders. We discuss future research priorities and consider intervention implications for ADHD and comorbid psychopathology in girls. [ABSTRACT FROM AUTHOR]

Although there are likely to be multiple mechanisms underlying parent attention-deficit/hyperactivity disorder (ADHD) symptoms as a key risk factor for offspring ADHD, potential explanatory factors have yet to be reliably identified. Given that parent ADHD symptoms independently predict parenting behavior and child ADHD symptoms, we tested whether individual differences in multiple dimensions of positive and negative parenting behavior (i.e., corporal punishment, inconsistent discipline, positive parenting behavior, observed negative talk, and observed praise) mediated the association between parental and offspring ADHD. We used a prospective design that featured predictors (i.e., parent ADHD symptoms) and mediators (i.e., parenting behavior) that temporally preceded the outcome (i.e., offspring ADHD symptoms). Using a well-characterized sample of 120 children with and without ADHD (ages 5–10 at Wave 1, 7–12 at Wave 2) and their biological parents, we examined multimethod (i.e., observed, self-report) measures of positive and negative parenting behavior as simultaneous mediators of the association of Wave 1 parent and Wave 2 offspring ADHD symptoms. Using a multiple mediation framework, consisting of rigorous bootstrapping procedures and controlling for parent depression, child's baseline ADHD and oppositional defiant disorder, and child's age, corporal punishment significantly and uniquely mediated the association of Wave 1 parent ADHD symptoms and Wave 2 offspring ADHD. We consider the role of parenting behavior in the intergenerational transmission of ADHD as well as implications of these findings for the intervention and prevention of childhood ADHD. [ABSTRACT FROM PUBLISHER]

Abstract: The 44-base-pair polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) has been implicated in the etiology of depression, but relatively little is known about potential mediators of this association. Although dimensions of temperament are likely to be proximal to the neurobiological and genetic factors underlying depression, studies have yet to formally evaluate temperament as a potential causal pathway. We examined individual differences in dimensions of temperament [negative emotionality (NE), prosociality (PRO), and daring (DA)] as potential mediators of 5-HTTLPR genotype and child depression. Using a multiple mediation framework, we tested the association of child 5-HTTLPR genotype and these dimensions of temperament with multi-informant ratings of child depression in a sample of 218 children with and without attention-deficit/hyperactivity disorder (ADHD). The long allele of 5-HTTLPR was associated with higher NE and lower PRO, but not DA. High NE mediated the association of 5-HTTLPR genotype and separate parent and teacher ratings of depression. ADHD status did not moderate the mediational role of NE for 5-HTTLPR and depression. Results suggest that NE may constitute a pathway between 5-HTTLPR and child depression. The role of genetic variation and temperament dimensions as intermediate traits in the development of depression is discussed. [Copyright &y& Elsevier]

Background: Although the association of the dopamine transporter (DAT1) gene and attention-deficit/hyperactivity disorder (ADHD) has been widely studied, far less is known about its potential interaction with environmental risk factors. Given that maltreatment is a replicated risk factor for ADHD, we explored the interaction between DAT1 and maltreatment with ADHD symptoms defined dimensionally and using latent class analysis (LCA). Method: We tested the association of the 40 base-pair variable number of tandem repeats polymorphism in DAT1, maltreatment, and their interaction in 2,488 boys and girls from the National Longitudinal Study of Adolescent Health. Results: In boys, ADHD symptoms were optimally defined by four classes (Combined, Hyperactive/Impulsive, Inattentive, and Normal), whereas in girls, ADHD symptoms were defined by three classes (Combined, Combined-Mild, Normal). A significant DAT1 × maltreatment interaction revealed that maltreated girls homozygous for the 10-repeat allele had more symptoms of ADHD, and were also 2.5 times more likely to be classified in the Combined ADHD group than in the Normal Group. Conclusions: The underlying structure of ADHD symptoms differed between boys and girls and DAT1 interacted with maltreatment to predict ADHD symptoms and ADHD status derived from LCA. Interactive exchanges between maltreatment and DAT1 for ADHD symptoms, and their implications for intervention, are discussed. [ABSTRACT FROM AUTHOR]

Relatively little is known about the potential interplay between genetic and environmental influences on attention-deficit/hyperactivity disorder (ADHD), including gene-environment interaction (G×E). There is evidence that parenting behavior interacts with offspring genotype in the development of externalizing problems, but studies have largely focused on explicit maltreatment rather than differentiated measures of parenting behavior, including positive and negative parenting. We tested the interactive effects of the 30-base pair variable number tandem repeat (VNTR) polymorphism of the monoamine oxidase A gene (MAO-A) with positive and negative parenting behavior on parent- and teacher ratings of inattention and hyperactivity symptoms among 150 6-9 year-old boys with and without ADHD. Negative parenting predicted parent and teacher ratings of inattention symptoms, but only among boys with high-activity MAO-A genotype. MAO-A genotype did not moderate the association of positive parenting and parent- and teacher ratings of ADHD. We discuss the potential role of interactive exchanges between parenting behavior and child genotype in the development and persistence of ADHD and related behavior problems. [ABSTRACT FROM AUTHOR]