To examine the association between weaknesses in executive functions and attention-deficit/hyperactivity disorder (ADHD).
Empirical studies examining executive functions in ADHD samples were ...reviewed, with particular attention to results of recent meta-analyses.
ADHD is associated with impaired performance on measures of response inhibition, working memory, and other aspects of executive functions, yet data also suggest significant neuropsychological variability within and across ADHD samples.
ADHD may be best conceptualized as a neuropsychologically heterogeneous condition. More work is needed to characterize this heterogeneity and its clinical and pathophysiologic implications.
One of the most prominent neuropsychologic theories of attention-deficit/hyperactivity disorder (ADHD) suggests that its symptoms arise from a primary deficit in executive functions (EF), defined as ...neurocognitive processes that maintain an appropriate problem-solving set to attain a later goal. To examine the validity of the EF theory, we conducted a meta-analysis of 83 studies that administered EF measures to groups with ADHD (total
N = 3734) and without ADHD (
N = 2969). Groups with ADHD exhibited significant impairment on all EF tasks. Effect sizes for all measures fell in the medium range (.46–.69), but the strongest and most consistent effects were obtained on measures of response inhibition, vigilance, working memory, and planning. Weaknesses in EF were significant in both clinic-referred and community samples and were not explained by group differences in intelligence, academic achievement, or symptoms of other disorders. ADHD is associated with significant weaknesses in several key EF domains. However, moderate effect sizes and lack of universality of EF deficits among individuals with ADHD suggest that EF weaknesses are neither necessary nor sufficient to cause all cases of ADHD. Difficulties with EF appear to be one important component of the complex neuropsychology of ADHD.
Numerous adverse prenatal exposures have been individually associated with risk for psychiatric illness in the offspring. However, such exposures frequently co-occur, raising questions about their ...cumulative impact. We evaluated effects of cumulative adverse prenatal exposure burden on psychopathology risk in school-aged children.
Using baseline surveys from the U.S.-based Adolescent Brain and Cognitive Development (ABCD) Study (7,898 non-adopted, unrelated children from 21 sites, age 9-10, and their primary caregivers), we examined 8 retrospectively-reported adverse prenatal exposures in relation to caregiver-reported total and subscale Child Behavior Checklist (CBCL) scores. We also assessed cumulative effects of these factors on CBCL total as a continuous measure, as well as on odds of clinically significant psychopathology (CBCL total ≥60), in both the initial set and a separate ABCD sample comprising an additional 696 sibling pairs. Analyses were conducted before and after adjustment for 14 demographic and environmental covariates.
In minimally and fully adjusted models, 6 exposures (unplanned pregnancy; maternal alcohol, marijuana, and tobacco use early in pregnancy; pregnancy complications; and birth complications) independently associated with significant but small increases in CBCL total score. Among these 6, none increased the odds of crossing the threshold for clinically significant symptoms by itself. However, odds of exceeding this threshold became significant with 2 exposures (OR = 1.86, 95% CI 1.47-2.36), and increased linearly with each level of exposure (OR = 1.39, 95% CI 1.31-1.47), up to 3.53-fold for ≥4 exposures versus none. Similar effects were observed in confirmatory analysis among siblings. Within sibling pairs, greater discordance for exposure load associated with greater CBCL total differences, suggesting that results were not confounded by unmeasured family-level effects.
Children exposed to multiple common, adverse prenatal events showed dose-dependent increases in broad, clinically significant psychopathology at age 9-10. Fully prospective studies are needed to confirm and elaborate upon this pattern.
Before assigning full etiologic validity to a psycopathologic disorder, disease theory suggests that a causal dysfunction in a mechanism within the affect individuals must be identified. Existing ...theories on attention-deficit/hyperactivity disorder (ADHD) suggest such dysfunctions in cognitive, neuropsychological, or motivational processes in the child. To date, researchers have tested these theories by comparing groups with DSM-defined ADHD to children without ADHD. Using executive functioning as an illustration of an issue that exists across all such theories, this article describes substantial overlaps in the group performance data. Thus only a subgroup may have executive deficits. Noted are other supportive data suggesting multiple pathways to ADHD. The article explores implications and recommends that future theory and research give more consideration to the probability that only a subset of behaviorally defined children will have a deficit in a given neurocognitive mechanism believed to contribute to the disorder. Creation of a provisional set of criteria in DSM-V for defining an “executive deficit type” could stimulate research to validate the first etiologic subtype of ADHD and spur the development of more sophisticated causal models, which in the longer term may give clinicians ways to target and tailor treatments.
Unbiased genomewide association studies of tens of thousands of individuals are transforming our understanding of the origins and structure of psychopathology across the lifespan. Together with ...findings from epidemiology and cognitive neuroscience, these recent molecular genetic studies underscore the importance of studying phenotypes across as well as within conventional psychiatric diagnoses in order to construct a more pathophysiologically grounded taxonomy from the bottom up. Such efforts, promoted by NIMH's Research Domain Criteria (RDoC) framework, are critical to developing more accurate models of the risk mechanisms that are shared and distinct across various psychopathologic outcomes. In turn, these models could reveal new treatment targets and early intervention opportunities. In their article in the 2015 JCPP Annual Research Review, Scerif and Baker remind us that bottom‐up insights into psychiatric illness might also be gained by examining specific genetic disorders that often fall within the purview of pediatrics and neurology. These authors note high rates of symptoms of attention‐deficit hyperactivity disorder (ADHD) in syndromes with known and often monogenic genetic causes (e.g. Fragile X) and suggest that studying the ADHD‐like phenomena in these conditions may provide insight into ADHD itself. This commentary highlights themes from Scerif and Baker's review that overlap with the core tenets of RDoC and notes their significance for advancing our understanding of ADHD in the coming years. It concludes by suggesting ways in which further attention to the RDoC framework could also enhance Scerif and Baker's agenda.
Read the full article at doi: 10.1111/jcpp.12374
Mood disorders often co-occur with attention-deficit/hyperactive disorder (ADHD), disruptive behavior disorders (DBDs), and aggression. We aimed to determine if polygenic risk scores (PRSs) based on ...external genome-wide association studies (GWASs) of these disorders could improve genetic identification of mood disorders.
We combined 6 independent family studies that had genetic data and diagnoses for mood disorders that were made using different editions of the
(
). We identified mood disorders, either concurrently or in the future, in participants between 6 and 17 years of age using PRSs calculated using summary statistics of GWASs for ADHD, ADHD with DBD, major depressive disorder (MDD), bipolar disorder (BPD), and aggression to compute PRSs.
In our sample of 485 youths, 356 (73%) developed a subthreshold or full mood disorder and 129 (27%) did not. The cross-validated mean areas under the receiver operating characteristic curve (AUCs) for the 7 models identifying participants with any mood disorder ranged from 0.552 in the base model of age and sex to 0.648 in the base model + all 5 PRSs. When included in the base model individually, the ADHD PRS (OR = 1.65,
< .001), Aggression PRS (OR = 1.27,
= .02), and MDD PRS (OR = 1.23,
= .047) were significantly associated with the development of any mood disorder.
Using PRSs for ADHD, MDD, BPD, DBDs, and aggression, we could modestly identify the presence of mood disorders. These findings extend evidence for transdiagnostic genetic components of psychiatric illness and demonstrate that PRSs calculated using traditional diagnostic boundaries can be useful within a transdiagnostic framework.
Recent initiatives in psychiatry emphasize the utility of characterizing psychiatric symptoms in a multidimensional manner. However, strategies for applying standard self-report scales for multiaxial ...assessment have not been well-studied, particularly where the aim is to support both categorical and dimensional phenotypes.
We propose a method for applying natural language processing to derive dimensional measures of psychiatric symptoms from questionnaire data. We utilized nine self-report symptom measures drawn from a large cellular biobanking study that enrolled individuals with mood and psychotic disorders, as well as healthy controls. To summarize questionnaire results we used word embeddings, a technique to represent words as numeric vectors preserving semantic and syntactic meaning. A low-dimensional approximation to the embedding space was used to derive the proposed succinct summary of symptom profiles. To validate our embedding-based disease profiles, these were compared to presence or absence of axis I diagnoses derived from structured clinical interview, and to objective neurocognitive testing.
Unsupervised and supervised classification to distinguish presence/absence of axis I disorders using survey-level embeddings remained discriminative, with area under the receiver operating characteristic curve up to 0.85, 95% confidence interval (CI) (0.74,0.91) using Gaussian mixture modeling, and cross-validated area under the receiver operating characteristic curve 0.91, 95% CI (0.88,0.94) using logistic regression. Derived symptom measures and estimated Research Domain Criteria scores also associated significantly with performance on neurocognitive tests.
Our results support the potential utility of deriving dimensional phenotypic measures in psychiatric illness through the use of word embeddings, while illustrating the challenges in identifying truly orthogonal dimensions.
The association between executive function deficits (EFDs) and functional outcomes were examined among children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Participants were ...children and adolescents with (
n
= 259) and without (
n
= 222) ADHD, as ascertained from pediatric and psychiatric clinics. The authors defined EFD as at least 2 executive function measures impaired. Significantly more children and adolescents with ADHD had EFDs than did control participants. ADHD with EFDs was associated with an increased risk for grade retention and a decrease in academic achievement relative to (a) ADHD alone, (b) controlled socioeconomic status, (c) learning disabilities, and (d) IQ. No differences were noted in social functioning or psychiatric comorbidity. Children and adolescents with ADHD and EFDs were found to be at high risk for significant impairments in academic functioning. These results support screening children with ADHD for EFDs to prevent academic failure.
Suicide is among the leading causes of death in children and adolescents. There are well-known risk factors of suicide, including childhood abuse, family conflicts, social adversity, and ...psychopathology. While suicide risk is also known to be heritable, few studies have investigated genetic risk in younger individuals.
Using polygenic risk score analysis, we examined whether genetic susceptibility to major psychiatric disorders is associated with suicidal behaviors among 11,878 children enrolled in the ABCD (Adolescent Brain Cognitive Development) Study. Suicidal ideation and suicide attempt data were assessed using the youth report of the Kiddie Schedule for Affective Disorders and Schizophrenia for DSM-5. After performing robust quality control of genotype data, unrelated individuals of European descent were included in analyses (n = 4344).
Among 8 psychiatric disorders we examined, depression polygenic risk scores were associated with lifetime suicide attempts both in the baseline (odds ratio = 1.55, 95% CI = 1.10–2.18, p = 1.27 × 10−2) and in the follow-up year (odds ratio = 1.38, 95% CI = 1.08–1.77, p = 1.05 × 10−2), after adjusting for children’s age, sex, socioeconomic backgrounds, family history of suicide, and psychopathology. In contrast, attention-deficit/hyperactivity disorder polygenic risk scores were associated with lifetime suicidal ideation (odds ratio = 1.15, 95% CI = 1.05–1.26, p = 3.71 × 10−3), suggesting a distinct contribution of the genetic risk underlying attention-deficit/hyperactivity disorder and depression on suicidal behaviors of children.
The largest genetic sample of suicide risk data in U.S. children suggests a significant genetic basis of suicide risk related to attention-deficit/hyperactivity disorder and depression. Further research is warranted to examine whether incorporation of genomic risk may facilitate more targeted screening and intervention efforts.
Suicide rates have been increasing among youth in the US. While the heritability of suicide risk is well established, there is limited understanding of how genetic risk is associated with suicidal ...thoughts and behaviors in young children.
To examine whether genetic susceptibility to suicide attempts (SAs) is associated with suicidal thoughts and behaviors in children.
This case-control study examined data from the Adolescent Brain Cognitive Development (ABCD) study, a population-based longitudinal study of 11 878 US children enrolled at age 9 and 10 years from September 2016 to November 2018. Youth reports of suicidal ideation (SI) and SAs were obtained from the Kiddie Schedule for Affective Disorder and Schizophrenia at baseline and 2 subsequent years. After conservative quality control of genotype data, this analysis focused on 4344 unrelated individuals of European ancestry. Data analysis was conducted from November 2020 to February 2022.
Children's lifetime experiences of SI and SAs were assessed each year from ages 9 to 10 years to ages 11 to 12 years. Polygenic risk scores (PRSs) for SAs were calculated for ABCD study participants based on the largest genome-wide association study of SA cases and controls of European ancestry (total sample n = 518 612).
Of 4344 children of European ancestry (2045 47.08% female; mean SD age, 9.93 0.62 years), significant associations were found between children's SA PRSs and their lifetime SAs with the most robust association in the follow-up year 2 (odds ratio, 1.43 95% CI, 1.18-1.75; corrected P = 1.85 × 10-3; Nagelkerke pseudo R2 = 1.51%). These associations remained significant after accounting for children's sociodemographic backgrounds, psychopathology symptoms, parental histories of suicide and mental health, and PRSs for major depression and attention-deficit/hyperactivity disorder (likelihood ratio test P < .05). Children's depressive mood and aggressive behavior were the most significant partial mediators of SA genetic risk on SAs (mediation analysis P < 1 × 10-16). Children's behavioral problems, such as attention problems, rule-breaking behavior, and social problems, also partially mediated the association of SA PRSs with SAs (mediation analysis false discover rate < 0.05).
This study's findings indicate that there may be genetic factors associated with SA risk across the life span and suggest behaviors and conditions through which the risk could be mediated in childhood. Further research is warranted to examine whether incorporating genetic data could improve the identification of children at risk for suicide.
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