Research and clinical investigations in psychiatry largely rely on the de facto assumption that the diagnostic categories identified in the Diagnostic and Statistical Manual (DSM) represent ...homogeneous syndromes. However, the mechanistic heterogeneity that potentially underlies the existing classification scheme might limit discovery of etiology for most developmental psychiatric disorders. Another, perhaps less palpable, reality may also be interfering with progress—heterogeneity in typically developing populations. In this report we attempt to clarify neuropsychological heterogeneity in a large dataset of typically developing youth and youth with attention deficit/hyperactivity disorder (ADHD), using graph theory and community detection. We sought to determine whether data-driven neuropsychological subtypes could be discerned in children with and without the disorder. Because individual classification is the sine qua non for eventual clinical translation, we also apply support vector machine-based multivariate pattern analysis to identify how well ADHD status in individual children can be identified as defined by the community detection delineated subtypes. The analysis yielded several unique, but similar subtypes across both populations. Just as importantly, comparing typically developing children with ADHD children within each of these distinct subgroups increased diagnostic accuracy. Two important principles were identified that have the potential to advance our understanding of typical development and developmental neuropsychiatric disorders. The first tenet suggests that typically developing children can be classified into distinct neuropsychological subgroups with high precision. The second tenet proposes that some of the heterogeneity in individuals with ADHD might be "nested" in this normal variation.
Background
Intraindividual variability in reaction time (RT) has received extensive discussion as an indicator of cognitive performance, a putative intermediate phenotype of many clinical disorders, ...and a possible trans‐diagnostic phenotype that may elucidate shared risk factors for mechanisms of psychiatric illnesses.
Scope and Methodology
Using the examples of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD), we discuss RT variability. We first present a new meta‐analysis of RT variability in ASD with and without comorbid ADHD. We then discuss potential mechanisms that may account for RT variability and statistical models that disentangle the cognitive processes affecting RTs. We then report a second meta‐analysis comparing ADHD and non‐ADHD children on diffusion model parameters. We consider how findings inform the search for neural correlates of RT variability.
Findings
Results suggest that RT variability is increased in ASD only when children with comorbid ADHD are included in the sample. Furthermore, RT variability in ADHD is explained by moderate to large increases (d = 0.63–0.99) in the ex‐Gaussian parameter τ and the diffusion parameter drift rate, as well as by smaller differences (d = 0.32) in the diffusion parameter of nondecision time. The former may suggest problems in state regulation or arousal and difficulty detecting signal from noise, whereas the latter may reflect contributions from deficits in motor organization or output. The neuroimaging literature converges with this multicomponent interpretation and also highlights the role of top‐down control circuits.
Conclusion
We underscore the importance of considering the interactions between top‐down control, state regulation (e.g. arousal), and motor preparation when interpreting RT variability and conclude that decomposition of the RT signal provides superior interpretive power and suggests mechanisms convergent with those implicated using other cognitive paradigms. We conclude with specific recommendations for the field for next steps in the study of RT variability in neurodevelopmental disorders.
An emerging paradigm for understanding attention-deficit/hyperactivity disorder and other neurodevelopmental, mental, and behavioral disorders is analyzed. The psychiatric and neurodevelopmental ...conditions fundamentally epigenetic disorders. The genetic metaphor for developmental psychopathology has long been considered inadequate for the complex dynamics of human development.
A better characterization of how an individual's brain is functionally organized will likely bring dramatic advances to many fields of study. Here we show a model-based approach toward characterizing ...resting state functional connectivity MRI (rs-fcMRI) that is capable of identifying a so-called "connectotype", or functional fingerprint in individual participants. The approach rests on a simple linear model that proposes the activity of a given brain region can be described by the weighted sum of its functional neighboring regions. The resulting coefficients correspond to a personalized model-based connectivity matrix that is capable of predicting the timeseries of each subject. Importantly, the model itself is subject specific and has the ability to predict an individual at a later date using a limited number of non-sequential frames. While we show that there is a significant amount of shared variance between models across subjects, the model's ability to discriminate an individual is driven by unique connections in higher order control regions in frontal and parietal cortices. Furthermore, we show that the connectotype is present in non-human primates as well, highlighting the translational potential of the approach.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective: The role of diet and of food colors in attention-deficit/hyperactivity disorder (ADHD) or its symptoms warrants updated quantitative meta-analysis, in light of recent divergent policy in ...Europe and the United States. Method: Studies were identified through a literature search using the PubMed, Cochrane Library, and PsycNET databases through February 2011. Twenty-four publications met inclusion criteria for synthetic food colors; 10 additional studies informed analysis of dietary restriction. A random-effects meta-analytic model generated summary effect sizes. Results: Restriction diets reduced ADHD symptoms at an effect of g = 0.29 (95% CI, 0.07-0.53). For food colors, parent reports yielded an effect size of g = 0.18 (95% CI, 0.08-0.24; p = 0.0007), which decreased to 0.12 (95% CI, 0.01-0.23; p less than 0.05) after adjustment for possible publication bias. The effect was reliable in studies restricted to food color additives (g = 0.21, 95% CI = 0.06-0.36) but did not survive correction for possible publication bias and was not reliable in studies confined to Food and Drug Administration-approved food colors. Teacher/observer reports yielded a nonsignificant effect of 0.07 (95% CI = -0.03 to 0.18; p = 0.14). However, high-quality studies confined to color additives yielded a reliable effect (g = 0.22, 95% CI = 0.10-0.41, p = 0.030) that survived correction. In psychometric tests of attention, the summary effect size was 0.27 (95% CI = 0.07-0.47; p = 0.007) and survived correction. An estimated 8% of children with ADHD may have symptoms related to synthetic food colors. Conclusions: A restriction diet benefits some children with ADHD. Effects of food colors were notable were but susceptible to publication bias or were derived from small, nongeneralizable samples. Renewed investigation of diet and ADHD is warranted. (Contains 2 figures and 8 tables.)
Disinhibition is a common focus in psychopathology research. However, use of inhibition models often is piecemeal, lacking an overarching taxonomy of inhibitory processes. The author organizes key ...concepts and models pertaining to different kinds of inhibitory control from the cognitive and temperament/personality literatures. Within the rubrics of executive inhibitory processes, motivational inhibitory processes, and automatic attentional inhibition processes, 8 kinds of inhibition are distinguished. Three basic temperament traits may address key executive and motivational inhibitory processes. Future developmental psychopathology research should be based on a systematic conceptual taxonomy of the kinds of inhibitory function relevant to a given disorder. Such an approach can clarify which inhibition distinctions are correct and which inhibition deficits go with which disorders.
IMPORTANCE: Psychiatric nosology is limited by behavioral and biological heterogeneity within existing disorder categories. The imprecise nature of current nosologic distinctions limits both ...mechanistic understanding and clinical prediction. We demonstrate an approach consistent with the National Institute of Mental Health Research Domain Criteria initiative to identify superior, neurobiologically valid subgroups with better predictive capacity than existing psychiatric categories for childhood attention-deficit/hyperactivity disorder (ADHD). OBJECTIVE: To refine subtyping of childhood ADHD by using biologically based behavioral dimensions (ie, temperament), novel classification algorithms, and multiple external validators. DESIGN, SETTING, AND PARTICIPANTS: A total of 437 clinically well-characterized, community-recruited children, with and without ADHD, participated in an ongoing longitudinal study. Baseline data were used to classify children into subgroups based on temperament dimensions and examine external validators including physiological and magnetic resonance imaging measures. One-year longitudinal follow-up data are reported for a subgroup of the ADHD sample to address stability and clinical prediction. MAIN OUTCOMES AND MEASURES: Parent/guardian ratings of children on a measure of temperament were used as input features in novel community detection analyses to identify subgroups within the sample. Groups were validated using 3 widely accepted external validators: peripheral physiological characteristics (cardiac measures of respiratory sinus arrhythmia and pre-ejection period), central nervous system functioning (via resting-state functional connectivity magnetic resonance imaging), and clinical outcomes (at 1-year longitudinal follow-up). RESULTS: The community detection algorithm suggested 3 novel types of ADHD, labeled as mild (normative emotion regulation), surgent (extreme levels of positive approach-motivation), and irritable (extreme levels of negative emotionality, anger, and poor soothability). Types were independent of existing clinical demarcations including DSM-5 presentations or symptom severity. These types showed stability over time and were distinguished by unique patterns of cardiac physiological response, resting-state functional brain connectivity, and clinical outcomes 1 year later. CONCLUSIONS AND RELEVANCE: Results suggest that a biologically informed temperament-based typology, developed with a discovery-based community detection algorithm, provides a superior description of heterogeneity in the ADHD population than does any current clinical nosologic criteria. This demonstration sets the stage for more aggressive attempts at a tractable, biologically based nosology.
Background
Peripheral epigenetic marks hold promise for understanding psychiatric illness and may represent fingerprints of gene–environment interactions. We conducted an initial examination of CpG ...methylation variation in children with or without attention‐deficit/hyperactivity disorder (ADHD).
Methods
Children age 7–12 were recruited, screened, evaluated and assigned to ADHD or non‐ADHD groups by defined research criteria. Two independent age‐matched samples were examined, a discovery set (n = 92, all boys, half control, half ADHD) and a confirmation set (n = 20, half ADHD, all boys). 5‐methylcytosine levels were quantified in salivary DNA using the Illumina 450 K HumanMethylation array. Genes for which multiple probes were nominally significant and had a beta difference of at least 2% were evaluated for biological relevance and prioritized for confirmation and sequence validation. Gene pathways were explored and described.
Results
Two genes met the criteria for confirmation testing, VIPR2 and MYT1L; both had multiple probes meeting cutoffs and strong biological relevance. Probes on VIPR2 passed FDR correction in the confirmation set and were confirmed through bisulfite sequencing. Enrichment analysis suggested involvement of gene sets or pathways related to inflammatory processes and modulation of monoamine and cholinergic neurotransmission.
Conclusions
Although it is unknown to what extent CpG methylation seen in peripheral tissue reflect transcriptomic changes in the brain, these initial results indicate that peripheral DNA methylation markers in ADHD may be promising and suggest targeted hypotheses for future study in larger samples.
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.
Literature has suggested that ADHD may be associated with increased risk of obesity. If so, this would have important clinical implications.
To clarify the size of the association between ADHD and ...obesity and to evaluate key moderators of the association including medication, gender, age, and psychiatric comorbidity.
Two preliminary studies are presented to supply critical additional data for the meta-analysis: a two-year longitudinal study of an ADHD case–control sample of 313 children aged 7–11, and a national survey study of 45,309 families in the United States using the 2012 National Survey of Children's Health. Formal meta-analysis was then conducted. The identification procedure yielded 43 studies, reporting 225 comparisons or effect sizes, studying 703,937 participants An overall effect size was estimated with a random effects model (after pooling within study using a modified fixed effects model). Effect size was then examined in relation to medication, gender, age, and psychiatric comorbidity.
The new study of children revealed no reliable association of ADHD and body mass index at any age or time point. In the national survey, ADHD was associated with obesity only in adolescent girls but not in children or boys; this effect was statistically accounted for by covarying of depression and conduct disorder. In the meta-analysis, the composite effect size was OR=1.22 (95% CI=1.11–1.34); 22 studies provided effects with medication controlled, yielding a composite effect size of OR=1.30 (95% CI=1.12–1.50). Pooled across age the association without covariates was reliable in females (OR=1.19 1.01–1.41) but not males (OR=1.10 0.95–1.23) although males and females did not statistically differ. Pooled across gender, the association was significantly larger in adults (>18years) (OR=1.37 1.19–1.58) than in youth (OR=1.13 1.00–1.27), p=.04.
ADHD has a small overall association with obesity, but this effect is moderate in adults. The effect is likely to be of no clinical significance in children, possible clinical significance in adolescent girls with comorbid disorders, and of clinical relevance by adulthood.
•ADHD and obesity may be associated but effect moderators are unclear.•A meta-analysis of 43 studies was conducted.•A reliable overall ADHD-to-obesity association was found with a small effect size.•The effect was larger in adults over 18years old than in children.•This association may be of minimal clinical impact in children but more in adults.
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