Background
Attention‐deficit/hyperactivity disorder (ADHD) is a heterogeneous condition for which multiple efforts to characterize brain state differences are underway. The objective of this study ...was to identify distinct subgroups of resting electroencephalography (EEG) profiles among children with and without ADHD and subsequently provide extensive clinical characterization of the subgroups.
Methods
Latent class analysis was used with resting state EEG recorded from a large sample of 781 children with and without ADHD (N = 620 ADHD, N = 161 Control), aged 6–18 years old. Behavioral and cognitive characteristics of the latent classes were derived from semistructured diagnostic interviews, parent completed behavior rating scales, and cognitive test performance.
Results
A five‐class solution was the best fit for the data, of which four classes had a defining spectral power elevation. The distribution of ADHD and control subjects was similar across classes suggesting there is no one resting state EEG profile for children with or without ADHD. Specific latent classes demonstrated distinct behavioral and cognitive profiles. Those with elevated slow‐wave activity (i.e. delta and theta band) had higher levels of externalizing behaviors and cognitive deficits. Latent subgroups with elevated alpha and beta power had higher levels of internalizing behaviors, emotion dysregulation, and intact cognitive functioning.
Conclusions
There is population‐level heterogeneity in resting state EEG subgroups, which are associated with distinct behavioral and cognitive profiles. EEG measures may be more useful biomarkers of ADHD outcome or treatment response rather than diagnosis.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Atomoxetine is a nonstimulant medication used to treat attention‐deficit/hyperactivity disorder (ADHD). Cytochrome P450 (CYP)2D6 polymorphisms influence the metabolism of atomoxetine thereby ...affecting drug efficacy and safety. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for atomoxetine based on CYP2D6 genotype (updates at www.cpicpgx.org).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Research and practice in autism spectrum disorder (ASD) rely on quantitative measures, such as the Social Responsiveness Scale (SRS), for characterization and diagnosis. Like many ASD ...diagnostic measures, SRS scores are influenced by factors unrelated to ASD core features. This study further interrogates the psychometric properties of the SRS using item response theory (IRT), and demonstrates a strategy to create a psychometrically sound short form by applying IRT results.
Methods
Social Responsiveness Scale analyses were conducted on a large sample (N = 21,426) of youth from four ASD databases. Items were subjected to item factor analyses and evaluation of item bias by gender, age, expressive language level, behavior problems, and nonverbal IQ.
Results
Item selection based on item psychometric properties, DIF analyses, and substantive validity produced a reduced item SRS short form that was unidimensional in structure, highly reliable (α = .96), and free of gender, age, expressive language, behavior problems, and nonverbal IQ influence. The short form also showed strong relationships with established measures of autism symptom severity (ADOS, ADI‐R, Vineland). Degree of association between all measures varied as a function of expressive language.
Conclusions
Results identified specific SRS items that are more vulnerable to non‐ASD‐related traits. The resultant 16‐item SRS short form may possess superior psychometric properties compared to the original scale and emerge as a more precise measure of ASD core symptom severity, facilitating research and practice. Future research using IRT is needed to further refine existing measures of autism symptomatology.
Read the Commentary on this article at doi: 10.1111/jcpp.12801
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
In the current study we sought to dissociate the component processes of working memory (WM) (vigilance, encoding and maintenance) that may be differentially impaired in attention-deficit/ ...hyperactivity disorder (ADHD). We collected electroencephalographic (EEG) data from 52 children with ADHD and 47 typically developing (TD) children, ages 7-14 years, while they performed a spatial Sternberg working memory task. We used independent component analysis and time-frequency analysis to identify midoccipital alpha (8-12 Hz) to evaluate encoding processes and frontal midline theta (4-7 Hz) to evaluate maintenance processes. We tested for effects of task difficulty and cue processing to evaluate vigilance. Children with ADHD showed attenuated alpha band event-related desynchronization (ERD) during encoding. This effect was more pronounced when task difficulty was low (consistent with impaired vigilance) and was predictive of memory task performance and symptom severity. Correlated with alpha ERD during encoding were alpha power increases during the maintenance period (relative to baseline), suggesting a compensatory effort. Consistent with this interpretation, midfrontal theta power increases during maintenance were stronger in ADHD and in high-load memory conditions. Furthermore, children with ADHD exhibited a maturational lag in development of posterior alpha power whereas age-related changes in frontal theta power deviated from the TD pattern. Last, subjects with ADHD showed age-independent attenuation of evoked responses to warning cues, suggesting low vigilance. Combined, these three EEG measures predicted diagnosis with 70% accuracy. We conclude that the interplay of impaired vigilance and encoding in ADHD may compromise maintenance and lead to impaired WM performance in this group.
An expert review of the aetiology, assessment, and treatment of autism spectrum disorder, and recommendations for diagnosis, management and service provision was coordinated by the British ...Association for Psychopharmacology, and evidence graded. The aetiology of autism spectrum disorder involves genetic and environmental contributions, and implicates a number of brain systems, in particular the gamma-aminobutyric acid, serotonergic and glutamatergic systems. The presentation of autism spectrum disorder varies widely and co-occurring health problems (in particular epilepsy, sleep disorders, anxiety, depression, attention deficit/hyperactivity disorder and irritability) are common. We did not recommend the routine use of any pharmacological treatment for the core symptoms of autism spectrum disorder. In children, melatonin may be useful to treat sleep problems, dopamine blockers for irritability, and methylphenidate, atomoxetine and guanfacine for attention deficit/hyperactivity disorder. The evidence for use of medication in adults is limited and recommendations are largely based on extrapolations from studies in children and patients without autism spectrum disorder. We discuss the conditions for considering and evaluating a trial of medication treatment, when non-pharmacological interventions should be considered, and make recommendations on service delivery. Finally, we identify key gaps and limitations in the current evidence base and make recommendations for future research and the design of clinical trials.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
We explored patterns of concomitant psychiatric disorders in a large sample of treatment-seeking children and adolescents with autism spectrum disorder (ASD).
Participants were 658 children with ASD ...(age 3–17 years; mean = 7.2 years) in one of six federally-funded multisite randomized clinical trials (RCT) between 1999 and 2014. All children were referred for hyperactivity or irritability. Study designs varied, but all used the Child and Adolescent Symptom Inventory or Early Childhood Inventory to assess Attention Deficit Hyperactivity Disorder (ADHD), Oppositional-Defiant Disorder (ODD), Conduct Disorder (CD), Anxiety Disorders, and Mood Disorders. In addition, several measures in common were used to assess demographic and clinical characteristics.
Of the 658 children, 73% were Caucasian and 59% had an IQ >70. The rates of concomitant disorders across studies were: ADHD 81%, ODD 46%, CD 12%, any anxiety disorder 42%, and any mood disorder 8%. Two or more psychiatric disorders were identified in 66% of the sample. Of those who met criteria for ADHD, 50% also met criteria for ODD and 46% for any anxiety disorder. Associations between types of concomitant disorders and a number of demographic and clinical characteristics are presented.
In this well-characterized sample of treatment-seeking children with ASD, rates of concomitant psychiatric disorders were high and the presence of two or more co-occurring disorders was common. Findings highlight the importance of improving diagnostic practice in ASD and understanding possible mechanisms of comorbidity.
•We observed a high frequency of multiple concomitant DSM-defined disorders.•50% of children who met criteria for ADHD also met criteria for ODD.•46% of children who met criteria for ADHD also met criteria for an anxiety disorder.•Findings highlight the importance of improving diagnostic practices in ASD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective: To describe the clinical course of attention-deficit/hyperactivity disorder (ADHD) symptom severity and diagnosis from ages 3 to 5 up to 9 to 12 years during a 6-year follow-up after the ...original Preschool ADHD Treatment Study (PATS). Method: A total of 207 participants (75% male) from the original PATS, assessed at baseline (mean age, 4.4 years, when all met criteria for ADHD) and 3 months later (before medication treatment), were re-evaluated in three follow-up assessment visits (year 3, mean age 7.4 years; year 4, 8.3 years; and year 6, 10.4 years). Parents and teachers rated symptom severity, and clinicians established psychiatric diagnoses. Analyses examined longitudinal changes in symptom severity and ADHD diagnosis. Results: Parent- and teacher-rated symptom severity decreased from baseline to year 3 but remained relatively stable and in the moderate-to-severe clinical range through year 6. Girls showed generally steeper decreases in symptom T-scores. At year 6, 89% (160/180) of remaining participants met ADHD symptom and impairment diagnostic criteria. Comorbidity of oppositional defiant disorder and/or conduct disorder was associated with a 30% higher risk of having an ADHD diagnosis at year 6 in the multiple logistic model. Medication status during follow-up, on versus off, did not predict symptom severity change from year 3 to year 6 after adjustment for other variables. Conclusions: ADHD in preschoolers is a relatively stable diagnosis over a 6-year period. The course is generally chronic, with high symptom severity and impairment, in very young children with moderate-to-severe ADHD, despite treatment with medication. Development of more effective ADHD intervention strategies is needed for this age group. (Contains 2 figures and 7 tables.)
In 2017, facing lack of progress and failures encountered in targeted drug development for Autism Spectrum Disorder (ASD) and related neurodevelopmental disorders, the ISCTM with the ECNP created the ...ASD Working Group charged to identify barriers to progress and recommending research strategies for the field to gain traction. Working Group international academic, regulatory and industry representatives held multiple in-person meetings, teleconferences, and subgroup communications to gather a wide range of perspectives on lessons learned from extant studies, current challenges, and paths for fundamental advances in ASD therapeutics. This overview delineates the barriers identified, and outlines major goals for next generation biomedical intervention development in ASD. Current challenges for ASD research are many: heterogeneity, lack of validated biomarkers, need for improved endpoints, prioritizing molecular targets, comorbidities, and more. The Working Group emphasized cautious but unwavering optimism for therapeutic progress for ASD core features given advances in the basic neuroscience of ASD and related disorders. Leveraging genetic data, intermediate phenotypes, digital phenotyping, big database discovery, refined endpoints, and earlier intervention, the prospects for breakthrough treatments are substantial. Recommendations include new priorities for expanded research funding to overcome challenges in translational clinical ASD therapeutic research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Although evidence-based treatments for pediatric obsessive-compulsive disorder (OCD) exist, many youth fail to respond, and interventions tailored to the needs of specific subsets of patients are ...lacking. This study examines the efficacy of a family intervention module designed for cases of OCD complicated by poor family functioning.
Participants were 62 youngsters aged 8 to 17 years (mean age = 12.71 years; 57% male; 65% white) with a primary diagnosis of OCD and at least 2 indicators of poor family functioning. They were randomized to receive 12 sessions of individual child cognitive-behavioral therapy (CBT) plus weekly parent psychoeducation and session review (standard treatment ST) or the same 12 child sessions plus 6 sessions of family therapy aimed at improving OCD-related emotion regulation and problem solving (positive family interaction therapy PFIT). Blinded raters evaluated outcomes and tracked responders to 3-month follow-up.
Compared to ST, PFIT demonstrated better overall response rates on the Clinician Global Impression-Improvement scale (CGI-I; 68% versus 40%, p = .03, φ = 0.28) and rates of remission (58% PFIT versus 27% ST, p = .01, φ = 0.32). PFIT also produced significantly greater reductions in functional impairment, symptom accommodation, and family conflict, and improvements in family cohesion. As expected, these shifts in family functioning constitute an important treatment mechanism, with changes in accommodation mediating treatment response.
PFIT is efficacious for reducing OCD symptom severity and impairment and for improving family functioning. Findings are discussed in terms of personalized medicine and mechanisms of change in pediatric OCD treatment. Clinical trial registration information-Family Focused Treatment of Pediatric Obsessive Compulsive Disorder; http://clinicaltrials.gov/; NCT01409642.
Objective: We sought to examine predictors and moderators of treatment outcomes among 488 youths ages 7-17 years (50% female; 74% ≤ 12 years) meeting Diagnostic and Statistical Manual of Mental ...Disorders (4th ed., text rev.; American Psychiatric Association, 2000) criteria for diagnoses of separation anxiety disorder, social phobia, or generalized anxiety disorder who were randomly assigned to receive either cognitive behavioral therapy (CBT), sertraline (SRT), their combination (COMB), or medication management with pill placebo (PBO) in the Child/Adolescent Anxiety Multimodal Study (CAMS). Method: Six classes of predictor and moderator variables (22 variables) were identified from the literature and examined using continuous (Pediatric Anxiety Ratings Scale; PARS) and categorical (Clinical Global Impression Scale-Improvement; CGI-I) outcome measures. Results: Three baseline variables predicted better outcomes (independent of treatment condition) on the PARS, including low anxiety severity (as measured by parents and independent evaluators) and caregiver strain. No baseline variables were found to predict Week 12 responder status (CGI-I). Participants' principal diagnosis moderated treatment outcomes but only on the PARS. No baseline variables were found to moderate treatment outcomes on Week 12 responder status (CGI-I). Discussion: Overall, anxious children responded favorably to CAMS treatments. However, having more severe and impairing anxiety, greater caregiver strain, and a principal diagnosis of social phobia were associated with less favorable outcomes. Clinical implications of these findings are discussed.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
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