Faculty Bibliography

Objectives: Organizational Skills Training (OST), is a 10-week psychosocial intervention found effective in improving organizational, time management, and planning (OTMP) skills in children with Attention-Deficit/Hyperactivity Disorder (ADHD). Little is known about the feasibility of identifying brain markers for treatment response. Using resting state fMRI (R-fMRI), we aimed to examine neuronal correlates of post-treatment change as a first step toward larger controlled studies of objective predictors of treatment response. Methods: We examined pre- and post-OST R-fMRI data of 15 children (12 males; mean age: 9+/-1 year) with ADHD and significant impairments in OTMP skills indexed by total scores on Children's Organizational Skills Scales-Parent (COSS-P) or Teacher (COSS-T). Our primary outcome measure was the change in COSS-P scores. As secondary summary outcome measure, we used prepost Z-score differences averaged across COSS-T, Homework Problems Checklist, Academic Progress Report and Academic Performance Rating scales. We selected a priori the intrinsic functional connectivity (iFC) of the dorsal anterior cingulate cortex (dACC), based on its role on cognitive control. Multivariate distance matrix regression (MDMR) analysis additionally allowed for whole-brain explorations. Follow-up iFC analyses were conducted on regions with significant within-subject post-OST differences by MDMR analysis. Results: COSS-P decreased significantly (t=7.1, p< 0.0001). In a cluster involving striatum bilaterally, dACC iFC decreased post-OST; these decreases were positively correlated with COSS-P improvements (r=.34, NS) and to improvements in the summary outcome (r=.63; p<0.03). MDMR analyses revealed iFC changes in the right medial and lateral precentral cortex. Followup seed-based iFC analyses of this region showed significant decreases in cortico-striatal iFC post-OST. Conclusions: Results support the feasibility of identifying changes in brain iFC after OST. Two distinct analysis converged on decreased corticosubcortical iFC post-treatment which related to change in clinical measures. As decreases in striato-cortical iFC characterize typical development, results suggest regionally-specific enhanced maturational effects of OST

Objectives: Organization, time management, and planning (OTMP) difficulties have an impact on a substantial proportion (~50 percent) of children with ADHD, and they improve with behavioral intervention. Given symptomatic overlap between ASD and ADHD, children with ASD may also experience OTMP impairments. To date, examinations of this domain in ASD are missing. Objectives include the following: 1) to characterize the nature and extent of OTMP deficits in children with ASD and identify rates of ADHD comorbidity in children with ASD with and without OTMP impairments (ASD+, ASD-, respectively); and 2) to identify similarities and differences between the ASD+ and ASD- subgroups and children with ADHD and OTMP impairments (ADHD+). Methods: We examined data (N = 85) of children aged 8-13 years with DSM-IV-TR diagnoses of ASD (n = 35) or ADHD (n = 31), as well as typically developing children (TDC) (n = 19). ANOVA compared the groups on parent scores on the Children's Organizational Skills Scale (COSS-P) and the subgroups on ASD traits, ADHD traits, and executive functions (ratings on the Social Responsiveness Scale, Conners' Parent Rating Scale, and Behavior Rating Inventory of Executive Functions). A threshold for significance was set at P = 0.01. Results: Children with ASD and ADHD had higher (i.e., more severe) COSS-P Total T scores than TDC. Forty-two percent of the children with ASD were ASD+ (i.e., COSS-P Total T >65), and 47 percent were categorized as ADHD+. Eighty-seven percent of the ASD+ had comorbid ADHD per clinician's interview, in contrast with only 27 percent of the ASD- subgroup. The severity of ADHD traits and executive dysfunction was no different between ASD+ and ADHD+ groups. In contrast, ASD- children had significantly lower ratings of ADHD and executive function severity than children with OTMP deficits. It is noteworthy that the ASD+ and ASD- groups differed in ASD ratings. Results were replicated with a second, independent sample group (N = 150). Conclusions: A substantial proportion of children with ASD exhibited OTMP functional impairment difficulties, which accompanied other symptoms typically observed in ADHD. Given the availability of evidence-based interventions for OTMP impairments in ADHD, adaptations of this intervention for this population may be warranted

OBJECTIVE: To compare educational, occupational, legal, emotional, substance use disorder, and sexual behavior outcomes in young adults with persistent and desistent attention-deficit/hyperactivity disorder (ADHD) symptoms and a local normative comparison group (LNCG) in the Multimodal Treatment Study of Children with ADHD (MTA). METHOD: Data were collected 12, 14, and 16 years postbaseline (mean age 24.7 years at 16 years postbaseline) from 476 participants with ADHD diagnosed at age 7 to 9 years, and 241 age- and sex-matched classmates. Probands were subgrouped on persistence versus desistence of DSM-5 symptom count. Orthogonal comparisons contrasted ADHD versus LNCG and symptom-persistent (50%) versus symptom-desistent (50%) subgroups. Functional outcomes were measured with standardized and demographic instruments. RESULTS: Three patterns of functional outcomes emerged. Post-secondary education, times fired/quit a job, current income, receiving public assistance, and risky sexual behavior showed the most common pattern: the LNCG group fared best, symptom-persistent ADHD group worst, and symptom-desistent ADHD group between, with the largest effect sizes between LNCG and symptom-persistent ADHD. In the second pattern, seen with emotional outcomes (emotional lability, neuroticism, anxiety disorder, mood disorder) and substance use outcomes, the LNCG and symptom-desistent ADHD group did not differ, but both fared better than the symptom-persistent ADHD group. In the third pattern, noted with jail time (rare), alcohol use disorder (common), and number of jobs held, group differences were not significant. The ADHD group had 10 deaths compared to one death in the LNCG. CONCLUSION: Adult functioning after childhood ADHD varies by domain and is generally worse when ADHD symptoms persist. It is important to identify factors and interventions that promote better functional outcomes.

The present study examined whether the presence of comorbid ODD differentially moderated the outcome of two Behavioral Parent Training (BPT) programs in a sample of preschoolers with ADHD: One designed specifically for ADHD (NFPP: New Forest Parenting Programme) and one designed primarily for ODD (HNC: Helping the Noncompliant Child). In a secondary analysis, 130 parents and their 3-4 year-old children diagnosed with ADHD were assigned to one of the two programs. 44.6 % of the children also met criteria for ODD. Significant interactions between treatment conditions (NFPP vs. HNC) and child ODD diagnosis (presence vs. absence) indicated that based on some parent and teacher reports, HNC was more effective with disruptive behaviors than NFPP but only when children had a comorbid diagnosis. Further, based on teacher report, NFPP was more effective with these behaviors when children had a diagnosis of only ADHD whereas HNC was equally effective across ADHD only and comorbid ODD diagnoses. Comorbidity profile did not interact with treatment program when parent or teacher reported ADHD symptoms served as the outcome. Implications for clinical interventions are discussed and directions for future work are provided.

AIM: To determine the prevalence of bipolar disorder (BD) and sub-threshold symptoms in children with attention deficit hyperactivity disorder (ADHD) through 14 years' follow-up, when participants were between 21-24 years old. METHODS: First, we examined rates of BD type I and II diagnoses in youth participating in the NIMH-funded Multimodal Treatment Study of ADHD (MTA). We used the diagnostic interview schedule for children (DISC), administered to both parents (DISC-P) and youth (DISCY). We compared the MTA study subjects with ADHD (n = 579) to a local normative comparison group (LNCG, n = 289) at 4 different assessment points: 6, 8, 12, and 14 years of follow-ups. To evaluate the bipolar variants, we compared total symptom counts (TSC) of DSM manic and hypomanic symptoms that were generated by DISC in ADHD and LNCG subjects. Then we sub-divided the TSC into pathognomonic manic (PM) and non-specific manic (NSM) symptoms. We compared the PM and NSM in ADHD and LNCG at each assessment point and over time. We also evaluated the irritability as category A2 manic symptom in both groups and over time. Finally, we studied the irritability symptom in correlation with PM and NSM in ADHD and LNCG subjects. RESULTS: DISC-generated BD diagnosis did not differ significantly in rates between ADHD (1.89%) and LNCG 1.38%). Interestingly, no participant met BD diagnosis more than once in the 4 assessment points in 14 years. However, on the symptom level, ADHD subjects reported significantly higher mean TSC scores: ADHD 3.0; LNCG 1.7; P < 0.001. ADHD status was associated with higher mean NSM: ADHD 2.0 vs LNCG 1.1; P < 0.0001. Also, ADHD subjects had higher PM symptoms than LNCG, with PM means over all time points of 1.3 ADHD; 0.9 LNCG; P = 0.0001. Examining both NSM and PM, ADHD status associated with greater NSM than PM. However, Over 14 years, the NSM symptoms declined and changed to PM over time (df 3, 2523; F = 20.1; P < 0.0001). Finally, Irritability (BD DSM criterion-A2) rates were significantly higher in ADHD than LNCG (chi(2) = 122.2, P < 0.0001), but irritability was associated more strongly with NSM than PM (df 3, 2538; F = 43.2; P < 0.0001). CONCLUSION: Individuals with ADHD do not appear to be at significantly greater risk for developing BD, but do show higher rates of BD symptoms, especially NSM. The greater linkage of irritability to NSM than to PM suggests caution when making BD diagnoses based on irritability alone as one of 2 (A-level) symptoms for BD diagnosis, particularly in view of its frequent presentation with other psychopathologies.

OBJECTIVE: To describe the long-term psychopharmacological treatment of children first diagnosed with attention-deficit/hyperactivity disorder (ADHD) as preschoolers. METHOD: In a systematic, prospective, naturalistic follow-up, 206 (68.0%) of the 303 children who participated in the Preschool ADHD Treatment Study (PATS) were reassessed 3 years (mean age 7.4 years) and 179 (59.1%) were reassessed 6 years (mean age 10.4 years) after completion of the controlled study. Pharmacotherapy and clinical data were obtained from the parents. Pharmacotherapy was defined as use of a specific class of medication for at least 50% of the days in the previous 6 months. RESULTS: At year 3, a total of 34.0% of the participants were on no pharmacotherapy, 41.3% were on stimulant monotherapy, 9.2% were on atomoxetine alone or with a stimulant, 8.3% were on an antipsychotic usually together with a stimulant, and the remaining 7.2% were on other pharmacotherapy; overall, 65.0% were on an indicated ADHD medication. At year 6, a total of 26.8% of the participants were on no pharmacotherapy, 40.2% were on stimulant monotherapy, 4.5% were on atomoxetine alone or with a stimulant, 13.4% were on an antipsychotic, and 15.1% were on other pharmacotherapy; overall, 70.9% were on an indicated ADHD medication. Antipsychotic treatment was associated with more comorbidity, in particular disruptive behavior disorders and pervasive development disorders, and a lower level of functioning. CONCLUSION: In this study, the long-term pharmacotherapy of preschoolers with ADHD was heterogeneous. Although stimulant medication continued to be used by most children, about 1 child in 4 was off medication, and about 1 in 10 was on an antipsychotic.

AIMS: To examine the association between developmental trajectories of inattention, hyperactivity-impulsivity, and delinquency through childhood and adolescence (ages 8-16) and subsequent binge drinking and marijuana use in early adulthood (age 21). DESIGN: Prospective naturalistic follow-up of children with attention-deficit/hyperactivity disorder (ADHD) previously enrolled in a randomized controlled trial (RCT). Treatment-phase assessments occurred at 3, 9, and 14 months after randomization; follow-up assessments occurred at 24 months, 36 months, and 6, 8, and 12 years after randomization. SETTING: Secondary analysis of data from the Multimodal Treatment Study of ADHD (MTA), a multi-site RCT comparing the effects of careful medication management, intensive behavior therapy, their combination, and referral to usual community care. PARTICIPANTS: 579 children with DSM-IV ADHD combined type, aged 7.0 and 9.9 years old at baseline (M=8.5, SD=.80). MEASUREMENTS: Ratings of inattention, hyperactivity-impulsivity, and delinquency were collected from multiple informants at baseline and through the 8-year follow-up. Self-reports of binge drinking and marijuana use were collected at the 12-year follow-up (M age 21). FINDINGS: Trajectories of worsening inattention symptoms and delinquency (and less apparent improvement in hyperactivity-impulsivity) were associated with higher rates of early adult binge drinking and marijuana use, compared with trajectories of stable or improving symptoms and delinquency (of 24 comparisons, 22 p-values <.05), even when symptom levels in stable trajectories were high. CONCLUSIONS: Worsening inattention symptoms and delinquency during adolescence are associated with increased levels of early adult substance use; this pattern may reflect a developmental course of vulnerability to elevated substance use in early adulthood.

BACKGROUND: The 'New Forest Parenting Package' (NFPP), an 8-week home-based intervention for parents of preschoolers with attention-deficit/hyperactivity disorder (ADHD), fosters constructive parenting to target ADHD-related dysfunctions in attention and impulse control. Although NFPP has improved parent and laboratory measures of ADHD in community samples of children with ADHD-like problems, its efficacy in a clinical sample, and relative to an active treatment comparator, is unknown. The aims are to evaluate the short- and long-term efficacy and generalization effects of NFPP compared to an established clinic-based parenting intervention for treating noncompliant behavior ['Helping the Noncompliant Child' (HNC)] in young children with ADHD. METHODS: A randomized controlled trial with three parallel arms was the design for this study. A total of 164 3-4-year-olds, 73.8% male, meeting DSM-IV ADHD diagnostic criteria were randomized to NFPP (N = 67), HNC (N = 63), or wait-list control (WL, N = 34). All participants were assessed at post-treatment. NFPP and HNC participants were assessed at follow-up in the next school year. Primary outcomes were ADHD ratings by teachers blind to and uninvolved in treatment, and by parents. Secondary ADHD outcomes included clinician assessments, and laboratory measures of on-task behavior and delay of gratification. Other outcomes included parent and teacher ratings of oppositional behavior, and parenting measures. (Trial name: Home-Based Parent Training in ADHD Preschoolers; Registry: ClinicalTrials.gov Identifier: NCT01320098; URL: http://www/clinicaltrials.gov/ct2/show/NCT01320098). RESULTS: In both treatment groups, children's ADHD and ODD behaviors, as well as aspects of parenting, were rated improved by parents at the end of treatment compared to controls. Most of these gains in the children's behavior and in some parenting practices were sustained at follow-up. However, these parent-reported improvements were not corroborated by teacher ratings or objective observations. NFPP was not significantly better, and on a few outcomes significantly less effective, than HNC. CONCLUSIONS: The results do not support the claim that NFPP addresses putative dysfunctions underlying ADHD, bringing about generalized change in ADHD, and its underpinning self-regulatory processes. The findings support documented difficulties in achieving generalization across nontargeted settings, and the importance of using blinded measures to provide meaningful assessments of treatment effects.

This study examines the prevalence and characteristics of services reported by school staff for 543 high school students participating in the 8 year follow-up of the multi-site Multimodal Treatment study of ADHD (MTA). Overall, 51.6% of students with a history of attention-deficit/hyperactivity disorder (ADHD) were receiving services through an Individualized Educational Plan (IEP) or a 504 plan, a rate higher than expected for this age group. Less than 5% of these had 504 plans; 35.5% attended special education classes. Very few services (except tutoring) were provided outside of an IEP or 504 plan. Almost all students with services received some type of academic intervention, whereas only half received any behavioral support or learning strategy. Less than one-fourth of interventions appear to be evidence-based. Students receiving services showed greater academic and behavioral needs than those not receiving services. Services varied based upon type of school, with the greatest number of interventions provided to students attending schools that only serve those with disabilities. Original MTA treatment randomization was unrelated to services, but cumulative stimulant medication and greater severity predicted more service receipt. Results highlight a need for accommodations with greater evidence of efficacy and for increased services for students who develop academic difficulties in high school.