Jeffery N. Epstein

The MTA at 8 Years: Prospective Follow-up of Children Treated for Combined-Type ADHD in a Multisite Study

OBJECTIVES To determine any long-term effects, 6 and 8 years after childhood enrollment, of the randomly assigned 14-month treatments in the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA; N = 436); to test whether attention-deficit/hyperactivity disorder (ADHD) symptom trajectory through 3 years predicts outcome in subsequent years; and to examine functioning level of the MTA adolescents relative to their non-ADHD peers (local normative comparison group; N = 261). METHOD Mixed-effects regression models with planned contrasts at 6 and 8 years tested a wide range of symptom and impairment variables assessed by parent, teacher, and youth report. RESULTS In nearly every analysis, the originally randomized treatment groups did not differ significantly on repeated measures or newly analyzed variables (e.g., grades earned in school, arrests, psychiatric hospitalizations, other clinically relevant outcomes). Medication use decreased by 62% after the 14-month controlled trial, but adjusting for this did not change the results. ADHD symptom trajectory in the first 3 years predicted 55% of the outcomes. The MTA participants fared worse than the local normative comparison group on 91% of the variables tested. CONCLUSIONS Type or intensity of 14 months of treatment for ADHD in childhood (at age 7.0-9.9 years) does not predict functioning 6 to 8 years later. Rather, early ADHD symptom trajectory regardless of treatment type is prognostic. This finding implies that children with behavioral and sociodemographic advantage, with the best response to any treatment, will have the best long-term prognosis. As a group, however, despite initial symptom improvement during treatment that is largely maintained after treatment, children with combined-type ADHD exhibit significant impairment in adolescence. Innovative treatment approaches targeting specific areas of adolescent impairment are needed.

Neuropsychology of adults with attention-deficit/hyperactivity disorder: a meta-analytic review.

A comprehensive, empirically based review of the published studies addressing neuropsychological performance in adults diagnosed with attention-deficit/hyperactivity disorder (ADHD) was conducted to identify patterns of performance deficits. Findings from 33 published studies were submitted to a meta-analytic procedure producing sample-size-weighted mean effect sizes across test measures. Results suggest that neuropsychological deficits are expressed in adults with ADHD across multiple domains of functioning, with notable impairments in attention, behavioral inhibition, and memory, whereas normal performance is noted in simple reaction time. Theoretical and developmental considerations are discussed, including the role of behavioral inhibition and working memory impairment. Future directions for research based on these findings are highlighted, including further exploration of specific impairments and an emphasis on particular tests and testing conditions.

Self-perceptions of competence in children with ADHD and comparison children

The self-perceptions of children with attention-deficit/hyperactivity disorder (ADHD; n = 487) were compared with those of children in a local normative comparison group (n = 287), relative to teacher- and parent-rated perceptions of their competence. Children were participants in the ongoing follow-up portion of the Multimodal Treatment Study of Children with ADHD. Children with ADHD were much more likely than comparison children to overestimate their competence relative to adult report, regardless of who was used as the criterion rater (teacher, mother, or father). Examination by comorbidity subgroups revealed that children with ADHD inflated their self-perceptions the most in domains of greatest deficit. Gender effects also are reported.

Reaction time distribution analysis of neuropsychological performance in an ADHD sample.

Differences in reaction time (RT) variability have been documented between children with and without Attention Deficit Hyperactivity Disorder (ADHD). Most previous research has utilized estimates of normal distributions to examine variability. Using a nontraditional approach, the present study evaluated RT distributions on the Conners’ Continuous Performance Test in children and adolescents from the Multimodal Treatment Study of ADHD sample compared to a matched sample of normal controls (n = 65 pairs). The ex-Gaussian curve was used to model RT and RT variability. Children with ADHD demonstrated faster RT associated with the normal portion of the curve and a greater proportion of abnormally slow responses associated with the exponential portion of the curve. These results contradict previous interpretation that children with ADHD have slower than normal responding and demonstrate why slower RT is found when estimates of variability assume normal Gaussian distributions. Further, results of this study suggest that the greater number of abnormally long RTs of children with ADHD reflect attentional lapses on some but not all trials. The MTA is a cooperative treatment study performed by six independent research teams in collaboration with the staff of the Division of Clinical and Treatment Research of the National Institute of Mental Health (NIMH), Rockville, Maryland and the Office of Special Education Programs (OSEP) of the U.S. Department of Education (DOE). The NIMH Principal Collaborators are Peter S. Jensen, M.D., L. Eugene Arnold, M.Ed., M.D., John E. Richters, Ph.D., Joanne B. Severe, M.S., Donald Vereen, M.D., and Benedetto Vitiello, M.D. Principal Investigators and coinvestigators from the six sites are as follows: University of California at Berkeley/San Francisco (UO1 MH50461): Stephen P. Hinshaw, Ph.D., Glen R. Elliott, M.D., Ph.D.; Duke University (UO1 MH50447): C. Keith Conners, Ph.D., Karen C. Wells, Ph.D., John S. March, M.D., M.P.H.; University of California at Irvine/Los Angeles (UO1 MH50440): James M. Swanson, Ph.D.; Dennis P. Cantwell, M.D.; Timothy Wigal, Ph.D.; Long Island Jewish Medical Center/Montreal Childrens Hospital (UO1 MH50453): Howard B. Abikoff, Ph.D., Lily Hechtman, M.D.; New York State Psychiatric Institute/Columbia University/Mount Sinai Medical Center (UO1 MH50454): Laurence L. Greenhill, M.D., Jeffrey H. Newcorn, M.D.; University of Pittsburgh (UO1 MH50467): William E. Pelham, Ph.D., Betsy Hoza, Ph.D. Helena C. Kraemer, Ph.D. (Stanford University) is statistical and design consultant. The OSEP/DOE Principal Collaborator is Thomas Hanley, Ed.D. Aaron Hervey, Ph.D. was supported on this project by a midcareer development award to the second author (K24 MH64478).

Racial Differences on the Conners Teacher Rating Scale

Factor congruence and mean differences on the Conners Teacher Rating Scale were assessed across African-American and Caucasian school children. Factor analyses conducted separately by gender revealed similar factors across races for males and females. The main differences in factor structure within gender were the presence of an Antisocial factor in black males and an Inattention factor in white females. Across both males and females, teachers tended to rate black children higher than white children on factors relating to externalizing behaviors. Whether mean differences are a result of teacher bias or actual behavioral differences in the classroom needs further research.

Familial aggregation of ADHD characteristics

Patterns of familial aggregation of ADHD symptoms in parents of ADHD and non-ADHD children were examined. Within the ADHD sample, symptom aggregation was examined as a function of biological relationship, parent and child gender, and childrens comorbid diagnoses. Participants consisted of parents of 579 children with ADHD, Combined Type participating in the multimodal treatment study of children with ADHD and parents of 288 normal control participants. Adult symptoms of ADHD were measured by both self-report and report of a significant other. Results indicated that the parents of children with ADHD had higher ratings of inattention/cognitive problems, hyperactivity/restlessness, impulsivity/emotional lability, and lower self-concept than parents of children without ADHD on both self-report and other-report ratings. Within the ADHD sample of children, other-report ratings of inattention/cognitive problems and impulsivity/emotional lability were higher for biological parents compared to nonbiological parents whereas self-ratings were not related to biological status. These findings support previous research documenting familial aggregation of ADHD and appear to strengthen the hypothesis that there is a genetic contribution to ADHD.

Psychometric Properties of an Adult ADHD Diagnostic Interview

Although research has been conducted to support the psychometric properties of rating scales used to assess ADHD in adults, little work has been published examining semi-structured interviews to assess ADHD in adults. The present study examined the test-retest reliability and concurrent validity of the Conners Adult ADHD Diagnostic Interview for Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) in a sample (N = 30) of patients referred to an outpatient clinic. Kappa statistics for individual symptoms of inattention and hyperactivity-impulsivity were in the fair to good range for current report and retrospective childhood report. Kappa values for overall diagnosis, which included all DSM-IV symptoms, were fair for both current (adult) ADHD diagnosis (kappa = .67) and childhood report (kappa = .69). Concurrent validity was demonstrated for adult hyperactive-impulsive symptoms and child inattentive symptoms. The findings are discussed in the context of overall issues pertaining to adult ADHD assessment.

Response to Commentary on the Multimodal Treatment Study of ADHD (MTA): Mining the Meaning of the MTA

In the December 2000 issue of the Journal of Abnormal Child Psychology, we published a set of papers presenting secondary analyses of the Multimodal Treatment Study of ADHD (MTA), and R. A. Barkley (2000) provided a commentary. A critique of the design of the study (MTA Cooperative Group, 1999) was presented based on a theoretical perspective of a “behavioral inhibition” deficit that has been hypothesized as the core deficit of ADHD (R. A. Barkley, 1997). The commentary questioned the design and analysis of the MTA in terms of (1) the empirical criteria for selection of components of behavioral (Beh) intervention, (2) the effectiveness of the Beh intervention, (3) the methods for analyses at the group and individual level, (4) implications of the MTA findings for clinical practice, (5) the role of genetics in response to treatment, and (6) the lack of a nontreatment control group. In this response, we relate the content of the papers to the commentary, (1) by reviewing the selection criteria for the Beh treatment, as outlined by K. C. Wells, W. E. Pelham, et al. (2000), (2) by addressing the myth that the MTA Beh treatment was ineffective (Pelham, 1999), (3) by describing the use of analyses at the level of the individual participant, as presented by J. S. March et al. (2000) and W. E. Pelham et al. (2000) as well as elsewhere by J. M. Swanson et al. (2001) and C. K. Conners et al. (2001), (4) by relating some of the suggestions from the secondary analyses about clinically relevant factors such as comorbidity (as presented by J. S. March et al., 2000) and family and parental characteristics (as presented by B. Hoza et al., 2000, S. P. Hinshaw et al., 2000, and K. C. Wells, J. N. Epstein, et al., 2000), (5) by discussing the statistical concept of heritability and the lack of a significant difference in the presence of ADHD symptoms in parents of the MTA families compared to parents in the classmate-control families (as presented by J. N. Epstein, et al., 2000), and (6) by acknowledging that an ethically necessary weakness of the MTA design is that it did not include a no-treatment control group. We discuss the use of secondary analyses to suggest how, when, and for what subgroups effectiveness of the Beh treatment may have been manifested. Finally, we invite others to use the large and rich data set that will soon be available in the public domain, to perform secondary analyses to mine the meaning of the MTA and to evaluate theories of ADHD and response to treatments.

Gestational and postnatal tobacco smoke exposure as predictor of ADHD, comorbid ODD/CD, and treatment response in the MTA

Abstract Objective: To examine relationships among early smoke exposure (ESE), attention-deficit/hyperactivity disorder (ADHD), oppositional-defiant or conduct disorder (ODD/CD), and whether ESE affects symptom severity, comorbidity, and later treatment response. Study design: The Multimodal Treatment Study of Children with ADHD (MTA) had 468 children with ADHD and 279 others from the same classrooms (local normative comparison group, LNCG) with smoke-exposure data. We compared ESE as ‘gestational’ or ‘postnatal’ (ambient house smoke only, without gestational) between ADHD and LNCG, and tested its association with ADHD severity, comorbid ODD/CD, methylphenidate response, and differential treatment response to four randomly assigned treatments. Results: About 1/3 more ADHD than LNCG children had ESE (both types), but association with gestational smoke attenuated from P =0.024 to 0.094 when subjects with comorbid ODD/CD were excluded, although total smoke exposure retained significance ( P =0.006). In the MTA/ADHD participants, comorbid ODD/CD, and parent/teacher-rated ADHD and ODD symptom severity were not associated with gestational smoking, but severity of ODD was associated with postnatal smoke, and for boys only, ADHD severity at 14 months associated with postnatal smoke. When ODD and CD were ‘unbundled’, CD was associated ( P =0.005) with gestational smoke. Neither ESE moderated response to methylphenidate, optimal dose, 2-year growth slowing, or differential ODD symptom response to 14-months of 4 randomly assigned treatments. However, for ADHD symptoms, postnatal smoke moderated ( P =0.008) the 14-month advantage of behavioral treatment (Beh) over community-treated comparison (CC): postnatally exposed boys benefited relatively more from Beh ( d >0.5). ADHD symptom improvement also showed significant interaction of sex with gestational ( P =0.015) and postnatal ( P =0.044) smoke moderator effect for the contrast of MTA medication algorithm vs. Beh and CC: smoke-exposed girls did not show the usual algorithm superiority. Conclusions: These findings suggest possible moderating effects of postnatal ESE on the advantage of intensive behavioral treatment and sex-differential moderating effects of ESE on the advantage of intensive medication over behavioral treatment. This exploratory result requires replication. The findings do not convincingly support the hypothesis that the association of gestational smoking with offspring ADHD is accounted for by comorbid ODD/CD.