Faculty Bibliography

OBJECTIVE: To evaluate the hypothesis of stimulant medication effect on physical growth in the follow-up phase of the Multimodal Treatment Study of Children With ADHD. METHOD: Naturalistic subgroups were established based on patterns of treatment with stimulant medication at baseline, 14-, 24-, and 36-month assessments: not medicated (n = 65), newly medicated (n = 88), consistently medicated (n = 70), and inconsistently medicated (n = 147). Analysis of variance was used to evaluate effects of subgroup and assessment time on measures of relative size (z scores) obtained from growth norms. RESULTS: The subgroup x assessment time interaction was significant for z height (p <.005) and z weight (p <.0001), due primarily to divergence of the newly medicated and the not medicated subgroups. These initially stimulant-naive subgroups had z scores significantly >0 at baseline. The newly medicated subgroup showed decreases in relative size that reached asymptotes by the 36-month assessment, when this group showed average growth of 2.0 cm and 2.7 kg less than the not medicated subgroup, which showed slight increases in relative size. CONCLUSIONS: Stimulant-naive school-age children with Combined type attention-deficit/hyperactivity disorder were, as a group, larger than expected from norms before treatment but show stimulant-related decreases in growth rates after initiation of treatment, which appeared to reach asymptotes within 3 years without evidence of growth rebound

OBJECTIVE: To compare delinquent behavior and early substance use between the children in the Multimodal Treatment Study of Children With ADHD (MTA; N = 487) and those in a local normative comparison group (n = 272) at 24 and 36 months postrandomization and to test whether these outcomes were predicted by the randomly assigned treatments and subsequent self-selected prescribed medications. METHOD: Most MTA children were 11 to 13 years old by 36 months. Delinquency seriousness was coded ordinally from multiple measures/reporters; child-reported substance use was binary. RESULTS: Relative to local normative comparison group, MTA children had significantly higher rates of delinquency (e.g., 27.1% vs. 7.4% at 36 months; p = .000) and substance use (e.g., 17.4% vs. 7.8% at 36 months; p = .001). Children randomized to intensive behavior therapy reported less 24-month substance use than other MTA children (p = .02). Random effects ordinal growth models revealed no other effects of initial treatment assignment on delinquency seriousness or substance use. By 24 and 36 months, more days of prescribed medication were associated with more serious delinquency but not substance use. CONCLUSIONS: Cause-and-effect relationships between medication treatment and delinquency are unclear; the absence of associations between medication treatment and substance use needs to be re-evaluated at older ages. Findings underscore the need for continuous monitoring of these outcomes as children with attention-deficit/hyperactivity disorder enter adolescence

OBJECTIVE: To evaluate two hypotheses: that self-selection bias contributed to lack of medication advantage at the 36-month assessment of the Multimodal Treatment Study of Children With ADHD (MTA) and that overall improvement over time obscured treatment effects in subgroups with different outcome trajectories. METHOD: Propensity score analyses, using baseline characteristics and severity of attention-deficit/hyperactivity disorder symptoms at follow-up, established five subgroups (quintiles) based on tendency to take medication at the 36-month assessment. Growth mixture model (GMM) analyses were performed to identify subgroups (classes) with different patterns of outcome over time. RESULTS: All five propensity subgroups showed initial advantage of medication that disappeared by the 36-month assessment. GMM analyses identified heterogeneity of trajectories over time and three classes: class 1 (34% of the MTA sample) with initial small improvement followed by gradual improvement that produced significant medication effects; class 2 (52%) with initial large improvement maintained for 3 years and overrepresentation of cases treated with the MTA Medication Algorithm; and class 3 (14%) with initial large improvement followed by deterioration. CONCLUSIONS: We failed to confirm the self-selection hypothesis. We found suggestive evidence of residual but not current benefits of assigned medication in class 2 and small current benefits of actual treatment with medication in class 1

OBJECTIVE: In the intent-to-treat analysis of the Multimodal Treatment Study of Children With ADHD (MTA), the effects of medication management (MedMgt), behavior therapy (Beh), their combination (Comb), and usual community care (CC) differed at 14 and 24 months due to superiority of treatments that used the MTA medication algorithm (Comb+MedMgt) over those that did not (Beh+CC). This report examines 36-month outcomes, 2 years after treatment by the study ended. METHOD: For primary outcome measures (attention-deficit/hyperactivity disorder [ADHD] and oppositional defiant disorder [ODD] symptoms, social skills, reading scores, impairment, and diagnostic status), mixed-effects regression models and orthogonal contrasts examined 36-month outcomes. RESULTS: At 3 years, 485 of the original 579 subjects (83.8%) participated in the follow-up, now at ages 10 to 13 years, (mean 11.9 years). In contrast to the significant advantage of MedMgt+Comb over Beh+CC for ADHD symptoms at 14 and 24 months, treatment groups did not differ significantly on any measure at 36 months. The percentage of children taking medication >50% of the time changed between 14 and 36 months across the initial treatment groups: Beh significantly increased (14% to 45%), MedMed+Comb significantly decreased (91% to 71%), and CC remained constant (60%-62%). Regardless of their treatment use changes, all of the groups showed symptom improvement over baseline. Notably, initial symptom severity, sex (male), comorbidity, public assistance, and parental psychopathology (ADHD) did not moderate children's 36-month treatment responses, but these factors predicted worse outcomes over 36 months, regardless of original treatment assignment. CONCLUSIONS: By 36 months, the earlier advantage of having had 14 months of the medication algorithm was no longer apparent, possibly due to age-related decline in ADHD symptoms, changes in medication management intensity, starting or stopping medications altogether, or other factors not yet evaluated

OBJECTIVE: Little is known about maintenance treatment for panic disorder. The purpose of this naturalistic study is to compare outcomes of remitted panic disorder patients continued on versus those successfully discontinued from maintenance medication. METHODS: After 3 years of sustained remission with medication in a naturalistic setting, 168 patients were continued on, whereas 37 successfully discontinued from medication. Continued and discontinued groups were followed for an additional 4 to 8 years and compared for differences in treatment outcome using chi(2) and Wilcoxon rank sum tests. Times to relapse were analyzed using the Kaplan-Meier product-limit method, and risk factors for relapse were assessed using Cox proportional hazards regression. RESULTS: The discontinued group was healthier at baseline but had a significantly worse outcome compared with the continued group. Panic-free survival probabilities for the continued group at 1, 2, 3, and 4 years were 0.87, 0.81, 0.71, and 0.64, respectively, and were significantly higher than respective probabilities of 0.53, 0.35, 0.29, and 0.15 for the discontinued group. Median survival time in the continued group was significantly longer, at 5.67 years, than in the discontinued group, at 1.17 years. Cognitive behavioral therapy significantly reduced hazard in the discontinued but not in the continued group. Residual symptoms in either group at time of assignment predicted poorer outcome. CONCLUSION: Our small study suggests that relapse of panic disorder in routine clinical practice occurs even after long-standing remission on maintenance medication, and that relapse risk appears to be markedly higher after medication discontinuation. Discontinuation may be more successful in candidates who received cognitive behavioral therapy and have minimal residual symptoms

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays an important role in synaptic plasticity. In this issue of Molecular Pharmacology, Ou and Gean (p. 350) thoroughly describe the molecular cascade by which fear learning leads to an increase in BDNF expression in the lateral amygdala (LA). Calcium influx through N-methyl-D-aspartate receptors and L-type voltage-dependent calcium channels, which occurs in the LA during fear conditioning, activates protein kinase A and Ca2+/calmodulin-dependent protein kinase IV. Each induces phosphorylation of cAMP response element-binding protein, which binds to the BDNF promoter, leading to BDNF expression in the LA, and contributes to fear memory consolidation

Children in child welfare are especially likely to have unmet mental health needs. The role of family factors in children's use of mental health services was examined in a longitudinal sample of 1075 maltreated or at-risk children. Vulnerable family environment (poor family functioning, low social support, and caregiver psychological distress) is an important predictor of children's mental health needs. It also predicts them not having these needs met.

Verbal skills were assessed at approximately ages 2, 3, 5, and 9 years for 206 children with a clinical diagnosis of autism (n = 98), pervasive developmental disorders-not otherwise specified (PDD-NOS; n = 58), or nonspectrum developmental disabilities (n = 50). Growth curve analyses were used to analyze verbal skills trajectories over time. Nonverbal IQ and joint attention emerged as strong positive predictors of verbal outcome. The gap between the autism and other 2 groups widened with time as the latter improved at a higher rate. However, there was considerable variability within diagnostic groups. Children with autism most at risk for more serious language impairments later in life can be identified with considerable accuracy at a very young age, while improvement can range from minimal to dramatic