Abstracts For Child and Adolescent Psychiatry

Birmaher B, Ryan ND, Williamson DE, Brent DA, Kaufman J, Dahl RE, Perel J, Nelson B

Objective: To qualitatively review the literature of the past decade covering the epidemiology, clinical characteristics, natural course, biology, and other correlates of early-onset major depressive disorder (MDD) and dysthymic disorder (DD). Method: A computerized search for articles published during the past 10 years was made and selected studies are presented. Results: Early-onset MDD and DD are frequent, recurrent, and familial disorders that tend to continue into adulthood, and they are frequently accompanied by other psychiatric disorders. These disorders are usually associated with poor psychosocial and academic outcome and increased risk for substance abuse, bipolar disorder, and suicide. In addition, DD increases the risk for MDD. There is a secular increase in the prevalence of MDD, and it appears that MDD is occurring at an earlier age in successive cohorts. Several genetic, familial, demographic, psychosocial, cognitive, and biological correlates of onset and course of early-onset depression have been identified. Few studies, however, have examined the combined effects of these correlates. Conclusions: Considerable advances have been made in our knowledge of early-onset depression. Nevertheless, further research is needed in understanding the pathogenesis of childhood mood disorders. Toward this end, studies aimed at elucidating mechanisms and interrelationships among the different domains of risk factors are needed.

Beardslee WR, Gladstone TR

Traditionally, research on childhood mood disorders has focused on clinical trials and longitudinal course and outcome studies, rather than on prevention. Recently, however, advances in the design, methodology, and evaluation of prevention approaches and progress in understanding what factors predispose children to depression have made possible the development of theoretically driven, empirically justified approaches to the prevention of depression in youngsters who are at high risk, either because of elevated symptom levels or parental mood disorder. In this review, we outline recent empirical findings on risk factors for depression in nonreferred samples of youngsters and also in children of depressed parents. Additionally, we review three trials of preventive interventions for childhood depression that yield promising initial findings. We emphasize the need to understand both risks for depression and factors that protect youngsters at risk from succumbing to depression in guiding the development of prevention programs. We also argue that consideration of prevention of depression requires addressing broader social adversity influences that lead to poor mental health outcomes in children, even beyond the effects of parental mood disorder. We conclude with an emphasis on the importance of a developmental-transactional perspective that highlights opportunities for intervention at different points across the lifespan.

Castellanos FX, Giedd JN, Marsh WL, Hamburger SD, Vaituzis AC, Dickstein DP, Sarfatti SE, Vauss YC, Snell JW, Lange N, Kaysen D, Krain AL, Ritchie GF, Rajapakse JC, Rapoport JL

Background: Anatomic magnetic resonance imaging (MRI) studies of attention-deficit hyperactivity disorder (ADHD) have been limited by small samples or measurement of single brain regions. Since the neuropsychological deficits in ADHD implicate a network linking basal ganglia and frontal regions, 12 subcortical and cortical regions and their symmetries were measured to determine if these structures best distinguished ADHD. Methods: Anatomic brain MRIs for 57 boys with ADHD and 55 healthy matched controls, aged 5 to 18 years, were obtained using a 1.5-T scanner with contiguous 2-mm sections. Volumetric measures of the cerebrum, caudate nucleus, putamen, globus pallidus, amygdala, hippocampus, temporal lobe, cerebellum; a measure of prefrontal cortex; and related right-left asymmetries were examined along with midsagittal area measures of the cerebellum and corpus callosum. Interrater reliabilities were .82 or greater for all MRI measures. Results: Subjects with ADHD had a 4.7% smaller total cerebral volume (P=.02). Analysis of covariance for total cerebral volume demonstrated a significant loss of normal right > left asymmetry in the caudate (P=.006), smaller right globus pallidus (P=.005), smaller right anterior frontal region (P=.02), smaller cerebellum (P=.05), and reversal of normal lateral ventricular asymmetry (P=.03) in the ADHD group. The normal age-related decrease in caudate volume was not seen, and increases in lateral ventricular volumes were significantly diminished in ADHD. Conclusion: This first comprehensive morphometric analysis is consistent with hypothesized dysfunction of right-sided prefrontal-striatal systems in ADHD.

Biederman J, Faraone S, Milberger S, Guite J, Mick E, Chen L, Mennin D, Marrs A, Ouellette C, Moore P, Spencer T, Norman D, Wilens T, Kraus I, Perrin J

Background: Previous cross-sectional data showed that children and adolescents with attention-deficit hyperactivity disorder (ADHD) are at increased risk of comorbid conduct, mood, and anxiety disorders as well as impairments in cognitive, social, family, and school functioning. However, longitudinal data were needed to confirm these initial impressions. Methods: Using DSM-III-R structured diagnostic interviews and raters blinded as to diagnosis, we reexamined psychiatric diagnoses at 1- and 4-year follow-ups in children with ADHD and controls. In addition, subjects were evaluated for cognitive, achievement, social, school, and family functioning. Results: Analyses of follow-up findings revealed significant differences between children with ADHD and controls in rates of behavioral, mood, and anxiety disorders, with these disorders increasing markedly from baseline to follow-up assessments. In addition, children with ADHD had significantly more impaired cognitive, family, school, and psychosocial functioning than did controls. Baseline diagnosis of conduct disorder predicted major depression and bipolar disorder at follow-up, and anxiety disorders at baseline predicted anxiety disorders at follow-up. Conclusion: These results confirm and extend previous retrospective results indicating that children with ADHD are at high risk of developing a wide range of impairments affecting multiple domains of psychopathology such as cognition, interpersonal, school, and family functioning. These findings provide further support for the value of considering psychiatric comorbidity in both clinical assessment and research protocols involving children with ADHD.

Gillberg C, Melander H, von Knorring AL, Janols LO, Thernlund G, Hagglof B, Eidevall-Wallin L, Gustafsson P, Kopp S

Background: We wanted to study the effects of amphetamine on symptoms of attention-deficit hyperactivity disorder (ADHD) over a longer period than has been reported in previous studies of central stimulants in this condition. Methods: Sixty-two children, aged 6 to 11 years, meeting DSM-III-R symptom criteria for ADHD participated in a parallel-group design, randomized, double-blind, placebo-controlled study of amphetamine treatment. Treatment was not restricted to children with “pure” ADHD, ie, some had comorbid diagnoses. In the amphetamine group, children received active treatment for 15 months. Results: Amphetamine was clearly superior to placebo in reducing inattention, hyperactivity, and other disruptive behavior problems and tended to lead to improved results on the Wechsler Intelligence Scale for Children–Revised. Treatment failure rate was considerably lower and time to treatment failure was longer in the amphetamine group. Adverse effects were few and relatively mild. Conclusion: The results of this long-term, placebo-controlled study of the central stimulant amphetamine in the treatment of ADHD indicate that there are remaining positive effects of the drug 15 months after starting treatment.

MTA Cooperative Group

Objective: In the Multimodal Treatment Study of ADHD (MTA), the effects of medication management (MedMgt) and behavior modification therapy (Beh) and their combination (Comb) and usual community comparison (CC) in the treatment of attention-deficit/hyperactivity disorder (ADHD) differed at the 14-month assessment as a result of superiority of the MTA MedMgt strategy (Comb or MedMgt) over Beh and CC and modest additional benefits of Comb over MedMgt alone. Here we evaluate the persistence of these beneficial effects 10 months beyond the 14 months of intensive intervention. Methods: Of 579 children who entered the study, 540 (93%) participated in the first follow-up 10 months after the end of treatment. Mixed-effects regression models explored possible persisting effects of the MTA medication strategy, the incremental benefits of Comb over MedMgt alone, and the possible superiority of Beh over CC on 5 effectiveness and 4 service use domains. Results: The MTA medication strategy showed persisting significant superiority over Beh and CC for ADHD and oppositional-defiant symptoms at 24 months, although not as great as at 14 months. Significant additional benefits of Comb over MedMgt and of Beh over CC were not found. The groups differed significantly in mean dose (methylphenidate equivalents 30.4, 37.5, 25.7, and 24.0 mg/day, respectively). Continuing medication use partly mediated the persisting superiority of Comb and MedMgt. Conclusion: The benefits of intensive MedMgt for ADHD extend 10 months beyond the intensive treatment phase only in symptom domains and diminish over time.

MTA Cooperative Group

Objective: Intent-to-treat analyses of the Multimodal Treatment Study of ADHD (MTA) revealed group differences on attention-deficit/hyperactivity disorder symptoms ratings, with better outcome in groups of participants who were assigned the medication algorithm—medication alone (MedMgt) and combined (Comb)—than in those who were not—behavior modification (Beh) alone and community comparison (CC). However, the effect size was reduced by 50% from the end of treatment to the first follow-up. The convergence of outcomes suggests differential changes by treatment group beween 14 and 24 months, which this report explores, both for benefits of treatment and for side effects on growth. Methods: We documented reported medication use at 14- and 24-month assessments and formed 4 naturalistic subgroups (Med/Med, Med/NoMed, NoMed/Med, and NoMed/NoMed). Then we performed exploratory mediator analyses to evaluate effects of changes in medication use on 14- to 24-month change scores of effectiveness (symptom ratings) and growth (height and weight measures). Results: The randomly assigned groups with the greatest improvement at the end of the treatment phase (Comb and MedMgt) deteriorated during the follow-up phase, but the other 2 groups (Beh and CC) did not. There were no significant differences in the 14- to 24-month growth rates among the randomly assigned groups, in contrast to significant growth suppression in the Comb and MedMgt at the end of the treatment phase. Changes in medication use mediated the 14- to 24-month change in attention-deficit/hyperactivity disorder symptom ratings: the subgroup that reported stopping medication (Med/NoMed) showed the largest deterioration, the subgroup that consistently reported (Med/Med) or never reported (NoMed/NoMed) medication use showed modest deterioration, and the subgroup that reported starting medication (NoMed/Med) showed improvement. Changes in medication use also mediated growth effects: the subgroup that consistently reported medication use (Med/Med) showed reduced height gain compared with the subgroup that never reported medication use (NoMed/NoMed), which actually grew faster than predicted by population norms. Conclusion: In the MTA follow-up, exploratory naturalistic analyses suggest that consistent use of stimulant medication was associated with maintenance of effectiveness but continued mild growth suppression.

Olfson M, Shaffer D, Marcus SC, Greenberg T

Context: A decade of increasing antidepressant medication treatment for adolescents and corresponding declines in suicide rates raise the possibility that antidepressants have helped prevent youth suicide. Objective: To evaluate the relationship between regional changes in antidepressant medication treatment and suicide in adolescents from 1990 to 2000. Design: Analysis of prescription data from the nation’s largest pharmacy benefit management organization, national suicide mortality files, regional sociodemographic data from the 1990 and 2000 US Census, and regional data on physicians per capita. Participants: Youth aged 10 to 19 years who filled a prescription for antidepressant medication and same-aged completed suicides from 588 three-digit ZIP code regions in the United States. Main outcome measures: The relationship between regional change in antidepressant medication treatment and suicide rate stratified by sex, age group, regional median income, and regional racial composition. Results: There was a significant adjusted negative relationship between regional change in antidepressant medication treatment and suicide during the study period. A 1% increase in adolescent use of antidepressants was associated with a decrease of 0.23 suicide per 100,000 adolescents per year (beta = −.023, t = −5.14, P<.001). In stratified adjusted analyses, significant inverse relationships were present among males (beta = −.032, t = −3.81, P<.001), youth aged 15 to 19 years (beta = −.029, t = −3.43, P<.001), and regions with lower family median incomes (beta = −.023, t = −3.73, P<.001). Conclusions: An inverse relationship between regional change in use of antidepressants and suicide raises the possibility of a role for using antidepressant treatment in youth suicide prevention efforts, especially for males, older adolescents, and adolescents who reside in lower-income regions.

Klin A, Jones W, Schultz R, Volkmar F, Cohen D

Objective: Genetic and neurofunctional research in autism has highlighted the need for improved characterization of the core social disorder defining the broad spectrum of syndrome manifestations. Method: This article reviews the advantages and limitations of current methods for the refinement and quantification of this highly heterogeneous social phenotype. Results: The study of social visual pursuit by use of eye-tracking technology is offered as a paradigm for novel tools incorporating these requirements and as a research effort that builds on the emerging synergy of different branches of social neuroscience. Conclusions: Advances in the area will require increased consideration of processes underlying experimental results and a closer approximation of experimental methods to the naturalistic demands inherent in real-life social situations.

Volkmar FR, Lord C, Bailey A, Schultz RT, Klin A

The quantity and quality of research into autism and related conditions have increased dramatically in recent years. Consequently we selectively review key accomplishments and highlight directions for future research. More consistent approaches to diagnosis and more rigorous assessment methods have significantly advanced research, although the boundaries of the ‘broader phenotype’ remain to be defined and the validity of Asperger’s disorder as a discrete syndrome remains controversial. Recent epidemiological studies have shown that Autism Spectrum Disorders are common, but there continues to be debate about the causes of the increase in the frequency with which autism is diagnosed. Psychological research has helped to develop new developmental models for the disorder and there have also been significant advances in the molecular genetics of autism and understanding of the underlying neurobiological processes. Areas important for future research include the study of autism as it first develops, i.e., in infants and very young children, and of specific processes (psychological and neurobiological) which underlie the disorder. Significant challenges lie ahead in evaluating the growing number of treatments for autism and in integrating the results of research into treatment and educational settings.

Fairburn CG, Cooper Z, Doll HA, Norman P, O’Connor M

Background: Little is known about the relative course and outcome of bulimia nervosa and binge eating disorder. Methods: Two community-based cohorts were studied prospectively over a 5-year year period. One comprised 102 participants with bulimia nervosa and the other 48 participants with binge eating disorder (21% [9/42] of whom had comorbid obesity). All participants were female and aged between 16 and 35 years at recruitment. The assessments were at 15-month intervals and addressed eating disorder features, general psychiatric symptoms, and social functioning. Results: Both cohorts showed marked initial improvement followed by gradual improvement thereafter. Between half and two thirds of the bulimia nervosa cohort had some form of eating disorder of clinical severity at each assessment point, although only a minority continued to meet diagnostic criteria for bulimia nervosa. Each year about a third remitted and a third relapsed. The outcome of the binge eating disorder cohort was better, with the proportion with any form of clinical eating disorder declining to 18% (7 of 40) by the 5-year follow-up. The relapse rate was low among this cohort. There was little movement of participants across the 2 diagnostic categories and few sought treatment. Both groups gained weight, with 39% of the binge eating disorder cohort (14 of 36) meeting criteria for obesity at 5-year follow-up. Conclusions: These findings suggest that, among young women in the community, bulimia nervosa and binge eating disorder have a different course and outcome. Whereas the prognosis of those with bulimia nervosa was relatively poor, the great majority of those with binge eating disorder recovered.

Zito JM, Safer DJ, DosReis S, Gardner JF, Magder L, Soeken K, Boles M, Lynch F, Riddle MA

Objective: To examine changes in the full spectrum of psychotropic medication treatment for youths from 1987 to 1996. Methods: A population-based analysis of community treatment data on nearly 900,000 youths enrolled in 2 US health care systems included (1) computerized Medicaid data from 2 states (a midwestern state and a mid-Atlantic state) composed of outpatient prescription claims and enrollment records and (2) computerized prescription dispensing records from a group-model health maintenance organization. Ten 1-year cross-sectional data sets from 1987 through 1996 were analyzed. Results: Total psychotropic medication prevalence for youths increased 2- to 3-fold and included most classes of medication. The rapid growth since 1991 of alpha-agonists, neuroleptics, and “mood stabilizer” anticonvulsants was particularly notable. The 1996 prevalence of any psychotropic medication among youths younger than 20 years was remarkably similar (5.9%–6.3%) across all 3 sites, with stimulants and antidepressants consistently ranked first and second. Medicaid rates almost always exceeded health maintenance organization rates by large margins, particularly for alpha-agonists, neuroleptics, “mood stabilizer” anticonvulsants, and lithium. Youths in health maintenance organizations had rates similar to Medicaid-insured youths for antidepressants and hypnotics. Over the decade, there was a proportional increase in females receiving stimulants and in males receiving antidepressants, particularly for the 10- to 14-year-old group. The prevalence ratios of whites to African Americans narrowed substantially in 1 Medicaid site. Conclusions: Youth psychotropic treatment utilization during the 1990s nearly reached adult utilization rates. Youth findings can be used to accurately assess the duration of treatment and unforeseen practice pattern changes, and to identify safety concerns.