Agenda | Abstracts | Speakers | What is Public Health? | Research | Conclusions

Peter S. Jensen, M.D., New York State Psychiatric Institute

Attention Deficit Hyperactivity Disorder, or ADHD, is the most common behavioral disorder of childhood and is generally thought to account for the lion’s share of referrals for mental health treatment (Richters et al., 1995). Despite the continuing ongoing controversies that have surrounded the syndrome, it is the most widely studied of all of the behavioral/emotional disorders affecting children and adolescents, having been the focus of literally thousands of studies since the mid 1960’s. In its most current diagnostic iteration (DSM-IV, American Psychiatric Association, 1994), its prevalence has been variously estimated as ranging from 3 to 18%, depending upon the specific methods one employs in implementing the diagnostic criteria (e.g., face-to face diagnostic interviews vs. checklists, single vs. multiple informants, etc.). While its exact diagnostic criteria have changed over the last 3 decades, the general symptoms thought to characterize the syndrome have remained largely unchanged. Studies that have examined the relations between previous diagnostic categorizations (e.g., DSM-III, DSM-IIIR) and DSM-IV indicate a high degree of overlap of previous and current definitions (Lahey et al., 1994).

Despite lingering controversies, the many research studies conducted to date have enabled a substantial body of information to be amassed. As a result of the continuing controversies, the NIH (via the Office of Medical Applications of Research, NIMH, and NIDA) sponsored a consensus conference in November, 1998. The goal of this conference was to identify those areas where evidence was such that definitive conclusions could be drawn, as well as those areas where more research was needed. Of note, several of the areas of greatest need for more research are those to be addressed in this presentation, namely:

- validity of the syndrome itself, particularly with regard to whether it constitutes the far end of a normal spectrum versus a qualitatively different and distinct condition;

- etiology

- prevention

- issues of over- vs. under-diagnosis in "real world" settings

- factors underpinning differences in treated prevalence; and diagnostic and treatment practices

Validity of the syndrome: Current evidence indicates that ADHD can be reliably diagnosed under research conditions (Jensen et al., 1995; Schwab-Stone et al., 1996; Shaffer et al., 1996). In fact, ADHD as a condition is unsurpassed among other child psychiatric disorders, and consistently demonstrates the highest levels of test-retest reliability coefficients. Validity coefficients are also consistently high when done under ideal conditions (Jensen et al., in press). When applying the classic validational criteria outlined by Robins and Guze (1970), the weight of evidence indicates that ADHD does indeed meet criteria as a valid behavioral syndrome that has reasonably discrete defining characteristics and can be reliably diagnosed. As noted by the consensus conference final statement, there is substantial evidence for the validity of the disorder. However, like hypertension, ADHD likely has multiple causes, and may instead reflect a final common pathway of behavioral manifestations rather than a single disorder. As noted by the consensus conference, further validational work on the syndrome is needed, including determining whether the syndrome is best characterized along dimensional lines or as a discrete category. This determination is likely to be of great importance, since if there is indeed no natural cut-off, additional efforts to identify subthreshold cases or prodromal presentations would be quite important. Such efforts could yield substantial benefits, ranging from identifying persons at risk, to identifying a "broader" phenotype that could provide greater scientific benefits for genetic studies, to developing preventive interventions.

Prevalence: Given the fact that there appears indeed to be no natural cut-off or discontinuous function that characterizes ADHD, it should not be surprising that wide differences in prevalence have been noted. Across cultures, prevalence rates ranging from 1 to 20% have been reported (Bird et al., 1999). These rates vary as a function of the diagnostic criteria, methods for establishing the presence of symptoms, nature of the informants, and degree of impairment (Bird, 1999). Within the United States, prevalence rates of 4-5% are generally accepted. In Europe, application of ICD-10 criteria ("Hyperkinetic Disorder") are substantially more demanding, and tend to yield substantially lower rates, usually in the range of 1% (Swanson et al., 1997). Most evidence to date suggests that children are not particularly good reporters of the full syndrome. Inclusion of children’s reports tends to raise prevalence rates by 25-33% (Jensen et al., in press). Similarly, counting cases regardless of the presence of impairment, or without requiring the presence of symptoms in multiple settings, can raise rates by as much as 50%. Regardless, these variations indicate the need not just for standard definitions (as in DSM-IV), but also uniform measures and methods for instantiation of the disorder.

Evidence to date indicates a 6:1 to 9:1 ratio of males to females in clinical settings. However, in epidemiology studies, ratios drop to 3:1. Further, by adulthood, prevalence rates appear to be equal (Barkley, 1999; Johnston, 1999). There is no significant or sizable body of evidence concerning possible differences as a function of ethnicity or SES. However, minority and lower SES families are less likely to seek out care and obtain treatment for their children (Zito et al., 1998). Further, SES factors may complicate the treatment of the disorder, and/or increase the likelihood of poorer long-term outcomes (MTA Cooperative Group, in press; Biederman et al., 1995).

Etiology: Current evidence implicates multiple factors in the etiology of ADHD, yet it is unclear how these factors interact at the level of the single case. The best studied factor is familiality/heritability. Depending upon the nature of the study, heritability has been estimated to be between 50-80%. Yet these factors do not appear to be "all or none," instead, specific traits of ADHD appears to be heritable in a continuous function (Levy et al., 1997).

Most recently, evidence indicates that ADHD symptoms have a central nervous system basis (as do all normal and abnormal behaviors, thoughts, and emotions). However, such brain-behavior correlations do not constitute proof that ADHD reflects a disordered biologic state. Nonetheless, there now exist a range of neuropsychologic, electrophysiologic, and neuroimaging studies that have shown fairly consistent differences in prefrontal cortical, parietal, and basal ganglia functioning associated with ADHD symptomatology. In addition, there now have been a number of candidate gene studies exploring the dopamine transporter (DAT1) or dopamine receptor (DRD4) genes, each of which has now had several independent replications (Swanson & Castellanos, 1999). While these studies generally indicate an association with ADHD and specific polymorphisms, effects are quite small. It is likely that a host of other genes are involved, and that specific components or combinations of environmental forces are necessary to switch on these genes and lead to the expression of the full phenotype.

Other factors implicated by correlational evidence in the onset, maintenance, and severity of ADHD include pre- and perinatal factors (hypoxia, maternal smoking, hyperbilirubinemia), lead, child abuse, specific genetic mutation associated with thyroid disease, acquired forms of ADHD due to traumatic brain injury, and early attachment difficulties. Remarkably, however, despite intermittent leads in these areas, none have been subjected to systematic programmatic research (Swanson & Castellanos, 1999).

Despite these few hints, in truth we know little concerning etiology, a conclusion also reached by the consensus conference. As a result, we know also essentially nothing about primary or secondary prevention. More however is known about tertiary prevention, in that effective treatments have been demonstrated to improve longer-term outcomes several years post treatment (Gilberg et al., 1997; MTA Cooperative Group, in press; Loney et al., in press; Biederman et al., 1999). The lack of research in the prevention area is striking, even thought there is ample evidence that subthreshold and/or pre-morbid states can be reasonably identified. In effect, the research field appears to have unwittingly excluded this area of research from consciousness, perhaps because of the taken-for-granted assumptions that ADHD symptoms are fully biologic or inborn (immutable). Such assumptions, cannot be correct, however, given the number of children who over the course of development show significant remission (20-40%) (e.g., Hechtman, 1992). How and why do such significant improvements in symptoms take place? What developmental processes are at work? Could similar factors come into play and be used to clinical advantage early in the course of the disorder, perhaps before full expression of symptoms, via some targeted prevention strategies?

Avenues of exploration that appear to be understudied include the study of a) specific perinatal/prenatal influences in interaction with susceptibility genes, b) the impact of home and environmental factors that might modulate the development of children’s attentional capacities, c) early learning experiences, exposure to television or other factors that may up-regulate or shape children’s attention styles, and d) early intervention strategies designed to remediate attentional and executive functional capacities in children at risk.

Future studies of ADHD risk should ideally combine assessments of some of the currently identified candidate genes with neuropsychologic and neurophysiologic studies, coupled with direct observations. Given the evidence the cultural factors can and do exert important effects on defining specific behavioral characteristics of the syndrome, the search for risk factors vis-à-vis the underlying phenotype must not rely on behavioral descriptions alone. Methods for discriminating signal from noise will likely depend upon multi-method and multi-informant strategies, direct observation, the use of genetically informative designs coupled with the examination of environmental forces, and methods for compiling and sorting through the many characteristics of a "case" to determine which indeed are true cases vs. non-cases (e.g., best estimate methods with input from experienced clinicians).

REFERENCES

American Psychiatric Association. Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: 1994.

Biederman J, Milberger S, Faraone S, Kiely K, Guite J, Mick E, Ablon S, Warburton R, Reed E (1995), Family-environmental risk factors for attention-deficit hyperactivity disorder. Arch Gen Psychiatry 52:464-470.

Biederman J, Wilens T, Mick E, Spencer T, Faraone SV (1999), Pharmacotherapy of attention-deficit/Hyperactivity disorder reduces risk for substance use disorder. Pediatrics 104:20.

Gilberg C, Melander H, Von Knorring AL, et al: Long-term stimulant treatment of children with attention-deficit hyperactivity disorder symptoms. Arch.Gen.Psychiatry 1997;54:857-864.

Jensen PS, Martin D, Cantwell DP. Comorbidity in ADHD: implications for research, practice, and DSM-V. J Am Acad Child Adolesc Psychiatry. 1997;36:1065-79.

Jensen PS, Roper M, Fisher P, Piacentini J, Canino G, et al.: "Test-Retest Reliability of the Diagnostic Interview Schedule for Children (DISC 2.1): Parent, Child, and Combined Algorithms." Archives of General Psychiatry, 52:61-71, 1995.

*Jensen P, *Rubio-Stipec M, Dulcan M, Canino G, Bird H, Lahey B, Richters J, Schwab-Stone M: "The NIMH Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study: Are Both Parent and Child Informants Always Needed?", J Am Acad Child Adol Psychiatry, in press (* designates joint first authorship).

Jensen PS, Mrazek D, Knapp P, et al. "Evolution and Revolution in Child Psychiatry: ADHD as a Disorder of Adaptation", J. Am. Acad. Child Adol. Psychiatry, 36:1672-1679, 1997.

Jensen PS, Kettle L, Roper MS, Sloan MT, Dulcan Mk, Hoven C, Bird HR, Bauermeister JJ, Payne JD: "Are Stimulants Over-prescribed? Treatment of ADHD in Four U.S. Communities", J. Am. Acad. Child Adol. Psychiatry, 38:797-804, 1999.

Lahey B, Applegate B, McBurnett K, Biederman J, Greenhill L, Hynd G, Barkley R, Newcorn J, Jensen P, Richters J, Garfinkel B, Kerdyk L, Frick P, Ollendick T, Perez D, Hart E, Waldman I, Shaffer D: "DSM IV Field Trials for Attention Deficit/Hyperactivity Disorder in Children and Adolescents," American Journal of Psychiatry, 151:1673-1685, 1994.

Levy F, Hay DA, McStephen M, Wood C, Waldman I. Attention-deficit hyperactivity disorder: a category or a continuum? Genetic analysis of a large-scale twin study. Journal of American Academic Child and Adolescent Psychiatry. 1997;36:737-744.

MTA Cooperative Group: 14-month Randomized Clinical Trial of Treatment Strategies for Attention Deficit Hyperactivity Disorder. Arch Gen Psychiatry, in press.

MTA Cooperative Group: Moderator and Mediator Challenges to the MTA Study: Effects of Comorbid Anxiety Disorder, Family Poverty, Session Attendance, and Community Medication on Treatment Outcome. Arch Gen Psychiatry, in press.

National Institutes of Health: Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder. NIH Consensus Statement 1998 Nov 16-18; 16(2). J Am Acad Child Adolesc Psychiatry, in press.

Rappley MD, Gardiner JC, Jetton JR, Houang RT: The use of methylphenidate in Michigan. Arch.Pediatr.Adolesc.Med. 1995;149:675-679.

Richters J, Arnold LEA, Jensen PS, Abikoff H, Conners CK, Greenhill L, Hechtman L, Hinshaw S, Pelham W, Swanson J: "NIMH Collaborative Multisite, Multimodal Treatment Study of Children with ADHD: I. Background and Rationale," J. Am. Acad. Child Adol. Psychiatry, 34:987-1000, 1995.

Schwab-Stone M, Dulcan M, Jensen P, Canino G, Bird H, Lahey B, Rae D: "The NIMH Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study: Validity of the DISC - 2", J. Am. Acad. Child Adol. Psychiatry, 35:878-888, 1996.

Shaffer D, Fisher P, Dulcan M, Davies M, Piacentini J, Schwab-Stone M, Lahey B, Bourdon K, Jensen P, Bird H, Canino G, Regier D: "The Second Version of the NIMH Diagnostic Interview Schedule for Children (DISC - 2)", J. Am. Acad. Child Adol. Psychiatry, 35:865-877, 1996.

Sloan M, Jensen P, Kettle L: "Assessing Services for Children with ADHD: Gaps and Opportunities." Journal of Attention Disorders, 3:13-29, 1999.

Swanson JM, Sergeant J, Taylor E, Sonuga-Burke E, Cantwell D, Jensen P: "Attention Deficit Hyperactivity Disorder and Hyperkinetic Disorder," Lancet, 351:429-33, 1998.

Weisz JR, Jensen PS: Efficacy and Effectiveness of Psychotherapy and Pharmacotherapy with Children and Adolescents. Mental Health Services, in press.

Zito JM, Safer DJ, Riddle MA, Johnson RE, Speedie SM, Fox M: Prevalence variations in psychotropic treatment of children. J.Child.Adolesc.Psychopharmacology 1998;8:99-105.

Zito JM, Safer DJ, Dosreis S, Riddle MA: Racial disparity in psychotropic medications prescribed for youths with medicaid insurance in Maryland. J.Am.Acad.Child Adolesc.Psychiatry 1998;37:179-184.

Thomas M. Achenbach, Ph.D., University of Vermont

Having metamorphosed from Minimal Brain Damage (MBD) through Hyperkinetic Reaction of Childhood and Attention Deficit Disorder (ADD), what is now known as Attention Deficit Hyperactivity Disorder (ADHD) is receiving enormous publicity in the popular media, as well as in the professional literature. Its precise nature, etiology, prevalence, developmental course, and appropriate treatment remain subject to debate. However, existing findings can help us focus in on what we need to learn.

1. Criteria for ADHD. The DSM criteria for ADHD changed in 1980 (DSM-III), 1987 (DSM-III-R), and 1994 (DSM-IV), and they differ from the ICD-10 (1992) criteria. The different diagnostic criteria classify different groups and proportions of children. In addition to these diagnostic criteria, there are numerous rating scales and other procedures for assessing ADHD. Because there is no single gold standard, data from multiple procedures must be aggregated for both research and clinical purposes.

2. Gender and Age Differences. Most research, clinical services, and diagnostic criteria focus on young boys. Fewer girls and fewer older children meet DSM criteria for ADHD, possibly owing to lower base rates for disruptive behaviors in these groups. Adult ADHD has become widely publicized, but the DSM does not provide criteria for adult ADHD.

3. Prevalence. Studies suggest prevalence rates of about 2 to 6% for 7-10-year-old boys. Lower prevalence rates for girls and other ages may reflect the differential relevance of ADHD diagnostic criteria rather than real differences in prevalence. Both epidemiologic data and the many referrals for clinical and special education services indicate that large numbers of boys are identified as having ADHD.

4. Correlates and Comorbidity. Poor school achievement, poor peer relations, and conduct problems are commonly reported correlates of ADHD. Reports of comorbidity with other disorders may reflect biases (e.g., Berkson’s bias) arising in the study of clinical samples.

5. Etiology. Hyperactive behavior was initially viewed as reflecting brain damage, but, brain damage has not been supported as a typical cause. Indicating moderate heritability, genetic research suggests polygenic influences on quantitative parameters, rather than single gene causation of a disease entity.

6. Treatment. Research has documented the efficacy of stimulant medications, but the effects may not be specific to ADHD, because similar effects on attention have been found with nonADHD subjects. Parent training, behavior modification, and special educational services are widely used, often in conjunction with stimulant medications.

7. Long-term Outcomes. Follow-ups of clinical samples show that children diagnosed as ADHD subsequently manifest a variety of problems, suggesting that ADHD leads to multiple kinds of psychopathology. However, longitudinal studies of general population samples indicate that attention problems per se mainly predict poor academic achievement.

8. Cross-cultural Comparisons. Standardized ratings of children’s attention problems vary modestly across epidemiologic samples from diverse cultures. U.S. children are not exceptionally high in attentional problems.

9. Long-term Trends. Comparisons of U.S. general population samples over a 13-year period showed significant increases in ADHD problems. However, the increases in ADHD problems may reflect general increases found in many behavior problems rather than in ADHD per se.

What We Need to Learn

Epidemiologic tabulations of cases meeting current diagnostic criteria are not likely to be helpful until we learn more about the issues listed below.

1. How Can We Take Account of Differences Related to Gender, Age, Assessment Procedures, and Sources of Data? The application of the same a priori diagnostic cutpoints to both genders, all ages, different assessment procedures, and different sources of data may obscure differences related to these factors. More research needs to focus on females in general and on adolescents and adults of both genders. Empirically based multi-source assessment instruments can provide more precise data on the base rates and correlates of ADHD symptoms by gender, age, and source.

2. How Can We Better Aggregate Diagnostic Data? Prevailing diagnostic procedures for ADHD fail to specify how different kinds of data should be aggregated in determining caseness. Rather than assuming that all procedures are co-equivalent or that diagnosticians accurately combine all relevant data, we need to compare algorithms for quantifying the probability and severity of ADHD.

3. How Can We Use Epidemiological Findings Based on Better Diagnostic Criteria to Improve Research on Etiology? Norms and findings from epidemiological research can help us refine etiological hypotheses and can improve ascertainment of true cases for testing such hypotheses.

4. How Can We Use Epidemiological and Etiological Findings to Improve Prevention and Treatment? More accurate identification of true cases, better documentation of incidence and prevalence, and better knowledge of etiologies will lead to more precisely targeted prevention and treatment efforts.

Andrew S. Rowland Ph.D., National Institute for Environmental Health Sciences

ADHD is one of the most common childhood disabilities, yet its prevalence, etiology, and developmental course remain poorly described. In part, these data gaps exist because few population-based epidemiologic studies of ADHD have been conducted. Several recent developments underscore the need for additional epidemiologic studies of ADHD. First, there has been a major paradigm shift; the literature suggests ADHD is best conceptualized as a lifelong disability rather than as a childhood disorder. This implies that treatment and monitoring may last a lifetime and impairment from ADHD probably has been significantly underestimated. The evidence suggesting a biologic basis for ADHD has become more persuasive; for example, several studies suggest a possible etiologic role for two genes involved in dopamine regulation and several imaging studies suggest possible differences in brain structure and function among adults with ADHD. Finally, at least two million children in the U.S. are being treated for ADHD with stimulant medication and the average number of years children are being treated is increasing. This should make epidemiologic research to identify preventable risk factors, a public health priority.

Case definition and Epidemiologic study of ADHD

There have been many years of controversy over dimensional versus categorical approaches to measuring psychopathology and over the validity of particular screening instruments, diagnostic interviews, and classification schemes. Although developing a clear consensus around these issues may not be possible, this must not prevent us from making informed choices and collecting the epidemiologic data that are needed to guide public health decision making. Because DSM-IV is the basis of current diagnoses and treatment, we need to collect data applying these criteria.

For an epidemiologic study we are conducting in North Carolina, we developed a methodology for operationalizing the DSM-IV criteria for ADHD. The key decisions we made included using a population-based sample, using multiple respondents including parents and teachers, and requiring moderate agreement between respondents about symptoms and impairment. I will talk about difficulties we faced in defining impairment, and assigning case status to children taking medication. I will also discuss how we plan to validate our screening diagnoses and analyze our data dimensionally as well as categorically. Merits of alternative study designs and possible use of national surveys like NHANES will also be addressed.

Preliminary data from this study have been promising. The early data suggest that the standard ADHD prevalence estimate of 3% to 5% among school-aged children probably underestimates prevalence by a factor of two or three, that many children with ADHD are not being identified and that many children continue to meet ADHD criteria despite stimulant treatment. We also found that African-American children were being treated with stimulant medication less frequently than White children, even though the prevalence of ADHD in the two groups was similar.

Historically, ADHD was believed to be the sequelae of brain damage caused during pregnancy. The concept of minimal brain dysfunction (which combined learning disabilities and hyperactivity) was discarded long ago but unfortunately so have many of the etiologic leads that suggested adverse pregnancy events might be important risk factors. My perspective is that ADHD should be viewed as a developmental disorder and the primary hypothesis of our study is that preterm delivery is an important, etiologic risk factor. I will summarize the data supporting this perspective and hypothesis. We also hypothesize that exposures to environmental toxicants like cigarette smoke, alcohol, and lead during early brain development may be etiologic risk factors. We also collected data on a number of potential social risk factors. Even if one is only interested in biologic risk factors, social factors cannot be overlooked because they probably play an important role in which children get identified, treated, and suffer the most severe impairment.

We plan to look whether the social characteristics and risk factors for children who are primarily inattentive are different from children who are primarily hyperactive or have the combined subtype. Researchers have proposed that children who have ADHD with co-morbid anxiety or ADHD with co-morbid conduct problems have different developmental pathways. Examining how the social characteristics and the developmental trajectory of children with these conditions differ from other ADHD children should help clarify whether these sub-classifications are important.

Public Health Priorities:

Although some researchers have proposed creating age, gender and race-based norms for ADHD, examining how prevalence varies between sub-groups is a critical step in understanding possible risk factors, and for understanding gaps in who is being identified and who is being treated. Collecting better epidemiologic data on ADHD is critical for setting public health priorities.