Making Sense of the Rise in ADHD
Larry Culpepper, MD, Medscape
Jun 26, 2013

More Attention for Rising ADHD
The New York Times[1] recently reported that attention-deficit/hyperactivity disorder (ADHD) is being diagnosed in "nearly 1 in 5 high school-age boys in the United States and 11% of school-age children." The article's author commented that this is a 16% increase since 2007 and a 41% increase over the past decade. The article then immediately jumps to the editorial concern that this represents overdiagnosis and overmedication by physicians pressured by parents and influenced by the pharmaceutical industry.

The New York Times took the somewhat unusual step for a newspaper of obtaining raw data from the Centers for Disease Control and Prevention's (CDC's) 2011-2012 National Survey of Children's Health and analyzing and reporting these data, rather than waiting for the CDC or other professional groups to do so. The Times article is primarily an editorial presenting the downside of such overdiagnosis and consequent medication abuse, addiction, and "diversion long tolerated in college settings and gaining traction in high-achieving high schools." It goes further and raises the concern that DSM-5 will open the door to even broader mislabeling of normal child behavior as ADHD.

However, there might be more to this story. The concern about overdiagnosis and overmedication has received much attention in the popular press over the past 40 years. My first insights into the passions raised in this quarter came in 1971 when I attended a meeting with a Midwest school board called specifically to address overmedication of school children for attention deficit disorder (ADD). In 2007, Sciutto and Eisenberg[2] nicely summarized the legacy of claims of overdiagnosis and overmedication (including concerns voiced by Hillary Clinton in a March 2000 press conference). Their review of the evidence found little evidence to support or refute these claims. Parent report, the basis of the CDC data, is known to overreport the prevalence of ADHD.[2,3] Clearly, rapid diagnosis without adequately collecting and weighing information from multiple sources can lead to diagnostic error both in terms of false positives (eg, the hyperactive problematic child) and underdiagnosis (eg, the inattentive child).

But what if the prevalence of the behaviors that lead to the label of ADHD really are increasing? Is the automatic conclusion about overdiagnosis and overmedication correct? What issues might be raised by a more balanced consideration of the CDC data (assuming that the Times analysis used the appropriate statistical methods)?

Toxins, Genes, and Poverty
In his 2012 Archives of Pediatric and Adolescent Medicine editorial about the 22% increase in parent-reported ADHD between the CDC surveys in 2003 and 2007 (precursors to the 2011-2012 survey reported by the New York Times), Lanphear[4] reminded us that ADHD "is not a specific disorder but a medley of maladaptive behaviors, the most prominent of which are hyperactivity, impulsivity, and inattention." He commented that we have no serial surveys of ADHD using a validated instrument and raised the concern that we might be in the midst of a "preventable epidemic." He demonstrated that small shifts in lead and tobacco exposures turn into dramatic increases in the frequency of ADHD symptoms in children. Because dopamine neurons in the prefrontal cortex are particularly sensitive to environmental toxins, he voiced concern about other toxins (mercury, insecticides, polychlorinated biphenyls, and bisphenol A) and their relationship to ADHD behaviors, which is little understood. He concluded by calling for a national scientific advisory panel to evaluate environmental influences on ADHD and make recommendations.

Others have different concerns. Webb,[5] writing from her experience in Wales, in the March 2013 issue of the British Medical Journal analyzed the possibility that poverty and maltreatment are major sources of the behaviors that lead to a diagnosis of ADHD. Webb cited evidence that ADHD runs in families, suggesting that ADHD has a genetic basis. However, poor, disorganized, and abusive families are rarely recruited for such genetic studies. Living in adverse environments leads to children who are anxious, highly aroused, and who have high cortisol levels. She raised the concern that when this occurs early in childhood, it may interact with genetic risk, with the resulting changes being written permanently into the affected toddler's brain by epigenetic processes. The child becomes permanently hardwired for the phenotypic behaviors of ADHD. Hypervigilance about conflict and the consequent difficulties with attention and restlessness, which may further promote dysfunctional interactions with parents, become the basis for the label of ADHD. Such stressful early-life environments are strongly associated with poverty.

In 2007, Froehlich and colleagues[6] reported a very similar association in US population studies, with the poorest children more than twice as likely as the wealthiest to meet criteria for ADHD. They suggest that this might be the result of an increase in ADHD risk factors (including premature birth and exposure to toxins in utero and in early childhood[7]) and the high hereditability of ADHD, with affected families clustering over generations in the lower socioeconomic strata. Perhaps we should consider the increases over the decades, and particularly in the most recent CDC data, as being related to the increasing concentration of wealth in the United States. The least wealthy 80% of the US population has only 7% of the country's wealth, whereas the wealthiest 1% of the population has 24% of the wealth (up from 9% in 1971 when I attended the school meeting). The lowest-income group in the United States has the least chance among all developed countries of moving up the socioeconomic ladder.[8,9] The authors of the New York Times article can take comfort from the finding that only a small minority of low-income children receive medication for ADHD.

The Sun and Sleep Hypothesis
Perhaps the increase in ADHD stems from completely different sources. Arns and colleagues[10] provide an intriguing analysis of the geographic variation in ADHD prevalence. ADHD is least prevalent in sunny states in the United States and in sunny countries internationally. One third of medication-naive children with ADHD have idiopathic sleep-onset insomnia and a delayed circadian phase. Adults with ADHD have melatonin signaling deficiencies, clock gene abnormalities, and are more likely to be "evening types." Light and melatonin treatment can improve ADHD symptoms. Arns and colleagues found that 34%-41% of the variance in the pediatric diagnosis of ADHD between states in the United States, and 57% of the variance in adult prevalence in non-US countries, can be explained by solar intensity, and correcting for low birth weight and infant mortality only strengthens this association. The most dramatic increase in ADHD prevalence between 2003 and 2007 CDC data occurred in adolescents, and particularly in those who were 15-17 years old. Arns and colleagues hypothesized that recent increases in ADHD prevalences may be exacerbated by technology developments. Use of television, computers, and mobile technologies for social media by children and adolescents, particularly before bedtime, may increase ADHD behaviors by interfering with the circadian pacemaker to further delay sleep onset, shorten sleep duration, and suppress melatonin.

ADHD might also interact with developmental lag, proposed as yet another explanation for this diagnosis. Doehnert and colleagues,[11] in a longitudinal study of children with ADHD, found no evidence for a lag in the development of the brain system responsible for attention and only partial support for a lag in the development of the system responsible for inhibitory control. This is in contrast to imaging studies that demonstrate a delay of approximately 3 years in the development of cortical thickness in patients with ADHD. Doehnert and colleagues postulated that maturation, if it is delayed, terminates at the same age in children who do and do not experience developmental lag; in the former, delayed maturation leads to termination of development before "catch-up," resulting in continued impairment into adulthood.

A Call for a Different Response
This is not an exhaustive look at the mechanisms postulated to explain ADHD and how they might contribute to the increases in parental report of ADHD in the CDC data analyzed by the New York Times. Clearly, inadequate clinical attention to diagnostic accuracy is a contributing factor. In 1999, Wasserman and colleagues[12] reported that only 38% of pediatricians used the DSM-IV criteria to make the diagnosis of ADHD. Since that time, professional groups have developed guidelines and toolkits to improve practice, but we have no updated data on current practice.

Still, a diverse set of recent developments in society -- the increased economic chasm engulfing the poor, toxin exposures, light technology exposures -- might be contributing significantly to a real increase in the behaviors leading to a diagnosis of ADHD. At Kaiser Permanente, the costs of care increase at least 2 years before the ADHD diagnosis is made and are persistently higher thereafter. ADHD is highly associated with other behavioral problems, substance abuse (especially if ADHD is untreated), learning disorders, school failures, unintended and early pregnancies, legal difficulties, occupational difficulties, and family disruption.[13]

Perhaps the primary conclusion to be drawn from the CDC data as analyzed by the New York Times is that a significant population of our children and the future of our country are in distress and at risk. Instead of prematurely labeling the increase as overdiagnosis by physicians swayed by pharmaceutical interests, a more beneficial response would be a call for a funded initiative to track ADHD prevalence using valid measures and to expand research funding to determine its origins and means of preventing further increases.

References
  1. Schwarz A, Cohen S. A.D.H.D. seen in 11% of US children as diagnoses rise. The New York Times. March 13, 2013. http://www.nytimes.com/2013/04/01/health/more-diagnoses-of-hyperactivity-causing-concern.html?pagewanted=2&hp&pagewanted=all&_r=1& Accessed May 30, 2013.
  2. Sciutto MJ, Eisenberg M. Evaluating the evidence for and against the overdiagnosis of ADHD. J Atten Disord. 2007;11:106-113. Abstract
  3. Getahun D, Jacobsen SJ, Fassett MJ, Chen W, Demissie K, Rhoads GG. Recent trends in childhood attention-deficit/hyperactivity disorder. JAMA Pediatr. 2013;167:282-288.
  4. Lanphear BP. Attention-deficit/hyperactivity disorder: a preventable epidemic? Arch Pediatr Adolesc Med. 2012;166:1182-1184.
  5. Webb E. Poverty, maltreatment and attention deficit hyperactivity disorder. Arch Dis Child. 2013;98:397-400. Abstract
  6. Froehlich TE, Lanphear BP, Epstein JN, Barbaresi WJ, Katusic SK, Kahn RS. Prevalence, recognition, and treatment of attention-deficit/hyperactivity disorder in a national sample of US children. Arch Pediatr Adolesc Med. 2007;161:857-864. Abstract
  7. Froehlich TE, Anixt JS, Loe IM, Chirdkiatgumchai V, Kuan L, Gilman RC. Update on environmental risk factors for attention-deficit/hyperactivity disorder. Curr Psychiatry Rep. 2011;13:333-344. Abstract
  8. Blodget H. America today: 3 million overlords and 300 million serfs. Business Insider. April 10, 2013. Wealth And Income Inequality In America - Business Insider Accessed May 30, 2013.
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  10. Arns M, van der Heijden KB, Arnold LE, Kenemans JL. Geographic variation in the prevalence of attention-deficit/hyperactivity disorder: the sunny perspective. Biol Psychiatry. 2013 March 20. [Epub ahead of print]
  11. Doehnert M, Brandeis D, Imhof K, Drechsler R, Steinhausen HC. Mapping attention-deficit/hyperactivity disorder from childhood to adolescence -- no neurophysiologic evidence for a developmental lag of attention but some for inhibition. Biol Psychiatry. 2010;67:608-616. Abstract
  12. Wasserman RC, Kelleher KJ, Bocian A, et al. Identification of attentional and hyperactivity problems in primary care: a report from pediatric research in office settings and the ambulatory sentinel practice network. Pediatrics. 1999;103:e38.
  13. Cuffe SP, Moore CG, McKeown RE. Prevalence and correlates of ADHD symptoms in the national health interview survey. J Atten Disord. 2005;9:392-401. Abstract