I promised you that I would write more about ADHD, including the neurodevelopmental findings.

Different types of studies demonstrate the heterogeneity of ADHD. One is to look for latent class trajectories through a method called growth mixture modeling. That means the researchers are using mathematical models to see whether ADHD children sort out into different groupings over time. Many studies have shown that there are two “symptom clusters” in ADHD – inattentiveness (In) and hyperactivity and impulsivity (H/I). One recent study (Arnold et al, 2014) followed 684 children over 3 years. Although these children were originally chosen to study a mood disorder, a large percentage of them (526) of them met the criteria for ADHD. In the group of ADHD children, the researchers were able to show that the children did sort out into several groups that followed different paths in the severity of their symptoms during the course of the 3-year follow-up. There was a high overlap in severity of the In and H/I symptoms over time, confirming that there is a link between these two symptom clusters. Yet, it also seemed clear that the hyperactivity/impulsivity symptoms waned over time, whereas the inattentiveness did not. This finding is consistent with other studies and with clinical experience that suggests that children with HA/I and Inattentiveness become less hyperactive and impulsive as they grow older, but they may continue to be inattentive and distractible.

A study approaching ADHD from the point of view of specificity of current diagnostic criteria looked at the effect of increasing the age of onset listed in the diagnostic criteria for ADHD in the old – DSM-IV – diagnostic manual to see if there was something specific to the children diagnosed by 7-yo (Vande Voort et al, 2014). In fact, the researchers found that if you extend the age of onset for diagnosing a child with ADHD from 7-yo to 12-yo, you get a condition that is indistinguishable from what you get if you use 7-yo as a cut off. Interestingly, the later onset group tended to come from lower income and ethnic minority populations, suggesting that these children had less access to clinical evaluation (or perhaps a different cultural bias against evaluation) and that was the reason they received the diagnosis later. Again this study challenges the specificity of the ADHD diagnosis and suggests that there are many other variables involved in making the diagnosis than valid diagnostic guidelines.

Another approach to “capturing the heterogeneity” of ADHD is to see whether some children with ADHD symptoms also have another kind of problem, whereas other ADHD children do not. One group of researchers did a recent study in which they tried to determine whether emotional reactivity and regulation could distinguish different groups of ADHD children (Musser et al, 2013). In other words, they were testing qualities of the children’s stress regulatory system. They found that ADHD is not only heterogeneous clinically, but it is also heterogeneous with respect to these traits. One ADHD group showed atypically elevated parasympathetic reactivity (associated with emotional dysregulation) along with increased sympathetic activity (associated with elevated arousal) when the child was stressed in the laboratory situation. By contrast, another group had reduced parasympathetic reactivity and reduced sympathetic activity (low emotional arousal). This second group was also more clinically symptomatic, having more conduct problems, peer problems, and more total difficulties, than the first group. In sum, the study showed that both groups of ADHD children had altered autonomic nervous system functioning, but of different types.

A recent prospective study demonstrating the fact that there is not just “one ADHD” is that by (Ramos Olazogasti et al, 2013). This study is unusual in that it is a 33-year prospective study of a large number, 135, boys with ADHD in childhood. Some of the boys also had conduct disorders, and some did not. The researchers wondered about the link between ADHD and adverse life events in the future, such as accidents related to risky behavior associated with impulsivity or even medical illness. What they found was the group that had both ADHD and conduct disorders had more risky behavior in adult life and a significantly greater incidence of problems related to that risky behavior such as admissions to the emergency department, head injury, and sexually transmitted diseases. Interestingly, they did not report a greater number of medical illnesses. This study also found that psychostimulant medication did not predict for cardiac illness.

Finally, many genes in pathways involved in dopamine/norepinephrine and serotonin neurotransmission, and also genes involved in neuritic outgrowth, are implicated in the etiology of ADHD but thought to have a small effect at the individual level (“small effect size”). One study used multivariable analysis to combine the effect of single genetic variants thought to play a role in ADHD (Bralten et al, 2013). When they summed the genetic effects of these genes they found a significant association with H/I symptoms but not with inattention symptoms! This offers yet more evidence that ADHD is not a discrete disorder but a “final common pathway” of many genetic and structural factors, all of them contributing in some way to the development of the nervous system. Whether these neurodevelopment end points are appropriately called “disorders” or are instead extremes in a spectrum of neurodevelopmental positions is yet to be determined.

References (See Post for Aug 31, 2014 )

Bralten J, Franke B, Waldman I, Rommelse N, Hartman C, Asherson P, Banaschewski T, Ebstein R, Gill M, Miranda A et al (2013). Candidate genetic pathways for Attention-Deficit/Hyperactivity Disorder (ADHD) show association to Hyperactive/Impulsive symptoms in children with ADHD, JAACAP, 52(11):1204-1212.

Photograph by Ginger Gregory