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Open Access

## Do the ADHD subtypes exist on a physiological continuum? A reply to Reiersen and Todorov (2013)

Keith Fluegge

Institute of Health and Environmental Research, Cleveland Ohio, USA

Corresponding author:

keithfluegge@gmail.com

To the Editor:

Reiersen  and  Todorov  (1)  published  their  findings exploring the relationship between the various subtypes  of  attention-deficit/hyperactivity  disorder (ADHD)  and  related  psychopathologies  in  a  large population-based sample of adolescents and children.  The  authors  reported  that  subjects  who presented with symptoms from both the inattentive subtype and the hyperactive subtype experienced a greater  severity  of  co-occurring  psychopathology. This led the authors to conclude that, although the continued  clinical  use  of  ADHD  subtypes  may  be appropriate,  these  distinct  diagnostic  subtypes  may be  resulting  in  a  failure  to  identify  an  important subgroup of ADHD patients-those who experience symptoms from both subtypes-and thus potentially leading to more severe psychopathological  outcomes.  The  authors  advised that upcoming editions of the Diagnostic and Statistical Manual  of  Mental  Disorders be  revised  to  include  a diagnostic category of ADHD  'not  elsewhere classified.'

In  support  of  this  idea,  another  recent  metaanalysis qualified the role of hyperactivity in patients with ADHD (2) and indicated that hyperactivity may not  be  a  ubiquitous  feature  of  ADHD.  Rather,  its manifestation  may  be  particularly  dependent  on environmental factors, including cognitive functioning demands. Prolonged cognitive load has been  associated  with  sympathetic  hyperactivity  in healthy  humans  (3).  Given  that  medication-naïve patients  with  ADHD  experience  parasympathetic overarousal  (4),  it  may  be  that  excessive  motor activity  is  associated  with  sympathetic  mechanisms that are affected by changing cognitive demands (5).

Other recent findings have corroborated an association  between  air  pollution  and  childhood behavior  problems  (6).  It  has  subsequently  been suggested  that  chronic  environmental  exposure  to the  widespread  and  underestimated  air  pollutant nitrous  oxide  (N2O)  may  be  the  primary  etiologic factor in neurodevelopmental disorders like ADHD (7-9). Subanesthetic and subanalgesic N2O exposures in humans have been characterized by impairments in attention and working memory (10,11) as well as by the induction of a parasympathetic dominant state (8), thereby suggesting that a compensatory hyperkinetic  state  may  reverse  these  physiological effects (3,5).

When  considering  the  role  of  hyperactivity  in ADHD for the facilitation of sympathetic resuscitation,  it  may  be  important  to  consider  the spontaneously hypertensive rat, which is a validated model of ADHD  (12) before the onset of hypertension (i.e., sympathetic overflow) (13). It may therefore be reasonable to speculate that a hyperactive state precedes (in spontaneously hypertensive rats) and possibly potentiates (in humans) sympathetic resuscitation. This would imply that  the  various  ADHD  subtypes  may  not  be exclusive conditions; rather, the subtypes may exist on a continuum in a significant contingent of patients with ADHD, as Reiersen and Todorov have found (1). Therefore, chronic environmental N2O exposure may lead to attention deficits and a parasympathetic dominance, whereas a hyperkinetic phenotype may be a compensatory mechanism of sympathetic and cognitive  resuscitation.  However,  a  recent  metaanalysis contradicts the notion of autonomic dysregulation  and  parasympathetic  dominance  in patients with ADHD (14). Therefore, the relationship between the  ADHD  subtypes  and chronic environmental N2O  exposure warrants further clarification to understand whether the subtypes  exist  on  a  physiological  continuum  in response to environmental exposure to N2O.

## Conflict of Interest

The author declares no conflict of interest.

## Disclosure

Similar  manuscripts  related  to  this  hypothesis  may  be under review, in press  or published elsewhere, although the specific content contained in this manuscript is original and not in review or previously published. Relevant prior works are cited.

## References

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