The literature on pathophysiology of ADHD is quite inconsistent with mixed results to synthesize all the findings in any domain of neuropsychological, neuroanatomical, neurochemical or genetics to link them to the correspondent clinical phenotypes of the current ADHD subtypes. On a descriptive level, the symptomatology of two distinct ADHD subtypes of hyperactive-impulsive (ADHD-HI) and inattentive (ADHD-I) are quite different and hardly seem to come under the same disease entity as it has long been categorized by DSM classifications with no change in the recent DSM5 (1). While ADHD-I or ADD as it was labeled in the past, it is an “attention-deficit” disorder, ADHD-HI beyond an attention-deficit disorder, it is a behavioural disorder with cardinal symptoms of hyperactivity, impulsivity and behavioural disinhibition (2-4). As a result, the majority of research samples, hence the conclusions of the literature for clinical practice have relied heavily on the “combined subtype” that is an ill-defined combination of both subtypes. This ill-defined combined subtype usually is not consisted of 6 symptoms of either subtypes as required by DSM5, but some of the symptoms of each, in a mixed and arbitrary construct with no clear underlying pathophysiology as either subtypes. This contradicting fact has long caused an intense argument in the literature on the total validity of ADHD as a homogenous or single disorder with a single pathophysiology or two or more heterogeneous disorders with different pathophysiology (5-7), that I will attempt to review and explore in this paper.
ADHD: Homogenous or Heterogeneous?
In fact throughout the history, ADHD has been a homogeneous condition, first described as “hyperkinetic” or “hyperactive” syndrome or disorder of children, with recognition of “impulsivity” as a component of hyperactivity first by Laufer et al. (8) in 1957. The second edition of DSM, i.e. DSM-II in 1968, (9) published by the APA, that for the first time recognized the condition as a disorder, labeled it as “hyperkinetic reaction of children”. It was not until the third edition of DSM (10) in 1980 that recognized the condition as an attention deficit with hyperactivity and labeled it as such, i.e. ADHD, that we started facing a combined and heterogeneous disorder. Unfortunately since then the research samples have been mostly undifferentiated or of combined subtype with rare comparison between the two subtypes, so to clarify any distinctions between the two if any.
The few available comparison studies between the subtypes have shown that there is a distinct difference between the two with the conclusion of the most that ADHD is a heterogeneous condition with differences not only in symptomatology and the course of illnesses across the brain development, but differences in cognitive functions and different etiopathophysiology (11-12). Goth-Owens et al. (13) in their comparison study of 572 children and adolescents with pure inattentive subtype (ADD), combined type (ADHD-C) and non-ADHD controls, reported slower cognitive interference speed in the ADD vs. ADHD-C and controls comparisons. A similar result was reported by Carr et al. (14) who reported an attenuated attentional blink versus controls and ADHD-combined addressed in a sample of 145 ADD/ADHD and typically developing comparison adolescents (aged 13-17). A similar result has been reported by Solanto et al. (15 ) that predominantly inattentive subtype show worse performance than combined subtype and control groups on the WISC-III Processing Speed Index. This has made some researchers to question the validity of DSM current diagnostic criteria of ADHD to include two distinct subtypes of inattentive and hyperactive/impulsive under the same diagnostic umbrella. (16) Martel et al. (17) in comparison between the two subtypes, reported “a composite executive function factor was significantly related to inattentive but not hyperactive-impulsive symptoms.” The authors concluded “Executive function weakness in adolescent ADHD is specifically related to symptoms of inattention-disorganization.” Nigg et al. (18) also reported that symptoms of inattention-disorganization were uniquely related to executive functioning when hyperactivity-impulsivity controlled. “Inattention was associated with slower response speed, and hyperactivity-impulsivity with faster output speed. Results were not accounted for by IQ, age, gender, education level, or comorbid disorders.” Also Marshal et al. (19) found academic underachievement in a group of 6-12 years old with ADHD without hyperactivity. Friedman et al. (20) have reported that such cognitive deficits continue until late adolescence and Nigg et al. (21) who report their extensions to adulthood.
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