ADHD Atten Def Hyp Disord (2015) 7:249–269
DOI 10.1007/s12402-015-0171-4
REVIEW ARTICLE
ADHD symptomatology is best conceptualized as a spectrum:
a dimensional versus unitary approach to diagnosis
Rebeca Heidbreder1
Received: 18 January 2015 / Accepted: 18 April 2015 / Published online: 10 May 2015
 Springer-Verlag Wien 2015
Abstract The aim of this paper is to build a case for the
utility of conceptualizing ADHD, not as a unitary disorder
that contains several subtypes, but rather as a marker of
impairment in attention and/or impulsivity that can be used
to identify one of several disorders belonging to a spec-
trum. The literature will be reviewed to provide an over-
view of what is known about ADHD in terms of
heterogeneity in symptomatology, neuropsychology, neu-
robiology, as well as comorbidity with other diseases and
treatment options. The data from these areas of research
will be critically analyzed to support the construct of a
spectrum of disorders that can capture the great variability
that exists between individuals with ADHD and can dis-
criminate between separate disorders that manifest similar
symptoms. The symptoms associated with ADHD can be
viewed as dimensional markers that point to a spectrum of
related disorders that have as part of their characteristics
impairments of attention and impulsivity. The spectrum
can accommodate symmetrically and asymmetrically co-
morbid psychiatric disorders associated with ADHD as
well as the wide heterogeneity known to be a part of the
ADHD disorder. Individuals presenting with impairments
associated with ADHD should be treated as having a
positive marker for a spectrum disorder that has as part of
its characteristics impairments of attention and/or impul-
sivity. The identification of impairment in attention and/or
impulsivity should be a starting point for further testing
rather than being an endpoint of diagnosis that results in
pharmacological treatment that may or may not be the
& Rebeca Heidbreder
rebeca.heidbreder@psychresearchcenter.com
1
PsychResearchCenter, LLC, 3669 Michaux Mill Drive,
Powhatan, VA 23139, USA
optimal therapy. Rather than continuing to attribute a large
amount of heterogeneity in symptom presentation as well
as a high degree of symmetric and asymmetric comorbidity
to a single disorder, clinical evaluation should turn to the
diagnosis of the type of attentional deficit and/or impul-
sivity an individual has in order to colocate the individual’s
disorder on a spectrum that captures the heterogeneity in
symptomatology, the symmetrical and asymmetrical co-
morbidity, as well as subthreshold presentation and other
variants often worked into the disorder of ADHD. The
spectrum model can accommodate not only the psy-
chophysiological profiles of patients, but is also consistent
with what is known about the functional heterogeneity of
the prefrontal cortex as well as the construct that cognitive
processes are supported by overlapping and collaborative
networks.
Keywords ADHD
Heterogeneity
Spectrum disorder

Diagnosis
Prefrontal cortex
Comorbidity
Neural
circuitry
Neural networks
Attention
Impulsivity

Mental health disorders
Introduction
The century-long observation that certain children exhibit a
behavior pattern that is characterized by fidgetiness and/or
frank hyperactivity and that often presents along with a
lack of attention or focus as well as impulsivity (Anasto-
poulos et al. 1994; Barkley and Peters 2012; Lange et al.
2010; Taylor 2011) has resulted in decades of research
about the disorder now known as Attention Deficit
Hyperactivity Disorder (ADHD) [Diagnostic and Statistical
Manual of Mental Disorders 5th ed., American Psychiatric
Association 2013, (DSM V)]. This disorder has been
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characterized in terms of types and traits (Fair et al. 2012;
Sonuga-Barke 2002), age (Feldman and Reiff 2014;
Volkow and Swanson 2013; Wolraich 2006), gender (Ar-
nett et al. 2014; Skogli et al. 2013, Berry et al. 1985),
treatment (Bolea-Alamañac et al. 2014; Cunill et al. 2015;
Ollendorf et al. 2013; Evan et al. 2014; Stevenson et al.
2014), duration (Faraone 2005; Mattfeld et al. 2014; van
Lieshout et al. 2013), comorbidity with other syndromes
(Biederman et al. 1991; DSM V 2013; Patel et al. 2012;
Pliska et al. 1999; Williamson et al. 2014), as well as
differences in neuroanatomical structure and function (Cao
et al. 2014; Valera et al. 2007; for review see Rubia et al.
2014a). The DSM V (2013) characterizes ADHD as a
single disorder the diagnosis of which can be made more
specific in terms of the presence or absence of inatten-
tiveness or hyperactivity to varying degrees as a function of
the fulfillment of several criteria across different settings.
There is growing evidence, however, that ADHD is a much
more heterogeneous disorder than such a diagnosis is able
to capture not only in children and adolescents (Fair et al.
2012; Balázs and Keresztény 2014; Koziol and Budding
2012; Sonuga-Barke 2002; Williamson et al. 2014), but
also, and perhaps to an even greater extent, in adults (De
Quiros and Kinsbourne 2001; Kessler et al. 2011). Fur-
thermore, it has even been proposed that the presentation of
inattentiveness as the primary symptom in some indi-
viduals that are given the diagnosis of ADHD may be
indicative of a similar, but separate disorder (Barkley 2001;
Barkley 2013; Carlson 1986; Diamond 2005; Hinshaw
2001; Lee et al. 2014; Milich et al. 2001). ADHD is also
highly comorbid with other psychiatric disorders with some
estimates as high as 60–70 % (MTA Cooperative Group
1999; Patel et al. 2012). This comorbidity is bidirectional
as well as in that not only will the ADHD-diagnosed pa-
tient have one or more psychiatric or learning disorders,
but those patients with a primary diagnosis of one of sev-
eral psychiatric disorders also meet criteria for ADHD at
rates higher than the general population (Biederman et al.
1991; Pliszka 2015), further complicating the etiology of
ADHD and adding to the great variability in the ADHD
population. Given the increasing rate in the diagnosis of
ADHD in children (Visser et al. 2014) and adults (Kessler
et al. 2011) as well as the exponential increase in the
treatment of ADHD with pharmacological agents over the
last decade, it is increasingly becoming more important to
refine the characterization of ADHD to allow health care
workers to delineate specific dysfunctions and maximize
efficacy of treatment.
The aim of this paper is to build a case for the utility of
conceptualizing ADHD not as a unitary disorder that
contains several subtypes, but rather as a marker of im-
pairment in attention and/or impulsivity that can be used to
identify one of several disorders belonging to a spectrum.
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R. Heidbreder
The present review will provide an overview of what is
known about ADHD in terms of heterogeneity in symp-
tomatology, neuropsychology, neurobiology, as well as
comorbidity with other diseases and treatment options. The
data from these areas of research will be critically scruti-
nized in order to build a case that the current DSM system
used as the gold standard for the diagnosis of ADHD is
insufficient either to capture the great variability that can
exist between individuals in their manifestation of the
disorder or to discriminate between separate disorders that
manifest similar symptoms. The review will conclude with
the suggestion that the construct of a spectrum is not only
better able to handle individual variability and hetero-
geneity among the ADHD population in terms of external
manifestations such as symptom presentation, neuropsy-
chological assessment and comorbidity, but given what is
known about the cytoarchitecture and heterogeneity of the
prefrontal cortex (Chudasama 2011; Heidbreder and
Groenewegen 2003; Kesner and Churchwell 2011) as well
as strong evidence supporting that different cognitive
processes are subserved by different subregions of the
prefrontal cortex, such a model can better explain the
overlap in symptoms and strong interrelations ADHD has
with other psychiatric diseases.
Prevalence of ADHD
There are many reviews on the historical evolution of
ADHD (Anastopoulos et al. 1994; Barkley and Peters
2012; Lange et al. 2010; Matthews et al. 2014; Tarver et al.
2014) that reveal a disorder first characterized by a hy-
perkinetic aspect and then the inability to focus in the
presence of excessive distractibility. Over the last few
decades, research has concentrated more on the attention
and impulsivity aspects of the disorder as the understand-
ing of the neural substrates that govern these aspects of
cognition has increased, and pharmacological treatment has
become more widespread (Douglas 1972, 1994, 1999,
2005; Konrad et al. 2006; Leth-Steensen et al. 2000; Rubia
et al. 2005, 2014a). This is particularly meaningful given
that (1) the hyperkinetic portion of the disorder may di-
minish with age (Barkley 1990, 1997; AACAP 1997) and
(2) the disorder may persist into adulthood when the ob-
vious hyperactivity has all but disappeared (Volkow and
Swanson 2013; Willoughby 2003). The fact that the dis-
order may manifest as a constellation of different symp-
toms depending on the individual has contributed to the
variability in the estimation of the frequency of the disorder
in the population. Whereas the DSM V (2013) states that
the prevalence of ADHD across cultures is about 5 % in
children and 2.5 % in adults, data from the most recent
National Survey of Children’s Health (NSCH) (Visser et al.
ADHD symptomatology is best conceptualized as a spectrum: a dimensional versus unitary approach…
2014) indicate that as of 2011, the prevalence in children
4–17 years of age who had ever received a diagnosis of
ADHD by a health care provider as reported by a parent in
the USA is approximately 11 % (6.4 million children). The
study also states that this figure represents a 42 % increase
in parent-reported history of ADHD diagnosis since 2003.
In addition, the national yearly rate at which ADHD has
been diagnosed has increased by 5 % since 2003; however,
the rate of diagnosis varies substantially by state, from a
low of 5.6 % in Nevada to a high of 18.7 % in Kentucky.
All told the NSCH reveals that, relative to 2003, in 2011
approximately 2 million more American children had re-
ceived a diagnosis of ADHD. When Polanczyk et al.
(2014) conducted a meta-analysis of the data found in 135
studies published from 1985 to 2012 and aimed at inves-
tigating the prevalence of ADHD worldwide, the results
suggested that differences in the estimates of prevalence
were significantly associated with the diagnostic criteria,
impairment criterion and source of information. The au-
thors concluded that accurate prevalence rates can only be
estimated if standardized diagnostic procedures are im-
plemented in representative samples of the community. In
their study, standardized diagnostic criteria were defined as
those studies that used the diagnostic criteria from The
Diagnostic and Statistical Manual of Mental Disorders 3rd
ed., American Psychiatric Association, (1980) (DSM III),
Diagnostic and Statistical Manual of Mental Disorders 3rd
ed., text rev. American Psychiatric Association (1987),
(DSM III-R), Diagnostic and Statistical Manual of Mental
Disorders 4th ed., text rev. American Psychiatric Asso-
ciation (2000) (DSM IV) and the International Statistical
Classification of Diseases and Related Health Problems.
World Health Organization, (1992) (ICD 10). The authors
state that when such an approach is taken, not only does the
variability in ADHD prevalence estimates disappear, but so
does the increase over time (1994–2010) in the number of
children who meet the criteria for ADHD. Wolraich et al.
(2014) also set out to disentangle the epidemiology of
ADHD using the strict definition provided by the DSM IV
(2000), which as in the DSM V (2013) requires information
from multiple informants and settings to establish the di-
agnosis. Their results yielded an overall prevalence more in
line with the Visser et al. (2014) study than the Polanczyk
et al. (2014). Both Wolraich et al. (2014) and Visser et al.
(2014) also found geographical differences in the preva-
lence range within the USA. In contrast, Polanczyk et al.
(2014) found no prevalence variations as a function of
geographical regions of the world.
Though the net objectives in the Polanczyk et al. (2014)
study and the Wolraich et al. (2014) study were the same,
that is, to use the DSM diagnostic criteria to provide an
estimate of the prevalence of ADHD, the prevalence rates
found by Wolraich et al. (2014) are more than 1.5 times
251
greater than Polanczyk et al. (2014). This difference could
indicate that the suspicion and/or diagnosis of ADHD re-
mains subjective even when formal diagnostic criteria
established by the DSM are implemented. This subjectivity
comes primarily from two sources. First, the presence or
absence of symptoms necessary for diagnosis are provided
by parents, teachers and the patient himself, which are then
interpreted and evaluated by a clinician. Second, certain
combinations of symptoms are more likely to prompt
clinical intervention and a subsequent diagnosis. There are
data supporting that it is the symptomatology associated
with hyperactivity, behavior disruption and disorganization
rather than inattention and even impulsivity that will
prompt consideration for clinical or therapeutic interven-
tion (Diamond 2005, Feldman and Reiff 2014; Nigg et al.
2005; Weiss et al. 2003). In addition, there is also evidence
suggesting that girls with ADHD are underidentified (Berry
et al. 1985; Bruchmüller et al. 2012). This underidentifi-
cation may be due to the qualitative differences between
the genders in their presentation of ADHD, which include
symptom severity, (Arnett et al. 2014), behavior differ-
ences (Gaub and Carlson 1997) and cognitive differences
(Arnett et al. 2013). The qualitative gender difference may,
at least in part, also be responsible for the significant
quantitative gender differences in ADHD (Willcutt 2012).
All of these factors can ostensibly interact with cultural/
individual perceptions of what is or is not considered
symptoms of a behavior disorder. Therefore, the very same
factors that would tend to encourage over diagnosis in
some cases make it impossible to account for all of the
possible cases that were not included in the studies because
of differences in thresholds for seeking clinical help for a
child with ADHD in other cases. This variability in
threshold holds particularly true with respect to compar-
isons across geographical regions, and may account for the
difference between the Polanczyk et al. (2014) study which
failed to find a significant effect of geographical region and
the variance in prevalence among the different geo-
graphical regions found by Visser et al. (2014) and Wol-
raich et al. (2014).
Diagnosis
The historical evolution of ADHD since the second edition
of the DSM (DSM II) (Diagnostic and Statistical Manual of
Mental Disorders 2nd ed., American Psychiatric Asso-
ciation 1968) until the current fifth edition (DSM V) has
seen ebb and flow in terms of subtyping in an attempt to
capture the heterogeneity in the disorder evident to re-
searchers and clinicians. As suggested by the work on
prevalence (Polanczyk et al. 2014; Visser et al. 2014;
Wolraich et al. 2014) reviewed in the previous section,
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variability in the identification of ADHD in a patient occurs
not only as a function of differences in methodology, but
between clinical evaluations even when there is adherence
to the criteria of the DSM. Typically, the suspicion of a
clinical problem begins when either the parent or the tea-
cher starts to notice, among other things, that the child
cannot sit still, struggles to focus and has behavioral issues,
which may also negatively impact academic performance
(Sibley et al. 2014). The physician who ultimately sees the
child may reach a diagnosis of ADHD simply based on the
anecdotal evidence from the parent and/or teacher without
actually subjecting the child to a comprehensive assess-
ment (Sciutto and Eisenberg 2007). The physician may rely
on further interviews, including with the patient himself,
rather than standardized assessment tools and may or may
not adhere to the DSM criteria in order to reach their di-
agnosis and start the child on medication (Wasserman et al.
1999). Even many psychologists do not regularly follow
assessment procedures that are consistent with the best
practice guidelines, which can result in a false-positive
diagnosis and the inception of pharmacological therapy
(Handler and DuPaul 2005). These scenarios seem to
indicate that clinical practitioners still view ADHD as a
compartmentalized disorder that presents with a concrete
and highly recognizable set of symptoms (Bruchmüller
et al. 2012). This narrowed view on positive clinical pre-
sentation is particularly vexing in the area of what defines a
clinically significant academic problem that is specific to
the ADHD patient as compared to the academic problems
observed in the normal age-matched population (Sibley
et al. 2014). The lack of objective delineation not only
muddies the waters, but can also lead to a failure to identify
a child who actually has a clinical problem. For example,
teachers may fail to detect children with symptoms of
inattention because they exhibit no hyperactivity and are
often quiet and less likely to act out in the classroom. These
children may appear to be working, but they are often not
paying attention to what they are doing. Conversely, some
children who are actually exhibiting the clinical hyperac-
tivity and impulsivity that are characteristic of some forms
of ADHD in the classroom setting will be considered as
merely having disciplinary problems, and rather than being
evaluated for the disorder will simply be subject to punitive
practices to correct their behavior.
In their review, Nigg et al. (2005) point out that though
most theorists do not believe that individuals with ADHD
have a unitary disorder with a ‘‘common pathway to their
problems,’’ there is still a need to address empirically the
heterogeneity that everyone accepts as fact. Beyond pos-
sible differences in neuropsychological profiles that the
authors were specifically addressing, the heterogeneity
among the ADHD population can also be a function of
comorbidity, the manner in which the symptoms that are
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part of the ADHD criteria for diagnosis combine and pre-
sent in any one patient, as well as the ‘‘subthreshold’’
(Balázs, and Keresztény 2014) presentation of symptoms
that does not lead to a true diagnosis of ADHD, but can still
cause impaired function. Furthermore, data are building in
support of the idea that some patients that receive the di-
agnosis of ADHD may actually be suffering from a dis-
order that is separate, but somehow similar to ADHD (e.g.,
Diamond 2005; Hinshaw 2001; Milich et al. 2001).
Subtype or separate disorder?
The DSM V (2013) allows for the specification of ADHD
along several dimensions based on the number of criteria
that have been fulfilled in the categories of ‘‘Inattention’’
and ‘‘Hyperactivity and Impulsivity.’’ As a result, the pa-
tient with ADHD can be considered to have a Combined
Presentation (the abbreviation ‘‘CT’’ will be used, which
refers to the virtually identical ‘‘Combined Type’’ presen-
tation from the DSM IV-TR) if sufficient criteria from both
categories have been met, a Predominantly Inattentive
presentation (PI) if sufficient criteria are met only for the
‘‘Inattention’’ category, or a Predominantly hyperactive/
impulsive type (HI) if sufficient criteria are met only for the
‘‘Hyperactivity and impulsivity’’ category. The DSM V
(2013) further suggests specifying the disorder in terms of
the severity of presentation (mild, moderate and severe).
Several studies have investigated the cognitive differences
between these subtypes with varying results (e.g., Baeyens
et al. 2006; Bonafina et al. 2000; Chhabildas et al. 2001;
Fair et al. 2012; Faraone et al. 1998; Geurts et al. 2005;
Lockwood et al. 2001; Nigg et al. 2002; Riccio et al. 2006;
Song and Hakoda 2014). However, it has been proposed
that the differences between the CT subtype and the PI
subtype are significant enough and that rather than being
two different subtypes of the same disorder, the CT and PI
subtypes should be considered as two distinct disorders
(Baeyens et al. 2006; Barkley 2001; Diamond 2005; Hin-
shaw 2001; Milich et al. 2001). Both Milich et al. (2001)
and Diamond (2005) provide detailed reviews of the
qualitative differences between the two subtypes, which
make a strong case for positing CT and PI as nearly
diametrically opposite conditions. Although the PI subtype
represents about 25–30 % of the ADHD cases seen in the
clinic (Faraone et al. 1998; Weiss et al. 2003), in the
community it is the more prevalent subtype (Carlson and
Mann 2000) by nearly double relative to the CT subtype
(Gaub and Carlson 1997). The CT subtype has almost
exactly the opposite prevalence profile, namely in the clinic
the CT subtype is seen nearly twice as much as the PI
subtype (Faraone et al. 1998). Furthermore, whereas gen-
der differences in prevalence ratios for the CT subtype in
ADHD symptomatology is best conceptualized as a spectrum: a dimensional versus unitary approach…
the community and in the clinic are significantly different,
the PI subtype has practically the same gender distribution
in both the community and the clinic. This discrepancy
suggests that not only are individuals with the PI subtype
receiving clinical care at a lower frequency than the CT
subtype, but the CT subtype is associated with symptoms
that are more readily identifiable as being part of a disor-
der. It is likely that the very character attributes that dis-
tinguish the CT from the PI subtypes are what prompt the
visit to the clinician for further evaluation. Diamond (2005)
reminds us that while individuals with the CT subtype are
hyperactive, fidgety, impulsive, talkative, disinhibited,
disorganized and impatient, the PI subtype is characterized
by the inability to pay close attention to detail, difficulty in
planning and remembering to do what is required, and
disorganization. Diamond (2005) also points out that
though both the PI and CT subtypes could have the qua-
lifier ‘‘easily distracted’’ added into their characterization;
the difference between them has to do with the type of
distractibility that they experience. Whereas the individual
with CT subtype could become easily distracted by another
stimulus that enters his sphere of awareness, the individual
with the PI subtype becomes distracted because she loses
interest in the activity she is engaging in. This difference
can be qualified as an external versus internal mode of
distractibility. According to Weiss et al. (2003), an indi-
vidual suffering from the constellation of symptoms asso-
ciated with the CT subtype is also more functionally
impaired than someone suffering from the symptoms as-
sociated with the PI subtype. Furthermore, the individual
with the CT subtype has a higher likelihood of not only
being medicated, but being medicated at a higher dose
(Barkley 2001; Diamond 2005; Milich et al. 2001; Weiss
et al. 2003). In fact, Faraone et al. (1998) report that the CT
subtype is associated with a more clinically severe syn-
drome than either the PI subtype or the HI subtype. Finally,
although both subtypes appear to respond to treatment with
stimulants, the CT subtype has a higher probability of
being rated as improved relative to the PI subtype (Weiss
et al. 2003).
Although the data are compelling, there is as yet no
absolute consensus regarding the separation of the PI and
CT subtypes into two separate disorders. However, the
research that has set in motion part of this debate has
inadvertently opened the metaphorical ‘‘Pandora’s Box,’’
which has postulated the possibility of splitting the PI
subtype itself into two different disorders of attention
(Carlson and Mann 2002). The idea that ‘‘sluggish cogni-
tive tempo’’ (SCT) could be indicative of an impairment
that is separate from the PI subtype was proposed by
Carlson and Mann (2002) as an extension to the findings
from McBurnett et al. (2001). In their view, it may be
possible to distinguish two different disorders in patients
253
who have no symptoms of hyperactivity and impulsivity,
but who manifest problems with attention. Namely, one
disorder is characterized by the Inattentive criteria outlined
in the DSM, and the second disorder, seen only in a subset
of PI patients, is characterized by specific traits including
hypoactivity, dreaminess and forgetfulness. There has been
a recent resurgence in the number of investigations aimed
at providing evidence for the validity of qualifying SCT as
a separate disorder (Barkley 2013; Bauermeister et al.
2012; Becker et al. 2014; Lee et al. 2014; Saxbe and
Barkley 2014). The utility of these and future investiga-
tions is not only in their ability to reach consensus, but
more importantly to increase the understanding in psy-
chopathological problems of attention. As Becker et al.
(2014) point out, ‘‘SCT may be useful as a transdiagnostic
construct,’’ which could fit in neatly with the reminder
from Barkley (2001) that ‘‘attention is multidimensional
such that several distinct disorders of attention are likely to
be identified besides ADHD.’’
With respect to the CT and HI subtypes, there is evi-
dence to suggest that these may not be separate conditions
that remain stable over time, but rather subsets of each
other. On the one hand, investigators such as Lahey et al.
(2005) suggest that HI is a less severe form of CT, perhaps
due to the fact that hyperactivity reduces or disappears with
age. On the other hand, Barkley (2007) suggests that the HI
form of ADHD is simply a precursor to the CT form. Data
to support either position only adds greater weight to the
proposition that ADHD may not really be one disorder with
dimensional presentations, but rather several disorders that
are tied together by ‘‘etiological vicinity.’’
Finally, the diagnostic criterion of impulsivity has been
used to subcategorize patients diagnosed with ADHD for at
least two decades. However, the question about how to
define impulsivity in particular with respect to psychiatric
illness still continues to be debated (for review see Moeller
et al. 2014). The list of ‘‘Hyperactivity/Impulsivity’’ cri-
teria in the DSM V (2013) fails to capture the hallmark
traits of delayed gratification, rapid and unplanned actions,
as well as reduced sensitivity to negative consequences that
have historically been associated with impulsivity. In fact,
though ADHD is highly comorbid with conduct disorder
and oppositional disorder (Biederman et al. 1991), the
DSM V (2013) definition of the impulsivity associated with
‘‘Disruptive impulse control and conduct disorders’’ is very
different from the impulsivity associated with ADHD; yet,
when referring to the comorbidity with ADHD, the DSM V
(2013) says that since ADHD individuals are impulsive,
then it is not unusual that they should show this comor-
bidity. Although the paragraph on diagnostic features as-
sociated with ADHD does mention the hallmark traits
associated with impulsivity, the examples provided for an
impulsive action ‘‘darting into the street without looking’’
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or ‘‘taking a job without adequate information’’ only add to
the ambiguity for several reasons. Whereas it is not diffi-
cult to envision an individual who cannot wait his turn,
who is on the go and who runs about and intrudes and
interrupts as capable of darting into traffic or making poor
career choices, the individual who fits the profile of the PI
subtype can find themselves engaging in these same actions
for reasons that have nothing to do with impulsivity, but
instead everything to do with the quality of the attentional
processes these individuals may have access to. Though
Barkley (1997) suggests that the differences in the attention
difficulties between the PI and CT subtypes are related to
problems with selective attention in the former and prob-
lems with disinhibition in the latter, it is also possible to
look at both subtypes in terms of opposite ends of an at-
tentional spectrum. Specifically, whereas the PI subtype
may have an ‘‘attentional spotlight’’ that is too narrow, the
CT and HI subtypes may have ‘‘attentional spotlights’’ that
are too wide. The analogy of an ‘‘attentional spotlight’’
(Posner and Petersen 1989) or the fact that it may be too
wide in ADHD is not new (Shalev and Tsal 2003); how-
ever, the idea that the subtypes may vary as a function of
the breadth of the attentional spotlight is. On the one hand,
the wide attentional spotlight of the CT and HI subtypes
prevents those individuals from focusing selectively on any
one stimulus for an interval long enough to make eval-
uative judgments. In other words, they are overwhelmed by
stimuli, and as such, no one stimulus necessarily has more
salience than another. In contrast, the narrowness of the PI
subtype spotlight does not give them access to many other
competing stimuli that may be available at any one time
and are necessary to form an evaluative judgment. As a
result, on the one hand, the person with CT or HI subtype
may dart across the street or make a bad decision because
they do not rest their focus long enough among the wide
range of stimuli available to them to avoid making a de-
cision that might have negative consequences. In other
words, those individuals cannot stop moving their spotlight
across the wide range of stimuli that are available to them.
On the other hand, the PI subtype may have a stagnant
spotlight, such that even when the appropriate information
is available, they do not have the ability to access the in-
formation that would permit a better decision. In other
words, they are not giving their attention to all that they
can. Nevertheless, in both cases, the end result is the same.
In sum, there is an abundance of data indicating that the
variety in the symptomatology of patients seeking clinical
help for suspected ADHD exceeds the current nosology for
the delineation of this disorder. Furthermore, it would appear
that the manner in which patients present these symptoms do
not necessarily fall into clear-cut categories that are varia-
tions within only one disorder as proposed by the DSM.
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Comorbidity
Beyond the recognized variety in symptomatology of
ADHD, the accurate diagnosis of a patient can be con-
founded by the presence of one or more comorbid disor-
ders. It is now well established that 50–75 % of patients
diagnosed with ADHD will have at least one comorbid
learning disorder, psychiatric disorder or neurodevelop-
mental disorder (Barkley 2005; Biederman et al. 1991;
Jensen et al. 1997; Patel et al. 2012; Pliszka et al. 1999). In
addition, an adult with ADHD throughout his lifetime will
have six times the likelihood of developing another psy-
chiatric disorder (Brown 2006). The extensive review by
Biederman et al. (1991) tells us that ADHD is comorbid
with conduct disorder at a rate of between 30 and 50 %,
with oppositional defiant disorder at a rate of at least 35 %,
with mood disorders at a rate ranging from 15 to 75 %,
with anxiety disorders at a rate of at least 25 %, and with
learning disabilities at a rate between 10 and 92 %. ADHD
has also been associated with a greater risk for substance
abuse (Wilens and Morrison 2011). We also know that
comorbidity with ADHD can be asymmetrical, that is,
while the rate of ADHD in certain disorders can exceed
that in the general population, patients with ADHD do not
necessarily show those same disorders at a rate higher than
in the normal population (Pliszka 2015). For example,
60 % of Tourette patients will be concurrently diagnosed
with ADHD; nevertheless, people with ADHD are not di-
agnosed with Tourette’s at a rate higher than what occurs in
the general population (Jummani and Coffey 2015). Ap-
proximately 40 % of those diagnosed with borderline
personality disorder will also have received a diagnosis of
ADHD (Ferrer et al. 2010), but borderline personality
disorder does not occur more frequently in those whose
primary diagnosis is ADHD. Patients with bipolar disorder
have comorbid ADHD at a rate of 60–90 %, but only 22 %
of patients with ADHD as a primary diagnosis will have
comorbid bipolar disorder (Wilens et al. 2003). Obsessive
compulsive disorder is highly comorbid with ADHD par-
ticularly in boys in whom the rate of comorbidity is about
50 % (Geller 2006). Finally, there is even some evidence
that the presence of ADHD symptoms may be indicative of
premorbid schizophrenia or even be linked with a ‘‘distinct
neurodevelopmental progression of schizophrenia’’ (Marsh
and Williams 2006).
Certain patterns of comorbidity are also more strongly
correlated with ADHD than others (Greene et al. 1996;
Jensen et al. 1997; Lynam 1996). For example, the rela-
tionship between ADHD, conduct disorder and opposi-
tional defiant disorder often makes it difficult to
distinguish one from the other (Biederman et al. 1991).
Though large epidemiological studies do not usually
ADHD symptomatology is best conceptualized as a spectrum: a dimensional versus unitary approach…
provide comorbidity rates in ADHD by subtype, Faraone
et al. (1998) found that it is actually the CT form of
ADHD that is associated with the highest rate of co-
morbidity with conduct disorder and oppositional defiant
disorder. Furthermore, the difference in the rate of co-
morbidity between the CT and PI groups for these dis-
orders, the so-called externalizing disorders, was
significant. Though the relationship between internalizing
disorders and the different subtypes is not as well defined
(for review see Garner et al. 2013), children with the PI
subtype tend to be more socially isolated and may be
associated with a higher rate of comorbid internalizing
disorders, including anxiety and depression, or at the very
least are less prone to externalizing disorders (Diamond
2005). Schaughency et al. (1987) report that 43 % of
individuals with ADD without hyperactivity, the DSM III
(1980) subtype that is equivalent to the PI subtype of later
editions, also received diagnoses of either anxiety or de-
pression. Patients that have ADD with hyperactivity, the
DSM III subtype that is equivalent to the CT subtype of
later editions, were diagnosed with these disorders only at
a rate of about 10 %. Faraone et al. (1998) also noted that
the PI subtype was associated with a higher lifetime rate
of major depressive disorder relative to the other sub-
types. The study by Weiss et al. (2003) that involved
comprehensive and multidisciplinary evaluations also re-
vealed higher rates of anxiety and depression in the PI
subtype than in the CT subtype. Finally, it may be the
case that some of the impairment associated with ADHD
subtypes may be more related to the influence of the
comorbid disorder rather than to the disorder of ADHD
itself (Milich et al. 2001). For example, Lockwood et al.
(2001) were able to show significant neuropsychological
differences at 80 % accuracy between the CT and PI
types of ADHD when effect of presence of comorbidity
was controlled.
To summarize, there can be no doubt that the relationship
that ADHD has with a variety of psychiatric disorders is a
tangled and intricate one and many questions are left beg-
ging. There is still no clear understanding as to why there is
such a high incidence of comorbidity between ADHD and
other psychiatric diseases or how the diagnosis of ADHD can
seemingly predispose an individual to another psychiatric
disorder at a future date. One explanation may be that ADHD
and its comorbid psychiatric disorders may share a common
neural substrate involving the prefrontal cortex, which as a
result of heterogeneity in its neural circuitry can account for a
range of neurological, cognitive and psychiatric disorders
(Chudasama 2011; Heidbreder and Groenewegen 2003;
Kesner and Churchwell 2011). Recent evidence also sug-
gests that there may be a common neural substrate across
multiple mental illnesses (Goodkind et al. 2015).
255
Pharmacotherapy and alternative therapy
for ADHD
Although not an exhaustive review, the evidence provided
so far argues against describing a patient as simply having
ADHD or simply amassing together groups of patients that
may have important differences at the level of symptom
presentation, underlying psychiatric disease, and symptom
severity leading to impairment under one disorder. Nev-
ertheless, the prescription of pharmacotherapy to treat the
symptoms of what appears to be ADHD often starts with-
out an in-depth assessment of the true nature of the disorder
in the patient. The finding by Wolraich et al. (2014) that
5.7 % of the children sampled in their study received a
diagnosis of ADHD and were prescribed ADHD medica-
tion despite the fact that they did not meet the DSM IV-TR
(2000) criteria for ADHD underscores the willingness to
treat pharmacologically a set of symptoms that look like a
disorder, but for which there is no objective evidence of its
presence in the patient. Furthermore, even when a diag-
nosis is made using the criteria provided by the DSM,
pharmacological treatment efficacy may vary significantly
depending on the constellation of symptoms present in the
patient (del Campo et al. 2011; Feldman and Reiff 2014;
Hale et al. 2011). As of 2011, 1 million more children are
taking ADHD medication than in 2003 (Visser et al. 2014).
The very significant increase in use of ADHD pharmaco-
logical therapy is best described in the March 2014 Express
Scripts Lab Report ‘‘U.S. MEDICATION TRENDS for
ATTENTION DEFICIT HYPERACTIVITY DISORDER.’’
This report states that ADHD medication use among
Americans has risen 35.5 % from 2008 to 2012. This in-
crease has translated into a spending increase on ADHD
medication of 14.2 % in 2012 and represents the greatest
increase seen among any traditional drug category. ADHD
medication sales are also forecast to continue to grow to
nearly 25 % by 2015.
The willingness to prescribe pharmacological therapy,
specifically stimulants, for the patient presenting with
ADHD symptoms comes in part from the awareness that
this type of treatment seems to work best at alleviating the
core symptoms of ADHD (Faraone and Buitelaar 2010),
may be equally effective across subtypes (Solanto et al.
2009) and affects various aspects of cognition (Coghill
et al. 2014) by exerting their effects on the frontal cortex
(Rubia et al. 2014a). These findings are not surprising since
it is well known that stimulants exert their effects on the
dopaminergic network (for review see Segal and Kuczenski
1994; Kuczenski and Segal 1997), and these effects pro-
duce changes in behavior (Volkow et al. 1998). Given that
even a single dose of methylphenidate can enhance cog-
nitive performance in healthy volunteers and that there is a
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256
dose-dependent and a dose–response relationship that dif-
fers across a variety of cognitive domains (Linssen et al.
2014), pharmacotherapy as a global treatment for all pa-
tients diagnosed with ADHD without sensitivity to the
array of symptoms and functional deficits in any one in-
dividual may be akin to taking a canon to an anthill. For
example, though there may be an initial improvement in
some of the symptoms, pharmacotherapy does not always
‘‘normalize’’ cognition and/or behavior (e.g., Bédard et al.
2015; Gualtieri and Johnson 2008; Rapport et al. 1994;
Hale et al. 2011; Rubia et al. 2009), and worse yet can end
up precipitating far more serious symptoms, including
psychosis if pharmacotherapy is begun when the relation-
ship between the impairment due to any detected or un-
detected comorbid disorder and that due to the ADHD
symptoms is unclear (Schaeffer and Ross 2002). Further-
more, as suggested earlier, though the evidence to date
indicates that pharmacotherapy seems to eliminate the core
symptoms of ADHD irrespective of subtype, there is evi-
dence that the CT subtype has a higher probability of being
rated as improved relative to the PI subtype (Weiss et al.
2003). Whether or not the differences in efficacy across the
different presentations of ADHD as well as their associated
effects on cognition and behavior are linked with differ-
entiable changes in the aberration patterns of brain activity,
and/or, for example, a related change in catecholamine
availability (del Campo et al. 2011; Schmeichel and Ber-
ridge 2013) has yet to be fully clarified. Taken together all
of these factors point to the great need for the refinement
and deepening of the diagnostic process in order to identify
a clear clinical presentation that can optimize the clinical
outcome.
In parallel to the increased use of pharmacotherapy to
treat ADHD, there has also been an explosion in the search
for alternatives to the pharmacological treatment of ADHD
(Sonuga-Barke et al. 2013) even though many of these
alternative treatments show no evidence of efficacy. The
development of these alternatives has been fueled by
variability in efficacy of pharmacotherapy (Faraone and
Buitelaar 2010), the desire to avoid the known side effects
(Graham et al. 2011; Bolea-Alamañac et al. 2014; Clemow
and Walker 2014) and the unknown consequences of long-
term treatment with pharmacotherapy (Volkow and Insel
2003; Vitiello 2001) or simply by the desire to find a more
holistic solution in lieu of the pharmacological one (Tim-
imi 2004).
One area that has received significant attention is the
role of diet in ADHD either as the etiological basis for its
symptoms (Wolraich et al. 1985; Wolraich et al. 1994) or
as an option for treating the symptoms of the patient
(Millichap and Yee 2012; Nigg et al. 2012). Recent re-
views and meta-analyses of randomized controlled studies
to investigate the effects of dietary treatments for ADHD
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R. Heidbreder
(Stevenson et al. 2014; Sonuga-Barke et al. 2013) con-
cluded that though supplementation with free fatty acid
appears to have a small effect on ADHD-related behaviors,
there is no definitive effect of dietary treatment on these
behaviors.
There have also been numerous studies that have looked at
the effect of exercise on children with ADHD. A review by
Kamp et al. (2014) on the effects of exercise on ADHD-
related behaviors in children under 14 years of age con-
cluded that a wide variety of exercises, if implemented for
1–10 weeks, can have a positive effect on motor skills, social
behavior and strength in this population. However, when
Hoza et al. (2015) compared the effects of physical activity
and sedentary activity before the start of school on the be-
havior of early elementary school age children at risk for
ADHD, they were unable to assert conclusively that there
was a difference between interventions. Though the benefits
of exercise for the treatment of ADHD may still be unclear,
there is sufficient preclinical as well as clinical data on non-
ADHD populations that show that exercise has a beneficial
effect on neurobehavioral functioning and as such may be a
direction worth pursuing (Halperin et al. 2014).
Psychosocial interventions for children and adolescents
with ADHD have a long and controversial history (see
Antshel and Barkley 2011, for a historical review; Pelham
and Fabbiano 2008). Evans et al. (2014) conducted a meta-
analysis on 122 recent studies that investigated evidenced-
based effects of training intervention and behavior man-
agement treatments. Their results confirm that traditional
behavior management therapies have a well-established ef-
ficacy and that organization training also appears to be ef-
fective; however, improvement in function comes only with
the implementation of behavior management techniques
(Feldman and Reiff 2014). Other training interventions in-
cluding neurofeedback (for review see Holtmann et al.
2014), cognitive training (for review see Sonuga-Barke et al.
2014) and social skills training (for review see Mikami et al.
2014) show little or no efficacy. There are at least two caveats
to these findings. First, most studies do not look at effects of
these alternative therapies by subtype. Mikami et al. (2014),
however, did notice that social skills training seemed to be
more effective for the PI subtype than for the CT subtype.
Second, the addition of a behavioral therapy component to
the pharmacological treatment does not appear to confer any
advantage to the resolution of symptoms (Jensen et al. 2001a,
b; Sonuga-Barke et al. 2013).
Neural substrates of ADHD
The rationale behind why the core symptoms of ADHD
improve with stimulants comes from decades of research
that has revealed the effect of amphetamines on the
ADHD symptomatology is best conceptualized as a spectrum: a dimensional versus unitary approach…
dopaminergic network (for review see Segal and
Kuczenski 1994; Kuczenski and Segal 1997) and its
consequent effects on behavior (Volkow et al. 1998). The
effects of varying levels of dopamine in the brain have
been linked specifically to the frontal cortex in normal
subjects as well as in a variety of neurological and psy-
chiatric disorders (for review see Clark and Noudoost
2014). In particular, levels of dopamine in the frontal
cortex seem to modulate among other things impulsivity
(Dagher and Robbins 2009; Volkow et al. 2009; for re-
view see Sebastian et al. 2014), motivation (Volkow et al.
2011) and inattention (Rosa-Neto et al. 2005) all hallmark
characteristics of ADHD. As a result, there has been a
virtual explosion of studies aimed at uncovering differ-
ences in anatomy and function in the brains of ADHD
patients relative to normal cohorts. The scientific impetus
to conduct such studies stems presumably from a need to
understand what may be dysfunctional or aberrant in the
brain of the ADHD patient as well as the hope of finding
a biomarker that could render a diagnosis conclusive (for
review see Shaw et al. 2013). There are basically four
main lines of research with this aim that have identified
functional and anatomical differences in the brains of
ADHD patients relative to age-matched normal controls:
(1) analysis of brain volume and cortical thickness, (2)
functional MRI (fMRI), (3) diffusion tensor imaging
studies (DTI) and (4) most recently, connectomics. The
combined results from these studies as well as a plethora
of meta-analyses across such studies suggest that on av-
erage children and adolescents with ADHD have reduced
brain volumes (Castellanos et al. 2002; Nakao et al. 2011;
Lim et al. 2015), reduced cortical thickness (McLaughlin
et al. 2014; Almeida et al. 2010; Shaw et al. 2013), show
deactivation in function relative to controls predominantly
in fronto-striatal, fronto-parietal and fronto-cerebellar re-
gions (for review see Cubillo et al. 2011 and Rubia et al.
2014b) and appear to have abnormalities in functional
connections (Cao et al. 2014; Tomasi and Volkow 2012;
Sripada et al. 2014) primarily between these areas as well
as a lag in brain maturation both in terms of structure
(Shaw et al. 2007) and functional architecture (Sripada
et al. 2014).
The regions of brain that show decreased activation
in the ADHD patient as measured by fMRI have his-
torically been thought to support executive function
(EF) given in part to the now well-documented finding
that patients who have suffered lesions in these areas
perform poorly on tasks that recruit EF such as, but
not limited to the Stroop test, Stop-signal task, or Go/
no-go task (Shallice and Burgess 1991; Stuss et al.
2001). By extension, when a patient who does not
have an observable injury of the brain performs poorly
on such neuropsychological instruments, the
257
implication is that there is a correlated dysfunction in
the areas of brain that support that task (Miyake et al.
2000). In other words, the rather circular argument
states that objective evidence of injury to these areas
is correlated with poor EF as measured by neuropsy-
chological tests, and poor performance on those same
tests is assumed to be the result of underlying abnor-
mality in those same brain regions. Neuroimaging
studies of ADHD patients that have required the per-
formance of tasks that measure EF during image ac-
quisition, ostensibly in order to activate the neural
substrates which support task execution, have not re-
liably and consistently shown a significant correlation
between performance on tasks of EF and the activation
of the neural substrates supporting the task. Namely,
some studies were successful in demonstrating a cor-
relation between poor performance and hypoactivation
(Booth et al. 2005; Konrad et al. 2006), but many have
failed to show a correlation between performance on
these tasks and deactivation of brain regions recruited
during these tasks (Bell et al. 2006; Rubia et al. 2010;
Cubillo et al. 2011; Rubia et al. 2011; Smith et al.
2006, Congdon et al. 2014; Konrad et al. 2006; Banich
et al. 2009), or even to detect significant differences
either in performance on the measure of EF or in the
brain activation patterns (Congdon et al. 2014). Fur-
thermore, data from resting state fMRI studies suggest
that the hypoactivation seen on fMRI is unrelated to
the performance of the task during image acquisition
(Tian et al. 2008; Yu-Feng et al. 2007; Hoekzema
et al. 2014; Li et al. 2014).
Although the absence of a corroborative behavioral
effect does not make neuroimaging findings irrelevant, it
does beg the question as to which of the potential ‘‘cog-
nitive algorithms’’ is the subject able and not able to re-
cruit during the performance of the task, and how if at all
are they linked to the ongoing detectable activity in the
brain (Mostofsky and Simmonds 2008; for commentary
see Wilkinson and Halligan 2004). With respect to
ADHD, there are at least three issues that need to be
evaluated before it will be possible to answer this ques-
tion. First, is the variability in the corroboration between
performance and activation in the associated neural sub-
strates due to the neuropsychological task? Second, given
the reviewed evidence for significant differences between
subtypes, is the variability in the corroboration between
performance and activation in the neural substrates a
function of the heterogeneity in ADHD? Third, is the
variability in the corroboration between performance and
activation in the neural substrates a function of an in-
complete understanding about the interaction between
heterogeneity of cognitive processes and heterogeneity in
the architecture of the frontal cortex?
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258
Is the variability in the corroboration
between performance and activation
in the associated neural substrates due
to the neuropsychological task?
One could argue that the sample size in the studies that
failed to show a correlation between hypoactivation in
brain regions and performance was too small (in gener-
al \ 20) to detect performance differences given that pre-
vious studies of purely cognitive or neuropsychological
deficits in ADHD with similar sample sizes also failed to
show effects associated with deficits in EF (Barkley 1997).
However, there is also evidence showing that robustness in
EF may not be a valid or reliable measure for the identi-
fication of ADHD patients (Barkley 2012; for review see
Lange et al. 2014). For example, Wåhlstedt et al. (2009)
report that 20–40 % of children with ADHD do not score
in the clinically significant impairment range on a variety
of EF measures. Duff and Sulla (2014) also make the case
that although poor performance on an EF measure may be
strongly suggestive of the presence of a clinical disorder,
failure to demonstrate impairment on the measure does not
belie the existence of a disorder. In addition, there seems to
be a continuum effect such that there is a significant cor-
relation between level of impairment on EF measures and
negative behavioral symptoms. Furthermore, the use of any
one ‘‘cold’’ cognitive construct such as those used in task-
related fMRI studies may or may not be truly representa-
tive of EF functioning (Barkley 2012). For example, there
are data suggesting that simply the addition of a working
memory component, which requires the maintenance of an
attentional set in order to complete the task, increases the
probability of detecting differences in neural substrates that
are correlated with the performance of a go/no-go task in
normal adults, (e.g., Mostofsky et al. 2003; Mostofsky and
Simmonds 2008), a color-word Stroop test in ADHD pa-
tients (Burgess et al. 2010) and an n-back test of working
memory for spatial position (Bédard et al. 2014).
The inconsistency in the findings relative to the per-
formance of neuropsychological tests by patients with
ADHD may be related to the idea that the heterogeneity of
symptom presentation does not warrant the assumption that
the diagnosis of ADHD should lead to a homogeneous
response pattern across patients during a neuropsycho-
logical assessment. An analysis conducted by Fair et al.
(2012) clearly indicates that neuropsychological subtypes
can be discerned with high precision not only in children
with ADHD, but also in typically developing control youth.
Furthermore, there appears to be an overlap between the
heterogeneity found in children with ADHD and the var-
iation found in typically developing children. With respect
to the deficit in response inhibition that many studies on
123
R. Heidbreder
ADHD assume for purposes of their experiments, the Fair
et al. (2012) analysis reveals that though valid at the group
level, if individual results from the ADHD group are
compared with the normal controls, the differences are
significant only in about 50 % of the comparisons. A
similar pattern was detected for working memory as well as
temporal information processing. The finding that only
about 50 % of the comparisons were significant when
looked at individually rather than as a group follows the
general trend that the percentage of children with ADHD
who show clinically significant impairment varies within
the ADHD population and also as a function of the task
being used to measure EF (Wåhlstedt et al. 2009). Beyond
just the individual versus group comparisons on neu-
ropsychological tests, a neuroimaging study of the neural
substrates of response inhibition in normal adults indicates
that single-subject analysis reveals a pattern of activation
associated with inhibitory response that is different from
the pattern of activation produced in group analysis
(Mostofsky et al. 2003).
Koziol and Budding (2012) argue that precisely because
of the highly heterogeneous character of ADHD, the sub-
types provided by the DSM cannot capture the individual
nature of the disorder at the neuropsychological level, and
as such, cannot be used to characterize the disorder in
terms of dysfunction of a specific set of neuroanatomical
substrates. Rather, ADHD may perhaps best be described
in terms of a continuum or spectrum (Haslam et al. 2006;
for review see Bell 2011) a notion that is lent even more
support from the observation that there are individuals with
subthreshold ADHD. Balázs and Keresztény (2014) report
a wide range (0.8–23.1 %) in the prevalence of sub-
threshold ADHD due to the lack of uniformity regarding
the minimum number of symptoms that should be used to
define subthreshold ADHD functional impairment. This is
the case despite the fact that the DSM V (2013) includes
both an ‘‘Other Specified Attention-Deficit/Hyperactivity
Disorder’’ category as well as an ‘‘Unspecified Attention-
Deficit/Hyperactivity Disorder’’ category meant to be used
to identify individuals who have some of the symptoms
characteristic of ADHD that cause clinically significant
problems in academics or the work place.
In addition to the heterogeneity in neuropsychological
profiles within the ADHD population, there exists one
other caveat that may be confounding the results on neu-
ropsychological tasks of EF as well as neuroimaging during
task execution. There is evidence suggesting that ADHD
performance on many experimental tasks is subject to at-
tentional inconsistency (Castellanos and Tannock 2002;
Douglas 1999; Epstein et al. 2003; Leth-Steensen et al.
2000). This finding is not surprising given that lapses in
attention can be, by definition, part of the ADHD disorder
ADHD symptomatology is best conceptualized as a spectrum: a dimensional versus unitary approach…
(DSM V 2013). What is of much greater interest is how
these lapses in attention present. Leth-Steensen et al.
(2000) discovered abnormally slow reaction times in the
tails, but not the leading edges of the distribution of the
reaction times. Further analysis revealed that group dif-
ferences disappeared when only leading edge reaction
times for the ADHD group were compared with those of
the control group. Thus, the attentional lapse may be oc-
curring as a function of duration of the test, suggesting that
the longer the test goes on, the poorer the performance of
the subject. However, and in addition, each individual re-
action time is made up of a constellation of several steps
each of which may also be affected by attentional lapses. In
other words, within any one response, there is the moment
when the subject sees the response, decides what to do with
it and then decides how to respond. Each of these steps
could be subject to an attentional lapse, resulting in not
only reaction time differences, but variability in the times
at which areas of brain devoted to the execution of the steps
are recruited. This is an especially important consideration
when attempting to describe the neural substrates of the
disorder. Namely, the differences measured during the
performance of these tasks as well as the associated dif-
ferences in activation of brain regions across groups may
be the result of a comparison made between different
portions of the sequence of operations required to complete
the task. The assumption that any variability simply aver-
ages out particularly when such small sample sizes are used
may inadvertently be washing out the very effect that is
being sought.
In sum, variability in the performance on neuropsy-
chological tests of EF across the ADHD population can be
attributable to at least four issues. First, it is still not clear
how or if each of the neuropsychological tests used to
measure EF in individuals with ADHD is actually mea-
suring EF or at the very least what aspects of EF it is
measuring. Second, there are not enough data to know how
much of a cognitive load needs to be introduced into a
neuropsychological test in order for performance differ-
ences relative to controls to be observed. Third, ex-
perimental designs do not take into account either the
variability in performance as a function of test duration or
the variability in performance across the span of the test.
Both of these points are especially relevant when testing
performance in subjects who are known to have variations
in attention, focus and impulsivity over a span of time.
Finally, there are little data regarding performance differ-
ences on neuropsychological tests as a function of ADHD
subtype or severity of symptomatology. Given the evidence
presented thus far in the review, there is not only sufficient
support to warrant such investigations, but more impor-
tantly there is no rationale for assuming that patients in
259
which ADHD symptoms have been observed will all per-
form in a homogeneous manner.
Is the variability in the corroboration
between performance and activation
in the neural substrates a function
of the heterogeneity in ADHD?
A great majority of task-dependent neuroimaging studies
do not make any distinctions in terms of symptom pre-
sentation or subtype of the ADHD subjects (Booth et al.
2005; Hart et al. 2013; Konrad et al. 2006; Rubia et al.
2005; Rubia et al. 2010; Simmonds et al. 2008). As has
been discussed earlier in this review, there is converging
evidence suggesting that not only are the differences be-
tween the variants of ADHD important, but in some cases,
the differences are so remarkable that they may warrant
being considered as separate disorders rather than subtypes
of ADHD. Therefore, as our understanding about ADHD
continues to grow, the evidence must confirm or deny the
rationale for using ADHD as an umbrella term for the
various subtypes and/or using only one subtype in ex-
perimental designs.
The comparison of some of the data that have been
collected to elucidate the neural substrates that support
working memory exemplify the need to take into account
the heterogeneity seen in ADHD. When adult patients with
ADHD (collapsed across all subtypes) performed an n-back
task during the acquisition of fMRI data, significant dif-
ferences between adults with and without ADHD were
found in the bilateral prefrontal cortices. However, only
men with ADHD showed less activation in a network of
brain regions that was lateralized to right frontal and sub-
cortical regions and left occipital and cerebellar regions
relative to controls. Adult females with and without ADHD
were indistinguishable despite the fact that ADHD symp-
tomatology in both the females and males was similar
(Valera et al. 2010). Burgess et al. (2010) looked at the
brains of adult males and females specifically with CT
subtype ADHD with fMRI while they performed either a
working memory digit span or spatial span task. They
found decreased function in the left dorsolateral prefrontal
cortex relative to normal controls; however, this study did
not look at gender differences. Mills et al. (2012) found
evidence for atypical thalamic connectivity with cortical
structures in children with ADHD (collapsed across sub-
types) related to their performance on a task of spatial span
working memory using rs-fcMRI. Massat et al. (2012) also
studied children with CT subtype ADHD using fMRI to
investigate differences in activation patterns between that
group and normal controls while performing an n-back
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260
working memory task, and their data found no evidence for
differences in prefrontal areas between children with CT
subtype ADHD and normal cohorts, but did find decreased
activation in inferior parietal cortex, as well as decreased
activity in the striatum and the cerebellum.
When Lockwood et al. (2001) explicitly targeted the
identification of differences between ADHD subtypes with
respect to neuropsychological performance, all attempts
were made to minimize methodological limitations in-
cluding insuring that all participants were medication free,
that clinical diagnosis was accurate, that there was no co-
morbidity and that there was equal representation across
genders. Their results indicate that the PI subtype had
greater difficulty selecting previously presented auditory
information from prompted material. This finding agrees
with the hypothesis discussed earlier in this review that the
PI subtype is associated with a narrow focus of attention. In
other words, one explanation for their findings could be
that the discrimination between previously heard and cur-
rently heard material was difficult because the children
stagnated their attention at different times during the pre-
viously presented stimuli and as such some of the infor-
mation was not encoded into memory. In contrast, children
with the CT subtype showed impaired response inhibition
and reengagement as well as difficulty carrying out goal-
directed activities. This finding also fits with the previously
presented hypothesis that the CT subtype is associated with
the inability to stop shifting focus, which in this case re-
sulted in attending to inappropriate stimuli.
The postulates from the Barkley (1997) model of ADHD
that only the CT and HI subtypes, but not the PI subtype,
are associated with EF deficits, have led to several studies
aimed at investigating the validity of this claim. Though
several studies did not find differences in EF across sub-
types (e.g., see Duff and Sulla 2014 for review; Geurts
et al. 2005; Riccio et al. 2006; Song and Hakoda 2014), the
failure to find differences may be the result of assuming a
binary response across a homogeneous test. That is to say,
the expectation is that the response from individuals of one
subtype will somehow be discrete from the other subtype.
What is lacking in most of these studies, and
serendipitously discovered in the Song and Hakoda (2014)
study is that cognitive load, particularly with respect to
working memory, may elicit the difference that is being
investigated. In fact, Diamond (2005) suggests that the
primary deficit of the PI subtype is in working memory.
Furthermore, in their study on the comparison between
children with low working memory and children with the
CT subtype of ADHD, Holmes et al. (2014) report that
children with a diagnosis of low working memory are al-
most indistinguishable to CT subtype children across many
assessments, including EF and degree of inattentive be-
havior. However, what distinguished the two groups were
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R. Heidbreder
the externalized behaviors, namely the hyperactivity and
impulsivity associated with the CT subtype and the sig-
nificantly slower response times in the low-working-
memory group. These findings led the authors to postulate
that individuals diagnosed with low working memory may
actually be manifesting the PI subtype of ADHD.
Finally, there are preliminary data that provide some
justification for taking into account the heterogeneity seen
in ADHD when designing experiments that measure brain
activity. Although their study did not seek to uncover task-
related differences in brain using fMRI, Fair et al. (2013)
did discover that resting-state functional connectivity MRI
(rs-fcMRI) was able to differentiate between the CT and PI
subtypes of ADHD. Another study using DTI uncovered a
network of connections in the right frontal regions that was
able to differentiate between the CT and PI subtypes;
specifically, there was decreased connectivity in the CT
subtype compared with the PI subtype (Hong et al. 2014).
Both studies suggest that there could be neural signatures
that are specific to at least two ADHD subtypes. As such,
not taking into consideration the heterogeneity that exists
in ADHD and mixing the results of qualitatively different
groups can actually end up canceling out the differences
one is searching for (Barkley 2001).
Taken together, all of these results point to the conclu-
sion that there is no rationale for using exclusively one
subtype in an experimental design; or worse yet, to group
together several subtypes under one umbrella category la-
beled as ADHD. Additionally, the Lockwood et al. (2001)
study underscores the importance of using heterogeneous
attentional measures if the aim is to assess neuropsycho-
logical differences between ADHD subtypes. Failure to do
so could lead to the inaccurate collection of data and the
erroneous interpretation of results. Finally, the data that do
exist pertaining to the neural substrates associated with the
heterogeneity found in ADHD actually provide some evi-
dence that symptomatological variants may be supported
by different brain circuits, and as such, could theoretically
be considered as related, but separate disorders.
Is the variability in the corroboration
between performance and activation
in the neural substrates a function of
an incomplete understanding about the interaction
between heterogeneity of cognitive processes
and heterogeneity in the architecture of the frontal
cortex?
The data pointing to impairment of EF in ADHD as well as
an observed hypoactivation of the frontal cortex in patients
with ADHD can lead to the assumption that EF is exclu-
sively a function of the prefrontal cortex. However,
ADHD symptomatology is best conceptualized as a spectrum: a dimensional versus unitary approach…
paraphrasing from both Dimond (1980) and Barkley
(2012), the functions of the frontal lobe are as varied as it is
large, and the dimensionality of EF is as broad as it is deep.
Therefore, perhaps a better way to conceive of the pre-
frontal cortex is as a way station to different functions
given its various interconnections with cortical and sub-
cortical regions (Cubillo et al. 2011; Stuss and Benson
1986), particularly since there is strong evidence support-
ing that different cognitive processes are subserved by
different subregions of the prefrontal cortex (Chudasama
2011; Heidbreder and Groenewegen 2003; Kesner and
Churchwell 2011). In a meta-analysis of lesion and func-
tional neuroimaging studies that investigated the role of the
frontal lobes and EF, Alvarez and Emory (2006) concluded
that the participation of the frontal lobes in EF is linked to
the sensitivity of the different tests used to measure EF,
each of which might be recruiting different cognitive pro-
cesses. Their findings support the idea that EF is ‘‘frac-
tionable’’ (Lopez-Vergara and Colder 2013; Miyake et al.
2000). However, as the review by Donohoe and Robertson
(2003) points out, though there is evidence for the discrete
neuroanatomical separation of the different ‘‘fractions’’ of
EF, there remains an overlap between the different ex-
ecutive measures because they are correlated with each
other and are causally related to each other. Furthermore, in
their review on working memory and EF, Carpenter et al.
(2000) provide converging evidence for a system in which
rather than there being an association between each frac-
tion of EF and a single cortical area, each cortical region
has more than one function, and the functions of each of
the regions may overlap each other. The authors suggest
further that each task may prompt a different combination
of several brain regions depending on the requirements of
the task. Since this ‘‘nondiscreteness of specialization’’
proposed by Carpenter et al. (2000) is probably a reality of
cortical organization in general, it can also serve as a point
of departure for a novel way of conceptualizing ADHD.
Do ADHD symptoms point to a spectrum instead
of a disorder?
If the DSM is correct, then there are more than 70 million
children and more than 60 million adults worldwide that
have ADHD. These estimates have been made despite the
fact that as Brown (2006) so succinctly puts ‘‘There is no
one test that can determine whether a given individual
meets DSM diagnostic criteria for ADHD. This is a diag-
nosis that depends on the judgment of a skilled clinician
who knows what ADHD looks like and can use data from
multiple aspects of the individual’s daily life over pro-
tracted periods of time to differentiate it from other pos-
sible causes of impairment.’’ What is so interesting about
261
Brown’s statement is that, on the one hand, he acknowl-
edges that there is no single test to determine if someone
has ADHD, but at the same time suggests that skilled
clinicians nevertheless somehow ‘‘know’’ what ADHD
looks like. Brown’s comment is actually corroborated by
what the team of scientists from Johns Hopkins who won
the ‘‘The ADHD-200 Global Competition’’ (http://f-
con_1000.projects.nitrc.org/indi/adhd200/) discovered.
They were able to demonstrate that there was a much
greater probability of correctly discriminating between
typically developing children and children with ADHD
than there was for correctly identifying children with a
true-positive diagnosis of ADHD. Interestingly, the Johns
Hopkins team was also able to discern the subtypes of
ADHD with high accuracy. This pattern of discrimination
indicates that the individual who receives a diagnosis of
ADHD is different from a normal individual, yet the di-
agnosis of ADHD is not associated with a signature that
either renders the diagnosis unequivocable or is sufficiently
unique that variations in presentation are not easily dis-
tinguishable. The primary aim of the present review was to
elucidate whether or not there is something unique to
‘‘know’’ about ADHD such that every one of those tens of
millions of individuals could somehow fit under the same
single disorder; or rather, if there was some way to take
what is known about ADHD and use it as a diagnostic tool
for a spectrum of disorders that as Asperger (1979) said are
‘‘…at once so alike, but so different…’’ and yet the
‘‘…differences are so great…’’
The data on the prevalence, diagnosis, heterogeneity and
comorbidity of ADHD described in this review all point to
the struggle at trying to fit a wide variety of clinical pre-
sentations into the diagnostic criteria for a single disorder
that usually leads to a debate about what should and should
not be included. Though the observation of certain be-
havioral traits as indicated by the DSM V (2013) is un-
deniably necessary to identify individuals at risk, the
diagnostic process is limited by the assumed need to fit a
wide variety of symptoms under one rubric in part because
of the limitation of therapeutic avenues, but more impor-
tantly because of the urgency to bring relief to an indi-
vidual whose ability to engage in the everyday functions of
life can be severely compromised. One way out of the
conundrum of having to use a single diagnosis for so many
clinical presentations is to think of ADHD as a ‘‘psy-
chophysiological modality’’ that can be expressed across a
spectrum that can accommodate the wide heterogeneity
observed in ADHD. Earlier in this review, the idea of
varying widths of attentional spotlights was introduced as a
way in which to describe the differences in attention and
hence impulsivity exhibited by the PI and CT subtypes of
ADHD. Specifically, whereas the PI subtype was described
as having a narrow spotlight of attention, the CT and HI
123
262
subtypes were described as having wide spotlights of at-
tention. The width of the spotlight dictated the degree to
which an individual had access to information as well as
the ability the individual had to focus on information. As a
result of a narrow spotlight of attention, the patient with PI
subtype fails to detect certain external stimuli because they
are outside of his attentional focus. The extended spotlight
width of the CT subtype creates a stimulus overload by
allowing too many external stimuli to flood the attentional
space, making it difficult for the patient to focus on any one
of the myriad of external stimuli to which these patients
have access. Each subtype can also be associated with an
observed or perceived impulsivity. The PI subtype may
appear impulsive only because decisions made were based
strictly on information that the patient could access. On the
other hand, the impulsivity of the CT subtype could be the
result of an inability to focus on the necessary bits of in-
formation to which the patient has access. In other words,
the difference between the two can be summarized as ‘‘not
having access’’ versus ‘‘not knowing what to select.’’
Barkley (1997) suggests that problems with selective at-
tention are associated with the PI subtype and inhibition
was the problem with the CT subtype. The suggestion here
is that both inhibition and selective attention are a problem
for the CT subtype. That is, though the patient with the CT
subtype may not be able to inhibit competing responses,
they also cannot select the appropriate responses for eval-
uation. On the other hand, although the patient with PI
subtype may have a deficit of selective attention, it is un-
clear whether or not the selection of what to attend to is
under his voluntary control. As such, the CT and PI sub-
types can be considered to lie on a spectrum that varies as a
function of attention and impulsivity.
A spectrum of attention and impulsivity could also ac-
commodate the extremely high symmetrical and asym-
metrical comorbidity linked with ADHD since so many of
these comorbid disorders also show impairment in atten-
tion and/or impulsivity as part of their own clinical profiles.
Although it is neither the intention nor the scope of this
review to map out entirely what such a spectrum of dis-
orders could look like, three separate psychiatric disorders
that have been associated with ADHD (schizophrenia,
obsessive compulsive disorder (OCD) and conduct disor-
der) will be used to illustrate how they could be colocalized
on the spectrum.
Schizophrenia is associated with a vast number of
symptoms, including delusions, hallucinations, flat affect
and inappropriate emotional expression that originate from
completely within the schizophrenic patient rather than as a
reaction to external stimuli. As a result, the schizophrenic
can be viewed as having an extremely narrow attentional
focus inasmuch as the patient is focused almost exclusively
on internally generated stimuli, leaving little breadth of
123
R. Heidbreder
attention to dedicate to the external world. The schizo-
phrenic patient also shows no impulsivity to the extent that
he can be considered even risk aversive (Reddy et al.
2014). Thus, schizophrenia would be colocalized on the
part of the spectrum that is associated with the most narrow
attentional focus and the lowest degree of impulsivity,
giving it a greater ‘‘etiological vicinity’’ to the PI subtype
than the CT subtype.
Conversely, the CT subtype and conduct disorder could
be seen as having a very proximal ‘‘etiological vicinity’’ and
would be extremely close in terms of their colocalization on
the proposed spectrum. Both disorders are characterized by
high levels of impulsivity and both have an overly wide
attentional spotlight, making it difficult for patients with
either disorder to focus on the appropriate stimuli that would
lead to good decision making. Though their very high sym-
metrical comorbidity and similarity in characteristics invite
the tendency to want to consider them as a single disorder
(Biederman et al. 1991), there are sufficient fine differences,
for example in the exhibition of defiance, that would separate
these disorders on the spectrum.
OCD would be colocalized somewhere between the PI
subtype and schizophrenia and the CT subtype and conduct
disorder. The patient with OCD is characterized by the
presence of obsessions and/or compulsions with some pa-
tients showing relatively more impulsivity than others
(Kashyap et al. 2012). OCD patients are also classified
according to the degree of insight they have related to the
nature of their disorder. The OCD patient who shows the
greatest impulsivity also has the poorest insight where poor
insight is defined by the patient’s belief that his OCD
compulsions are warranted and true (Kashyap et al. 2012).
Poor insight is thus considered a form of delusion, and
since delusion is the result of internally generated beliefs,
the attentional spotlight would be narrowed. However,
because the internally generated beliefs are about external
stimuli, and not an imagined construct as in schizophrenia,
the attentional spotlight would not be as narrow as in
schizophrenia. Thus, this type of OCD would be colocal-
ized partly in the direction of the spectrum associated with
some impulsivity and partly in the direction of a narrowing
width of attentional spotlight. Conversely, some OCD pa-
tients have low impulsivity and high insight. This type of
OCD would be colocalized in the direction of that part of
the spectrum associated with little or no impulsivity and in
the direction of a growing width of attentional spotlight.
The spectrum approach to identifying disorders of attention
and impulsivity avoids many pitfalls by permiting less
subjectivity and more objectivity by shifting the focus to
the quality of the defect rather than using the presence of
the defect to position the disorder under one category or a
subset of the same category. It is not inconceivable that
such a system could lead to customizable treatment even as
ADHD symptomatology is best conceptualized as a spectrum: a dimensional versus unitary approach…
medicine moves toward individual gene-based treatment
approaches.
The concept of looking at a group of psychiatric disor-
ders as interrelated because they share a common psy-
chophysiological modality that comprises varying degrees
of two major cognitive functions in this case, attention and
impulsivity, is plausible not only as part of psychological
theory, but also as part of what we know about the function
of the brain. The neurological construct supporting this
idea would be similar to the one Carpenter et al. (2000)
write about, that is, of a ‘‘cognitive process that spans
multiple cortical sites with closely collaborative and
overlapping functions’’. Data about the symmetric and
asymmetric comorbidity associated with ADHD as well as
the heterogeneity that have been observed within the dis-
order implicate the prefrontal cortex (PFC) as a major site
for the dysfunction. There is an abundance of evidence
indicating that the PFC is a heterogeneous structure that is
divisible not only in terms of its cytoarchitectonics,
(Heidbreder and Groenewegen 2003), but also on the basis
of differences in connectivity patterns with structures such
as the amygdala, the temporal cortex, the parietal cortex,
thalamic nuclei, hippocampus, dorsal and ventral striatum,
hypothalamus and midbrain, as well as with one another
(Chudasama 2011). Furthermore, the manipulation of the
different regions of the PFC produces distinct and disso-
ciable cognitive deficits including impaired attention, poor
working memory, dysregulated affect, abnormal decision
making, impulsivity, inflexibility and profound disinhibi-
tion (Kesner and Churchwell 2011). Therefore, it is not
difficult to envision a neural circuit governing attention and
impulsivity that allocates dynamically to a vast number of
other neural circuits that underlie any number of disorders.
The contribution of this ‘‘attentional/impulsivity neural
circuit’’ to the network of neural circuits associated with a
particular disorder allow for that disorder to be colocated
along the spectrum defined by the ‘‘attentional/impulsivity
neural circuit’’. Finally, such a spectrum is not limited to
clinically disordered states, but can also capture the
heterogeneity in the ‘‘attentional/impulsivity’’ dimension
seen in the general population that may affect behavior, but
does not necessarily cause impairment.
The benefit of characterizing comorbid disorders and
interrelated impairments as varying along one dimension
that spans a spectrum and using it as a starting point for
diagnosis and treatment has several advantages. For exam-
ple, in the case of ADHD, diagnosis is the result of a con-
vergence of opinions (teachers, parents, clinicians and
multiple settings) that confirm that a child is impaired from
the point of view of attention and/or from the point of view
of hyperactivity/impulsivity. In other words, the endpoint of
the diagnosis is the confirmation of impairment in those
domains. In contrast, that convergence of opinions could
263
become the starting point if we accept that the presence of
those symptoms could point to any one of the disorders that
make up part of the spectrum. The physician, therefore, will
be prompted to start a deeper clinical investigation rather
than simply halted after observing that a patient has a par-
ticular constellation of symptoms. Thus, the impairment in
attention/hyperactivity/impulsivity will itself not be the
disorder, but rather the marker for any of several disorders
that are interrelated. This type of diagnostic also allows for
greater flexibility in the identification of individuals who do
not naturally come to mind when we think of the disorder
ADHD, for example, patients who show an SCT profile or
subthreshold patients. Additionally, if clinicians use the at-
tentional/impulsivity marker as the start of their diagnosis,
the diagnostic tools that will be used to refine their opinion
about the patient could not only reduce the total number of
patients treated pharmacologically, but also reduce the
number of individuals who engage in the feigning and ma-
lingering to obtain a prescription for ADHD medication, a
problem which is currently on the rise (Bagot and Kaminer
2014; Lensing et al. 2013; Quinn 2003; Rabiner 2013; Tucha
et al. 2014).
In order to develop better and more varied treatment
options for people who have impairments in the ‘‘attention/
impulsivity’’ dimension, data sets generated with much
greater scrutiny reliability and validity must be construct-
ed. Data are lacking in the ability to discriminate among
the heterogeneity in what today is known as ADHD. Few
data have been collected under conditions that elucidate,
for example, within subject differences across neuropsy-
chological tests, or between subtype differences on the
same neuropsychological test. There remains an urgent
need to create experimental designs that carefully control
for the different presentations of attention/impulsivity/hy-
peractivity, including as a function of age and gender. As
the pieces of the puzzle come together not only will we be
able to increase our understanding about how impairments
in attention and impulsivity can present, but we will also
elucidate how the different cognitive processes may be
distributed across the neural networks that make up the
heterogeneity of the prefrontal cortex. Data already exist
that point to similarities in the underlying neural pathology
associated with some psychiatric diseases and patients
presenting with ADHD (e.g., for review see Banaschewski
et al. 2005; Rubia et al. 2010); however, there is also
evidence for shared neural substrates across diverse psy-
chopathologies (Goodkind et al. 2015). Further clarification
related to the neural networks that support the different
disorders that lie across the spectrum will lead to both the
prescription of the appropriate treatments that are available
today as well as the identification of new treatments that
target specific populations of neurotransmitters associated
with the neural networks.
123
264
In summary, precisely because the symptoms of inat-
tention and impulsivity are not unique to ADHD and there
is an exceedingly high and unexplained symmetrical and
asymmetrical comorbidity of many psychiatric diseases
with ADHD, it is reasonable to stop considering ADHD as
a single disorder. Rather, future investigations should use
what is known about ADHD to develop further the idea
that individuals who show the symptoms typical of ADHD
may be pointing to a different more specific disorder that is
part of a larger spectrum.
References
Almeida LG, Ricardo-Garcell J, Prado H, Barajas L, Fernández-
Bouzas A, Ávila D, Martı́nez RB (2010) Reduced right frontal
cortical thickness in children, adolescents and adults with ADHD
and its correlation to clinical variables: a cross-sectional study.
J Psychiatr Res 44(16):1214–1223
Alvarez JA, Emory E (2006) Executive function and the frontal lobes:
a meta-analytic review. Neuropsychol Rev 16(1):17–42
American Psychiatric Association (1968) Diagnostic and statistical
manual of mental disorders, 2nd edn. Author, Washington, DC
American Psychiatric Association (1980) Diagnostic and statistical
manual of mental disorders, 3rd edn. Author, Washington, DC
American Psychiatric Association (1987) Diagnostic and statistical
manual of mental disorders, 3rd edn. Author, Washington, DC
American Psychiatric Association (1994) Diagnostic and statistical
manual of mental disorders, 4th edn. Author, Washington, DC
American Psychiatric Association (2000) Diagnostic and statistical
manual of mental disorders DSM-IV-TR, 4th edn. Author,
Washington, DC
American Psychiatric Association (2013) Diagnostic and statistical
manual of mental disorders, (DSM-5). American Psychiatric
Pub, Washington, DC
Anastopoulos A, Barkley R, Shelton T (1994) The history and
diagnosis of attention deficit/hyperactivity disorder. Ther Care
Educ 3:96
Antshel KM, Barkley R (2011) Overview and historical background
of attention deficit hyperactivity disorder. In: Evans SW, Hoza B
(eds) Treating attention-deficit = hyperactivity disorder: assess-
ment and intervention in developmental context. Civic Research
Institute, New York, NY, pp 1–30
Arnett AB, MacDonald B, Pennington BF (2013) Cognitive and
behavioral indicators of ADHD symptoms prior to school age.
J Child Psychol Psychiatry 54(12):1284–1294
Arnett AB, Pennington BF, Willcutt EG, DeFries JC, Olson RK
(2014) Sex differences in ADHD symptom severity. J Child
Psychol Psychiatry. doi:10.1111/jcpp.12337
Asperger H (1979) Problems of infantile autism. Communication
13:45–52
Baeyens D, Roeyers H, Walle JV (2006) Subtypes of attention-deficit/
hyperactivity disorder (ADHD): distinct or related disorders across
measurement levels? Child Psychiatry Hum Dev 36(4):403–417
Bagot KS, Kaminer Y (2014) Efficacy of stimulants for cognitive
enhancement in non-attention deficit hyperactivity disorder
youth: a systematic review. Addiction 109(4):547–557
Balázs J, Keresztény Á (2014) Subthreshold attention deficit hyper-
activity in children and adolescents: a systematic review. Eur
Child Adolesc Psychiatry 23:1–16
Banaschewski T, Hollis C, Oosterlaan J, Roeyers H, Rubia KWE
(2005) Towards an understanding of unique and shared pathways
in the psychopathophysiology of AD/HD. Dev Sci 8:132–140
123
R. Heidbreder
Banich MT, Burgess GC, Depue BE, Ruzic L, Bidwell L, Hitt-
Laustsen S, Du YP, Willcutt EG (2009) The neural basis of
sustained and transient attentional control in young adults with
ADHD. Neuropsychologia 47(14):3095–3104
Barkley RA (1997) Behavioral inhibition, sustained attention, and
executive functions: constructing a unifying theory of ADHD.
Psychol Bull 121(1):65
Barkley RA (2001) The inattentive type of ADHD as a distinct
disorder: what remains to be done. Clin Psychol Sci Pract
8(4):489–493
Barkley RA (2005) Attention-deficit hyperactivity disorder: a hand-
book for diagnosis and treatment (Vol 1). Guilford Press,
Newyork
Barkley RA (2007) What may be in store for DSM-V. ADHD Rep
15:1–7
Barkley RA (2012) Executive functions: what they are, how they
work, and why they evolved. Guilford Press, Newyork
Barkley RA (2013) Distinguishing sluggish cognitive tempo from
ADHD in children and adolescents: executive functioning,
impairment, and comorbidity. J Clin Child Adolesc Psychol
42(2):161–173
Barkley R, Peters H (2012) The earliest reference to ADHD in the
medical literature? Melchior Adam Weikard’s description in
1775 of ‘‘attention deficit’’ (Mangel der Aufmerksamkeit,
Attentio Volubilis). J Atten Disord 16(8):623–630
Bauermeister JJ, Barkley RA, Bauermeister JA, Martinez JV,
McBurnett K (2012) Validity of the sluggish cognitive tempo,
inattention, and hyperactivity symptom dimensions: neuropsy-
chological and psychosocial correlates. J Abnormal Child
Psychol 40:683–697
Becker SP, Marshall SA, McBurnett K (2014) Sluggish cognitive
tempo in abnormal child psychology: an historical overview and
introduction to the Special Section. J Abnormal Child Psychol
42(1):1–6
Bédard ACV, Newcorn JH, Clerkin SM, Krone B, Fan J, Halperin
JM, Schulz KP (2014) Reduced Prefrontal efficiency for
visuospatial working memory in attention-deficit/hyperactivity
disorder. J Am Acad Child Adolesc Psychiatry 53(9):1020–1030
Bédard ACV, Stein MA, Halperin JM, Krone B, Rajwan E, Newcorn
JH (2015) Differential impact of methylphenidate and atomox-
etine on sustained attention in youth with attention-deficit/
hyperactivity disorder. J Child Psychol Psychiatry 56(1):40–48
Bell AS (2011) A critical review of ADHD diagnostic criteria: what
to address in the DSM-V. J Atten Disord 15(1):3–10
Bell EC, Willson MC, Wilman AH, Dave S, Silverstone PH (2006)
Males and females differ in brain activation during cognitive
tasks. Neuroimage 30(2):529–538
Berry CA, Shaywitz SE, Shaywitz BA (1985) Girls with attention
deficit disorder: a silent minority? A report on behavioral and
cognitive characteristics. Pediatrics 76(5):801–809
Biederman J, Newcorn J, Sprich S (1991) Comorbidity of attention
deficit hyperactivity disorder. Am J Psychiatry 148(5):564–577
Bolea-Alamañac B, Nutt DJ, Adamou M, Asherson P, Bazire S,
Coghill D, Heal D, Müller U, Nash J, Santosh P, Sayag K,
Sonuga-Barke E, Young SJ (2014) Evidence-based guidelines
for the pharmacological management of attention deficit hyper-
activity disorder: update on recommendations from the British
Association for Psychopharmacology. J Psychopharmacol
28(3):179–203
Bonafina MA, Newcorn JH, McKay KE, Koda VH, Halperin JM
(2000) ADHD and reading disabilities a cluster analytic
approach for distinguishing subgroups. J Learn Disabil
33(3):297–307
Booth JR, Burman DD, Meyer JR, Lei Z, Trommer BL, Davenport
ND, Li W, Parrish TB, Gitleman DR, Marsel Mesulam M (2005)
Larger deficits in brain networks for response inhibition than for
ADHD symptomatology is best conceptualized as a spectrum: a dimensional versus unitary approach…
visual selective attention in attention deficit hyperactivity
disorder (ADHD). J Child Psychol Psychiatry 46(1):94–111
Brown TE (2006) Executive functions and attention deficit hyperac-
tivity disorder: implications of two conflicting views. Int J
Disabil Dev Educ 53(1):35–46
Bruchmüller K, Margraf J, Schneider S (2012) Is ADHD diagnosed in
accord with diagnostic criteria? Overdiagnosis and influence of
client gender on diagnosis. J Consult Clin Psychol 80(1):128
Burgess GC, Depue BE, Ruzic L, Willcutt EG, Du YP, Banich MT
(2010) Attentional control activation relates to working memory
in attention-deficit/hyperactivity disorder. Biol Psychiatry
67(7):632–640. Child Psychol 29(6):529–540
Cao M, Shu N, Cao Q, Wang Y, He Y (2014) Imaging functional and
structural brain connectomics in attention-deficit/hyperactivity
disorder. Mol Neurobiol 50:1–13
Carlson CL (1986) Attention deficit disorder with and without
hyperactivity: a review of preliminary experimental evidence. In:
Lahey BB, Kazdin AE (eds) Advances in clinical child
psychology, vol 9. Plenum, New York, NY, pp 153–175
Carlson CL, Mann M (2000) Attention-deficit/hyperactivity disorder,
predominately inattentive subtype. Child Adolesc Psychiatr Clin
N Am 9(3):499–510, vi. Review
Carlson CL, Mann M (2002) Sluggish cognitive tempo predicts a
different pattern of impairment in the attention deficit hyperac-
tivity disorder, predominantly inattentive type. J Clin Child
Adolesc Psychol 31(1):123–129
Carpenter PA, Just MA, Reichle ED (2000) Working memory and
executive function: evidence from neuroimaging. Curr Opin
Neurobiol 10(2):195–199
Castellanos FX, Proal E (2012) Large-scale brain systems in ADHD:
beyond the prefrontal–striatal model. Trends Cogn Sci
16(1):17–26
Castellanos FX, Tannock R (2002) Neuroscience of attention-deficit/
hyperactivity disorder: the search for endophenotypes. Nat Rev
Neurosci 3(8):617–628
Castellanos FX, Lee PP, Sharp W, Jeffries NO, Greenstein DK,
Clasen LS, Blumenthal JD, James RS, Ebens CL, Walter JM,
Zijdenbos A, Evans AC, Giedd JN, Rapoport JL (2002)
Developmental trajectories of brain volume abnormalities in
children and adolescents with attention-deficit/hyperactivity
disorder. JAMA 288(14):1740–1748
Chhabildas N, Pennington BF, Willcutt EG (2001) A comparison of
the neuropsychological profiles of the DSM-IV subtypes of
ADHD. J Abnorm Child Psychol 29(6):529–540
Chudasama Y (2011) Animal models of prefrontal-executive func-
tion. Behav Neurosci 125(3):327
Clark KL, Noudoost B (2014) The role of prefrontal catecholamines
in attention and working memory. Front Neural Circuits 8:33.
doi:10.3389/fncir.2014.00033 [Erratum in: Front Neural
Circuits 2014;8:142]
Clemow DB, Walker DJ (2014) The potential for misuse and abuse of
medications in ADHD: a review. Postgrad Med 126(5):64–81
Coghill DR, Seth S, Pedroso S, Usala T, Currie J, Gagliano A (2014)
Effects of methylphenidate on cognitive functions in children
and adolescents with attention-deficit/hyperactivity disorder:
evidence from a systematic review and a meta-analysis. Biol
Psychiatry 76(8):603–615
Congdon E, Altshuler LL, Mumford JA, Karlsgodt KH, Sabb FW,
Ventura J, McGough JJ, London ED, Cannon TD, Bilder RM,
Poldrack RA (2014) Neural activation during response inhibition
in adult attention-deficit/hyperactivity disorder: preliminary
findings on the effects of medication and symptom severity.
Psychiatry Res Neuroimaging 222(1):17–28
Cubillo A, Halari R, Giampietro V, Taylor E, Rubia K (2011) Fronto-
striatal underactivation during interference inhibition and atten-
tion allocation in grown up children with attention deficit/
265
hyperactivity disorder and persistent symptoms. Psychiatry Res
Neuroimaging 193(1):17–27
Cunill R, Castells X, Tobias A, Capellà D (2015) Pharmacological
treatment of attention deficit hyperactivity disorder with co-
morbid drug dependence. J Psychopharmacol 29(1):15–23
Dagher A, Robbins TW (2009) Personality, addiction, dopamine:
insights from Parkinson’s disease. Neuron 61(4):502–510
De Quiros GB, Kinsbourne M (2001) Adult ADHD: behavior, self-
rating and medication assessment. Ann N Y Acad Sci
931:287–296
del Campo N, Chamberlain SR, Sahakian BJ, Robbins TW (2011)
The roles of dopamine and noradrenaline in the pathophysiology
and treatment of attention-deficit/hyperactivity disorder. Biol
Psychiatry 69(12):e145–e157
Diamond A (2005) Attention-deficit disorder (attention-deficit/hyper-
activity disorder without hyperactivity): a neurobiologically and
behaviorally distinct disorder from attention-deficit/hyperactivity
disorder (with hyperactivity). Dev Psychopathol 17(03):807–825
Donohoe G, Robertson IH (2003) Can specific deficits in executive
functioning explain the negative symptoms of schizophrenia? A
review. Neurocase 9(2):97–108
Douglas VI (1972) Stop, look and listen: the problem of sustained
attention and impulse control in hyperactive and normal
children. Can J Behav Sci 4(4):259
Douglas VI (1999) Cognitive control processes in attention deficit/
hyperactivity disorder. In: Quay HC, Hogan AE (eds) Handbook
of disruptive behavior disorders. Springer, Berlin, pp 105–138
Douglas VI (2005) Cognitive deficits in children with attention deficit
hyperactivity disorder: a long-term follow-up. Can Psychol
46(1):23
Duff CT, Sulla EM (2014) Measuring executive function in the
differential diagnosis of attention-deficit/hyperactivity disorder:
does it really tell Us anything? Appl Neuropsychol Child 1–9.
doi:10.1080/21622965.2013.848329
Epstein JN, Erkanli A, Conners CK, Klaric J, Costello JE, Angold A
(2003) Relations between continuous performance test perfor-
mance measures and ADHD behaviors. J Abnorm Child Psychol
31(5):543–554
Evans S, Owens J, Bunford N (2014) Evidence-based psychosocial
treatments for children and adolescents with attention-deficit/
hyperactivity disorder. J Clin Child Adolesc Psychol 43(4):1–25
Fair D, Bathula D, Nikolas M, Nigg J (2012) Distinct neuropsycho-
logical subgroups in typically developing youth inform hetero-
geneity in children with ADHD. Proc Natl Acad Sci
109(17):6769–6774
Fair DA, Nigg JT, Iyer S, Bathula D, Mills KL, Dosenbach NU,
Schlaggar BL, Mennes M, Gutman D, Bangaru S, Buitelaar JK,
Dickstein DP, Di Martino A, Kennedy DN, Kelly C, Luna B,
Schweitzer JB, Velanova K, Wang YF, Mostofsky F, Castellanos
FX, Milham MP (2013) Distinct neural signatures detected for
ADHD subtypes after controlling for micro-movements in
resting state functional connectivity MRI data. Front Syst
Neurosci 6:80. doi:10.3389/fnsys.2012.00080
Faraone S (2005) The scientific foundation for understanding
attention-deficit/hyperactivity disorder as a valid psychiatric
disorder. Eur Child Adolesc Psychiatry 14:1–10
Faraone SV, Buitelaar J (2010) Comparing the efficacy of stimulants
for ADHD in children and adolescents using meta-analysis. Eur
Child Adolesc Psychiatry 19(4):353–364
Faraone SV, Biederman J, Weber W, Russell RL (1998) Psychiatric,
neuropsychological, and psychosocial features of DSM-IV
subtypes of attention-deficit/hyperactivity disorder: results from
a clinically referred sample. J Am Acad Child Adolesc
Psychiatry 37(2):185–193
Feldman HM, Reiff MI (2014) Attention deficit-hyperactivity disor-
der in children and adolescents. N Engl J Med 370(9):838–846
123
266
Ferrer M, Andión Ó, Matalı́ J, Valero S, Navarro JA, Ramos-Quiroga
JA, Torrubia R, Casas M (2010) Comorbid attention-deficit/
hyperactivity disorder in borderline patients defines an impulsive
subtype of borderline personality disorder. J Pers Disord
24(6):812–822
Garner AA, Mrug S, Hodgens B, Patterson C (2013) Do symptoms of
sluggish cognitive tempo in children with ADHD symptoms
represent comorbid internalizing difficulties? J Atten Disord
17(6):510–518. doi:10.1177/1087054711431456
Gaub M, Carlson CL (1997) Gender differences in ADHD: a meta-
analysis and critical review. J Am Acad Child Adolesc
Psychiatry 36(8):1036–1045
Geller DA (2006) Obsessive-compulsive and spectrum disorders in
children and adolescents. Psychiatr Clin North Am
29(2):353–370
Geurts HM, Verté S, Oosterlaan J, Roeyers H, Sergeant JA (2005)
ADHD subtypes: do they differ in their executive functioning
profile? Arch Clin Neuropsychol 20(4):457–477
Goodkind M, Eickhoff SB, Oathes DJ, Jiang Y, Chang A, Jones-
Hagata LB, Ortega BN, Zaiko YV, Roach EL, Korgaonkar MS,
Grieve SM, Galatzer-Levy I, Fox PT, Etkin A (2015) Identifi-
cation of a common neurobiological substrate for mental illness.
JAMA Psychiatry 72(4):305–315. doi:10.1001/jamapsychiatry.
2014.2206
Graham J, Banaschewski T, Buitelaar J, Coghill D, Danckaerts M,
Dittmann RW, Döpfner M, Hamilton R, Hollis C, Holtmann M,
Hulpke-Wette M, Lecendreux M, Rosenthal E, Rothenberger A,
Santosh P, Sergeant J, Simonoff E, Sonuga-Barke E, Wong ICK,
Zuddas A, Steinhausen HC, Taylor E (2011) European guide-
lines on managing adverse effects of medication for ADHD. Eur
Child Adolesc Psychiatry 20(1):17–37
Greene RW, Biederman J, Faraone SV, Ouellette CA, Penn C, Griffin
S (1996) Toward a new psychometric definition of social
disability in children with Attention-Deficit Hyperactivity
Disorder. J Am Acad Child Adolesc Psychiatry 35:571–578
Gualtieri CT, Johnson LG (2008) Medications do not necessarily
normalize cognition in ADHD patients. J Atten Disord
11(4):459–469
Hale JB, Reddy LA, Semrud-Clikeman M, Hain LA, Whitaker J,
Morley J, Lawrence K, Smith A, Jones N (2011) Executive
impairment determines ADHD medication response: implica-
tions for academic achievement. J Learn Disabil 44(2):196–212
Halperin JM, Berwid OG, O’Neill S (2014) Healthy body, healthy
mind?: the effectiveness of physical activity to treat ADHD in
children. Child Adolesc Psychiatr Clin N Am 23(4):899–936
Handler MW, DuPaul GJ (2005) Assessment of ADHD: differences
across psychology specialty areas. J Atten Disord 9(2):402–412
Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K (2013) Meta-
analysis of functional magnetic resonance imaging studies of
inhibition and attention in attention- deficit/hyperactivity disor-
der: exploring task-specific, stimulant medication, and age
effects. JAMA Psychiatry 70(2):185–198
Haslam N, Williams B, Prior M, Haslam R, Graetz B, Sawyer M
(2006) The latent structure of attention-deficit/hyperactivity
disorder: a taxometric analysis. Aust N Z J Psychiatry
40(8):639–647
Heidbreder CA, Groenewegen HJ (2003) The medial prefrontal
cortex in the rat: evidence for a dorso-ventral distinction based
upon functional and anatomical characteristics. Neurosci Biobe-
hav Rev 27(6):555–579
Hinshaw SP (2001) Is the inattentive type of ADHD a separate
disorder? Clin Psychol Sci Pract 8(4):498–501
Hoekzema E, Carmona S, Ramos-Quiroga JA, Richarte Fernández V,
Bosch R, Soliva JC, Rovira M, Bulbena A, Tobeña A, Casas M,
Vilarroya O (2014) An independent components and functional
connectivity analysis of resting state fMRI datapoints to neural
123
R. Heidbreder
network dysregulation in adult ADHD. Hum Brain Mapp
35(4):1261–1272
Holmes J, Hilton KA, Place M, Alloway TP, Elliott JG, Gathercole
SE (2014) Children with low working memory and children with
ADHD: same or different? Front Hum Neurosci 8:976. doi:10.
3389/fnhum.2014.00976
Holtmann M, Sonuga-Barke E, Cortese S, Brandeis D (2014)
Neurofeedback for ADHD: a review of current evidence. Child
Adolesc Psychiatr Clin N Am 23(4):789–806
Hong SB, Zalesky A, Fornito A, Park S, Yang YH, Park MH, Song
IC, Sohn CH, Shin MS, Kim BN, Cho SC, Han DH, Cheong JH,
Kim JW (2014) Connectomic disturbances in attention-deficit/
hyperactivity disorder: a whole-brain tractography analysis. Biol
Psychiatry 76(8):656–663
Hoza B, Smith AL, Shoulberg EK, Linnea KS, Dorsch TE, Blazo JA,
Alerding CL, McCabe GP (2015) A randomized trial examining
the effects of aerobic physical activity on attention-deficit/
hyperactivity disorder symptoms in young children. J Abnorm
Child Psychol 43(4):655–667. doi:10.1007/s10802-014-9929-y
Jensen PS, Martin D, Cantwell DP (1997) Comorbidity in ADHD:
implications for research, practice, and DSM-V. J Am Acad
Child Adolesc Psychiatry 36(8):1065–1079
Jensen PS, Hinshaw SP, Kraemer HC, Lenora N, Newcorn JH,
Abikoff HB, March JS, Arnold LE, Cantwell DP, Conners CK,
Elliott GR, Greenhill LL, Hechtman L, Hoza B, Pelham WE,
Severe JB, Swanson JM, Wells KC, Wigal T, Vitiello B (2001a)
ADHD comorbidity findings from the MTA study: comparing
comorbid subgroups. J Am Acad Child Adolesc Psychiatry
40(2):147–158
Jensen PS, Hinshaw SP, Swanson JM, Greenhill LL, Conners CK,
Arnold LE, Abikoff HB, Elliott G, Hechtman L, Hoza B, March
JS, Newcorn J, Severe JB, Vitiello B, Wells K, Wigal T (2001b)
Findings from the NIMH Multimodal Treatment Study of
ADHD (MTA): implications and applications for primary care
providers. J Dev Behav Pediatr 22(1):60–73
Jummani R, Coffey B (2015) ADHD and tic disorders. In: Adler L,
Spencer T, Wilens T (eds) Attention-deficit hyperactivity
disorder in adults and children. Cambridge University Press,
Cambridge, pp 343–352
Kamp CF, Sperlich B, Holmberg HC (2014) Exercise reduces the
symptoms of attention-deficit/hyperactivity disorder and im-
proves social behaviour, motor skills, strength and neuropsy-
chological parameters. Acta Paediatr 103(7):709–714. doi:10.
1111/apa.12628
Kashyap H, Fontenelle LF, Miguel EC, Ferrão YA, Torres AR,
Shavitt RG, Ferreira-Garcia R, do Rosario M, Yücel M (2012)
‘Impulsive compulsivity’ in obsessive-compulsive disorder: a
phenotypic marker of patients with poor clinical outcome.
J Psychiatr Res 46(9):1146–1152
Kesner RP, Churchwell JC (2011) An analysis of rat prefrontal cortex in
mediating executive function. Neurobiol Learn Mem 96(3):417–431
Kessler RC, Adler LA, Barkley R, Biederman J, Conners CK,
Greenhill LL, Spencer T (2011) The prevalence and correlates of
adult ADHD. In: Buitelaar JK, Kan CC, Asherson P (eds) ADHD
in adults: characterization, diagnosis, and treatment. Cambridge
University Press, Cambridge, pp 9–17
Konrad K, Neufang S, Hanisch C, Fink GR, Herpertz-Dahlmann B
(2006) Dysfunctional attentional networks in children with
attention deficit/hyperactivity disorder: evidence from an event-
related functional magnetic resonance imaging study. Biol
Psychiatry 59(7):643–651
Koziol LF, Budding D (2012) Requiem for a diagnosis: attention-
deficit hyperactivity disorder. Appl Neuropsychol Child 1(1):2–5
Kuczenski R, Segal DS (1997) Effects of methylphenidate on
extracellular dopamine, serotonin, and norepinephrine: compar-
ison with amphetamine. J Neurochem 68(5):2032–2037
ADHD symptomatology is best conceptualized as a spectrum: a dimensional versus unitary approach…
Lahey BB, Schaughency EA, Hynd GW, Carlson CL, Nieves N
(1987) Attention deficit disorder with and without hyperactivity:
comparison of behavioral characteristics of clinic-referred chil-
dren. J Am Acad Child Adolesc Psychiatry 26(5):718–723
Lahey BB, Pelham WE, Loney J, Lee SS, Willcutt E (2005)
Instability of the DSM- IV subtypes of ADHD from preschool
through elementary school. Arch Gen Psychiatry 62:896–902
Lange K, Reichl S, Lange K, Tucha L, Tucha O (2010) The history of
attention deficit hyperactivity disorder. ADHD 2(4):241–255
Lee S, Burns GL, Snell J, McBurnett K (2014) Validity of the
sluggish cognitive tempo symptom dimension in children:
sluggish cognitive tempo and ADHD-inattention as distinct
symptom dimensions. J Abnorm Child Psychol 42(1):7–19
Lensing MB, Zeiner P, Sandvik L, Opjordsmoen S (2013) Adults with
ADHD: use and misuse of stimulant medication as reported by
patients and their primary care physicians. ADHD 5(4):369–376
Leth-Steensen C, King Elbaz Z, Douglas VI (2000) Mean response
times, variability, and skew in the responding of ADHD
children: a response time distributional approach. Acta Psychol
104(2):167–190
Li F, He N, Li Y, Chen L, Huang X, Lui S, Guo L, Kemp GJ, Gong Q
(2014) Intrinsic brain abnormalities in attention deficit hyperac-
tivity disorder: a resting- state functional MR imaging study.
Radiology 272(2):514–523. doi:10.1148/radiol.14131622
Lim L, Chantiluke K, Cubillo AI, Smith AB, Simmons A, Mehta MA,
Rubia K (2015) Disorder-specific grey matter deficits in attention
deficit hyperactivity disorder relative to autism spectrum disorder.
Psychol Med 45(5):965–976. doi:10.1017/S0033291714001974
Linssen AMW, Sambeth A, Vuurman EFPM, Riedel WJ (2014)
Cognitive effects of methylphenidate in healthy volunteers: a
review of single dose studies. Int J Neuropsychopharmacol
17(6):961–977
Lockwood KA, Marcotte AC, Stern C (2001) Differentiation of
attention- deficit/hyperactivity disorder subtypes: application of
a neuropsychological model of attention. J Clin Exp Neuropsy-
chol 23(3):317–330
Lopez-Vergara HI, Colder CR (2013) An examination of the
specificity of motivation and executive functioning in ADHD
symptom-clusters in adolescence. J Pediatr Psychol 38(10):
1081–1090
Lynam DR (1996) The early identification of chronic offenders: who
is the fledgling psychopath? Psychol Bull 120:209–234
Marsh PJ, Williams LM (2006) ADHD and schizophrenia phe-
nomenology: visual scanpaths to emotional faces as a potential
psychophysiological marker? Neurosci Biobehav Rev 30(5):
651–665
Massat I, Slama H, Kavec M, Linotte S, Mary A, Baleriaux D, Metens
T, Mendlewicz J, Peigneux P (2012) Working memory-related
functional brain patterns in never medicated children with
ADHD. PLoS ONE 7(11):e49392
Mattfeld AT, Gabrieli JD, Biederman J, Spencer T, Brown A, Kotte
A, Kagan E, Whitfield-Gabrieli S (2014) Brain differences
between persistent and remitted attention deficit hyperactivity
disorder. Brain 137(Pt 9):2423–2428. doi:10.1093/brain/awu137
Matthews M, Nigg JT, Fair DA (2014) Attention deficit hyperactivity
disorder. Curr Topics Behav Neurosci 2014(16):235–266
McBurnett K, Pfiffner LJ, Frick PJ (2001) Symptom properties as a
function of ADHD type: an argument for continued study of
sluggish cognitive tempo. J Abnorm Child Psychol 29(3):207–213
McLaughlin KA, Sheridan MA, Winter W, Fox NA, Zeanah CH,
Nelson CA (2014) Widespread reductions in cortical thickness
following severe early-life deprivation: a neurodevelopmental
pathway to attention-deficit/hyperactivity disorder. Biol Psy-
chiatry 76(8):629–638
Mikami AY, Jia M, Na JJ (2014) Social skills training. Child Adolesc
Psychiatr Clin N Am 23(4):775–788
267
Milich R, Balentine AC, Lynam DR (2001) ADHD combined type
and ADHD predominantly inattentive type are distinct and
unrelated disorders. Clin Psychol Sci Pract 8(4):463–488
Millichap JG, Yee MM (2012) The diet factor in attention-deficit/
hyperactivity disorder. Pediatrics 129(2):330–337
Mills KL, Bathula D, Dias TGC, Iyer SP, Fenesy MC, Musser ED,
Stevens CA, Thurlow BL, Carpenter SD, Nagel BJ, Nigg JT,
Fair DA (2012) Altered cortico-striatal–thalamic connectivity
in relation to spatial working memory capacity in children
with ADHD. Front Psychiatry 3:2. doi:10.3389/fpsyt.2012.
00002
Miyake A, Friedman NP, Emerson MJ, Witzki AH, Howerter A,
Wager TD (2000) The unity and diversity of executive functions
and their contributions to complex ‘‘frontal lobe’’ tasks: a latent
variable analysis. Cogn Psychol 41(1):49–100
Moeller FG, Barratt ES, Dougherty DM, Schmitz JM, Swann AC
(2014) Psychiatric aspects of impulsivity. Amer J Psychiatry
158(11):1783–1793
Mostofsky S, Simmonds D (2008) Response inhibition and response
selection: two sides of the same coin. J Cogn Neurosci
20(5):751–761
Mostofsky SH, Schafer JG, Abrams MT, Goldberg MC, Flower AA,
Boyce A, Courtney SM, Calhoun VD, Kraut MA, Denckla MB,
Pekar JJ (2003) fMRI evidence that the neural basis of response
inhibition is task-dependent. Cogn Brain Res 17(2):419–430
MTA Cooperative Group (1999) A 14-month randomized clinical
trial of treatment strategies For attention-deficit/hyperactivity
disorder. Arch Gen Psychiatry 56:1073–1086
Nakao T, Radua C, Rubia K, Mataix-Cols D (2011) Gray matter
volume abnormalities in ADHD and the effects of stimulant
medication: voxel-based meta-analysis. Am J Psychiatry
168(11):1154–1163
Nigg JT, Blaskey LG, Huang-Pollock CL, Rappley MD (2002)
Neuropsychological executive functions and DSM-IV ADHD
subtypes. J Am Acad Child Adolesc Psychiatry 41(1):59–66
Nigg JT, Willcutt EG, Doyle AE, Sonuga-Barke EJ (2005) Causal
heterogeneity in attention-deficit/hyperactivity disorder: do we
need neuropsychologically impaired subtypes? Biol Psychiatry
57(11):1224–1230
Nigg JT, Lewis K, Edinger T, Falk M (2012) Meta-analysis of
attention- deficit/hyperactivity disorder or attention-deficit/hy-
peractivity disorder symptoms, restriction diet, and synthetic
food color additives. J Am Acad Child Adolesc Psychiatry
51(1):86–97
Ollendorf DA, Migliaccio-Walle K, Colby JA, Pearson SD (2013)
Management options for children with attention-deficit/hyperac-
tivity disorder: a regional perspective on value. J Comp Eff Res
2(3):261–271
Patel N, Patel M, Patel H (2012) ADHD and comorbid conditions.
Atten Deficit Hyperact Disord 1:978–979
Pelham WE Jr, Fabiano GA (2008) Evidence-based psychosocial
treatments for attention-deficit/hyperactivity disorder. J Clin
Child Adolesc Psychol 37(1):184–214
Pliszka SR (2015) ADHD and tic disorders. In: Adler L, Spencer T,
Wilens T (eds) Attention-deficit hyperactivity disorder in adults
and children. Cambridge University Press, Cambridge, pp 63–71
Pliszka SR, Carlson CL, Swanson JM (1999) ADHD with comorbid
disorders: clinical assessment and management. Guilford Press,
Newyork
Polanczyk GV, Willcutt EG, Salum GA, Kieling C, Rohde LA (2014)
ADHD prevalence estimates across three decades: an updated
systematic review and meta- regression analysis. Int J Epidemiol
43(2):434–442
Posner MI, Petersen SE (1989) The attention system of the human
brain (No. TR-89-1). Washington Univ ST Louis MO Dept of
Neurology
123
268
Quinn CA (2003) Detection of malingering in assessment of adult
ADHD. Arch Clin Neuropsychol 18(4):379–395
Rabiner DL (2013) Stimulant prescription cautions: addressing
misuse, diversion and malingering. Curr Psychiatry Rep
15(7):1–8
Rapport MD, Denney C, DuPaul GJ, Gardner MJ (1994) Attention
deficit disorder and methylphenidate: normalization rates,
clinical effectiveness, and response prediction in 76 children.
J Am Acad Child Adolesc Psychiatry 33(6):882–893
Reddy LF, Lee J, Davis MC, Altshuler L, Glahn DC, Milowitz DJ,
Green MF (2014) Impulsivity and risk taking in bipolar disorder
and schizophrenia. Neuropsychopharmacology 39(2):456–463
Riccio CA, Homack S, Jarratt KP, Wolfe ME (2006) Differences in
academic and executive function domains among children with
ADHD predominantly inattentive and combined types. Arch
Clin Neuropsychol 21(7):657–667
Rosa-Neto P, Lou HC, Cumming P, Pryds O, Karrebaek H, Lunding
J, Gjedde A (2005) Methylphenidate-evoked changes in striatal
dopamine correlate with inattention and impulsivity in adoles-
cents with attention deficit hyperactivity disorder. Neuroimage
25(3):868–876
Rubia K, Smith AB, Brammer MJ, Toone B, Taylor E (2005)
Abnormal brain activation during inhibition and error detection
in medication-naive adolescents with ADHD. Am J Psychiatry
162(6):1067–1075
Rubia K, Halari R, Cubillo A, Mohammad AM, Brammer M, Taylor
E (2009) Methylphenidate normalises activation and functional
connectivity deficits in attention and motivation networks in
medication-naive children with ADHD during a rewarded
continuous performance task. Neuropharmacology 57(7):
640–652
Rubia K, Cubillo A, Smith AB, Woolley J, Heyman I, Brammer MJ
(2010) Disorder-specific dysfunction in right inferior prefrontal
cortex during two inhibition tasks in boys with attention-deficit
hyperactivity disorder compared to boys with obsessive–com-
pulsive disorder. Hum Brain Mapp 31(2):287–299
Rubia K, Cubillo A, Woolley J, Brammer MJ, Smith A (2011)
Disorder-specific dysfunctions in patients with attention-deficit/
hyperactivity disorder compared to patients with obsessive-
compulsive disorder during interference inhibition and attention
allocation. Hum Brain Mapp 32(4):601–611
Rubia K, Alegria AA, Cubillo AI, Smith AB, Brammer MJ, Radua J
(2014a) Effects of stimulants on brain function in attention-
deficit/hyperactivity disorder: a systematic review and meta-
analysis. Biol Psychiatry 76(8):616–628
Rubia K, Alegria A, Brinson H (2014b) Imaging the ADHD brain:
disorder-specificity, medication effects and clinical translation.
Exp Rev Neurother 0:1–20
Saxbe C, Barkley RA (2014) The second attention disorder? Sluggish
cognitive tempo vs. attention-deficit/hyperactivity disorder:
update for clinicians. J Psychiatr Pract 20(1):38–49
Schaeffer JL, Ross RG (2002) Childhood-onset schizophrenia:
premorbid and prodromal diagnostic and treatment histories.
J Am Acad Child Adolesc Psychiatry 41(5):538–545
Schmeichel BE, Berridge CW (2013) Neurocircuitry underlying
the preferential sensitivity of prefrontal catecholamines to
low-dose psychostimulants. Neuropsychopharmacology 38(6):
1078–1084
Sciutto MJ, Eisenberg M (2007) Evaluating the evidence for and
against the overdiagnosis of ADHD. J Atten Disord 11(2):
106–113
Sebastian A, Jung P, Krause-Utz A, Lieb K, Schmahl C, Tüscher O
(2014) Frontal dysfunctions of impulse control–a systematic
review in borderline personality disorder and attention-deficit/
hyperactivity disorder. Front Hum Neurosci 8:698. doi:10.3389/
fnhum.2014.00698
123
R. Heidbreder
Segal DS, Kuczenski R (1994) Behavioral pharmacology of am-
phetamine. Amphetamine and its analogs: psychopharmacology,
toxicology and abuse. San Diego, Academic Press, Inc., 115–150
Shalev L, Tsal Y (2003) The wide attentional window a major deficit
of children with attention difficulties. J Learn Disabil
36(6):517–527
Shallice T, Burgess P (1991) Higher-order cognitive impairments and
frontal lobe lesions in man. In: Levin HS, Eisenberg HM, Benton
AL (eds) Frontal lobe function and dysfunction. Oxford
University Press, Oxford, New York, pp 125–138
Shaw P, Eckstrand K, Sharp W, Blumenthal J, Lerch JP, Greenstein
D, Clasen L, Evans A, Giedd J, Rapoport JL (2007) Attention-
deficit/hyperactivity disorder is characterized by a delay in
cortical maturation. Proc Natl Acad Sci 104(49):19649–19654
Shaw P, Malek M, Watson B, Greenstein D, de Rossi P, Sharp W
(2013) Trajectories of cerebral cortical development in child-
hood and adolescence and adult attention- deficit/hyperactivity
disorder. Biol Psychiatry 74(8):599–606
Sibley MH, Altszuler AR, Morrow AS, Merrill BM (2014) Mapping
the academic problem behaviors of adolescents with ADHD. Sch
Psychol Q 29(4):422
Simmonds DJ, Pekar JJ, Mostofsky SH (2008) Meta-analysis of Go/
No-go tasks demonstrating that fMRI activation associated with
response inhibition is task- dependent. Neuropsychologia
46(1):224–232
Skogli EW, Teicher MH, Andersen PN, Hovik KT, Øie M (2013)
ADHD in girls and boys–gender differences in co-existing
symptoms and executive function measures. BMC Psychiatry
13(1):298
Smith A, Taylor E, Brammer M, Toone B, Rubia K (2006) Task-
specific hypoactivation in prefrontal and temporoparietal brain
regions during motor inhibition and task switching in medica-
tion-naive children and adolescents with attention deficit hyper-
activity disorder. Am J Psychiatry 163(6):1044–1051
Solanto M, Newcorn J, Vail L, Gilbert S, Ivanov I, Lara R (2009)
Stimulant drug response in the predominantly inattentive and
combined subtypes of attention- deficit/hyperactivity disorder.
J Child Adolesc Psychopharmacol 19(6):663–671
Song Y, Hakoda Y (2014) Executive and non-executive functions in
attention deficit hyperactivity disorder of the inattentive type
(ADHD-I): a cognitive profile. J Behav Brain Sci 4:1–10
Sonuga-Barke EJ (2002) Psychological heterogeneity in AD/HD—a
dual pathway model of behaviour and cognition. Behav Brain
Res 130(1):29–36
Sonuga-Barke EJ, Brandeis D, Cortese S, Daley D, Ferrin M,
Holtmann M, Stevenson J, Danckaerts M, van der Oord S,
Döpfner M, Dittmann RW, Simonoff E, Zuddas A,
Banaschewski T, Buitelaar J, Coghill D, Hollis C, Konofal E,
Lecendreux M, Wong ICK, Sergeant J (2013) Nonpharmaco-
logical interventions for ADHD: systematic review and meta-
analyses of randomized controlled trials of dietary and psycho-
logical treatments. Am J Psychiatry 170(3):275–289
Sonuga-Barke E, Brandeis D, Holtmann M, Cortese S (2014)
Computer-based cognitive training for ADHD: a review of
current evidence. Child Adolesc Psychiatr Clin N Am
23(4):807–824
Sripada CS, Kessler D, Angstadt M (2014) Lag in maturation of the
brain’s intrinsic functional architecture in attention-deficit/hy-
peractivity disorder. Proc Natl Acad Sci 111(39):14259–14264
Stevenson J, Buitelaar J, Cortese S, Ferrin M, Konofal E, Lecendreux
M, Simonoff E, Wong CK, Sonuga-Barke E (2014) Research
review: the role of diet in the treatment of attention- deficit/
hyperactivity disorder–an appraisal of the evidence on efficacy
and recommendations on the design of future studies. J Child
Psychol Psychiatry 55(5):416–427
Stuss DT, Benson DF (1986) The frontal lobes. Raven, New York
ADHD symptomatology is best conceptualized as a spectrum: a dimensional versus unitary approach…
Stuss DT, Floden D, Alexander MP, Levine B, Katz D (2001) Stroop
performance in focal lesion patients: dissociation of processes
and frontal lobe lesion location. Neuropsychologia 39(8):
771–786
Tarver J, Daley D, Sayal K (2014) Attention-deficit hyperactivity
disorder (ADHD): an updated review of the essential facts. Child
Care Health Dev 40(6):762–774. doi:10.1111/cch.12139
Taylor E (2011) Antecedents of ADHD: a historical account of
diagnostic concepts. ADHD 3(2):69–75
Tian L, Jiang T, Liang M, Zang Y, He Y, Sui M, Wang Y (2008)
Enhanced resting- state brain activities in ADHD patients: a
fMRI study. Brain Dev 30(5):342–348
Timimi S (2004) Developing nontoxic approaches to helping children
who could be diagnosed with ADHD and their families:
reflections of a United Kingdom Clinician. Ethical Hum Sci
Serv 6(1):41–52
Tomasi D, Volkow ND (2012) Abnormal functional connectivity in
children with attention-deficit/hyperactivity disorder. Biol Psy-
chiatry 71(5):443–450
Tucha L, Fuermaier AB, Koerts J, Groen Y, Thome J (2014)
Detection of feigned attention deficit hyperactivity disorder.
J Neural Transm 1–12. doi:10.1007/s00702-014-1274-3
Valera EM, Faraone SV, Murray KE, Seidman LJ (2007) Meta-
analysis of structural imaging findings in attention-deficit/
hyperactivity disorder. Biol Psychiatry 61(12):1361–1369
Valera EM, Brown A, Biederman J, Faraone SV, Makris N,
Monuteaux MC, Whitfield-Gabrielli S, Vitulano M, Schiller M,
Seidman LJ (2010) Sex differences in the functional neuroanato-
my of working memory in adults with ADHD. Am J Psychiatry
167(1):86–94
van Lieshout M, Luman M, Buitelaar J, Rommelse NNJ, Oosterlaan J
(2013) Does neurocognitive functioning predict future or
persistence of ADHD? Syst Rev Clin Psychol Rev
33(4):539–560
Visser SN, Danielson ML, Bitsko RH, Holbrook JR, Kogan MD,
Ghandour RM, Perous R, Blumberg SJ (2014) Trends in the
parent-report of health care provider- diagnosed and medicated
attention-deficit/hyperactivity disorder: United States,
2003–2011. J Am Acad Child Adolesc Psychiatry 53(1):34–46
Vitiello B (2001) Long-term effects of stimulant medications on the
brain: possible relevance to the treatment of attention deficit
hyperactivity disorder. J Child Adolesc Psychopharmacol
11(1):25–34
Volkow ND, Insel TR (2003) What are the long-term effects of
methylphenidate treatment? Biol Psychiatry 54(12):1307–1309
Volkow ND, Swanson JM (2013) Adult attention deficit-hyperactivity
disorder. N Engl J Med 369(20):1935–1944
Volkow ND, Wang GJ, Fowler JS, Gatley SJ, Logan J, Ding YS,
Hitzemann R, Pappas N (1998) Dopamine transporter occupan-
cies in the human brain induced by therapeutic doses of oral
methylphenidate. Am J Psychiatry 155(10):1325–1331
Volkow ND, Fowler JS, Wang GJ, Baler R, Telang F (2009) Imaging
dopamine’s role in drug abuse and addiction. Neuropharma-
cology 56:3–8
Volkow ND, Wang GJ, Newcorn JH, Kollins SH, Wigal TL, Telang
F, Fowler JS, Goldstein RZ, Klein N, Logan J, Wong C,
Swanson JM (2011) Motivation deficit in ADHD is associated
269
with dysfunction of the dopamine reward pathway. Mol
Psychiatry 16(11):1147–1154
Wåhlstedt C, Thorell LB, Bohlin G (2009) Heterogeneity in ADHD:
neuropsychological pathways, comorbidity and symptom do-
mains. J Abnorm Child Psychol 37(4):551–564
Wasserman RC, Kelleher KJ, Bocian A, Baker A, Childs GE,
Indacochea F, Stulp C, Gardner WP (1999) Identification of
attentional and hyperactivity problems in primary care: a report
from pediatric research in office settings and the ambulatory
sentinel practice network. Pediatrics 103(3):e38
Weiss M, Worling D, Wasdell M (2003) A chart review study of the
inattentive and combined types of ADHD. J Atten Disord
7(1):1–9
Wilens TE, Morrison NR (2011) The intersection of attention-deficit/
hyperactivity disorder and substance abuse. Curr Opin Psy-
chiatry 24(4):280
Wilens TE, Biederman J, Forkner P, Ditterline J, Morris M, Moore H,
Galdo M, Spencer TJ, Wozniak J (2003) Patterns of comorbidity
and dysfunction in clinically referred preschool and school-age
children with bipolar disorder. J Child Adolesc Psychopharmacol
13(4):495–505
Wilkinson D, Halligan P (2004) The relevance of behavioural
measures for functional- imaging studies of cognition. Nat Rev
Neurosci 5(1):67–73
Willcutt EG (2012) The prevalence of DSM-IV attention-deficit/
hyperactivity disorder: a meta-analytic review. Neurotherapeu-
tics 9(3):490–499
Williamson KD, Combs HL, Berry DT, Harp JP, Mason LH,
Edmundson M (2014) Discriminating among ADHD alone,
ADHD with a comorbid psychological disorder, and feigned
ADHD in a college sample. Clin Neuropsychol 28(7):1182–1196
Willoughby MT (2003) Developmental course of ADHD symptoma-
tology during the transition from childhood to adolescence: a
review with recommendations. J Child Psychol Psychiatry
44(1):88–106
Wolraich ML (2006) Attention-deficit/hyperactivity disorder: can it
be recognized and treated in children younger than 5 years?
Infants Young Child 19(2):86–93
Wolraich M, Milich R, Stumbo P, Schultz F (1985) Effects of sucrose
ingestion on the behavior of hyperactive boys. J Pediatr
106(4):675–682
Wolraich ML, Lindgren SD, Stumbo PJ, Stegink LD, Appelbaum MI,
Kiritsy MC (1994) Effects of diets high in sucrose or aspartame
on the behavior and cognitive performance of children. N Engl J
Med 330(5):301–307
Wolraich ML, McKeown RE, Visser SN, Bard D, Cuffe S, Neas B,
Geryk LL, Doffing M, Bottsi M, Abramowitz AJ, Beck L,
Holbrook JR, Danielson M (2014) the prevalence of ADHD: its
diagnosis and treatment in four school districts across two states.
J Atten Disord 18(7):563–575
Yu-Feng Z, Yong H, Chao-Zhe Z, Qing-Jiu C, Man-Qiu S, Meng L,
Li-Xia T, Tian-Zi J, Yu-Feng W (2007) Altered baseline brain
activity in children with ADHD revealed by resting-state
functional MRI. Brain Dev 29(2):83–91
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