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Assessing Adult ADHD Through Objective Neuropsychological Measures: A

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JADXXX10.1177/10870547231167564Journal of Attention DisordersRosso et al.

Article
Journal of Attention Disorders

Assessing Adult ADHD Through Objective

1­–9
© The Author(s) 2023
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DOI: 10.1177/10870547231167564
https://doi.org/10.1177/10870547231167564

Overview journals.sagepub.com/home/jad

Gianluca Rosso1,2, Caterina Portaluppi1 , Elena Teobaldi1 ,

Gabriele Di Salvo1,2,3, and Giuseppe Maina1,2,3

Abstract
Objective: This review examines the role of neuropsychological tests in the diagnostic assessment of adult ADHD,
focusing on their ability to discriminate individuals with ADHD from those with other psychiatric conditions. Method:
PubMed, Embase, and PsycINFO were searched for eligible peer-reviewed studies from inception to September 2022.
Results: Ten studies were included. Among the objective measures analyzed, Continuous Performance Tests were the
only capable to reliably distinguish individuals with ADHD from other psychiatric patients, in a combined approach with
clinical interview instruments. The other objective tests showed mixed and inconsistent results. Conclusion: This finding
suggest that further studies are needed to develop objective measures more tailored to the core symptoms of ADHD, in
order to improve the discriminatory ability of the tests and help the clinicians in the complex differential diagnosis between
ADHD and other psychiatric disorders.

Keywords
ADHD, adult, assessment, neuropsychological testing, clinical sample

Introduction coexists with other psychiatric diseases such as major

Attention-deficit hyperactivity disorder (ADHD) is a clini-
cally heterogeneous neurodevelopmental disorder that
includes age-inappropriate levels of inattention, hyperactiv-
ity, and impulsivity. ADHD has been associated with high
risk of comorbid psychiatric disorders and severe functional
impairment (Biederman et al., 2006; Gjervan et al., 2012;
Kooij et al., 2012). Despite it has long been thought to occur
only in childhood, more recent studies suggest that it can
persist into adulthood in a high proportion of cases, with a
prevalence of approximately 2.5% in adult population
(Simon et al., 2009; Song et al., 2021).
The number of adults seeking evaluation for ADHD has
risen dramatically as knowledge of the nature of the disor-
der and the benefits of being diagnosed with ADHD has
increased (Paris et al., 2015; Song et al., 2021); thus, great
attention needs to be paid to the assessment phase, in order
to correctly identify those who suffer from the neurodevel-
opmental disorder. From a neuropsychological perspective,
this means that more emphasis should be placed on stan-
dardized instruments that improve the diagnostic accuracy
of adult ADHD assessments, particularly in case of sus-
pected diagnosis or psychiatric disorder with overlapping
symptoms. In more than 80% of patients adult ADHD
depression, anxiety disorders, bipolar disorder, personality
disorder, and substance or alcohol abuse (Grazioli et al.,
2019; Katzman et al., 2017; Mucci et al., 2019; Xenaki &
Pehlivanidis, 2015). Therefore, differentiating ADHD from
other clinical disorders is actually the most difficult part of
making an ADHD diagnosis in adults (Luo et al., 2019;
McGough et al., 2005; Whlstedt et al., 2009). The current
diagnostic clinical assessment of ADHD according to the
criteria set in the fifth edition of the Diagnostic and
Statistical Manual of Mental Disorders (DSM-5; American
Psychiatric Association, 2013) is behaviorally based and
does not require psychometric testing to make the diagno-
sis. However, objective measures are frequently used in the
routine examination of individuals in the ADHD diagnostic
assessment. Certain neuropsychological batteries or test
(e.g., Color Word interference, California Verbal Learning
1
University of Turin, Turin, Italy
2
San Luigi Gonzaga University Hospital, Orbassano, Turin, Italy
3
Regional Coordination Centre for adult ADHD, Orbassano, Turin, Italy
Corresponding Author:
Elena Teobaldi, Department of Neurosciences “Rita Levi Montalcini,”
University of Turin, Via Cherasco 15, Turin 10126, Italy.
Email: elena.teobaldi@unito.it
2 Journal of Attention Disorders 00(0)

Test, Continuous Performance Test, and Wisconsin Card

Sorting Test) have been recommended as being particularly
appropriate measures in ADHD assessment (Fuermaier et
al., 2019; Marshall et al., 2021), even if is still debated
whatever or not cognitive assessment should be considered
in the diagnostic algorithm (Barkley, 2019; Lange et al.,
2014; Mapou, 2019).
Comparing with healthy controls, it is established that
adult ADHD is associated with impairments in various cog-
nitive domains, with attention and executive functions defi-
cits being far more prevalent than others (Boonstra et al.,
2010; Fuermaier et al., 2015, 2022; Torgalsbøen et al.,
2021; Tucha et al., 2017), as confirmed in a recent and
extended systematic review (Onandia-Hinchado et al.,
2021).
However, despite the extensive literature on comparison
with healthy controls, only little is known about the neuro-
psychological functions of ADHD patients when compared
to psychiatric conditions and whether a specific neuropsy-
chological profile for adult ADHD can be identified.
This article brings together recent evidence about the
critical contribution of neuropsychological tests in the diag-
nostic assessment of adult ADHD, focusing on whether or
not objective measures can differentiate individuals with
ADHD from individuals with other psychiatric disorders.
Figure 1. Flow diagram.

Method
We conducted a narrative review of published articles on
the neuropsychological test used in the assessment of adult
ADHD in a clinical sample. The electronic databases
PubMed, Embase, and PsycINFO were used for literature
published in the last decade, from 2012 to September
2022, using the following keywords adapted to the search-
ing requirements in each database: “neuropsycholog*”
AND “assessment” AND “adult*” AND “attention hyper-
activity disorder” AND “clinical controls.” Handsearching
the reference lists of the retrieved articles yielded addi-
tional relevant articles. The inclusion criteria for this
review were as follows: (a) adult participants (aged
18 years and above); (b) participants diagnosed with
ADHD according to DSM-5 criteria; (c) the occurrence of
a comparison clinical control group (participants with
other psychiatric disorders); (e) the use at least of one
objective cognitive test at the assessment; (f) peer-
reviewed English-language articles. The presence of
comorbid medical and psychiatric disorders (either current
or lifetime) in participants with ADHD did not constitute
an exclusion criterion provided that ADHD was the pri-
mary diagnosis. The following studies were excluded: sys-
tematic or narrative review articles, meta-analysis articles,
commentaries or editorials, case report/series. Articles
were assessed for inclusion at three stages: title screening,
abstract screening, and full text screening. Three
reviewers (CP, ET, and GDS) independently decided
which articles to include according to clinical importance
and eligibility criteria. In case of disagreement, the senior
authors (GR and GM) were consulted to mediate consen-
sual decision. Given the wide variety of outcomes reported
and the lack of diagnostic accuracy statistics in extant
studies reviewed a meta-analysis was not performed.
Results
The literature search revealed nine qualifying studies, as
shown from the flow diagram provided in Figure 1. From
all databases combined, the initial search yielded 1,382
results. After duplicates had been removed, 962 articles
remained. At title and abstract screening, 923 articles were
removed as they were not relevant or did not meet the inclu-
sion criteria. A total of 41 articles were found to be suitable
for full-text screening. The full-text screening of these arti-
cles eliminated 28 articles that still did not meet the inclu-
sion criteria. The studies included in the synthesis are listed
in Table 1.
The results of selected articles looked into the ability of
objective neuropsychological measures to distinguish indi-
viduals receiving or confirming a diagnosis of adult ADHD
from those with other psychiatric disorders or with ADHD
symptoms who do not meet the diagnostic criteria at the
time of assessment.
 Table 1. Neuropsychological Assessment Using Single Objective Measures.
Authors (publication
year) Participants (n) Age = mean (SD) ADHD group features Cognitive domains Objective measures (test) Relevant outcomes

Edebol et al. (2012) ADHD (53) ADHD = 35.89 (12.25) Psychiatric Attention/hyperactivity/ QBTest Plus Sensitivity of the QBTest was higher for the
CC: BD II, BPD (45) CC = 42.33 (11.63) comorbidities: yesb impulsivity ADHD group. Analyses yielded 87% sensitivity
CC-ND (29) CC-ND = 35.21 (10.31) Stimulants treatment: for the ADHD group, 85% specificity for the
HC (179) HC = 31.45 (10.33) off healthy controls, 36% sensitivity for the clinical
controls, and 41% sensitivity for the group with
a disconfirmed diagnosis of ADHD.
Söderström et al. (2014) ADHD (41) ADHD = 32.46 (8.99) Psychiatric Attention/hyperactivity/ QBTest Plus QBTest Plus shows high degree of specificity
CC: mixed diagnosis CC = 30.00 (9.76) comorbidities: yesc impulsivity for the cardinal symptoms of inattention and
(23) Stimulants treatment: impulsivity (100.0 and 80.0%) but low sensitivity
off (36.6 and 58.5%) when the cut-off score of
1.5 was applied. Inattention classified 87.8% of
ADHD patients correctly but identified only
40% of the Non-ADHD group as not having
the diagnosis.
Fasmer et al. (2016) ADHD (50) ADHD = 37.7 (10.3) Psychiatric Attention CPT II The CPT II omission and commission errors,
CC: mixed diagnosis CC = 37.8 (11.8) comorbidities: yesd skewness, and variability measures were
(49) Stimulants treatment: effective in discriminating between participants
off with ADHD and those with other psychiatric
diagnoses.

Neuropsychological assessment using multiple objective measures

Authors (publication
year) Participants (n) ADHD group features Cognitive domains Objective measures (test) Relevant outcomes

Holst and Thorell ADHD (57) ADHD = 26.8 (5.9) Psychiatric Verbal working memory/ D-KEFS (Color word interference; Verbal Significant group differences were found for
(2013) CC: mixed diagnosis CC = 25.5 (5) comorbidities: yese spatial working memory/ fluency; Sorting; Tower)/WAIS-IV inhibition assessed with the Color Word task
(53) Stimulants treatment: interference control/ (Letter-Number Sequencing; Digit Span and for Letter fluency. Sensitivity of these tests
ona inhibition/set shifting/ backward; Digit Span Forward; Block ranged between 64 and 75% and specificity
planning/fluency/reaction- Design; Vocabulary)/Computerized EF between 66 and 81%.
time variability task (Find-the-Phone task and Navon-
like task)
Marshall et al. (2016) ADHD (102) Overall = 26.38 (7.79) Psychiatric Verbal working memory/ WAIS-IV (Vocabulary; Block Design; The performances obtained at the TOVA test
CC: mood disorders comorbidities: yesg spatial working memory/ Digit span; Letter Number Sequencing; and NAB Number and Letters Part A errors
and GAD (326) Stimulants treatment: interference control/long Symbol search)/NAB (Numbers and led a significant difference between the ADHD
off term memory/inhibition/ Letters test)/Word memory test/ patients and those in the control group.
set shifting/planning/ TOVA/Word memory test/Sentence
fluency/reaction-time repetition test/PASAT/CVLT/DCT/
variability WMS-IV (spatial addition)/B Test/D-
KEFS (Color word interference; Tower;
Design Fluency; Verbal fluency)

(continued)

3
4
Table 1. (continued)
Neuropsychological assessment using multiple objective measures

Authors (publication year) Participants (n) ADHD group features Cognitive domains Objective measures (test) Relevant outcomes

Pettersson et al. (2018) ADHD (60) ADHD = 28.18 (9.09) Psychiatric Attention/working memory/ WAIS-IV (Digit Span Backward and Significant group differences were found for
CC: mixed diagnosis CC = 32.75 (10.61) comorbidities: yesf verbal long-term memory/ Digit Symbol-Coding)/RAVLT/D-KEFS QBTest Plus (inattention, action, omission
(48) Stimulants treatment: verbal fluency/executive (Verbal Fluency)/TMT B/PASAT/ errors, RT variability), CPT II (commission
off functions QBTest Plus/CPT II errors, variability and reaction time), and
RAVLT VI.
Nikolas et al. (2019) ADHD (109) ADHD = 24.8 (6.2) Psychiatric Attention/verbal working WAIS-IV (Vocabulary; Block Design; Worse performance on the CVLT short-delay
CC: unipolar mood CC = 22.9 (4.5) comorbidities: NS memory/spatial working Digit span; Letter Number Sequencing; free recall (OR = 1.4) and TOVA Reaction Time
disorder (52) HC = 23.6 (5.4) Stimulants treatment: memory/interference Symbol search)/NAB (Numbers and (OR = 1.6) were associated with the ADHD
HC (85) off control/long-term Letters test)/Word memory test/ group, with a classification accuracy of 70.4%. A
memory/inhibition/set TOVA/Sentence repetition test/PASAT/ combined approach correctly classified 87% of
shifting/planning ability/ CVLT/DCT/WMS-IV spatial addition the ADHD cases.
fluency/reaction-time subtest/B Test/D-KEFS (Color word
variability interference; Tower; D e V Fluency)
Guo et al. (2021) ADHD (78) ADHD = 31.9 (10.3) Psychiatric Selective attention/vigilance/ CFADHD of VTS (Perceptual and Profiles of neuropsychological impairments were
CC: mixed diagnosis CC = 38.8 (11.2) comorbidities: yesh working memory/figural Attention Functions-Selective; similar between groups.
(71) CC-ND = 35.4 (12.1) Stimulants treatment: fluency/interference/ Attention Perceptual and Attention
CC-ND (50) NS processing speed/ Functions-Vigilance; N-back verbal task;
flexibility/planning ability/ 5-point test Figural Fluency; Stroop
inhibition/task switching Interference Test; TMT-L; Tower of
London; Go/No-Go test paradigm;
SWITCH)
Guo et al. (2022) ADHD (173) ADHD = 33.2 (9.6) Psychiatric Selective attention/vigilance/ CFADHD of VTS (Perceptual and No difference in neurocognitive performance
CC: mixed diagnosis CC = 35.3 (11.2) comorbidities: yesi working memory/figural Attention Functions-Selective; between ADHD and non-ADHD group, except
(54) CC-ND = 35.3 (11.2) Stimulants treatment: fluency/interference/ Attention Perceptual and Attention in the number of omissions of the vigilance test
CC-ND (92) NS processing speed/ Functions-Vigilance; N-back verbal task; (median: 2 vs. 1; p:0.003)
flexibility/planning ability/ 5-point test Figural Fluency; Stroop
inhibition/task switching Interference Test; TMT-L; Tower of
London; Go/No-Go test paradigm;
SWITCH)

Note. CC = Clinical Comparison group; CC-ND = Clinical Comparison group Not Diagnosed or disconfirmed; HC = Healthy Control; NS = Not Specified; BD II = Bipolar Disorder type II; BPD = Borderline Personality Disorder;
GAD = General Anxiety Disorder; CFADHD = Test battery Cognitive Functions ADHD; VTS = Vienna Test System; RAVLT = Rey Auditory Verbal Learning Test; BVMT-R = Brief Visuospatial Memory Test Revised; WAIS-
IV = Wechsler Adult Intelligence Scale – Fourth Edition; NAB = Neuropsychological Assessment Battery; TOVA = Test of Variables Attention; PASAT = Paced Auditory Serial Addition Task; CVLT = California Verbal Learning Test;
WMS-IV = Wechsler Memory Scale; D-KEFS = Delis Kaplan Executive System; TMT type B = Trail Making Test Part B; CVLT = California Verbal Learning Test; DCT = Dot Counting Test; QBTest Plus = Quantitative Behaviour
Test Plus; CPT II = Conner’s continuous performance test second edition; SCIP = Screen for Cognitive Impairments in Psychiatry
a
18/57.
b
Social phobia (3/53); dyslexia (3/53); GAD (1/53); depression (2/53); stress reaction (1/53); personality disorder (1/53).
c
Mood disorders (16/41); anxiety disorders (13/41); cluster B disorders (2/41); substance-dependence disorders (3/41).
d
Bipolar disorder (15/50); unipolar depression (16/50); anxiety disorder (19/50); alcohol or drug abuse (13/50); other diagnoses (14/50).
e
Major depression (9/57); bipolar disorder (3/57); unspecified anxiety disorder (3/57); panic disorder (2/57); DOC (1/57); social phobia (1/57); personality disorder (3/57).
f
Mood disorder (15/60); anxiety disorder (26/60); other axis I disorder (10/60); axis II cluster A disorder (3/60); axis II cluster B disorder (5/60); axis II cluster C disorder (6/60).
g
Prevalence in ADHD group not specified. Of the total of the participants: major depression (51/428); depression not otherwise specified (94/428); dysthymia (8/428); mood disorder not otherwise specified (21/428); GAD
(51/428).
h
Mood disorders (19/78); addiction disorders (5/78); adjustment disorders (5/78); anxiety disorders (3/78); DOC (2/78); personality disorders (1/78); oppositional defiant disorders (1/78); intellectual developmental disorders
(1/78); autistic disorders (1/78).
i
Mood disorders (27/173); addiction disorders (11/173); adjustment disorders (5/173); anxiety disorders (6/173); personality disorders (8/173); oppositional defiant disorders (1/173); autistic disorders (2/173); post-traumatic
stress disorders (1/173).
Rosso et al.
Neuropsychological Assessment Using
Single Objective Measures
Three studies attempt to compare neuropsychological func-
tioning between ADHD patients and other psychiatric
patients using the Quantitative Behaviour Test Plus (QBT
Test Plus) as objective measures. It is a cognitive computer-
based test that combines a continuous performance test with
the measurement of motor activity and evaluates the three
ADHD core symptoms: hyperactivity, inattention, and
impulsivity.
Edebol et al. (2012) included 53 patients, 9 of whom had
mixed psychiatric comorbidities, assessed by clinical
records, and were free from/not receiving psychostimulants
treatment. They showed that the QBTest cardinal variables
had a high sensitivity (87%) in distinguishing individuals
diagnosed with ADHD from patients with bipolar II disor-
der, borderline personality disorder, or a disconfirmed diag-
nosis of ADHD. Similarly, Söderström et al. (2014),
analyzing a medication free ADHD sample with psychiatric
comorbidities (23/41), found that the QBImpulsivity and
QBInattention variables had high specificity but low sensi-
tivity in their analysis in distinguishing from a mixed clini-
cal group. To explore the diagnostic utility of the instrument,
a stepwise discriminant function analysis was conducted.
The variable with the highest discriminant power was
QBInattention, with a discriminant load of 0.826.
Fasmer et al. (2016), instead, objectively measured cog-
nitive performance in ADHD and mood or anxiety patients
using the Conner’s continuous performance test second edi-
tion (CPT-II). The ADHD group, which suffered from a mix
of comorbidities specifically assessed by MINI Interview
and multiple psychometric scales, was treated by psycho-
tropic drug treatment but no stimulants. Compared to the
clinical control group, they had more omission and com-
mission errors and a higher reaction time variability. In
addition, the authors analyzed the differences between the
subtypes of ADHD (combined type and inattentive type),
observing that the only difference was a higher reaction
time in the combined subtype.
Neuropsychological Assessment Using
Multiple Objective Measures
The other studies included in the analysis used a combined
approach of different objective neuropsychological mea-
sures to distinguish ADHD patients from those with other
psychiatric disorders.
First of all, Holst and Thorell (2013) explored numerous
cognitive domains using a variety of objective measures to
see if the objective measures chosen (see Table 1) could
better differentiate between real-word ADHD patients with
mixed comorbidities (DSM-IV) and those with other psy-
chiatric disorders (mostly mood and/or anxiety disorders).
5
After controlling for sex and the respective control tests,
significant group differences were found for inhibition
assessed with the Color Word task and for Letter fluency
task with low sensitivity and specificity. However, exclud-
ing the patients on psychostimulants (n = 18), the result at
the Letter fluency task changed from significant to nonsig-
nificant, whereas inhibitory errors on the Navon Task and
the effect of spatial working memory, when controlling for
IQ, turned out significant. Nevertheless, when only drug-
free participants were included in the logistic regression
analysis, the overall classification rate increased only
slightly.
Marshall et al. (2016) conducted a retrospective study in
a sample with mixed psychiatric diagnoses to examine how
many patients would have plausibly receive a primary diag-
nosis of ADHD if performance and symptom validity mea-
sures were not administered during neuropsychological
evaluations. Analyses were conducted on patients treated
with psychotropic drugs, but participants with ADHD were
washed out from stimulants to perform the cognitive assess-
ment. Results revealed that the Test of Variable Attention—
TOVA (omission errors and RT variability scores) and the
Neuropsychological Assessment Battery—NAB (Number
and Letters Part A errors) were able to discriminate between
ADHD patients and suspect efforts even though with low
specificity; thus, the study concluded that impairment in
neurocognitive performance is not sufficient to distinguish
ADHD patients from those who exaggerate or mimic
symptoms.
A more recent study (Pettersson et al., 2018) examined a
range of cognitive domains (see Table 1) in a naturalistic
psychiatric sample of stimulant-free ADHD and non-
ADHD patients, both characterized by Axis I and Axis II
diagnoses made through semi-structured interviews SCID-I
and SCID-II. The authors showed significant differences
between groups in the RAVLT memory and learning test, in
attentional processes assessed by CPT II (Commission
errors, Hit reaction time SE, and Variability of SE) and in
some QBTest measures (Inattention, Activity, Omission
errors, and Reaction time variance). However, the study
concluded that only variables from CPT II allow to discrim-
inate between ADHD and non-ADHD group with a sensi-
tivity of 90% and a specificity of 83.3% if used in
combination with the Diagnostic Interview for ADHD in
adults (DIVA).
Consistent with the results just mentioned about the use-
fulness of combined approach (e.g., a CPT with a clinical
diagnostic instrument), Nikolas et al. (2019) used a large
subset of neuropsychological tests at clinical evaluation of
ADHD, comparing the performance of the ADHD group,
not under stimulants during the cognitive testing, to a group
with unipolar depression and a healthy control group. All
patients underwent a clinical evaluation for depressive and
anxious symptoms through the BDI and BAI scales,
6 Journal of Attention Disorders 00(0)
showing comparable levels of anxiety between the ADHD
and clinical groups but significantly different levels of
depressive symptoms, significantly major for the latter, even
when no codified ADHD comorbidities were specified.
Results of the stepwise binary logistic regression analysis of
ADHD performance versus depressed patients, revealed that
worse performance on the episodic verbal learning CVLT
short-delay free recall and TOVA reaction time were associ-
ated with membership in the ADHD group, with a classifica-
tion accuracy of 70.4%. Moreover, the authors calculated cut
scores for six measures (CVLT short delay free recall,
Salthouse Listening Span trials, DKEFS inhibition/switch-
ing, TOVA reaction time variability, reaction time, and omis-
sion errors) that maximized sensitivity and specificity for
each of it in predicting ADHD group membership and next
evaluated the utility of using these cut scores in combination
with rating scale information’s. Of the six neuropsychologi-
cal measures, TOVA allowed the combined approach to
reach the 87% of classification accuracy.
Exploring neuropsychological functioning of individu-
als at clinical evaluation of adult ADHD with the Test bat-
tery Cognitive Functions ADHD (CFADHD) of the Vienna
Test System (VTS), Guo et al. (2021) recorded no meaning-
ful differences between patients with ADHD and the clini-
cal comparison group (CCG). At the evaluation, ADHD
patients showed psychiatric comorbidities (see Table 1), but
no information was provided about the diagnostic criteria or
the ADHD treatment status. In line with this, 1 year later
and on an independent sample with similar features (comor-
bidities/treatment), the same authors found no difference in
neurocognitive measures between the study groups, except
for the number of omissions in the vigilance test (Guo et al.,
2022).
Discussion
The purpose of this paper was to conduct a literature review
on the discriminative ability of neuropsychological objec-
tive measures in the diagnosis of adult ADHD when com-
pared to a clinical sample.
Guidelines vary on the importance of including a neuro-
psychological evaluation to establish the diagnosis (Canadian
ADHD Resource Alliance [CADDRA], 2018; Fuermaier et
al., 2019; National Collaborating Centre for Mental Health,
2009) and the role of objective neuropsychological tests in
the adult ADHD diagnostic algorithm is still debated
(Barkley & Murphy, 2010; Barkley, 2019; Mapou, 2019).
According to the literature, neuropsychological tasks
have high sensitivity and specificity in distinguishing
ADHD patients from healthy controls (Barkley &
Grodzinsky, 1994; Doyle et al., 2000; Lovejoy et al., 1999);
however, the role of neuropsychological measurements in
distinguishing ADHD patients from other psychiatric
patients is inconsistent.
To date, there is no current support for any single test or
battery of neuropsychological tests that can satisfactorily
distinguish between individuals with ADHD and those with
other psychiatric diagnoses.
Two large studies of Guo et al. (2021, 2022) showed no
differences in neuropsychological impairments in ADHD
sample compared to other psychiatric patients, displaying
how neuropsychological impairments are prominent in psy-
chiatric outpatients seeking a clinical evaluation of adult
ADHD but are not specific for ADHD itself. Indeed, the
difference recorded in the two studies (Guo et al., 2021,
2022) in the omission errors of the CFADHD of VTS high-
lights how the neurocognitive measures are inconsistent
and conflicting in the diagnostic assessment. However,
given the potential influence of psychostimulant treatment,
the lack of difference between groups should be discussed.
In fact, the authors make no mention of whether or not the
ADHD patients were receiving any kind of treatment.
Previous studies on the effects of psychostimulants on cog-
nitive functions have yielded conflicting results (Bron et al.,
2014; Tucha et al., 2011). For example, methylphenidate
has been shown in ADHD patients to be effective in improv-
ing attention (Hadar et al., 2021) and other higher-order
cognitive functions (Butzbach et al., 2019; Fuermaier et al.,
2017; Rubio Morrell & Hernández Expósito, 2019), poten-
tially reducing the cognitive gap between ADHD and non-
ADHD patients. Nevertheless, even if in a small sample,
Holst and colleagues highlighted how including partici-
pants on medication did not appears to significantly affect
the results; indeed, the authors conducted some comple-
mentary analyses excluding patients on medications and
found only small differences between the two groups (Holst
et al., 2013). Furthermore, the observation of similar pat-
terns of neuropsychological functions between ADHD and
other psychiatric patients could be supported by the view of
ADHD as dimensional construct, with ADHD-like symp-
toms and impairments occurring in large proportion of the
general psychiatric population (McLennan, 2016).
Even studies on free-stimulant ADHD samples that
found differences in objective neuropsychological mea-
sures, highlighted a general lack of specificity in distin-
guishing ADHD patients from other psychiatric patients
(Edebol et al., 2012; Fasmer et al., 2016; Holst & Thorell,
2013; Pettersson et al., 2018). Thus, these studies concluded
that the performance on neuropsychological tests indepen-
dently from treatment status may have limited incremental
value in supporting the psychiatric differential diagnosis.
A possible exception might be the Continuous Per­
formance Tests (e.g., the CPTII or TOVA test), a widely used
neuropsychological approach to assess attentional deficits
troughs the evaluation of omission or commission errors, the
reaction time and its variability. Indeed, in a combined
approach with clinical interview instruments, a continuous
performance test appears to be capable of distinguishing
Rosso et al.
individuals with adult ADHD from mixed clinical control
groups (Fasmer et al., 2016; Marshall et al., 2016; Nikolas et
al., 2019; Pettersson et al., 2018). In particular, parameters
belonging to the Inattention item (i.e., Omission Errors and
RT Variability) of the QBTest Plus (Qb+), a CPT combining
also the evaluation of the motor activity, has shown high
specificity in differentiating the two cohort of patients
(Edebol et al., 2012; Söderström et al., 2014). This makes
CPTs, in combination with clinical interviews, potentially
promising tools for assessing the core symptoms of ADHD
in psychiatric patients.
The findings of this review should be considered under
certain limitations.
First of all, ADHD patients had comorbid psychiatric
disorders in almost all of the studies examined (Edebol et
al., 2012; Fasmer et al., 2016; Guo et al., 2021, 2022; Holst
& Thorell, 2013; Marshall et al., 2016; Pettersson et al.,
2018; Söderström et al., 2014). These may have affected the
cognitive performance of the patients, making it difficult to
isolate the contribution of other conditions from the effect
of ADHD itself. However, in clinical practice the comorbid-
ity between ADHD and other psychiatric disorders is usual,
as confirmed by epidemiological studies (Haavik et al.,
2010; Katzman et al., 2017). Patients seeking evaluation for
ADHD frequently exhibit overlapping symptoms with other
disorders, such as anxiety or depression, making differen-
tial diagnosis one of the major challenges in the diagnostic
assessment (Luo et al., 2019; McGough et al., 2005;
Whlstedt et al., 2009). Therefore, the samples of the studies
included in this review are representative of real-world
adult patients with ADHD.
Moreover, in the majority of these studies, the comorbid-
ity rates between the ADHD group and the control group
are similar (Fasmer et al., 2016; Guo et al., 2022; Pettersson
et al., 2018; Söderström et al., 2014), supporting the hypoth-
esis that any potential group differences that occurred in
cognitive performances are attributable to ADHD.
Second, the studies described here were not always com-
parable because of differences in methodologies (e.g., neuro-
cognitive batteries versus single objective cognitive measures).
Third, most studies have been performed in small samples and
the clinical control group were often heterogeneous or not
well identified by defined diagnostic criteria. Moreover, as
previously discussed, ADHD patients on medication with
central stimulants were sometimes mixed together with drug-
naive ones (Guo et al., 2021, 2022), making the results less
solid as previous studies have found that pharmacological
treatments improve cognitive performance (e.g., Aron et al.,
2003; Boonstra et al., 2005). Lastly, ADHD has been col-
lapsed into one diagnostic group without analyzing cognitive
function in different subtypes (inattentive, hyperactive and
combined). In fact, different subtypes of ADHD may correlate
differently with neurocognitive measures, affecting the degree
of sensitivity and specificity of the instruments (Salvi et al.,
2019).
7
In conclusion, the role of neurocognitive assessment in
the diagnosis of adult ADHD should be deepened.
The results of this review highlights that up to date no
specific test or structured neurocognitive batteries are use-
ful to discriminate between patients with adult ADHD and
patients with other psychiatric disorders. However, despite
the stated limitations, some continuous performance test
items have shown promising sensitivity and specificity in
helping to identify adult patients with ADHD.
Even in light of the high rate of psychiatric comorbidi-
ties acting as possible confounders, additional efforts are
needed to develop objective measures targeted to the core
and specific domains of ADHD, perhaps by combining dif-
ferent CPTs items with evidence supporting their discrimi-
native power. Further prospective, controlled studies on
larger samples, conducted with a more rigorous methodol-
ogy in defining the ADHD group and the clinical control
group, are needed to give a definitive answer on whether or
not cognitive assessment is useful in the differential diagno-
sis of adult ADHD.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
ORCID iDs
Caterina Portaluppi https://orcid.org/0000-0002-1984-7346
Elena Teobaldi https://orcid.org/0000-0003-0806-057X
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Author Biographies
Gianluca Rosso, MD, PhD, psychiatrist, is Associate Professor of
psychiatry at Department of Neurosciences, University of Turin,
Italy. He is currently working at Psychiatric Unit of San Luigi
Gonzaga University Hospital of Orbassano (Turin), Italy.
Caterina Portaluppi clinical psychologist, is research scholar-
ship recipient at Department of Neurosciences, University of
Turin, Italy. She is currently working at Psychiatric Unit of San
Luigi Gonzaga University Hospital of Orbassano (Turin), Italy.
Elena Teobaldi, MD, psychiatrist, is PhD student in Neuroscience
at Department of Neurosciences, University of Turin, Italy.
Gabriele Di Salvo, MD, PhD, psychiatrist, is Researcher in psy-
chiatry at Department of Neurosciences, University of Turin,
Italy. He is currently working at Psychiatric Unit of San Luigi
Gonzaga University Hospital of Orbassano (Turin), Italy.
Giuseppe Maina, MD, psychiatrist, is Full Professor of psychia-
try at Department of Neurosciences, University of Turin, Italy. He
is the head of the Psychiatric Unit of San Luigi Gonzaga University
Hospital of Orbassano (Turin), Italy.