Neuropsychological Studies of Late Onset and

Subthreshold Diagnoses of Adult Attention-Deficit/

Hyperactivity Disorder
Stephen V. Faraone, Joseph Biederman, Alysa Doyle, Kate Murray, Carter Petty, Joel J. Adamson,
and Larry Seidman
Background: Diagnosing attention-deficit/hyperactivity disorder (ADHD) in adults is difficult when the diagnostician cannot
establish an onset prior to the DSM-IV criterion of age 7 or if the number of symptoms recalled does not achieve the DSM-IV threshold
for diagnosis. Because neuropsychological deficits are associated with ADHD, we addressed the validity of the DSM-IV age at onset and
symptom threshold criteria by using neuropsychological test scores as external validators.
Methods: We compared four groups of adults: 1) full ADHD subjects met all DSM-IV criteria for childhood-onset ADHD; 2) late-onset
ADHD subjects met all criteria except the age at onset criterion; 3) subthreshold ADHD subjects did not meet full symptom criteria; and
4) non-ADHD subjects did not meet any of the above criteria.
Results: Late-onset and full ADHD subjects had similar patterns of neuropsychological dysfunction. By comparison, subthreshold
ADHD subjects showed few neuropsychological differences with non-ADHD subjects.
Conclusions: Our results showing similar neuropsychological underpinning in subjects with late-onset ADHD suggest that the DSM-IV
age at onset criterion may be too stringent. Our data also suggest that ADHD subjects who failed to ever meet the DSM-IV threshold
for diagnosis have a milder form of the disorder.

Key Words: Attention deficit disorder (ADD), attention-deficit/hy-
peractivity disorder (ADHD), neuropsychology, diagnosis, adult,
subthreshold
to the age of 7 years. This age at onset criterion (AOC) was
selected based on clinical experience but had not been validated
(Barkley and Biederman 1997). The scant empirical data avail-
able question the validity of the AOC. One study comparing
teenagers with onset before or after age 13 found no link

P
ediatricians and child psychiatrists and psychologists reg-
between age at onset and severity of symptoms, types of
ularly diagnose and treat attention-deficit/hyperactivity
adjustment difficulties, or the persistence of the disorder
disorder (ADHD) in children (Faraone 2005), but recogni-
(Schaughency et al 1994). Rohde et al (2000) compared clinical
tion of ADHD in adulthood has faced many obstacles. Diagnos-
features between adolescents meeting full criteria for ADHD and
ing ADHD in adults requires clinicians to obtain an accurate
those meeting all criteria except the AOC. Because these two
retrospective diagnosis of childhood-onset ADHD (Adler and
groups had similar profiles of clinical features, the authors
Chua 2002), and although some studies suggest these retrospec-
concluded that the DSM-IV age at onset criterion should be
tive diagnoses are valid (Biederman et al 1990; Faraone et al
revised. In an epidemiologically ascertained sample of adoles-
2000; Murphy and Schachar 2000), others question their validity
cents, Willoughby et al (2000) found that adolescents meeting
(Mannuzza et al 2002; Shaffer 1994). As a result, despite data
full criteria for combined type ADHD had worse clinical out-
showing adult ADHD to have a high prevalence (Faraone and
comes than those failing to meet the AOC but found no
Biederman 2005; Kessler et al 2006) and well described neuro-
differences attributable to the AOC for the inattentive subtype of
biological features (Faraone 2004a, 2004b), adult ADHD has not
ADHD. In the DSM-IV field trials, requiring an AOC of 7 years
received the same level of clinical attention as pediatric ADHD,
reduced the accuracy of identifying currently impaired cases of
leading to low levels of identification and treatment (Faraone
ADHD and reduced agreement with clinician judgments (Apple-
2000; Faraone et al 2004). Two particularly vexing diagnostic
gate et al 1997).
questions are: 1) should the age at onset criterion of ADHD be
When making the diagnosis of ADHD in adults, clinicians
modified when making the adult diagnosis; and 2) should
must establish that diagnostic criteria for the disorder were met in
changes be made to the diagnostic items and symptom count
childhood. Because the passage of time may make the onset of
thresholds when making retrospective diagnoses of ADHD in
symptoms as well as symptoms themselves difficult to recall, it is
adults?
possible that the threshold for caseness should be lowered when
Several studies of children and adolescents have challenged
making these retrospective diagnoses. However, since lowering
the validity of the DSM-IV requirement that ADHD onset be prior
symptom thresholds would likely increase the risk for false-
positive diagnoses, systematic research is needed to address this
From the Department of Psychiatry and Behavioral Sciences (SVF), SUNY
issue.
Upstate Medical University, Syracuse, New York; and Department of We previously addressed the validity of the DSM-IV age at
Psychiatry (SVF, JB, AD, KM, CP, JJA, LS), Harvard Medical School, Massa- onset and symptom threshold criteria by comparing four groups
chusetts General Hospital, Pediatric Psychopharmacology Unit, Yawkey of adults: 1) full ADHD subjects met all DSM-IV criteria for
Center for Outpatient Care, Boston, Massachusetts. childhood-onset ADHD; 2) late-onset ADHD subjects met all
Address reprint requests to Stephen V. Faraone, Ph.D., SUNY Upstate Medi- criteria except the AOC; 3) subthreshold ADHD subjects had
cal University, Department of Psychiatry and Behavioral Sciences, 750 three or more inattentive or three or more hyperactive/impulsive
East Adams Street, Syracuse, NY 13210; E-mail: faraones@upstate.edu. symptoms without meeting full criteria for ADHD (we chose
Received September 6, 2005; revised March 9, 2006; accepted March 14, these cutoffs based on our prior work [Biederman et al 2000]);
2006. and 4) non-ADHD subjects did not meet any of the above criteria

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doi:10.1016/j.biopsych.2006.03.060 © 2006 Society of Biological Psychiatry
1082 BIOL PSYCHIATRY 2006;60:1081–1087
(Faraone et al, in press). We found that late-onset and full ADHD
subjects had similar patterns of psychiatric comorbidity, func-
tional impairment, and familial transmission. By comparison,
subthreshold ADHD was milder and showed a differing pattern
of familial transmission. These data suggested that late-onset
adult ADHD was valid and that in some cases, subthreshold
ADHD might be a milder form of the disorder.
This article extends our prior work by examining the neuro-
psychological functioning of these ADHD groups. A large em-
pirical literature has documented the presence of neuropsycho-
logical impairments in individuals with ADHD. In youth,
impairments of moderate effect sizes have been found in atten-
tion, executive functions, and processing speed (Willcutt et al
2005). Although there have been fewer studies of adults, reviews
suggest that adults with this diagnosis show impairments similar
to those found in children and adolescents (Hervey et al 2004;
Seidman et al 2005), although a recent meta-analysis has raised
some questions regarding the magnitude of the executive deficit
in adults with ADHD (Schoechlin and Engel 2005). Based on our
prior work, we hypothesized that late-onset ADHD would show
a pattern of neuropsychological dysfunction similar to that seen
for full ADHD. We further hypothesized that subthreshold ADHD
would not show a pattern of dysfunction similar to that seen for
full ADHD.
Methods and Materials
Subjects
Men and women between the ages of 18 and 55 were eligible
for the study. We excluded potential subjects if they had major
sensorimotor handicaps (deafness, blindness), psychosis, inade-
quate command of the English language, or a full-scale intelli-
gence quotient (IQ) less than 75. No ethnic or racial group was
excluded. We used two ascertainment sources to recruit ADHD
subjects: 1) referrals to psychiatric clinics at the Massachusetts
General Hospital (MGH); and 2) advertisements in the greater
Boston area. We recruited potential non-ADHD subjects through
advertisements in the greater Boston area. After receiving thor-
ough verbal and written explanations of all study procedures,
subjects provided written informed consent under procedures
approved by the Institutional Review Board of Massachusetts
General Hospital.
Assessment Measures
We interviewed all subjects about adult-onset diagnoses with
the Structured Clinical Interview for DSM-IV (First et al 1997) and
about childhood-onset diagnoses with modules from the Sched-
ule for Affective Disorders and Schizophrenia for School-Age
Children, Epidemiologic Version (Kiddie SADS-E) (Orvaschel
1994). Initial diagnoses were prepared by the study interviewers
and were then reviewed by a diagnostic committee of board-
certified child and adolescent psychiatrists or licensed psychol-
ogists. The diagnostic committee was blind to the subject’s
ascertainment group and all nondiagnostic data (e.g., cognitive
functioning). Diagnoses were made for two points in time:
lifetime and current (past month).
The interviewers had been instructed to take extensive notes
about the symptoms for each disorder. These notes and the
structured interview data were reviewed by the diagnostic com-
mittee so that the committee could make a best estimate diag-
nosis as described by Leckman et al (1982). Definite diagnoses
were assigned to subjects who met all diagnostic criteria. Diag-
noses were considered definite only if a consensus was achieved
www.sobp.org/journal
S.V. Faraone et al
that criteria were met to a degree that would be considered
clinically meaningful. By clinically meaningful, we mean that
the data collected from the structured interview indicated that
the diagnosis should be a clinical concern due to the nature
of the symptoms, the associated impairment, and the coherence
of the clinical picture.
Using the methods of Sattler (1988), we estimated full-scale IQ
from the vocabulary and block design subtests of the Wechsler
Adult Intelligence Scales-Third Edition (WAIS-III) (Wechsler
1997). Our interviewers assessed academic achievement with the
arithmetic and reading subtests of the Wide Range Achievement
Test-Third Edition (WRAT-III) (Jastak and Jastak 1993). The
definition of learning disabilities under Public Law 94-142 re-
quires a significant discrepancy between a child’s potential and
achievement (United States Office of Education 1977). Recom-
mended by Reynolds (1984), we used a statistically corrected
discrepancy between IQ and achievement to define learning
disability.
We used a battery of neuropsychological tests to assess
different components of executive functions commonly found to
be impaired in ADHD youth (Willcutt et al 2005). These compo-
nents included vigilance and distractibility, planning and organi-
zation, interference control, set shifting and categorization, se-
lective attention, visual scanning, and verbal learning. The tests
and variables utilized were: 1) the copy organization and delay
organization of the Rey-Osterrieth Complex Figure (Osterrieth
1944; Rey 1941), scored by the Waber-Holmes method (Bern-
stein and Waber 1996), which are meant to test planning and
organization; 2) an auditory continuous performance test devel-
oped by one of the authors (L.S.) (Seidman et al 1998b) to assess
working memory; 3) perseverative errors and loss of set of the
computerized Wisconsin Card Sorting test (WCST) (Heaton et al
1993), which measures reasoning ability, concept formation, and
cognitive flexibility; 4) the total words learned on the California
Verbal Learning Test-Second Edition (CVLT-II) (Delis et al 2000),
which is intended to be an index of left prefrontal systems, as
well as a measure of verbal learning and working memory; 5) the
color-word raw score of the Stroop test (Golden 1978), which is
meant to measure response inhibition; and 6) the arithmetic and
digit span subtests of the WAIS-III to further assess attention and
working memory.
Additionally, we developed a global measure of neuropsy-
chological dysfunction based on previous analyses (Biederman
et al 2006), linking neurocognitive deficits to functional impair-
ment. Here, our operational definition of executive function
deficits (EFD) was based on two or more measures in which the
individual scored below 1.5 standard deviations of control
subjects. For this global measure of EFD, we used a linear
combination of oral arithmetic and digit span as a single score,
again for consistency with previous analyses (Biederman et al
2004).
The interviewers were blind to the subject’s baseline ascer-
tainment group, the ascertainment site, and all prior assessments.
The interviewers had undergraduate degrees in psychology and
were extensively trained. First, they underwent several weeks of
classroom style training, learning interview mechanics, diagnos-
tic criteria, and coding algorithms. Then, they observed inter-
views by experienced raters and clinicians. They subsequently
conducted at least six practice (nonstudy) interviews and at least
three study interviews while being observed by senior inter-
viewers. Trainees were not permitted to conduct interviews
independently until they executed at least three interviews
that achieved perfect diagnostic agreement with an observing
S.V. Faraone et al BIOL PSYCHIATRY 2006;60:1081–1087 1083

Table 1. Demographic Features

Not ADHD Subthreshold ADHD Late-Onset ADHD Full ADHD

(n ⫽ 123) (n ⫽ 41) (n ⫽ 79) (n ⫽ 127) Test Statistic Omnibus p-Value

Age (Mean ⫾ SD) 29.9 ⫾ 9.0 35.5 ⫾ 9.1a,b 36.5 ⫾ 10.8a,b 36.1 ⫾ 10.8a,b F(3,366) ⫽ 10.89 ⬍.001
Age of Onset (Mean ⫾ SD) — — 10.2 ⫾ .7 4.4 ⫾ .2 t ⫽ 10.1 ⬍.001
Number of Males (%) 56 (46) 23 (56) 38 (48) 67 (53) ␹2(3) ⫽ 2.09 .55
Marital Status, n (%) ␹2(12) ⫽ 9.45 .66
Never Married 93 (77) 20 (53) 43 (56) 72 (59)
Married Once 19 (16) 12 (32) 21 (27) 32 (26)
Divorced 6 (5) 4 (11) 8 (10) 13 (11)
Divorced and Remarried 3 (2) 2 (5) 5 (6) 5 (4)
Widowed 0 (0) 0 (0) 0 (0) 1 (1)
ADHD, attention-deficit/hyperactivity disorder.
a
For pairwise comparison versus control subjects.
b
p ⱕ .001.

senior interviewer. A senior investigator (J.B.) supervised the
interviewers throughout the study. We computed kappa coef-
ficients of agreement by having experienced, board certified
child and adult psychiatrists and licensed clinical psychologists
diagnose subjects from audio taped interviews. Based on 500
assessments from interviews of children and adults, the median
kappa coefficient was .98. Kappa coefficients for individual
diagnoses included ADHD (.88), conduct disorder (1.0), major
depression (1.0), mania (.95), separation anxiety (1.0), agorapho-
bia (1.0), panic (.95), substance use disorder (1.0), and tics/
Tourette’s (.89).
Statistical Analyses
Based on the retrospective reports of ADHD symptoms, we
classified subjects into the following lifetime diagnostic catego-
ries. Full ADHD was defined as meeting full DSM-IV criteria for
ADHD with onset of some symptoms prior to age 7 (n ⫽ 127).
Late-onset ADHD was defined as meeting full DSM-IV criteria for
ADHD except for the age at onset criterion (n ⫽ 79). Subthresh-
old ADHD was defined as never having met DSM-IV criteria for
ADHD and reporting a chronic history of three or more inatten-
tive symptoms or three or more hyperactive-impulsive symptoms
(n ⫽ 41). The remaining subjects were defined as non-ADHD
(n ⫽ 123). We first compared the four groups of subjects on
potentially confounding demographic variables. Then we exam-
ined differences in neuropsychological functioning between the
four groups while controlling for potential demographic con-
founds. Our analyses used logistic regression for binary out-
comes, ordinal logistic regression for ordinal outcomes, multino-
mial logistic regression for categorical outcomes, and Gaussian
regression for continuous outcomes. For our analyses of execu-
tive function deficits, we used Poisson regression to analyze the
number of impaired tests between the four groups. We used the
.01 alpha level to assert statistical significance for omnibus tests.
If that was significant, we used the .05 alpha level to assert
significance for pairwise comparisons.
Results
Table 1 shows that the four comparison groups did not differ
in gender or marital status. Because subjects without ADHD were
significantly younger, subsequent analyses were corrected for
group differences in age. Table 2 presents mean intellectual test
scores. The four groups did not differ significantly in WRAT-III
reading or digit span scores. In contrast, we found significant
differences for the WRAT-III arithmetic as well as estimated
verbal, performance, and full-scale IQ. Pairwise comparisons
showed that for all test scores, except WRAT-III reading, the
late-onset subgroup showed worse performance than the non-
ADHD subgroup. Compared with control subjects, the full
ADHD group showed worse performance on WRAT-III arith-
metic and the subthreshold group was worse on WRAT-III
arithmetic and verbal IQ. The only significant differences among
ADHD subgroups were the higher verbal, performance, and
full-scale IQ scores among full ADHD compared with late-onset
ADHD subjects and lower performance IQ among late-onset
subjects compared with subthreshold subjects.
Table 3 shows test scores for the other neuropsychological
tests. The strongest evidence for executive dysfunction was seen
among the full ADHD subjects. Nevertheless, subjects with

Table 2. Intelligence and Achievement Test Scores of Subjects

Not ADHD Subthreshold ADHD Late-Onset ADHD Full ADHD

(n ⫽ 123) (n ⫽ 41) (n ⫽ 79) (n ⫽ 127) ␹2(3) p-Value

WRAT Reading 108.4 ⫾ 8.7 104.1 ⫾ 10.5 104.0 ⫾ 9.2 106.1 ⫾ 10.5 7.08 .07
WRAT Arithmetic 106.8 ⫾ 12.5 98.2 ⫾ 14.4a,e 95.0 ⫾ 12.7a,d 98.4 ⫾ 14.4a,d 25.28 ⬍.001
Full Scale IQ 116.2 ⫾ 12.6 111.0 ⫾ 13.3 106.6 ⫾ 13.1a,d 114.3 ⫾ 14.3 18.42 ⬍.001
Performance IQ 110.0 ⫾ 14.2 107.5 ⫾ 13.0 101.3 ⫾ 13.5a,b,e,f 108.5 ⫾ 16.3c,e 12.78 .005
Verbal IQ 119.0 ⫾ 13.2 112.0 ⫾ 14.6a,f 109.8 ⫾ 13.7a,d 116.7 ⫾ 14.6c,d 16.02 .001
ADHD, attention-deficit/hyperactivity disorder; WRAT-III, Wide Range Achievement Test-Third Edition; IQ, intelligence quotient.
a
For pairwise comparison versus Control subjects.
b
For pairwise comparison versus Subthreshold ADHD.
c
For pairwise comparison versus Late-Onset ADHD.
d
p ⱕ .001.
e
p ⱕ .01.
f
p ⱕ .05.

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1084 BIOL PSYCHIATRY 2006;60:1081–1087 S.V. Faraone et al

Table 3. Neuropsychological Test Scores by Diagnosis

No ADHD Subthreshold ADHD Late-Onset ADHD Full ADHD

(n ⫽ 123) (n ⫽ 39) (n ⫽ 78) (n ⫽ 123) Statistic p-Value

Stroop Test T-Scores

Word 47.9 ⫾ 8.2 48.3 ⫾ 8.6 44.9 ⫾ 7.6a,b 46.5 ⫾ 8.7 F(3,354) ⫽ 3.06 .03
Color 46.5 ⫾ 8.0 44.3 ⫾ 8.0 43.4 ⫾ 8.6a,b 43.9 ⫾ 7.3a,b F(3,353) ⫽ 2.89 .04
Color-Word 52.1 ⫾ 10.3 48.0 ⫾ 10.0 46.3 ⫾ 9.4a,b 46.4 ⫾ 9.8a,b F(3,352) ⫽ 5.86 ⬍.001
Interference 53.9 ⫾ 8.2 50.8 ⫾ 8.1 50.8 ⫾ 7.8 50.2 ⫾ 7.8a,b F(3,352) ⫽ 2.63 .05
Wisconsin Card Sorting Task
Categories 5.6 ⫾ 1.2 5.2 ⫾ 1.6 5.2 ⫾ 1.7 5.3 ⫾ 1.6 F(3,349) ⫽ .48 .70
No. Trials 87.5 ⫾ 19.4 99.6 ⫾ 22.3a,b 99.4 ⫾ 21.0a,b 97.8 ⫾ 21.7a,b F(3,349) ⫽ 4.23 .006
No. Correct 68.1 ⫾ 8.8 72.2 ⫾ 9.2a,b 71.4 ⫾ 11.4a,b 72.1 ⫾ 11.4a,b F(3,349) ⫽ 3.87 .01
California Verbal Learning Test
Total Correct 57.5 ⫾ 10.0 54.4 ⫾ 10.5 52.2 ⫾ 9.4a,b 53.9 ⫾ 10.4 F(3,353) ⫽ 3.25 .02
Semantic Total 23.1 ⫾ 13.1 20.3 ⫾ 11.8 16.7 ⫾ 9.3a,b 19.2 ⫾ 11.9 F(3,353) ⫽ 3.90 .009
Serial Total 5.1 ⫾ 4.3 4.1 ⫾ 3.2 4.8 ⫾ 3.6 4.7 ⫾ 3.3 F(3,353) ⫽ .60 .62
Rey-Osterreith
Copy Organization 10.4 ⫾ 2.8 9.5 ⫾ 3.2 9.7 ⫾ 3.0 8.9 ⫾ 3.4a,b F(3,354) ⫽ 3.09 .03
Copy Style 3.1 ⫾ 1.1 2.7 ⫾ 1.2 3.0 ⫾ 1.1 2.8 ⫾ 1.1 F(3,354) ⫽ 1.97 .12
Copy Accuracy 63.6 ⫾ 1.2 63.6 ⫾ .9 63.0 ⫾ 2.1 67.9 ⫾ 52.1 F(3,354) ⫽ .53 .66
Copy Time 146.7 ⫾ 44.7 148.4 ⫾ 40.6 161.3 ⫾ 62.9 152.3 ⫾ 47.4 F(3,357) ⫽ 1.00 .39
Delay Organization 9.0 ⫾ 4.0 8.0 ⫾ 3.7 7.9 ⫾ 3.9 7.6 ⫾ 3.9 F(3,354) ⫽ 1.51 .21
Delay Style 2.5 ⫾ .8 2.3 ⫾ .8 2.5 ⫾ .8 2.4 ⫾ .8 F(3,354) ⫽ .39 .76
Delay Accuracy 48.3 ⫾ 9.2 45.5 ⫾ 7.1 41.5 ⫾ 11.6a,b 44.3 ⫾ 10.1 F(3,354) ⫽ 3.61 .01
Delay Time 131.1 ⫾ 54.8 119.6 ⫾ 45.0 124.9 ⫾ 59.1 119.7 ⫾ 55.4 F(3,356) ⫽ 1.06 .36
Auditory CPT
Memory Correct 20.4 ⫾ 4.3 20.0 ⫾ 4.1 18.8 ⫾ 4.0 18.7 ⫾ 4.7 F(3,355) ⫽ 1.07 .36
Vigilance Correct 29.2 ⫾ 1.7 29.2 ⫾ 1.1 29.0 ⫾ 1.9 28.7 ⫾ 3.0 F(3,357) ⫽ 1.82 .14
Interference Correct 24.9 ⫾ 6.6 22.6 ⫾ 6.6 21.6 ⫾ 7.0 22.2 ⫾ 7.4 F(3,356) ⫽ 1.41 .24
WAIS-III Subtests of Attention
and Working Memory
Oral Arithmetic 11.9 ⫾ 2.4 10.2 ⫾ 3.0a,c 10.2 ⫾ 2.7a,d 10.8 ⫾ 2.9 13.16 .004
Digit Span 11.8 ⫾ 3.0 10.5 ⫾ 3.0 11.4 ⫾ 2.9 11.2 ⫾ 3.0 5.85 .12
ADHD, attention-deficit/hyperactivity disorder; CPT, continuous performance test; WAIS-III, Wechsler Adult Intelligence Scales-Third Edition.
a
For pairwise comparison versus Control subjects.
b
p ⱕ .001.
c
p ⱕ .01.
d
p ⱕ .05.

late-onset ADHD showed significant deficits on the Stroop test,
the Wisconsin Card Sorting test, the California Verbal Learning
Test, the Rey-Osterreith Complex Figure, and oral arithmetic. In
contrast, the subthreshold ADHD group only showed deficits on
the Wisconsin Cart Sorting Test and oral arithmetic. There were
no significant differences among the ADHD subgroups. Linear
regression showed a negative effect of ADHD onset age on
full-scale IQ [F (1,215) ⫽ 6.73, p ⫽ .01] and verbal IQ [F (1,215) ⫽
7.60, p ⫽ .006) among the ADHD groups.
The four groups also differed significantly in frequencies of
subjects showing EFD [␹2(3) ⫽ 17.2, p ⫽ .001], with subthreshold
ADHD (34.2% of subjects) and full ADHD (31.5% of subjects)
having the highest frequencies. Late-onset ADHD had a lower
frequency (26.6%) than subthreshold ADHD or full ADHD.
Non-ADHD had the smallest frequency of individuals showing
EFD (11.4%). There were no significant differences between the
ADHD subgroups in the frequency of subjects showing EFD
[␹2(2) ⫽ .90, p ⫽ .64]. We found a significant relationship
between group membership and the number of neuropsycho-
logical tests showing executive function impairment, controlling
for age of subjects [␹2(4) ⫽ 13.8, p ⫽ .003]: subthreshold ADHD
and full ADHD showed the highest average number of impaired
tests (1.2 ⫾ 1.3), with late-onset ADHD showing fewer impaired
tests (1.1 ⫾ 1.2) and non-ADHD showing the smallest number of
impaired tests (.6 ⫾ 1.1). We found no differences between the
three ADHD groups in the number of tests showing executive
function impairment.
Discussion
We have used neuropsychological outcomes to test hypoth-
eses about the DSM-IV diagnostic criteria for ADHD when
applied to the diagnosis of ADHD in adults. Our findings provide
further support for the idea that late-onset ADHD is valid and that
the DSM-IV age at onset criterion may be too stringent. In
contrast, the more limited neuropsychological differences be-
tween non-ADHD and subthreshold subjects suggest this group
of subjects may suffer from a milder form of the disorder or that
some may be valid cases and others not.
Both the full and late-onset ADHD groups showed more
impaired neuropsychological test scores than the non-ADHD
group. They also showed more impairment on an index of
executive function disorder, which we have validated in prior
work (Biederman et al 2004). These results confirm prior studies
showing academic and cognitive problems in ADHD youth
(Barkley et al 2001; Faraone et al 1993; Nigg et al 2002),
longitudinal studies of ADHD youth documenting the continua-
tion of intellectual deficits into adulthood (Fischer et al 1990;

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S.V. Faraone et al
Gittelman et al 1985; Hoy et al 1978; Weiss et al 1985), and
neuropsychological studies of ADHD adults (Hervey et al 2004;
Seidman et al 1998a; Taylor and Miller 1997; Weyandt et al 1998).
The mean IQ in each of our subgroups is above average,
indicating most subjects are not impaired in a normative sense.
Within this range of normal IQ, the late-onset and full ADHD
groups differed in estimated full scale, verbal, and performance
IQ scores, and in each case, the late-onset ADHD group per-
formed worse than the full ADHD group. This raises the intrigu-
ing possibility that late-onset ADHD may be a more cognitively
impaired form of adult ADHD. This idea is highly speculative,
given that the mean IQ scores were above average and no other
neuropsychological tests showed differences between late-onset
and full ADHD subjects.
Our data supporting the validity of late-onset ADHD are
consistent with a prior report from this sample (Faraone et al, in
press), which found that compared with full ADHD subjects,
late-onset subjects showed similar patterns of ADHD symptoms,
psychiatric comorbidity, and familial transmission. Taken to-
gether, our prior work, the present study, and other studies
reviewed suggest that the DSM-IV requirement of onset prior to
age 7 may be too stringent. When viewed in the light of these
studies, our data suggest that the DSM-IV criteria for ADHD
should be modified to allow for onset of symptoms in childhood
but after the age of 7. The range of late age at onset was wide
(age 7 to 45); 63% of the late-onset cases had an age at onset of
7, 8, or 9 years and 83% had onset in the age 7 to 12 range.
However, our study was not designed to determine what AOC
would be the most valid. Such a study would require sufficient
numbers of subjects for each age category to be considered as
potentially valid. Ideally, the next DSM field trial for ADHD
would incorporate such sampling considerations.
An alternative interpretation of our findings is that the DSM-IV
AOC for ADHD is correct but that due to recall biases, patients
that actually onset prior to age 7 report their ages at onset to be
greater than 7. If that idea is correct, then increasing the reliability
of the AOC assessment should decrease evidence for the validity
of late-onset ADHD. The reliability of an AOC assessment could
be increased by using multiple informants or by selecting adult
subjects from prospective follow-up studies. Although our study
cannot determine if such a bias exists, data from longitudinal
follow-up studies would be able to make that determination.
Although our data suggest that retrospective late-onset diag-
noses of ADHD in adults are valid, work by Mannuzza et al
(2002) suggests that any retrospective diagnosis of ADHD in
adults should be used cautiously in epidemiologic studies and
primary care settings. They followed 176 ADHD children and 168
children known to not have ADHD in childhood to a mean age
of 25. Eleven percent of subjects from the non-ADHD group
were retrospectively diagnosed as having had ADHD in child-
hood. They concluded that retrospective diagnoses might yield
many false positives among adults not referred for ADHD.
Subthreshold cases differed from control subjects in relatively
few test scores. Nevertheless, where differences were observed,
they were not small. For example, the subthreshold group
performed about one-third to a half standard deviation lower
than control subjects on WRAT-III arithmetic and verbal IQ. They
also showed few significant differences with the full ADHD
group. Our data about subthreshold ADHD are consistent with
our prior work (Faraone et al, in press), which showed modest
psychiatric comorbidity and an ambiguous pattern of familial
transmission. Although the relatively small sample size of the
subthreshold group clouds interpretation of these findings, both
BIOL PSYCHIATRY 2006;60:1081–1087 1085
studies suggest further work is needed to determine if subthresh-
old ADHD is severe enough to warrant clinical attention.
Our findings should be viewed in light of some methodolog-
ical limitations. The diagnoses of adult ADHD relied entirely on
the self-report of adult subjects. Although this method allowed us
to evaluate the validity of retrospective self-reports, these find-
ings may not generalize to diagnoses defined using data from
informants. As Barkley et al (2002) showed in a study of ADHD
youth followed into adulthood, informant reports can boost the
validity of diagnosing ADHD in adulthood.
The mean IQ scores of our ADHD and control subjects were
relatively high, which raises questions about generalizability.
These high scores are, however, consistent with our exclusion
criteria: we excluded subjects with a full-scale IQ less than 75.
Also, subjects with ADHD were excluded from our normal
control sample. Given that both social class (Matarazzo 1972) and
ADHD are predictive of intellectual functioning, our control
group should have higher than average full-scale IQ scores.
Furthermore, we estimated IQ scores from the vocabulary and
block design subtests, which do not specifically tap aspects of
executive functions. Had we used the full WAIS-III, which also
incorporates subtests more likely to be impacted by executive
dysfunction into IQ estimates (e.g., the arithmetic and digit span
subtests), IQ scores in our sample would likely have been lower.
Finally, the ascertainment of relatively high-functioning samples
is not unusual in studies of ADHD. For example, in the Welner et
al (1977) study, Wechsler Intelligence Scale for Children (WISC)
IQs were 115 for brothers of control subjects and 111 for sisters.
From their follow-up study of ADHD children, Mannuzza and
Gittelman (1984) report mean Wechsler Adult Intelligence Scale
(WAIS) IQs of 106 for ADHD male subjects and 110 for male
control subjects. O’Neill and Douglas (1991) found mean Pea-
body IQ scores of 115 and 114 for attention-deficit disorder with
hyperactivity (ADDH) and normal control children, respectively.
In the study by Frost et al (1989), the mean Wechsler Intelligence
Scale for Children-Revised (WISC-R) IQs were 98 and 109 for
attention-deficit disorder (ADD) and normal children, respec-
tively. In the Barkley et al (1990) report, these values were 106
and 114. Thus, the relatively high IQ scores of our sample are not
unusual. They indicate limits to the generalizability of our results
but do not suggest problems with the internal validity of our
research design.
Despite these limitations, our data suggest that the DSM-IV
age at onset criterion for ADHD may too stringent for the
diagnosis of adults. Although this requires more research, clini-
cians should not dismiss the diagnosis of ADHD in adults when
onset occurs later than allowed by DSM-IV, especially when the
onset age is no later than 12. More work is needed to better
characterize adults with a lifetime history of subthreshold symp-
toms and to determine if this relatively mild form of ADHD
warrants clinical attention.
This work was supported in part by grants to SVF from the
National Institutes of Health (R01MH57934) and McNeil Con-
sumer & Specialty Pharmaceuticals.
JB receives research support from the following sources: Shire
Laboratories Inc, Eli Lilly & Company, Pfizer Pharmaceutical,
Cephalon Pharmaceutical, Janssen Pharaceutical, Neurosearch
Pharmaceuticals, Stanley Medical Institute, Lilly Foundation,
Prechter Foundation, National Institute of Mental Health, Na-
tional Institute of Child Health and Human Development, and
National Institute of Drug Abuse.
JB is a speaker for the following speaker’s bureaus: Eli Lilly &
www.sobp.org/journal
1086 BIOL PSYCHIATRY 2006;60:1081–1087
Company, Pfizer Pharmaceutical, Novartis Pharmaceutical,
Wyeth Ayerst, Shire Laboratories Inc, McNeil Pharmaceutical,
and Cephalon Pharmaceutical.
JB is on the advisory board for the following pharmaceutical
companies: Eli Lilly & Company, CellTech, Shire Laboratories Inc,
Novartis Pharmaceutical, Noven Pharmaceutical, McNeil Phar-
maceuticals, Janssen, Johnson & Johnson, Pfizer, and Cephalon
Pharmaceuticals.
SVF receives research support from the following sources: McNeil
Consumer & Specialty Pharmaceuticals, Shire Laboratories, Eli Lilly
& Company, the National Institute of Mental Health, the National
Institute of Child Health and Human Development, and the Na-
tional Institute of Neurological Diseases and Stroke.
SVF is a speaker for the following speaker’s bureaus: Eli Lilly
& Company, McNeil Consumer & Specialty Pharmaceuticals,
and Shire Laboratories.
SVF has had an advisory or consulting relationship with the
following pharmaceutical companies: McNeil Consumer & Spe-
cialty Pharmaceuticals, Noven Pharmaceuticals, Shire Labora-
tories, and Eli Lilly & Company.
AD is a member of the McNeil speaker’s Bureau and has
served on the Eli Lilly Cognition advisory board.
Adler LA, Chua HC (2002): Management of ADHD in adults. J Clin Psychiatry
63:29 –35.
Applegate B, Lahey B, Hart E, Biederman J, Hynd G, Barkley R, et al (1997):
Validity of the age of onset criterion for attention-deficit/hyperactivity
disorder: A report from the DSM-IV field trials. J Am Acad Child Adolesc
Psychiatry 36:1211–1221.
Barkley R, Murphy K, Bush T (2001): Time perception and reproduction in
young adults with attention deficit hyperactivity disorder. Neuropsychol-
ogy 15:351–360.
Barkley RA, Biederman J (1997): Toward a broader definition of the age-of-
onset criterion for attention-deficit hyperactivity disorder [see com-
ments]. J Am Acad Child Adolesc Psychiatry 36:1204 –1210.
Barkley RA, DuPaul GJ, McMurray MB (1990): Comprehensive evaluation of
attention deficit disorder with and without hyperactivity as defined by
research criteria. J Consult Clin Psychol 58:775–798.
Barkley RA, Fischer M, Smallish L, Fletcher K (2002): The persistence of
attention-deficit/hyperactivity disorder into young adulthood as a func-
tion of reporting source and definition of disorder. J Abnorm Psychol
111:279 –289.
Bernstein JH, Waber DP (1996): Developmental Scoring System for the Rey-
Osterreith Complex Figure [Manual]. Odessa, FL: Psychological Assess-
ment Resources, Inc.
Biederman J, Faraone SV, Knee D, Munir K (1990): Retrospective assessment
of DSM-III attention deficit disorder in non-referred individuals. J Clin
Psychiatry 51:102–106.
Biederman J, Faraone SV, Spencer T, Mick E, Monuteaux MC, Aleardi M
(2006): Functional impairments in adults with self-reports of diagnosed
ADHD: A controlled study of 1,001 adults in the community. J Clin Psychi-
atry 67(4):524 –540.
Biederman J, Mick E, Faraone SV (2000): Age-dependent decline of symp-
toms of attention deficit hyperactivity disorder: Impact of remission
definition and symptom type. Am J Psychiatry 157:816 – 818.
Biederman J, Monuteaux M, Seidman L, Doyle AE, Mick E, Wilens T, et al
(2004): Impact of executive function deficits and ADHD on academic
outcomes in children. J Consult Clin Psychol 72:757–766.
Delis DC, Kramer JH, Kaplan E, Ober BA (2000): California Verbal Learning Test,
2nd ed. San Antonio, TX: The Psychological Corp.
Faraone SV (2000): Attention deficit hyperactivity disorder in adults: Impli-
cations for theories of diagnosis. Curr Dir Psychol Sci 9:33–36.
Faraone SV (2004a): Etiology and pathophysiology of adult attention deficit
hyperactivity disorder. Prim Psychiatry 11:28 – 40.
Faraone SV (2004b): Genetics of adult attention-deficit/hyperactivity disor-
der. Psychiatr Clin North Am 27:303–321.
Faraone SV (2005): The scientific foundation for understanding attention-
deficit/hyperactivity disorder as a valid psychiatric disorder. Eur Child
Adolesc Psychiatry 14:1–10.
www.sobp.org/journal
S.V. Faraone et al
Faraone SV, Biederman J (2005): What is the prevalence of adult ADHD?
Results of a population screen of 966 adults. J Atten Disord 9:384 –391.
Faraone SV, Biederman J, Feighner JA, Monuteaux MC (2000): Assessing
symptoms of attention deficit hyperactivity disorder in children and
adults: Which is more valid? J Consult Clin Psychol 68:830 – 842.
Faraone SV, Biederman J, Lehman BK, Spencer T, Norman D, Seidman L, et al
(1993): Intellectual performance and school failure in children with at-
tention deficit hyperactivity disorder and in their siblings. J Abnorm
Psychol 102:616 – 623.
Faraone SV, Biederman J, Spencer TJ, Mick E, Murray K, Petty C, et al (in press):
Diagnosing adult ADHD: Are late onset and subthreshold diagnoses
valid? Am J Psychiatry.
Faraone SV, Spencer T, Montano CB, Biederman J (2004): Attention deficit
hyperactivity disorder in adults: A survey of current practice in psychia-
try and primary care. Arch Intern Med 164:1221–1226.
First M, Spitzer R, Gibbon M, Williams J (1997): Structured Clinical Inter-
view for DSM-IV Axis I Disorders. Washington, DC: American Psychiatric
Press.
Fischer M, Barkley RA, Edelbrock CS, Smallish L (1990): The adolescent out-
come of hyperactive children diagnosed by research criteria: II. Aca-
demic, attentional, and neuropsychological status. J Consult Clin Psychol
58:580 –588.
Frost LA, Moffitt TE, McGee R (1989): Neuropsychological correlates of psy-
chopathology in an unselected cohort of young adolescents. J Abnorm
Psychol 98:307–313.
Gittelman R, Mannuzza S, Shenker R, Bonagura N (1985): Hyperactive boys
almost grown up: I. Psychiatric status. Arch Gen Psychiatry 42:937–947.
Golden CJ (1978): Stroop Color and Word Test: A Manual for Clinical and
Experimental Use. Chicago: Stoelting, Co.
Heaton RK, Chelune GJ, Talley JL, Kay GG, Curtiss G (1993): Wisconsin Card
Sort Test Manual: Revised and Expanded. Odessa, FL: Psychological As-
sessment Resources, Inc.
Hervey AS, Epstein J, Curry JF (2004): Neuropsychology of adults with atten-
tion-deficit/hyperactivity disorder: A meta-analytic review. Neuropsy-
chology 18:485–503.
Hoy E, Weiss G, Minde K, Cohen N (1978): The hyperactive child at adoles-
cence: Cognitive, emotional and social functioning. J Abnorm Child Psy-
chol 6:311–324.
Jastak J, Jastak S (1993): Wide Range Achievement Test, 3rd ed. Wilmington,
DE: Jastak Associates.
Kessler RC, Adler L, Barkley R, Biederman J, Conners CK, Demler O, et al
(2006): The prevalence and correlates of adult ADHD in the United
States: Results from the national comorbidity survey replication. Am
J Psychiatry 163(4):716 –723.
Leckman JF, Sholomskas D, Thompson D, Belanger A, Weissman MM (1982):
Best estimate of lifetime psychiatric diagnosis: A methodological study.
Arch Gen Psychiatry 39:879 – 883.
Mannuzza S, Gittelman R (1984): The adolescent outcome of hyperactive
girls. Psychiatry Res 13:19 –29.
Mannuzza S, Klein RG, Klein DF, Bessler A, Shrout P (2002): Accuracy of adult
recall of childhood attention deficit hyperactivity disorder. Am J Psychi-
atry 159:1882–1888.
Matarazzo JD (1972): Wechsler’s Measurement and Appraisal of Adult Intelli-
gence, 5th ed. New York: Oxford University Press.
Murphy P, Schachar R (2000): Use of self-ratings in the assessment of symp-
toms of attention deficit hyperactivity disorder in adults. Am J Psychiatry
157:1156 –1159.
Nigg JT, Butler K, Huang-Pollock CL, Henderson JM (2002): Inhibitory pro-
cesses in adults with persistent childhood onset ADHD. J Consult Clin
Psychol 70:153–157.
O’Neill ME, Douglas VI (1991): Study strategies and story recall in attention
deficit disorder and reading disability. J Abnorm Child Psychol 19:671–
692.
Orvaschel H (1994): Schedule for Affective Disorder and Schizophrenia for
School-Age Children Epidemiologic Version, 5th ed. Ft. Lauderdale, FL:
Nova Southeastern University, Center for Psychological Studies.
Osterrieth PA (1944): Le test de copie d’une figure complexe. Arch de Psy-
chologie 30:206 –256.
Rey A (1941): L’examen psychologique dans les cas d’encephalopathie trau-
matique. Les Arch de Psychologie 28:286 –340.
Reynolds CR (1984): Critical measurement issues in learning disabilities.
J Spec Educ 18:451– 476.
S.V. Faraone et al
Rohde LA, Biederman J, Zimmermann H, Schmitz M, Martins S, Tramontina S
(2000): Exploring ADHD age-of-onset criterion in Brazilian adolescents.
Eur Child Adolesc Psychiatry 9:212–218.
Sattler JM (1988): Assessment of Children, 3rd ed. San Diego: Jerome M.
Sattler.
Schaughency E, McGee R, Raja SN, Feehan M, Silva PA (1994): Self reported
inattention, impulsivity and hyperactivity at ages 15 and 18 in the gen-
eral population. J Am Acad Child Adolesc Psychiatry 33:173–184.
Schoechlin C, Engel RR (2005): Neuropsychological performance in adult
attention-deficit hyperactivity disorder: Meta-analysis of empirical data.
Arch Clin Neuropsychol 20:727–744.
Seidman L, Biederman J, Monuteaux M, Valera E, Doyle AE, Faraone S (2005):
Impact of gender and age on executive functioning: Do girls and boys
with and without attention deficit hyperactivity disorder differ neuro-
psychologically in pre-teen and teenage years? Dev Neuropsychol 27:79 –
105.
Seidman LJ, Biederman J, Weber W, Hatch M, Faraone SV (1998a): Neuropsy-
chological function in adults with attention-deficit hyperactivity disor-
der. Biol Psychiatry 44:260 –268.
Seidman LJ, Breiter HC, Goodman JM, Goldstein JM, Woodruff PW, O’Craven
K, et al (1998b): A functional magnetic resonance imaging study of
auditory vigilance with low and high information processing demands.
Neuropsychology 12:505–518.
BIOL PSYCHIATRY 2006;60:1081–1087 1087
Shaffer D (1994): Attention deficit hyperactivity disorder in adults. Am
J Psychiatry 151:633– 638.
Taylor CJ, Miller DC (1997): Neuropsychological assessment of attention in
ADHD adults. J Atten Disord 2:77– 88.
United States Office of Education (1977): Assistance to states for education
for handicapped children: Procedures for evaluating specific learning
disabilities. Federal Register 42:62082– 62085.
Wechsler D (1997): Wechsler Adult Intelligence Scale III [Manual], 3rd ed. San
Antonio, TX: The Psychological Corporation.
Weiss G, Hechtman L, Milroy T, Perlman T (1985): Psychiatric status of hyper-
actives as adults: A controlled prospective 15-year follow-up of 63 hy-
peractive children. J Am Acad Child Adolesc Psychiatry 24:211–220.
Welner Z, Welner A, Stewart M, Palkes H, Wish E (1977): A controlled study of
siblings of hyperactive children. J Nerv Ment Dis 165:110 –117.
Weyandt LL, Rice JA, Linterman I, Mitzlaff L, Emert E (1998): Neuropsycho-
logical performance of a sample of adults with ADHD, developmental
reading disorder, and controls. Dev Neuropsychol 14:643– 656.
Willcutt EG, Doyle AE, Nigg JT, Faraone SV, Pennington BF (2005): Validity of
the executive function theory of ADHD: A meta-analytic review. Biol
Psychiatry 57:1336 –1346.
Willoughby MT, Curran PJ, Costello EJ, Angold A (2000): Implications of early
versus late onset of attention-deficit/hyperactivity disorder symptoms.
J Am Acad Child Adolesc Psychiatry 39:1512–1519.
www.sobp.org/journal