European Psychiatry Toward operationalizing deficient emotional

www.cambridge.org/epa
self-regulation in newly referred adults with
ADHD: A receiver operator characteristic
curve analysis
Research Article
Cite this article: Biederman J, DiSalvo M, Joseph Biederman1,2, Maura DiSalvo1, K. Yvonne Woodworth1, Ronna Fried1,2,
Woodworth KY, Fried R, Uchida M, Biederman I,
Spencer TJ, Surman C, Faraone SV (2020).
Mai Uchida1,2, Itai Biederman1, Thomas J. Spencer1,2, Craig Surman1,2 and
Toward operationalizing deficient emotional Stephen V. Faraone3
self-regulation in newly referred adults with
ADHD: A receiver operator characteristic 1
Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital,
curve analysis. European Psychiatry, 63(1), e21,
1–9 https://doi.org/10.1192/j.eurpsy.2019.11 Boston, Massachusetts, USA; 2Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA and
3
Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, New York, USA
Received: 12 August 2019
Revised: 06 November 2019 Abstract
Accepted: 09 November 2019
Background. A growing body of research suggests that deficient emotional self-regulation
Key words: (DESR) is common and morbid among attention-deficit/hyperactivity disorder (ADHD)
ADHD; comorbidity; psychopharmacology
patients. The main aim of the present study was to assess whether high and low levels of DESR
Author for correspondence: in adult ADHD patients can be operationalized and whether they are clinically useful.
Joseph Biederman, Methods. A total of 441 newly referred 18- to 55-year-old adults of both sexes with Diagnostic
E-mail: [email protected] and Statistical Manual of Mental Disorders: Fifth Edition (DSM-5) ADHD completed self-
reported rating scales. We operationalized DESR using items from the Barkley Current Behavior
Scale. We used receiver operator characteristic (ROC) curves to identify the optimal cut-off on
the Barkley Emotional Dysregulation (ED) Scale to categorize patients as having high- versus
low-level DESR and compared demographic and clinical characteristics between the groups.
Results. We averaged the optimal Barkley ED Scale cut-points from the ROC curve analyses
across all subscales and categorized ADHD patients as having high- (N = 191) or low-level
(N = 250) DESR (total Barkley ED Scale score ≥8 or <8, respectively). Those with high-level
DESR had significantly more severe symptoms of ADHD, executive dysfunction, autistic
traits, levels of psychopathology, and worse quality of life compared with those with low-
level DESR. There were no major differences in outcomes among medicated and unmedi-
cated patients.
Conclusions. High levels of DESR are common in adults with ADHD and when present
represent a burdensome source of added morbidity and disability worthy of further clinical
and scientific attention.

Introduction
Symptoms of low frustration tolerance, impatience, and quickness to anger have long been
associated with ADHD [1–3], and emotional symptoms deficits in emotional regulation have
been included as associated features of ADHD in the DSM [4]. Yet, there has been limited
research on the subject.
Barkley has argued that the emotional symptoms associated with ADHD are the result
of a weak self-regulatory process in ADHD that leads to emotionally reactive behavior
© The Author(s) 2020. This is an Open Access [2,5] and termed it deficient emotional self-regulation (DESR) to distinguish it from
article, distributed under the terms of the mood disorders. Using selected items from the Barkley Current Behavior Scale (CBS), we
Creative Commons Attribution-NonCommercial- previously reported that 61% of adults with ADHD had DESR of greater severity than
ShareAlike licence (http://creativecommons.org/ 95% of controls [6] and when present, it was associated with significant functional
licenses/by-nc-sa/4.0/), which permits non-
commercial re-use, distribution, and
impairments. Although these data suggest that DESR is common and morbid at the
reproduction in any medium, provided the group level, uncertainties remain on how to best operationalize DESR at the individual
same Creative Commons licence is included level.
and the original work is properly cited. The The main aim of the present study was to assess whether high and low levels of DESR
written permission of Cambridge University
in adult ADHD patients can be operationalized. To this end, we analyzed data from a
Press must be obtained for commercial re-use.
large sample of consecutively newly referred adults with ADHD assessed in multiple
domains of functioning. We hypothesized that high levels of DESR would be common in
adults with ADHD and that their presence would be associated with morbidity and
dysfunction.
2 Joseph Biederman et al.

Methods medication status (medication versus no medication) to examine

the effect medication had on the association between DESR level
Sample
and the outcome of interest. If the interaction term was not signif-
The sample consisted of 441 newly referred adults 18–55 years of icant, we collapsed across medication status; if it was significant, we
age of both sexes with DSM-5 ADHD. There was no selection bias examined the outcome within the strata of medication status. Tests
based on social class or insurance restrictions. We received insti- were two-tailed and performed at the 0.05 alpha level using Stata
tutional review board approval to review, analyze, and report (version 15.1) [16].
anonymously on these subjects.

Results
Assessment procedures
Psychometric analyses of the Barkley ED Scale
Patients completed a battery of rating scales before their initial
evaluation. The demographic interview collected information on We calculated Cronbach’s alpha as 0.89 for the Barkley ED Scale,
age, race, sex, socioeconomic status (SES), and history of head which indicates a high level of internal consistency. The alphas with
injury or trauma. Medication history collected information on one item deleted at a time ranged from 0.87 to 0.91.
current and past treatments for ADHD and other disorders.
The Adult ADHD Self-Report Scale (ASRS) is an 18-item ROC curve analysis
patient-rated questionnaire to determine how often ADHD
symptoms occur [7,8]. The Behavior Rating Inventory of Execu- The ROC curve and conditional probability analyses for each rating
tive Function—Adult version (BRIEF-A) is a 75-item patient- scale are presented in Table 1. Of all the clinical scales used, the
rated questionnaire to assess an adult’s cognitive, emotional, and Barkley ED Scale best identified clinical impairment on the ASR
behavioral functions within the past month [9]. Raw scores are aggressive behavior subscale (area under the curve (AUC) = 0.94).
calculated and used to generate t-scores for nine scales, two Of the 12 subscales examined, 4 had an optimal Barkley ED Scale
summary index scales, and one scale reflecting overall function- cut-point of 6, 4 had an optimal cut-point of 8, 3 had an optimal cut-
ing. The Social Responsiveness Scale—Second edition (SRS-2) point of 9, and 1 had an optimal cut-point of 14 (Table 1). Sensi-
Adult form is a 65-item self-rated assessment used to measure the tivity ranged from 61% (ASRS hyperactivity) to 88% (ASR Exter-
severity of autism spectrum symptoms [10]. Raw scores are nalizing Problems) and specificity ranged from 56% (ASR
calculated and used to generate t-scores for five subscales and Attention Problems) to 91% (ASR Aggressive Behavior). Based
one total scale. The adult self-report (ASR) is a 126-item on the ROC curve analyses, we averaged the optimal Barkley ED
self-rated assessment of adult behavior, social competence, and Scale cut-points across all subscales and categorized patients as
substance use [11]. Raw scores are calculated and used to generate having high-level DESR (N = 191) and low-level DESR (N = 250), as
t-scores for eight scales, two composite scales, and one total scale. defined by having a Barkley ED Scale score of ≥8 or <8, respectively.
The Barkley Emotional Dysregulation (ED) Scale is a subset of Subsequent comparisons were made between subjects with low
eight questions from the CBS designated by Barkley as measuring versus high Barkley ED scores.
DESR [12,13] that asks subjects to describe their behavior in
the past 6 months. The Quality of Life Enjoyment and Satisfac-
tion Questionnaire (Q-LES-Q) is a self-rated 16-item rating scale Demographic characteristics
to assess enjoyment and satisfaction levels in various areas of
daily life [14]. As shown in Table 2, there were no significant differences in age, SES,
sex, or race between those with high- and low-level DESR. Fifty
percentage (N = 214) of patients reported currently taking psychiatric
medications. The most commonly reported medication types were
Statistical analysis stimulants (64%), followed by antidepressants (42%), antianxiety
We computed inter-item correlations for all eight items of the (18%), antipsychotic (7%), nonstimulants for ADHD (6%), and mood
Barkley ED Scale and Cronbach’s alpha for the entire Barkley ED stabilizers (4%). Sixty-nine percentage of patients reported currently
Scale to determine the scale’s internal consistency. taking only one medication type while 23% reported currently being
We used receiver operator characteristic (ROC) curves to exam- on 2 different medication types and 8% reported currently being on
ine the ability of the Barkley ED Scale to identify those with and ≥3 different medication types. When we compared the two DESR
without clinical impairment on the ASRS, BRIEF, SRS, and ASR. groups, there was no significant difference in the rate of those
Based on the information from the ROC curve analysis, we used the currently taking stimulant medications (Table 2). However, there
Liu approach [15] to calculate the optimal cut-point on the Barkley was a significant difference in the rate of those taking other psychiatric
ED Scale to identify those with and without impairment on each medications, with more patients currently taking other psychiatric
rating scale and used conditional probabilities to examine the diag- medications in the high-level DESR group.
nostic utility of those optimal cut-points. We then averaged the
optimal cut-points across all the rating scales and used it to catego-
DESR and ADHD symptoms
rize patients in our sample as having high- versus low-level DESR.
We compared demographic characteristics of those with high- The interaction between DESR level and medication status was not
versus low-level DESR using t-tests, Kruskal–Wallis rank sum tests, significant for the ASRS subdomain and total scores (all p > 0.05),
and Pearson’s chi-square tests. We analyzed clinical characteristics and was removed from the models. As shown in Figure 1A, patients
using linear, logistic, ordered logistic, or truncated Poisson regres- with high-level DESR had significantly more impaired scores in
sion models depending on the outcome. We included an interaction both the ASRS inattention and hyperactivity domains and on the
term in the model between DESR level (high versus low) and total scale score (all p < 0.001). Upon examining the individual
European Psychiatry 3

Table 1. ROC curve (AUC) and conditional probability analyses to identify the optimal cut-off point of the Barkley Emotional Dysregulation (ED) Scale using clinical
scores on scales measuring ADHD, executive function deficits (EFDs), autism spectrum disorder (ASD), and psychopathology (ASR)

Barkley ED Positive Negative

RS clinical AUC optimal cut- predictive predictive Correctly
Rating scale scores statistic point Sensitivity Specificity value value classified

ADHD symptomatology
ASRS total ≥24 in either 0.74 6 73% 64% 70% 68% 69%
subdomain
ASRS inattention ≥24 0.72 6 72% 62% 66% 68% 67%
ASRS hyperactivity ≥24 0.75 9 61% 76% 42% 87% 72%
Executive function deficits
BRIEF-GEC ≥65 0.81 6 80% 72% 77% 75% 76%
ASD symptomatology
SRS total ≥60 0.78 9 63% 79% 54% 85% 74%
SRS total ≥66 0.75 9 66% 74% 33% 92% 73%
Psychopathology (ASR)
ASR total ≥64 0.84 8 75% 77% 68% 83% 76%
ASR externalizing ≥64 0.87 8 88% 70% 48% 95% 75%
ASR internalizing ≥64 0.79 8 71% 74% 64% 80% 73%
ASR attention problems ≥70 0.69 6 77% 56% 49% 81% 63%
ASR aggressive behavior ≥70 0.94 14 85% 91% 36% 99% 90%
ASR anxious/depressed ≥70 0.79 8 80% 67% 41% 92% 70%
Average optimal Barkley ED Scale cut-point = 8

Table 2. Demographic and medication characteristics of subjects with high-level deficient emotional self-regulation (DESR; total Barkley ED score ≥ 8) and low-level
(total Barkley ED score < 8)

Low-level DESR (N = 250) High-level DESR (N = 191)

Mean  SD Mean  SD Test statistic p-Value

Age 34.5  13.5 32.5  11.4 t439 = 1.66 0.10

Socioeconomic status a
1.8  0.9 1.8  0.9 z = 0.21 0.84
N (%) N (%)
Gender (% male) 105 (42) 90 (47) χ2 = 1.15 0.28
Race (% Caucasian) a
202 (82) 139 (76) χ = 2.73
2
0.10
a
Current psychiatric medications
Stimulants 80 (33) 57 (31) χ2 = 0.27 0.69
Other psychiatric medications 53 (22) 68 (37) χ = 11.03
2
<0.001
a
Smaller sample sizes. Socioeconomic status: low-level: N = 181, high-level: N = 128; race: low-level: N = 245, high-level: N = 183; current psychiatric medications: low-level: N = 241, high-level:
N = 185.

ASRS symptoms, the interaction between DESR level and between the two DESR groups among unmedicated patients on this
medication status was not significant for all hyperactive symptoms item (p = 0.12; Table S1). As shown in Figure 1B,C, for the rest of the
(all p > 0.05) and all but one inattentive symptom (all p > 0.05 except inattentive items and all of the hyperactive items, patients with
“delay starting tasks that require a lot of thought,” p = 0.04). We high-level DESR experienced the symptoms significantly more
removed the interaction from all models except the significant one, often than patients with low-level DESR (all p < 0.001).
in which case, we performed the analysis stratified by medication
status. For “delaying starting tasks that require a lot of thought,”
DESR and executive functioning
medicated patients with high-level DESR experienced the symptom
significantly more often than medicated patients with low-level The interaction between DESR level and medication status was
DESR (p < 0.001). Conversely, there was no significant difference significant for only the BRIEF initiate subscale as both a continuous
4 Joseph Biederman et al.

Low-Level DESR High-Level DESR

A
60
50 p<0.001

Mean Score
40
30 p<0.001 p<0.001
20
10
0
Inattentive Hyperactive Total

B
5.0
4.0 p<0.001
Mean Score

* p<0.001
p<0.001 p<0.001
3.0 p<0.001 p=0.001 p<0.001
p<0.001

2.0
1.0
0.0
Make careless Difficulty keeping Difficulty Trouble wrapping Difficulty Delay starting Difficulty finding Distracted by Problems
mistakes attention during concentrating up final details organizing tasks that require things activity/noise remembering
repetitive work during a lot of thought
conversations

C
5.0
4.0
Mean Score

p=0.001
3.0 p<0.001 p=0.001
p=0.009 p<0.001 p<0.001 p<0.001
p<0.001 p<0.001
2.0
1.0
0.0
Fidget while Leave seat when Feel restless Difficulty Feel overly Talk too much Finish other Difficulty Interrupt others
sitting expected to relaxing active in social people's sentences waiting turn when they are
remain seated situations busy

Figure 1. Adult ADHD Self-Report Scale scores of subjects with high (total Barkley ED score ≥ 8) and low (total Barkley ED score < 8) DESR scores. (A) Subdomain and total scores; (B)
inattentive symptom scores; and (C) hyperactive symptom scores. Patients with high-level DESR were significantly more impaired than those with low-level DESR. *Significant
interaction between DESR level and medication status ( p = 0.04). Stratified analyses revealed significantly higher scores in those with high-level DESR among medicated patients but
not unmedicated patients.

(p = 0.01) and dichotomized (p = 0.04) outcome. Thus, we stratified were dichotomized into clinical range (t-score ≥ 60) versus non-
by medication status for analysis of this subscale and removed the clinical range (t-score < 60), those with high-level DESR had
interaction for all other subscales. Patients with high-level DESR significantly higher rates of patients with scores in the clinical range
demonstrated worse executive functioning as measured by the (all p < 0.001; Figure 2D).
BRIEF-A. Those with high-level DESR had significantly more
impaired mean scores (all p < 0.001; Figure 2A) and higher rates
DESR and psychopathology
of patients with scores in the clinical range (t-score ≥ 65) versus
nonclinical range (t-score < 65; all p < 0.001; Figure 2B). This The interaction between DESR level and medication status was
remained true when we stratified by medication status for the significant for the ASR attention problems and intrusive subscales
initiate subscale. Both medicated and unmedicated patients with as continuous outcomes and the ASR somatic complaints subscale
high-level DESR were significantly more impaired than those with as a dichotomous outcome (all p < 0.05). Thus, we stratified by
low-level DESR; however, the difference between those with high- medication status for analysis of those three subscales and removed
and low-level DESR was greater among the medicated (p < 0.001) the interaction for all other subscales and composite scales. Those
than unmedicated (p = 0.01; Table S1). with high-level DESR had significantly more impaired scores on six
In examining the SRS, there were no significant interactions clinical scales, all composite scales, and all adaptive functioning
between DESR level and medication status (all p > 0.05) and the scales (all p < 0.001; Figure 3A,C). Among medicated and unmedi-
interaction and medication status variables were removed from the cated patients, those with high-level DESR had more impaired
models. Patients with high-level DESR were more socially scores on the attention problems and intrusive subscales, with the
impaired, with significantly higher scores on all SRS subdomains difference between high- and low-level DESR greater for medicated
and the total score (all p < 0.001; Figure 2C). When the SRSs (both p < 0.001) compared with unmedicated (both p < 0.001;
European Psychiatry 5

Low-Level DESR High-Level DESR

A
85
80 p<0.001 p<0.001
p<0.001 p<0.001
75 p<0.001
Mean T-Score

p<0.001 p<0.001 * p<0.001

70 p<0.001 p<0.001
65 p<0.001
60
55
50
45
40
Inhibit Shift Emotional Self Initiate Working Planning/ Task Organization BRI MI GEC
Control Monitor Memory Organizing Monitor of Materials

B
100
90 p<0.001 p<0.001 p<0.001
Clinical T-Scores

80 p<0.001 p<0.001
Percent with

70 * p<0.001
60 p<0.001 p<0.001 p<0.001
50 p<0.001
40 p<0.001
30
20
10
0
Inhibit Shift Emotional Self Initiate Working Planning/ Task Organization BRI MI GEC
Control Monitor Memory Organizing Monitor of Materials

C D
70 70
Clinical T-Scores

p<0.001 p<0.001
60
Mean T-Score

65 p<0.001 p<0.001
Percent with

p<0.001 p<0.001 p<0.001 p<0.001 p<0.001 p<0.001

60 p<0.005 50
55 40 p<0.001
30
50 20
45 10
40 0

Figure 2. Behavior Rating Inventory of Executive Function—Adult version (BRIEF-A) and Social Responsiveness Scale—Second edition (SRS-2) adult self-report scores of subjects
with high (total Barkley ED score ≥ 8) and low (total Barkley ED score < 8) DESR scores. (A) BRIEF-A subscales; (B) subjects with T-scores in the clinical range on the BRIEF-A subscales;
(C) SRS-2 subscales; and (D) subjects with T-scores in the clinical range on the SRS-2. Patients with high-level DESR were significantly more impaired than those with low-level DESR.
*Significant interaction between DESR level and medication status (both p-values <0.05). Stratified analyses revealed significantly higher T-scores and a greater percentage of
scores in the clinical range in those with high-level DESR among both medicated and unmedicated patients.

Table S1). When we dichotomized the ASR scale t-scores rated their degree satisfaction significantly lower than those with
into clinical range (clinical scales: t-scores ≥70, composite scales: low-level DESR on 13 of the 14 items (all p < 0.05 except “vision in
t-scores ≥64, adaptive functioning scales: t-scores ≤30) versus terms of ability to do work or hobbies,” p = 0.08; Figure 4B).
nonclinical range (clinical scales: t-scores <70, composite scales: There were no significant interactions between DESR level and
t-scores <64, adaptive functioning scales: t-scores >30), a signifi- medication status when examining rates of employment and
cantly greater proportion of patients with high-level DESR had completion of 4 years of college (both p > 0.05), but there was a
scores in the clinical range on the seven clinical scales analyzed significant interaction when examining rates of learning disabil-
unstratified (all p < 0.001), all composite scales (all p < 0.001) and on ities (p < 0.05). We found no significant differences between the
five of the six adaptive functioning scales (all p < 0.05 except spouse/ two DESR groups when we examined the rates of patients who
partner scale, p = 0.05; Figure 3B,D). For somatic complaints, there were currently employed (high-level: 73%, N = 135/186 versus
was a significant difference in the proportion of patients with scores low-level: 80%, N = 195/246; p = 0.05) or who completed at least
in the clinical range between the two DESR groups among the 4 years of college (high-level: 73%, N = 130/178 versus low-level:
medicated patients (p = 0.003) but not among the unmedicated 73%, N = 175/241; p = 0.92). Among the medicated patients, there
patients (p = 0.37; Table S1). was no significant difference in the rates of those with learning
disabilities between two DESR groups (p = 0.44). However, there
DESR and quality of life was a significant difference among the unmedicated, with
higher rates of learning disabilities in those with high-level DESR
In examining the Q-LES-Q total score and individual items, there (p = 0.03; Table S1).
were no significant interactions between DESR level and medication
status (p > 0.05) and they were removed from the models. Overall
Impact of medication on DESR
quality of life was significantly lower in patients with high-level
DESR (p < 0.001; Figure 4A). When we examined the individual Given that half of the sample was taking psychiatric medications
items of the Q-LES-Q, we found that patients with high-level DESR at the time of the referral, we examined whether medication
6 Joseph Biederman et al.

Low-Level DESR High-Level DESR

A
75
p<0.001 * p<0.001
70 p<0.001
Mean T-Score

p<0.001 p<0.001
65 p<0.001 p<0.001 p<0.001 p<0.001
60 *

55
50
45
Aggressive Anxious/ Attention Intrusive Rule-Breaking Somatic Thought Withdrawn Externalizing Internalizing Total
Behavior Depressed Problems Behavior Complaints Problems Problems Problems Problems

B
90
80 p<0.001
Clinical T-Scores

70 p<0.001
Percent with

60 p<0.001 p<0.001
50 p<0.001
40
30 p<0.001 p<0.001
p<0.001 p<0.001
20 p<0.001 *
10
0
Aggressive Anxious/ Attention Intrusive Rule-Breaking Somatic Thought Withdrawn Externalizing Internalizing Total
Behavior Depressed Problems Behavior Complaints Problems Problems Problems Problems

C D
55 60
50 p=0.02
Clinical T-Scores
50
Mean T-Score

Percent with

40
45 p=0.005
p<0.001 30 p<0.001
40 p<0.001
p<0.001 20 p<0.001
p=0.01 p=0.05
35 p<0.001 p<0.001 10
p<0.001
30 0
Friends Spouse/ Family† Job† Education† Mean Friends Spouse/ Family † Job † Education† Mean
Partner † Adaptive Partner † Adaptive

Figure 3. Adult self-report (ASR) scores in subjects with high (total Barkley ED score ≥ 8) and low (total Barkley ED score < 8) DESR scores. (A) ASR Clinical and Composite Scales; (B)
subjects with T-scores in the Clinical Range on the ASR Clinical and Composite Subscales; (C) ASR Adaptive Functioning Scales; and (D) subjects with T-scores in the clinical range.
†Sample sizes vary. Spouse/partner: low-level: N = 115, high-level: N = 79; family: low-level: N = 245, high-level: N = 188; job: low-level: N = 200, high-level: N = 150; education: low-level:
N = 76, high-level: N = 68. Patients with high-level DESR were significantly more impaired than those with low-level DESR. *Significant interaction between DESR level and medication
status (all three p-values <0.05). Stratified analyses revealed significantly higher T-scores on the attention problems and intrusive subscales in those with high-level DESR among
both medicated and unmedicated patients. They also revealed a significantly greater percentage of scores in the clinical range on the somatic complaints subscale in those with
high-level DESR among the medicated patients but not the unmedicated patients.

treatment impacted DESR level. To this end, we compared rates of taking a combination of stimulant and antidepressant/antianxiety
high-level DESR among patients taking different types of psychi- medications (p = 0.001). Additionally, those taking a combination
atric medications and patients who were unmedicated. At the of stimulant and antidepressant/antianxiety medications also had
broadest level, there were neither statistically nor clinically mean- a significantly higher rates of high-level DESR compared with
ingful differences in the rate of high-level DESR among patients those who were unmedicated (p = 0.01). No other pairwise com-
taking any psychiatric medication (N = 214) compared with those parisons were statistically significant (all p > 0.05).
who were unmedicated (N = 212; any medication: 46% versus
unmedicated: 41%, p = 0.32). Next, we compared patients taking
stimulant medication (regardless of if they were taking other
Discussion
medication types; N = 137) to unmedicated patients and again
failed to find statistically or clinically meaningful differences in Relying on ROC curves and conditional probability analyses, we
the rates of high-level DESR between the groups (stimulant med- operationalized high and low levels of DESR based on scores on
ication: 42% versus unmedicated: 41%, p = 0.92). Lastly, selected items from the Barkley Scale in a sample of consecutively
we compared patients who were taking stimulant medication only referred adults with DSM-5 ADHD. These analyses showed that
(N = 93), antidepressant/antianxiety medication only (N = 71), a 43% of adult ADHD patients had high levels of DESR and those
combination of stimulant and antidepressant/antianxiety medi- affected had significantly more severe symptoms of ADHD, exec-
cations (N = 41), and those who were unmedicated. We did not utive dysfunction, autistic traits, levels of psychopathology, and
include the other medication types because the groups were too worse quality of life when compared with ADHD patients with
small. The omnibus test revealed that there were significant low levels of DESR. These findings indicate that high levels of DESR
differences among the four groups (p = 0.004). As shown in are common in adults with ADHD and represent a source of added
Figure 5, those taking stimulant medication only had a signifi- morbidity and dysfunction.
cantly lower rate of high-level DESR compared with those taking Our findings are consistent with previously reported results in a
antidepressant/antianxiety medications only (p = 0.01) and those separate community sample that showed that 61% of adults with
European Psychiatry 7

Low-Level DESR High-Level DESR

A
60

55 p<0.001

50

Mean Score
45

40

35

30
Q-LES-Q Total Score

B
5

4 p=0.04
p=0.08
Mean Score

3 p<0.001 p<0.001 p<0.001

p<0.001 p<0.001 p<0.001 p<0.001
p<0.001 p<0.001 p<0.001 p<0.001
p<0.001
2

0
Physical Mood Work Household Social Family Leisure Ability to Sexual Drive, Economic Living/Housing Ability to Your Vision in Overall Sense of
Health Activities Relationships Relationships Time Function in Interest and/or Status Situation Get Around Terms of Ability Well Being
Activities Daily Life Performance Physically to do Work or
without Hobbies
Feeling Dizzy
or Unsteady

Figure 4. Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) scores of subjects with high (total Barkley ED score ≥ 8) and low (total Barkley ED score < 8) DESR
scores. (A) Q-LES-Q mean total score and (B) Q-LES-Q individual items. Patients with high-level DESR were significantly more impaired than those with low-level DESR.

100
Omnibus test: p=0.004
90

80 p=0.01 vs. Unmedicated

p=0.001 vs. Stimulants Only
Percent with High-Level DESR

NS vs.
70 Antidepressant/Antianxiety
Only
60
NS vs. Unmedicated
p=0.01 vs. Stimulants Only
50

40
NS vs. Unmedicated
30

20

10

0
Unmedicated Stimulant Only Antidepressant/ Stimulant and
Antianxiety Only Antidepressant/
Antianxiety

Figure 5. Rates of high DESR scores (total Barkley ED score ≥ 8) by treatment. Abbreviation: NS, not significant.
8 Joseph Biederman et al.

ADHD had DESR symptoms of greater severity than 95% of control Conflict of Interests. Dr. Joseph Biederman is currently receiving research
subjects [6]. They are also consistent with data from a family study support from the following sources: AACAP, Feinstein Institute for Medical
[17] and two clinical trial studies [18,19] showing that DESR is Research, Food & Drug Administration, Genentech, Headspace Inc., Lundbeck
highly prevalent among ADHD adults and predict persistence of AS, Neurocentria Inc., NIDA, Pfizer Pharmaceuticals, Roche TCRC Inc.,
Shire Pharmaceuticals Inc., Sunovion Pharmaceuticals Inc., and NIH.
symptoms. As we argued previously [17], these findings are con-
Dr. Biederman has a financial interest in Avekshan LLC, a company that
sistent with the hypothesis that DESR is an important comorbidity develops treatments for attention deficit hyperactivity disorder (ADHD); his
within ADHD. interests were reviewed and are managed by Massachusetts General Hospital
Our finding showing that ADHD adults with high levels of DESR and Partners HealthCare in accordance with their conflict of interest policies.
have significantly more impaired ADHD symptoms and higher level Dr. Biederman’s program has received departmental royalties from a copy-
of psychopathology than those with low levels of DESR indicates that righted rating scale used for ADHD diagnoses, paid by Bracket Global, Ingenix,
the clinical picture is more severe in ADHD adults with DESR. Prophase, Shire, Sunovion, and Theravance; these royalties were paid to the
The finding that high levels of DESR is associated with higher Department of Psychiatry at MGH. In 2019, Dr. Biederman is a consultant for
levels of comorbid psychopathology and executive dysfunction are Akili, Jazz Pharma, and Shire. Through MGH corporate licensing, he has a US
consistent with results from previous studies documenting similar Patent (#14/027676) for a nonstimulant treatment for ADHD, and a patent
pending (#61/233686) on a method to prevent stimulant abuse. In 2018,
findings [6,17,18,19]. The finding that high levels of DESR were
Dr. Biederman was a consultant for Akili and Shire. In 2017, Dr. Biederman
associated with higher levels of autism spectrum symptoms are received research support from the Department of Defense and PamLab. He
consistent with previously reported findings in a pediatric sample was a consultant for Aevi Genomics, Akili, Guidepoint, Ironshore, Medgenics,
documenting high prevalence and morbidity of autistic traits in and Piper Jaffray. He was on the scientific advisory board for Alcobra and
youth with ADHD [20]. Shire. He received honoraria from the MGH Psychiatry Academy for tuition-
Our finding that high levels of DESR were significantly associated funded CME courses. In 2016, Dr. Biederman received honoraria from the
with lower quality of life expand our previous finding showing that MGH Psychiatry Academy for tuition-funded CME courses, and from Alcobra
DESR was associated with significantly lower quality of life, signif- and APSARD. He was on the scientific advisory board for Arbor Pharmaceu-
icantly worse social adjustment, reduced marital status, and higher ticals. He was a consultant for Akili and Medgenics. He received research
risk for traffic accidents and arrests in adults with ADHD [6]. support from Merck and SPRITES.
The high Cronbach’s alpha of 0.89 for the DESR items derived In the past year, Dr. Faraone received income, potential income, travel
from the Barkley Scale are consistent with those reported previously expenses continuing education support, and/or research support from Tris,
Otsuka, Arbor, Ironshore, Shire, Akili Interactive Labs, Enzymotec, Sunovion,
[6], indicating a high level of internal consistency for DESR items
Supernus, and Genomind. With his institution, he has US Patent US20130217707
used to define DESR in this study. A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of
Our results failing to identify meaningful differences in the rates ADHD. He also receives royalties from books published by Guilford Press:
of high levels of DESR among patients taking stimulant medication “Straight Talk about Your Child’s Mental Health,” Oxford University Press:
are consistent with results from recent meta-analyses [21] and “Schizophrenia: The Facts,” and Elsevier: “ADHD: Nonpharmacologic Interven-
Moukhtarian et al. [22] showing that stimulants were less effective tions.” He is principal investigator of www.adhdinadults.com.
in the treatment of ED than on core symptoms of ADHD. Although Dr. Thomas Spencer has, in the last 3 years, received research support or was
Asherson et al. [23] suggested that atomoxetine was associated with a consultant from the following sources: Avekshan, Ironshore, Lundbeck, Shire
improvements in emotional control in adults with ADHD, our Laboratories Inc., Sunovion, the FDA, and the Department of Defense. Con-
findings showed that antidepressant/antianxiety medications had sultant fees are paid to the MGH Clinical Trials Network and not directly to
a worsening effect on DESR. More work is needed to further Dr. Spencer. Dr. Spencer received support from Royalties and Licensing fees on
copyrighted ADHD scales through MGH Corporate Sponsored Research and
examine what treatments can best target DESR in ADHD.
Licensing. Through MGH corporate licensing, Dr. Spencer has a US Patent
Our findings need to be viewed in light of some methodological (#14/027676) for a nonstimulant treatment for ADHD and a patent pending
limitations. Our sample was primarily Caucasian and, thus, may (#61/233686) for a method to prevent stimulant abuse.
not generalize to other ethnic groups. We assessed DESR using Dr. Ronna Fried is currently receiving research support from Shire Phar-
selected items from the Barkley CBS [12,13] and do not know maceuticals and Roche Pharmaceuticals. In the past, Dr. Fried has received grant
whether similar results would be obtained using different instru- support from the Food & Drug Administration, Lundbeck AS, and the National
mentation to assess DESR. Although we cannot identify from our Institutes of Health. Previously, she had been on the scientific advisory board for
data whether DESR should be considered as co-occurring with Johnson & Johnson and Lundbeck AS. She also had received honoraria from the
ADHD or a result of ADHD, the fact that it is not universally MGH Psychiatry Academy for tuition-funded CME courses.
associated with ADHD supports the hypothesis that DESR should Dr. Craig Surman has received, in his lifetime, consulting fees or honorarium
be best conceptualized as a comorbidity of ADHD. Future research from McNeil, Nutricia, Pfizer, Rhodes, Shire, Somaxon, Takeda, Sunovion, and
NLS. He has also received payments for lectures for Alcobra, McNeil, Janssen,
comparing comorbid and noncomorbid ADHD subjects could
Janssen-Ortho, Novartis, Shire, GME Psychiatry, and Reed/MGH Academy
further clarify this issue. Although our analyses demonstrate inter-
(funded by multiple companies). Royalties have been given to Dr. Surman from
nal consistency of the items that we chose as a measure of DESR and Berkeley/Penguin for “Fastminds” How to Thrive if You have ADHD (or think
suggest that DESR as identified by these items has external validity you might)” and from Humana/Springer for “ADHD in Adults: A Practical Guide
because they are associated with greater impairment on measures of to Evaluation and Management.” Additionally, Dr. Surman has conducted clin-
functioning, further study could clarify the validity of the eight-item ical research at Massachusetts General Hospital supported by Abbot, Cephalon,
scale we utilized to identify DESR. Hilda and Preston Davis Foundation, Eli Lilly, Magceutics, Johnson & Johnson/
Despite these considerations, we identified a robust association McNeil, Lundbeck, Merck, and Nordic Naturals.
between DESR and ADHD in a large sample of clinically referred Dr. Mai Uchida, Ms. Maura DiSalvo, Ms. K. Yvonne Woodworth, and
adults with ADHD that correlated with impaired quality of life and Mr. Itai Biederman have no potential conflicts of interest to report.
a wide range of functional impairments indicating that the clinical
picture is more severe in ADHD adults with DESR. More work is
needed to help identify appropriate interventions for DESR in Financial Support. This study was supported in part by the MGH Pediatric
ADHD including psychosocial treatments. Psychopharmacology Council Fund.
European Psychiatry 9

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