VU Research Portal Lifestyle in adult ADHD Bron, T.I. 2017 document version Publisher's PDF, also known as Version of record Link to publication in VU Research Portal citation for published version (APA) Bron, T. I. (2017). Lifestyle in adult ADHD: From a Picasso point of view. [PhD-Thesis - Research and graduation internal, Vrije Universiteit Amsterdam]. General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. E-mail address: [email protected] Download date: 09. Feb. 2023
Attention-deficit hyperactivity disorder symptoms add risk to circadian rhythm sleep proplems in depression and anxiety
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Chapter 4document version Publisher's PDF, also known as Version of record
Link to publication in VU Research Portal
citation for published version (APA) Bron, T. I. (2017). Lifestyle in adult ADHD: From a Picasso point of view. [PhD-Thesis - Research and graduation internal, Vrije Universiteit Amsterdam].
General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.
• Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ?
Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
E-mail address: [email protected]
Brenda W.J.H. Penninx, Aartjan T.F. Beekman,
and J.J. Sandra Kooij
rhythm disturbances in depression and anxiety disorders.
Methods: Self-reported sleep characteristics of 2,090 participants in the
Netherlands Study of Depression and Anxiety were assessed using the Munich
with lifetime depression and/or anxiety disorders (LDA), and those with both
LDA and high ADHD symptoms (LDA+ADHD), using the Conner’s Adult ADHD
Rating Scale.
Results: Sleep characteristics were least favorable in the LDA+ADHD group.
extremely late chronotype (12% vs. 5% vs. 3%; p
(15% vs. 5% vs. 4%; p
Syndrome (DSPS; 16% vs. 8% vs. 5%; p
including depression and anxiety, presence of ADHD symptoms increased
the odds ratio for late chronotype (OR=2.6; p=.003), indication of DSPS (OR=2.4;
p p=.007).
Limitations: ADHD conceptually overlaps with symptom presentation of
depression and anxiety. We used a cross-sectional study design, and used self
reported sleep characteristics.
Conclusions: High ADHD symptoms were associated with an increased rate of
circadian rhythm sleep disturbances in an already at-risk population of people
with depression and/or anxiety disorders. Circadian rhythm sleep disorders, as
often seen in ADHD are not entirely due to any comorbid depression and/or
anxiety disorder. Adequate treatment of such sleep problems is needed and
may prevent serious health conditions in the long term.
ADHD symptoms add risk to circadian rhythm sleep problems | 53
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4
INTRODUCTION
Sleep problems are highly prevalent and impairing in depression [190] and
anxiety disorders [191-193]. These patients have reported both shorter and
longer sleep durations, and trouble falling asleep [192, 194, 195]. Also, sleep
problems constitute independent risk factors for developing a new episode of
depression or anxiety in those who had previously recovered [196]. Similarly,
(ADHD) [30, 32, 197, 198], and severity of sleep problems relates to ADHD
severity [199-201]. Moreover, depression, anxiety disorders, and ADHD are often
comorbid [22, 24, 202].
Circadian rhythm disturbances may contribute to the development or severity
of mental disorders, such as depression, anxiety disorders, and ADHD [25, 31,
198]. One of the most prominent circadian rhythm sleep disorders in ADHD is
the delayed sleep phase syndrome (DSPS). DSPS is marked by a phase delay
in melatonin secretion [31, 41], and is characterized by chronic late sleep, late
rising, and the inability to fall asleep or to wake up at earlier times [78]. Those with
DSPS are often referred to as having extremely late chronotypes, which is the
term for one’s biologically driven preference for timing of sleep and wake [35].
The prevalence of DSPS in the general population is estimated at 0.2–3.1% [203-
205], but it is much more common in psychiatric disorders [206]. Amongst DSPS
patients, there are high rates of depression (16%) [207], social phobia (18%), and
panic disorder (8%) [208]. The rate of ADHD in patients with DSPS is yet unknown.
It has been suggested that psychological features of depression, such as social
withdrawal, may induce a loss of social cues that normally help to synchronize
the circadian rhythm [209]. Also in other studies, late chronotype has been
related to depressive mood [210-213], higher levels of depressive symptoms
[214], and increased number of ADHD symptoms [201]. Of adult ADHD patients,
26 to 78% has DSPS [31, 201]. A delayed sleep pattern results in short sleep
duration when there are early morning obligations such as work or school [215].
a risk factor for various serious health conditions, such as obesity, diabetes,
We assessed whether ADHD symptoms add risk to developing circadian
rhythm sleep disturbances, in those with or without depression and anxiety.
We used data from a large Dutch cohort. If ADHD independently increases the
54 | CHAPTER 4
risk for circadian rhythm sleep disturbances, it seems important that clinicians
become more aware of both delayed sleep and its consequences, as well
as possible ADHD, when encountering sleep disturbances in depression and
anxiety disorders.
METHODS
Participants
We analyzed data from the Netherlands Study of Depression and Anxiety
(NESDA) in which sleep and circadian rhythm disturbances were assessed.
The NESDA study is a longitudinal cohort study designed to investigate the
long-term course and consequences of depressive and anxiety disorders
in individuals aged 18 to 65 years old. NESDA included 2,981 participants at
baseline, and consisted of healthy controls, persons with a remitted or current
depressive and/or anxiety disorder. A detailed description of the study can
be found elsewhere [76]. The research protocol was approved by the Ethical
Committee of participating universities and written informed consent was
obtained from all participants. Circadian rhythm information was collected at
the 2-year follow-up assessment, which was considered the baseline for the
present analyses (n=2,327). ADHD symptoms were measured in 2,092 of these
subjects at the 4-year assessment, of which we excluded two participants (1%)
who had clinical ADHD symptoms without having lifetime depression and/or
anxiety disorders, leading to the ultimate sample size of 2,090 for the present
analyses. The low prevalence rate of clinical ADHD symptoms among healthy
controls (1-3%), compared to the international prevalence rate of 3 to 6% may
be explained by the exclusion of psychiatric comorbidities during the initial
sampling for the control group in NESDA, decreasing the chance of including
people with ADHD in the control group.. Several studies have indicated that
66-78% of adult ADHD patients has at least one comorbid psychiatric disorder,
and in clinical practice the mean number of psychiatric comorbidities is three
[10, 22, 60]. Since ADHD is a childhood-onset, chronic disorder [78], ADHD was
assumed to be present throughout the NESDA study, which allowed for the
use of circadian rhythm information at the 2-year follow-up, and the ADHD
information at the 4-year follow-up assessments.
Circadian rhythm sleep outcomes
Sleep outcomes were assessed using the 11-item Munich Chronotype
Questionnaire (MCTQ) [219]. The MCTQ is a self-report measure consisting of
ADHD symptoms add risk to circadian rhythm sleep problems | 55
s id
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questions on bedtime, wake-up time, midsleep, sleep-onset latency, and sleep
duration on nights before work and free days, and chronotype in childhood and
adulthood. Following Roenneberg et al. (2007), sleep outcomes on free days
Sleep outcomes on work days are regarded as the extrinsically imposed
rhythm, since (very) late chronotypes often report having a long sleep-onset
latency [220] and chronic short sleep duration [219]. In this case, work schedules
do not match the intrinsic circadian rhythm. The main circadian rhythm sleep
outcomes were late chronotype, and an indication of DSPS (which both are
indicators of the underlying circadian disturbance), and short sleep duration on
work days (which is one of the consequences of a delayed sleep). We used the
time of mid-sleep on free days, corrected for sleep debt on work days (MSFsc)
.
2*SDF]/7), in which MSF is the midpoint of sleep on free days, SDF is the
sleep duration on free days, and SDW is the sleep duration on work days. The
time before 00:30 h, and having a sleep-onset latency of 30 minutes or more on
work days, or a self-rating of being an extremely late chronotype in childhood
ADHD symptoms
ADHD symptoms were assessed at the 4-year follow-up of NESDA using the
Conners’ Adult ADHD Rating Scale – Screening Version (CAARS-S:SV) [179], a
30-item self-report questionnaire addressing the presence of DSM-IV criteria
for ADHD symptoms. The CAARS contains two subscales: the 9-item ‘Inattentive
symptoms’ (range 0-27) and the 9-item ‘Hyperactivity/Impulsivity symptoms’
(range 0-27), and also the 12-item ‘ADHD index’ (range 0-36). The ADHD index
behaviors such as sensation-seeking, extraversion, distractibility, low self-
esteem, and mood swings. In order to identify high scores per subscale, the
raw scores on subscales were converted into standardized scores (T-scores)
using American age- and gender normative data, following the CAARS manual
[179]. T
score’ to determine any relationship between ADHD and circadian rhythm
sleep problems. Then, we used the continuous scores to examine if circadian
Lastly, the continuous ADHD index score was used in order to investigate
any dose-response relationship between ADHD and circadian rhythm sleep
problems. The CAARS has good test-retest reliability (r=0.89-0.95) and has high
discriminant validity for the ADHD index (73% sensitivity). Although the Dutch
between German and American norm data [222], justifying the CAARS as a
reliable and cross-culturally valid measure of ADHD symptoms in adults [223].
Depression and anxiety
In each NESDA wave, the DSM-IV criteria-based Composite International
Diagnostic Interview (CIDI, version 2.1) [166] was used to investigate the presence
of depressive and anxiety disorders. Depressive and anxiety disorders were
lifetime if a person ever had a depressive or anxiety disorder during his
or her life, of which current
present within 6 months prior to the interview, and remitted when not present
within 6 months prior to the interview. The CIDI has a high test-retest reliability
and high validity for depressive and anxiety disorders [169-171].
Covariates
Sociodemographics included age, gender, years of education, having a
cohabitant partner, and having cohabitant children. Additionally various health
indicators were considered as covariates since they have been related to
sleep. Somatic health factors included body mass index (BMI), presence of
chronic diseases, and smoking. Presence of chronic diseases included self-
reported lung disease, diabetes, cardiovascular diseases, cancer, osteoarthritis,
intestinal disorders, liver disease, epilepsy, and thyroid disease. Smoking status
impact sleep, we also assessed current medication use based on drug container
medication use included frequent use of selective serotonin reuptake inhibitors
(SSRIs, ATC code NO6AB), tricyclic antidepressants (TCAs, ATC code NO6AA),
other antidepressants (ATC codes N06AF and N06AX), and/or benzodiazepines
(ATC codes NO5BA, NO5CF, NO5CD and NO3AE).
ADHD symptoms add risk to circadian rhythm sleep problems | 57
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Statistical analyses
between healthy controls (HC), persons with a lifetime depressive and/or anxiety
disorder without ADHD (LDA), and persons with a lifetime depressive and/or
anxiety disorder with ADHD (LDA+ADHD), using analysis of variance (ANOVA) for
continuous data and chi-square analyses for nominal or ordinal data. We were
LDA+ADHD group. In order to investigate if ADHD status was associated with a
higher odds ratio for circadian rhythm disturbance as dependent variable (i.e.,
late chronotype in adulthood, an indication of DSPS, and a short sleep duration
on nights prior to work days), we conducted multivariate logistic regression
independent variable. Second, we analyzed if circadian rhythm disturbances
were related to symptom domains of ADHD, using the continuous score on
Inattentive symptoms and Hyperactive/Impulsive symptoms as predictor
variables. Third, we investigated any dose-response relationship between
ADHD and circadian rhythm disturbances, using the continuous ADHD index
score as the predictor variable. All multivariate logistic regression models were
adjusted for sociodemographics, depression and anxiety status (current: yes/
no; remitted: yes/no), somatic health factors and current medication use, using
a forward stepwise method. We subdivided lifetime depressive and anxiety
disorders into current and remitted disorder, since prior NESDA results implicate
a stronger relationship between sleep problems [191] and chronotype [225, 226]
in current than in remitted depressive and anxiety disorder. Data were analyzed
using
test, and applied the Benjamini-Hochberg correction for multiple testing in the
logistic regression.
Table 1 shows the ADHD symptoms, sociodemographics, somatic health
factors, and current medication use of all three groups. Overall group
more medication in comparison to the LDA and HC groups. Compared to the
58 | CHAPTER 4
psychostimulants more often.
Sleep characteristics
Table 2 presents the sleep characteristics of the three groups. Overall group
late chronotype in childhood as well as in adulthood. On work days, they more
had a sleep duration of less than 6 hours, they had a longer sleep-onset latency,
and more often a sleep-onset latency of 30 minutes or more. Also on free days,
they more often had a longer sleep-onset, and more often a sleep latency of 30
an indication of DSPS, compared to the HC and LDA groups.
Added risk of ADHD on circadian rhythm sleep parameters
Table 3 presents the odds ratios for high ADHD symptoms, inattentive symptoms,
hyperactive symptoms and ADHD index in extremely late chronotype in
adulthood, an indication of DSPS, and a short sleep duration on work days. Even
after full adjustment for sociodemographics, current and remitted depression
and anxiety, somatic health factors and current medication use, high ADHD
an indication of DSPS (OR=1.3 per SD increase, p
increased the odds for late chronotype in adulthood (OR=1.2 per SD increase,
p=.055), and short sleep duration on work days (OR=1.3 per SD increase, p=.057);
whereas hyperactive-impulsive symptoms did not increase the odds on any of
the circadian rhythm parameters. Regarding any dose-response relationship
between ADHD symptoms and circadian rhythm sleep disturbances, the ADHD
(OR=1.3 per SD increase, p=.014), and an indication of DSPS (OR=1.3 per SD
increase, p=.004).
ADHD symptoms add risk to circadian rhythm sleep problems | 59
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2 =9
3 .5
2 =1
4 .7
2 =3
4 .9
2 =3
7. 0
2 =1
3 .6
.2 12
.0 8
2 =4
9
0
ADHD symptoms add risk to circadian rhythm sleep problems | 61
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DISCUSSION
We examined the added risk of ADHD symptoms for circadian rhythm
disturbances in an already at-risk population with depression and anxiety. We
found that ADHD symptoms were independently associated with adverse
sleep outcomes. Persons with high ADHD symptoms were almost three times
as likely to have circadian rhythm sleep disturbances, which seems particularly
related to inattentive symptoms of ADHD.
times more likely to have circadian rhythm disturbances (OR= 2.4 - 2.7), beyond
in adolescents, where the symptom domains inattention and hyperactivity/
impulsivity were the most prominent predictors of delayed sleep, exceeding
the odds for depression and anxiety [227]. Furthermore, studies among adults
awakenings and daytime sleepiness, that are often seen in people with a
delayed sleep pattern [41], were not related to comorbidities like depression and
on circadian parameters per ADHD symptom domain. Most of the previous
rhythm disturbances [200, 201, 229-231]. However, in our study only inattentive
symptoms, and not hyperactive-impulsive symptoms, increased the odds for
circadian sleep disturbances, as has been found by others [232-235]. Several
authors have argued that this may be because inattention leads to forgetting
the time, or rumination before falling asleep, late bedtimes, and hence short
sleep [236, 237].
We found that an extremely late chronotype was almost twice as prevalent in
persons with lifetime depression and/or anxiety disorders without comorbid
ADHD as compared to healthy controls (4.8% vs. 2.7%), which was consistent
2.7%). Other factors such as severity of depression and anxiety [225, 226], age
[241], and other psychiatric disorders [242] are known to impact on the link
between late chronotype and depression or anxiety disorders. In contrast to
groups when using the MSFsc, which is a well-established continuous measure
ADHD symptoms add risk to circadian rhythm sleep problems | 63
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4
for chronotype [219]. This may be explained by the fact that sleep length is
generally shorter, especially for people with an extremely late chronotype, than
for people with earlier chronotypes. Because of morning obligations, extremely
late chronotypes therefore often have a relatively early mid-sleep, which has
were in the highest quintile of the MSFsc (27.4% vs. 21.1% for LDA and 14.8% for
HC), supporting the association between late chronotype and ADHD symptoms.
ADHD group needed more than 30 minutes to fall asleep. Other studies also
found longer sleep-onset latencies in both children and adults with ADHD [30,
31, 243]. Late chronotypes had long sleep-onset latencies and a short sleep
duration on work days, emphasizing that DSPS is indeed likely to be associated
with sleep debt when individuals have early morning obligations such as work.
Contrary to the study by Robillard et al. in patients with unipolar and bipolar
later bedtimes nor did they sleep shorter than controls. The LDA group did
need more time to fall asleep, corroborating frequent complaints of sleep-
A clear dose-response relationship was found between ADHD symptomatology
and the odds for an indication of DSPS. This emphasized that the severity of
ADHD was linked to a behavioral pattern of delayed sleep-onset, late bedtimes
and/or late chronotype. Prior research in children [243, 248] and adults with
ADHD [197, 198, 201, 227] already proposed that delayed circadian rhythm and
evening chronotype may be inherent to ADHD, and to ADHD-related behaviors
[249, 250].
In conclusion, ADHD symptoms add to the odds for circadian misalignment
in patients with depression and/or anxiety. Circadian misalignment in the
short term is associated with sleepiness during the day, and increase of
mood and cognitive problems. In the long term, due to sleep debt, chronic
diseases may develop like obesity, diabetes, cardiovascular disease, increased
of delayed sleep consists of psycho-education on sleep hygiene, evening
treated with psycho-education, medication, coaching and cognitive behavior
64 | CHAPTER 4
therapy [60]. More research is needed to investigate whether combined
treatment of ADHD and circadian rhythm sleep problems ameliorates the long-
term health consequences of chronic sleep debt.
CAARS-SV, which is a self report measure and not a clinical diagnostic tool.
ADHD has overlaps in symptom presentation with depression and anxiety, such
as concentration problems and daytime fatigue. Moreover, sleep problems
may mimic or exacerbate ADHD symptoms [251, 252]. Nevertheless, this study
indicated that ADHD symptoms clearly contribute to the prevalence and risk
for circadian rhythm sleep disturbances, even after adjustment for depression
and/or anxiety status. Second, DSPS could not be diagnosed in this study,
because no information about the duration of symptoms (i.e., presence of
symptoms in the past 6 months or more) was available [78]. We were therefore
used the ‘indication of DSPS’ to identify these cases. A third limitation was that
we used a cross-sectional study design. Longitudinal designs are needed to
test causal relationships between ADHD, circadian rhythm sleep problems,
and depression and/or anxiety disorders. Fourth, we only used self-reported
behavioral measures and did not include biological measures, such as
melatonin curves or actigraphy, to validate circadian rhythm misalignment in
circadian rhythm [221].
In summary, this study stresses the interrelatedness of ADHD symptoms and
circadian rhythm sleep problems, which is independent of any depressive and
anxiety disorders. Detection and treatment of ADHD in depressed or anxious
persons is important, since ADHD is independently related to circadian rhythm
sleep disturbances. Due to its chronic pattern, a circadian rhythm disruption
may lead to chronic sleep debt and subsequent adverse health outcomes
when left untreated. Therefore, ADHD needs to be recognized in people with
sleep problems, and vice versa. Adequate treatment of such circadian rhythm
sleep problems is needed and may prevent serious health conditions in the
long term.
Link to publication in VU Research Portal
citation for published version (APA) Bron, T. I. (2017). Lifestyle in adult ADHD: From a Picasso point of view. [PhD-Thesis - Research and graduation internal, Vrije Universiteit Amsterdam].
General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.
• Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ?
Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
E-mail address: [email protected]
Brenda W.J.H. Penninx, Aartjan T.F. Beekman,
and J.J. Sandra Kooij
rhythm disturbances in depression and anxiety disorders.
Methods: Self-reported sleep characteristics of 2,090 participants in the
Netherlands Study of Depression and Anxiety were assessed using the Munich
with lifetime depression and/or anxiety disorders (LDA), and those with both
LDA and high ADHD symptoms (LDA+ADHD), using the Conner’s Adult ADHD
Rating Scale.
Results: Sleep characteristics were least favorable in the LDA+ADHD group.
extremely late chronotype (12% vs. 5% vs. 3%; p
(15% vs. 5% vs. 4%; p
Syndrome (DSPS; 16% vs. 8% vs. 5%; p
including depression and anxiety, presence of ADHD symptoms increased
the odds ratio for late chronotype (OR=2.6; p=.003), indication of DSPS (OR=2.4;
p p=.007).
Limitations: ADHD conceptually overlaps with symptom presentation of
depression and anxiety. We used a cross-sectional study design, and used self
reported sleep characteristics.
Conclusions: High ADHD symptoms were associated with an increased rate of
circadian rhythm sleep disturbances in an already at-risk population of people
with depression and/or anxiety disorders. Circadian rhythm sleep disorders, as
often seen in ADHD are not entirely due to any comorbid depression and/or
anxiety disorder. Adequate treatment of such sleep problems is needed and
may prevent serious health conditions in the long term.
ADHD symptoms add risk to circadian rhythm sleep problems | 53
s id
e v
ie w
4
INTRODUCTION
Sleep problems are highly prevalent and impairing in depression [190] and
anxiety disorders [191-193]. These patients have reported both shorter and
longer sleep durations, and trouble falling asleep [192, 194, 195]. Also, sleep
problems constitute independent risk factors for developing a new episode of
depression or anxiety in those who had previously recovered [196]. Similarly,
(ADHD) [30, 32, 197, 198], and severity of sleep problems relates to ADHD
severity [199-201]. Moreover, depression, anxiety disorders, and ADHD are often
comorbid [22, 24, 202].
Circadian rhythm disturbances may contribute to the development or severity
of mental disorders, such as depression, anxiety disorders, and ADHD [25, 31,
198]. One of the most prominent circadian rhythm sleep disorders in ADHD is
the delayed sleep phase syndrome (DSPS). DSPS is marked by a phase delay
in melatonin secretion [31, 41], and is characterized by chronic late sleep, late
rising, and the inability to fall asleep or to wake up at earlier times [78]. Those with
DSPS are often referred to as having extremely late chronotypes, which is the
term for one’s biologically driven preference for timing of sleep and wake [35].
The prevalence of DSPS in the general population is estimated at 0.2–3.1% [203-
205], but it is much more common in psychiatric disorders [206]. Amongst DSPS
patients, there are high rates of depression (16%) [207], social phobia (18%), and
panic disorder (8%) [208]. The rate of ADHD in patients with DSPS is yet unknown.
It has been suggested that psychological features of depression, such as social
withdrawal, may induce a loss of social cues that normally help to synchronize
the circadian rhythm [209]. Also in other studies, late chronotype has been
related to depressive mood [210-213], higher levels of depressive symptoms
[214], and increased number of ADHD symptoms [201]. Of adult ADHD patients,
26 to 78% has DSPS [31, 201]. A delayed sleep pattern results in short sleep
duration when there are early morning obligations such as work or school [215].
a risk factor for various serious health conditions, such as obesity, diabetes,
We assessed whether ADHD symptoms add risk to developing circadian
rhythm sleep disturbances, in those with or without depression and anxiety.
We used data from a large Dutch cohort. If ADHD independently increases the
54 | CHAPTER 4
risk for circadian rhythm sleep disturbances, it seems important that clinicians
become more aware of both delayed sleep and its consequences, as well
as possible ADHD, when encountering sleep disturbances in depression and
anxiety disorders.
METHODS
Participants
We analyzed data from the Netherlands Study of Depression and Anxiety
(NESDA) in which sleep and circadian rhythm disturbances were assessed.
The NESDA study is a longitudinal cohort study designed to investigate the
long-term course and consequences of depressive and anxiety disorders
in individuals aged 18 to 65 years old. NESDA included 2,981 participants at
baseline, and consisted of healthy controls, persons with a remitted or current
depressive and/or anxiety disorder. A detailed description of the study can
be found elsewhere [76]. The research protocol was approved by the Ethical
Committee of participating universities and written informed consent was
obtained from all participants. Circadian rhythm information was collected at
the 2-year follow-up assessment, which was considered the baseline for the
present analyses (n=2,327). ADHD symptoms were measured in 2,092 of these
subjects at the 4-year assessment, of which we excluded two participants (1%)
who had clinical ADHD symptoms without having lifetime depression and/or
anxiety disorders, leading to the ultimate sample size of 2,090 for the present
analyses. The low prevalence rate of clinical ADHD symptoms among healthy
controls (1-3%), compared to the international prevalence rate of 3 to 6% may
be explained by the exclusion of psychiatric comorbidities during the initial
sampling for the control group in NESDA, decreasing the chance of including
people with ADHD in the control group.. Several studies have indicated that
66-78% of adult ADHD patients has at least one comorbid psychiatric disorder,
and in clinical practice the mean number of psychiatric comorbidities is three
[10, 22, 60]. Since ADHD is a childhood-onset, chronic disorder [78], ADHD was
assumed to be present throughout the NESDA study, which allowed for the
use of circadian rhythm information at the 2-year follow-up, and the ADHD
information at the 4-year follow-up assessments.
Circadian rhythm sleep outcomes
Sleep outcomes were assessed using the 11-item Munich Chronotype
Questionnaire (MCTQ) [219]. The MCTQ is a self-report measure consisting of
ADHD symptoms add risk to circadian rhythm sleep problems | 55
s id
e v
ie w
questions on bedtime, wake-up time, midsleep, sleep-onset latency, and sleep
duration on nights before work and free days, and chronotype in childhood and
adulthood. Following Roenneberg et al. (2007), sleep outcomes on free days
Sleep outcomes on work days are regarded as the extrinsically imposed
rhythm, since (very) late chronotypes often report having a long sleep-onset
latency [220] and chronic short sleep duration [219]. In this case, work schedules
do not match the intrinsic circadian rhythm. The main circadian rhythm sleep
outcomes were late chronotype, and an indication of DSPS (which both are
indicators of the underlying circadian disturbance), and short sleep duration on
work days (which is one of the consequences of a delayed sleep). We used the
time of mid-sleep on free days, corrected for sleep debt on work days (MSFsc)
.
2*SDF]/7), in which MSF is the midpoint of sleep on free days, SDF is the
sleep duration on free days, and SDW is the sleep duration on work days. The
time before 00:30 h, and having a sleep-onset latency of 30 minutes or more on
work days, or a self-rating of being an extremely late chronotype in childhood
ADHD symptoms
ADHD symptoms were assessed at the 4-year follow-up of NESDA using the
Conners’ Adult ADHD Rating Scale – Screening Version (CAARS-S:SV) [179], a
30-item self-report questionnaire addressing the presence of DSM-IV criteria
for ADHD symptoms. The CAARS contains two subscales: the 9-item ‘Inattentive
symptoms’ (range 0-27) and the 9-item ‘Hyperactivity/Impulsivity symptoms’
(range 0-27), and also the 12-item ‘ADHD index’ (range 0-36). The ADHD index
behaviors such as sensation-seeking, extraversion, distractibility, low self-
esteem, and mood swings. In order to identify high scores per subscale, the
raw scores on subscales were converted into standardized scores (T-scores)
using American age- and gender normative data, following the CAARS manual
[179]. T
score’ to determine any relationship between ADHD and circadian rhythm
sleep problems. Then, we used the continuous scores to examine if circadian
Lastly, the continuous ADHD index score was used in order to investigate
any dose-response relationship between ADHD and circadian rhythm sleep
problems. The CAARS has good test-retest reliability (r=0.89-0.95) and has high
discriminant validity for the ADHD index (73% sensitivity). Although the Dutch
between German and American norm data [222], justifying the CAARS as a
reliable and cross-culturally valid measure of ADHD symptoms in adults [223].
Depression and anxiety
In each NESDA wave, the DSM-IV criteria-based Composite International
Diagnostic Interview (CIDI, version 2.1) [166] was used to investigate the presence
of depressive and anxiety disorders. Depressive and anxiety disorders were
lifetime if a person ever had a depressive or anxiety disorder during his
or her life, of which current
present within 6 months prior to the interview, and remitted when not present
within 6 months prior to the interview. The CIDI has a high test-retest reliability
and high validity for depressive and anxiety disorders [169-171].
Covariates
Sociodemographics included age, gender, years of education, having a
cohabitant partner, and having cohabitant children. Additionally various health
indicators were considered as covariates since they have been related to
sleep. Somatic health factors included body mass index (BMI), presence of
chronic diseases, and smoking. Presence of chronic diseases included self-
reported lung disease, diabetes, cardiovascular diseases, cancer, osteoarthritis,
intestinal disorders, liver disease, epilepsy, and thyroid disease. Smoking status
impact sleep, we also assessed current medication use based on drug container
medication use included frequent use of selective serotonin reuptake inhibitors
(SSRIs, ATC code NO6AB), tricyclic antidepressants (TCAs, ATC code NO6AA),
other antidepressants (ATC codes N06AF and N06AX), and/or benzodiazepines
(ATC codes NO5BA, NO5CF, NO5CD and NO3AE).
ADHD symptoms add risk to circadian rhythm sleep problems | 57
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Statistical analyses
between healthy controls (HC), persons with a lifetime depressive and/or anxiety
disorder without ADHD (LDA), and persons with a lifetime depressive and/or
anxiety disorder with ADHD (LDA+ADHD), using analysis of variance (ANOVA) for
continuous data and chi-square analyses for nominal or ordinal data. We were
LDA+ADHD group. In order to investigate if ADHD status was associated with a
higher odds ratio for circadian rhythm disturbance as dependent variable (i.e.,
late chronotype in adulthood, an indication of DSPS, and a short sleep duration
on nights prior to work days), we conducted multivariate logistic regression
independent variable. Second, we analyzed if circadian rhythm disturbances
were related to symptom domains of ADHD, using the continuous score on
Inattentive symptoms and Hyperactive/Impulsive symptoms as predictor
variables. Third, we investigated any dose-response relationship between
ADHD and circadian rhythm disturbances, using the continuous ADHD index
score as the predictor variable. All multivariate logistic regression models were
adjusted for sociodemographics, depression and anxiety status (current: yes/
no; remitted: yes/no), somatic health factors and current medication use, using
a forward stepwise method. We subdivided lifetime depressive and anxiety
disorders into current and remitted disorder, since prior NESDA results implicate
a stronger relationship between sleep problems [191] and chronotype [225, 226]
in current than in remitted depressive and anxiety disorder. Data were analyzed
using
test, and applied the Benjamini-Hochberg correction for multiple testing in the
logistic regression.
Table 1 shows the ADHD symptoms, sociodemographics, somatic health
factors, and current medication use of all three groups. Overall group
more medication in comparison to the LDA and HC groups. Compared to the
58 | CHAPTER 4
psychostimulants more often.
Sleep characteristics
Table 2 presents the sleep characteristics of the three groups. Overall group
late chronotype in childhood as well as in adulthood. On work days, they more
had a sleep duration of less than 6 hours, they had a longer sleep-onset latency,
and more often a sleep-onset latency of 30 minutes or more. Also on free days,
they more often had a longer sleep-onset, and more often a sleep latency of 30
an indication of DSPS, compared to the HC and LDA groups.
Added risk of ADHD on circadian rhythm sleep parameters
Table 3 presents the odds ratios for high ADHD symptoms, inattentive symptoms,
hyperactive symptoms and ADHD index in extremely late chronotype in
adulthood, an indication of DSPS, and a short sleep duration on work days. Even
after full adjustment for sociodemographics, current and remitted depression
and anxiety, somatic health factors and current medication use, high ADHD
an indication of DSPS (OR=1.3 per SD increase, p
increased the odds for late chronotype in adulthood (OR=1.2 per SD increase,
p=.055), and short sleep duration on work days (OR=1.3 per SD increase, p=.057);
whereas hyperactive-impulsive symptoms did not increase the odds on any of
the circadian rhythm parameters. Regarding any dose-response relationship
between ADHD symptoms and circadian rhythm sleep disturbances, the ADHD
(OR=1.3 per SD increase, p=.014), and an indication of DSPS (OR=1.3 per SD
increase, p=.004).
ADHD symptoms add risk to circadian rhythm sleep problems | 59
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2 =9
3 .5
2 =1
4 .7
2 =3
4 .9
2 =3
7. 0
2 =1
3 .6
.2 12
.0 8
2 =4
9
0
ADHD symptoms add risk to circadian rhythm sleep problems | 61
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DISCUSSION
We examined the added risk of ADHD symptoms for circadian rhythm
disturbances in an already at-risk population with depression and anxiety. We
found that ADHD symptoms were independently associated with adverse
sleep outcomes. Persons with high ADHD symptoms were almost three times
as likely to have circadian rhythm sleep disturbances, which seems particularly
related to inattentive symptoms of ADHD.
times more likely to have circadian rhythm disturbances (OR= 2.4 - 2.7), beyond
in adolescents, where the symptom domains inattention and hyperactivity/
impulsivity were the most prominent predictors of delayed sleep, exceeding
the odds for depression and anxiety [227]. Furthermore, studies among adults
awakenings and daytime sleepiness, that are often seen in people with a
delayed sleep pattern [41], were not related to comorbidities like depression and
on circadian parameters per ADHD symptom domain. Most of the previous
rhythm disturbances [200, 201, 229-231]. However, in our study only inattentive
symptoms, and not hyperactive-impulsive symptoms, increased the odds for
circadian sleep disturbances, as has been found by others [232-235]. Several
authors have argued that this may be because inattention leads to forgetting
the time, or rumination before falling asleep, late bedtimes, and hence short
sleep [236, 237].
We found that an extremely late chronotype was almost twice as prevalent in
persons with lifetime depression and/or anxiety disorders without comorbid
ADHD as compared to healthy controls (4.8% vs. 2.7%), which was consistent
2.7%). Other factors such as severity of depression and anxiety [225, 226], age
[241], and other psychiatric disorders [242] are known to impact on the link
between late chronotype and depression or anxiety disorders. In contrast to
groups when using the MSFsc, which is a well-established continuous measure
ADHD symptoms add risk to circadian rhythm sleep problems | 63
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4
for chronotype [219]. This may be explained by the fact that sleep length is
generally shorter, especially for people with an extremely late chronotype, than
for people with earlier chronotypes. Because of morning obligations, extremely
late chronotypes therefore often have a relatively early mid-sleep, which has
were in the highest quintile of the MSFsc (27.4% vs. 21.1% for LDA and 14.8% for
HC), supporting the association between late chronotype and ADHD symptoms.
ADHD group needed more than 30 minutes to fall asleep. Other studies also
found longer sleep-onset latencies in both children and adults with ADHD [30,
31, 243]. Late chronotypes had long sleep-onset latencies and a short sleep
duration on work days, emphasizing that DSPS is indeed likely to be associated
with sleep debt when individuals have early morning obligations such as work.
Contrary to the study by Robillard et al. in patients with unipolar and bipolar
later bedtimes nor did they sleep shorter than controls. The LDA group did
need more time to fall asleep, corroborating frequent complaints of sleep-
A clear dose-response relationship was found between ADHD symptomatology
and the odds for an indication of DSPS. This emphasized that the severity of
ADHD was linked to a behavioral pattern of delayed sleep-onset, late bedtimes
and/or late chronotype. Prior research in children [243, 248] and adults with
ADHD [197, 198, 201, 227] already proposed that delayed circadian rhythm and
evening chronotype may be inherent to ADHD, and to ADHD-related behaviors
[249, 250].
In conclusion, ADHD symptoms add to the odds for circadian misalignment
in patients with depression and/or anxiety. Circadian misalignment in the
short term is associated with sleepiness during the day, and increase of
mood and cognitive problems. In the long term, due to sleep debt, chronic
diseases may develop like obesity, diabetes, cardiovascular disease, increased
of delayed sleep consists of psycho-education on sleep hygiene, evening
treated with psycho-education, medication, coaching and cognitive behavior
64 | CHAPTER 4
therapy [60]. More research is needed to investigate whether combined
treatment of ADHD and circadian rhythm sleep problems ameliorates the long-
term health consequences of chronic sleep debt.
CAARS-SV, which is a self report measure and not a clinical diagnostic tool.
ADHD has overlaps in symptom presentation with depression and anxiety, such
as concentration problems and daytime fatigue. Moreover, sleep problems
may mimic or exacerbate ADHD symptoms [251, 252]. Nevertheless, this study
indicated that ADHD symptoms clearly contribute to the prevalence and risk
for circadian rhythm sleep disturbances, even after adjustment for depression
and/or anxiety status. Second, DSPS could not be diagnosed in this study,
because no information about the duration of symptoms (i.e., presence of
symptoms in the past 6 months or more) was available [78]. We were therefore
used the ‘indication of DSPS’ to identify these cases. A third limitation was that
we used a cross-sectional study design. Longitudinal designs are needed to
test causal relationships between ADHD, circadian rhythm sleep problems,
and depression and/or anxiety disorders. Fourth, we only used self-reported
behavioral measures and did not include biological measures, such as
melatonin curves or actigraphy, to validate circadian rhythm misalignment in
circadian rhythm [221].
In summary, this study stresses the interrelatedness of ADHD symptoms and
circadian rhythm sleep problems, which is independent of any depressive and
anxiety disorders. Detection and treatment of ADHD in depressed or anxious
persons is important, since ADHD is independently related to circadian rhythm
sleep disturbances. Due to its chronic pattern, a circadian rhythm disruption
may lead to chronic sleep debt and subsequent adverse health outcomes
when left untreated. Therefore, ADHD needs to be recognized in people with
sleep problems, and vice versa. Adequate treatment of such circadian rhythm
sleep problems is needed and may prevent serious health conditions in the
long term.
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