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SLEEP, Vol. 36, No. 7, 2013
1059
Review of Sleep Disturbances, Anxiety and Depression—Alvaro et al
INTRODUCTION
Sleep disturbances encompass various potentially overlap-
ping symptoms and disorders including insomnia, hypersomnia,
excessive daytime sleepiness, circadian rhythm disturbance, and
extrinsic sleep disorders (related to insufcient sleep and sleep
hygiene). Sleep disturbances, anxiety and depression are common
problems that lead to neuropsychological impairment,
1-3
alcohol
and drug abuse,
4
and suicidal ideation.
5-7
Recent studies have es-
tablished high comorbidity rates between sleep disturbances (such
as insomnia, narcolepsy, sleep apnea, and circadian rhythm com-
plaints), and depression and anxiety,
8-10
rates which vary across
different anxiety disorders.
11
Longitudinal associations have also
been established between sleep disturbances, anxiety, and depres-
sion.
12,13
Nevertheless, the etiological relationship between these
problems remains unclear. Understanding the etiological relation-
ship could help determine whether the onset of one is a risk-factor
for the onset of the others, and inform public health campaigns
and clinical interventions for each disorder.
11,14,15
Research on bidirectionality can achieve such goals. Bidi-
rectionality is established by accounting for the base rate of
outcome variables,
16
considering whether a sleep disturbance
independently predicts the onset of anxiety or depression, and
whether anxiety or depression independently predicts the onset
of a sleep disturbance.
REVIEW OF SLEEP DISTURBANCES, ANXIETY AND DEPRESSION
http://dx.doi.org/10.5665/sleep.2810
A Systematic Review Assessing Bidirectionality between Sleep Disturbances,
Anxiety, and Depression
Pasquale K. Alvaro, B Psych (Honors)
1
; Rachel M. Roberts, BA (Hons), MPsych (Clinical), PhD
1
; Jodie K. Harris, BPsych (Hons), PhD (Clin Psych)
2,3,4
1
School of Psychology, University of Adelaide, South Australia;
2
Flinders University of South Australia;
3
Centre for Treatment of Anxiety and Depression
(CTAD), Adelaide Health Service;
4
University of Adelaide, South Australia
Submitted for publication June, 2012
Submitted in nal revised form February, 2013
Accepted for publication February, 2013
Address correspondence to: Pasquale Alvaro, School of Psychology, The
University of Adelaide, SA, Australia, 5005; Tel: +61 (08) 8313 3399; Fax:
+61 (08) 8303 3770; E-mail: pasquale.alvaro@adelaide.edu.au
Study Objectives: To investigate whether sleep disturbances are bidirectionally related to anxiety and depression, and thus identify potential risk
factors for each problem.
Design: A systematic review was conducted on 9 studies (8 longitudinal, 1 retrospective) that assessed bidirectionality between a sleep distur-
bance, and anxiety or depression. Treatment studies were excluded, along with those solely based on clinical samples or cohorts at high risk of suf-
fering from a sleep disturbance, anxiety and depression. Eligible studies were identied by searching PubMed, PsychINFO, Embase, and Scopus
databases, and reference lists of eligible studies. Publication dates ranged from the beginning of each database to December 2011.
Measurements and Results: Syntheses of longitudinal studies suggested insomnia and sleep quality were bidirectionally related to anxiety and
depression, and depression/anxiety, respectively. Childhood sleep problems signicantly predicted higher levels of depression and a combined
depression/anxiety variable, but not vice-versa. A one-way relationship was found where anxiety predicted excessive daytime sleepiness, but
excessive daytime sleepiness was not associated with depression.
Conclusions: Denitive conclusions regarding bidirectionality cannot be made for most sleep disturbances due to the small number and hetero-
geneity of cohort samples used across studies. Nevertheless, best available evidence suggests insomnia is bidirectionally related to anxiety and
depression. Clinical and theoretical implications are discussed.
Keywords: Anxiety, depression, insomnia, sleep disturbances, systematic review
Citation: Alvaro PK; Roberts RM; Harris JK. A systematic review assessing bidirectionality between sleep disturbances, anxiety, and depression.
SLEEP 2013;36(7):1059-1068.
Various studies have found a bidirectional relationship be-
tween sleep disturbances, anxiety and depression, suggesting
that each contribute to the development and are a consequence
of one another.
14,15,17
Other studies have suggested the existence
of two distinct cause-effect associations, where anxiety predicts
a sleep disturbance and a sleep disturbance predicts depression,
but not vice-versa.
11,18
The inconsistent nature of the research
may relate to variations of sleep disturbances that have been
assessed across studies. The statistical signicance and mag-
nitude of the relationship between sleep disturbances, anxiety
and depression differs across sleep and mental health variables
(anxiety and depression),
18-21
which in turn may affect the re-
sults of bidirectionality studies. The current study, therefore,
presents a systematic review that aims to determine whether
a variety of sleep disturbances are risk factors for the develop-
ment of anxiety or depression, and whether anxiety or depres-
sion are risk factors for the development of sleep disturbances.
METHODS
Data Sources and Study Selection
An extensive search of PubMed, PsychINFO, Embase, and
Scopus was conducted using the following search terms in com-
binations specied for each database: (anxiety OR anxious*
OR phobic OR phobia* OR psychological stress OR stress
OR stresses OR internalization OR internalization OR obses-
sive compulsive OR asthenia OR depression OR depress* OR
depressive disorder OR dysthym* OR seasonal affective dis-
order OR rumination) AND (sleep initiation and maintenance
disorders OR sleep* OR insomnia OR early awakening OR
early waking OR non-restorative OR non-restorative OR night
waking). The Embase and Scopus searches also included the
SLEEP, Vol. 36, No. 7, 2013
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Review of Sleep Disturbances, Anxiety and Depression—Alvaro et al
following terms to account for the large number of search hits:
NOT (neoplasm OR cancer OR tumor OR tumour OR carcino-
ma* OR oncolog* OR ‘cardiovascular disease’ OR dementia*
OR Alzheimer* OR parksinson* OR therapy’ OR ‘psychiatric
treatment’ OR medicat* OR treatment). Publication dates for
the searches ranged from the beginning of each database to De-
cember 2011, and all searches were limited to English and hu-
man studies. The Reference lists of retrieved studies were also
assessed for other citations.
Studies were eligible if the following criteria was met: (1)
Study assessed any sleep disturbance; (2) Study assessed an
anxiety or depression variable; (3) Study reported a signi-
cance test when assessing bidirectionality; (4) Study accounted
for baseline/previous sleep, anxiety or depression variable.
Based on the recommendations of Jansson-Frojmark and Lind-
blom,
15
treatment studies, along with those who solely included
clinical samples or cohorts at high risk of suffering from a sleep
disturbance, anxiety, and depression were excluded due to the
potential bias towards a stronger association between sleep
disturbances, anxiety, and depression. The inclusion/exclusion
criteria were developed by the primary author and reviewed by
the secondary author.
Quality Assessment
The methodological quality of the eligible studies was as-
sessed by the rst author who used a modied version of a 15-
item checklist from a recent meta-analysis (Table 1).
22
Items
10 and 11 were included because the nature and magnitude of
associations between sleep disturbances, anxiety, and depres-
sion often differs across sleep and mental health variables.
18-21
Sleep disturbances, anxiety and depression have been found
to be associated with demographic information (e.g., age and
gender),
23,24
circadian rhythm disorders,
25-27
alcohol and drug
use,
4,28
exercise,
29,30
and caffeine,
31-33
thus providing the ratio-
nale behind items 12 and 13. Each item was labelled with a
(+) or (-), depending on whether the study satised the cri-
terion or not. A cutoff score was not used as a reference for
quality because such methods assign equal importance to all
criteria. However, items were not weighted: the Cochrane Col-
laboration recommend against this method due to difculties
in justifying the weights assigned to each item.
34
Instead, qual-
ity was assessed along a continuum that ranged from 0-15,
where lower scores indicated lower quality and higher scores
indicated higher quality.
Data Extraction and Synthesis
A coding form was developed to extract the following data
from each study: geographical location of the study, sample
size at baseline and follow-up, response rate, method of partici-
pant recruitment, method of data collection, use of medication,
study methodology, possible biases, prediction and outcome
variables, demographic statistics at baseline and (when avail-
able) follow-up, descriptive statistics for the variables of sleep
disturbance, anxiety and depression, statistical analyses, vari-
ables controlled for, results, interpretation of results, author(s)’
conclusions, and cited articles that were potentially relevant.
Data extraction was conducted by the rst author.
A meta-analysis could not be conducted due to the heteroge-
neous characteristics of the studies that met the inclusion cri-
teria. Therefore, the research questions were analyzed by two
narrative syntheses. The rst presented an overall representa-
tion of the ndings from each study, whereas the second com-
pared results across different sleep variables.
RESULTS
Included and Excluded Studies
The PubMed, PsychInfo, Embase, and Scopus database
searches identied 2,273, 2,352, 1,252, and 2,664 studies, re-
spectively, and one study was identied from the reference
searches. Ninety-three studies were selected as potentially rel-
evant following the application of the inclusion criteria to the
titles and abstracts. Most articles were excluded because they
did not assess bidirectionality. Five studies
13,35-38
assessed bi-
directionality but not between a sleep disturbance and anxiety
or depression; one study assessed bidirectionality but used a
cohort that was at risk for sleep disturbances, anxiety, and de-
pression
39
; and one study did not report a signicance test when
assessing bidirectionality.
18
Therefore, 10 studies were eligible
for analysis in the systematic review (12% of the original ar-
ticles). Two eligible studies contained identical samples
40,41
and
hence were collapsed into 1, leaving 9 independent studies that
were included in the systematic review (refer to Figure 1 for
a representation of the database searches and summary of the
reasons for exclusion). Eligibility of each study was assessed
by the rst author.
Table 2 displays the general characteristics of each study.
All studies were conducted between 2002 and 2010; 8 were
longitudinal and prospective, and the other study was retro-
spective and cross-sectional. Studies were set in various coun-
tries; 2 in the USA, 2 in the UK, and 1 each in Switzerland,
Sweden, Japan, South Korea, and the Netherlands. Sample
populations also differed across studies; adolescents were as-
sessed by 3 studies, adults by 2, and young adults, the elderly,
child twin pairs, and adopted children were assessed by 1
study each. Participants were recruited by random selection in
Table 1—Items for quality assessment
1. Sampling procedure of cohort described?
2. Population characteristics described?
3. Inclusion and exclusion criteria described?
4. Studied population ≥ 75% of originally selected population?
5. Information about responders vs nonresponders
6. Lost to follow-up < 20%?
7. Information about completers vs noncompleters?
8. Are insomnia, anxiety and depression assessments for clinical
diagnosis?
9. Same measures at both baseline and follow-up?
10. Are depression and anxiety assessed separately?
11. Does the sleep variable assess a specic sleep related problem?
12. Correction for potential demographic confounders?
13. Correction for circadian rhythm disorders, alcohol & drug use,
exercise or caffeine intake?
14. Correction for other potential non-demographic confounders such
as physical disorders or medication?
15. Are given data usable/transformable for meta-analysis?
SLEEP, Vol. 36, No. 7, 2013
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Review of Sleep Disturbances, Anxiety and Depression—Alvaro et al
3 studies, high schools in 2, and a 2-stage sampling procedure,
the Colorado adoption agency, birth records, and a national
registrations list of all community residents were used in 1
study each. Participants were recruited by self-report ques-
tionnaires in 4 studies (2 were postal surveys), interviews in 3
(2 were structured and 1 was semi-structured), parent report-
ed questionnaires in 1, and parent reported and self-reported
questionnaires in 1 study.
Quality Assessment
Study quality ratings ranged from 7 to 13 (M = 9.9, SD = 1.9).
All studies described the sampling procedure and population
characteristics, used the same measures at baseline and follow-
up, and gave data useable for a meta-analysis. Seven stud-
ies compared responders to non-responders and completers
to non-completers, assessed a specic sleep disturbance, and
corrected for potential demographic confounders; 6 studies re-
tained 75% of the originally selected population and assessed
depression and anxiety separately; 4 studies lost more than 20%
of participants at follow-up; 3 studies described the inclusion
and exclusion criteria, and corrected for other potential non-
demographic confounders such as physical disorders; 2 studies
assessed insomnia, anxiety, and depression according to a clini-
cal diagnosis; 1 study corrected for alcohol and exercise; and
no study corrected for circadian rhythm disorders, drug use, or
caffeine intake (Table 3).
Overall Synthesis
Table 4 presents the data for the overall synthesis. Four of the
9 independent studies supported the bidirectional theory,
14,15,17,42
2 of which assessed insomnia, anxiety, and depression,
15,17
1 as-
sessed insomnia and depression,
42
and 1 assessed insomnia and
mental health status.
14
The unidirectional theory discussed above
was supported by 3 studies.
11,43,44
One study found 2 one-way
relationships where anxiety predicted insomnia and insomnia
predicted depression but not vice-versa
11
; the other reported that
childhood sleep problems predicted depression but not vice-ver-
sa
43
; and the last suggested that childhood sleep problems pre-
dicted higher levels of depression/anxiety, but not vice-versa.
44
However, this does not necessarily support the unidirectional
theory discussed above, as the mental health variable that was
used (depression/anxiety) assessed anxiety and depression as a
single construct rather than separate variables.
Two independent studies reported mixed results.
40,41,45
One
study found no relationship between excessive daytime sleepi-
ness and major depressive episodes or “pure insomnia” (in-
somnia without concurrent depression) and “pure depression”
(depression without concurrent insomnia), a bidirectional rela-
tionship between insomnia and major depressive episodes, and
a one-way relationship where anxiety predicted excessive day-
time sleepiness.
40,41
The other found a bidirectional relationship
between sleep quality and depression/anxiety and a one-way
relationship between time in bed and depression/anxiety, where
less time in bed at baseline predicted higher levels of depres-
sion/anxiety, but not vice-versa.
45
Therefore, 6 independent
studies supported the bidirectional theory,
14,15,17,40-42,45
5 sup-
ported a unidirectional relationship,
11,40,41,43-45
and 1 study did
not nd a signicant relationship between excessive daytime
sleepiness and major depressive episodes or “pure insomnia”
and “pure depression.”
40,41
Figure 2 depicts the number of stud-
ies and analyses that supported each type of relationship.
Synthesis of Sleep Variables
Insomnia was the most commonly assessed sleep vari-
able,
11,15,17,40,42
followed by childhood sleep problems,
43,44
sleep
quality,
14,45
excessive daytime sleepiness,
41
and time in bed
(Table 5).
45
Studies that assessed bidirectionality between anxi-
ety, depression, and other common sleep disturbances such as
sleep apnea were not found.
For insomnia, 3 of the 5 studies supported the bidirectional
theory.
15,17,42
One study supported the unidirectional theory,
where anxiety disorders predicted insomnia, which predicted
major depressive disorder.
11
The remaining independent study
reported several analyses across 6 time points over 20 years. No
relationship was found in either direction between “pure insom-
nia” and “pure depression,” along with a bidirectional relation-
ship between insomnia and insomnia comorbid with depression
across 5 separate bidirectional analyses over 20 years.
40
The
same study also found conicting results across these 5 analy-
ses when assessing bidirectionality between “pure depression”
and insomnia comorbid with depression (2 bidirectional rela-
tionships, a one-way relationship where insomnia comorbid
with depression predicted pure depression but not vice-versa,
and 2 relationships where no association was found in either
direction). Finally, insomnia without concurrent depression
predicted the development of depression at the interview di-
rectly following baseline and interviews at any given follow-
up, whereas depression without concurrent insomnia predicted
insomnia at the interview at any given time-point only.
40
Regarding sleep quality, both studies found a bidirectional
relationship, one with depression/anxiety
45
and the other with
mental health status (a variable that contains a depression/anxiety
scale).
14
Childhood sleep problems predicted depression and de-
pression/anxiety but not vice-versa.
43,44
One study found that less
time in bed at baseline is associated with more severe symptoms
of depression/anxiety at follow-up, but not vice-versa.
45
Finally,
Figure 1—Summary of the reasons for exclusion.
93 potentially relevant articles from initial searches
10 articles eligible for the systematic review
Reasons for exclusion
• 76 studies did not assess directionality
• 5 studies did not assess directionality
of sleep related problems, anxiety or
depression
• 1 study assessed an “at risk”
population
• 1 study did not control for relevant
baseline variables
2 articles assessed the same population
9 articles included in the systematic review
SLEEP, Vol. 36, No. 7, 2013
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Review of Sleep Disturbances, Anxiety and Depression—Alvaro et al
one study found a one-way relationship where anxiety predicted
excessive daytime sleepiness, but no relationship between exces-
sive daytime sleepiness and depression (i.e., excessive daytime
sleepiness did not predict depression and vice-versa).
41
DISCUSSION
Each study included in the systematic review reported at
least one signicant relationship between a sleep disturbance,
anxiety and/or depression, which further consolidates the no-
tion of an association between these problems.
8,23,44
Interest-
ingly, one study
41
found that anxiety predicted later excessive
daytime sleepiness but no relationship between excessive day-
time sleepiness and major depressive disorder symptoms, sug-
gesting that a bidirectional relationship is not consistent across
mental health problems. This is surprising given the overlap
of abnormalities in neurotransmitters and brain structures in-
volved in problems with the sleep wake cycle, anxiety, and
depression,
46-53
but Hasler and colleagues
41
suggested that the
association between excessive daytime sleepiness and depres-
sion may be mediated by sleep disorder symptoms and co-
morbid anxiety. More studies are needed to draw a denitive
conclusion on whether excessive daytime sleepiness, anxiety,
and depression are bidirectionally related.
Best available evidence suggests that insomnia is bidirec-
tionally related to anxiety and depression. One retrospective
study reported a one-way relationship where anxiety predicted
Table 2—General Characteristics of Each Study Included in the Systematic Review
Study
Sample
size
Study
design
City/
Country Population
Age
range at
baseline
Method of participant
recruitment
Method of
participant
assessment
N time
points
(N years
between
follow
up)
40/41 457 Longitudinal,
Prospective
Switzerland Young adults,
representative,
stratied
sample
20-21 Two stage sampling procedure:
(1) Participants were screened
for health problems, (2) Those
at risk for psychiatric syndromes
were identied using a stratied
sampling procedure and selected
for interviews. Males recruited
through conscription, females
recruited through electoral
register. Males were investigated
in groups of 10, and females
received postal surveys
Semi-structured
interview
6 (2, 5, 2,
5, 6)
44 360 Longitudinal,
Prospective
USA Adopted
children
4 Participants recruited from the
Colorado Adoption Project
Parent reported
questionnaires
2 (11)
43 500 Longitudinal,
Prospective
Wales &
England
Child twin pairs 8 Twin pairs identied through birth
records. Parents were contacted
by the UK Ofce for National
Statistics after screening for
infant mortality.
Questionnaires.
Parent reported
at baseline, and
Self-report at
follow up
2 (2)
15 1,498 Longitudinal,
Prospective
Sweden Adult 20-60 Random selection, identied via
public register
Self-report
questionnaires,
postal
2 (1)
11 1,014 Cross-
sectional,
Retrospective
USA Adolescents,
metropolitan
13-15 Random selection, Youth-parents
pairs identied from a 400,000
member Health Maintenance
Organisation
Structured
interviews
1 (n/a)
14 516 Longitudinal,
Prospective
Japan Adolescents 13-15 High schools from metropolitan
Tokyo
Self-report
questionnaires
2 (2)
42 909 Longitudinal,
Prospective
South Korea Elderly, general
population
65+ All community residents within
2 geographic catchment areas
(one urban, one rural) were
identied and approached
through national registration list.
Structured
interview, home
based
2 (2)
45 493 Longitudinal,
Prospective
Netherlands Adolescents 12-15 High schools Self-report
questionnaires
3 (1)
17 1,589 Longitudinal,
Prospective
UK Adults 18+ Random selection, adults
registered to 1 of 5 general
practices from urban and rural
areas
Self-report
questionnaires,
postal
2 (1)
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Review of Sleep Disturbances, Anxiety and Depression—Alvaro et al
depression, but not vice-versa.
11
Conversely, four longitudinal
studies found a bidirectional relationship between insomnia,
anxiety and/or depression.
15,17,40,54
Due to the retrospective na-
ture of, and hence the memory bias apparent in retrospective
methodology,
55
longitudinal study designs allow for more ac-
curate causal inferences and reliable assessment of bidirec-
tionality, and are therefore the preferred methodology for
bidirectional studies.
14
Interestingly, insomnia could predict depression more con-
sistently than depression predicts insomnia. Buysse and col-
Table 3—Amount of studies (n) that met each criterion of quality assessment
Criterion Number (n) +, n/a Studies
Sampling procedure of cohort described? 9 11, 14, 15, 17, 40, 42-45
Population characteristics described? 9 11, 14, 15, 17, 40, 42-45
Inclusion and exclusion criteria described? 3 11, 15, 42
Studied population ≥ 75% of originally selected population? 6 14, 40, 42-45
Information about responders vs nonresponders 7 11, 15, 17, 40, 42, 44, 45
Lost to follow-up < 20%? 4 11, 15, 43, 45
Information about completers vs noncompleters? 7 11, 17, 40, 42-45
Are insomnia, anxiety and depression assessments for clinical diagnosis? 2 11, 42
Same measures at both baseline and follow-up? 9 11, 14, 15, 17, 40, 42-45
Are depression and anxiety assessed separately? 6 11, 15, 17, 40, 42, 44
Does the sleep variable assess a specic sleep related problem? 7 11, 14, 15, 17, 40, 42, 45
Correction for potential demographic confounders? 7 11, 14, 15, 17, 42, 44, 45
Correction for circadian rhythm disorders, alcohol & drug use, exercise, or caffeine intake? 1 42
Correction for other potential non-demographic confounders, such as physical disorders or medication? 3 14, 17, 42
Are given data usable/transformable for meta-analysis? 9 11, 14, 15, 17, 40, 42-45
Figure 2—Summary of the total number of studies (analyses) that supported each type of relationship between sleep disturbances, anxiety and depression.
1(2)
Unidirectional relationships
No relationships
Bidirectional relationships
Sleep disturbance
Sleep disturbance
Sleep disturbance
Depression/Anxiety
Depression
Insomnia/Depression
3(3)
Sleep disturbance/
Depression
2(2)
4(4)
2(2)
1(2)
3(3)
Anxiety
Sleep disturbance
Sleep disturbance/
Depression
Sleep disturbance
Sleep disturbance
Anxiety
Depression
Depression
Depression/Anxiety
1(6)
Sleep disturbance
Depression Depression
2(2)
1(5)
SLEEP, Vol. 36, No. 7, 2013
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Review of Sleep Disturbances, Anxiety and Depression—Alvaro et al
leagues
40
assessed bidirectionality over a 20-year period across
six time-points. They found consistent bidirectional relation-
ships between “pure insomnia” and insomnia comorbid with
depression, yet conicting relationships between “pure depres-
sion” and insomnia comorbid with depression. Such results
suggest that insomnia at baseline is a stronger and more persis-
tent predictor of follow-up depression than baseline depression
is of follow-up insomnia.
Various types of mechanisms may explain the bidirectional
association between insomnia, anxiety and depression. Com-
Table 4—Main ndings from each study
Study
Sleep variable
(instrument name)
Mental health
variables (instrument
name) Baseline/past variables accounted for Results
40, 41 Insomnia – immediate
follow up only (SPIKE
63
)
MDE – immediate follow
up only (SPIKE
63
)
Concurrent MDE when predicting insomnia, and vice-versa.
Insomnia immediate follow up
depression.
Insomnia – any follow
up (SPIKE
63
)
MDE – any follow up
(SPIKE
63
)
Concurrent MDE when predicting insomnia, and vice-versa. Bidirectional: baseline variable and
follow up at any time
“Pure insomnia”
(SPIKE
63
)
“Pure depression”
(SPIKE
63
)
Only participants who reported no baseline symptoms of the outcome
variable were included in the analysis.
5 analyses, all no relationship
“Pure insomnia”
(SPIKE
63
)
Insomnia comorbid with
depression (SPIKE
63
)
“Pure insomnia” refers to those without concurrent depression 5 analyses, all bidirectional
Insomnia comorbid with
depression (SPIKE
63
)
“Pure depression”
(SPIKE
63
)
“Pure depression” refers to those without concurrent insomnia 5 analyses: 2 bidirectional, 2 no
relationship, 1insomnia + depression
depression
EDS (SPIKE
63
) Cumulative MDE
(SPIKE
63
), Cumulative
Anxiety (SPIKE
63
)
Baseline EDS when assessing anxiety and depression as predictors, and
vice-versa. Gender and stratied sampling for both analyses.
Anxiety EDS. No relationship
between EDS and MDE
44 Childhood sleep
problems (CBC
64
)
Depression/Anxiety
(CBC
64
)
Baseline depression/anxiety, when assessing childhood sleep problems
as a predictor, and vice-versa. Adoptive status and child sex for both
analyses.
Childhood sleep problems
Depression/Anxiety
43 Childhood sleep
problems (CSHQ
65
)
Depression (CDI
66
) When predicting depression: the effects of depression at age 8 on
depression at age 10 and the association between sleep and depression
at age 8. When predicting childhood sleep problems: the effects of
childhood sleep problems at age 8 on childhood sleep problems at age 10
and the association between sleep and depression at age 8.
Childhood sleep problems
Depression
15 Insomnia (BNSQ
67
&
USI
68
)
Depression (HADS
69
),
Anxiety (HADS
69
)
Only participants who reported low or no symptoms of the outcome
variable at baseline were included in analyses, e.g., if assessing anxiety
as an outcome variable, only participants with low scores of anxiety were
used. Age and gender were used as predictor variables for all analyses.
Bidirectional
11 Insomnia (DSM-IV)
70
* Depression (DSM-
IV)
70
*, Any Anxiety
Disorder(DSM-IV)
70
*
Prior depression was controlled for in the insomnia – anxiety disorders
models and prior anxiety disorders in the insomnia – depression models.
Gender and race/ethnicity were also controlled for in each analysis.
Anxiety Insomnia Depression
14 Sleep quality (PSQI
71
) Mental Health Status
(GHQ-12)
72
Only participants who did not report symptoms of the outcome variable at
baseline were included in the analyses, e.g. only those without poor sleep
quality were used when assessing sleep quality as an outcome variable.
Predictor variables, gender, and lifestyle and contentment with daily life at
baseline were used as covariates.
Bidirectional
42 Insomnia
(10/66DDCRG)
73
*
Depression (GMS B3)
74
* Only participants who did not report symptoms of the outcome variable
at baseline were included in the analyses, e.g. those without insomnia at
baseline were used when assessing insomnia as an outcome variable.
Number of physical disorder, age, gender, education, housing, past
occupation, current employment, living area, life events, social decit,
physical activity, organicity, anxiety, and daily drinking were controlled for
in all analyses.
Bidirectional
45 Sleep quality (SQS)
75
Depression/Anxiety
(YSR)
76
Time is included as a covariate, along with time 1, sleep quality, and mean
time in bed.
Bidirectional
Time in Bed (TBS)
45
Depression/Anxiety
(YSR)
76
Time is included as a covariate, along with time 1, sleep quality, and mean
time in bed.
Less time in bed Depression/
Anxiety
17 Insomnia (ISRS)
77
Depression (HADS
69
),
Anxiety (HADS
69
)
Only participants who did not report symptoms of the outcome variable
at baseline were included in analyses, e.g., if assessing insomnia as an
outcome variable, only participants who were not categorised as having
insomnia were used. Age and gender were used as predictor variables for
all analyses. Baseline covariates such as age, sex, social class and pain
areas were also controlled for.
Bidirectional
*Diagnosis. EDS, excessive daytime sleepiness; MDE, major depressive episode; SPIKE, The Structured Psychopathological Interview and Rating of Social Consequences of Psychic
Disturbances for Epidemiology; CBC, Child Behavior Checklist; CSHQ, Child Sleep Habits Questionnaire; CDI, Child Depression Inventory; BNSQ, Basic Nordic Sleep Questionnaire; USI,
Uppsala Sleep Inventory; HADS, Hamilton Anxiety Depression Scale; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders-IV; PSQI, Pittsburgh Sleep Quality Index; General Health
GHQ, Questionnaire; 10/66DDCRG, 10/66 Dementia in Developing Countries Research Group; GMS B3, Geriatric Mental State diagnostic schedule; SQS, Sleep Quality Scale; YSR, Youth
Self-report; TBS, Time in Bed Scale; ISRS, Insomnia Self-report Scale.
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Review of Sleep Disturbances, Anxiety and Depression—Alvaro et al
mon neurobiological underpinnings (i.e., neurotransmitters
and brain structures, discussed above) have been associated
with insomnia, anxiety, and depression.
46-53
Batterham and col-
leagues
56
hypothesize there may also be biological factors such
as increased inammatory dysregulation in response to sleep
disturbances
57
that are associated with anxiety
58
and depres-
sion.
59
Three other potential mechanisms discussed by Kaneita
and colleagues,
14
which may coexist, include common factors
(e.g., genetic, familial, social, or environmental) that indepen-
dently contribute to the development of insomnia, anxiety and
depression; insomnia, anxiety, and depression may be related,
in which only the order of appearance of symptoms may alter;
and insomnia, anxiety, and depression may be independent, but
mutually inuencing disorders.
A denitive conclusion is difcult to make regarding whether
sleep disturbances, anxiety, and depression are bidirectionally
related. Firstly, the small number of studies that assessed each
sleep disturbance variable prevents an accurate representation
of the true relationship between sleep disturbances, anxiety,
and depression. Further longitudinal studies are needed to un-
derstand whether there is a bidirectional relationship between
sleep disturbances, anxiety, and depression.
Secondly, sleep disturbance variables that were assessed by
the studies in this systematic review were limited and some-
times problematic. Prevalent sleep disorders such as obstruc-
tive sleep apnea and circadian rhythm sleep disorders were not
investigated, while insomnia symptoms such as problems with
sleep latency, nighttime awakenings, and daytime functioning
decits as a result of sleep were incorporated in the denition of
sleep quality
14,45
and childhood sleep problems.
43,44
The deni-
tion of childhood sleep problems also incorporated other sleep
disturbances such as nightmares, sleep duration, overtiredness,
bedtime resistance, sleep anxiety, parasomnias, sleep disor-
dered breathing, and daytime sleepiness. Therefore, implying
differences in ndings across sleep variables is problematic be-
cause distinctions between sleep variables are obscured and the
denition of childhood sleep problems was overly inclusive.
Future bidirectionality studies should focus on a broader range
of clearly dened sleep disturbances that contain reasonable
conceptual overlap.
Variables of anxiety and depression were also sometimes de-
ned using conceptually overlapping and overly inclusive vari-
ables, along with non-diagnostic self-report questionnaires, and
may variably reect current diagnostic criteria. Such cases in-
clude a combined depression/anxiety variable, which assessed
depression and anxiety as one construct. These inventories
could mask potential differences in bidirectionality across vari-
ables, and are problematic because bidirectional inferences can-
not be made about the relationship between sleep disturbances.
Indeed, only two studies assessed diagnosed insomnia, anxiety,
and depressive disorders.
11,42
Future studies should refrain from
using overly inclusive variables, and use denitions based on
established diagnostic criteria.
Moreover, bidirectionality between anxiety, depression,
and different types of insomnia symptoms (i.e., sleep onset in-
somnia, early morning awakening) was not assessed. Recent
Table 5—Comparison of study ndings between sleep variables
Sleep variables Study
Mental health
variable(s) Study design Results
Insomnia 40, 41 MDE Longitudinal
(immediate only)
Insomnia immediate follow up depression
40, 41 MDE Longitudinal (any
follow up)
Bidirectional
40, 41 “Pure depression” Longitudinal All no relationship
40, 41 Insomnia comorbid with
depression
Longitudinal All bidirectional
15 Depression, Anxiety Longitudinal Bidirectional
42 Depression* Longitudinal Bidirectional
17 Depression, Anxiety Longitudinal Bidirectional
11 Depression*, Anxiety* Retrospective
Anxiety Insomnia Depression
Insomnia comorbid
with depression
40, 41 “Pure depression” Longitudinal
2 bidirectional, 2 no relationship, 1 insomnia + depression
depression
EDS 40/41 MDE, Anxiety Longitudinal
Anxiety EDS, No relationship between EDS & major depression
Childhood sleep
problems
44 Depression/Anxiety Longitudinal
Childhood sleep problems Depression/Anxiety
43 Depression Longitudinal
Childhood sleep problems Depression
Sleep quality 14 Mental Health Status Longitudinal Bidirectional
45 Depression/Anxiety Longitudinal Bidirectional
Time in bed 45 Depression/Anxiety Longitudinal
Less time in bed Depression/Anxiety
*Diagnosis. EDS, Excessive Daytime Sleepiness; MDE, Major Depressive Episode.
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studies have suggested that the association between insomnia,
anxiety and depression may differ across specic insomnia
symptoms.
19,20
Therefore, it remains unclear whether anxiety
and depression are bidirectionally related across insomnia
symptoms. Further contributions to the eld may consider
different insomnia proles.
Also, studies did not consider bidirectionality across different
types of anxiety disorders. Johnson et al.,
11
found that comor-
bidity rates of insomnia vary across different subtypes. Future
research can assess whether sleep disturbances are consistently
bidirectionally associated with different anxiety proles.
Furthermore, the samples used by the included studies were
heterogeneous, assessing children, adolescents, young adults,
adults, and the elderly. Recent evidence has suggested age
may be related to types and prevalence rates of sleep distur-
bances,
60-62
rendering a comparison between studies potentially
awed at this time. The heterogeneous samples across studies
also prevented the use of meta-analytic techniques to perform
quantitative analyses.
Finally, important potential covariates were not controlled
for. One study corrected for alcohol and exercise, but no study
accounted for variables that have been associated with sleep dis-
turbances, anxiety, and depression such as lifestyle factors, med-
ical conditions, and other sleep disorders.
4,25-33
Bidirectionality
is difcult to infer without controlling for such variables. Future
research should account for variables such as circadian rhythm
disorders, drug and alcohol use, caffeine intake, and exercise.
Although few conclusions can be made, this study contrib-
utes to the burgeoning understanding of the etiological relation-
ship between, and prevention of anxiety, depression and various
sleep disturbances. At the very least, patients who present with
a sleep disturbance should also be assessed for anxiety and de-
pression, and vice-versa.
Bidirectionality was found between insomnia, anxiety, and de-
pression, suggesting that insomnia predicts and is predicted by
anxiety and depression. Therefore, successful treatment of in-
somnia may prevent the onset of subsequent or exacerbation of
comorbid anxiety or depression, and vice-versa.
14
Future research
should consider the most appropriate and cost-effective targets of
prevention and intervention for insomnia, anxiety and depression.
The unidirectional relationship between childhood sleep
problems and depression suggests that some sleep disturbances
may signicantly contribute to depression, at least in children,
but not vice-versa. Such conclusions should be treated with
caution due to the limited research in this area, the overly inclu-
sive nature of the childhood sleep problems variable, and the
conceptual overlap with insomnia. Further research is needed
to identify the specic sleep disturbance proles that indepen-
dently predict anxiety and depression.
In conclusion, due to the small number of studies in this area
and the heterogeneity of cohort samples used across studies,
few denitive conclusions about the bidirectionality of most
sleep disturbances can be made. Best available evidence to
date suggests depression bidirectional relationship between in-
somnia, anxiety, and depression, and further consolidates the
association found between sleep disturbances, anxiety, and de-
pression. Therefore, treatment of insomnia may prevent the de-
velopment of anxiety and depressive disorders, and vice-versa.
Future research should consider whether insomnia, anxiety,
or depression should be targeted to ensure the most efcient
and cost-effective method for prevention and intervention
of these disorders.
ACKNOWLEDGMENTS
Authors did not have conict of interests, including specic
nancial interests and relationships and afliations relevant to
the subject of this manuscript. The principal author “had full
access to all of the data in the study and takes responsibility for
the integrity of the data and the accuracy of the data analysis.”
DISCLOSURE STATEMENT
This was not an industry supported study. The authors have
indicated no nancial conicts of interest.
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