ARTICLE IN PRESS

Depression Status Is Associated with Functional Decline Over

1-Year Following Acute Stroke

Nada El Husseini, MD, MHS,*,† Larry B. Goldstein, MD,‡

Eric D. Peterson, MD, MHS,§ Xin Zhao, MHS,§ DaiWai M. Olson, RN, PhD,‖
John W. Williams Jr., MD, MHS,¶ Cheryl Bushnell, MD, MHS,* and
Daniel T. Laskowitz, MD, MHS†

Background: We investigated the independent association of depression status at

3 and 12 months after stroke and functional decline. Methods: Data were ob-
tained as part of the multicenter Adherence eValuation After Ischemic stroke
Longitudinal (AVAIL) registry. Depression was assessed with the Patient Health
Questionnaire-8 (depression, PHQ-8 ≥ 10), and functional status was assessed with
the modified Rankin score (mRS) at 3 and 12 months following hospitalization
for ischemic stroke. We used logistic regression analyses to evaluate the indepen-
dent association between the change in depression rating and the change in mRS.
Results: Among 1444 patients, 75% did not have depression at either time point,
9.2% had persistent depression, 8.7% had resolving depression, and 7% had in-
cident depression at 12 months. After covariate adjustment, depression status at
3 and 12 months remained associated with worsening mRS (P = .01). Compared
with patients without depression, those with resolving depression were less likely
to have a worsening mRS (odds ratio [OR] = .49, 95% confidence interval [CI]:
.29-0.83). There was no difference in functional decline between those with no
depression and those with persistent depression; however, those with persistent
depression had worse mRS at both time points (median mRS: 2.5 [Q1-Q3: 2-3] at
3 months; 2 [2-3] at 12 months) than those with no depression (mRS: 1 [0-2] at
both 3 and 12 months), P < .0001. Conclusions: Patients with resolving depres-
sion in the first year after stroke were less likely to have functional deterioration
than those without depression. Greater functional impairment was present in the
setting of depression. Key Words: Depression after stroke—functional
recovery—stroke—functional decline.
© 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

From the *Department of Neurology, Wake Forest Baptist University Health Sciences, Winston-Salem, North Carolina; †Department of Neu-
rology, Duke University Medical Center, Durham, North Carolina; ‡Department of Neurology, University of Kentucky, Lexington, Kentucky;
§Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina; ‖Department of Neurology, UT Southwestern,
Dallas, Texas; and ¶Department of Medicine, Durham Veterans Affairs, Durham, North Carolina.
Received November 10, 2016; revision received February 24, 2017; accepted March 21, 2017.
Sources of Funding: The AVAIL project was supported by unrestricted funds from Bristol-Myers Squibb/Sanofi Pharmaceuticals Partner-
ship and conducted through collaboration with the American Heart Association and the “Get With The Guidelines–Stroke” program. AVAIL
analyses were also supported in part by the Agency for Healthcare Research and Quality cooperative agreement U18HS016964.
Address correspondence to Nada El Husseini, MD, MHS, Wake Forest Baptist Medical Center, Department of Neurology, Division of Vascular
Neurology, 6th Floor Janeway Tower, Medical Center Boulevard, Winston-Salem, NC 27157. E-mail: nelhusse@wakehealth.edu.
1052-3057/$ - see front matter
© 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2017.03.026

Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2017: pp ■■–■■ 1
 ARTICLE IN PRESS
2 N. EL HUSSEINI ET AL.
Introduction
Stroke can cause acute loss of functional indepen-
dence and may be associated with progressive functional
loss for up to 5 years.1 The annual increase in disability
before stroke more than triples after stroke.2 Even after
excluding patients with recurrent clinical stroke, there
is a steeper decline in functional status after an isch-
emic stroke compared with before stroke.3 Up to one
third of stroke survivors experience depression.4,5 The
duration of depression also varies, with up to half of
those with depression recovering and a smaller percent-
age having persistent or new-onset depression within
the first year.5,6
Studies evaluating the impact of depression on post-
stroke functional outcome are inconsistent, in part due
to heterogeneity in study designs.7-10 Several reports find
both an association between depression and a function-
al status measured at the same time point,7,11 and between
baseline depression and subsequent functional outcome,6,12
but it remains unclear whether changes in post-stroke de-
pression influence functional decline.13
Understanding whether post-stroke depression con-
tributes to functional decline, beyond its known association
with functional outcome, may identify additional targets
in the care of patients with stroke experiencing function-
al decline in the first year post stroke. In the current study,
we hypothesized that the changes in depression in the
first year after stroke were associated with functional
decline. We specifically aimed to compare the effects of
resolving and incident depression with persistent or no
depression.
Methods
Study Population and Design
This is a secondary analysis of a multicenter prospec-
tive cohort registry (Adherence eValuation After Ischemic
stroke Longitudinal [AVAIL] study), which was de-
signed to assess adherence to stroke prevention medications
from hospital discharge to 1 year in patients admitted
with stroke or transient ischemic attack (TIA). The AVAIL
study methodology has been published.14 Our study in-
cluded only patients with stroke and excluded patients
with TIA. Briefly, 2492 patients with stroke were re-
cruited from hospitals participating in the Get With The
Guidelines (GWTG)–Stroke program from July 2006 to
July 2008. The 12-month follow-up was completed in
August 2009. Outcome Sciences, Inc., served as the data
collection and coordinating center for GWTG–Stroke. The
Duke Clinical Research Institute served as the data anal-
ysis center for both GWTG and AVAIL. Each participating
site obtained institutional review board approval before
enrolling patients into AVAIL. The Strengthening the Re-
porting of Observational Studies in Epidemiology statement
was followed for reporting this study.15
Initial AVAIL cohort
N = 2492
Exclusions:
1) Without GWTG enrollment admission (N = 9)
2) Follow-up not performed at 3 or 12 months (N = 325)
3) Died before 12 month interview (N = 84)
4) Proxy records-PHQ-8 not performed (N = 526)
5) PHQ-8 missing at 3 or 12 months (N = 52)
6) Antidepressant dose missing at 3 or 12 months (N = 46)
7) mRS missing at 3 or 12 months (N = 6)
Stroke
N=1444
Stroke
N = 1444
Figure 1. Cohort selection.
Subject Recruitment
The inclusion criteria for this study were age 18 years
or older; hospitalization for a primary diagnosis of acute
ischemic stroke based on the GWTG–Stroke Internation-
al Classification of Diseases, Ninth Edition Codes; direct
admission based on physician evaluation or arrival through
the emergency department; patient or legally autho-
rized representative consent to participate; and patient
inclusion in the GWTG–Stroke program.
Subjects were excluded from the present analysis if base-
line data were missing or if the Patient Health
Questionnaire-8 (PHQ-8), antidepressant drug dose, or
modified Rankin score (mRS) were missing at the 3-month
or 12-month follow-up (Fig 1). Subjects were contacted
by telephone by research personnel at the Duke Clini-
cal Research Institute at 3 months and 12 months after
hospital discharge. Centralized interviewers used stan-
dardized scripts for follow-up.
Outcomes and Covariates
Depression was assessed prospectively with a self-
reported depressive symptoms scale (PHQ-8) at both 3
months and 12 months following hospitalization.
The PHQ-8, based on symptoms within the previous
2 weeks, includes 8 of the 9 criteria from the Diagnostic
and Statistical Manual of Mental Disorders, Fourth Edition,
for diagnosis of major depressive disorder.16 The PHQ-8
yields a score from 0 to 24, with a score of ≥10 indicat-
ing a clinically significant depressive disorder.17 This cutoff
has a sensitivity and specificity of 88% and positive pre-
dictive value of 57% for major depression.17 The PHQ-8
performance as a depression screening tool is comparable
 ARTICLE IN PRESS
DEPRESSION STATUS AND FUNCTIONAL DECLINE
with the PHQ-9 with excellent agreement between the
2. 18 The PHQ-9 has been validated for post-stroke
depression19 and is sensitive to change.20 The PHQ-8 rather
than PHQ-9 was more appropriate for this observa-
tional study in which real-time monitoring of individual
positive responses to the question about suicidal thoughts
was not possible. The PHQ-8 could not be administered
by proxy. The main predictor variable was the change
in depression score between 3 months and 12 months,
classified as follows: no depression (PHQ-8 < 10 at both
3 months and 12 months); incident depression (PHQ-
8 < 10 at 3 months but PHQ-8 ≥ 10 at 12 months); resolved
depression (PHQ-8 ≥ 10 at 3 months but <10 at 12 months);
and persistent depression (PHQ-8 ≥ 10 at both 3 months
and 12 months).
Medication use was subject-reported and ascertained
through a series of questions aimed at comparing current
and previous use. Antidepressant use at doses at or above
those recommended for treatment of depression was iden-
tified based on a previously validated algorithm.21
The primary outcome for this analysis was the change
in mRS between 3 months and 12 months following hos-
pitalization for stroke. The mRS is a global disability scale
ranging between 0 and 6, with increasing score indicat-
ing greater disability (a score of 6 reflects death). The mRS
was prospectively scored at each follow-up with a stan-
dardized telephone interview. The change in functional
status was determined by comparing the 3-month and
12-month mRS and was dichotomized as “stable or im-
proved” versus “worse.” Any increase in the mRS between
3 and 12 months was considered worsening.
Covariates for this analysis included age, sex, race, post-
hospital rehabilitation, recurrent stroke or TIA between
3 months and 12 months, antidepressant use at 3 months
or 12 months, initial stroke severity assessed with Na-
tional Institutes of Health Stroke Scale, medical history
of diabetes, history of coronary artery disease or myo-
cardial infarction, insurance status, and marital status. These
variables were selected because they were previously as-
sociated with post-stroke functional outcome.22-25 Because
recurrent stroke or TIA is likely to be associated with the
primary outcome of worsening functional outcome, a sen-
sitivity analysis excluding those with recurrent stroke or
TIA was performed.
Trained hospital personnel abstracted baseline time-
independent demographic information from inpatient
medical records as part of the GWTG–Stroke admis-
sion. Time-dependent patient characteristics were self-
reported by patients on follow-up at each time point as
part of the AVAIL protocol.
Statistical Analysis
Frequency distribution was used for categorical vari-
ables. Median, first, and third quartiles were calculated
for continuous variables. The association between the
3
change in depression status and the change in mRS
between 3 and 12 months was examined by multivari-
able logistic modeling adjusted for relevant covariates.
Backward selection was used to remove variables with
P value > .1 to obtain the final models. The rate of missing
covariate data was low, with the exception of the Na-
tional Institutes of Health Stroke Scale, which was missing
in about 30%. Missing data were imputed to the most
popular category or based on clinical perspective. All P
values are 2-sided, with P < .05 considered as statistical-
ly significant. All analyses were performed using SAS
version 9.3 (SAS Institute Inc., Cary, North Carolina).
Results
Data were available for 1444 patients (44.1% female,
82.4% white) from 97 hospitals in the United States (Fig 1).
Median age was 64 years (Q1-Q3: 55-74); 57.4% re-
ceived rehabilitation and 18.2% were using antidepressant
medications. Overall, 1081 subjects (75% of the entire study
cohort) did not have depression at either time point, 134
(9.2%) had persistent depression, 126 (8.7%) had resolv-
ing depression, and 103 (7%) had incident depression at
12 months (Table 1). Those with persistent depression were
more likely than the other groups to be younger, using
antidepressant medications, and to be unmarried (Table 1).
A total of 1112 subjects (77.0%) had an mRS <3 at 3
months as compared with 1157 (80.1%) at 12 months. Rel-
ative to 3 months, the 12-month mRS was stable or
improved in 1095 (75.8%) and worse in 349 (24.2%) pa-
tients. A total of 79 subjects had recurrent stroke or TIA
between 3 months and 12 months. Among those with re-
current stroke or TIA, 53 subjects had stable or improved
mRS by 12 months (4.8% of total subjects with stable or
improved mRS), whereas 26 subjects had a poorer mRS
by 12 months (7.4% of total subjects with increased mRS).
A similar proportion of patients used antidepressant medi-
cations in both groups (18.2%; n = 200 of those with a
stable or improved mRS versus 18.3%; n = 63 of those
with a worse mRS).
On univariate analysis, functional worsening was more
common among those with incident depression (31.7%)
and least common among those with resolving depres-
sion (13.5%), P = .001. Subjects with persistent depression
had a higher median mRS (median mRS: 2.5 [Q1-Q3: 2-3]
at 3 months and 2 [2-3] at 12 months) than subjects with
no depression (median mRS: 1 [Q1-Q3: 0-2] at both 3
months and 12 months), P < .001.
Worsening functional outcome was not associated with
recurrent stroke or TIA (P = .062) or with antidepres-
sant use (P = .969). Both recurrent stroke or TIA and
antidepressant use were excluded by backward selec-
tion from the final regression model. After adjustment
for covariates, only depression status at 3 months and
12 months (P = .010) and older age (odds ratio [OR] = 1.02,
95% confidence interval [CI]: 1.01-1.03 per 10 years, P < .001)
 ARTICLE IN PRESS
4 N. EL HUSSEINI ET AL.
Table 1. Subject characteristics classified by depression at 3 and 12 months

Incident Resolved Persistent

Total No depression depression depression depression P value

Variable level N = 1444 n = 1081 n = 103 n = 126 n = 134

Age (y)
Median (Q1-Q3) 64 (55-74) 66 (57-75) 60 (52-72) 60 (53-70) 56 (49-61) <.0001
Sex
Female (%) 637 (44.1) 458 (42.3) 52 (50.4) 59 (49.8) 68 (50.7) .112
Race or ethnicity
White (%) 1191 (82.4) 915 (84.6) 80 (77.6) 98 (77.7) 98 (73.1) .014
Black or African American (%) 159 (11.0) 97 (8.9) 17 (16.5) 23 (18.2) 22 (16.4)
Hispanic (%) 36 (2.4) 22 (2.0) 4 (3.8) 4 (3.1) 6 (4.4)
Marriage status
Married (%) 869 (60.1) 671 (62.0) 55 (53.4) 74 (58.7) 69 (51.4) <.0001
Rehabilitation (physical, occupational,
speech therapy or rehabilitation)
between 3 and 12 months
Yes 829 (57.4) 609 (56.3) 61 (59.2) 76 (60.3) 83 (61.9) .511
Recurrent stroke or TIA between 3
and 12 months
Yes (%) 79 (5.4) 47 (4.3) 9 (8.7) 12 (9.5) 11 (8.2) .013
Antidepressant use at 3 or 12 months
Yes (%) 263 (18.2) 160 (14.8) 27 (26.2) 33 (26.1) 43 (32.0) <.0001
Medical history of diabetes mellitus
Yes (%) 383 (29.3) 275 (28.3) 31 (31.9) 32 (28.3) 45 (35.7) .343
Medical history of CAD or MI
Yes (%) 307 (23.4) 233 (24.0) 21 (21.6) 30 (26.5) 23 (18.2) .418
NIHSS
Median (Q1-Q3) 3 (1-6) 3 (1-6) 3 (1-6) 3 (1-6) 3 (2-9) .050
mRS at 3 months 2 1 2 2 2.5 <.0001
Median (Q1-Q3) (1-2) (0-2) (1-3) (2-3) (2-3)
mRS at 12 months 2 1 2 2 2 <.0001
Median (Q1-Q3) (1-2) (0-2) (2-3) (1-2) (2-3)
Worsening mRS between 3 and 12 months 349 (24.2) 273 (25.3) 33 (31.7) 17 (13.5) 26 (19.4) .0001

Abbreviations: CAD, coronary artery disease; MI, myocardial infarction; mRS, modified Rankin score; NIHSS, National Institutes of Health
Stroke Scale; TIA, transient ischemic attack.

were associated with worsening mRS (Table 2). Com-
pared with no depression at either time point, persistent
depression (OR = .85, 95% CI: .53-1.34) and incident de-
pression (OR = 1.48, 95% CI: .95-2.30) were not significantly
associated with worsening mRS. In contrast, those with
resolving depression were less likely to have a worsen-
ing mRS (OR = .49, 95% CI: .29-0.83). A sensitivity analysis
excluding those with recurrent stroke or TIA yielded similar
results (Table 2).
When persistent depression was used as the refer-
ence group, depression status at 3 months and 12 months
remained associated with change in functional outcome
(P = .023). Compared with persistent depression, resolv-
ing depression tended to be associated with a lower
likelihood of worsening mRS, although the difference was
not statistically significant (OR .45, 95% CI: .20-1.02). There
was no significant difference in functional deterioration
between incident and persistent depression (OR = 1.74;
95% CI: .86-3.51) (Table 2).
Discussion
Post-stroke depression may worsen functional outcome
by interfering with both cognitive and physical recov-
ery and impeding participation in rehabilitation. In addition,
depression may alter brain regulatory mechanisms that
may in turn affect outcomes; for example, depression is
associated with decreased cortical regulation of limbic ac-
tivation in response to various stimuli.26 In a systematic
review of the association between post-stroke depres-
sion and post-stroke functional outcome (14 cohorts with
4498 participants), post-stroke depression was inversely
associated with functional outcome.27 Most of the cohorts
in this review, however, included patients with intracranial
 ARTICLE IN PRESS
DEPRESSION STATUS AND FUNCTIONAL DECLINE 5
Table 2. Multivariate logistic regression analysis of depression and functional decline with “never depressed” and with
“persistently depressed” as the reference groups

Adjusted OR (95% CI) for

worsening in functional
Adjusted OR (95% CI) for decline after excluding
worsening in functional subjects with recurrent
Variable decline P value stroke or TIA P value

Incident depression versus never depressed 1.48 (.95-2.30) .010 1.49 (.94-2.36) .013
Resolving depression versus never depressed .49 (.29-0.83) .49 (.28-0.86)
Persistent depression versus never depressed .85 (.53-1.34) .78 (.48-1.27)
Incident depression versus persistently depressed 1.74 (.86-3.51) .023 2.10 (.98-4.46) .023
Resolving depression versus persistently depressed .45 (.20-1.02) .58 (.24-1.38)
Never depressed versus persistently depressed 1.10 (.64-1.88) 1.26 (.70-2.26)

Abbreviations: CAD, coronary artery disease; CI, confidence interval; MI, myocardial infarction; NIHSS, National Institutes of Health
Stroke Scale; OR, odds ratio; TIA, transient ischemic attack.
Sex, race or ethnicity, post-hospital rehabilitation, recurrent stroke or TIA between 3 and 12 months post stroke, baseline NIHSS, medical
history of diabetes, medical history of CAD or MI, insurance status, marital status, and antidepressant use at 3 or 12 months were excluded
from the final model by backward selection. The analysis was also adjusted for age. The table also includes the results of the sensitivity anal-
ysis excluding subjects with recurrent stroke or TIA.

hemorrhage in addition to those with ischemic stroke and
assessed functional outcome days to years after the as-
sessment of depression. 27 Depression did not affect
functional improvement in 2 studies.28,29 Both of these
studies were rehabilitation based and did not evaluate
whether change in depression affected the trajectory of
functional outcome. One study found that function im-
proved over time regardless of depression in the first year
after stroke, but functional outcome was better among
those who were not initially depressed.28 In another study,
depression was associated with increased disability at both
admission and follow-up in the first 6 months after stroke,
but depression was not associated with functional
improvement.29 In another study, both early-onset (within
2 weeks) and late-onset post-stroke depression (after 2
weeks and within the first year following stroke) were
independently associated with disability and poor func-
tional outcome at 1 year after stroke.30 Recovery from
depression within 1 year decreased but did not elimi-
nate the adverse impacts of post-stroke depression on
functional outcome and quality of life. In this study, out-
comes including disability (mRS ≥ 2) and quality of life
(Short Form-36 Health Survey) were assessed at 1-year
follow-up but not longitudinally.30 Even a decade after
stroke in individuals aged 18-50 years, depressive symp-
toms and anxiety were more prevalent and associated with
poor functional outcome.31
Whereas multiple studies showed an association between
post-stroke depression and poor functional outcome, fewer
studies evaluated changes in psychological symptoms in
relation to changes of functional outcome after stroke.32
One study found an association between the trajectory
of psychological symptoms assessed by the General Health
Questionnaire and the functional outcome measured by
the Barthel Index in the first 52 weeks after stroke, but
functional outcome was assessed at only a single time
point.33 Similarly, increases in positive emotion score (as-
sessed by 4 items from the Center for Epidemiologic Studies
Depression Scale) following stroke compared with no change
or a decline was associated with better functional status
assessed at 3 months.34 Another study of an inpatient medical
rehabilitation-based cohort evaluated depression trajec-
tory (measured by change in Center for Epidemiologic
Studies Depression Scale score) in relation to change in
functional status (Functional Independence Measure in-
strument) in the first year following stroke found greater
improvement in functional status among those who were
not depressed at discharge and had fewer depressive symp-
toms on follow-up. This study, however, combined ischemic
and hemorrhagic stroke and was limited to subjects aged
65 years and older, limiting generalizability.35 In contrast
to these findings, another smaller rehabilitation based-
study of 64 patients comparing those with and without
depression assessed at 1 time point within weeks of first
stroke found similar improvements in functional status
between the 2 groups, but greater functional impairment
among those who were depressed.10
Because post-stroke depression is dynamic, with inci-
dent and resolving depression occurring in the first year
after stroke, we determined if changes in depression status
were associated with functional decline. We found that
the improvement in depression following hospitaliza-
tion for ischemic stroke was associated with a lower
likelihood of having a worsening in functional status
between 3 months and 12 months post stroke. The lower
likelihood of functional deterioration with resolving de-
pression in comparison with no depression may be due
to a worse initial mRS in those who were initially
 ARTICLE IN PRESS
6 N. EL HUSSEINI ET AL.
depressed. We previously found that poor functional
outcome at 3 months was associated with depression at
12 months (OR 1.49, 95% CI: 1.29-1.73 for each 1-unit in-
crease in mRS) and with persistent depression (OR 1.93,
95% CI: 1.62-2.30).6 In the current analysis, worsening in
functional outcome did not occur in patients who were
persistently depressed, likely because functional outcome
was “poor” (mRS was high) at both time points in this
group.10
Our findings could indicate that the resolution of de-
pression prevents worsening in functional status.
Alternatively, no worsening or improvement in function-
al status might lead to improved mood. In addition,
although heavily motor weighted, the mRS may be af-
fected by nonphysical attributes such as post-stroke mood
disturbances that can contribute to perceived disability.7,36
The positive association between incident depression
at 12 months and worsening mRS scores was not sig-
nificant. The lack of significance may be due to the
relatively small sample size, but it is also plausible that
the effect of late-onset depression on functional outcome
may be qualitatively different from early onset depres-
sion, as most stroke recovery takes place over the first
several months. Surprisingly, recurrent stroke or TIA was
not associated with functional decline. This could be at-
tributed to how recurrent stroke or TIA was ascertained
in AVAIL (participant self-report).
This study has several limitations. It is a secondary anal-
ysis of a prospective cohort registry. The majority of the
cohort had mild disability (mRS < 3), likely explaining the
lower rate of depression in this cohort as compared with
other studies.4 About 82.6% were white, which may limit
the generalizability to other race or ethnic groups. The
demographics of the AVAIL population, however, did not
differ substantially from the overall GWTG–Stroke cohort.
Because subjects rather than proxies were required to com-
plete the PHQ-8, 526 patients were excluded. For this
reason, the results may be biased toward those with mild
disability including those without aphasia or significant
cognitive impairments. In addition, prestroke depres-
sion, shown to be strongly associated with poststroke
depression, was not assessed in our study.27 Given this
limitation, we cannot exclude the possibility that a pro-
portion of subjects in the cohort had a prestroke history
of depression. A confounding effect of selective sero-
tonin reuptake inhibitors that are often used for the
treatment of post-stroke depression on motor recovery
is possible.37 Although antidepressant medications in this
study were not analyzed by category, we adjusted for
antidepressant use in the regression analyses, and only
antidepressants used at a commonly prescribed dose for
depression indication based on a previously validated al-
gorithm were included to help ensure that they were being
used for depression and not for other indications.21
The strengths of this study were the large cohort of
patients with stroke with complete follow-up who had
prospectively and longitudinally evaluated depressive
symptoms, antidepressant use, and functional outcome
in the first year post stroke. In AVAIL, subjects were re-
cruited from geographically diverse hospitals participating
in the American Heart Association GWTG–Stroke program.
Hospitals participating in the GWTG–Stroke program do
tend to be larger, urban, and teaching centers. Despite
these differences, a study of the representativeness of the
GWTG–Stroke registry indicates that the data are gen-
erally representative of national fee-for-service Medicare
ischemic stroke populations, providing support for ex-
ternal validity.38
In contrast to cross-sectional or only baseline data, our
study provides a longitudinal analysis of the changes in
both depression and functional outcome in the first year
following ischemic stroke. Our observations suggest that
recovery from post-stroke depression is associated with
a decrease in post-stroke functional decline. Although func-
tional decline occurred in those without depression and
in those with persistent depression at a similar rate, de-
pression was associated with worse functional outcome.
These results point to the importance of the longitudi-
nal evaluation of depression in the first year following
stroke.
References
1. Dhamoon MS, Moon YP, Paik MC, et al. Long-term
functional recovery after first ischemic stroke: the Northern
Manhattan Study. Stroke 2009;40:2805-2811.
2. Mandip S, Dhamoon MSE. Disability trajectories before
and after vascular events: the Cardiovascular Health
Study. International Stroke Conference oral
abstracts—session title: clinical rehabilitation and recovery
oral abstracts II: abstract 142. Stroke 2015;46:A142.
3. Dhamoon MS, Moon YP, Paik MC, et al. Trajectory of
functional decline before and after ischemic stroke: the
Northern Manhattan Study. Stroke 2012;43:2180-2184.
4. Hackett ML, Pickles K. Part I: frequency of depression
after stroke: an updated systematic review and meta-
analysis of observational studies. Int J Stroke 2014;9:1017-
1025.
5. Hackett ML, Yapa C, Parag V, et al. Frequency of
depression after stroke: a systematic review of
observational studies. Stroke 2005;36:1330-1340.
6. El Husseini N, Goldstein LB, Peterson ED, et al.
Depression and antidepressant use after stroke and
transient ischemic attack. Stroke 2012;43:1609-1616.
7. Dennis M, O’Rourke S, Lewis S, et al. Emotional outcomes
after stroke: factors associated with poor outcome. J
Neurol Neurosurg Psychiatry 2000;68:47-52.
8. Donnellan C, Hickey A, Hevey D, et al. Effect of mood
symptoms on recovery one year after stroke. Int J Geriatr
Psychiatry 2010;25:1288-1295.
9. Andersen G, Vestergaard K, Ingemann-Nielsen M, et al.
Risk factors for post-stroke depression. Acta Psychiatr
Scand 1995;92:193-198.
10. Sinyor D, Amato P, Kaloupek DG, et al. Post-stroke
depression: relationships to functional impairment, coping
strategies, and rehabilitation outcome. Stroke 1986;17:1102-
1107.
 ARTICLE IN PRESS
DEPRESSION STATUS AND FUNCTIONAL DECLINE
11. Schwab-Malek S, Vatankhah B, Bogdahn U, et al. De-
pressive symptoms and quality of life after thrombolysis
in stroke: the TEMPiS study. J Neurol 2010;257:1848-1854.
12. Willey JZ, Disla N, Moon YP, et al. Early depressed mood
after stroke predicts long-term disability: the Northern
Manhattan Stroke Study (NOMASS). Stroke 2010;41:1896-
1900.
13. Schmid AA, Kroenke K, Hendrie HC, et al. Poststroke
depression and treatment effects on functional outcomes.
Neurology 2011;76:1000-1005.
14. Bushnell C, Zimmer L, Schwamm L, et al. The Adherence
eValuation After Ischemic Stroke Longitudinal (AVAIL)
registry: design, rationale, and baseline patient
characteristics. Am Heart J 2009;157:428-435. e422.
15. Vandenbroucke JP, von Elm E, Altman DG, et al.
Strengthening the Reporting of Observational Studies in
Epidemiology (STROBE): explanation and elaboration.
Ann Intern Med 2007;147:W163-W194.
16. American Psychiatric Association. Diagnostic and statistical
manual of mental disorders. 4th ed. Washington, DC:
American Psychiatric Association, 1994.
17. Kroenke K, Strine TW, Spitzer RL, et al. The PHQ-8 as
a measure of current depression in the general population.
J Affect Disord 2009;114:163-173.
18. Wells TS, Horton JL, LeardMann CA, et al. A comparison
of the PRIME-MD PHQ-9 and PHQ-8 in a large military
prospective study, the Millennium Cohort Study. J Affect
Disord 2013;148:77-83.
19. Williams LS, Brizendine EJ, Plue L, et al. Performance
of the PHQ-9 as a screening tool for depression after
stroke. Stroke 2005;36:635-638.
20. Lowe B, Kroenke K, Herzog W, et al. Measuring
depression outcome with a brief self-report instrument:
sensitivity to change of the Patient Health Questionnaire
(PHQ-9). J Affect Disord 2004;81:61-66.
21. Damush TM, Jia H, Ried LD, et al. Case-finding algorithm
for post-stroke depression in the veterans health
administration. Int J Geriatr Psychiatry 2008;23:517-522.
22. Berges IM, Kuo YF, Ottenbacher KJ, et al. Recovery of
functional status after stroke in a tri-ethnic population.
PM R 2012;4:290-295.
23. Hankey GJ, Spiesser J, Hakimi Z, et al. Rate, degree, and
predictors of recovery from disability following ischemic
stroke. Neurology 2007;68:1583-1587.
24. Jorgensen HS, Reith J, Nakayama H, et al. What
determines good recovery in patients with the most severe
strokes? The Copenhagen Stroke Study. Stroke 1999;30:
2008-2012.
25. Mikami K, Jorge RE, Adams HP Jr, et al. Effect of
antidepressants on the course of disability following
stroke. Am J Geriatr Psychiatry 2011;19:1007-1015.
7
26. Anand A, Li Y, Wang Y, et al. Activity and connectivity
of brain mood regulating circuit in depression: a functional
magnetic resonance study. Biol Psychiatry 2005;57:1079-
1088.
27. Kutlubaev MA, Hackett ML. Part II: predictors of
depression after stroke and impact of depression on stroke
outcome: an updated systematic review of observational
studies. Int J Stroke 2014;9:1026-1036.
28. Bacher YK-BN, Mayo N, Becker R, et al. A longitudinal
study of depression among stroke patients participating
in a rehabilitation program. Can J Rehabi 1990;4:27-37.
29. van de Weg FB, Kuik DJ, Lankhorst GJ. Post-stroke
depression and functional outcome: a cohort study
investigating the influence of depression on functional
recovery from stroke. Clin Rehabil 1999;13:268-272.
30. Shi YZ, Xiang YT, Yang Y, et al. Depression after minor
stroke: the association with disability and quality of life—a
1-year follow-up study. Int J Geriatr Psychiatry
2016;31:421-427.
31. Maaijwee NA, Tendolkar I, Rutten-Jacobs LC, et al.
Long-term depressive symptoms and anxiety after
transient ischaemic attack or ischaemic stroke in young
adults. Eur J Neurol 2016;23:1262-1268.
32. Ghosal MK, Burman P, Singh V, et al. Correlates of
functional outcome among stroke survivors in a
developing country—a prospective community-based
study from India. J Stroke Cerebrovasc Dis 2014;23:2614-
2621.
33. West R, Hill K, Hewison J, et al. Psychological disorders
after stroke are an important influence on functional
outcomes: a prospective cohort study. Stroke 2010;41:
1723-1727.
34. Seale GS, Berges IM, Ottenbacher KJ, et al. Change in
positive emotion and recovery of functional status
following stroke. Rehabil Psychol 2010;55:33-39.
35. Ostir GV, Berges IM, Ottenbacher A, et al. Patterns of
change in depression after stroke. J Am Geriatr Soc
2011;59:314-320.
36. Banks JL, Marotta CA. Outcomes validity and reliability
of the modified Rankin scale: implications for stroke
clinical trials: a literature review and synthesis. Stroke
2007;38:1091-1096.
37. Chollet F, Tardy J, Albucher JF, et al. Fluoxetine for motor
recovery after acute ischaemic stroke (FLAME): a
randomised placebo-controlled trial. Lancet Neurol
2011;10:123-130.
38. Reeves MJ, Fonarow GC, Smith EE, et al.
Representativeness of the Get With The Guidelines–Stroke
Registry: comparison of patient and hospital characteristics
among Medicare beneficiaries hospitalized with ischemic
stroke. Stroke 2012;43:44-49.