Journal of Clinical Neuroscience 98 (2022) 133–136

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Journal of Clinical Neuroscience

journal homepage: www.journals.elsevier.com/journal-of-clinical-neuroscience

Clinical study

Association of in-hospital depression and anxiety symptoms following

stroke with 3 months- depression, anxiety and functional outcome
Cintasha Redmond a, Cheryl Bushnell b, Pamela Duncan b, Ralph D’Agostino Jr c,
Walter T. Ambrosius c, Laura Bishop d, Sabina Gesell e, Janet Prvu-Bettger f, Nada El Husseini b, g, *
a
Novant Health, Winston Salem, NC, United States
b
Department of Neurology, Wake Forest Baptist Medical Center, Winston-Salem, NC, United States
c
Department of Biostatistical Sciences, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, United States
d
Department of Neurology, Medical University of South Carolina, United States
e
Department of Social Sciences and Health Policy, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, United States
f
Department of Orthopedic Surgery, Duke University School of Medicine, Durham, NC, United States
g
Department of Neurology, Duke University Medical Center, Durham NC, United States

A R T I C L E I N F O A B S T R A C T

Keywords: Background: Post-stroke depression and anxiety are common and are associated with worse post-stroke outcomes.
Depression after stroke Even though checking for depression during stroke hospitalization has become a common practice, the prog­
ED-Q5-3L nostic value of a positive in-hospital depression screen following stroke remains unclear.
Stroke
Methods: This is a retrospective cohort study of patients with stroke or TIA discharged home from a tertiary care
Anxiety
center. We examined the association between premorbid history of depression and in-hospital anxiety/depressive
symptoms, with anxiety/depressive symptoms and functional outcome at 3-months post-stroke. Logistic
regression models were generated using two different main predictors: 1) pre-hospital history of depression (N =
117) and 2) in-hospital depression/anxiety measured by the EQ-5D-3L (N = 66).
Results: In the cohort of 117 patients, the mean age was 66 years, with median NIHSS 2;44% were women and
70% White. A history of pre-stroke depression was reported by 7% (8/117). Anxiety/depression on ED-5D-3L
was reported by 29/66 (43%) in the hospital and by 22/66 (33%) at three months’ post-stroke. In the first
adjusted model, previous history of depression was associated with 3 months EQ-5D-3L anxiety/depression (OR
= 10.2;95%CI:1.12–90.9, p = 0.038). In the second adjusted model, in-hospital anxiety/depression was asso­
ciated with 3-month EQ-5D-3L anxiety/depression (OR = 3.9; 95% CI:1.16–13.1, p = 0.027). In-hospital anxi­
ety/depression was associated with a higher mRS at 3 months but not after adjusting for covariates.
Conclusion: A previous history of depression and in-hospital anxiety/depression symptoms are associated with
anxiety/depression symptoms 3-months post-stroke but not with functional outcome. Screening stroke patients
for both during hospitalization is warranted because of the association with later symptoms.

1. Introduction
Stroke is a leading cause of long-term disability [1]. Post stroke
depression (PSD) is common, affecting about one third of stroke survi­
vors and is associated with worse post-stroke outcomes including
increased mortality and poor functional outcome [2]. The frequency of
depression is highest in the first year after stroke at nearly 1 in 3 S
survivors and declines thereafter.[2] Depressive symptoms may be
associated with decreased rehabilitation efficiency in stroke patients.
However, early identification can potentially lead to improved outcomes
[3]. Multiple studies have evaluated predictors of PSD, but because of
differences in inclusion and exclusion criteria and statistical methods,
generalizability is limited [2]. Despite the importance of recognizing
and treating PSD, there is still no widely adopted consensus regarding
when to screen for PSD[2] Evaluating whether depressive symptoms
early after stroke predict post-discharge outcomes would help inform
future policies regarding the timing of depression screening . For
example, one study that evaluated PSD depression in the “acute phase”
after stroke found an association with post stroke depression and func­
tional impairment three years later [4]. In this study, participants were

* Corresponding author at: Duke University Medical Center, Department of Neurology, United States.
E-mail address: nada.elhusseini@duke.edu (N. El Husseini).

https://doi.org/10.1016/j.jocn.2022.02.010
Received 15 October 2021; Accepted 9 February 2022
Available online 15 February 2022
0967-5868/© 2022 Elsevier Ltd. All rights reserved.
C. Redmond et al. Journal of Clinical Neuroscience 98 (2022) 133–136

recruited from rehabilitation facilities rather than during their acute

hospitalization [4].
Depression in the first few days after stroke is common affecting
about half of hospitalized stroke patients [5]. As there is concern that
inpatient screening may be affected by the acute reaction to illness and
the limited time a patient is in the hospital, with depression diagnosis
usually requiring persistent depressive symptoms for at least 2 weeks,
the prognostic value of a positive inpatient depression screen following
stroke remains unclear [6–9].
Onset of anxiety disorders is also common post-stroke affecting about
a quarter of stroke survivors [10,11] and is associated with worse
functional outcome and quality of life [10]. Anxiety is often co-morbid
with depression. Similar to depression, the prognostic value of a posi­
tive anxiety screen during stroke hospitalization remains unclear [12].
This study aims to 1) evaluate whether a history of pre-stroke
depression is associated with 3- month post stroke depressive/anxiety
symptoms, 2) evaluate if in-hospital depressive and anxiety symptoms
are associated with similar symptoms 3 months after stroke and 3)
evaluate if a history of depression and inpatient depression/anxiety
symptoms are associated with 3 months functional outcome [13]. We
hypothesized that pre-stroke history of depression is a strong risk factor
Fig. 1. Selection of participants.
for PSD and that early screening of hospitalized stroke patients for
depressive and anxiety symptoms is associated with clinically relevant
hospital discharge and at 3-months post-stroke. Covariates included in
short term (3 months) outcomes.
the models were selected a priori based on their possible association with
the outcome.
2. Methods
Depressive/anxiety symptoms in the hospital and at 3-months
follow-up were assessed using the EuroQol five dimensions question­
Study design: This is a retrospective study of patients admitted for
naire (EQ-5D-3L). The EQ-5D-3L descriptive system comprises the
acute stroke (ischemic or hemorrhagic) or Transient Ischemic Attack
following five dimensions: mobility, self-care, usual activities, pain/
(TIA) at a tertiary referral academic medical center. The cohort included
discomfort and anxiety/depression. Each dimension has 3 levels: “no
patients enrolled in the TRAnsition Coaching for Stroke (TRACS) pro­
problems”, “some problems”, and “extreme problems”. Responses of the
gram prospectively and discharged home from the hospital between
3-level version of the EQ-5D on anxiety/depression were dichotomized
September 2011 and April 2015, (N = 567) [14]. The TRACS program
into the following: “I am not anxious or depressed” were classified in the
was developed as a model of post-discharge prevention care that mea­
study as “no symptoms” and responses of “I am moderately anxious or
sures and addresses medication-taking. It included personalized educa­
depressed” or “I am extremely anxious or depressed” were classified as
tion about risk factors and medications prior to discharge, follow-up
“at least some symptoms” indicating a positive screen. Results of a val­
telephone calls, and appointments with a stroke nurse practitioner. A
idity assessment of the EQ-5D-5L and EQ-5D-3L published by Golicki et
more detailed description of this program has been previously published
al support using this descriptive system as a generic health outcome
[14]. Since TRACS was designed to be a quality improvement program,
measure specifically in stroke patients [13].
written informed consent was waived. This protocol was approved by
Statistical Analyses: For categorical variables, we calculated the
the Wake Forest University Health Sciences Institutional Review Board.
frequency of responses. Means and standard deviations were calculated
Patients enrolled in TRACS received stroke education prior to
for continuous variables. Median, first and third quartiles were calcu­
discharge, a follow-up phone call within 7 days, an in-person clinic
lated for categorical/ordinal variables. History of pre-hospital depres­
follow-up with a trained stroke nurse practitioner within 2–3 weeks of
sion and in-hospital depression were highly correlated with each other
discharge, and an outcomes questionnaire mailed at 3 months post-
and were not included in the same model. EQ-5D-3L dimension of
discharge. Those patients who did not return the questionnaires were
anxiety/depression at 3 months dichotomized as “no symptoms” or “at
contacted by telephone for the outcomes. When possible, patients were
least some symptoms” was the primary outcome. Using backwards se­
interviewed for completion of the EQ-5D-3L prior to discharge. Medical
lection of variables selected a priori, stepwise logistic regression models
history/comorbidities, initial stroke severity, sociodemographic data,
were generated adjusting for age, history of congestive heart failure, and
and outcomes at 3 months were collected. A total of 129 patients
baseline NIHSS (per 3 points): 1) using pre-hospital depression as the
enrolled in TRACS had complete outcome data for analysis. After
main predictor (N = 117) and 2) using in-hospital depression/anxiety
excluding those patients without 3-month depression screens (N = 5)
symptoms as the main predictor (N = 66). Covariates were chosen due to
and NIHSS (N = 7), 117 patients were included in the model with pre-
their association with post-stroke depression in previous studies and the
stroke depression as the main predictor variable. For the model using
need to adjust for possible confounders in the models (2). Similarly,
in-hospital depression/anxiety as the main predictor variable, an addi­
different logistic regression models were generated with 3 months mRS
tional 51 patients were missing this assessment, leaving 66 patients to be
as a dichotomous outcome variable (≥3 vs. < 3) with 1) Previous history
included in the analysis (Fig. 1).
of depression and 2) inpatient depression/anxiety symptoms as the main
Measures: Patients with Stroke/TIA were identified using the hos­
predictors and adjusted for baseline NIHSS, age and sex. All p-values
pital’s stroke census list and confirmed with chart review and discharge
were 2-sided with p < 0.05 considered as statistically significant. All
diagnosis for ischemic or hemorrhagic stroke and TIA. The following
analyses were performed using SAS software version 9.4.
variables were extracted from the electronic health record and included
initially in the models: pre-stroke history of depression, pre-stroke his­
3. Results
tory of anxiety, previous history of stroke, history of comorbid condi­
tions (diabetes, hypertension, hyperlipidemia, chronic heart failure,
A total of 117 patients (44% female, 70% white, mean age 66, me­
atrial fibrillation, and tobacco abuse), National Institutes of Health
dian NIHSS 2) who had assessment for history of pre-stroke depression
Stroke Scale (NIHSS) on admission, modified rankin scale (mRS) at

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C. Redmond et al. Journal of Clinical Neuroscience 98 (2022) 133–136

and the primary outcome of EQ-5D-3L documented were included in the Table 2
first analysis (Table 1). In this cohort, a pre-hospital history of depres­ Association between 3 month EQ-5D-3L depression/anxiety and pre-hospital
sion was reported by 8 patients (7%). The cohort of patients with anx­ history of depression (Model 1) and in-hospital EQ-5L depression/anxiety
iety/depression evaluated during the in-hospital stay (N = 66) had (Model 2).
similar baseline demographic and clinical characteristics except fewer Variable Model 1: 3 month p= Model 2: 3 month p=
had experienced a prior stroke (Table 1). EQ-5D value EQ-5D value
depression/ depression/
A total of 66 patients (45% female, 73% White, mean age 65, median
anxiety anxiety
NIHSS 2) who had data available regarding in-hospital depression/ n = 117 n = 66
anxiety and the primary outcome of 3 months EQ-5D-3L were included OR (95% CI) OR (95% CI)
in the second analysis (Table 1). A previous history of depression was Age (per 10 years 0.97 (0.94–1.01) 0.208 0.96 (0.94–1.01) 0.134
associated with 3-months EQ-5D-3L anxiety/depression (OR = 10.2, increase)
95% CI 1.12–90.9, p = 0.038) (Table 2). History of CHF 5.4 (0.96–33.3) 0.055 9.3 (0.94–90.9) 0.056
A positive in-hospital EQ-5D-3L for depression/anxiety was reported (Yes)
NIHSS (per 3 1.07 (0.99–1.16) 0.071 0.97 (0.85–1.11) 0.691
by 29 (44%) subjects in the hospital and by 22 (33.3%) at 3- months
points increase)
post-stroke. In-hospital anxiety/depression was associated with 3 Pre-stroke history 10.2 (1.12–90.9) 0.038 NA
months EQ-5D-3L anxiety/depression (OR = 3.9, 95%CI 1.16–13.1; p = of Depression
0.027) (Table 2). (Yes)
History of depression was not associated with the 3-months mRS. In-hospital EQ-5D- NA 3.9 (1.16–13.1) 0.027
3L anxiety/
Depressive and anxiety symptoms were associated with a higher 3-
depression (Yes)

NA: Not applicable, CHF: congestive heart.

Table 1
Demographics and clinical characteristics of the analysis cohorts. months mRS (OR 3.4, 95%CI 1.2–9.8, p = 0.020) but not after adjust­
Characteristics Cohort with history of Cohort with In-hospital ing for covariates including sex, age and baseline NIHSS (OR 2.1, 95%CI
depression as main EQ-5D-3L (Anxiety/ 0.6–7.0, p = 0.198).
predictor (n = 117) Depression) as main
predictor (n = 66)
4. Discussion
Age (in years)Mean (SD) 66 (12) 65 (13)
Female n (%) 51 (44%) 30 (45%)
Race/Ethnicity n (%): In this study of hospitalized stroke patients, a previous history of
White depression and in-hospital depression/anxiety symptoms was associated
Black 57 (70%) 48 (73%) with 3-months depressive/anxiety symptoms. A total of 22/66 (33%)
Asian 22 (27%) 17 (26%)
reported “some depressive symptoms” at 3 months on EQ-5D-3L anxi­
American 2 (2%) 1 (2%)
Indian/Alaska Native 1 (1%) 0 (0%) ety/depression which is consistent with the rate of PSD in prior reports
Pre-Stroke History of 8 (7%) 5 (8%) [2,15].
Depression n (%) Prior studies have identified several risk factors for post-stroke
Pre-Stroke History of 7 (6%) 4 (6%) depression including female sex, prior history of depression, higher
Anxiety n (%)
Previous History of 40 (35%) 19 (29%)
stroke-related disability, cognitive impairment, poor social support
Stroke/TIA network, multiple comorbidities, recent stressful life event, and poverty
n (%) [2,16]. We found that a history of pre-stroke depression is strongly
Family History of 37 (32%) 25 (38%) associated with symptoms of anxiety/depression at 3- months post-
stroke/TIA n (%)
stroke. This is consistent with several previous studies suggesting that
History of comorbid
conditions n (%): pre-stroke depression is an important predictor of PSD. For example,
DM Ayerbe et al in 2013 in their systematic review reported pre-stroke
HTN 34 (29%) 18 (27%) depression, pre-stroke treatment for depression, and medical history of
HLD 96 (82%) 54 (82%) psychiatric disorders were associated with depression after stroke [15].
CHF 54 (46%) 33 (50%)
MI 9 (8%) 6 (9%)
Other studies found that physical disability, stroke severity, and a per­
A fib 4 (3%) 3 (5%) sonal history of depression and cognitive impairment, poor family and
Tobacco use (current 13 (11%) 7 (11%) social support were associated with depression [17,18].
or past) 62 (53%) 36 (55%) We also found that depression/anxiety symptoms on in-hospital EQ-
Caretaker at discharge
5D-3L predicted 3-months depressive/anxiety symptoms. These findings
(not mutually 42 (36%) 41 (62%)
exclusive) n (%): 26 (22%) 24 (36%) are important with regard to early identification and possibly treatment
Spouse/Significant 13 (11%) 13 (20%) of those at greatest risk for the development of PSD and anxiety. Existing
Other 7 (6%) 1 (2%) literature regarding the association of in-hospital anxiety/depression
Adult child/children 1 (1%) 4 (6%) with 3-months assessment is limited. A previous study found that among
Other relative 4 (3%) 0 (0%)
Friend
medically stable acute stroke patients, the accuracy of Hospital Anxiety
Paid caregiver and Depression Scale (HADS) did not correlate with 1 month follow up,
Other however they report that a significant number of subjects needed
NIHSS on admission assistance with the questionnaire secondary to cognitive impairments
Median (Q1-Q3) 2 (1–5) 2 (1–4)
[19].
mRS
Median (Q1-Q3) We did not find a significant difference in short-term (3 months)
Hospital discharge 3 (2–4) 3 (2–4) functional outcome based on previous history of depression or on
3 month mRS 2 (0–3) 1 (0–3) inpatient depression/anxiety symptoms. Previous studies have not
DM: Diabetes Mellitus, HTN: hypertension, HLD: hyperlipidemia, CHF: shown a consistent association of post-stroke depression with functional
congestive heart failure, MI: myocardial infarction, a fib: atrial fibrillation, TIA: outcome [17,20]. This is likely due to cohort characteristics included in
transient ischemic attack, NIHSS: National Institutes of Health Stroke Scale, the different studies and different measures used to assess for post stroke
mRS: modified rankin score, Q1-Q3: 25-75th percentile. depression and functional outcome.

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C. Redmond et al.
5. Limitations
The cohort was not consecutive, and was only a subset of the total
TRACS population [14]. This was because the in-hospital interview was
often not possible for patients discharged on the weekends or who had
very short hospital stays. Therefore, there is a possibility of selection bias
in addition to a small sample size. The small number limits the number
of variables that could be included in the multivariate analyses, and we
did not correct for multiple comparisons [2]. Assessment for cognitive
impairment, which is known to be associated with PSD was not avail­
able. In addition, the mean NIHSS of the cohort was low indicating
milder stroke severity, although this is consistent with patients dis­
charged home, rather than to an inpatient rehabilitation or skilled
nursing facility. The focus on patients discharged home limits the
generalizability of the study to stroke patients discharged directly home
from the hospital and in need of hospital-to-home care coordination.
Pre-stroke and post-stroke antidepressant use was not captured [21].
Although the EQ-5D-3L may be used to evaluate depression and anxiety
in the stroke population, it does lump depression/anxiety in one cate­
gory whereas other screening tools have been studied in more depth and
may have a higher sensitivity for detecting PSD and anxiety [13,22,23].
6. Conclusion
Self-reported depressive and anxiety symptoms in the hospital
measured with EQ-5D-3L and previous history of depression were
associated with 3-months post-stroke depression and anxiety symptoms
but not with short-term functional outcome. In light of the paucity of
data on the association between inpatient depression and anxiety
screening during stroke hospitalization predicting outpatient symptoms,
our study supports the need for future research on the optimal follow-up
and treatment of post-stroke depressive/anxiety symptoms identified in
the hospital.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
References
[1] Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart
disease and stroke statistics—2016 update: A report from the American heart
association. Circulation 2016;133(4). https://doi.org/10.1161/
CIR.0000000000000350.
[2] Towfighi A, Ovbiagele B, El Husseini N, Hackett ML, Jorge RE, Kissela BM, et al.
Poststroke depression: A scientific statement for healthcare professionals from the
136
Journal of Clinical Neuroscience 98 (2022) 133–136
American Heart Association/American Stroke Association. Stroke 2017;48(2).
https://doi.org/10.1161/STR.0000000000000113.
[3] Gillen R, Tennen H, McKee TE, Gernert-Dott P, Affleck G. Depressive symptoms
and history of depression predict rehabilitation efficiency in stroke patients. Arch
Phys Med Rehabil 2001;82(12):1645–9.
[4] Schöttke H, Gerke L, Düsing R, Möllmann A. Post-stroke depression and functional
impairments – A 3-year prospective study. Compr Psychiatry 2020;99:152171.
https://doi.org/10.1016/j.comppsych.2020.152171.
[5] Saxena A, Suman A. Magnitude and determinants of depression in acute stroke
patients admitted in a rural tertiary care hospital. Journal of Neurosciences in
Rural Practice 2015;6(02):202–7.
[6] Prisnie JC, Fiest KM, Coutts SB, Patten SB, Atta CAM, Blaikie L, et al. Validating
screening tools for depression in stroke and transient ischemic attack patients. Int J
Psychiatry Med 2016;51(3):262–77.
[7] Burton L-J, Tyson S. Screening for mood disorders after stroke: a systematic review
of psychometric properties and clinical utility. Psychol. Med. 2015;45(1):29–49.
[8] van Dijk MJ, de Man-van Ginkel JM, Hafsteinsdóttir TB, Schuurmans MJ.
Identifying depression post-stroke in patients with aphasia: a systematic review of
the reliability, validity and feasibility of available instruments. Clin Rehabil 2016;
30(8):795–810.
[9] Volz M, Möbus J, Letsch C, Werheid K. The influence of early depressive symptoms,
social support and decreasing self-efficacy on depression 6 months post-stroke.
J Affect Disord 2016;206:252–5.
[10] Chun H-Y, Whiteley WN, Dennis MS, Mead GE, Carson AJ. Anxiety after stroke:
The importance of subtyping. Stroke 2018;49(3):556–64.
[11] Burton CAC, Murray J, Holmes J, Astin F, Greenwood D, Knapp P. Frequency of
anxiety after stroke: A systematic review and meta-analysis of observational
studies. Internat J Stroke 2013;8(7):545–59.
[12] Cumming TB, Blomstrand C, Skoog I, Linden T. The high prevalence of anxiety
disorders after stroke. Am J Geriat Psych 2016;24(2):154–60.
[13] Golicki D, Niewada M, Buczek J, Karlińska A, Kobayashi A, Janssen MF, et al.
Validity of EQ-5D-5L in stroke. Qual Life Res 2015;24(4):845–50.
[14] Bushnell C, Arnan M, Han S. A new model for secondary prevention of stroke:
transition coaching for stroke. Front Neurol 2014;5:219. https://doi.org/10.3389/
fneur.2014.00219.
[15] Ayerbe L, Ayis S, Wolfe CDA, Rudd AG. Natural history, predictors and outcomes of
depression after stroke: systematic review and meta-analysis. Br J Psychiatry 2013;
202(1):14–21.
[16] Hirata S, Ovbiagele B, Markovic D, Towfighi A. Key factors associated with major
depression in a national sample of stroke survivors. J Stroke Cerebrovasc Dis 2016;
25(5):1090–5.
[17] 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. Internat J Stroke 2014;9(8):1026–36.
[18] De Ryck A, Brouns R, Geurden M, Elseviers M, De Deyn PP, Engelborghs S. Risk
factors for poststroke depression: identification of inconsistencies based on a
systematic review. J Geriatr Psychiatry Neurol 2014;27(3):147–58.
[19] Lees R, Stott DJ, Quinn TJ, Broomfield NM. Feasibility and diagnostic accuracy of
early mood screening to diagnose persisting clinical depression/anxiety disorder
after stroke. Cerebrovasc Dis 2014;37(5):323–9.
[20] Sharma GS, Gupta A, Khanna M, Prakash NB. Post-stroke depression and its effect
on functional outcomes during inpatient rehabilitation. J Neurosci Rural Pract
2021;12(03):543–9.
[21] Chollet F, Tardy J, Albucher J-F, Thalamas C, Berard E, Lamy C, et al. Fluoxetine
for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-
controlled trial. Lancet Neurol 2011;10(2):123–30.
[22] Meader N, Moe-Byrne T, Llewellyn A, Mitchell AJ. Screening for poststroke major
depression: a meta-analysis of diagnostic validity studies. J Neurol Neurosurg
Psychiatry 2014;85(2):198–206.
[23] Quinn TJ, Elliott E, Langhorne P. Cognitive and mood assessment tools for use in
stroke. Stroke 2018;49(2):483–90.