Accepted Manuscript

Effects of depression and anxiety on quality of life in five

common neurological disorders

Joey C. Prisnie, Tolulope T. Sajobi, Meng Wang, Scott B. Patten,

Kirsten M. Fiest, Andrew G.M. Bulloch, Tamara Pringsheim,
Samuel Wiebe, Nathalie Jette

PII: S0163-8343(17)30544-3
DOI: doi:10.1016/j.genhosppsych.2018.03.009
Reference: GHP 7304
To appear in: General Hospital Psychiatry
Received date: 28 November 2017
Revised date: 27 March 2018
Accepted date: 29 March 2018

Please cite this article as: Joey C. Prisnie, Tolulope T. Sajobi, Meng Wang, Scott B. Patten,
Kirsten M. Fiest, Andrew G.M. Bulloch, Tamara Pringsheim, Samuel Wiebe, Nathalie
Jette , Effects of depression and anxiety on quality of life in five common neurological
disorders. The address for the corresponding author was captured as affiliation for all
authors. Please check if appropriate. Ghp(2017), doi:10.1016/j.genhosppsych.2018.03.009

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 ACCEPTED MANUSCRIPT

Title: Effects of depression and anxiety on quality of life in five common neurological
disorders

Authors:
Joey C. Prisnie, MD a, b
Tolulope T. Sajobi, PhD b, c
Meng Wang, MSc b, c
Scott B. Patten, MD, PhD c, d
Kirsten M. Fiest, PhD c, e
Andrew G.M. Bulloch, PhD c, d

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Tamara Pringsheim, MD, MSc a, b, c

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Samuel Wiebe, MD, MSc a, b, c
Nathalie Jette, MD, MSc a, b, c, f

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a. Department of Clinical Neurosciences, University of Calgary
b. Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary
c. Department of Community Health Sciences and O’Brien Institute for Public Health,

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Cumming School of Medicine, University of Calgary
d. Department of Psychiatry and Mathison Centre for Mental Health Research, University
of Calgary
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e. Department of Critical Care Medicine, University of Calgary
f. Department of Neurology, Icahn School of Medicine at Mount Sinai
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Corresponding Author: N Jette, Department of Neurology, Icahn School of Medicine at Mount

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Sinai, One Gustave L. Levy Place, Box 1137, Annenberg 14 Floor Room 1410, New York, New
York 10029-6574, nathalie.jette@mssm.edu

Tables: 2
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Figures: 3
Article word length: 3,056
Abstract word length: 211
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Abstract:

Background: It is unclear whether anxiety and depression impact health-related quality of life
(HRQoL) equally across neurological diseases. This study examines the association between
anxiety or depression and HRQoL in select neurological disorders.

Methods: HRQoL was measured using the Short Form Health Survey (SF-12) in neurological
patients: epilepsy (n=279), migraine (n=268), multiple sclerosis (MS) (n=222), stroke (n=204),
and Parkinson’s disease (PD) (n=224). Depression and anxiety symptoms were assessed using
the Patient Health Questionnaire (PHQ-9) and Hospital Anxiety and Depression Scale (HADS-

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A), respectively. Multiple linear regression was used to evaluate variables associated with the

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SF-12 mental health component (MCS) and physical health component scores (PCS). Pratt index
was used to estimate the relative importance of anxiety and depression on HRQoL.

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Results: Anxiety and depression had the largest contribution to PCS in stroke and to MCS in
epilepsy. Overall, anxiety and depression had a larger contribution to MCS as compared to PCS,
except in stroke patients. Different patterns were seen across neurological diseases, with mental

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health variables strongly affecting MCS in all conditions, with a also sizable contribution to PCS
in migraine, MS, and stroke.
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Conclusions: Anxiety and depression have varying impacts on HRQoL across neurological
diseases. It is important for clinicians to be aware of how these patterns differ in each condition.
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Introduction

It is well known that patients with neurological disorders have decreased health-related

quality of life (HRQoL) compared with healthy controls. Such findings have been reported in

epilepsy [1], migraine [2], multiple sclerosis (MS) [3], stroke [4], and Parkinson’s disease (PD)

[5]. Determining specific variables associated with quality of life measurements is important as it

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can have significant implications for disease management and patient outcomes. One of the most

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consistently reported findings is that depression and anxiety are strong predictors of low HRQoL,

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both in neurological patients [6-10] and general population patients without other medical

comorbidities [11]. It is not known, however, whether depression and anxiety contribute equally

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to low HRQoL in all neurological disorders. Although many studies have examined quality of
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life in individual neurological disorders, very few have included a comparative analysis of

variables between conditions.

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The objective of this study was to determine the relative impact of anxiety and depression
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on physical and mental quality of life as measured by the 12-item Short-Form Health Survey

(SF-12) in five neurological conditions (epilepsy, migraine, MS, stroke, and PD) using
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standardized methodology. This systematic approach (standardized recruitment methodology,

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questionnaires, data collection and clinical interviews) allows for the creation of a uniform

statistical model using common variables across all conditions to explore factors that influence
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quality of life between the different cohorts. We can therefore estimate what percentage of the

variance in HRQoL scores is explained by mental health variables (anxiety and depression) from

one condition to the next. In addition to standardized administration, we wanted to use real world

measures that would be easily administered in a clinical setting in relatively little time.

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Methods

Participants and procedures

Data were collected as part of the Neurological Disease and Depression Study (NEEDS)

[12-16]. Consecutive follow-up patients were recruited at five outpatient neurology clinics in

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Calgary, Alberta, Canada: the Calgary Epilepsy Program, the Calgary Headache Assessment &

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Management Program, the Calgary Multiple Sclerosis Clinic, the Stroke Prevention Clinic, and

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the Movement Disorders Clinic. The study protocol was approved by the Conjoint Health

Research Ethics Board at the University of Calgary.

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In all five clinic settings, patients were excluded from participating if they were under the
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age of 18, lived outside Alberta (except patients with epilepsy who had to live within the City of

Calgary), were not fluent in English, had a hearing impairment (as the study included a telephone
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interview within two weeks after filling out the questionnaires), had severe aphasia, moderate to
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severe developmental delay, or dementia. Upon arriving at the clinic, patients were approached

to obtain consent for participation in the study. Full participation consisted of: (1) completing a
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written questionnaire including depression and anxiety screening tools as well as the SF-12, and
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(2) a follow-up telephone interview (Structured Clinic Interview for DSM-IV disorders – SCID)

within two weeks of the clinic visit.

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The written questionnaire varied slightly according to the specific condition (disease

specific disability scales were added when available), however most portions were identical for

all cohorts, including those related to HRQoL, depression, and anxiety. The questionnaires

contained a demographics section (including marital status, education, income source, etc.), the

Patient Health Questionnaire 9-item version (PHQ-9) [17], the Hospital Anxiety and Depression

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Scale (HADS) [18], and the SF-12 HRQoL questionnaire [19]. The order of the PHQ-9 and the

HADS was randomized.

The medical chart of each patient was reviewed following the clinic appointment to

obtain further information on disease-specific variables as well as any current medications or

non-pharmacological therapy received.

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SF-12 (HRQoL measure)

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The SF-12 [19] contains twelve of the questions from the Medical Outcomes Study 36-

item Short-Form Health Survey (SF-36) [20]. The SF-12 was intended to be quicker and easier to

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complete during a clinic visit, or as a self-report questionnaire, while maintaining a strong
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correlation (> 90%) with scores from the longer SF-36 [19]. Scoring of the SF-12 generates

scores in eight subscales, which can be further summarized into two domains: the physical health
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component score (PCS) and the mental health component score (MCS), as per the scoring
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guidelines [21]. Scores for the PCS and the MCS range from 0 to 100, with higher scores

indicating better HRQoL. The SF-12 does not attempt to combine physical and mental health
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into a single index, and only outputs the two MCS and PCS summary scores.
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PHQ-9 (depression measure)

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The PHQ-9 contains nine items, one for each of the DSM-5 criteria for major depressive

episode [17]. Each item is scored from 0 to 3, and total scores range from 0 to 27. Higher scores

indicate greater levels of depressive symptoms.

The PHQ-9 was chosen as the measure for depression status, as it has been validated

against the SCID in previous studies using these same data for epilepsy [13], migraine [12], MS

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[15], stroke [16], and PD [14]. Scale scores from the PHQ-9 were treated as a continuous

variable and not categorized in the present analysis.

HADS-A (anxiety measure)

The HADS anxiety subscale (HADS-A) consists of the seven odd numbered questions of

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the full HADS [18]. Each question is scored from 0 to 3, for a total score ranging from 0 to 21.

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As with the PHQ-9, higher scores indicate greater levels of anxiety symptoms. Scores from the

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HADS-A were treated as a continuous variable and not categorized in the present analysis.

Statistical analysis
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Patients’ demographic and clinical characteristics were summarized using means and

standard deviations for continuous variables and frequency distributions for categorical
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variables. For each neurological cohort and each summary component of the SF-12, the
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relationship between patients’ reported quality of life and socio-demographic, clinical, and self-

reported characteristics was assessed using a multiple linear regression model. The regression
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model variables included age, sex (female vs. male), psychotropic medication use, medication
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side-effects (yes vs. no as per a self-reported question), relationship status (in a relationship

[married/common law] vs. not in a relationship [single/separated/widowed/divorced]), smoking

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status (yes vs. no), alcohol use (yes vs. no), illicit drug use (yes vs. no), education (high school or

less vs. greater than high school), employment status (employed vs. unemployed), depression (as

measured by PHQ-9), anxiety (as measured by HADS-A), and disease severity (a single self-

reported question with seven levels categorized into two groups: “not severe” to “moderately

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severe” vs. “quite severe” to “extremely severe”). Collinearity among model predictors was

assessed using variance inflation factor.

Multiple imputation was conducted to minimize the potential bias from missing data on

both outcome and explanatory variables. The multiple imputation model adjusted for important

variables including age, gender, relationship status, smoking status, alcohol use, drug use,

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education, employment status, depression, anxiety, and disease severity based on Markov chain

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Monte Carlo methods. Consistent with previous research that suggests that between 3 and 10

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copies of the original data are sufficient to get coherent estimates, our multiple imputation model

was used to create 10 imputed datasets using the Markov chain Monte Carlo methods. For each

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imputation dataset, multiple linear regression was conducted and model fit was assessed using
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model R-squared, the proportion of variance in the HRQoL explained by explanatory variables.

The relative importance of each explanatory variable was determined by the Pratt index, which
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quantifies each variable’s contribution to the explained variance (i.e. R-squared), measured as a
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percentage [22]. The index generally ranges in value from zero (0%) to one (100%), with large

negative values indicating collinearity with other explanatory variables. The larger the
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percentage, the greater the contribution to the model R-squared. Based on the R-squared value
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and the Pratt index percentage, the component of R-squared contributed to by anxiety and

depression was calculated by multiplying the sum of the Pratt indices for anxiety and depression
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by the overall R-squared for each model [23]. The overall estimates of regression coefficients

and Pratt index for each explanatory variable were derived via Rubin’s formula for multiple

imputation. All analyses were conducted in SAS 9.4 [24]. A two-tailed alpha level of p < 0.05

was considered statistically significant in all analyses.

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Results

Following multiple imputation on missing data, the final numbers used for analysis were:

279 for epilepsy, 268 for migraine, 222 for MS, 204 for stroke, and 224 for PD. Figure 1

highlights the total number of patients seen in each clinic, the number of patients eligible, the

number of patients who consented, and the number of patients who ultimately completed part of

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all of the questionnaire and formed the present sample used for statistical analysis. Missing data

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for all outcome and explanatory variables ranged from 0 to 15%. Descriptive statistics of the

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study population for each neurological condition are provided in Table 1. Mean values for PHQ-

9 scores, HADS-A scores, and SF-12 MCS and PCS scores are also reported in this table.

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Notably, migraine patients had the highest mean PHQ-9 and HADS-A scores, as well as the
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lowest mean MCS score. PD patients had the lowest mean PCS score. Our analyses suggest that

the variance inflation factors associated with each of the predictors was less than 5, suggesting
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that the predictors are not collinear.

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Figure 1: Flow diagram of total patients seen, eligible, consented, and participated in the study.

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Table 1: Descriptive Characteristics of Patients for each Neurological Condition

Patient Characteristics EPILEPSY MIGRAINE MULTIPLE STROKE PARKINSON’S
SCLEROSIS DISEASE
(N=279) (N=268) (N=222) (N=204) (N=224)
Age (in years; mean) [SD] 40.3 [15.1] 42.8 [13.3] 49.6 [11.8] 61.4 [15.4] 67.5 [10.6]
Sex (% female) 54.8% 80.2% 75.2% 52.5% 36.6%
Psychotropic medication use (based 14.0% 37.7% 22.1% 13.2% 29.9%
on chart review)
Medication Side-Effects (self- 37.7% 49.2% 26.4% 21.9% 46.3%

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reported)
Marital status

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In a relationship 53.4% 68.7% 72.9% 68.1% 78.5%
Not in a relationship 46.6% 31.3% 27.2% 31.9% 21.5%

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Smoking 21.9% 12.8% 17.6% 10.3% 1.8%
Alcohol use 62.8% 63.7% 74.3% 66.2% 65.5%
Currently uses illicit drugs 15.8% 6.3% 9.9% 4.9% 1.4%
Education

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Greater than high school 35.3% 41.2% 29.3% 35.5% 43.1%
High school or less 64.8% 58.8% 70.7% 65.5% 57.0%
Working at a paid job 66.9% 62.9% 55.4% 44.1% 26.0%
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Disease severity
Not severe – moderately severe 90.0% 60.4% 91.7% 87.4% 88.4%
Quite severe – extremely severe 10.0% 39.6% 8.3% 12.6% 11.7%
PHQ-9 (mean, SD) 6.3 [5.8] 8.0 [6.2] 6.4 [5.7] 5.1 [5.3] 2.3 [3.3]
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HADS-A (mean, SD) 6.8 [4.2] 7.6 [4.4] 6.0 [4.2] 5.5 [4.0] 5.9 [3.8]
SF-12 PCS (mean, SD) 48.8 [8.0] 41.6 [9.6] 42.1 [9.8] 45.0 [9.7] 41.4 [8.9]
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SF-12 MCS (mean, SD) 46.0 [10.8] 43.2 [10.8] 46.0 [10.1] 48.2 [9.1] 47.0 [9.9]

SD = Standard deviation; PHQ-9 = 9-item Patient Health Questionnaire; HADS-A = Hospital

Anxiety and Depression Scores – Anxiety Domain; PCS = SF-12 Physical Component Summary
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Score; MCS = SF-12 Mental component summary score

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Results of the multivariate regression analysis are presented in Table 2 with R-squared

values and the relative R-squared contribution from anxiety and depression. All variables that

had statistically significant correlation coefficients are indicated in the table. Figures 2 and 3 also

represent the total model R-squared and the contribution from PHQ-9 and HADS-A scores for

PCS and MCS, respectively.

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Table 2: Relative contributions of determinants of SF-12 PCS and MCS summary scores for five neurological conditions

PCS EPILEPSY MIGRAINE MULTIPLE SCLEROSIS STROKE PARKINSON’S DISEASE

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Coefficient (SE) Pratt Index Coefficient (SE) Pratt Index Coefficient (SE) Pratt Index Coefficient (SE) Pratt Index Coefficient (SE) Pratt Index
Age -0.09 (0.03) 6.59%** 0.02 (0.04) 0.20% -0.20 (0.06) 16.96%** -0.06 (0.05) 2.48% -0.10 (0.06) 8.02%

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Sex (F) -1.50 (0.82) 3.08% -1.74 (1.16) -0.11% (0%) 0.72 (1.25) 0.20% -2.32 (1.33) 5.92% 0.05 (1.23) 0.10%

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Psychotropic medications -6.23 (1.23) 25.56%*** -1.61 (0.98) 4.33% -0.22 (1.38) 0.49% 0.37 (2.03) -0.34% (0%) -0.21 (1.30) 0.54%
Side-effects -1.10 (0.87) 2.55% -2.50 (0.88) 4.89%** 1.05 (1.25) -0.15% (0%) -0.62 (1.61) 0.95% -2.60 (1.31) 9.37%

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Married/In a relationship 0.82 (0.87) 1.28% -0.65 (1.00) -0.52% (0%) 0.44 (1.20) 0.19% -0.40 (1.37) 0.38% 2.38 (1.50) 1.96%
Smoking -6.06 (1.07) 30.81%*** -1.33 (1.42) 1.69% -2.25 (1.61) 2.26% 1.11 (2.25) 0.04% 12.85 (5.08) 10.40%*

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Alcohol use 0.16 (0.90) 0.29% 1.57 (0.97) 2.24% 1.68 (1.35) 2.19% 1.59 (1.44) 3.89% 1.81 (1.36) 5.33%
Drug use 0.59 (1.20) -0.13% (0%) -0.06 (1.87) 0.06% 0.57 (2.01) 0.00% 2.07 (3.11) -0.15% (0%) 9.00 (6.15) 3.93%
Education greater than HS
Working a paid job
Disease severity scale
PHQ-9 depression score
1.23 (0.88)
-0.70 (0.94)
1.79 (1.37)
-0.32 (0.10)
3.08%
-0.85% (0%)
-0.70% (0%)
24.09%**
0.05 (0.88)
3.21 (0.98)
-4.40 (0.95)
-0.88 (0.10)
0.03%
9.80%**
18.34%***
66.24%***
-0.96 (1.27)
4.76 (1.16)
-5.36 (2.08)
-0.88 (0.14)
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12.78%*
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-0.33% (0%)
21.33%***

48.93%***
2.86 (1.37)
2.23 (1.47)
-1.42 (2.23)
-0.72 (0.17)
7.72%*
6.94%
1.99%
51.68%***
2.17 (1.27)
2.09 (1.39)
-2.17 (1.83)
-0.63 (0.23)
7.28%
7.79%
6.24%
29.65%**
HADS anxiety score
Model R-squared (%)

R-squared contribution from

-0.10 (0.13) 4.30%

40.32%
0.27 (0.13) -7.36% (0%)*

52.13%
0.35 (0.20)

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46.08%
-0.42 (0.23) 18.36%

36.99%
-0.25 (0.20) 9.40%

31.24 %

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anxiety and depression (%) 28.39% 66.24% 48.93% 70.04% 39.05%

MCS EPILEPSY MIGRAINE MULTIPLE SCLEROSIS STROKE PARKINSON’S DISEASE

Age
Sex (F)
Coefficient (SE)
0.04 (0.03)
0.34 (0.87)
Pratt Index
0.99%
-0.16% (0%)
Coefficient (SE)
0.02 (0.04)
0.90 (1.14)
0.27%
0.68%

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Pratt Index Coefficient (SE)
-0.04 (0.05)
-1.26 (1.16)
Pratt Index
-0.32% (0%)
0.52%
Coefficient (SE)
0.02 (0.06)
2.53 (1.40)
Pratt Index
2.25%
3.83%
Coefficient (SE)
-0.08 (0.05)
-0.25 (1.02)
Pratt Index
0.31%
-0.06% (0%)

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Psychotropic medications -2.06 (1.24) 1.84% -3.12 (0.95) 8.09%** -0.30 (1.24) 0.43% -1.98 (2.18) 4.91% -2.28 (0.98) 4.11%*
Side-effects -1.17 (0.84) 1.64% -1.01 (0.86) 0.94% -1.02 (1.18) 1.35% -3.21 (1.64) 14.03% -1.10 (0.88) 1.71%

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Married/In a relationship 0.48 (0.89) 0.55% -0.65 (1.00) -0.92% (0%) 0.21 (1.09) 0.09% -0.65 (1.43) 1.82% 2.52 (1.08) 2.37%*
Smoking 1.46 (1.08) -1.61% (0%) -1.33 (1.42) 1.59% -1.03 (1.43) 1.37% 3.04 (2.39) 2.92% 0.18 (3.84) 0.05%

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Alcohol use -1.39 (0.89) 0.30% -1.54 (0.98) 0.01% 0.04 (1.12) 0.03% 3.00 (1.44) 9.85%* 1.07 (0.95) 0.24%
Drug use -0.10 (1.21) 0.06% -1.62 (1.40) -0.25% (0%) -0.52 (1.75) 0.29% -2.88 (3.14) 2.92% -16.59 (4.48) 6.46%**
Education greater than HS -0.33 (0.87) -0.28% (0%) -0.07 (0.92) -0.01% (0%) -1.56 (1.10) 0.58% -3.16 (1.42) 9.72%* -1.00 (0.94) -0.40% (0%)
Working a paid job
Disease severity scale
PHQ-9 depression score
0.98 (0.90)
0.37 (1.41)
-1.11 (0.10)
0.97%
-0.26% (0%)

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69.16%*** C
0.38 (1.82)
-0.42 (0.87)
-0.55 (0.95)
-0.24% (0%)
1.66%
59.24%***
1.68 (1.04)
-0.24 (1.77)
-0.87 (0.14)
2.04%
0.25%
61.21%***
0.23 (1.66)
-1.30 (2.33)
0.00 (0.20)
0.32%
2.77%
0.97%
-1.21 (1.09)
-0.24 (1.66)
-1.19 (0.17)
-0.08% (0%)
-0.40% (0%)
41.17%***

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HADS anxiety score -0.69 (0.13) 26.68%*** -0.99 (0.92) 28.72%*** -0.69 (0.18) 32.29%** -0.68 (0.22) 43.96%** -1.09 (0.16) 43.86%***
Model R-squared (%)
67.60% 64.76% 55.87% 19.39% 66.95 %
R-squared contribution from
anxiety and depression (%) 95.84% 87.96% 93.50% 44.93% 85.03%

*P<0.05, **P <0.01, ***P <0.0001

Shaded lines indicate statistically significant regression coefficients (P < 0.05)

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Figure 2: PCS model R-squared and relative contribution from PHQ-9 and HADS-A scores

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Figure 3: MCS model R-squared and relative contribution from PHQ-9 and HADS-A scores
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Anxiety/depression and PCS

The stroke cohort had the largest PCS R-squared contribution from anxiety and

depression (Pratt index 70.04%). A higher PHQ-9 score alone was a significant

contributor towards PCS R-squared in all five conditions: epilepsy (Pratt index 24.09%),

migraine (Pratt index 66.24%), MS (Pratt index 48.93%), stroke (Pratt index 51.68%),

and PD (Pratt index 29.65%). Higher PHQ-9 scores were associated with lower PCS

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scores. HADS-A scores contributed significantly towards PCS R-squared only in

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migraine (Pratt index -7.36%).

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Anxiety/depression and MCS

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The epilepsy group had the largest MCS R-squared contribution from anxiety and
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depression (Pratt index 95.84%). For MCS R-squared, higher HADS-A scores

contributed significantly to lower MCS in all five conditions (Pratt indices 26.68%,
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28.72%, 32.29%, 43.96%, 43.86% in epilepsy, migraine, MS, stroke, and PD

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respectively) while PHQ-9 scores also contributed to MCS in all conditions except

stroke: epilepsy (Pratt index 69.16%), migraine (Pratt index 59.24%), MS (Pratt index
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61.21%), and PD (Pratt index 41.17%). In all patient groups except for stroke, anxiety
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and depression had a greater contribution to MCS as compared to PCS.

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In the epilepsy cohort, smoking was the most important factor negatively

associated with PCS scores, accounting for 30.81% of the total R-squared. Psychotropic

medication use, PHQ-9 scores, and age were also associated with PCS in epilepsy. For

MCS in the epilepsy group, PHQ-9 scores and HADS-A scores were the only significant

factors, accounting for over 95% of the explained variance.

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Depression was the variable that explained the largest amount of variation in PCS

scores in the migraine group (Pratt index 66.24%), with self-reported disease severity,

employment status, medication side-effects, and anxiety also contributing significantly to

R-squared. Depression (Pratt index 59.24%), anxiety (Pratt index 28.72%), and

psychotropic medication use (Pratt index 8.09%) were the only significant variables

associated with MCS scores in this group.

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In the MS group, the PHQ-9 score was most strongly associated with PCS (Pratt

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index 48.93%). Employment status, age, and disease severity were also significant factors

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associated with PCS. Only PHQ-9 score (Pratt index 61.21%) and HADS-A score (Pratt

index 32.29%) were significantly associated with MCS in the MS cohort.

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In stroke, PHQ-9 score was the largest single factor associated with the PCS
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score, accounting for 51.68% of the total R-squared. Education was the only other

significant variable associated with PCS in this group. In terms of MCS, HADS-A score
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was the largest predictor with a Pratt index of 43.96%, while alcohol use (correlated with
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higher MCS) and education also contributed. Education was associated significantly with

both PCS and MCS; however higher education (greater than high school) was correlated
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with higher PCS scores while it was correlated with lower MCS scores. Notably, the
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stroke group had the lowest overall R-squared in the MCS model of the five conditions.

Finally, the PD group had PHQ-9 score as the largest factor associated with PCS
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with a Pratt index of 29.65%. The only other significant factor associated with PCS was

smoking which had a positive correlation with PCS scores and a Pratt index of 10.40%.

For MCS, the largest predictor was again HADS-A score with a Pratt index of 43.86%,

while other significant MCS predictors were PHQ-9 score, illicit drug use, use of

psychotropic medications, and relationship status.

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Discussion

These results suggest that anxiety and depression may play a different role in

impacting quality of life in different neurological conditions.

In the epilepsy and PD cohorts, the impact of depression and anxiety was almost

exclusively on MCS. This can be explained by the fact that epilepsy is not usually as

inherently physically disabling as other neurological conditions, while disease-specific

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disability such a postural instability and bradykinesia may have a greater impact on PCS

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in the PD population. Over 95% of the R-squared was accounted for by anxiety and

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depression in the epilepsy group, and over 85% in the PD group. Epilepsy patients face

considerable stigma [25], and it has been hypothesized that this may be a driving factor

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for depression and consequently lower quality of life [26].
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Alternatively, in the stroke cohort the impact of anxiety and depression was much

more prominent on PCS as opposed to MCS. This suggests that stroke patients presenting
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with anxiety or depression should be asked about their physical well-being and quality of
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life, and conversely, stroke patients with physical impairments may be at an increased

risk for anxiety and depression. The stroke group was one of the older cohorts, and late-
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life depression and anxiety has been associated with physical disability in the general
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geriatric population [27], a finding which in some studies could be reversed with

treatment of depression [28, 29].

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The migraine and MS cohorts were similar in that depression and anxiety in these

populations had a sizeable correlation to both PCS and MCS, although the contribution

was greater for MCS. The larger influence on MCS for both conditions is not surprising,

as there are likely other important factors that contribute to physical quality of life, so

depression and anxiety do not account for as much of the variation in PCS. Furthermore,

migraine and MS patients had the highest mean PHQ-9 scores, reinforcing the conclusion

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that mental health is a significant concern for these patients that can have broad effects in

multiple domains of their lives. Migraine is also a highly stigmatized condition, with

some studies reporting even greater stigmatization than epilepsy [30]. Also, the response

to headache as well as chronic pain is highly intertwined with anxiety and depression [31]

again underlining the significant impact of mental health on both migraine and MS

patients.

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With the notable exception of MCS in the stroke cohort, depression had a greater

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contribution towards quality of life as compared to anxiety in all conditions. There are a

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number of reasons why this may have been observed. First, anxiety as compared to

depression can be much more situationally dependent, especially certain forms such as

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panic disorder or agoraphobia. Such situational forms of anxiety might be expected to
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have a less pervasive effect on quality of life, especially if the anxiety symptoms are not

present at the time of assessment. Second, due to the inherently subjective nature of
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quality of life assessment, cognitive distortions about one’s health status associated with
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depression would likely impact quality of life reporting. Although cognitive distortions

can be present with anxiety symptoms as well, these tend to relate to themes of danger
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and threat [32], and may not have as large of an impact on overall health status.
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The differing patterns of MCS and PCS in the different conditions have important

clinical and research implications. The differences themselves suggest that patterns are
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more complex and condition-specific than the simplistic view that psychiatric symptoms

affect MCS and the neurological conditions themselves affect PCS. This would imply

that there may be alternative methods of improving overall HRQoL depending on the

neurological condition. For example, psychiatric symptoms may impede people regaining

physical function in stroke, or alternatively, poor physical health may have especially

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negative implications for anxiety and depression in stroke. Ultimately, further research is

needed to more fully delineate the patterns and directions of such effects.

Previous studies have identified that depression in particular in neurology patients

is often persistent, and new cases present across longitudinal follow-up [33]. Resolution

of depressive symptoms has been shown in this same study to improve overall health

statues as measured by the SF-36. While our study did not have a longitudinal follow-up

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component, this further supports the idea that treatment of depressive disorders will result

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in improvement in overall HRQoL. The expected value of doing so may improve not

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only mental health but physical health as well.

The major limitation of this study is that caution should be exercised when

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making direct comparisons from one neurological condition to the next. Although the
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statistical models were created using data that were commonly collected across all the

conditions, the different populations may not be equally sensitive to those variables, and
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the approximate importance of anxiety and depression is only relative to the variables
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that we were able to include. To create uniform statistical models, we were unable to

include disease-specific variables that were unique to each condition to increase the
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precision of the regression analysis. Finally, while it would have been interesting to
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examine the effects of anxiety and depression on total HRQoL, we were limited by the

fact that the SF-12 does not output a total combined score.
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These results highlight the important connections between depression or anxiety,

and quality of life in neurological patients. Depression and anxiety are not only prevalent

in neurological conditions, but they may also have different manifestations depending on

the condition. By analyzing the two domains of quality of life, PCS and MCS separately,

important distinctions can be seen between the neurological conditions. For example, as

suggested by the stroke results, efforts to improve PCS are likely to lead to improvements

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in depression and anxiety. It is important for clinicians to be aware of variables

associated with quality of life, as identifying and treating factors such as anxiety and

depression has the potential to improve the lives of patients living with chronic

neurological diseases.

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Acknowledgements

The current study was funded by the Cumming School of Medicine and Alberta Health

Services. Funding was also received from the Hotchkiss Brain Institute. KMF was funded

at the time of this research by an Alberta Innovates Health Solutions studentship. SBP

was supported by a Senior Health Scholar award from Alberta Innovates Health Solutions

during the study. NJ held a Canada Research Chair (Tier 2) in Neurological Health

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Services Research and an Alberta Innovates Health Solutions Population Health

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Investigator Award during the study.

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