biopsychosocial correlates of health-related quality of life in migraine without aura

253 Pages·2017·2.13 MB·English

by  Govender, Catherine

BIOPSYCHOSOCIAL CORRELATES OF HEALTH-RELATED
QUALITY OF LIFE IN MIGRAINE WITHOUT AURA

by

CATHERINE OLLY GOVENDER

submitted in accordance with the requirements
for the degree of

DOCTOR OF PHILOSOPHY

In the subject

PSYCHOLOGY

at the

UNIVERSITY OF SOUTH AFRICA

SUPERVISOR: Prof J Elander

CO-SUPERVISOR: Professor D J G Rees

NOVEMBER 2016
Declaration

I hereby declare that this thesis “Biopsychosocial correlates of health-related quality
of life in migraine without aura” is my own work, unless otherwise stated. All the sources that
I have used or quoted have been indicated and acknowledged by means of complete
references.
Student number: 54671051
30 June 2016
Signature Date

i
Acknowledgements
This PhD journey has been gruelling and I would not have been able to finish it
without the various forms of support I received. I therefore have a number of people that
I need to thank for walking various parts of the journey with me. Though the list seems
extensive, it is probably not complete…

Thank you to the Creator for the opportunity to improve myself and for the
wonderful people that helped make it possible.

Academic and financial support
It took me almost two years to find a promoter and I am infinitely grateful to
Professors Elander and Rees for taking the journey with me. I also thank Professor Michael
Pepper who stood by me in the first few steps of the journey.
I acknowledge the National Research Foundation for funding my PhD through the
Thuthuka Programme. I am grateful to Professor Rhena Delport who helped me to apply for
the NRF funds, along with Christiaan Labuschagne who offered the initial advice on gene
sequencing. I am incredibly thankful to Mrs Hanneke Nieuwoudt who kept the books for my
grant and always helped when I was confused or frustrated; and Ms Kentse Mabalane and
Mrs Bettie de Beer of the NRF for their advice on funding.
Thank you, Charles Wairuri from Whitehead Scientific for always answering my
questions.
I am sincerely grateful to Dr Lisa Zimmerman for helping with my conceptual clarity
and Dr Dion van Zyl for statistical clarity.
Heartfelt thanks are also in order for my statistician, Dr Mardé Booyse, for her
patience and help.
Thank you, Dr André Stander for letting me utilise space in your laboratory. This was
crucial to my study. Thank you also for guiding me through the qPCR process – you are a
very patient gentleman and lecturer.

The participants
I am grateful to all the participants: You sacrificed time and blood for this – thank
you.
ii
Moral support
I am incredibly grateful to my super supporters: Angelo, Boshadi, Christine L., Ed, Liz,
Martin, Nico, Nikki, Puleng and Vanessa. Thank you for listening to my woes and helping
me keep my spirits up. It meant more than I can express.
Thank you also to all my family who helped out when I had to work. I am especially
grateful to Anna, Carina and Ingrid, Cass, Christine M., Cecilia, Christopher, Ian and Jaqui,
Jacky, Jutta, Melinda and Shainaaz for making time for last-minute visits, babysitting and
play-dates!

Technical support
My gratitude is extended to Benita Colmanet for organising all the phlebotomy.
Thank you to Sr Jean-Louise Brits for being our traveling phlebotomist. I acknowledge with
much appreciation the Ampath teams at Zuid-Afrikaans Hospital, Linksfield Hospital,
Morningside Clinic, Rosebank Clinic and Flora Clinic for collecting the samples and running
the panel of tests. In particular I want to thank Marisa, Errol, Kagisho, Carlos and Beverley
for caring about my study.
I am incredibly appreciative of the people that helped me to advertise my study:
Angela Cogzell and friends and a number of colleagues who were willing to lend a hand.
There were also a few organisations that allowed me to advertise. Though I can’t name you, I
remain grateful.
The gentlemen at the Agricultural Research Council’s OVI were wonderful and I am
grateful for your expert help, Dr Shaun Reeksting and Dr Liberty Sibanda.
Jaqueline Harvey: Thank you for all the competent help with the laboratory work and
the encouragement when it was hard going. I would not have been able to finish this year if
you had not been there – even on weekends!

Mentorship
Annelies Cramer: Many years ago you inspired me to take up a career in
neuropsychology. You continue to be a mentor and I feel blessed that our paths crossed.
Nafisa Cassimjee: Thank you for believing in me enough to send me to Canada to be
inspired.
To my longstanding friend and one of the most courageous researchers I know, Dr
Alida Koorts: I value your friendship and the way you selflessly share your expertise, your
iii
laboratory, your pipettes and your time. Thank you for encouraging and inspiring me over the
years.
Inspiration
During this journey I have continually been grateful for the privilege of my education.
That was a gift of untold value from my parents. My mother, Iris, died in 2011 and my father,
Krish, died while I was completing this thesis journey in 2016. May they both rest in peace.
I also acknowledge the women in my family who believed in education though they
were not able to receive it to the level they may have wanted.
Finally, warm and infinite thanks go to Liz, Grace, Cecilia and Christopher for the
constancy of their love.

iv
This thesis is dedicated to three of the most
influential women in my life:
For Liz, whose courage astounds me…
For Grace, who makes sunshine wherever she goes…
And especially for my mother, Iris Beryl Govender, who
attended every one of my graduations, but will not be in the
audience for this one…
v
Abstract
Migraine - with or without aura - is an enervating primary headache disorder that
represents a heavy economic and social burden. The health-related quality of life of
migraineurs is poor. The aim of this research was to investigate the health-related quality of
life of migraine without aura sufferers.
As the thesis was approached from a biopsychosocial perspective, potential
determinants were chosen for investigation from the molecular, individual, interpersonal and
wider societal levels. The research was executed in two phases: Phase 1 data (N = 341) were
gathered using a survey of health-related quality of life (Short Form 6), temperament (the
Tridimensional Personality Questionnaire), catastrophizing as a pain coping strategy (the
four-item Pain Coping Scale) and the amount of perceived social support (the six-item Social
Support Questionnaire). For phase 2, participants were requested to provide blood specimens
for ELISA serum quantification of glutamate (n = 66) and gene expression analysis of the
main glutamate transporter gene SLC1A2 on real-time reverse-transcription polymerase chain
reaction (n = 20).
Of the 341 adult residents of Gauteng Province, South Africa that participated in the
survey, 94 (28%) met the criteria for migraine without aura and a further 60 (18%) suffer
from possible migraine without aura, using the International Classification of Headache
Diagnosis (2nd edition) criteria. This indicates that migraine without aura is a significant
burden for South Africa.
Health-related quality of life was significantly poorer for migraineurs versus those
without migraine (p < .001), and is in fact comparable to that of liver transplant, cardiac
bypass and elderly populations. This raises concerns about the severe burden of the disease on
the mental and physical well-being of South African sufferers.
Investigation of the predictors of health-related quality of life yielded two significant
variables when controlling for sex, head and neck injury and language - Harm Avoidance and
vi
Catastrophizing. The regression model accounts for 29% of the variance in health-related
quality of life. A reciprocal relationship likely exists between Harm Avoidance and
Catastrophizing, in which a harm avoidant migraineur interprets the headache pain as a
catastrophic event to be avoided – even at high cost to the self.
Though there have been calls for more biopsychosocial studies of migraine, this thesis
did not find added understanding of health-related quality of life through the combination of
biological and psychosocial data. The implication is that the role of glutamate in migraine
without aura still requires further investigation. Further study is also required with regard to
which biological factors may influence the sufferer’s quality of life.
The thesis indicates a key role for psychological intervention in aiding migraineurs to
live a life of quality. The inclusion of interventions for the psychological aspects of migraine
may yield improved outcomes for patients. However, Gauteng residents suffering from MO
are potentially unaware of their diagnosis and therefore of potential management for their
disorder. Awareness around migraine needs to be the first step in limiting this disorder’s
devastating impact on individuals, their relationships and their potential to contribute
meaningfully to society.

Key terms: health-related quality of life, biopsychosocial, glutamate, migraine
without aura, pain coping, SLC1A2, temperament
vii
List of abbreviations

CSD Cortical spreading depression
DA Dopamine
DTI Diffusion tensor imaging
EAAT-2 Excitatory amino acid transporter
EDTA Ethylenediaminetetraacetic acid
EEG Electroencephalography
ELISA Enzyme-linked immunosorbance assay
FHM Familial hemiplaegic migraine
Glu Glutamate
GWAS Genome-wide association study
HA Harm avoidance
HRQOL Health-related quality of life
MA Migraine with aura
MO Migraine without aura
NA Noradrenalin
NM Non-migraineur(s)
NS Novelty seeking
P Perseverance
PET Positron emission tomography
QOL Quality of life
qPCR Quantitative polymerase chain reaction
rCBF Regional cerebral blood flow
RD Reward dependence
RT2 Real-time reverse transcription
Ser Serotonin
SLC1A2 Solute-carrier family 1 glial high affinity glutamate
transporter 2
SSQ Social Support Questionnaire
SPECT Single-photon emission computed tomography
TPQ Tridimensional Personality Questionnaire

viii
Table of contents

Chapter 1: Introduction to the Study .............................................................................. 1
1.1 Health-Related Quality of Life in a Biopsychosocial Framework ........................... 1
1.2 Problem Statement ................................................................................................... 3
1.3 Motivation for the Study .......................................................................................... 6
1.4 Aims, Objectives and Research Questions ............................................................... 8
1.5 Comparing health-related quality of life .................................................................. 9
1.6 Exploring temperament and pain coping in migraine without aura ....................... 10
1.7 Testing for determinants of health-related quality of life ...................................... 10
1.8 Outline of Chapters ................................................................................................ 11
1.9 Conclusion of Chapter 1 ......................................................................................... 13
Chapter 2: Migraine ..................................................................................................... 14
2.1 The migraine diagnostic criteria ............................................................................. 14
2.2 Diagnostic committees. .......................................................................................... 15
2.2.1 The International Classification of Headache Disorders and migraine. ...... 17
2.2.2 Controversy in diagnosis and the case definition for this study. ................. 20
2.3 Theories of causality .............................................................................................. 23
2.3.1 Early theories. .............................................................................................. 23
2.3.2 Neurovascular and neurogenic theories. ..................................................... 24
2.4 Determinants of migraine ....................................................................................... 33
2.4.1 Identified biomarkers. ................................................................................. 33
2.4.2 Genetic determinants of migraine without aura. ......................................... 33
2.4.3 Glutamate in migraine. ................................................................................ 34
2.4.4 Psychosocial markers in migraine. .............................................................. 40
2.5 Conclusion of Chapter 2 ......................................................................................... 45
Chapter 3: The Biopsychosocial Approach .................................................................. 46
3.1 Rationale for choice of this framework .................................................................. 46
3.2 George Engel’s proposal ........................................................................................ 47
3.2.1 Criticism of the Biopsychosocial Model. .................................................... 51
3.3 Today’s challenge .................................................................................................. 56
3.4 Conclusion of Chapter 3 ......................................................................................... 57
Chapter 4: Health-Related Quality of Life in a Biopsychosocial Framework ............. 58