Depressive symptomatology in Obstructive Sleep Apnoea ... symptomatology in Obstructive Sleep Apnoea

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  • Depressive symptomatology in Obstructive Sleep Apnoea

    Shenooka Nanthakumar

    Bachelor of Arts (Honours)

    This thesis is submitted in partial fulfilment of the requirements for the degree

    of Doctor of Philosophy (Ph.D.) at the University of Western Australia

    School of Psychological Science


  • Depressive symptomatology in OSA i

    I, Shenooka Nanthakumar certify that:

    This thesis has been substantially accomplished during enrolment in the degree.

    This thesis does not contain material which has been accepted for the award of any

    other degree or diploma in my name, in any university or other tertiary institution.

    No part of this work will, in the future, be used in a submission in my name, for any

    other degree or diploma in any university or other tertiary institution without the prior

    approval of The University of Western Australia and where applicable, any partner

    institution responsible for the joint-award of this degree.

    This thesis does not contain any material previously published or written by another

    person, except where due reference has been made in the text.

    The work(s) are not in any way a violation or infringement of any copyright, trademark,

    patent, or other rights whatsoever of any person.

    The research involving human data reported in this thesis was assessed:

     Study 2 (Chapter 3) and Study 4 (Chapter 5): Both studies used data from the

    Obstructive Sleep Apnoea and Related Symptoms (OSARS) study. The study

    was approved by the Sir Charles Gairdner Hospital Research Ethics

    Committee and reciprocal approval was provided by UWA HREC (NHMRC

    1031575). The study was registered with the ANZ Clinical Trials Register:

    ACTRN12612001136897. This study was performed in accordance with the

    protocol; ethical principles that have their origin in the Declaration of

    Helsinki (revised 1996), and adhered to the National Statement of Ethical

    Conduct in Human Research (2007) and in accordance with the ICH

    Harmonised Tripartate Guidelines for Good Clinical Practice (GCP).

     Study 3 (Chapter 4): Ethics Committee approval was obtained from

    University of Western Australia Human Research Ethics Committee;

    approval number: RA/4/1/2203.

    Written patient consent has been received and archived for the research involving

    patient data reported in this thesis.

    The work described in this thesis was supported by funding from two sources. Study

    2 (Chapter 3) and Study 4 (Chapter 5) were supported through a grant to R.S. Bucks

    and co-investigators from the NH&MRC (APP1031575), ‘Obstructive Sleep Apnoea

    and Depression’ (2012). Study 3 (Chapter 4) was supported through a grant to R.S.

    Bucks and co-investigators from the West Australian Government, to support the,

    ‘The Busselton Healthy Ageing Study’.

    This thesis contains published work and/or work prepared for publication, some of

    which has been co-authored.

    Signature: [ ] Date: [12/4/2017]

  • Depressive symptomatology in OSA ii


    The overall aim addressed of this thesis was to investigate the symptomatology

    of depression in Obstructive Sleep Apnoea (OSA), specifically, to determine the impact

    of symptom overlap on the expression and treatment of depressive symptoms in OSA.

    It begins with a general introduction (Chapter 1), which defines depression and OSA,

    and then considers factors underlying the relationship between these two conditions,

    symptom overlap, and the treatment of depressive symptoms in OSA by Continuous

    Positive Airway Pressure (CPAP). Four research studies (Chapters 2, 3, 4, and 5) are

    then reported, concluding with a general discussion (Chapter 6).

    Chapter 2 (Study 1) examined the impact of symptom overlap on the prevalence

    of depression in individuals with OSA. OSA is a frequent and often under-diagnosed

    disorder of breathing during sleep that involves partial or full obstruction to the upper

    airway. It is often characterised by symptoms that are also characteristic of depression

    (e.g. fatigue, psychomotor retardation, loss of libido). The assessment of depression in

    OSA is potentially confounded by symptom overlap, which may lead to the

    overestimation of depression in OSA. It is unclear whether the variable prevalence

    estimates found in the literature are a function of symptom overlap. A systematic

    literature search was conducted, identifying 13 studies that met eligibility criteria.

    Meta-analysis was used to synthesize the results from studies examining the prevalence

    of depression in OSA. Additionally, symptoms of depression within depression

    questionnaires were categorised (e.g. anhedonia, cognitive, cognition). The aggregated

    prevalence of depression in OSA was 27%, with estimates ranging from 8% to 68%,

    reflecting marked heterogeneity. OSA severity, BMI, and age did not moderate

    prevalence rates, whereas, depression questionnaire type, sample type (opportunity

    samples versus population-based samples), and gender, significantly moderated

  • Depressive symptomatology in OSA iii

    prevalence estimates. Importantly, prevalence estimates based on questionnaires with

    greater symptom overlap between OSA and depression were higher, whereas

    questionnaires with a higher proportion of anhedonia symptoms were associated with

    lower prevalence estimates. These data suggest that symptom overlap poses a difficulty

    in understanding the expression of depression in OSA.

    As the assessment of depression in OSA is confounded by symptom overlap, it

    is unclear whether CPAP ameliorates both overlapping (OSA-related symptoms) and

    non-overlapping depressive symptoms (OSA-independent). Chapter 3 (Study 2)

    examined the effect of CPAP in ameliorating overlapping and non-overlapping

    depressive symptoms from the Hamilton Rating Scale for Depression (HAM-D), in a

    12-week, single arm study (Obstructive Sleep Apnoea and Related Symptoms

    (OSARS)) study in individuals with OSA (N = 178 intention to treat data, and N = 135

    per protocol data), using latent growth curve modeling (LGCM). At baseline,

    individuals endorsed more severe overlapping compared to non-overlapping depressive

    symptoms. Both overlapping and non-overlapping symptom severity significantly

    decreased over time, but with a greater decrease in the severity of overlapping

    depressive symptoms. Critically, greater CPAP use and higher BMI were associated

    with faster decline in overlapping depressive symptoms, in a dose-response manner, but

    no such relationship was found with the decline of non-overlapping symptom scores.

    These findings suggest that, although overlapping and non-overlapping depressive

    symptoms significantly decrease over time, overlapping symptoms are more responsive

    to CPAP treatment.

    Chapter 4 (Study 3) examined the effect of symptom overlap in the Depression,

    Anxiety, and Stress Scale (DASS-21). The DASS-21 was examined for inclusion as an

    outcome measure in Study 4 (Chapter 5). There are two underlying factors predicting a

  • Depressive symptomatology in OSA iv

    person’s score on a depression measure in OSA, 1) the degree to which there are true

    differences in the degree to which the person is genuinely depressed, and 2) the degree

    to which they are also endorsing items (particularly overlapping depressive symptoms)

    as a function of their OSA. Therefore, questionnaires that consist of overlapping

    symptoms may not be assessing genuine depression in OSA: that is, they may not be

    measurement invariant, due to differential item functioning (DIF). The study examined,

    a) if Lovibond & Lovibond’s (1995) correlated three-factor structure of the DASS-21

    holds in an OSA sample (N = 185), compared to an age and gender matched non-OSA

    sample (N = 185), and b) measurement invariance across these samples. The OSA and

    non-OSA samples were recruited from the Busselton Healthy Ageing Study (BHAS).

    The correlated 3-factor structure of the DASS-21 was a better fit in the non-OSA

    sample. There was a degree of DIF for each of the subscales, especially for the Anxiety

    subscale, in which 2 symptoms (that are also physiological symptoms of OSA)

    produced lower severity scores in the OSA sample compared to the non-OSA sample.

    However, the effect of DIF on scale totals was very small. Such findings suggest that

    the DASS-21 is substantively measurement invariant in OSA and therefore suitable for

    use in an OSA sample.

    Chapter 5 (Study 4) then examined the effect of CPAP on the DASS-21. As the

    DASS-21 is measurement invariant in OSA, any change in depressive symptom scores

    over time represents a “true change” in depressive symptoms, rather than the effect of

    DIF, due to symp