PhD: SLEEP PROBLEMS AND FUNCTIONAL IMPAIRMENT IN YOUNG PEOPLE AT RISK OF DEVELOPING PSYCHIATRIC DISORDERS (Project 001) - AWARDED

Sleeping problems occur across the lifespan but appear particularly problematic in young people. Young people need more sleep than adults and the pressures of academic and social expectations add to the competing interests and the need for optimal sleep. Young people often have difficulties with insomnia and also sleep wake cycle rhythm. This is influenced by an individual’s chronotype or the tendency of an individuals to sleep at any point of the 24 hour cycle, some people being described as “owls” who are more likely to sleep late and “larks” who are more likely to wake early. Developmentally young people do appear to be more likely to sleep late and require longer periods of sleep.

Over 75% of mental disorders start before the age of 25. Most mental disorders have sleep pattern disturbances as a prominent part of the clinical picture. For some disorders it is known that the sleep problems, often insomnia, and other types of disturbed sleep are related to how an individual functions separately to the influence of other symptoms. However, this relationship has been less studied in young people, where need for sleep is even more important biologically. A new approach to the classification of mental disorders has been proposed that “stages” an illness in terms of the severity and impact from subthreshold to chronic. This is an attractive model in young people where distinct diagnostic categories are less distinctly defined and useful. This model identifies individuals who are presenting with some symptoms and distress but do not meet the criteria for a definite diagnosis and therefore are deemed at risk of developing a threshold disorder. There are current efforts to identify simple interventions in this population as secondary prevention of the development of psychiatric disorders.

One such intervention would be improvement in sleep patterns. There are currently no specific treatment approaches for sleep patterns aimed at this population. The use of technology such as apps and online approaches to deliver such interventions is particularly attractive in young people

In this studentship we propose the student investigates the nature and degree of these sleep problems in a young population at risk for developing psychiatric disorders using a mixture of techniques (questionnaires and objective sleep measurements). As part of the studentship we also propose that they investigate the feasibility of technological interventions to specifically address these sleep difficulties.

Supervisors: Dr A Thompson, Dr N Tang, Prof F P Cappuccio (University of Warwick) - Dr K Chisholm, Prof S Wood (University of Birmingham)

This studentship is funded by the Joint ESRC DTC (Warwick, Birmingham, Nottingham). Closing date: 29th April 2016.

Candidate: Ms Latoya Clarke (2016-2020)

---

MSc or PhD: RELATIONSHIP BETWEEN SLEEP DISTURBANCES AND ADVERSE PREGNANCY OUTCOMES (Project 002)

Even though both pregnancy and sleep are two normal events relevant to a large number of women during their life span, there is limited research on the effect of disturbed sleep on pregnancy outcomes. The optimal duration of sleep in pregnancy is unknown but studies have reported that total sleep time and sleepiness increases during the first 3 months of pregnancy suggesting that the need for sleep may increase at these early stages of pregnancy.

To date studies on this topic have been small and have used indirect methods to assess sleep.Our overall objective would be to investigate the independent role of early pregnancy sleep disturbances (quality and quantity) on glucose dysregulation in late pregnancy.

Our aim is to carry out a systematic review of the current literature and to use meta-analysis to pool the available evidence to determine whether sleep disorders, alongside insufficient and poor quality sleep is associated with higher risk of GDM.Sub-group analyses will be performed. This will allow us to analyze studies separately, based on major differences. For example, studies which have non-objective measures of sleep (questionnaires and sleep diaries) from studies in which objective measures (Actigraphy, Polysomnography) have been used. Likewise, studies that have been conducted in different ethnic groups or with different outcome measures will be analyzed separately.

We envisage that the project will extend into individual records meta-analysis by obtaining individuals datasets from independent authors in a multi-site international collaborative analysis.

The project will require a good understanding of epidemiology and data analysis, a proficient use of Microsoft Office platforms and a good grasp of the use of statistical packages like SPSS, SAS or Stata, and RevMan v.5.0 or above. A clinical background is not essential. Supervision will be provided.

Supervisors: Dr M A Miller and Prof F P Cappuccio (University of Warwick)

Currently available to self-funded candidates

---

PhD: LONGITUDINAL ANALYSES OF SLEEP AND COGNITION IN THE ELSA COHORT (Project 003)

Cognition is a broad term, which encompasses a variety of mental processes including memory, problem solving, language, forward planning and attention. Sleep may affect different aspects of cognitive function in different ways. Furthermore, sleep disturbances may be early markers of progressive brain disorders such as Alzheimer's disease. As we age, biological and physical changes occur which may affect both sleep and cognitive function.

In a recent cross-sectional study of a large representative sample of the British population aged 50 year or more (English Longitudinal Study of Aging or ELSA), we demonstrated that the relationship between sleep domains (quantity and quality) and both memory and non-memory brain functions differ between younger and older adults1.

The aim of this study is to extend our previous work by using data from open-access follow-up studies to determine if individuals with poor sleep have a faster rate of cognitive decline over time.

The project will require a good understanding of epidemiology and data analysis, a proficient use of Microsoft Office platforms and a good grasp of the use of statistical packages like SPSS, SAS or Stata. A clinical background is not essential, but familiarity with methods of assessment of cognitive functions would be an asset. Supervision will be provided.

Reference

1) Miller MA, Wright H, Ji C & Cappuccio FP. Cross-sectional study of sleep quantity and quality and amnestic and non-amnestic cognitive function in an ageing population: the English Longitudinal Study of Ageing (ELSA). PLOS ONE 2014; 9(6): e100991

Supervisors: Dr M A Miller and Prof F P Cappuccio (University of Warwick)

Currently available to self-funded candidates

---

MSc or PhD: SLEEP DEPRIVATION AND SLEEP DISTURBANCES AS PREDICTORS OF DEPRESSION. A SYSTEMATIC REVIEW AND META-ANALYSIS (Project 004)

Depression is a major cause of disability worldwide and is associated with physical and social morbidity, increased mortality, and large economic cost1. Psychiatric disorders, and depression in particular, are the most prevalent of all health conditions associated with disturbances of sleep. In many patients with depression, symptoms of insomnia herald the onset of the disorder and may persist into remission or recovery, even after adequate treatment. Several studies have raised the question whether symptoms of insomnia or indeed sleep disturbances may constitute an independent clinical predictor of the development or relapse of depression. Whilst some study suggests that poor quality of sleep may be a significant predictor of the development of depression2, there is no suggestion on what contributing role chronic sleep deprivation (reduced quantity of sleep) may have on the development of depression.

Our overall objective would be to investigate the independent role of sleep disturbances (quality and quantity) on the development of depression.

Our aim is to carry out a systematic review of the current literature and to use meta-analysis to pool the available evidence to determine whether sleep duration, alongside insufficient and poor quality sleep, is associated with higher risk to develop depression.

Sub-group analyses will be performed. This will allow us to analyze studies separately, based on major differences. For example, studies which have non-objective measures of sleep (questionnaires and sleep diaries) from studies in which objective measures (Actigraphy, Polysomnography) have been used. Likewise, studies that have been conducted in different ethnic groups or with different outcome measures will be analyzed separately.

The project will require a good understanding of epidemiology and data analysis, a proficient use of Microsoft Office platforms and a good grasp of the use of statistical packages like SPSS, SAS or Stata, and RevMan v.5.0 or above. A clinical background is not essential. Supervision will be provided.

References

1) Weich S. Chapter 8: The epidemiology of sleep and depression. In: Sleep, Health and Society; from aetiology to public health. Eds. Cappuccio FP, Miller MA, Lockley SW; Oxford University Press, 2010; pp. 178-190

2) Baglioni C, et al. Insomnia as a predictor of depression: a meta-analytic evaluation of longitudinal epidemiological studies. J Affective Disord 2011; 135: 10-19

Supervisors: Prof F P Cappuccio and Prof S Weich (University of Warwick)

Currently available to self-funded candidates

---

MSc: SLEEP DEPRIVATION AND SLEEP DISTURBANCES AS PREDICTORS OF ADVERSE CHANGES IN LIPID PROFILE. A SYSTEMATIC REVIEW AND META-ANALYSIS (Project 005) - AWARDED

Background. Cardiovascular disease is the main cause of morbidity, death and disability in the world, and large economic cost. Over the past ten years our research programme at the University of Warwick has established a strong epidemiological evidence that disturbances in sleep quantity and quality are long-term predictors of numerous chronic conditions including heart disease, stroke1 and total mortality2. The evidence has also identified a number of risk factors and mediators that can explain this increased risk, namely obesity3, diabetes4, hypertension5, inflammation6. Another possible mediator could be the blood lipid profile. From research at Wageningen University, where the role of nutrition and lifestyle in disease aetiology is extensively studied, the lipid profile is known to be affected by diet7 -8. Whilst there is some suggestion that sleep deprivation and poor quality sleep may also unfavorably affect the lipid profile, no systematic evidence has been published as yet.

Objective. To investigate the independent role of sleep disturbances (quality and quantity) on the development of atherogenic lipid profiles.

Methods. Systematic review of the current literature of prospective population studies and meta-analysis to pool the available evidence to determine whether sleep duration, alongside insufficient and poor quality sleep, is associated with changes in atherogenic circulating lipid profiles. Sub-group analyses will be performed. This will allow us to analyze studies separately, based on major differences. For example, studies which have non-objective measures of sleep (questionnaires and sleep diaries) from studies in which objective measures (Actigraphy, Polysomnography) have been used. Likewise, studies that have been conducted in different ethnic groups or with different outcome measures will be analyzed separately.

Skills. The project will require a good understanding of epidemiology and data analysis, a proficient use of Microsoft Office platforms and a good grasp of the use of statistical packages like SPSS, SAS or Stata, and RevMan or R.

Supervisors: Prof F P Cappuccio (University of Warwick); J M Gelejinse (Wageningen University)

Candidate: Ms Marlot Kruisbrink (2016)

---

PhD: STROKE IN BANGLADESHI IMMIGRANTS IN THE UNITED KINGDOM (Project 006) - AWARDED

Objective: Ethnicity is one of the independent predictors of the severity of stroke and South Asians mortality rate is 1.5 times higher than white Europeans. The aim of this study is to evaluate stroke in South Asians particularly in Bangladeshi immigrants in the UK.

Methods: Mixed method study.

Quantitative: Four quantitative studies are planned. First, secondary data analysis from the Wandsworth Heart and Stroke Study in South London which will be analysed for risk factors for stroke in the Bangladeshi population. The second study, which has already been undertaken, is a Freedom of Information request of Birmingham hospitals about stroke and ethnic minorities. The third study is an audit in secondary care of access to stroke units and the fourth study is an analysis of stroke registers from primary care.

Qualitative: A protocol for a qualitative study will be developed for one aspect of the quantitative data, in order to further explore and illuminate the quantitative findings.

Results: Once the raw data is collected it will be analysed and conclusions will be drawn.

Supervisors: Prof Francesco Cappuccio and Dr Wendy Robertson (University of Warwick, Warwick Medical School)

Candidate: Ms Raheela Shaikh (2014-2017)

---

MSc: DIETARY SALT REDUCTION TO CONTROL MENIERE'S DISEASE: A SYSTEMATIC REVIEW OF THE EVIDENCE (Project 007).

Background: Meniere’s Disease is a chronic illness that affects a substantial number of patients every year worldwide. It is characterised by intermittent episodes of spinning head (vertigo), lasting from minutes to hours, fluctuating hearing loss, perception of sound - ‘ringing of the ears’ – when no actual sound is present (tinnitus) and ear fullness (aural pressure). There is currently no cure. However, up to 85% of patients are helped by either life-style changes or various medical and surgical procedures. It has been suggested that a low-salt diet might reduce endolymphatic pressure in endolymphatic hydrops (raised endolymph pressure in the membranous labyrinth) hence relieving symptoms. However, it is unclear whether the evidence is available to support this practice.

Aims of this study: To systematically review the published literature on the efficacy of a reduction in salt intake on acute and symptoms or natural course of Meniere’s Disease (frequency of acute attacks, recurrence, prevention and rate of progression).

Summary of proposed research protocol: We shall search systematically databases of all publications worldwide for either observational or interventional studies suggesting an effect of reduced sodium (salt) intake on Meniere’s Disease (symptoms and/or natural course). The review will inform us on knowledge gaps for the design of a randomised clinical trial to provide an answer to an important therapeutic need.

Skills. The project will require a good understanding of systematic reviews and data extraction, and data analysis, a proficient use of Microsoft Office platforms and a good grasp of the use of statistical packages like SPSS, or Stata, and RevMan.

Supervisor: Prof F P Cappuccio (University of Warwick)

Currently available to self-funded candidates

---

PhD by Publication. ADVANCING KNOWLEDGE OF CARDIOVASCULAR HEALTH AND DISEASE THROUGH COHORT STUDIES AND NON-INVASIVE CARDIOVASCULR IMAGING (Project 008) - WITHDRAWN

Project outline

The focus of the work is around advancing knowledge of cardiovascular health and disease.

By using data carefully collected through cohort studies, coupled with phenotypic data obtained from a range of non-invasive cardiovascular imaging modalities, the work will contribute to:

a) Cardiovascular diagnosis and improvement of cardiac care through improved imaging techniques

b) Cardiovascular disease prognosis through a series of large prospective studies in myocardial infarction and the development and use of novel risk classification metrics to predict risk of adverse outcomes

c) Mechanistic discovery through enhanced imaging techniques and the discovery of mechanisms through which plaque vulnerability occurs.

Supervisor: Prof F P Cappuccio (University of Warwick)

Candidate: Dr Angela Sumei Koh (2016-2019)

---

PhD. THE PATHOPHYSIOLOGY OF HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFpEF) (Project 009) - AWARDED

Project Outline

Background. Although there are many evidence-based treatment options in terms of prognosis and symptoms for Heart Failure with Reduced Ejection Fraction (HFREF), to date there is no evidence-based treatment available for patients with HFpEF that lowers mortality. Most large scale phase III clinical trials, using pharmacological treatment to improve outcome, have been unsuccessful. Whilst there is no single reason contributing to the negative result of these trials, the most likely explanation is probably that our understanding of the pathophysiology of the HFpEF syndrome remains incomplete and we are therefore currently unable to produce therapies targeted at the underlying mechanisms causing the syndrome. In order to develop evidence-based treatments in patients with HFpEF, its underlying diverse pathophysiology needs to be fully understood through further research. This is therefore, the most important area of research need within HFpEF. Furthermore, there is growing evidence that HFpEF is a heterogeneous condition.

Hypothesis. Patients with HFpEF are heterogeneous and consist of different subsets in terms of pathophysiology. It is likely that this includes the following subtypes:

Type 1: patients with cardiac hypertrophy and fibrosis only, without significant vascular pathology (primary cardiac pathology, e.g. severe aortic stenosis or hypertrophic cardiomyopathy).

Type 2: patients with predominant vascular pathology involving larger arteries as well as the microvasculature (diffuse fibrosis and a degree of hypertrophy), with evidence of increased systemic vascular resistance (SVR), without primary cardiac pathology. Minor secondary cardiac effects may be seen.

Type 3: pre-capillary pulmonary hypertension and pure right heart failure wrongly classified as HFpEF

Summary of research protocol. (1) reviewing the studies on the pathophysiology of HFpEF; (2) observational, non-interventional study, to investigate the hypothesis that arterial stiffness increases with comorbidities, in addition to ageing, resulting in the HFpEF syndrome. This study will comprise of several participant groups matched for age and sex. The participants enrolled will comprise of five groups (21 patients in each group) all aged 70 years or above, including a parallel group (11 patients). Hence, 95 patients in total and the groups are as follows:

A) Normal healthy volunteers without major comorbidities

B) Patients with hypertension without diabetes mellitus

C) Patients with hypertension AND diabetes mellitus

D) Patients with HFpEF.

E) Parallel group will be a HFREF group.

Our primary objective is to demonstrate if there is increasing arterial resistance from group A to group D and a significant difference in arterial resistance between group D and E.

Supervisors: Prof F P Cappuccio, Dr M A Miller (University of Warwick), Prof P Banerjee, Prof M Weickert (UHCW NHS TRust)

Candidate: Dr Syed Danish Ali (2017-2022)

---

Supervisors

Projects