Proposal summaries

These are research proposals that have been approved by the ALSPAC exec. The titles include a B number which identifies the proposal and the date on which the proposals received ALSPAC exec approval.

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B3776 - Association of diet and physical activity with serum metabolites and cardiovascular disease risk in adolescents from the ALSPAC - 13/05/2021

B number: 
B3776
Principal applicant name: 
Laura Johnson | University of Bristol (United Kingdom)
Co-applicants: 
Mr Eduard Martinez
Title of project: 
Association of diet and physical activity with serum metabolites and cardiovascular disease risk in adolescents from the ALSPAC
Proposal summary: 

In this study I am going to look at how different lifestyle factors, like foods eaten, timing or frequency of eating, physical activity, sedentary behaviours and their timing or location, combine together to create an overall behavioural pattern score that indicates whether adolescents have good health. It has been previously found that a combination of factors is more important for health compared with single factors alone. I also plan to use a new, reproducible laboratory technique, known as metabolomics, to record over 220 measures of blood that indicate a range of metabolic processes. This will help to find out in much more detail than ever before how behaviour leads to better cardiovascular health via metabolic pathways. When it is known more about the pathway that leads from lifestyle to disease it will be easier to predict who will stay healthy and who will not from their behaviours.

I will be using information from diet diaries, activity monitors and blood samples that have already been provided by Children of the 90s participants when they were teenagers.

Impact of research: 
Identifying the metabolic intermediates between poor health behaviours and long-term metabolic risk has the potential to offer objective methods for monitoring health, looking at responses to intervention and preventing long-term risk of cardiometabolic disease.
Date proposal received: 
Thursday, 13 May, 2021
Date proposal approved: 
Thursday, 13 May, 2021
Keywords: 
Epidemiology, Diabetes, Hypertension, Obesity, Metabolomics, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Sex differences, Blood pressure, BMI, Cardiovascular, Cohort studies - attrition, bias, participant engagement, ethics, Metabolic - metabolism, Nutrition - breast feeding, diet, Physical - activity, fitness, function, Puberty

B3773 - Long COVID and mental health - 07/05/2021

B number: 
B3773
Principal applicant name: 
Alex | UoB (United Kingdom)
Co-applicants: 
Professor Nic Timpson, Dr Kate Northstone, Dr Rebecca Pearson
Title of project: 
Long COVID and mental health
Proposal summary: 

The COVID-19 pandemic and related mitigation measures have had a profound impact of society and wellbeing. Much research (including that of ALSPAC) has focused on the impact of the mitigation measures, rather than the impact of the disease. ALSPAC forms part of larger consortia examining the impact of contracting COVID-19 and Long COVID on later consequences, one of which is mental health.

This project will specifically focus on the impact of COVID-19 status and Long COVID throughout the pandemic, on later mental health by examining depression and anxiety in both generations of ALSPAC.

Impact of research: 
Results will be shared with PHE and HDRUK
Date proposal received: 
Wednesday, 5 May, 2021
Date proposal approved: 
Wednesday, 5 May, 2021
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Psychology - personality

B3764 - Assessing and taking account of measurement error using repeat measurements of exposure and outcome variables - 04/05/2021

B number: 
B3764
Principal applicant name: 
Rosie Cornish | University of Bristol (United Kingdom)
Co-applicants: 
Dr Willy Steven Kamgang, Professor Kate Tilling, Professor Deborah Lawlor
Title of project: 
Assessing and taking account of measurement error using repeat measurements of exposure and outcome variables
Proposal summary: 

Most measures in epidemiology are subject to error; despite this, the impacts of measurement error are often overlooked. Measurement error in an outcome variable will generally result in a loss of precision whereas measurement error in an exposure variable (or other covariate) will generally lead to bias in regression coefficients.
In this project we will quantify measurement error in systolic blood pressure, weight and height using repeated measurements made on a subsample of individuals attending ALSPAC clinics. We will then assess the impact of measurement error in these variables on regression coefficients and their standard errors.

Impact of research: 
Will help other users of ALSPAC data understand the extent of measurement error in these key variables and its likely impact on analyses.
Date proposal received: 
Wednesday, 21 April, 2021
Date proposal approved: 
Tuesday, 4 May, 2021
Keywords: 
Epidemiology, Statistical methods, Blood pressure, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Statistical methods

B3766 - An exploration into the impact of social contact on the risk of depressive symptoms during COVID-19 findings from a prospective - 04/05/2021

B number: 
B3766
Principal applicant name: 
Jessica Armitage | Co-Supervisor
Co-applicants: 
Professor Claire Haworth, Eunhee Kim
Title of project: 
An exploration into the impact of social contact on the risk of depressive symptoms during COVID-19: findings from a prospective
Proposal summary: 

COVID-19 has resulted in significant increases in psychological distress, concerns, and depressive symptoms. This increased vulnerability may have resulted from environmental and social changes caused by the pandemic crisis. Social contact modalities changed drastically due to lockdown restrictions throughout the COVID-19 pandemic. Stay at home and social distancing orders resulted in a decrease in in-person social contact, and a resulting increase in distant social contact via video calls, phone calls, and texts. Our study will explore whether these different forms of social contact influenced the levels of depression, and the possible factors driving this. Additionally, gender difference in the usage of social contact methods can have an association with the elevation of loneliness. Females are more susceptible to loneliness while keeping social distance due to COVID lockdown. Since females are more dependent on in-person social engagement, females could feel lonelier by the changes in social contact forms than males, which can further trigger depression. Hence, we will also consider whether the gender contributes to increasing depressive symptoms in relation to changes in social contact modalities caused by social distancing. Understanding how symptoms of depression may be predicted by different modes of social contact will prove key to ensuring those most at risk are supported to help prevent further increases in depression.

Impact of research: 
The research is extremely timely due to recent changes in social contact restrictions in the UK. By exploring possible benefits of in-person social contact, the present study could facilitate a crucial insight into its importance for mental health. By investigating predictors of symptoms of depression, our findings could also be used to help prevent later occurrences of depression by enforcing the importance of different forms of social contact. By also exploring the extent to which increases in depressive symptoms resulting from social contact may be explained by gender differences, increases in loneliness, and other COVID-related circumstances, our study will provide insight into how different forms of social contact may impact mental health.
Date proposal received: 
Thursday, 22 April, 2021
Date proposal approved: 
Tuesday, 4 May, 2021
Keywords: 
Immunology, Statistical methods, Statistical methods

B3769 - Investigating inflammation as a targetable mechanism in depression suicide and self-harm - 04/05/2021

B number: 
B3769
Principal applicant name: 
Hannah J Jones | University of Bristol (United Kingdom)
Co-applicants: 
Professor Golam Khandaker, Professor Stan Zammit, Dr Jon Heron, Professor Caroline Relton, Dr Carol Joinson, Dr Becky Mars, Professor Robert Yolken
Title of project: 
Investigating inflammation as a targetable mechanism in depression, suicide and self-harm
Proposal summary: 

Depression is common, devastating, disabling, and a major risk factor for suicide. About a third of individuals with depression are unresponsive to antidepressant treatment, suggesting that other mechanisms are involved in the onset and progression of the disorder. Emerging evidence implicates inflammation as a risk factor for depression and suicidal behaviour. However, little is known about the role inflammation plays in causing or worsening these mental health outcomes. As such, we aim to investigate whether inflammation represents a relevant and therapeutically targetable mechanism for depression and suicidal behaviour in young people.

Using repeated measures of inflammation (taken from blood samples collected over time), we will first define robust patterns of inflammation during childhood and adolescence in ALSPAC. Second, we will test whether early-life risk factors associated with both depression and suicidal behaviour, specifically adversity during childhood, infection, and timing of puberty, relate to patterns of inflammation during adolescence. Third, we will investigate if inflammation mediates the relationship between these early-life risk factors and depression, self-harm and suicide in young people.

Findings from this research will inform whether inflammation could be a target for treatment, prediction and prevention of depression, self-harm and suicidal behaviour in young people.

Impact of research: 
This research will improve our understanding of the role of early-life stressors in priming patterns of inflammation during childhood and adolescence, as well as the impact of these patterns on later mental-health outcomes. The longitudinal inflammatory patterns derived by this study may serve as a useful resource for other researchers interested in inflammation levels during the life-course. More specifically, findings from this research will inform whether inflammation could be a target for treatment, prediction and prevention of depression, self-harm and suicidal behaviour in young people. Findings could be used to direct future work investigating characteristics of inflammation-related depression and clinical trials of immuno-modulating therapies for depression and suicidal behaviour.
Date proposal received: 
Wednesday, 28 April, 2021
Date proposal approved: 
Tuesday, 4 May, 2021
Keywords: 
Epidemiology, Infection, Mental health, Inflammation, Statistical methods, Childhood - childcare, childhood adversity, Epigenetics, Immunity, Statistical methods

B3770 - Can neuroprotective strategies reduced cerebral visual impairment CVI - a pilot study into genetic susceptibility to CVI - 06/05/2021

B number: 
B3770
Principal applicant name: 
Cathy Wlliams | University of Bristol (United Kingdom)
Co-applicants: 
Dr Silvia Pregnolato, Professor Karen Luyt, Dr Santi Rodriguez, Dr David Odd, Dr Alexandra Creavin, Professor Jeremy Guggenheim
Title of project: 
Can neuroprotective strategies reduced cerebral visual impairment (CVI)? - a pilot study into genetic susceptibility to CVI
Proposal summary: 

Paediatric cerebral visual impairments (CVIs) are vision problems caused by damage to the brain rather than the eyes. Injuries to the newborn brain are by far the most common causes, including injuries associated with prematurity, hypoxia-ischemia and/or infections in the perinatal period. Many of these children have multiple neurodevelopmental impairments affecting movement, cognition and/or behaviour, and require extra educational support. There is concern that in some of these children CVIs go unnoticed or mistaken for other problems. Recent work by our group has shown that CVIs might be more prevalent than previously appreciated in the population, highlighting the need for a panel of biomarkers/predictors which can promote earlier and more accurate identification of high-risk children.
Genetic variants may affect how the newborn brain responds to perinatal stresses capable of causing brain injury. Compared to other neurodevelopmental disorders, research into the genetic contributions to CVIs is lacking, although a few genetic associations have been reported (1, 2).
This study aims at evaluating whether candidate genetic variants in the main candidate pathways involved in perinatal brain injuries (glutamate signalling and inflammation) are associated with CVIs. This hypothesis has derived partly from work carried out by two of the applicants (CW and KL) in the DRIFT study(3), in which children were assessed 10-years after a new intervention to treat brain bleeds. A high proportion of these children had CVIs and the number of CVIs correlated with the degree of structural damage to the brain that the children sustained in infancy. The genetic variants we will investigate have been identified both from the wider literature and from our own previous work (4). This includes preliminary findings within the Bristol Neonatal Gene Study, implicating candidate genetic variants in the glutamate signalling and inflammation pathways in childhood motor and cognitive outcomes. For some of these variants, us and others have explicitly shown functional effects on glutamatergic and inflammatory regulation in in vivo models relevant to brain injuries.
Associations between candidate genetic variants and vision outcomes in children from the general population will be explored within ALSPAC. By combining research from the Bristol Neonatal Gene Study with the rich database of visual function data within ALSPAC, we will be able to consider of a range of potentially important perinatal factors (e.g. prematurity, birth complications, evidence of brain injuries during the neonatal stay in the hospital) that may modify the effect of genotype on visual outcomes. We will also examine the associations between the same SNPs with (a) cognitive and (b) motor findings. From the existing literature we expect there is to be associations and we will compare the effect sizes (ES) in analyses of associations between the vision data and the SNPs of interest, with those obtained when using the motor and cognitive data. These results will be used to onform designs for future powered studies.
Additionally, we will collect new prospective data for children at risk for CVIs, enrolled by the PI at the Bristol Eye Hospital. This new clinical data will include additional more in-depth vision assessments compared to those routinely offered in the standard clinic, which will be evaluated as novel biomarkers for CVIs. Genetic profiles of these children with clinical diagnoses of CVIs will be compared to those from ALSPAC representing the general population.
This work is a collaboration between research groups in Bristol and is complementary to a proposal already approved, submitted in 2019 by SR. Some of the work proposed here is already approved as part of that proposal - however use of the vision data is unique to this proposal

References

1. Bosch DG, Boonstra FN, de Leeuw N, Pfundt R, Nillesen WM, de Ligt J, et al. Novel genetic causes for cerebral visual impairment. European journal of human genetics : EJHG. 2016;24(5):660-5.
2. Bosch DG, Boonstra FN, Reijnders MR, Pfundt R, Cremers FP, de Vries BB. Chromosomal aberrations in cerebral visual impairment. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. 2014;18(6):677-84.
3. Luyt K, Jary SL, Lea CL, Young GJ, Odd DE, Miller HE, et al. Drainage, irrigation and fibrinolytic therapy (DRIFT) for posthaemorrhagic ventricular dilatation: 10-year follow-up of a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2020;105(5):466-73.
4. Pregnolato S, Chakkarapani E, Isles AR, Luyt K. Glutamate Transport and Preterm Brain Injury. Front Physiol. 2019;10:417.
5. Williams C, Northstone K, Sabates R, Feinstein L, Emond A, Dutton GN. Visual perceptual difficulties and under-achievement at school in a large community-based sample of children. PLoS One. 2011;6(3):e14772.

Impact of research: 
No studies yet have reported on whether genetic vulnerability to neurotoxic damage can lead to CVIs, despite these being the leading cause of childhood blindness in high-income settings. We propose to collect pilot data to see whether children with CVI do have such vulnerabilities, by investigating whether known genetic markers for vulnerability to neurological damage are overrepresented in children with vision problems and CVI. Therefore, this pilot study may contribute to our understanding of the role that genetic factors play in these debilitating impairments, promoting further research in this field. Genetic biomarkers supported by robust evidence may find clinical utility by promoting earlier and more accurate identification of high risk newborns, especially in combination with sensitive and specific neuroimaging biomarkers. Genetic biomarkers may also provide a tool to identify affected babies who are more likely to respond to neuroprotective treatments. Both glutamate signalling and inflammation are ideal candidates for a pharmacogenomics approach for existing and novel drugs targeting these pathways. We expect that a better understanding of the genetic contributions to CVIs will enable improvements in early identification, diagnosis, and treatment. This has the potential not only to improve prognosis for these newborns, but also to help mothers, families and clinicians making more informed and personalised decisions when planning pregnancy, childbirth, and child follow-up. The subsequent push of neonatal care towards prediction and prevention may have impactful consequences on health and wellbeing in childhood. Finally, CVI occurs more frequently than neurodevelopmental impairments also caused by newborn brain injuries, such as cerebral palsy. Therefore, the study may also assist in evaluating whether vision outcomes reflecting perinatal brain injuries (e.g. visual function, clinical CVI diagnosis or RNFL thickness) are a more sensitive outcome measure for future clinical trials of neuroprotective interventions.
Date proposal received: 
Monday, 3 May, 2021
Date proposal approved: 
Tuesday, 4 May, 2021
Keywords: 
Ophthalmology, Developmental disorders - autism, Cognitive impairment, Congenital abnormalities, Learning difficulty, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Birth outcomes, Cognition - cognitive function, Development, Environment - enviromental exposure, pollution, Genetics, Injury (including accidents), Vision

B3762 - Young peoples barriers to mental health services - 26/04/2021

B number: 
B3762
Principal applicant name: 
Corine Driessens | ARC-Wessex @ University of Southampton (UK)
Co-applicants: 
Peter W Smith, Fiona Lacey
Title of project: 
Young people's barriers to mental health services
Proposal summary: 

Research has discovered that on any given day in England, 28.5% of young people experience mental health problems, and that as little as one in four of them receive formal support for these problems. There is a lack of knowledge of what happens to those young people not receiving mental health services. For those individuals receiving mental health services, mental health problems have been shown to limit economic, vocational, and social functioning. International studies suggest that 50 to 70% of young people who receive services for their mental health problems continue to experience these problems in adulthood.

The proposed project will learn from cohort data which young people are less likely to receive professional support for their mental health problems and what the characteristics are of those young people not receiving mental health services for their problems. It will also be determined how many young people who do not receive mental health services for their problems continue to experience mental health problems in young adulthood and how resilient these young people were during the COVID pandemic.

The feedback provided by Young People will help direct the course of the project. While researchers from the University of Southampton will share the findings with the academic community, YOUNGMINDS will spread the word about our research and findings to their members and followers, young people, mental health service providers and policy makers using a variety of different media. Output activities will increase awareness and promote discussion among the stakeholder groups and ease the way for more effective mental health support for young people.

Impact of research: 
By focusing our research on causative ameliorating childhood factors of young people’s mental health and focus special attention on those young people not accessing formal mental health services we hope to contribute to the identification of at-risk adolescents, barriers for accessing mental health services, and need for public awareness campaigns, while also spark professional and political interest for those young people not accessing services for their mental health problems. The information gathered can stimulate young people’s mental health campaigns aimed at adolescents at risk. The Young People recruited from Young Minds to advise on this project will have an ‘advisory’ work contract with Young Minds. They will be trained by Young Minds to lead workshops with their peers to discuss our project and will feed information back to research team regarding development of project, adjustments to existing analyses, and interpretation of findings. The staff at Young Minds will lead on the dissemination to the public and Young People by posting updates of the study on their website, post information on social media, and mail information to their members. They will also lead on professional and policy dissemination by organizing a round table with mental health professionals at the NHS and other charities, as well as policy makers. Birth cohort studies are best placed to gather evidence relating to development and management of mental health. Although their representativeness tends to diminish over time as different groups drop out of the study differentially, this bias can be controlled statistically. By successfully applying a nonignorable missing data model to the field of mental health research, we further advance a missing data approach that can be promoted within the wider field of applied health care research.
Date proposal received: 
Monday, 19 April, 2021
Date proposal approved: 
Tuesday, 20 April, 2021
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Statistical methods

B3759 - Are poorer attendance and oral hygiene behaviours associated with greater dental anxiety in adolescents - 16/04/2021

B number: 
B3759
Principal applicant name: 
Kate Northstone | University of Bristol (United Kingdom)
Co-applicants: 
Dr Tom Dudding, Jenny Clow
Title of project: 
Are poorer attendance and oral hygiene behaviours associated with greater dental anxiety in adolescents?
Proposal summary: 
Impact of research: 
Understanding which oral health behaviours (attendance and oral hygiene) are most strongly associated with dental anxiety may help focus prevention initiatives.
Date proposal received: 
Monday, 12 April, 2021
Date proposal approved: 
Friday, 16 April, 2021
Keywords: 
Dentistry, Dental health, Dental

B3760 - The impact of the COVID-19 pandemic on OCD symptoms in young adults - 15/04/2021

B number: 
B3760
Principal applicant name: 
Kate Northstone | University of Bristol, UK (United Kingdom)
Co-applicants: 
Beca Morrell, Dr Alex Kwong, Dr Rebecca Pearson
Title of project: 
The impact of the COVID-19 pandemic on OCD symptoms in young adults
Proposal summary: 

Obsessive compulsive disorder (OCD) symptoms have increased over the COVID-19 pandemic in the ALSPAC cohort compared to pre-pandemic reported levels. As an anxiety disorder, it is probable that anxiety induced by fear of contamination and illness has contributed to additional or heightened obsessive behaviours during the pandemic, but it is unclear who has been most affected.

Impact of research: 
Understanding which sub-groups of the population have suffered detrimental changes in OCD may help in providing appropriate support.
Date proposal received: 
Monday, 12 April, 2021
Date proposal approved: 
Thursday, 15 April, 2021
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health

B3761 - Prevalence and Factors Associated with Behavioral Difficulties in 5-year-old Children Born with Cleft Lip and/or Palate - 15/04/2021

B number: 
B3761
Principal applicant name: 
Evie Stergiakouli | MRC IEU, UoB
Co-applicants: 
Sammy Berman
Title of project: 
Prevalence and Factors Associated with Behavioral Difficulties in 5-year-old Children Born with Cleft Lip and/or Palate
Proposal summary: 

Cleft lip and/or palate (CLP) or orofacial cleft is a group of congenital birth defects affecting 1 in 700 newborns annually [1]. Commonly associated with structural problems relating to feeding, hearing, speech, and tooth development, recent research shows that affected individuals may also be at an elevated risk for psychological, social, and behavioral challenges [1],[2]. While many studies have sought to investigate the psychosocial effects of CLP, a 2005 systematic review was inconclusive, citing a dearth of longitudinal research and a lack of consistency and uniformity between studies [3]. In 2017, a Cleft Care UK study of five-year old children with unilateral CLP (UCLP) found that children born with UCLP had higher levels of behavioral problems than the general population, but that these findings required replication [1]. Researchers also suggest that children born with CLP may experience heightened psychosocial challenges around the school transition, and that this is worthy of investigation [1]. All of the contributing research cites a sufficient lack of large, longitudinal studies, focused on the psychological development of children born with CLP, and that this research is critical to the development of appropriate interventions for this population [1],[3].
1. Waylen A, Mahmoud O, Wills AK, Sell D, Sandy JR, Ness AR. Centre-level variation
in behaviour and the predictors of behaviour in 5-year-old children with non-
syndromic unilateral cleft lip: The Cleft Care UK study. Part 5. Orthodontics &
Craniofacial Research. 2017;20(S2):40–7.
2. Cleft lip and palate [Internet]. nhs.uk. 2017 [cited 2019 Apr 2]. Available from:
https://www.nhs.uk/conditions/cleft-lip-and-palate/
3. Hunt O, Burden D, Hepper P, Johnston C. The psychosocial effects of cleft lip and
palate: a systematic review. Eur J Orthod. 2005 Jun;27(3):274–85.
4. Bjerke SM, Feragen KB, Bergvik S. Strengths and Difficulties Questionnaire
(SDQ): Informant Agreement Between Children Born With Cleft Lip and/or
Palate and Their Parents. Cleft Palate Craniofac J. 2018;55(2):204–12.

Impact of research: 
The results of this study will provide valuable information for better understanding the needs of the CLP population and can advance our understanding of a potentially unmet service need from a public health perspective.
Date proposal received: 
Tuesday, 13 April, 2021
Date proposal approved: 
Thursday, 15 April, 2021
Keywords: 
Epidemiology, Congenital abnormalities

B3750 - Fit body fit mind The relationship between cardiorespiratory fitness and muscular strength during adolescence with future risk - 13/04/2021

B number: 
B3750
Principal applicant name: 
Gemma Lewis | UCL (United Kingdom)
Co-applicants: 
Tia Urgasova
Title of project: 
Fit body, fit mind? The relationship between cardiorespiratory fitness and muscular strength during adolescence with future risk
Proposal summary: 

THis project is linked to dataset B2857

There is growing evidence that exercise is good for brain and mental health. We know much less about whether keeping in good physical shape during adolescence can prevent onset of mental illness later in life. Research shows that higher levels of cardiorespiratory fitness and muscular strength are associated with lower incidence of common mental disorders in adults (Baumeister et al., 2017; Hallgreen et al., 2020; Kandola, Ashdown-Franks, Stubbs, Osborn & Hayes, 2019; Kandola, Osborn, Stubbs, Choi & Hayes, 2020), but we know little about these associations in adolescents. Physical activity has been found to be a positive predictor of better mental health in students (Velten, Bieda, Scholten, Wannemüller & Jürgen, 2018), and light activity during childhood lowers the incidence of depressive and anxiety symptoms in adolescence (Hamer, Patalay, Bell & Batty, 2020; Kandola, Lewis, Osborn, Stubbs & Hayes, 2020). This study will aim to investigate the association between cardiorespiratory fitness and muscular strength during adolescence with the incidence of common mental disorders later in life.

Impact of research: 
Inform public health strategies for the prevention of adolescent depression and anxiety.
Date proposal received: 
Saturday, 3 April, 2021
Date proposal approved: 
Tuesday, 13 April, 2021
Keywords: 
Epidemiology, Mental health, Statistical methods, Cohort studies - attrition, bias, participant engagement, ethics

B3755 - Do childhood ADHD symptoms predict anxiety disorders in adolescence - 13/04/2021

B number: 
B3755
Principal applicant name: 
Gemma Lewis | UCL (United Kingdom)
Co-applicants: 
Natasha Melineck
Title of project: 
Do childhood ADHD symptoms predict anxiety disorders in adolescence?
Proposal summary: 

This project is linked to dataset B2857

Attention deficit hyperactivity disorder (ADHD) is a common childhood neuropsychiatric disorder characterised by impaired levels of inattention, hyperactivity, and impulsivity (American Psychiatric Association, 2013). Meta-analyses estimate the global pooled prevalence of ADHD to be 7.2% in children and adolescents (Thomas et al., 2015) and 3.4% in adults (Fayyad et al., 2007). Cross-sectional studies have shown anxiety disorders are more prevalent in individuals with ADHD compared to the general population (Van Ameringen, Mancini, Simpson, & Patterson, 2010) and the rates increase with age; up to 30% of young people and 50% of adults (Kooji et al., 2012) with ADHD meet the diagnostic criteria for an anxiety disorder.
Although anxiety is highly prevalent in those with ADHD, much of the longitudinal research focuses on whether ADHD is associated with subsequent behaviour disorders and substance misuse. A 2008 systematic review by Jarret and Ollendick specifically identified a lack of longitudinal research on ADHD and subsequent anxiety; this finding still applies today. Longitudinal research on the matter is of importance to see whether ADHD symptoms predispose an individual to the development of anxiety. A recent study examined the association between co-occurring ADHD and anxiety from early to late adolescence and identified a bidirectional relationship between ADHD symptoms and anxiety (Murray et al., 2020) however, no study has examined longitudinal associations between childhood ADHD symptoms and anxiety in adolescence. This would provide a fuller picture of the association between ADHD and anxiety considering the onset of ADHD is often in childhood.

This project is linked to B2857.

Impact of research: 
Improving the prevention of anxiety.
Date proposal received: 
Tuesday, 13 April, 2021
Date proposal approved: 
Tuesday, 13 April, 2021
Keywords: 
Epidemiology, Mental health, Statistical methods

B3757 - Early metabolic features of breast cancer susceptibility - 07/04/2021

B number: 
B3757
Principal applicant name: 
Vanessa Tan | IEU
Co-applicants: 
Francisca Ibacache Fuentes, Caroline Bull, Josh Bell, Emma Vincent
Title of project: 
Early metabolic features of breast cancer susceptibility
Proposal summary: 

Cancers develop for many years before they are diagnosed. Using data from first-generation ALSPAC offspring, we aim in this study to estimate the effects of being more genetically susceptible to breast cancer on metabolic traits measured in blood across early life; this should help to reveal what early stages of breast cancer development look like and when they occur. More specifically, we will examine associations of genetic risk scores for breast cancer that has been shown to be influenced by obesity with traits from targeted metabolomics measured in childhood (age 8y), adolescence (age 15y), and young adulthood (age 18y and 25y). This allows us to view subtle changes in metabolism over time which precede the onset of clinically detectable breast cancer by several decades. Recognizing the early signs of breast cancer development is vital for informing early detection, preventing its onset in older age, and improving survival

Impact of research: 
The likely output of this research will be at least one publication in a general medical or epidemiology journal, the impact of which may be theoretical advancement in active research fields of metabolism and cancer, and recommendations for clinical practice.
Date proposal received: 
Wednesday, 31 March, 2021
Date proposal approved: 
Wednesday, 7 April, 2021
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Cancer, Metabolomics, Mendelian randomisation

B3758 - EMBED - 07/04/2021

B number: 
B3758
Principal applicant name: 
Robi Tacutu | Institute of Biochemistry of the Romanian Academy (Romania)
Co-applicants: 
Prof. Moshe Szyf
Title of project: 
EMBED
Proposal summary: 

Around 40% of the EU population suffers from a mental disorder. Healthy development can be derailed by excessive or prolonged activation of stress response systems in the body and brain during fetal life. Such toxic stress exposure can have damaging effects on learning, behavior, and mental health across the lifespan. Our ERA-NET consortium (Project EMBED) focuses on two cohorts (offspring of obese or stressed mothers), aiming to address specific questions on mental health risk factors. This might be then used in the clinic for disease prevention and health promotion during pregnancy.

Our hypothesis is that maternal obesity and inadequate nutrition during prenatal life can trigger similar responses to maternal stress, altering developmental trajectories and increasing the risk for mental health in adulthood. These adverse experiences can increase the likelihood of developmental delays and later health problems.

Our consortium analyzes epigenetic modifications from the abovementioned cohorts, assessing whether common biological signals characterize early exposure to metabolic and psychological stress, affecting the long-lasting expression and methylation of genes involved in depression, obesity, and immune-metabolic function. We propose to use the ALSPAC data to compare and validate the findings from our consortium-generated data, in a larger/complementary context.

Impact of research: 
Major depression constitutes an enormous medical, individual, societal and economical challenge (depression afflicts up to 10-15% of the population worldwide). Despite extensive investigations, the exact mechanisms responsible for depression have not been identified, and current therapeutics are based on serendipitous discoveries rather than on bench-to-bedside, targeted drug discovery. In addition, although clinically efficient antidepressant drugs do exist, they show high treatment-resistance rates, slow onset of action, side effects, and drug–drug interactions. Currently, there is a clear consensus that early adverse experiences can impinge upon stress/metabolic pathways to coordinate body responses, increasing adult individual susceptibility for mental disorders such as depression. By carrying out the EMBED project, the consortium aims to advance this field of research by studying in more depth the links between pre-natal stresses and post-natal epigenetic modification, and by doing so, potentially enable preventive measures in risk populations, new diagnostics and new therapeutic approaches - for example by nutritional strategies reducing neuroinflammatory mechanisms implemented in the offspring.
Date proposal received: 
Friday, 2 April, 2021
Date proposal approved: 
Wednesday, 7 April, 2021
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Obesity, Computer simulations/modelling/algorithms, Statistical methods, major depression, mental disorders, obesity, prenatal, metabolic stress, psychosocial stress

B3752 - What are the antecedents of multiple adolescent cancer risk behaviours - 01/04/2021

B number: 
B3752
Principal applicant name: 
Caroline Wright | University of Bristol (United Kingdom)
Co-applicants: 
Dr Jon Heron, Paul Okediji
Title of project: 
What are the antecedents of multiple adolescent cancer risk behaviours?
Proposal summary: 

This project will explore the predictors of multiple cancer risk behaviours in adolescence.

Impact of research: 
Successful completion of an MSc dissertation, possible peer-reviewed paper
Date proposal received: 
Monday, 29 March, 2021
Date proposal approved: 
Thursday, 1 April, 2021
Keywords: 
Epidemiology, Behaviour - e.g. antisocial behaviour, risk behaviour, etc., Statistical methods, Birth outcomes, BMI, Childhood - childcare, childhood adversity, Contraception, Physical - activity, fitness, function

B3754 - The relationship between timing of menarche and risky behaviours in early adulthood - 01/04/2021

B number: 
B3754
Principal applicant name: 
Carol Joinson | Population Health Sciences, Bristol Medical School
Co-applicants: 
Caroline Wright, Rose Hawes
Title of project: 
The relationship between timing of menarche and risky behaviours in early adulthood
Proposal summary: 

There is some evidence that girls who experience an earlier onset of menarche than their peers are at greater risk of engaging in a range of risky behaviours in adolescence such as: early initiation of sexual activity; substance use, and antisocial behaviour. Early maturing girls' more mature physical appearance and tendency to affiliate with older peer groups could expose them to increased opportunities for risk taking. It is unclear, however, if the relationship between early timing of menarche and increased risky behaviours persists into later adolescence and early adulthood.

Impact of research: 
Risky behaviours are associated with long term adverse outcomes for physical and mental health, and educational attainment. Our findings will add to the understanding of the challenges that early maturing girls experience during puberty and could contribute to the evidence base for psychoeducational interventions to prepare young people for puberty.
Date proposal received: 
Tuesday, 30 March, 2021
Date proposal approved: 
Thursday, 1 April, 2021
Keywords: 
Epidemiology, Mental health, Statistical methods, Puberty

B3744 - Almost exact Mendelian randomisation - 08/04/2021

B number: 
B3744
Principal applicant name: 
Kate Tilling | University of Bristol (United Kingdom)
Co-applicants: 
Mr Matthew Tudball, Dr Qingyuan Zhao
Title of project: 
Almost exact Mendelian randomisation
Proposal summary: 

Mendelian randomisation (MR) is an epidemiological design which uses the allocation of genes from parents to children as a random source of variation in exposures of interest. To perform MR exactly, we need genetic data on children and one or both of their parents. Due to ease of data collection, however, MR has typically been performed using data from unrelated individuals. As family data becomes more widely available, there has been renewed interest in a better within-family method for MR. Our project involves the development of an (almost) exact test for MR which is explicitly based on the randomisation of genes from parents to children. We are using ALSPAC to demonstrate our new method using real data. In particular, we aim to explore the effect of childhood BMI on systolic blood pressure and risk of diabetes in adulthood, which was recently explored using the UK Biobank cohort (Richardson et al, 2020).

Impact of research: 
As an exact approach to statistical inference, we hope that our method will be the gold standard approach for within-family MR and receive wide uptake among practitioners.
Date proposal received: 
Thursday, 18 March, 2021
Date proposal approved: 
Thursday, 1 April, 2021
Keywords: 
Statistics/methodology, Hypertension, Obesity, DNA sequencing, Statistical methods, BMI, Genetic epidemiology, Mendelian randomisation, Statistical methods

B3753 - Risk behaviours for cancer in adolescence and young adulthood a qualitative analysis - 11/05/2021

B number: 
B3753
Principal applicant name: 
Caroline Wright | University of Bristol (United Kingdom)
Co-applicants: 
Prof. Rona Campbell, Dr Laura Tinner, Dr Ruth Kipping, Ruth Bartlett
Title of project: 
Risk behaviours for cancer in adolescence and young adulthood: a qualitative analysis
Proposal summary: 

We conducted a quantitative analysis of ALSPAC participants to investigate patterns of multiple cancer risk behaviours across adolescence (11-18 years) and their associations with future cancer risk behaviours in early adulthood (24 years). We found there was a very strong association between adolescent and young adult behaviours. While there has been some quantitative work examining the association between adolescent risk profiles and early adult risk, there has been little in the way of qualitative work to explore how young people and/or early adults themselves understand this relationship. Researchers have called for young people to have a stronger voice as key to improving adolescent health, and means being sensitive to young people’s construction of risk behaviour. As such, this qualitative study attempts to address this gap in the literature.

Impact of research: 
An MSc dissertation,
Date proposal received: 
Monday, 29 March, 2021
Date proposal approved: 
Thursday, 1 April, 2021
Keywords: 
Epidemiology, Cancer, Obesity, Sexually transmitted diseases, chlamydia, gonorrhoea, Qualitative study, BMI, Physical - activity, fitness, function

B3756 - Evaluation of recording of Long-COVID in whole population databases using linked LPS data - 26/04/2021

B number: 
B3756
Principal applicant name: 
Andy Boyd | University of Bristol
Co-applicants: 
Jonathan Sterne, Nic Timpson, John Macleod, Kate Northstone
Title of project: 
Evaluation of recording of Long-COVID in whole population databases using linked LPS data
Proposal summary: 

Children of the 90s and some other UK longitudinal studies have been approached directly by Sir Patrick Vallance and Sir Chris Whitty to help with understanding the nature of Long-COVID. This is part of the National Core Studies for COVID research that Children of the 90s is playing a major role in. The NHS and government planners need evidence to inform UK NHS strategies for managing this new and complex condition. At this stage the NHS planners are concerned that it is not clear who has Long COVID and if the national data they are working with properly represents the scale of this new and poorly understood condition. In this project we will compare the data of consenting Children of the 90s participants who have reported having Long-COVID with English GP records to determine the level of agreement between the two. If not all Children of the 90s participants can be identified from the GP records alone as having Long-COVID then this may indicate that national estimates of how many people have these symptoms/outcomes may be inaccurate and the scale of the challenge is under-estimated. This will help identify if new GP coding practice is needed, and to determine how best to help people with this form of COVID.

Impact of research: 
A greater understanding as to whether inferences on Long-COVID drawn from whole population GP databases are accurate based on a greater understanding on whether those with Long-COVID are readily identifiable from coded GP data.
Date proposal received: 
Wednesday, 31 March, 2021
Date proposal approved: 
Thursday, 1 April, 2021
Keywords: 
Epidemiology, CoVID-19, Data Linkage, Linkage

B3751 - You are what your mother ate exploring the effects of maternal and paternal Mediterranean diet on childhood health - 01/04/2021

B number: 
B3751
Principal applicant name: 
Kayleigh Easey | Population Health Sciences (United Kingdom)
Co-applicants: 
Dr Giulia Mancano, Ms Jessica Minkoff, Dr Gemma Sharp
Title of project: 
You are what your mother ate: exploring the effects of maternal and paternal Mediterranean diet on childhood health
Proposal summary: 

We urgently need better evidence about how our experiences before birth might influence our long-term health. Most research in this area has focused on the diets and lifestyles of pregnant mothers, but the evidence is patchy and health advice offered to pregnant women can be confusing and inconsistent. More recent research suggests that a father's diet and behaviour can influence the health of his unborn children, but very little public health advice is currently offered to fathers-to-be.

Some studies have found that children born to mothers who adhere to a Mediterranean diet (typified by a high intake of vegetables, legumes, fruits and nuts, unrefined cereals, fish and olive oil) during pregnancy have better health than their peers. But does this represent a causal effect of Mediterranean diet on offspring health or is it merely correlated due to confounding factors? And what about fathers? Can their adherence to a Mediterranean diet affect their child’s health?

Impact of research: 
Student dissertation, and contribute towards publication in a peer reviewed journal.
Date proposal received: 
Monday, 29 March, 2021
Date proposal approved: 
Thursday, 1 April, 2021
Keywords: 
Epidemiology, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Nutrition - breast feeding, diet

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