Written evidence submitted by the William Templeton Foundation for Young People’s Mental Health (CYP0073)

Scope of evidence

This evidence addresses the following points in the terms of reference:

1. The wider changes needed in the system as a whole, and to what extent it should be reformed in favour of a model that focuses on early intervention

2. What measures are needed to tackle increasing rates of self-harming and suicide among children and young people?

Organisation providing the evidence

This evidence is provided by the charity The William Templeton Foundation for Young People’s Mental Health (YPMH) registered Charity Number 1182312. www.ypmh.org

YPMH is a charitable foundation working to improve the lives of young people by facilitating innovative approaches to resolve mental health conditions.

Our mission is to:

• Reduce the number of young people who experience mental health problems, particularly anxiety and depression
• Help young people enter adulthood with greater resilience to mental health conditions
• Reduce the number of young people who take their own lives.

YPMH is striving to help build a future where:

• The pathways and mechanisms of key mental health disorders, especially depression and anxiety, are understood and widely applied to innovations in practice and policy
• Knowledge and skills for protecting and nurturing mental health are available to young people and their families, to clinicians, and to community organisations supporting young people
• Healthcare policy and practice address the ‘whole self’ at the earliest appropriate points in the development cycle of mental health conditions.

Our approach is to:

• Collaborate with researchers to understand the underlying causes of mental health problems, and how to diagnose, treat and, ultimately, to prevent them
• Build ‘communities of interest’ between researchers, health practitioners, policymakers, innovators and families to focus on specific causes and potential solutions, and bringing those into effect sooner
• Inspire innovations, nurturing effective ideas emerging from research which can develop into viable solutions to make a difference in practice
• Help enhance practice through better understanding of underlying causes of mental health disorders, and by enabling a more joined-up approach to treating the ‘whole self’ across the lifespan.

Summary

The UK is experiencing a significant and growing mental health crisis among young people. For example, rates of depression, self-harm and suicide in young people are each increasing year-on-year. The COVID-19 pandemic will increase these outcomes still further.

Current treatments for depression in under-18s are effective in 60% of cases. Even after successful treatment for depression, 50%-75% of individuals experience a relapse. In many cases, depression recurs over the life course, leading to significant individual, social and economic costs.

The good news is that research published over the last ~15 years provides the basis for a new approach to understanding and treating mental health conditions, such as depression, in young people. This research shows that mental health conditions such as depression develop via interrelated networks of factors spanning an individual’s context and experiences, their body’s biological systems, and psychological factors.

However, this new understanding is not immediately translatable into practice. We need to:

1. Use engineering analysis methods to ‘join up’ the science to understand the causal pathways for priority conditions, such as depression

2. Use this understanding of the causal pathways to identify opportunities for early intervention, including prevention, prediction, early detection, diagnosis of causes and treatment of, for example, the biological conditions that lead to the mental health condition

3. Develop a time-phased portfolio of innovations for early intervention for priority conditions

4. Understand how the innovations can be deployed (at the earliest appropriate points in the care cycle) across self-care by individuals and their families; community care in schools, through social workers and by mental health support charities; in primary care by GPs; in secondary care; and in expert tertiary care for complex, severe conditions

5. Redesign and reconfigure the healthcare ecosystem to enable coherent prevention, prediction, detection, diagnosis and treatment –using integrated well-being (e.g. through diet and nutrition, exercise, sleep), biological and psychological approaches– across the health ecosystem.

We have an opportunity, enabled by recent and ongoing research, to develop a portfolio of early interventions for children and young people which, if deployed effectively, can reduce the individual, social and economic cost of mental health conditions.

Peter Templeton

Founder

February 2021

Contents

1. Why should we focus on early intervention?

2. Recent research, together with engineering analysis methods, provide the basis for a new approach to understanding and treating mental health conditions in young people

3. Using innovation management methods to generate, evaluate and select ideas for early interventions

4. Mental health ecosystem capabilities

5. The economics of early intervention

6. Suicide and self-harm

7. Recommendations

8. Sources

1. Why should we focus on early intervention?

• 75% of people with a mental health problem develop it before the age of 24 and 50% develop it before the age of 14.[1]
• Current treatments for depression in under-18s are effective in 60% of cases.[2]
• Even after successful treatment for depression, 50%-75% experience a relapse [2]
• Research conducted over the last ~15 years shows that most mental health conditions are not ‘all in the mind’ but are the result of an individual’s context and experiences, the body’s biological systems and psychological factors.

The consequences of not addressing these issues early in their development are substantial for the individual. For example:

• Mental health problems among UK adolescents increased between 2005 and 2015, when 14.8% reported depressive symptoms and 14.4% self-harm.[3]
• The proportion of children experiencing a probable mental disorder has increased from one in nine in 2017 to one in six in July 2020. The rate has risen in boys aged 5 to 16 from 11.4% in 2017 to 16.7% in July 2020 and in girls from 10.3% to 15.2% over the same time period [4]
• More than 7% of children have attempted suicide by age 17. [5]

The consequences of not addressing these issues early in their development are substantial for the economy. For example:

• By 2030, mental health problems are predicted to be the main cause of global ill-health and mortality[6]
• Some 322 million people globally suffer from depression.[7]
• Depression accounts for the biggest share of the world’s burden of disease, measured by years lost to disability[8]
• 1 in 4 people in England experience a mental health problem in any given year. [9]
• The economic cost of mental health problems in Europe, including the UK, is more than 4% of GDP.[10]

The COVID-19 pandemic appears to be resulting in at least two factors that are implicated in the development of depression: chronic stress and chronic inflammation. Increases in these factors will lead to further increases in depression, both in the near term and over the life course.

2. Recent research, together with engineering analysis methods, provide the
    basis for a new approach to understanding and treating mental health
    conditions in young people

Research conducted over the last ~15 years has identified a diverse range of factors associated with mental health conditions in children and young people (CYP). These include economic, social, environmental, biological and psychological factors. Although this research is promising, it can be difficult to see the associations between the different factors, and how they contribute to the development of a particular mental health condition.

YPMH identified an opportunity to analyse the scientific research into depression in CYP using engineering analysis methods, such as ‘root cause analysis’ to ‘join up’ the science into a coherent set of causal pathways for depression. Using this approach, YPMH conducted a project in 2019-2020 with the aim of:

1. Understanding how these economic, social, environmental, biological and psychological factors contribute to the development of depression in CYP
2. Identifying points in the causal pathways for early interventions, including prevention, prediction, early detection, diagnosis of causes and treatment
3. Providing the foundation for a subsequent project to engage researchers, clinicians and other stakeholders to generate ideas for early interventions.

The findings of the project are described below.

Example: Depression This is a summary of the publication Changing Minds: A new approach to understanding and treating depression - available at www.ypmh.org/changing minds.

Introduction

An increasing body of research suggests that depression is not ‘all in the mind’. Rather, it arises from a complex set of interactions within and between:

• Our body’s biological systems, in particular our nervous, endocrine and immune systems, our gut microbiota; and our genes and how they are turned on or off (epigenetics)
• Underlying health conditions we might have
• The choices we make about diet, exercise, sleep and substance use
• Our economic, emotional, social and physical environments
• Psychological factors such as our perceptions of stress and the effectiveness of our coping strategies.

Current research also indicates that any adverse changes to the body’s biological systems during critical periods of development can affect mental health over the long term. Young people are at particularly high risk given that they are still developing mentally and physically, and any assaults to their body systems during these critical periods – from the fetal period through to young adulthood – can have a lasting effect on their mental health.

This knowledge has the potential to bring about a radical change in how we understand and treat depression. By allowing us to identify and diagnose it much earlier and to treat the biological conditions that precede it, we can significantly reduce both its prevalence and its severity. Also, by understanding better the effects of individuals’ choices and actions regarding diet, exercise, sleep and use of intoxicants, we can help inform and empower people to take control of their risk factors for depression.

Causal pathways and mechanisms for the development of depression

After reviewing the research literature regarding depression in CYP, to make the challenge more approachable, we structured clusters of similar topics in the five systems shown in Figure 1, and analysed this as a system of interrelated systems.

Figure 1: A systems approach to understanding mental health

We started by looking at studies that examined associations between observable characteristics of depression, such as brain function, structure and metabolites, in people who have experienced depression with those who have not. We then used ‘root cause analysis’ to identify factors most closely associated with depression, and worked ‘backwards’ from these factors to identify those that are further away in the causal chain.

Factors most closely related to depression

The medical literature has shown that biological processes in the brain and periphery (the body outside the brain) are directly related to the onset of depression. These may be triggered by a number of preceding factors.

Factors further ‘up’ the causal chain

There are a number of preceding factors that can trigger the harmful biological processes that lead to the onset of depression. The individual’s socioeconomic environment, for example, living in deprivation with inadequate material and social resources; their choices and actions regarding diet, sleep, exercise, use of intoxicants and smoking; and their health conditions, such as physical diseases, and use of certain medications. Each of these can place the body under strain, lead to stress and/or inflammation, and subsequently to poor mental health.

Combining insights from such studies with human and pre-clinical research into the body’s biological systems, we began to see the emergence of pathways for the development of depression (see Fig 2).

The next step was to identify those sub-systems within the body’s biological systems that have been shown to play a part in the development of depression (Figure 3).

By understanding the causal pathways and some of the underlying mechanisms using this model, we have been able to identify opportunities for the prevention, prediction, early detection, diagnosis of causes and treatment of depression. The key points in the system considered for early intervention are:

• Biological systems including genes and epigenetics; the gut microbiota; the stress response system (HPA axis); and inflammation
• An individual’s choices and actions regarding diet, exercise, sleep and use of intoxicants
• An individual’s underlying health conditions, including anxiety, the effects of antibiotics, nutritional deficits, obesity, and inflammatory conditions
• An individual’s economic, emotional, social and physical (e.g. pollutants) environments
• Psychological factors, such as coping strategies.

The project considered the factors contributing to the development of depression:

1. Firstly in young adults aged ~18-25 years old, and then
2. Across the life course, including inter-generational factors, fetal, infant, childhood and adolescent development.

Project publication

The results of this study were published in September 2020. The publication Changing Minds: A new approach to understanding and treating depression is available at www.ypmh.org/changing minds.

3. Using innovation management methods to generate, evaluate and select       
    ideas for early interventions

The deep, highly focused work of researchers and clinicians in the disciplines of young people’s mental health unintentionally creates barriers (silos) to looking at opportunities for early interventions in a strategic, systematic way.

Having previously been involved with the leading innovation methods used in industry, YPMH saw an opportunity to use these structured, collaborative methods to bring together a range of expert stakeholders from research, clinical practice, industry and schools, together with young people and parents to explore using these methods to address depression.

In 2020-2021, YPMH conducted a project with the University of Cambridge Centre for Technology Management (experts in innovation management methods) and the Department of Psychiatry to apply the innovation management methods and the causal pathways described above to generate, evaluate and select ideas for early intervention to address depression. The project will be complete in March 2021, and the findings published in May.

In the report, the innovations will be mapped against key elements of the care cycle, including:

• Self-care by young people and their families and carers
• Community care by schools, social workers and mental health support charities
• Primary care (GPs)
• Secondary care (clinical psychologists, psychiatrists)
• Tertiary care (psychiatrists; specialists in endocrine, immune and nervous systems, genes and the gut microbiota)
  

4. Mental health ecosystem capabilities

The current approved pathways for treating depression in CYP up to age 18 include anti-depressants and cognitive behavioural therapy (CBT). The current ecosystem does not have the capabilities, regulatory approval, methods and processes needed to deliver effective early intervention strategies, such as those outlined above for depression.

We need to re-design the physical and mental health ecosystem to implement these new approaches. YPMH recommends that:

1. The capabilities needed to deploy the early innovations in practice and policy across the ecosystem are defined. This should consider, for the priority conditions such as depression, the innovations that enable prevention, prediction, early detection, diagnosis of causes and treatment across the range of social, biological and psychological factors, and their anticipated availability for deployment over time.

2. The key elements in the ecosystem and what can realistically be delivered by each element be considered. These include:
1. Self-care by individuals and their families and carers
2. Community care, such as in schools, by social workers and by mental health support charities
3. Primary care, such as through GPs and by specialist CYP mental health nurses
4. Secondary care involving clinical psychologists and psychiatrists
5. Tertiary care involving psychiatrists and specialists is relevant aspects of physical health

3. These approaches be piloted in a small number of geographies, understanding developed of key success factors, followed by configuration and packaging for national deployment at scale.

5. The economics of early intervention

The individual, social and economic cost of mental health conditions are substantial. Section 1 describes the individual and economic costs, and it is clear that the scale of the problem is increasing.

Current treatments for depression in under-18s are effective in 60% of cases, with a 50%-75% relapse rate. The cost of treating only the mental health outcome of key conditions is not sustainable and the UK simply cannot afford to train and employ sufficient clinical psychologists and psychiatrists to address the growing number of people developing mental health conditions.

However, early intervention through prevention, prediction, early detection, diagnosis of causes and treatment of the biological condition before it becomes a mental health condition will:

1. Reduce the number of people developing the biological conditions that lead to mental health outcomes, and their individual, social and economic consequences
2. Enable scarce expert clinicians to focus on a smaller number of patients with severe or complex conditions
3. Lead to lower social and economic costs and a better quality of life for individuals.

6. Suicide and self-harm

Suicide and self-harm appear from the research literature to share many of the same aspects of the causal pathways of depression. The above early interventions for depression should reduce the number of people self-harming and taking their own lives.

A recent important finding is that neutrophils, and in particular the neutrophil-to-lymphocyte ratio, appear to have a potentially important role as a predictor of suicide.[11, 12, 13] Given the growing number of cases of suicide in young people, early detection using measures including neutrophil-to-lymphocyte ratio should be considered as a matter of urgency. Consideration should also be given to developing approaches to restore the individual’s normal neutrophil-to-lymphocyte ratio by identifying the causes of the changed levels and taking action to treat or remove the underlying causes.

7. Recommendations

1. Early intervention should be developed and deployed as key strategy to address:
• The increasing number and severity of mental health conditions in children and young people, and
• The resulting social and economic costs.

2. Early intervention should address the interrelated systems of:
• Behavioural, psychological and cognitive factors
• Biological systems including genes and epigenetics; the gut microbiota; the stress response system (HPA axis); and inflammation
• An individual’s choices and actions regarding diet, exercise, sleep and use of intoxicants
• An individual’s underlying health conditions, including anxiety, the effects of antibiotics, nutritional deficits, obesity, and inflammatory conditions
• An individual’s economic, emotional, social and physical environments.

3. Understanding of the causal pathways of the principal mental health conditions should be developed by ‘joining up’ research from diverse disciplines using engineering analysis methods.

4. The causal pathways should be used as the basis for identifying where to intervene in the development of the priority mental health conditions.

5. Collaborative innovation management methods should be used to facilitate structured engagement between researchers, clinicians and other stakeholders to generate and evaluate ideas for prevention, prediction, early detection, diagnosis of causes and treatment of the condition, before the mental health condition develops, or to help prevent recurrence of the condition.

6. The Department of Health and Social Care and UKRI should together initiate an innovation programme to enable the accelerated development of early interventions. This should involve public, private and charity sector innovators.

7. Identify where in the care pathway the innovations should be deployed.
• Self-care by individuals and their families and carers
• Community care, such as in schools, by social workers and by mental health support charities
• Primary care, such as through GPs and by specialist CYP mental health nurses
• Secondary care involving clinical psychologists and psychiatrists
• Tertiary care involving psychiatrists and specialists is relevant aspects of physical health

8. Define the capabilities needed to deliver the early interventions across self, community, primary, secondary and tertiary care. Pilot the early interventions and the capabilities in a small number of geographies. Learn from the pilot programmes. Codify the interventions and capability developments for deployment at scale across the UK.

9. Develop an analysis of the economic benefits of early intervention.

10. Develop a roadmap for early intervention for each priority condition, e.g. depression. Cancer Research UK’s roadmap for early detection of cancer is a good example. https://www.cancerresearchuk.org/funding-for-researchers/research-opportunities-in-early-detection-and-diagnosis/early-detection-and-diagnosis-roadmap .
    

8. Sources

1. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Available from: archpsyc.jamanetwork.com

2. Goodyer, I.M. and Wilkinson, P.O. (2019), Practitioner Review: Therapeutics of unipolar major depressions in adolescents. J Child Psychol Psychiatr, 60: 232-243. doi:10.1111/jcpp.12940 Thornicroft

3. Praveetha Patalay, Suzanne H Gage, Changes in millennial adolescent mental health and health-related behaviours over 10 years: a population cohort comparison study, International Journal of Epidemiology, Volume 48, Issue 5, October 2019, Pages 1650–1664, https://doi.org/10.1093/ije/dyz006
    
4. https://digital.nhs.uk/data-and-information/publications/statistical/mental-health-of-children-and-young-people-in-england/2020-wave-1-follow-up

5. https://cls.ucl.ac.uk/wp-content/uploads/2020/11/Mental-ill-health-at-age-17-%E2%80%93-CLS-briefing-paper-%E2%80%93-website.pdf

6. WHO. (2011). Global burden of mental disorders and the need for a comprehensive, coordinated response from health and social sectors at the country level: Report by the Secretariat. Retrieved from apps.who.int/gb/ebwha/pdf_files/EB130/B130_9-en.pdf

7. Friedrich MJ. Depression Is the Leading Cause of Disability Around the World.

JAMA. 2017;317(15):1517. doi:10.1001/jama.2017.3826

8. www.nature.com/news/mental-health-aworld-of-depression-1.16318

9. McManus, S., Meltzer, H., Brugha, T. S., Bebbington, P. E., & Jenkins, R. (2009). Adult psychiatric morbidity in England, 2007: results of a household survey.

https://digital.nhs.uk/data-and-information/publications/statistical/adult-psychiatricmorbidity-survey

10. EU Cycle, OECD Publishing, Paris/European Union, Brussels, https://doi.org/10.1787/health_glance_eur-2018-en.

11. Gundogdu Meydaneri G, Meydaneri S. Can Neutrophil Lymphocyte Ratio Predict the Likelihood of Suicide in Patients with Major Depression? Cureus. 2018 Apr 19;10(4):e2510. doi: 10.7759/cureus.2510. PMID: 29930888; PMCID: PMC6007446.

12. Maja Ivković, Maja Pantović-Stefanović, Bojana Dunjić-Kostić, Vladimir Jurišić, Maja Lačković, Sanja Totić-Poznanović, Aleksandar A. Jovanović, Aleksandar Damjanović, Neutrophil-to-lymphocyte ratio predicting suicide risk in euthymic patients with bipolar disorder: Moderatory effect of family history, Comprehensive Psychiatry, Volume 66, 2016, Pages 87-95, ISSN 0010-440X, https://doi.org/10.1016/j.comppsych.2016.01.005.

13. Velasco Á, Rodríguez-Revuelta J, Olié E, et al. Neutrophil-to-lymphocyte ratio: A potential new peripheral biomarker of suicidal behavior. Eur Psychiatry. 2020;63(1):e14. Published 2020 Feb 17. doi:10.1192/j.eurpsy.2019.20