The serotonin theory of depression: a systematic umbrella review of the evidence

The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research. PubMed, EMBASE and PsycINFO were searched using terms appropriate to each area of research, from their inception until December 2020. Systematic reviews, meta-analyses and large data-set analyses in the following areas were identified: serotonin and serotonin metabolite, 5-HIAA, concentrations in body fluids; serotonin 5-HT1A receptor binding; serotonin transporter (SERT) levels measured by imaging or at post-mortem; tryptophan depletion studies; SERT gene associations and SERT gene-environment interactions. Studies of depression associated with physical conditions and specific subtypes of depression (e.g. bipolar depression) were excluded. Two independent reviewers extracted the data and assessed the quality of included studies using the AMSTAR-2, an adapted AMSTAR-2, or the STREGA for a large genetic study. The certainty of study results was assessed using a modified version of the GRADE. We did not synthesise results of individual meta-analyses because they included overlapping studies. The review was registered with PROSPERO (CRD42020207203). 17 studies were included: 12 systematic reviews and meta-analyses, 1 collaborative meta-analysis, 1 meta-analysis of large cohort studies, 1 systematic review and narrative synthesis, 1 genetic association study and 1 umbrella review. Quality of reviews was variable with some genetic studies of high quality. Two meta-analyses of overlapping studies examining the serotonin metabolite, 5-HIAA, showed no association with depression (largest n = 1002). One meta-analysis of cohort studies of plasma serotonin showed no relationship with depression, and evidence that lowered serotonin concentration was associated with antidepressant use (n = 1869). Two meta-analyses of overlapping studies examining the 5-HT1A receptor (largest n = 561), and three meta-analyses of overlapping studies examining SERT binding (largest n = 1845) showed weak and inconsistent evidence of reduced binding in some areas, which would be consistent with increased synaptic availability of serotonin in people with depression, if this was the original, causal abnormaly. However, effects of prior antidepressant use were not reliably excluded. One meta-analysis of tryptophan depletion studies found no effect in most healthy volunteers (n = 566), but weak evidence of an effect in those with a family history of depression (n = 75). Another systematic review (n = 342) and a sample of ten subsequent studies (n = 407) found no effect in volunteers. No systematic review of tryptophan depletion studies has been performed since 2007. The two largest and highest quality studies of the SERT gene, one genetic association study (n = 115,257) and one collaborative meta-analysis (n = 43,165), revealed no evidence of an association with depression, or of an interaction between genotype, stress and depression. The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.

Full article: Molecular Psychiatry (2022)

GP surgeries to provide specialist mental health support

Thousands of new mental health experts will be on hand to support people in their local GP practice amid record demand for services, the head of the NHS announced.

Fully trained experts from local NHS trusts will offer people with severe mental health problems such as bipolar, psychosis or eating disorders, a consultation, treatment, peer support, or a referral to hospital teams without needing a GP appointment.

Full article: NHS England

New research reveals 11 best ways to prevent common mental health problems

The 11 most effective ways for people to protect their mental health are revealed in a guide launched today by the Mental Health Foundation. 

The free guide, Our Best Mental Health Tips is based on the Foundation’s own ground-breaking study on what protects people from common problems such as anxiety and depression.  

The innovative study on which the new guide is based combined existing evidence about how we can protect our mental health with experts’ views, alongside the opinions of members of the public. 

Full report: Mental Health Foundation

Changing Lives – Final Report

Every day in Scotland, three people suffer a drug-related death. Each death is a
personal tragedy for them, their friends and families, and their communities. And
every one of them is preventable.
Over the last three years, we in the Scottish Drug Deaths Taskforce have listened to
the voices of people from across Scotland and beyond – people with lived and living
experience of using drugs, families, service providers in the public, private and
voluntary sectors, community representatives, those in our justice and emergency
services, academics and many more. We have heard their stories and learned from
their experience. Combined with findings from our examination of the evidence base,
these stories and experiences are at the heart of our recommendations and actions.

Full report: Scottish Drugs Deaths Taskforce

Occupational mental health: Addressing patients’ occupational, educational and psychosocial needs as an essential aspect of mental health care

This position statement highlights the crucial, positive role that ‘good work’ can have on an individual’s mental health, and how poor experience of work both risks exacerbating pre-existing poor mental health and/or contributing to the emergence of a mental health condition.
This position statement provides advice and recommendations to the key organisations and individuals who have a role in ensuring work makes a positive impact on mental health.

Full report: The Royal College of Psychiatrists

Briefing: Improving children and young people’s mental health services

Key points
• Across the UK, the number of children and young people experiencing mental health problems is growing. Mental health services are expanding, but not fast enough to meet rising needs, leaving many children and young people with limited or no support. Too little is known about who receives support and who might be missing out.
• National prevalence data suggest large variations in need by sex, age, and socioeconomic deprivation. But data on who is using services are only publicly available for NHS specialist mental health care and are not detailed enough to capture variation by these characteristics.
• This briefing presents analysis from the Networked Data Lab (NDL) about children and young people’s mental health. Led by the Health Foundation, the NDL is a collaborative network of local analytical teams across England, Scotland and Wales. These teams analysed local, linked data sources to explore trends in mental health presentations across primary, specialist and acute services.
• Analysis by local teams highlights three areas for further investigation, nationally and by locality: the rapid growth of prescribing and use of general practice, the mental health of young women, and marked socioeconomic inequalities.

Full report: The Health Foundation

Suicide and Seafarers

Seafaring is a rewarding and important career. But it has unique challenges that for too long have gone unnoticed. It can be isolating, with months at sea, cut off from family and friends. This was made only worse by the recent pandemic which saw significant delays in ships able to dock. It’s physically demanding work and given crew rotations it can be hard to form essential bonds with others. Finally, add in precarious contracts, poor pay, and inconsistent wellbeing support into the mix and you have all the ingredients for a mental health crisis. This is the context behind the important issue of seafarer suicide at sea, which this report explores.

Full report: Department of Transport

Evaluating a young people’s enhanced mental health service at Centre 33

Mental health problems are particularly prevalent in the teenage and young adult years. But young people are less likely to access support for their mental health than other age groups, and those facing multiple barriers may be labelled ‘hard to reach’. In reality, too often services don’t reach out or are not flexible enough to meet young people’s needs.

This report is an evaluation of Centre 33’s Someone To Talk To Initiative, which set out to better meet the needs of young people facing multiple barriers, challenges or inequalities. They offered more flexible and longer-term support to young people without bureaucratic barriers on eligibility.

Someone to talk to finds that the project was able to engage young people with a more significant and complex range of needs who faced greater health inequalities, and that young people who engaged with Centre 33’s project benefited from greater and significant improvements to their mental health.

Crucially, it dismantles the myth that young people facing multiple barriers are ‘hard to reach’; instead, they simply require a more holistic and flexible approach from mental health services.

We’re calling on mental health services to:

  • Offer young people the help they need without requiring them to meet restrictive eligibility criteria
  • Offer young people more choice and autonomy about the support they get and how they want to access it
  • Recognise that complexity of need does not make a young person ‘hard to reach’; rather that the right offer, which includes high levels of autonomy and choice for the young person, results in good engagement and outcomes.

Link: Centre for Mental Health

Briefing 58: Poverty, economic inequality and mental health

The Covid-19 pandemic is being accompanied by a substantial rise in demand for mental health services. Whilst investment in mental health services is vital, it is also necessary to tackle the factors that cause and worsen mental ill health in the first place.

Poverty, economic inequality and mental health, by Ed Davie, explores evidence about the links between these factors, showing that living in poverty increases people’s risk of mental health difficulties, and that more unequal societies have higher overall levels of mental ill health. The briefing also demonstrates that poverty and economic inequality intersect with structural racism to undermine the mental health of racialised and marginalised groups in society.

The evidence is clear that poverty, deprivation and economic inequality are toxic to mental and physical health. Policy makers need to prioritise reducing them as an urgent public health necessity.

The briefing calls for concerted and concrete actions to improve mental health by increasing the incomes and reducing the costs of the poorest people in society. These include increasing benefits and paying the Living Wage, help with housing and childcare costs for the least well-off, and improving access to vital services in the most deprived areas.

Centre for Mental Health

Building the right support for people with a learning disability and autistic people

An action plan to strengthen community support for people with a learning disability and autistic people, and reduce reliance on mental health inpatient care | Department of Health and Social Care

People with a learning disability and autistic people should have the right support in place to live an ordinary life and fulfil their aspirations, in their own home. ‘Building the right support’ is the government’s policy to achieve this ambition by: strengthening community support; reducing the overall reliance on specialist inpatient care in mental health hospitals; and improving the experiences of people with a learning disability and autistic people across public services such as health, social care, education, employment, housing and justice.

This action plan brings together, in one place, the commitments that have been made by different organisations to realise these aims. It aims to make further and faster progress, and drive long-term change for people with a learning disability and autistic people.