HUNDREDS of genes have been newly linked to depression, shedding light on the origins of the condition and highlighting personality types that could be at risk.
The international study, involving more than two million people, is the largest of its kind. It could inform treatments for the condition, which affects one in five people in the UK and is the leading cause of disability worldwide.
Scientists led by the University of Edinburgh studied information pooled from three large datasets of anonymised health and DNA records and pinpointed 269 genes that were linked to depression.
They also used an innovative statistical method to identify sections of DNA that were common in people with depression and in those who adopted lifestyle behaviours such as smoking.
The findings suggest that depression could be a driving factor leading some people to smoke, but more research is needed to explain why, the team says.
Results also show that neuroticism – a tendency to be worried or fearful – could lead people to become depressed, which could shed light on personality factors that put people at risk. The statistical approach – known as Mendelian randomisation – allows scientists to look at how a condition impacts on behaviour, while ruling out other influences such as age or income.
Anonymised data, used with donor consent, is held by UK Biobank, the personal genetics and research company 23andMe and the Psychiatry Genomics Consortium.
Experts say that the study reflects the importance of data science in understanding mental health.
The study, published in Nature Neuroscience, was funded by the MRC and Wellcome.
Professor Andrew McIntosh, of the University of Edinburgh’s Centre for Clinical Brain Sciences, who led the research, said: “These findings are further evidence that depression is partly down to our genetics.
“We hope the findings will help us understand why some people are more at risk of depression than others, and how we might help people living with depression and anxiety more effectively in future.”
Sophie Dix, Director of Research at mental health charity MQ, who was not involved in the research, said: “This study adds to the weight of evidence that genes are one of the key risk factors in depression, which is also impacted by life events such as social environment and trauma. The value of this could really be seen when looking into the development of personalised treatments – a welcome step, given the dearth of innovation in identifying new approaches. We have seen very little advancement in nearly 50 years for people living with depression and right now the avenues available are not working for everyone.
“The power of this big genetic study is that it can point to systems in the brain which adds to our currently limited understanding in this area. By increasing our understanding of these systems, and how the social environment affects biological risk factors, we can begin to identify new targets for treatments that could help the millions of people worldwide affected by depression.”
The challenge of loneliness
INTERNATIONAL experts, including researchers from Swansea University, have published a letter in The Lancet medical journal calling for a unified approach to addressing the global challenge of loneliness.
In response to the growing concerns about the rates and consequences of loneliness, international experts based in universities, research and public health organisations have been working together to help address this issue.
The signatories include experts from the Institute of Public Health in Ireland; Columbia University; George Mason University; University of Auckland; Swansea University; Ulster University; St James’s Hospital; University of Chicago; Trinity College Dublin; Boston College; University of California; Vrije Universiteit Amsterdam; and Brunel University London.
The letter is based on discussions of international researchers at a meeting hosted in Belfast by the Institute of Public Health in Ireland. This has led to the establishment of an International Loneliness and Social Isolation Research Network.
While demographic shifts suggest that the number of people experiencing loneliness will increase, experts say that it is important to recognise that most older adults are not chronically lonely and that young adults are also affected.
Experts say that loneliness can be defined as a “subjective negative experience that results from inadequate meaningful connections”, and have called for a standardised approach to defining and measuring loneliness to help inform those developing policy and services in this area.
The expert group added that charities, community sectors, and governments, who are delivering programmes often have inadequate evidence to plan from and need a more coherent message from research, and a stronger evidence base.
And while more research is needed to find out the full consequences of loneliness, the evidence shows association with poor health and wellbeing, non-communicable diseases, and depression.
Professor Vanessa Burholt from the Centre for Innovative Ageing, in the College of Human and Health Sciences at Swansea University, said that in a time when as a society we have never had more opportunities to connect with people, there is a growing focus on loneliness and its association with poor health outcomes.
She said: “Our understanding of loneliness is still limited and is often stereotypical. While it is often confused with a lack of social engagement, the reality is that some people with lots of friends can still feel lonely and those who live alone may not.
Although loneliness is a very personal experience, addressing loneliness is not simply a matter for individuals but is also an issue for public health and society as a whole. By building evidence and pooling expertise, we can support governments and policymakers to make better-informed decisions to address this challenge.”
Protect your children from flu
Protect your children from flu
CAT1i-17.jpg – Flu vaccination: ‘Really important’ protection for children
PARENTS in Pembrokeshire are being urged to protect their children against flu
Flu is circulating and parents of 2 and 3-year-olds in Pembrokeshire are being asked to ensure their children receive the nasal spray flu vaccine as soon as possible.
Flu can be serious for children and every year children in Wales need treatment in Intensive Care Units because of flu. If you are in a risk group and think you have flu, it is important to speak to your GP surgery or community pharmacy as soon as possible.
Ros Jervis, Director of Public Health at Hywel Dda UHB, said: “We are starting to see more cases of flu so it is really important that as many of our youngest population are protected by the nasal spray vaccine.
“Having a flu vaccine will help protect your child from flu and protection starts around two weeks after having the vaccine.
“It also helps reduce the chance of children spreading flu to others who are at high risk from flu, such as young babies, grandparents, and those with long-term health conditions.”
If your child was aged 2 or 3 years old on 31 August 2019 contact your GP as soon as possible to book an appointment.
If you think you may have flu you can check your symptoms using the NHS Direct Wales symptom checker.
Research breakthrough in schizophrenia
WHAT comes to mind when you hear ‘schizophrenia’? Hallucinations and delusions? Cognitive impairment? Feeling withdrawn from everyone around you? Apathy? With all the above being symptoms of this mental disorder, and with 1 in every 100 people affected, each individual’s life becomes a relentless battle, struggling with habitual activities, social interaction, and general wellbeing and self-care.
Current treatments help to reduce the severity of symptoms and allow patients to maintain a more functional daily life. However, antipsychotic medications, which are typically required lifelong, are not guaranteed to work for all schizophrenia patients, with only about 4 in 5 people benefitting usually.
Advances in scanning have allowed researchers for the first time to show lower levels of a protein found in the connections between neurons in the living brains of people with schizophrenia.
The researchers, who conducted the scans at the psychiatric imaging facility at the MRC London Institute of Medical Sciences, say these changes could underlie the cognitive difficulties seen in schizophrenia and provide targets for research into new treatments.
Synapses are the junctions between neurons. Neurons communicate across the synapse via neurotransmitters; chemicals that transmit the nerve signal.
Researchers investigated the relationship between synaptic density and schizophrenia, questioning whether a reduction in these brain connections is present in schizophrenia and whether they result from treatment with antipsychotic drugs.
The study was inspired by findings from previous post-mortem studies that demonstrated synaptic reductions in the brains of schizophrenia patients compared to healthy controls.
Measuring synaptic protein levels in living patients was not possible before the development of a new PET (Positron Emission Tomography) radioactive tracer that binds to a specific protein associated with synapses. Being “one of the first centres in the world” to have access to this, Professor Oliver Howes, Head of the Psychiatric Imaging Group at the MRC LMS, and his team grasped this opportunity to investigate synaptic loss in schizophrenic brains through the synaptic marker protein SV2A, which is found on the nerve terminal preceding the synapse and is involved in regulating neurotransmitter release.
The team found lower levels of SV2A in the brains of schizophrenia patients, indicating a reduction of synapses. Certain areas exhibited significantly lower levels, such as the frontal cortex which coordinates use, recall and processing of memory, planning complex cognitive behaviour and personality expression. These findings were supported by the understanding that these areas are associated with some of the major cognitive impairments seen in schizophrenia, thus providing a potential clue that synaptic loss may underlie these problems.
But to test whether the loss was a result of the illness or in fact due to treatment, a preclinical study was conducted in rat models investigating the effect of antipsychotic drugs on the levels of SV2A. They found that the antipsychotics did not contribute to the synaptic loss seen in schizophrenic patients, thereby reinforcing their overall findings.
So, what does this mean for the development of schizophrenia treatment?
If the synaptic loss is an underlying key contributor in the disease, further research into the mechanisms could lead to exploring ways to prevent this loss. Moreover, since microglia, known as the immune cells of the brain, play a role in mediating synaptic pruning, there is also potential to target microglia and see if it could introduce a way of preventing excess synaptic loss; an investigation that the team have already begun.
“The human brain, with its approximately 100 trillion synapses, is an extraordinarily complex organ,” says Dr Ellis Chika Onwordi of the Psychiatric Imaging Group and first author of this study. “Having the means to characterise the distribution of these synapses in the living brain, and to find differences in synaptic distribution between patients with schizophrenia and healthy controls, represents a significant advance in our ability to study the neurobiology of schizophrenia.”
Professor Oliver Howes, who led the study, said: “Our current treatments for schizophrenia only target one aspect of the disease – the psychotic symptoms – but the debilitating cognitive symptoms, such as loss of abilities to plan and remember, often cause much more long-term disability and there’s no treatment for them at the moment. Synaptic loss is thought to underlie these symptoms.
“Our lab at the MRC London Institute of Medical Sciences is one of the few places in the world with this new tracer, which means we’ve been able for the first time to show there are lower levels of a synaptic protein in people with schizophrenia. This suggests that loss of synapses could underlie the development of schizophrenia.
“We need to develop new treatments for schizophrenia. This protein SV2A could be a target for new treatments to restore synaptic function.”
The people with schizophrenia who were scanned had all received antipsychotic medication, so the researchers wanted to exclude this as a factor in the synaptic dysfunction. They gave antipsychotic drugs, haloperidol and olanzapine, to rats for 28 days and found it did not affect the levels of the protein SV2A.
Professor Howes said: “This is reassuring as it’s suggesting that our antipsychotic treatments aren’t leading to loss of brain connections.
“Next we hope to scan younger people in the very early stages to see how synaptic levels change during the development of the illness and whether these changes are established early on or develop over time.”