A breakthrough has been made in understanding why severe depression affects men and women differently.
In a new study, the brains of people with depression at the time of death were examined, and alterations were found in different parts of the brain for each sex.
The team of scientists, from Université Laval, also identified a potential depression biomarker in women.
“Depression is very different between men and women,” said lead author Caroline Ménard, professor at the Faculty of Medicine at Université Laval and researcher at the CERVO Brain Research Centre.
“In women, the disease is twice as common, the symptoms are different, and the response to antidepressants is not the same as in men. Our goal was to find out why.”
In a previous study, Prof Ménard’s team showed that prolonged social stress in male mice weakened the blood-brain barrier separating the brain from peripheral blood circulation.
These changes were due to the loss of a protein called claudin-5 and were evident in the nucleus accumbens, a part of the brain associated with reward and the control of emotions.
The researchers found the same thing in the brains of men suffering from depression at the time of their death.
When Prof Ménard and her team repeated the experiment in female mice, they found that the brain barrier alterations caused by claudin-5 loss were located in the prefrontal cortex.
Their findings were the same when they examined the brains of women suffering from depression at the time of their death.
In men, however, the blood-brain barrier of the prefrontal cortex was not affected.
“The prefrontal cortex is involved in mood regulation, but also in anxiety and self-perception,” explained Professor Ménard.
“In chronically stressed male mice and in men with depression, this part of the brain was unaltered. These findings suggest that chronic stress alters the brain barrier differently according to gender.”
As they investigated further, the researchers discovered a blood marker linked to brain barrier health.
The marker, soluble E-selectin, is an inflammatory molecule found at higher concentrations in the blood of stressed female mice. It is also present in blood samples of women with depression, but not in men.
“Today, depression is still diagnosed through questionnaires,” said Prof Ménard.
“Our group is the first to show the importance of neurovascular health in depression and to suggest soluble E-selectin as a depression biomarker.
“It could potentially be used to screen for and diagnose depression. It could also be used to measure the efficacy of existing treatments or treatments in development.
“But first, large-cohort clinical studies will need to be conducted to confirm the biomarker’s reliability. These breakthroughs would not have been possible without the individuals and families who donate to the Douglas Bell Canada Brain Bank and the Signature Bank in Montréal.”
Mental health struggles of those shielding during pandemic revealed
Health anxiety increased significantly from the first COVID wave, research reveals
Health anxiety and mental health problems among clinically-vulnerable groups, who have shielded from COVID-19 at home for much of the past two years, have risen since the first wave of the pandemic, new research has revealed.
Around 40 per cent of those shielding were ‘clinically anxious about their health’; a higher proportion than rates reported during the first wave.
Additionally, the University of Bath research highlights how older populations were more anxious about their health and women continued to be more adversely affected when compared to men.
Around half of those shielding other people also experienced ‘vicarious health anxiety’ – the first time this specific issue has been explored by researchers.
The study is the first to use validated measures of mental health to focus on the effects of the pandemic for those who have been shielding or continue to shield.
It finds that health anxieties among these groups grew in line with the length of time they spent indoors.
Conversely, and in comparison with work carried out by the same research team during the first wave of COVID-19, anxiety among the wider population decreased over time.
Clinical psychologist Dr Jo Daniels, from the University of Bath’s Department of Psychology, explains: “As COVID-19 slips from the front pages, those who have been shielding – or continue to shield – have become a forgotten group. But the pandemic has had profound effects on their lives with a heavy mental health burden.
“Our latest findings reveal that whereas health-related anxieties among the general population have fallen over the past two years, which is of course likely to be related to the vaccine roll-out, it appears that anxieties among the shielding populations have grown.
“As final guidelines are reviewed, and potentially lifted, we must provide greater support to those in most need.
“Policy-makers need to be aware of the psychological impact of shielding over the course of the pandemic as they make decisions about the support and future plans in relation to the clinically vulnerable.
“Many who are continuing to follow guidance for the immunosuppressed will be anxious if forced to return to work, and to society in general.”
In March 2020, before lockdown, the government identified individuals who were ‘clinically vulnerable’ and advised them to shield. Guidelines included avoiding contact with others and asking friends and family to collect shopping. These applied to individuals with weakened immune systems and underlying health conditions.
From August 2021, government shielding guidance ended. However, due to further waves of COVID-19, many individuals chose to continue shielding and take additional precautions.
At the end of 2021, 22 per cent of people who met the clinically vulnerable status continued to shield, whilst 68 per cent were taking added precautions.
Set against this context, the research from the team at Bath explored the mental health effects of the second wave of COVID-19 (January 2021) for people shielding compared with the first wave (March – April 2020). Two separate research studies drew on questionnaire responses from individuals of all ages and health conditions.
The first study, conducted during the first lockdown in early 2020 involved 842 individuals from the general public; this second study, carried out during the second lockdown in early 2021 involved 723 individuals, specifically those from shielding groups.
Their results – which adds further to research around vulnerable groups during the pandemic – show that those shielding have been more fearful of contamination, more anxious about their health and more anxious generally when compared to the broader population.
The team, led by Dr Daniels and Dr Hannah Rettie, say these findings highlight a pressing need for increased psychological support for people who have been shielding in some cases for more than two years.
Their study offers insight into the ways psychological therapies, such as CBT, can be adapted to support shielders.
The researchers also stress that their findings should not be interpreted as meaning that shielding groups are over-anxious.
Given the threats of COVID-19, they say fear is a very normal response for those at risk of significant consequences, particularly in the absence of almost all protective measures and extended periods of social isolation.
Pre-school play ‘lowers risk of mental health problems later’
The findings give the first clear evidence that ‘peer play ability’ has a protective effect on mental health
Children who learn to play well with others at pre-school age tend to enjoy better mental health as they get older, new research has revealed.
The findings provide the first clear evidence that ‘peer play ability’, the capacity to play successfully with other children, has a protective effect on mental health.
Researchers at the University of Cambridge analysed data from almost 1,700 children, collected when they were aged three and seven, and found those with better peer play ability at age three consistently showed fewer signs of poor mental health four years later.
They tended to have lower hyperactivity, parents and teachers reported fewer conduct and emotional problems, and they were less likely to get into fights or disagreements with other children.
Importantly, this connection generally held true even when the researchers focused on sub-groups of children who were particularly at risk of mental health problems.
It also applied when they considered other risk factors for mental health – such as poverty levels, or cases in which the mother had experienced serious psychological distress during or immediately after pregnancy.
The findings suggest that giving young children who might be vulnerable to mental health issues access to well-supported opportunities to play with peers – for example, at playgroups run by early years specialists – could be a way to significantly benefit their long-term mental health.
Dr Jenny Gibson, from the Play in Education, Development and Learning (PEDAL) Centre at the Faculty of Education, University of Cambridge, said: “We think this connection exists because through playing with others, children acquire the skills to build strong friendships as they get older and start school.
“Even if they are at risk of poor mental health, those friendship networks will often get them through.”
Vicky Yiran Zhao, a PhD Student in PEDAL and first author on the study, added: “What matters is the quality, rather than the quantity, of peer play.
“Games with peers that encourage children to collaborate, for example, or activities that promote sharing, will have positive knock-on benefits.”
The new findings build on further recent research which has helped to show the power of play in children’s mental health.
The researchers used data from 1,676 children in the Growing up in Australia study, which is tracking the development of children born in Australia between March 2003 and February 2004.
It includes a record, provided by parents and carers, of how well the children played in different situations at age three. This covered different types of peer play, including simple games; imaginative pretend play; goal-directed activities (such as building a tower from blocks); and collaborative games like hide-and-seek.
These four peer play indicators were used to create a measure of ‘peer play ability’ – the underlying ability of a child to engage with peers in a playful way.
The researchers calculated the strength of the relationship between that measure and reported symptoms of possible mental health problems – hyperactivity, and conduct, emotional and peer problems – at age seven.
Across the entire dataset, children with a higher peer play ability score at age three consistently showed fewer signs of mental health difficulties at age seven.
For every unit increase in peer play ability at age three, children’s measured score for hyperactivity problems at age seven fell by 8.4 per cent, conduct problems by 8 per cent, emotional problems by 9.8 per cent and peer problems by 14 per cent.
The effect was evident even among the at-risk groups. In particular, among the 270 children in the ‘low persistence’ category, those who were better at playing with peers at age three consistently had lower hyperactivity, and fewer emotional and peer problems, at age seven.
The researchers suggest that assessing children’s access to peer play at an early age could be used to screen for those potentially at risk of future mental health problems.
They also argue that giving the families of at-risk children access to environments which promote high-quality peer play, such as playgroups or small-group care with professional child minders, could be an easily deliverable and low-cost way to reduce the chances of mental health problems later.
“The standard offer at the moment is to put the parents on a parenting course,” Gibson said.
“We could be focusing much more on giving children better opportunities to meet and play with their peers.
“There are already fantastic initiatives up and down the country, run by professionals who provide exactly that service to a very high standard.
“Our findings show how crucial their work is, especially given that the other risk factors jeopardising children’s mental health could often be down to circumstances beyond their parents’ control.”
A silent epidemic: traumatic brain injury in the community
Professor Nick Alderman, clinical director at Elysium Healthcare, looks at neurobehavioural support
In the UK there are an estimated 1.3 million individuals enduring the long-term effects of traumatic brain injury (TBI) living within the community. Often, symptoms of neurobehavioural disability, a legacy of TBI, can go undiagnosed and unsupported, inhibiting how successfully they can live within the community and putting a huge strain on their relationships and family life.
Professor Nick Alderman is clinical director, neurobehavioural rehabilitation services and head of psychology at Elysium Neurological Services. He is acknowledged internationally as one of the foremost experts in neurobehavioural rehabilitation, having more than three decades experience in this field. In June 2021, Professor Alderman, and his research colleagues at Swansea University, published a study which looked at the prevalence and predictors of neurobehavioural disability amongst survivors with TBI in the community.
In this EveryExpert article, we talk with Professor Alderman – also part of NR Times’ expert panel – about how the Swansea Neurobehavioural Outcome Scale (SASNOS) can be used in a community setting and the necessity to raise awareness about the silent epidemic of TBI survivors across the UK.
Hi Nick, thanks for talking with us today. Could you start by explaining more about how the lives of individuals, who are enduring the long-term effects of TBI, are impacted in a community setting?
Nick: “Neurobehavioural disabilities can be very complex. There is a large range of symptoms that are due to a variety of factors that people can inherit as a result of a traumatic brain injury. For example, there’s the organic damage to the brain itself. When the damage is to the frontal part of the brain this can have a significant impact on a person’s life within the community, because this is the part of the brain that’s responsible for controlling behaviour and picking up feedback. A function of the frontal lobe is also to enable us to adapt our behaviour to new and novel situations.
“So, when people have frontal lobe damage as a result of a TBI, not only are they more likely to have challenging behaviour, they can often have real difficulties in coping with novel situations. This produces a sort of dilemma as in situations, like a formal conversation or structured exchange, where people are well rehearsed in the behaviour, because before injury the behaviour was just habitual, there are no obvious problems. The person can seem to be functioning ok. This is why individuals can perform well in formal assessments but outside of the assessment they actually struggle in many aspects of life.
“As soon as you put someone into a new or novel situation where they’ve got to think on their feet, you see problems with planning and organisation. This can easily result in frustration, and because they may also have difficulties inhibiting behaviour as another legacy of TBI, they may express this by shouting or being aggressive, which can be frightening and intimidating to other people.
“So that’s the organic damage, but of course there’s damage to function as well, particularly to cognitive function, memory, attention and planning skills.”
So neurobehavioural disabilities is about a lot more than just challenging behaviour or aggression?
Nick: “Yes, exactly. It’s about all different sorts of impact on people that have a very subtle, but in many cases, a very catastrophic effect on their day-to-day lives. One common example is that individuals can often have difficulties with the ability to attend to multiple events. For instance, let’s take myself as I’m speaking here now. I’m having to think about what I’m saying, what I’m about to say, I’m looking at you to see if you’re paying attention to gather some feedback. So I’m having to process lots of things at the same time and that has an impact on my behaviour.
“For individuals with brain injury, often their ability to monitor, in that sense, is much more restricted. So in social situations where an individual with TBI is engaging in conversation with another person, and somebody else joins that conversation, perhaps the conversation changes direction, the individual with TBI can struggle to respond appropriately.
“Somebody with these sorts of difficulties can’t pick up on the fact that the conversation has changed, because they’re so intent on monitoring their own output in terms of their verbal behaviour. As a consequence, their behaviour therefore becomes socially inappropriate because they’re not adjusting it to the new set of circumstances. It can often be labelled as rude or ignorant, when they’re not deliberately being so. The behaviour is a product of the cognitive problems they have.”
And these are considered quite basic social interactions – conversations, exchanges etc. So if an individual can’t manage this it can be quite limiting on what they’re able to do in everyday life.
Nick: “Absolutely, and this issue is often missed in formal assessments – because of the reasons explained earlier. People will think of things like aggression because that’s easy to conceptualise and much easier to measure. But when it comes to the social niceties it’s much more difficult to establish their impact.
“For clinicians working face to face with individuals with brain injuries, we have long been cognisant of these issues but there weren’t really any good instruments out there to measure neurobehavioural disability in the round. That’s why we developed the SASNOS and why it’s important from a rehabilitation point of view. We need global measures to give us this all round assessment, otherwise they’re biased. If clinicians are only measuring aggression, for example, they’re not measuring these other very subtle symptoms that are often the bigger problem.
“The other thing is, which led to the development of the SASNOS, was the fact that nearly all of the measures that were being used had been modified from psychiatry so they hadn’t been specifically developed for brain injury. There’s obviously an assumption on the part of people who think that the psychiatry of aggression is going to be the same as the psychiatry of brain injury, and they’re not. The drivers are completely different.”
So let’s talk about your recent paper, looking at the use of the SASNOS in the community. What was the reasoning behind the study?
Nick: “The main motivation was to try and illustrate the prevalence of neurobehavioural disability holistically, not just with aggression, but with the whole range of symptoms that individuals experience. The SASNOS has been used extensively in patient settings. We’ve successfully been able to compare the prevalence and severity of neurobehavioural disability for people in specialist neurobehavioral units such as the Avalon Centre.
“But, we know from the research, that most people who have these sorts of difficulties are out in the community and they don’t get access to the appropriate support. There are 1.3 million people, it is estimated, that are living in the community with the long-term effects of an acquired brain injury, including traumatic brain injury. The research shows that these difficulties are chronic, they don’t go away and they don’t tend to get better. They are more disabling in terms of community reintegration than physical disabilities. They are the reasons why marriages and families break up, why people have hit out at home and ended up in prison or on the streets, or in long term psychiatric care.
“So the motivation to look at the community group is very much from that point of view. In the paper we show that the difficulties weren’t as severe as you would find in patients who’d been admitted to specialist neurobehavioural programmes, because they’re a particular sample. But the difficulties were still quite severe, even for violence and aggression. Particularly with interpersonal relationship problems and problems with cognitive function.”
Was there anything particular about the community sample in your study?
Nick: “Well the main point to stress here is that these individuals looked for all intents and purposes like they are fully recovered. However TBI is a silent epidemic, individuals seem to be functioning normally and, if you look at someone, there doesn’t seem to be anything wrong with them. But actually the reality is very different.
“It’s only when people are put in situations where their ability to direct frustration gets tested, or they are put into a very unique situation and they don’t have the capacity to cope. They’ve lost the ability to plan and change behaviours. If they’re in novel or new situations their difficulties really come to the fore.”
Could we talk a little more about contextualizing and self-awareness i.e. the individual has an awareness that they have this disability or that they’ve been impacted in this way. Does this self-awareness help them to manage behaviour and responses?
Nick: “You’d think it would, but it doesn’t always. Some people are very insightful about what has happened but this can lead to an increase in depression because they are very aware that their situation has changed. Others have less awareness and insight. For example, if you ask relatives or someone that knows the individual well, and talk to them about their difficulties, there’s often a disconnect.
“Relatives can describe numerous difficulties and then we talk to the person with TBI and they might say “I don’t have any problems and I don’t know why I’m here today”. It can be a barrier for rehab because if people don’t recognise that they are experiencing difficulties, they won’t necessarily want to seek out rehabilitation.
“An advantage of the SASNOS is that it has two versions. One version that people that know the person with TBI can complete, and another version that the person themselves can complete. So clinicians and researchers can look at that paradox.”
If the individual who has TBI doesn’t have that insight into their situation, they’re not going to come forward for help, so do you have to rely on the families to come forward?
Nick: “Yes often we do, the families are usually the torch bearers or flag bearers for trying to get their relatives into a rehabilitation programme. Or it’s because their behaviour is such that they’ve got into trouble with the law, and may need residential neurobehavioural support.
“An individual can suffer a TBI and make a good physical recovery whilst they are in hospital, because they’re in an environment that’s structured and supported. They get to know the environment and can make progress. However when they get discharged, often without a follow up, they’re just left to get on with it and that’s where the difficulties begin to show.
“That’s why it’s quite unusual for us to see patients within months of injury, it’s usually years before the full social impact of the injury is felt. So this is why the SASNOS is important, it makes these hidden disabilities, that have such a catastrophic impact on daily life, apparent and visible which gives them substance. And it can be done much more quickly, hopefully reducing the negative impact on the individual and their family.”
Thanks for your time today Nick, as we conclude our conversation is there anything else you’d like to add?
Nick: “Well I’d just like to reiterate the importance of continuing to try and educate people and raise awareness of the issues for individuals with TBI who are living within the community. I often refer to the startling statistic that there are 1.3 million people living with TBI in the UK, many of whom are living without adequate support. As a silent epidemic, they are hidden from sight, until their difficulties become so great they need help from residential services.
“The figure of 1.3 million people just refers to TBI but if you add to that the number of people with other forms of acquired brain injury, that’s a sizable portion of the population. And if this article can contribute to that growing movement of raising awareness and education, that would be a very positive contribution.”
- For more about Elysium Neurological Services, visit here
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