How can psychology help us to treat long covid? (Part one of two) At the beginning of the COVID-19 pandemic, I co-published a blog about how behavioural science could help us to understand and change human behaviour during a pandemic. Published in April last year, the blog focused optimistically on the different strategies the government could utilise to help slow the spread of coronavirus and prevent large proportions of the population becoming infected. More than a year has passed and sadly the situation is bleak. At the time of writing, the COVID-19 pandemic has caused over 185 million infections and over 4 million deaths worldwide. The UK is one of the worst affected countries, with over 5 million confirmed cases and over 128,000 deaths in total. But as the lifting of most covid guidance and legal restrictions in England occurred on the 19th July and most people’s lives return to some kind of normal, the NHS has been left to manage a hugely worrying knock-on effect of the pandemic, that of long covid. I am currently working in a long covid clinic in South East London and I wanted to use this two-part blog piece to share some of my experience in this new and challenging field. Specifically, I want to focus on the key psychological themes that have emerged in my consultations and how psychological interventions have the potential to help. The long covid experience Imagine this — you were hit with COVID-19 earlier this year and you become acutely ill for about three weeks. Each morning you wake up scared that you might not make it through the day. You contemplate writing letters to your kids in case you don’t make it through. You spend virtually every moment lying on the sofa falling in and out of sleep, totally disorientated, only getting up to use the toilet. Then you start to turn a corner. Each day the fever, cough and breathlessness get slightly easier to manage. You’re over the worst of this terrible disease and you think to yourself “give it a week or two, and I’ll be back to my usual self”. But weeks pass and whilst the worst of the symptoms have gradually disappeared, you are still not feeling like you. You’re struggling to function at work. On some days you can’t even read a whole email from beginning to end. You’re finding it hard to meet your responsibilities at home because you have virtually zero energy. Even small daily tasks like showering or cleaning the kitchen leave you utterly exhausted. You feel like you’re letting everyone down. Your body is in pain. You can’t concentrate on anything, not even watching the television. You keep forgetting simple everyday words that seem to be on the tip of your tongue but you just can’t reach them. You struggle to help your kids with their maths homework because you can’t compute the most basic of calculations. Your head feels like there is a marshmallow stuck between your ears and your brain feels like it’s in a fog. It feels like it’s not working the way it used to. You feel like a totally different person. Your GP discharges you because you don’t have the infection anymore. You should be feeling fine, but you’re not. Everyone around you seems to have bounced back from their infections without much difficulty. But you haven’t. This is long covid and it needs more attention. What is long covid? According to new NICE guidance, long covid or “Post-COVID-19 syndrome” occurs when physical, cognitive and/or psychological “signs and symptoms that develop during or following an infection consistent with Covid-19, continue for more than 12 weeks and are not explained by an alternative diagnosis”. Data from the ONS shows that at the beginning of May 2021, an estimated 1 million people in the UK (1.6% of the total population) were experiencing long covid, with nearly two-thirds experiencing a negative impact on their day-to-day activities. The most common symptoms reported include extreme tiredness, shortness of breath, muscle aches and difficulty concentrating. From the same report, self-reported long covid has been found to be most common in the UK in people aged 35 to 69 years, in women, in those living in the most deprived areas, and in those living with an existing disability or health condition. Health and social care workers also have a higher prevalence of long covid than those working in other sectors. It is estimated that 10% of people managing their COVID-19 infection will experience persistent symptoms beyond one month. That is a scarily large statistic to process as we appear to be entering a third wave, with cases rising across many parts of the UK. Long covid looks set to affect thousands more individuals and to have a profound effect on our economy and healthcare system. A multidisciplinary approach to treatment Long covid is a complex disease that affects the whole body and is difficult to treat. It involves a range of physical, cognitive and psychological symptoms with occupational, economic, and social implications. A holistic, person centred, multidisciplinary approach is crucial for patients to have the best chance of improvement and recovery. Thankfully this is starting to take shape. In December last year, NHS England announced £10 million of funding to set up a network of more than 60 long covid clinics around the country. These clinics bring together the expertise and skills of doctors, nurses, physiotherapists, psychologists and occupational therapists to jointly plan and manage care. In a recent Guardian article, Professor Carmine Pariante, Editor in Chief of InSPIre the Mind, emphasised the important role that psychological interventions can play in improving the physical health and mental wellbeing of individuals living with long term physical health conditions. In his article, he cites the well-known placebo effect to illustrate how our expectations and the beliefs we hold about ourselves and the world around us can have a powerful effect on our health and recovery from illness; effects which have been measured objectively by changes in the brain and the body. So how can psychology help treat long covid? Psychologists can help patients with long covid in a number of ways. In the remainder of this blog I will touch on the important role of validating patient’s experiences, as well as different techniques that can be used to manage fear and worry. On Thursday, part two will be published which will detail how psychologists can support patients with long covid to manage loss and transition, fatigue and depression. Validating experiences As Carmine mentions in his Guardian article, many patients with long covid are being dismissed by health professionals who think that because they cannot detect long covid physically in the bodies of their patients, that their symptoms must be “in their minds” and hence “not real”. Indeed many patients who I have met in clinic are fed up of not being believed. They are fed up of medical professionals attributing their experience to anxiety and they are desperate to be taken seriously. Simply because an individual’s original cause of the symptoms are now undetectable in the body does not mean they are not real. This narrative is extremely unhelpful and it has a damaging effect on patients and their help seeking behaviour. Therefore the first “intervention” that our whole multidisciplinary team can provide is to be non-judgemental and to validate each patient’s experience. We do this by allowing patients to tell us their story from beginning to end. We give them the time and space to talk and to express their concerns, and we let them know they are being listened to and believed. Managing Fear and Worry It is common for patients with long covid to experience fear. Some are scared of dying from long covid, others worry that they will never fully recover, and some are terrified of catching COVID-19 for a second time. Suffering from an unexplained illness is incredibly distressing. Fear, anxiety and worry are normal and understandable reactions to suddenly having your life turned upside down. Anxiety occurs because illness poses a threat to the patient. It threatens their physical health as well as their autonomy and independence. These threats can alter patient’s beliefs about themselves and their world. Patients might start to believe that they are vulnerable, that the world isn’t safe and that they are not good enough. A combination of increased vulnerability and a decreased sense of power can lead to patients feeling that they have lost control over their bodies and their ability to plan and predict, which often creates frustration and feeds a sense of helplessness. Patients will process this with emotions and the strength of these emotions can create a vicious cycle. Emotions can intensify the physical symptoms of long covid, which in turn can increase feelings of anxiety. In clinic, there are a number of interventions we can provide to help patients manage their anxiety. Firstly, we can provide psychological education to help patients to understand the causes of their anxiety and to normalise the symptoms they are experiencing. We can recommend stress reduction techniques which help to reduce the intensity of a patient’s emotional reactions and, by doing so, reduce the maintaining cycle in which emotions and symptoms intensify one another. Examples include breathing techniques that calm the body through effects on the respiratory, cardiovascular, cardiorespiratory and autonomic nervous systems, as well as attention refocusing exercises such mindfulness that help to keep the patient’s minds in the present moment and reduce worry. We can also support patients to problem solve more effectively and to plan an information diet that includes trusted and uplifting new sources, since the media is fully aware that our brains are built to fixate on threat. Cognitive restructuring can also be drawn upon to help patients discover, challenge and modify their negative or irrational thoughts and beliefs. It is a staple technique of Cognitive Behavioural Therapy (CBT) and aims to help individuals to reduce their anxiety through noticing and changing their negative thinking patterns and cultivating more positive and functional thought habits. Thank you for reading and I hope you learnt something new about the experience of people living with long covid. Please stay tuned on Thursday for part two of this blog which will detail how psychologists can support patients with long covid to manage loss and transition, fatigue and depression! Header Image Source: Marta Zubieta on The Bristol Cable

This is a blog about talent. It’s about how a talent, even kept under “seven keys” can be multiplied and bring hope to many people… Nice to meet you, I’m Daniela, Brazilian and this is the story of my life. It’s about how the pages of a diary revealed my true calling and made me the writer I am today. Nothing is by chance and life (in my opinion) is a process reserved for a purpose. I started writing the pages of my story at the age of 11, in a diary that I got as a gift from my mother. A gift that gave me voice and freedom to express myself more clearly, using the writing as a resource. By having a quiet borderline personality, I always needed to express my feelings and thoughts in a very particular way. I remember that whenever I had an intense crisis of crying and anger, I was called “dramatic” by my mother, and for this reason, suppressing my feelings seemed to be the best way to get along with my family. The diary came as an escape valve in my life. I could put all my pain, frustrations, and feelings on it, in a socially acceptable way, without hurting anyone. And so I did. From the silence of my soul to my fingertips, my story was taking shape and emotion (and the most important thing is that I didn’t need to keep quiet anymore, my lines would speak for me). By internalizing too much of my emotions, I started to sublimate my pain by writing about it. I remember staying late in the morning making up stories and writing about my deepest anxieties and questions about the world, about people, about relationships. And relationships have always been very intense to me. For example, I used to go from one extreme to another for idealizing too much a friend, and every time that this friend disappointed me, I became terribly devastated with the certainty that I could never trust anyone again. And this actually happened, I became a pistantrophobic person (always assuming the worst about people). I always had the feeling that my emotions were too intense to be understood by others, so I started to enjoy silence as a coping strategy and isolation as self-defence. Another defence mechanism that I developed is known as “emotional anorexia”. It is a type of behaviour in which affective involvement with friends, relatives or partners is avoided or superficial. Thus, a person with emotional anorexia may feel uncomfortable with too much praise or displays of affection. This can happen for many reasons: fear of not being accepted, of being rejected, of being betrayed, of not believing to be a good person, etc. In this way, my need to transcribe my feelings into words increased, and through the ink of the pen nothing was limited. The fact is, I have always been a highly responsive person to someone else’s feelings. This means that I can feel the pain of the other as if it were my own, often being unable to separate my own emotions from that of others. As a result, I end up developing endless ruminating thoughts, as if I were able to solve “all the problems in the world” with the “strength of my thinking”. It is precisely at that moment that the expression of my soul through a creative tool makes perfect sense. Like an empty page, my soul was filled with every sentence I wrote, and over time I realized in writing the ideal language to communicate my emotions. But it is not enough to communicate, you need to inspire (and be sure that there is a meaning to everything you are feeling). Because somewhere in the world there must be someone who also feels or thinks similarly as I do. It was from this moment that I realized how much writing had transformed me as a person. From diaries, reports in letters, and paragraphs written at the bottom of notebooks, my writing went from an escape valve to a deep tool of self-knowledge. I say deep because as far as I displace what I feel on paper, it’s like I was peeling an onion, layer by layer to be able to see its essence in the end. And seeing the essence is facing the most vulnerable part in us (our traumas, fears, and limiting beliefs that sometimes hinder our growth). The intensity that I once saw as a defect, today I see it as a creative potential to the service of emotional well-being. After all, talking about affection is talking about what affects us and how we can be more productive, considering Who we truly are and not what others expect us to be. With that in mind, I researched websites of mental health organizations and engaged in a project to help with educational mental health content. Having experience in the classroom, I developed lesson plans for teenagers to educate about mental illness and with this decreasing the stigma. The curriculum included activities both in the classroom and at home, with parents. It was an enriching experience. It was like going into a time machine and talking to myself when I was a teenager. I also contribute by writing about learning disorders for educational columns and in 2016 I had the opportunity to collaborate with a book on education and literacy for children, youth, and adults. Years later, in 2018, after completing a postgraduate degree in Neuroeducation, I published my monograph that had as its central theme creativity and neuroplasticity in childhood. I currently work as a freelance writer of content on mental health, education, and learning disorders. And this was my sensitive way of finding my place in the world through words. The word that screams (even in silence), that reaches people (even without having contact with anyone), and that transforms (even if I don’t see them). Time has passed since I touched that diary for the first time. That little treasure of mine remains until today, intact and locked with its pink lock, as it cannot be read by those who don´t understand what the heart is talking about. I just have to be grateful to (my mom and to) that little diary for staying so long with me, listening to me, assisting me, encouraging me, and making me the person that I am today: a writer who sees in the word a purpose without borders.

COVID-19 vaccine uptake in the UK — can we blame vaccine hesitancy? COVID vaccination programmes are underway all over the world. The UK government, somewhat controversially, was well stocked up with millions of vaccine doses and vaccinating over 80’s before most other countries had even received their first stocks of the COVID vaccine. As we attempt to emerge from a pandemic that has had most of us in some form of lockdown for almost 18 months, our hope for the future is not only dependent on confirming the real-world efficacy of COVID-19 vaccines but also, and most importantly, on the uptake of these vaccines. At first glance the snapshot for the UK is positive — nearly eight months after the approval of the first COVID-19 vaccine to be administered, over 45 million people have had their first dose, which represents 87% of the adult population. However, at close inspection, what the data does not really tell us is that the shocking disparity of vaccine uptake among different ethnic groups. Looking at the period from the start of December 2020 to the end of June 2021, 95% of white Britons over 50 have had at least one dose of the vaccine, while the percentages are much lower for Black Caribbean (66%), Black African (72%), Any other Black background (69%) and Pakistani (80%) people. I am a researcher in the biomedical field, who has worked inside and outside the lab for almost 10 years, and I have been fortunate enough to have been offered both doses of the Pfizer vaccine in the beginning of 2021. I started my career in clinical trials working on a vaccine trial that looked at rolling out HPV vaccines to all adults; so, this moment in history, where we’re looking to vaccinate virtually every adult on the planet, is very exciting for me. As a side note, I recently heard the expression “global majority” used instead of “ethnic minorities” or BAME and it is now part of my vocabulary. It does convey the disproportion in white versus all other ethic groups, overturning the view of “Black, Asian, and minority ethnic”, or BAME, to a realistic image of an actual global population majority that is non-white. So I will be using “global majority” in this blog as a term to indicate people from non-white ethnic groups. Many prospective studies — those done before the COVID-19 vaccine was available — indicated that there was higher vaccine hesitancy among the global majority, and this raised the alarm as the risk of requiring hospitalization and death due to COVID are higher in some of these groups. A recent study showed that in the UK, there is higher vaccine hesitancy across some global majority ethnic groups, especially Black and Pakistani/Bangladeshi, and lower literacy groups. As we know that COVID-19 disproportionally affects the global majority with more severe symptoms, higher likelihood of hospital admissions and higher mortality rate, we’re facing a double whammy here: the most at-risk populations are less likely to be vaccinated. These populations are also more likely to suffer from conditions such as diabetes, cardiovascular disease, depression and severe mental health problems. We have the perfect storm, where populations that are already more at risk of worse physical and mental health outcomes are also more at risk of worse COVID outcomes (for example, black males are 4.2 times more likely to die from COVID than their white counterparts) but less likely to be vaccinated. The pandemic itself exacerbates these inequalities, resulting in higher unemployment, worse living conditions and violence, and of course, worse health outcomes in these communities. A poll by the Royal Society for Public Health found at under 60% of the global majority was willing to take the COVID-19 vaccination. An example of this is the outbreak in Bolton (UK) of the delta variant. When looking at hospital admissions in Bolton in May 2021, most patients were eligible for the vaccine but were not vaccinated. On a recent news piece on the BBC, a local councillor has highlighted this issue as not of vaccine hesitancy but the direct result of deprivation, health inequalities and inadequate provision. Even though an easy argument can be made for lower cognitive function (mental ability) and COVID-19 vaccine hesitancy, further complicated by “fake news” being churned through social media channels at an incredible speed, it would be lazy and frankly prejudiced to consider this as the only factor. According to a government report, the barriers to vaccine uptake are “the perception of vaccine risk, low confidence in the vaccine, distrust, inconvenience, socio-demographic context and lack of endorsement, lack of vaccine offer or lack of communication from trusted providers and community leaders”. What is the solution then? Better engagement? Tailored solutions for each specific populations? A recent paper suggested using “local champions” in the communities where vaccine hesitancy is higher, as well as creating major vaccination centres in areas of deprivation and/or areas with a high representation of global majority citizens. The same paper also suggested endorsement of vaccination by celebrities of these backgrounds. The director of the NHS Race and Health Observatory has suggested that there are no “hard to reach” communities, just unsuitable communications — vaccination calls need to be translated to different languages and local faith leaders must be engaged in the rollout. A Financial Times study now offers a glimpse of hope, with a narrowing of the gap of vaccination uptake between different ethnic groups of the population, meaning that, on a par with a high uptake of white Britons, the global majority seems to be less hesitant to take the vaccine. Any efforts being done now to shorten this gap come across an afterthought and not part of an articulated vaccination plan that had into consideration the global majority at the start of the vaccination rollout in the UK. I believe that the only way to vaccinate the necessary amount of people to achieve some form of herd immunity — the achievement of low risk spread of a disease once the majority of a population is immune to the disease through vaccination  — is, for now, to engage specific populations appropriately and from an informed place. Otherwise “normal life” might never resume. Vaccine hesitators are not simply misinformed, they are mistrustful for valid historical and social reasons. While we do this, we might learn a thing of two about how to include the global majority in decision-making rather than creating a system built by, and for, a global white minority.

The month of June was a momentous milestone in the fight against Alzheimer’s disease. Regardless of your stance on the conditional approval of Aducanumab by the Food & Drug Administration, we clearly have the ability to reverse the pathology thought to be the major instigator in the devastating effects of Alzheimer’s. If administered at the right moment, to the correct individuals, there is real optimism that we are edging closer to a solution for a disorder that affects millions worldwide. The “right moment” and “correct individuals” is seemingly an obvious statement to make but it is a complex and relevant question in dementias like Alzheimer’s disease. We now know that Alzheimer’s disease has a “silent phase”, a period of time when the harmful pathology is developing in the brain but the symptom onset can be more than 10 years away. Thus, the “right moment” would be in this silent phase, before symptoms appear and pathology is developing and could cleared without causing long-term damage. However, trialling a drug in those with no symptoms and waiting to see if they develop Alzheimer’s, or not, has many financial and ethical complications. The majority of trials in Alzheimer’s have therefore been in the later phases of the disorder and has only shown minimal benefit but has established target engagement (e.g., cleared harmful pathology from the brain). Next, the “correct individuals”. Drug trials like Aducanumab specifically target a protein called amyloid-β and not all dementias are caused by amyloid-β (e.g., Frontotemporal dementia, Lewy Body dementia or Vascular Dementia). In fact, a proportion of patients diagnosed with Alzheimer’s by specialists do not have amyloid-β simply because the clinician cannot observe the brain pathology, and only have a detailed account of symptoms from the patient and carer to guide their decision. Therefore, it is of paramount importance that we find people with the right pathology and early as possible for these drugs to be the most effective. As I mentioned, this “right place at the right time” approach is very difficult when you cannot biopsy the diseased organ (the brain) of a patient and even more difficult if individuals are not experiencing any symptoms — thus, are not voluntarily walking into GP clinics complaining of memory problems. In the last two decades, we have developed extremely accurate tests to monitor the brain using molecular brain imaging and lumbar puncture examinations. These inform us, with very high confidence, if amyloid-β pathology is present in someone’s brain. However, these tests are not trivial and it is hard to envisage these being widely used for the general population to screen for dementia due to the cost and the specialism that it requires. A biological marker (biomarker) in the blood is the only way to engage a large enough population, sometimes those without symptoms, so that the correct people are recruited into these trials and, in the future, are prescribed the correct treatment for maximum benefit. We have to be realistic though, a blood test is not going to be 100% accurate. Blood is a complex matrix, receiving information from all organs in the body, not just the brain, but these tests will act as a triage to highlight potential issues which can be confirmed with more advanced techniques. The development of blood tests for dementia is a real neuroscience success story — progressing rapidly from academic curiosity to clinical utility. I often think back to standing in a half-empty room — mostly made up of supportive colleagues — at a late session of the 2014 Alzheimer’s Association International Conference, describing the potential of relationships between blood proteins with clinical symptoms in patients with dementia. Never did I think medical science could evolve so quickly — where a blood test for Alzheimer’s disease is no longer described as being “on the horizon” or “just not possible” by the majority but is now on the verge of widespread clinical routine in Europe. However, these early efforts I was describing in 2014 generated enthusiastic interest and persuaded a large research study to include standardised blood collections in their protocols. Now, it has certainly paid off. But, 2014 was not the start of this process. My mentors and PhD supervisors at the time, Dr. Abdul Hye and Professor Simon Lovestone, had already hinted that a blood biomarker could be a realistic possibility in a series of publications between 2006–2010. They described that proteins linked to biological processes like immune response are changed in the blood of Alzheimer’s disease patients. Importantly, these proteins are closely linked to Alzheimer’s pathology found at post-mortem and were later found to be genetic risk factors for Alzheimer’s. Although these reported blood tests did not have the required accuracy needed to be clinically relevant, they generated the necessary interest that propelled this area of neuroscience to where it is now. So, what has changed in such a short time? Well, certainly the intended targets have not. The “new” generation of blood biomarkers we talk about today are the classical candidates we have known about for many decades in the brains and cerebrospinal fluid (CSF) of Alzheimer’s disease patients. I believe there are three fundamental changes responsible for this rapid development of a blood test for Alzheimer’s. Firstly, we have recently begun to change the way we think about Alzheimer’s disease. In 2018, the National Institute on Ageing and Alzheimer’s Association (NIA-AA) defined Alzheimer’s disease as a biological construct — simply meaning, you must have evidence of Alzheimer’s disease biology in the brain related to the observed cognitive symptoms for the disease to be called “Alzheimer’s”. Secondly, there are now large well-characterised research cohorts (e.g., Swedish BioFINDER, the Alzheimer’s Disease Neuroimaging Initiative and Translational Biomarkers in Aging and Dementia, to name but a few) which have scrupulous details about their participants' biology, e.g., molecular imaging for tau and amyloid in the brain. These large studies gave us the best chance to see if our blood tests really reflect brain pathology. Lastly, our technology. These proteins exist at super-small concentrations in the blood — femtomolar: one millionth of a billionth! Previously we could only detect them in extreme cases. Owing to these advancements we can detect these proteins in all people, of any age. So, what are the next steps? Well, a blood test for neurofilament (NfL), a protein indicative for non-specific brain injury, has crucially been implemented into clinical routine in Sweden, and can now be requested by clinicians all around the country — other countries will rapidly follow suit. Blood NfL is also being used as a primary end-point in drug trials for multiple sclerosis and likely other disorders in the future. This blood test has wide implications for many disorders e.g., motor neurone disease, frontotemporal dementia and depression, as we have just reported in an article in Nature Communications. Importantly, it also works to identify dementia in people with Down’s syndrome, where wide varying intellectual ability can mask or confuse subtle cognitive changes — the NfL blood test is extremely useful in this context. A specific blood test for Alzheimer’s disease, p-tau, has also received a lot of attention in the last 18 months, with some high-profile publications in the Lancet, Nature and JAMA (Karikari TK et al; Janelidze S et al; Thijssen EH et al; Palmqvist S et al). Already, international efforts are underway to validate these p-tau blood tests for clinical use with the field unanimously convinced of their value to the clinical examination of dementia patients and the potential benefit to aid therapeutic trials. For those suffering with dementia, or caring for someone with dementia, an important question is always — is this Alzheimer’s disease or something else? Accurately knowing your diagnosis is often an important step to facing the years ahead for all concerned. It is also fundamentally important for the clinician to accurately prescribe symptomatic treatment. The new blood tests are a necessary tool to rapidly get an accurate diagnosis — in a way we haven’t been able to do before. More optimistically, while we now have one approved disease-modifying drug available, more will certainly follow, and we already have the tools available to ensure that these drugs are given to the correct people without delay.

Psychedelic drugs were not mentioned to me when training as a psychiatrist, as far as I remember. Perhaps they were, in passing, but probably only in reference to the general ‘drugs of abuse’ narrative that seemed to pepper theories about why mental illnesses develop. So, it was interesting to learn later on that both psilocybin (the active component of ‘magic’ mushrooms) and d-lysergic acid diethylamide (LSD) were synthesised by the same man (Albert Hofmann) whilst working for the pharmaceutical company Sandoz (now Novartis) during the 1940s and 1950s. Pre 1970 LSD (and to a lesser extent psilocybin) was used quite widely in psychiatry prior to 1971. Hundreds of papers were produced. Thousands of patients treated. Whilst there were exceptions (and sometimes serious ones) the drugs were generally used safely, usually in a hospital setting and within a wider process of therapy. These trials are summarised in various publications. The most compelling evidence was in alcoholism, where you were almost twice as likely to have reduced drinking having been given LSD when compared to a control intervention. In problems like depression, nearly 80% of patients treated with psychedelics showed clinician-judged improvement, 65% of patients with anxiety disorders and 69% of patients with functional neurological disorders. However, many of these trials had significant design flaws. So, treat those figures with caution! A key message from research prior to 1971 was that psychedelics seem to make people sensitive to context, so they needed to be given in a safe and supportive setting. If you didn’t do that, toxic reactions were more likely. Even so, psychedelics (not dissimilar to many drug treatments) were a bit of a gamble. It was hard to predict who would improve and who wouldn’t (or get worse). So, whether they were effective as treatments was a matter of debate up to 1970. 1971–2000 Whilst researchers were grappling with this, a legal guillotine came down. Psychedelics had diffused into recreational use and, as part of a moral panic, were swept up in the US-led ‘war on drugs’. Routine clinical use stopped and research quickly dwindled. The field entered a ‘dark age’ of prohibition, where rhetoric reigned, and stigmatised attitudes fermented for nearly 30 years. Growing up through the 1980s and 1990s, I believed firmly that psychedelic drugs were ‘bad’. 2000–2020 Since the turn of the millennium, the darkness has turned to dawn. Psychedelics are back. The reasons for this are complex and uncertain. Perhaps societies are growing tired of a ‘war on drugs’ that hasn’t worked. Perhaps clinicians are looking to history for new ideas. Perhaps a softening of socio-political attitudes is stimulating financial interest in a commercial development process that had been cut off after 1970. Doubtless, it is all these things, and more. Over the past twenty years, small scale trials (mostly with psilocybin) have been funded and authorised. They have established basic knowledge about how psilocybin is handled by the body in healthy volunteers. Subsequently, small scale pilot trials have taken place in patients, suggesting psilocybin (when given with psychological support) has antidepressant properties. Other small trials have investigated obsessive-compulsive disorder, tobacco addiction and the existential distress associated with life-threatening illnesses. Small-scale trials are good, but they don’t justify psilocybin becoming a treatment. For that, we need trials costing tens to hundreds of millions of dollars, in lots of independent centres, around the world. A similar process to the covid-19 vaccine. In 2016, a UK life sciences company called Compass Pathways announced production of psilocybin to medical standards and the intention to undertake a clinical trials program investigating psilocybin assisted therapy for difficult-to-treat (aka ‘treatment resistant’) major depression. A ‘for-profit’ entity that had previously been ‘not-for-profit’, the transition generated some tension within the psychedelic community that, long stigmatised by wider society as recreational drug users, were perhaps liable to be suspicious of the motivations of entities built on commercial principals. Meanwhile, the Usona Institute, a not-for-profit entity in the United States, announced its own process for manufacturing psilocybin and the intent to develop psilocybin therapy for major depressive disorder (however, importantly, not for depression that was ‘difficult-to-treat’). The process of developing a new treatment through to market usually rests on the presumption that the treatment can be patented, so allowing the developer to recuperate their costs and fund onward development. Psilocybin can’t be patented because Sandoz already did this in the late 1950s. This introduces a problem of economic sustainability. It isn’t one that I can shed much light on, as I’m not part of either Compass or Usona, but clearly, the process of getting psilocybin through to the clinic is somewhat atypical. 2021 Regardless, the development of psilocybin assisted therapy is now moving forward, apace. Compass and the Usona Institute have registered clinical trials programs for psilocybin therapy that have been given ‘Breakthrough Therapy designation’ (BTd) by the Food & Drug Administration (FDA) in the US. BTd is important because it allows speedy access to the FDA for the purposes of licensing new and promising therapies. Licensed psilocybin therapy for depression may be closer than we think. In late 2020, Compass went through a process of offering shares in the company to the public, generating very significant capital value. Meanwhile, ‘pop up’ psychedelic investment companies and paid psilocybin retreat centres (in countries where laws are less stringent) have appeared with almost magical speed. As investors have piled in to take advantage of the optimism, the field has the feel of something like Bitcoin. What is it exactly? Not quite sure yet. Where is it going? Uncertain, but it looks promising. A Psychedelic Future? In this heady mix of investor fever, therapeutic optimism and counter-cultural suspicion, we’d be wise to be cautious. I’ve argued recently that psychedelics need to be tested in a way that governments and wider society understand, or we may risk another legal crackdown. On the other hand, this is now a process with its own momentum. Not just clinical trials, but the emergence of paid retreat centres, activist organisations calling for liberalisation and speculating venture capitalists. In some senses, it feels like the unbridled, unregulated optimism of the pre-prohibition era. That ended in darkness. Can this be avoided today? This boils down to whether modern society and psychedelia can be reconciled. Opinion varies. I am, in general, optimistic. From a medical perspective, psychedelics seem very safe in terms of toxicity to the body. On the other hand, the subjective effects can be unpredictable, although it seems that we can manage this safely in a medically controlled environment. The effects are hard to measure and there are inherent problems with designing unbiased trials with psychedelics. This can make the evidence base harder to interpret. However, as more studies accumulate, a general theme is likely to emerge. The evidence base is growing (and largely encouraging). Meanwhile, the long history of human use of psychedelics and the legal crackdown on recreational use 50 years ago hint at the complex and deep-rooted cultural interplays that surround the use of psychedelics. Here, emotions run high (and deep). Whilst many are deeply opposed to the restrictive laws that surround psychedelics, the silver lining may be that those laws enable science and medicine to rediscover psychedelics in a way that governments and wider society can engage with. Few could argue with a reorientation of society’s relationship with psychedelics if they were found to have a confirmed use in healthcare. But, that is still an ‘if’. The jury will be out on this for a few years yet. My feeling is that both science and medicine have much to learn by studying psychedelics, regardless of their potential use in healthcare. They stimulate brain cells through chemical mechanisms (serotonin receptors) in unusual ways, modulate our immune systems, cause brain cells to form new connections, and change patterns of electrical activity and connectivity between different brain regions. The result of this is an altered state of consciousness that poets, mystics and artists through history have attempted to capture, yet inevitably with only partial success. No one medium, it seems, can ever really describe it. Whatever ‘it’ is, the creator of the term ‘psychedelic’ (a British psychiatrist called Humphrey Osmond) tried to capture it in a single word. A concatenation of two Greek words, ‘psychedelic’ literally means ‘mind manifesting’ or ‘soul revealing’. It’s a term that has spread all over the world, so perhaps it does mean something to many people. Perhaps, Osmond was on to something. What’s in the future? The clinical trials and wider research continues. The data from this will speak for itself. But if it is good, what then? Psilocybin is not like Prozac. Delivering psilocybin assisted therapy will be met with the logistical problem of adapting health care systems that left psychedelic therapy behind in 1970, and the practical problem of who pays. These are surmountable. What’s trickier, perhaps, is how to manage that within the context of what may be ongoing psychedelic stigma. I know now that psychedelics aren’t ‘bad’. But how many others do? Ideological change takes generations. Whilst we will come and go, psychedelics are here to stay. Declarations and Conflicts of Interest This work presents independent research part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. James Rucker is an honorary consultant psychiatrist at The South London & Maudsley NHS Foundation Trust, a consultant psychiatrist at Sapphire Medical Clinics and an NIHR Clinician Scientist Fellow at the Centre for Affective Disorders at King’s College London. James Rucker’s salary is funded by a fellowship (CS-2017–17–007) from the National Institute for Health Research (NIHR). James Rucker leads the Psychedelic Trials Group with Professor Allan Young at King’s College London. King’s College London receives grant funding from COMPASS Pathways PLC and Beckley PsyTech to undertake phase 1 and phase 2 trials. COMPASS Pathways PLC has paid for James Rucker to attend trial related meetings and conferences to present the results of research using psilocybin. James Rucker asserts that COMPASS Pathways & Beckley PsyTech had no influence over the content of this article. James Rucker has undertaken paid consultancy work for Beckley PsyTech and Clerkenwell Health. Payments for consultancy work are received and managed by King’s College London. James Rucker does not benefit personally. James Rucker has no shareholdings in pharmaceutical companies.

I first came across the study of depression as a biomedical science student. We discussed mental illness as a consequence or a side effect of the biological diseases that we were attempting to mitigate. I learned that people with chronic illnesses, such as rheumatoid arthritis, often feel depressed because they’re in pain. Any mental symptoms were framed as side effects that doctors shouldn’t be overly concerned with. “That’s for their psychiatrist to deal with,” I was told. The idea that depression could be the result of physical pain makes sense, but it didn’t seem like the complete picture. That year, I also sat in on the first-year psychology lectures. I wasn’t a psychology student at the time, but I was excited to learn more about the brain and my first neuroscience lecture was months away. Hearing psychologists talk about how the mind worked was fascinating to me, but I was met with a general unenthusiasm for the biological side of things. “Don’t worry too much if you don’t understand neurobiology. It doesn’t come up too often, unless you really want to focus on neuroscience.” Here were two scientists, both working towards the goal of improving their patients' lives, both unwilling to operate within the other’s framework and learn from their knowledge. This is what inspired me to study mental health from both perspectives. Now I study cognitive and clinical neuroscience at the University of Westminster in central London. I’m also an incoming placement student at the Institute of Psychology, Psychiatry, and Neuroscience. Like many others, I was taught the serotonin hypothesis, which is the idea that depression is a result of there being too little serotonin in the brain. Serotonin is a chemical called a neurotransmitter that helps cells in the brain communicate with each other. It regulates processes such as sleep, appetite, and emotion. Antidepressant medication, such as Selective-Serotonin Reuptake-Inhibitors (SSRIs) and tricyclic antidepressants, are thought to work by increasing the amount of serotonin available to cells in the brain to address the neurotransmitter deficit. The serotonin hypothesis is mainly supported by the fact that some people who take antidepressant medication can feel better after a few weeks, suggesting that the medicine gradually increased the serotonin available to the brain. A Brief History of Antidepressants: The Golden Age of Prozac I was surprised to find out the first modern antidepressants were not intended to be antidepressants at all, but a tuberculosis treatment. The breakthrough took place at Seaview Hospital, opened to tackle tuberculosis. When patients took Iproniazid they reported feeling happier, more social, and less tired. Not only did their tuberculosis improve, but their outlook on life became brighter. Patients who had lost their will to live were better again. For the first time, people left Seaview Hospital alive and happy, seemingly cured of both their tuberculosis and the accompanying depression. These findings prompted other pharmaceutical companies to explore precisely why iproniazid had these effects with the goal of developing similar drugs to be used in the treatment of mental illness. Iproniazid suppresses a chemical called monoamine oxidase, which breaks down neurotransmitters (including serotonin) in the brain. Because iproniazid blocks this chemical, neurotransmitters are broken down more slowly, increasing the amount of serotonin and other neurotransmitters available in the brain. Thus, the mechanism of action of iproniazid should ease depression, and for the patients at Seaview Hospital, it did. With the success of iproniazid, more drugs were developed to inhibit the breakdown of monoamine oxidase enzymes. These were the first pharmaceutical antidepressants, known as MAO inhibitors, which are still in use today (although they’re prescribed less often than SSRIs due to concerns about side effects). What came next remains one of the most common treatments for depression to this day, SSRIs. The development of SSRIs was based on the same idea: that increasing the amount of serotonin in the brain would decrease symptoms of depression. The first and probably most well-known SSRI is Prozac, or fluoxetine. Instead of suppressing the breakdown of serotonin, Prozac stops cells from reabsorbing (or reputaking) serotonin, making more serotonin available to the brain. Since the release of Prozac in 1988, many more SSRIs have been invented, but they all work in a similar way. However, not everyone who takes antidepressants feels better. People with mild depression tend to respond less than people with severe depression and some people don’t improve at all. Approximately one-third of people with major depressive disorder experience treatment resistance, meaning that they’ve tried antidepressants (sometimes more than one) and their symptoms didn’t improve. This suggests that serotonin is a piece of a much bigger puzzle. So, it’s especially important to research treatments that work differently in the hope that they’ll work better in treatment-resistant patients. So far, I’ve focused on the modern history of depression. But the use of mind-altering plants in the treatment of depression long outdates the use of MAO inhibitors or SSRIs. Indigenous people from all around the world have used psychedelic plants and fungi in healing ceremonies for centuries. Native cultures in North and Central America used a psychedelic cactus called peyote in traditional ceremonies. Archaeological evidence from carbon dating suggests that people consumed these psychedelic cacti over 5,000 years ago in what is now part of Texas and Mexico. However, the earliest evidence of psychedelic plants being used specifically to heal comes from South America. Ayahuasca for Depression: A three-pronged approach Ayahuasca refers to the combination of two Amazonian plants: Banisteriopsis caapi, a vine, and Psychotria viridis, a shrub from the same family as coffee. Traditionally, the leaves of Psychotria viridis are combined with Banisteriopsis caapi and brewed into tea. A recent study suggests that ayahuasca may be able to treat symptoms of depression with a three-pronged approach: increasing serotonin, temporarily blocking the enzyme that breaks down serotonin, and reducing inflammatory activity. Psychotria viridis contains dimethyltryptamine, known as DMT, which acts on serotonin receptors in the brain, causing hallucinations, time distortion, and out-of-body experiences. DMT is the chemical responsible for the spiritual experience associated with ayahuasca. A very small amount of DMT is found naturally in the brain, but it’s not nearly enough to produce a noticeable effect. When consumed on its own, DMT is quickly broken down by the same enzymes I mentioned earlier, the chemical that is suppressed by MAO inhibitors. In the ayahuasca tea, these enzymes are inhibited by chemicals in Banisteriopsis caapi, so the DMT from Psychotria viridis takes longer to be broken down, prolonging the psychedelic experience to hours instead of minutes. DMT can also affect sigma-1 receptors, which are responsible for regulating the inflammatory response. Inflammation is the body’s way of sounding the alarm by releasing chemicals called cytokines. Cytokines send a signal to our immune system to attack the invader. In return, the immune system releases more cytokines to send for backup. Sometimes, our own cells can get caught in the crossfire. When this inflammation occurs in the brain, it causes sickness behaviour. We’ve all experienced sickness behaviour, the brain fog and tiredness that comes after a vaccination or at the beginning of a cold. Sickness behaviour may have evolved to keep us away from members of our family when we’re sick and to help our body conserve energy by making us want to curl up in bed. Some of the symptoms of depression resemble many sickness behaviours, such as social withdrawal, fatigue, and lack of appetite or interest in activities. This has led many scientists to hypothesize that some depression symptoms are the result of increased inflammation. Psychedelics are complicated chemicals that science doesn’t fully understand yet. These are likely not the only effects that ayahuasca has. While it is possible that some of the antidepressant effects of ayahuasca are attributable to its anti-inflammatory effect, scientists aren’t sure what sigma-1 receptors actually do. It might have something to do with protecting brain cells from dying of oxygen deprivation, but for now, the role of sigma-1 receptors remains unclear. What comes next? Psychedelic therapy could be the beginning of a brave new world in psychiatry, but it is not without its flaws. Psychedelics are decriminalized in some parts of the world, particularly for religious use, but they remain illegal in the UK. This prompts many patients seeking psychedelic therapy to travel to countries where psychedelics are legal for medicinal or spiritual purposes. With the increasing popularity of ayahuasca ceremonies comes increased dangers. Ayahuasca tourism can be risky because not every company offering these services is safe or legitimate. Furthermore, there is a great deal of debate about cultural appropriation. It’s also important to note that these trials are imperfect and often suffer from methodological issues due to the nature of the experiment. Clinical trials have to prove that their new treatment is more effective than a placebo, or a sugar pill, which is difficult to do with psychedelic drugs because the effects are so intense and noticeable, so most participants can tell if they were given the placebo. This makes the results less meaningful because the participant’s knowledge of which drug they got could impact their experience. Some studies try to control for this by only recruiting participants who have never consumed a psychedelic substance before, but drug use is underreported in scientific research due to the stigma and illegality surrounding many of these chemicals. More trials with larger sample sizes are needed to establish psychedelics as an effective treatment for depression. As with any treatment, safety is a serious consideration. Not everyone is going to benefit from taking psychedelic drugs, even in a therapeutic, clinical setting. The risk of psychosis, particularly in those with a family history of schizophrenia, is not something to be taken lightly. Adverse effects can occur during psychedelic ceremonies, just like with any intervention. These substances have a great potential to heal, but no one treatment is going to work for everyone. Psychedelics must not be thought of as a one-size-fits-all approach to psychiatric disorders. Depression is a multifaceted, complex disease that likely has multiple causes and mechanisms that differ on an individual level. Each case of depression is unique and our treatments should reflect that. It’s unrealistic to expect any one kind of depression treatment to work for every single person with depression. By better understanding the various mechanisms that underlie depression and other mental illnesses, we can develop treatments that work where our current ones don’t. We have to do better than our current standard of care and develop a variety of treatments to help as many people as possible, not just those who respond to antidepressants. Depression is the single leading cause of disability globally; we have to do better than a one-size-fits-all approach. Header Image Source: The Conversation

When thinking about maternal mental health and how difficulties with it may influence a developing baby, it is only natural to imagine the postpartum period — that is, the year following a woman’s birth to her baby — given that this is when mothers can for the first time interact with their babies face-to-face. And in fact, the majority of research on maternal mental health to date has focused on the postpartum. Equally important, and less studied, though, is how a woman’s mental health during (and even before) pregnancy can frame how she will enter motherhood and how her baby will adjust accordingly. And, furthermore, how their relationship together may develop. An outcome of maternal depression in pregnancy that hasn’t been widely studied is the mother-infant relationship, which is my specific area of focus. I am a postdoctoral researcher at the Institute of Psychiatry, Psychology and Neuroscience in the perinatal psychiatry section of the Stress, Psychiatry, and Immunology Lab, the group who publishes InspireTheMind. The topic of my PhD was whether depression experienced prior to birth — in pregnancy or just in lifetime before pregnancy — may affect the development of one of the most fundamental relationships. Antenatal depression is defined as a depressive episode experienced during a woman’s pregnancy and has become increasingly common, especially during the COVID-19 pandemic. The core symptoms are typically low mood, lack of interest, changes in appetite, difficulties with sleep, and ongoing feelings of guilt and worthlessness. It is now thought to affect up to 1 in 5 pregnancies and can either occur spontaneously during pregnancy or as a continuation of symptoms that began prior to conception. While the root of its onset is not entirely understood, researchers believe that a combination of social and biological risk factors may underpin the emergence of symptoms. Notable risk factors for becoming unwell include: a history of childhood abuse, previous depressive episodes, socioeconomic difficulties, young age, lower education qualifications, lack of social support, changes to circulating stress hormones, and increased inflammation throughout the body. This is not to say that all pregnant women who meet the criteria for any of the above-listed experiences will become depressed; rather, that women who are depressed are much more likely to possess one or more of these risk factors. What impact does antenatal depression have? Many studies have investigated what (if any) effect antenatal depression can have on mothers’ outcomes and have found that expectant mothers who are depressed may have trouble with self-care and care of the unborn baby, are more likely to remain depressed in the postpartum, and are at heightened risk of having suicidal thoughts. Upsettingly, the leading cause of maternal death in the postpartum is in fact suicide, highlighting the importance and urgency of identification and treatment of depression. While care of expectant mothers is vital, clinicians and researchers also agree that care for the unborn baby is just as crucial, as antenatal depression is found to affect development throughout different stages of life: our research group has found that in the neonatal period, offspring are more likely to show behavioural difficulties in the first week of life, including decreased social-interactive behaviour, seen through reduced gaze and vocalizations; we have also found that in infancy, offspring are at risk for disruptions in their biological systems, including alterations in their stress hormones and inflammatory markers; as infants develop into children, they are more likely to experience mental health difficulties, including depression and anxiety; and finally, they are at risk for these psychopathologies to continue all the way through to adulthood. Put simply, there seems to exist a transmission of vulnerability from mother to child, highlighting the importance of breaking this chain at the outset. As I mentioned above, while there is a lot of research to date on the impact of antenatal depression on offspring development, few other studies have investigated the association between depression in pregnancy and the mother-infant relationship. As such, this was the focus of my PhD work. In addition to looking at antenatal depression, I also chose to examine maternal historical depression — women who had a history of a depressive episode but were well in pregnancy — to understand whether different timings of depressive episodes can differently affect mother-infant behavioural patterns. Depression and the mother-infant relationship Before I discuss my findings, it’s important to understand the significance of the mother-infant relationship. It is thought that mothers begin bonding with their babies as early as the first trimester of pregnancy, suggesting that this relationship begins in utero, not in the postpartum. In fact, studies have shown that a mother’s feelings towards her developing foetus and how she engages with it in her second trimester are highly predictive of what her parenting behaviours will be like later on. Additionally, researchers have long found connections between the quality of the mother-infant relationship (usually observed through attachment, which assesses an infant’s sense of security as a result of sensitive mothering behaviour) and the infant’s psychological wellbeing later in life. And so, given that a mother’s feeling about her foetus are predictive of their postpartum relationship, and that the infant’s attachment status is predictive of subsequent mental health, there’s an inherent importance in monitoring women during pregnancy to identify any risk factors that may affect the developing relationship. This is where my research fits in: I wanted to understand whether maternal depression in pregnancy or prior to pregnancy impacted the quality of the mother-infant relationship across the postpartum period, in order to explore whether mother-infant interventions need to be extended to the pregnancy period. Moreover, I also examined whether other risk factors in addition to depression — such as maternal socioeconomic difficulties, like lack of social support or low income, maternal history of childhood abuse, maternal postpartum depression, and infant difficult behaviour — played into the potential association between antenatal or history of depression and a decreased quality of interaction. The reason I chose to also look at these factors is because research shows that they are both associated with antenatal depression and the mother-infant relationship, which means it’s possible they’d be involved in the pathway from depression to relationship difficulties. To evaluate the quality of the relationship, I watched videos of mothers and their babies interacting at 2 months and 12 months postpartum, and assessed how well their interaction with each other went; that is, how well mothers could comfortably engage their babies, how babies responded to their mothers’ behaviour, and how in-sync the dyad were as a whole, almost as if the interaction is a dance. What I found was that dyads in both the antenatal depression group and the history of depression group didn’t have as smooth a back-and-forth and couldn’t connect as well as dyads in a healthy comparison group at both 2 and 12 months. While I expected to find this in the antenatal depression group, I was surprised to learn that the history of depression group was just as impacted, given that these mothers were well in pregnancy, the timepoint when women begin to bond with their babies. I also found that maternal socioeconomic difficulties and less-social neonatal behaviour contributed to this association, overall suggesting that mothers with depression are also likelier to experience socioeconomic hardship, their infants are more at risk to display behavioural difficulties early on, and altogether the two members of the dyad struggle to connect optimally across the postpartum period. These results above all point to the complexities with which women with depression can present, and that their vulnerabilities are often multi-layered and may transmit to their infants. And, as I have previously discussed, that not all mothers get the appropriate care they are entitled to because of barriers in our healthcare systems. Reassuringly, though, I did observe that the quality of the relationship improved significantly between 2 months and 12 months, suggesting that with time, early struggles in the relationship can be ameliorated. What does this mean clinically? With these results in mind, it’s important to consider the clinical implications of depression (in pregnancy and in lifetime) on the mother-infant relationship. While relationship support is routinely available for mothers with postpartum mental health problems and their infants, I believe this support should be extended to both mothers who are depressed in pregnancy and mothers who have a history of depression, even if they are well in pregnancy. Pregnancy is a period during which women are in routine contact with healthcare professionals and would therefore provide an optimal opportunity for support in bonding with the foetus and future infant by educating expectant mothers on sensitive caregiving, ways to engage and respond, and developmental milestones to look out for. Moreover, I believe that interventions proven to help the mother-infant relationship, such as video feedback and structured mother-baby activities, should be made more widely available. And that’s where my current research comes in: I am now working on SHAPER — recently written about in another blog — the world’s largest clinical trial to investigate the impact of guided mother-baby singing sessions on maternal depression and the mother-infant relationship. Ideally this kind of support can help women to feel more confident and prepared for their journey into motherhood by providing building blocks for an optimal, healthy relationship with their babies. And hopefully mothers will enjoy doing so in the process by singing along with other women and their babies!

All my teeth are going to fall out. All my teeth are going to fall out. All. My. Teeth. Are. Going. To. Fall. Out. For approximately three months, this was the thought that constantly swam around in my head. At the time I was back at university, retraining in science communication. I had left a secure and well-paying job to try and become a journalist and broadcaster. It was exciting, but it was also scary. Looking back now, I wonder if that was the seed of anxiety that was about to snowball. Even when I wasn’t actively focused on it, the idea that I would lose my teeth was always there. As soon as I had a moment alone, to pause, it would come up for air. I was anxious about it all the time. First, keeping it hidden, then, telling some friends and family in a joking, “aren’t I silly?!” sort of way, whilst actually feeling desperate for reassurance that my teeth weren’t going to end up on the floor or in the sink or a dentist’s hand. TEETH AREN’T THE PROBLEM One of the challenging things about obsessive thoughts is identifying that they are driven by your anxiety, and not the cause of it. As strange as it sounds, I knew my teeth wouldn’t fall out — but I was also really worried they would. I thought I was anxious because I might end up with a mouth full of gum. I was coming at it the wrong way around, and because of that when I finally got up the courage to go to the dentist and it turned out everything was fine, it wasn’t. The anxiety didn’t go away. Instead it picked a new target. Next, that I would be scammed out of my savings — the savings I was using to pay my way through my university course and career change. Aside from going to see a bank manager, this time it seemed as if there was no way to redirect my fear. Misunderstanding what was happening — I let the anxiety build. I checked my bank account multiple times a day and read personal accounts of being hacked and scammed and cheated until the early hours in the morning. I felt that if I wasn’t alert to it all the time, if I went to sleep without reading just one more article, I would wake up and my bank account would be empty. CAUSE OR SYMPTOM It wasn’t until the intrusive thoughts finally took on a different, darker tone, that I sought help — and by this point it was pretty clear I had depression. The anxiety was in the backseat, half-forgotten. In fact, it took years and many further bouts of anxiety to realise that the obsessive thoughts weren’t the root of the problem, but were instead the first warning sign that I needed to take stock of my mental health. It has been a long journey of panicking about housing, money, friendships, my own health. Innumerable late nights of endless googling. It is hard coming to the conclusion that one needs to stop being myopic and look at how you’re feeling generally. Accept that maybe your heart is racing not because the house is definitely falling down, but that you’re stressed and tired and mentally unwell. MENTAL SNEEZES Finally though, I learned to think of intrusive thoughts like sneezes during a cold. They were symptoms of the anxiety, and until I dealt with that, they would keep popping back up. Certainly, if you’re reading this and it seems familiar — take it from me, no amount of evidence or reassurance can dispel the nagging thought that The Bad Thing will happen. My best advice, take the feeling of your worry seriously. Don’t try and push the thoughts away or persuade yourself that you’re being silly. Instead think about the emotion, the feeling of panic or despair or nervousness, and seek help. If you’re a keen Googler like me, why not have a read of my first blog post for InspiretheMind, The opportunities and dangers of predicting mental health using social media: should one status reveal the other? In it, I explore the ethics of an emerging area of research; making mental health diagnoses using algorithms trained on data collected from sites like Instagram, Twitter and Facebook.

In A World Apt For Escapism, Why Stay? The world is brimming with content. Video games, books, movies, articles, social media posts — there is so much that it can be a drag to give attention to real life. Reality often pales in comparison to what endless media promises: the characters more intriguing, the settings more colourful, and consequences less harsh. This media collective has become so grand, so accessible that it constitutes a world away from reality. In the spring of 2020, I graduated from university with a bachelor’s degree in communication studies. The final few weeks of my degree were limited to distance learning because of the Covid-19 pandemic. What was supposed to be an exciting summer of career development and post-grad excitement was suddenly cancelled. I went from completing final projects, exams, job interviews and applications, to being stuck at home; the most opportune time of my life had gone stagnant. The momentum shift left me to cope with mental whiplash. I was lazy and excessive in my content consumption, which left me feeling guilty for wasting time and not being more productive. Throughout hours of the day, I occupied my mind by delving into video games, TV series, movies, and stories. I read one story in particular that granted me justification and insight about distractions during stressful times. That story was James Thurber’s The Secret Life of Walter Mitty. In 1939, the titular character was introduced to the public. The Walter Mitty archetype has since been known in popular culture to describe sheepish personalities who indulge in unobtainable fantasies. There are “Walter Mitty”s everywhere. The ability to withdraw from reality into imaginative content by means of storytelling has shaped human hopes, wishes, and escapes for aeons. While Mitty is an exaggerated example of a man who is defined by excessive dreaming, everyday people possess wandering minds that, when given a chance, will abandon the present for the clouds. In fact, as many as 96% of adults experience daily fantasies. It is by this measure that Walter Mitty has become a perpetually relatable character. The purpose of daydreaming isn’t exactly known, and researchers have theorized that it can serve functions such as insight into one’s experiences, to assist in decision making, and grant perspective into other’s feelings. It is, however, widely accepted to be an effective coping mechanism to deal with internal and external stressors, known as avoidance coping. Walter Mitty’s fantastical adventures are backdropped against the character’s luckless life, in which he is a timid individual subjugated by the people around him. The juxtaposition of his real-life and secret life shows how important escapism can be, as daydreaming is his only get away from the unwanted stress of his environment. In an afternoon of running errands for his controlling wife, the protagonist’s imagination runs rampant. From being a fierce pilot endeavouring through a terrible storm, to a world-class surgeon who miraculously saves the life of a millionaire banker, to a renowned marksman on trial — it’s all in a day of the (secret) life of Walter Mitty. Fantasy in the 21st Century Nowadays there is less rationale for a mind to be as venturesome as Mitty’s. His story was written before the technological revolution, which means that escapism has since taken on many different forms to be almost anything but profound daydreaming. Society has more entertainment and media than ever, and people need not rely on their imagination to step out from reality. If somebody wants to imagine themselves as something else, it is easy to simulate the experience through the plethora of available content amongst various forms of media. Immense catalogues can bring wandering minds to wherever they wish to be, whenever desired. Content production continues to increase at impressive rates alongside the booming entertainment industries. Over the past decade, the entertainment industry has grown considerably. Video gaming, movie and television streaming, and cell phone usage have all seen an increase in content from year to year. Likewise with books, in which more than a million new books are added to the collective annually. There is more than enough content to satisfy any fantasy, and large enough demand from audiences to merit the production of anything from small indie films to big-budget video games. This just goes to show many people do not want to be alone with their thoughts. It is a much more palatable coping strategy to get out of one’s head and into a Netflix series, than to venture further into a frazzled mind in search of imagination. The occupied mind is more accessible than ever. The extended catalogue of content competing for everybody’s attention is difficult to avoid. The case to partake in avoidance coping is a strong one that is further bolstered by feelings of stress, anxiety, and guilt. Expansive technology has led to greater awareness about societal problems such as climate change and wealth inequality, problems that define the modern generation. Such issues have been linked to elevated levels of mental health conditions, which are on the rise globally. Not only is an occupied mind more accessible than ever, but it is also more justified. The portrait of Walter Mitty is completed by a damning truth: his fantasies are, in part, responsible for his timid disposition. The man who misses the cue to go when the light turns green and who drives down the wrong lane in a parking lot is the same man who is planets away in imagination. He drives inattentively, says nonsensical things aloud, and is helplessly forgetful. All of which are consequences of his inability to remain in the present. Mitty’s self-consciousness and lack of dignity make him unhappier than his imaginary self, which in turn gives more reason to avoid reality. He dreams because he is unhappy, and he is unhappy because he dreams. A Cycle with Momentum This cyclical nature of avoidance coping is a common occurrence in today’s world. It demonstrates why it can be so difficult for people to escape the procrastination cycle, which is known to negatively affect happiness and life satisfaction. The circular nature of escapism and how appetizing it can be is precisely why it can be a slippery slope. It is an echo of the great challenges that people face today. In stressful times, escapism is necessary. However, when society’s psyche is barraged by feelings of stress, anxiety, and guilt, practicing escapism in moderation becomes difficult. Mentally, we can only be in one place at a time. Too little escape leads to burnout, and too much escaping leads to a loss of productivity, dissatisfaction, and a loss of self-esteem. The responsibility falls to the individual to practice escapism in moderation, as ignoring other, more important aspects of life that leads to stress if left unchecked. This is not to say that escapism is a bad thing. Life can be hard for a multitude of reasons, not the least of which can be subdued with avoidance coping. The necessity of which proves that our ability to shelter ourselves from undesirable feelings is a wondrous aspect of the human condition. Walter Mitty’s mind-wandering escapes are a fictional tale of a healthy coping mechanism gone unchecked. However, his resolution and resilience shine through his meekness. The author punctuates the character finally with a deliverance of solace in the last line of the story, where he refers to Walter Mitty as the “Undefeated”. It is fitting; in a world where people suffer and stress for countless reasons, escapism will always be there as a reliable coping method, and the circumstances are ideal to warrant justification in doing so. For better or worse our escapes can define us. Fortunately, it is our prerogative to employ them.

The beneficial effects of exercise on both mind and body have been public knowledge for years. Some of these benefits can be seen in previous InSPIre the Minds blogs by Professor Carmine Pariante, Dr Richard Simpson and Neuroscientist Juliette Giacobbe. However, as Juliette mentioned in her blog, exercise can also have negative impacts on mental health, many of which stem from social interaction. So, what happens when you factor the gym — an intense social environment- into this equation? As a qualified personal trainer, and Psychiatric Research MSc student, I’m extremely passionate about the cross over between mental and physical health. When studying to be a personal trainer, I completed a module on barriers to exercise, some of which have been outlined on the mentalhealth.org website. For some psychological barriers, their presence can often be associated with the gym environment rather than the exercise itself. As a social species, it’s somewhat in our nature to worry what other people think and make comparisons with other people’s lives. So, when attending the gym, this can often be a mixing pot of many positive and negative emotions. Our experience of these emotions are very much dependent on an exhaustive list of variable factors, including our personality traits, pre-existing anxieties or low self-esteem, whether we have any additional support (for example, gym buddies or personal trainers) and many more! The intention of this blog however is not to tell you what you will or will not experience, or that you will definitely experience anything I mention today. The aim is to simply shed light on the feelings people may have when they go to the gym, touching upon my own experiences from 8 years in the gym. Gym anxiety versus comfort In 2013 I started using the gym at my local health club. At just 15 years old I hated my body and felt a need to lose weight. With little confidence and low self-esteem, attending the gym wasn’t any easy task for me and for many years I experienced something now referred to as ‘gym anxiety.’ Gym anxiety is an umbrella term for the worries and concerns people have when attending the gym. Common anxieties include fear of people watching, of all equipment being used so wandering around aimlessly, of doing exercises incorrectly and not knowing how to use the equipment. Recently PureGym, one of the largest gym groups in the UK, shared an article by fear expert Dr. Kerr, who highlighted the social basis for gym anxiety and provided tips on how to deal with these difficulties. Some examples include, accepting your fears, making a plan and educating yourself. For many people beginning their fitness journey, or changing to a new gym, these anxieties can frequently occur. However, the gym environment can also be a comforting and relaxing place for many people. The beneficial effects of exercise in stress alleviation have long been public knowledge, but the additional support of a gym community can somewhat amplify this. For many people, exercising in a shared environment where support is available can be a comfort, particularly where they feel their own knowledge is lacking. The sharing of knowledge, and a collective goal to better oneself, can make the gym environment a reassuring place to be. In my early gym days, the support I received from personal trainers when in the gym provided a safety net for the times I doubted my knowledge, which ultimately provided me with comfort. 5 years into my fitness journey I moved to a bodybuilding gym after finding a passion for heavy weightlifting and muscle gain. Here, I found a level of comfort in the atmosphere created by people with similar goals. Self-comparison versus confidence Although I have now managed to find comfort in support from the gym community, for a long portion of my journey, the gym amplified the difficulties I had with body-image and performance. I often made comparisons in the way I looked, the weight I lifted and the speed and length I could run, constantly wishing I could do more. Given that the gym environment is a social space, it is common for people to feel pressured to look a certain way or perform at a certain level (The irony!). The very nature of human beings can often lead to self-comparison and dissatisfaction with oneself. Though only measured in male participants, group comparisons showed gym users had increased body dissatisfaction and eating pathology when compared to non-gym users. (Disclaimer: this does not mean you are going to develop disordered eating or body dissatisfaction if you attend the gym.) In women, 45% said they would be nervous in the gym if other gym goers were fitter than they were. On the flip side, with the right support, the gym environment boosted my confidence more than exercise outside of this community ever could. Reassurance and guidance from others helped develop my knowledge and inadvertently increase the confidence I had in my training. Many people starting their fitness journey worry about their lack of knowledge and subsequently doing things incorrectly. In another article by PureGym almost 40% of people said they were afraid to show people they didn’t know what they were doing. As a result, most lack the confidence to begin their fitness journey and thus sharing of knowledge and reassurance in the gym environment can boost confidence. Distraction versus motivation Sometimes the gym environment can be a distracting and counter-productive place to be. There are many reasons why people can get distracted at the gym, including others trying to socialise with them, poor spatial awareness and dismissal of personal space, loud noises (such as grunting and slamming of weights) and getting bogged down with self- comparison. When I was experiencing difficulty with self-comparison and body-image, the gym environment sometimes became a very distracting place to be and in fact deterred me from my goals. I was often so wrapped up in what other people were achieving that I couldn’t fully develop my own training. If you find your mind wandering in the gym and your eyes focusing more on other people than what you’re actually doing… don’t worry, most of us have been there and done that! It can be difficult to focus on your own goals when other people are grinding away at different milestones. However, sometimes being surrounded by others who are smashing their own milestones and pushing their own limits can be a good source of motivation for many people in their fitness journey. Working out with others can provide a sense of accountability and subsequent motivation that may often lack when embark on a fitness journey alone. As I became more confident in my own abilities, this was certainly the case for me. Attending a bodybuilding gym where others were lifting ridiculously heavy weights, the sheer atmosphere of no limits became a big source of motivation to hit heavier personal bests on my own lifts. A note on individuality We are all unique individuals — what works for one person may not work for another, and what one person experiences in the gym is not a guaranteed experience for another. Your journey is your own and only you can decide if the gym is the right place for you. In summary The gym environment can provide some beneficial additions to people’s fitness journeys, including a motivational atmosphere, sharing of knowledge and experience, and a sense of community and support. Overall, these factors can provide people with more comfort, confidence and motivation in their fitness journey. However, we should give equal weight to the struggles some people experience when attending the gym, including gym anxieties, distractions and increased risk for self-comparison. Experience of these effects (or any others not listed) is very much individualistic and dependent on many other factors, so please do not take all of these as a given! Header Image by Anna Tis on Pexels

Six months after graduating from University and starting my career at BMW UK, my world was torn apart when I found out a close friend from University died by suicide. As with many similar stories especially with men, none of us had any idea he was struggling. Shortly after, my cousin who had battled with Anorexia for about 25 years passed away in her 30s due to the impact the illness had had on her body. Coupled with some close friends struggling with their mental health, my naïve bubble was well and truly burst, but being a self-confessed ‘doer’, I knew I wanted to do something. As there were already several employee groups at BMW for other topics, some colleagues and I spoke about the potential value of setting up a Mental Health employee group. Whilst my instinct would naturally lead me on an impatient quest to fix everything, I realised this issue wasn’t going to be quite so simple. However setting up a group with like-minded individuals to reduce the mental health stigma and drive cultural change, even if it only positively impacted one person, would be both healing and rewarding. The timing couldn’t have been more perfect as an internal communication asked if there would be an appetite to establish a collective of Diversity & Inclusion network groups. Without hesitation, I offered to set up a Mental Health group alongside a couple of keen colleagues. Not long after we had 50 members and our group name, Minds Matter. Once we were up and running, we could start trying to raise awareness and reduce the stigma surrounding mental health…and I could really start doing! Having partnered with an external Mental Health Workplace Specialist (Steve Hoblyn), we’ve run numerous educational sessions on Understanding Anxiety, Depression and Self-care. This year we have a full calendar of sessions on topics such as sleep, mindfulness, mental health daily management and managing guilt, all scheduled to help individuals better manage their own mental health. Our biggest achievement and my proudest moment personally was training 32 Mental Health First Aiders last year. If an employee trips in the office, every company has first aiders and processes, but what if someone has a panic attack? After putting so much effort into raising awareness and encouraging openness, having individuals that are trained to have conversations and signpost to relevant help we realised was not a nice to have, it was crucial. Understandably, there is such a fear of starting a conversation around mental health due to the worry that you may not know what to say, you may say the wrong thing, or the individual may get upset. There’s a huge movement around the importance of starting a conversation and encouraging people to have conversations, to not only support each other but normalise the issue. I really agree with this and as a general rule of thumb I truly believe in the #AskTwice concept and that if you’re being authentic and caring, even if you maybe don’t have the best choice of words, it’s usually better than not saying anything at all. That being said, reflecting on the MHFA course and without wanting to deter people from starting a conversation, I think it’s important that we all take accountability to upskill ourselves on the language we use and understand how to be empathetic, not sympathetic — there’s a great video called Empathy by Brené Brown on this. And for me personally, if there’s one thing I’ve learned, it’s that listening is doing and it’s also hugely powerful. I’m so pleased that we were able to get the MHFA programme approved out at our campus comprising of BMW, BMW Financial Services and Alphabet. Not only that, we were overwhelmed with requests to attend the training and had to schedule an additional course — it just goes to show how much this topic resonated! Whilst, possibly naively, post-launch we were expecting people to reach out to the MHFAs to talk, we’ve found that it’s actually the MHFAs that start the conversation as they are more confident in doing so, as well as being more ‘in tune’ with spotting potential signs. If I could give one piece of advice, it’s to ensure at a company level you have a robust and holistic approach to rolling out MHFAs. You can’t simply train individuals and that be the end of it. It’s crucial that you have regular regroups as an MHFA team, ideally supported by the MHFA trainer, creating a safe space where associates can discuss what ‘interventions’ have taken place (confidentially) to guide and support one another. It is hard to put into words how crucial this part is but in essence these MHFAs are having highly emotive conversations and it’s important they have a space to unload and be supported. I am thankful to get so much praise for running Minds Matter but truthfully on reflection, as someone who may come across as comparatively unemotional, headstrong, and tenacious, this really is my way of coping even if it can be exhausting knowing I can’t fix it all. I’ve accepted that I’m never going to accept losing my friend Dan and I don’t think I’ll ever stop trying to take positive action to try to move the topic forwards, even if it’s just in my work-life bubble…for now at least.

The role of our genes and the role of the environment Numerous studies so far have shown there is a connection between depression and inflammation. Nearly 20%-30% of depressed patients have C-reactive protein (CRP) levels, an inflammatory biomarker, above 3mg/L indicating low-grade inflammation. Inflammation is a biological process activated by our immune system, usually as a response to an external threat that can cause an infection, and it is most of the time short-lived. However, in some cases, inflammation is triggered without any viruses or bacteria present, for example in people with obesity, diabetes or cardiovascular disorders, and it can even become chronic. One of these cases is depression. However, it isn’t exactly clear yet how these two are connected. Does depression cause inflammatory levels to rise, or is inflammation the one that causes depressive symptoms? What factors are involved in this relationship? While previous blogs in InSPIre the Mind have discussed the link between depression and inflammation, here I want to discuss my research addressing an important question in this context: Do our genes play a role, or is it our everyday choices that have a higher likelihood of causing inflammation in depression — an effect that keeps getting captured in different studies around the globe? A psychologist by training, I was until recently a research assistant at King’s College London, where I conducted this research; I am now a PhD student at University College London (UCL) and Birkbeck, University of London. In our recent study, we have decided to explore in more depth the association between depression and C-reactive protein (CRP). We used data from the UK Biobank, a large health resource. To our knowledge, our study is the largest of its kind to date to investigate the association between depression and inflammation, including data from 85,895 participants. To investigate the relationship between depression and inflammation, we used biomarker, genetic and questionnaire data. First, we were interested to see if we can find an association between depression and inflammation, as has been described in previous studies. We were also curious whether there is a genetic predisposition to inflammation when you are experiencing depression, and whether polygenic risk scores (PRS; I will explain it below) for depression are associated with CRP levels. In addition, we were interested in the role of other external factors, such as body mass index (BMI), smoking, childhood trauma, socioeconomic and health status and whether they influence the depression-inflammation association. Polygenic Risk Scores (PRS) Before we examine the role of polygenic risk scores, it is important to understand what they are. The human genome is almost identical for all of us. However, some parts differ, and those parts, called genetic variants, give us our unique characteristics. These genetic variants are often harmless but some of them can increase or decrease our chances of experiencing various illnesses. Using statistical genetic methodologies, we can identify which genetic variants are associated with diseases of interest and then calculate a total score, called a polygenic risk score, that represents our chances of experiencing a particular disorder based on our genes. Lifetime depression, raised CRP levels, and risk factors for inflammation 31.3% of the participants included in the study were classified as having major depressive disorder, matching the prevalence on a global scale that has been described in other studies. As expected, the participants with depression in our study had higher CRP levels compared to people without depression. They were also more likely to be smokers, to have experienced more childhood trauma, and to have higher Body Mass Index (BMI), more self-reported health problems and lower socioeconomic status. CRP levels were also strongly, associated with age (higher), sex (higher in males), BMI (higher), smoking (higher), socioeconomic status (higher in those with lower status) and ill health (higher), meaning that all the above factors are associated with CRP levels independently from depression. Depression PRS is associated with CRP levels We calculated PRSs for CRP and depression, and for a variety of autoimmune disorders, to investigate the genetic association with the measured CRP levels in our sample. A genetic correlation between depression and CRP showed that these two share some common genetic basis. As expected, the CRP PRS was strongly positively associated with the participants’ measured CRP levels, even after taking into account the age, sex, BMI and smoking status of our participants. Depression PRS was also positively associated with the measured CRP levels when considering the age and sex of the participants. To our surprise, this stopped being the case after taking into account the effect of BMI and smoking. To gain a better understanding and interpretation of the findings mentioned above, we used the PRSs calculated for different autoimmune disorders to see if and how these were associated with CRP levels in our sample. The PRSs for Crohn’s disease, biliary cirrhosis and rheumatoid arthritis were also positively associated with CRP levels, even after taking into consideration the age, sex, BMI and smoking habits of our sample, unlike the depression PRS. This shows that the genetic association between depression and CRP levels is mediated by BMI and smoking. Therefore, the genetic contribution to the increased inflammation in depression is due to the regulation of eating and smoking rather than an autoimmune genetic predisposition. Other factors and their effect on the association between depression and inflammation We performed further analyses, using the mental health questionnaire data we had at our disposal (no genetic data were used in this analysis), and we tested whether depression was associated with CRP levels. There was a positive association between depression and inflammation after considering the effect of age and sex. This remained the case after taking into account the effect of BMI and smoking as well, even though the effect was slightly reduced. We were interested then to see if other environmental factors could explain further the effect we were capturing in our analysis. The environmental factors refer to anything external, such as childhood trauma and socioeconomic status. We were also curious about the effect of general ill health, alcohol consumption and whether taking antidepressants or anti-inflammatory medication could explain the association between depression and inflammation fully. Our analyses showed that all these factors could explain a part of the association. However, even after considering all these, the association remains positively significant. Our findings show that inflammation is potentially a core feature of depression, but there might still be factors playing a role in this association that we haven’t investigated yet. However, it could also mean that the association between depression and inflammation remains no matter how many other factors, either internal or external, we take into consideration in our analyses. One of the important points to remember is that even though genetics are important and can increase or decrease our chances to experience an illness, quite often environmental factors can have an equal or bigger impact. Depression PRS was positively associated with CRP levels. Yet, when we take into account the two environmental factors we can control, BMI and smoking, the significant association disappeared. This shows that up to a certain point, we can actively affect different health outcomes in our life by making healthier decisions, such as adopting a healthier diet, exercising and stopping smoking. And these healthier decisions can improve not only physical health but also our mental health — possibly by reducing inflammation.