Only a little more than a month ago, on the morning of the 15th of February, I had my usual Italian breakfast in an unusual Airbnb in Turin. I left Italy two years ago to become a researcher, and now I had the chance to return to my home country to attend one of the most relevant international conferences for my area of interest: the 10th International Meeting “Steroids and Nervous System” (15th– 20th of February 2019). The meeting was organised in a historical building where lessons of science and anatomy were held back in the 19th century. The famous doctor Cesare Lombroso, (in)famous for having attributed moral quality to physical appearance, also opened the questioned museum of psychiatry and criminology in the same edifice. The amphitheatric room was evocative of centuries of knowledge. I was there, surrounded by the experts in the field, the air scented with ancient knowledge. The dissonance between old times and the new scientific insights gave the meeting a charming atmosphere. The meeting addressed the state-of-art of research on steroids — a class of hormones that regulates everything, from sugar levels to blood pressure to memory — and their role in the interplay between body and mind. Sixty-six studies were presented over five days of work. There are different types of steroid hormones, which can bring various types of messages to and from the brain, and regulate emotions and behaviours, including our stress response. However, the hormones that I am studying, and the reason I was there, were the sex hormones and the role of sex differences in mental health. By studying “sex differences” in mental health, I am investigating the underlying mechanisms which may causes some well-known differences between women and men. For example, depression is more common in women than in men. Indeed, in 2008 the lifetime incidence of depression in the USA was 1 in 8 in males and 1 in 5 in females. Moreover, sex differences could regulate the age of onset of mental disorders; for example, schizophrenia tends to show itself earlier in men than in women. These are just a couple of examples to highlight why sex differences in mental health are such a hot topic in research. So, what are the sex hormones, and what do they do? Female hormones, like estrogen and progesterone, and male hormones, like testosterone, are usually considered only important for the development of our body toward the biologically-assigned features of our sexes, and for sex-specific processes such as menstruation, pregnancy or spermatogenesis. But in reality they do much more. One study has looked at the socio-sexual behaviour and birdsong of canaries. An increase in testosterone levels in the brain leads to a rise in song’s tone frequency and thus change the way birds communicate. Let’s consider another example. You may think that running for 30 minutes has the same relaxing consequences in women and in men. However, one study found that, in mice, males seem to benefit from exercising with almost an anti-anxiety effect; yet, in females, exercising improves resilience to stress and increases physical arousal. Not surprisingly, the other researchers at the conference went on and on about the importance of studying sex hormones to understand sex differences in terms of the differential vulnerability and resilience to different mental disorders that we see in males and females. But what about timing? Sex hormones vary during the life-span; they increase and decrease at different times of the day and at different ages. So, when exactly do these hormones start to influence our mental health? Well, actually this is probably sooner than we think. As early as in our mum’s tummy. Previous studies from our research group have shown that mothers who are depressed in pregnancy have increased levels of another steroid, cortisol, which is important for the stress response. More interestingly, their babies tend to respond more to stress, by producing more cortisol. But are these effects different in male babies and female babies? Another series of studies conducted in mothers who were stressed at the time of pregnancy show that male children would tend to show earlier consequences, in the way that they developed skills such as language and movement, while in female children, it was observed that while they appeared unaffected until preadolescence, they then began to show signs of anxiety.

“A Jedi must have the deepest commitment, the most serious mind… All his life has he looked away… to the future, to the horizon. Never his mind on where he was” - Yoda (Episode V: The Empire Strikes Back). Many of us would love to receive Yoda or Obi-Wan’s guidance in this stormy ocean that is called life. In fact, sooner or later, the majority of us experiences stress or anxiety. One might even describe the thoughts and emotions as controlling and overwhelming to the point that it feels there is no sign “EXIT” at the end of the tunnel. In these cases, the predominant need may be to stop the world and to take a long, deep breath. I am here to tell you that you have the power to take control and to stop time. Is it a magic trick? Can only special people do it? Well, I am delighted to let you know that everyone can do it and that it is not, in fact, magic. There is an approach that is very easily accessible, and when mastered it can be profoundly liberating. The answer is: mindfulness. “Be mindful of your thoughts, Anakin. They will betray you.” - Obi-Wan (Episode II: Attack of the Clones). Mindfulness is a useful tool that you can use to handle every-day stressful situations and to reconnect with yourselves in order to improve your general well-being and mental health. First of all: A little bit of history Mindfulness derives from Buddhism which believes that individuals can eliminate suffering by having a neutral vision and awareness of reality and themselves in the present moment (here and now). We have Jon Kabat-Zinn to thank for the introduction of mindfulness in the Western world. The American professor emeritus of medicine and biologist created the “Stress Reduction Clinic” in 1979, with the intent of introducing it into medical practice, such as in hospitals, health centers and clinics, in order to mitigate chronic pain and to give additional help to those patients sadly facing terminal illnesses. This program was then modified, and today it is known as “Mindfulness-Based Stress Reduction” or “MBSR” programme. This meditation approach is based on focused attention meditation, and on open monitoring/non-directive meditation. In focused attention meditation, your focus is an object, that could be a mantra (from the Sanskrit “sacred message or text, charm, spell, counsel”; it is a word or sentence repeated during meditation), a part of your body, or even a sound. Whereas, in the second style, open-monitoring, you simply become a witness of everything is happening without judging it. The skeleton of the MBSR programme is a schedule of 8-weeks’ training. It requires learners to practice mindfulness techniques daily, both by themselves and in weekly group sessions. It may seem quite intense and challenging, but this period of time is the minimum needed in order to make using these techniques comfortable. Digital technology can also help you. In fact, there are many mobile applications and CDs/DVDs which will guide you in learning mindfulness and in feeling more comfortable in its practice. We are often distracted. Our minds fly over time and space and we lose touch of our bodies. We are soon absorbed in obsessive thoughts about something that just happened or, that may happen in future. It seems we have been on automatic pilot for our entire existence. However, paying closer attention to the flow and content of your experience can allow you to take control of your mind and to notice such patterns in your behaviour. Mindfulness has also been found to improve mood and cognitive functions, with regular practice being shown to be associated with structural changes in the brain and improvement in neural connectivity. “I’m alive. When I’m eating that’s all I think about. If I’m on the march, I just concentrate on marching… If you can concentrate always on the present, you’ll be a happy man. Life is the moment we are living now.” - Paulo Coelho, The Alchemist. Even though I am praising mindfulness as the answer to stress-related problems, I want to highlight the fact that it is not actually a form of psychotherapy, although, it could be used as a strategy in the rehabilitation pathway. However, a group of individuals called Zindel Segal, Mark Williams and John Teasdale, have actually developed a Mindfulness-Based Cognitive Therapy (MBCT), merging mindful meditative techniques with cognitive psychotherapy. The MBCT has been found to be effective when used in addition to medication in patients suffering from anxiety, depression and other psychiatric conditions such as bipolar disorder. And now: Some practice It is important to know that before feeling the benefit effects of mindfulness, you first need to learn how to breathe… Yes, I know, I know. You already know how to do it. But, what I am referring to is a special type of breathing. This breathing can be your anchor, keeping you in a focussed state in the conscious observation of experience. When practicing MBSR, you have to deeply inhale through your nose by lowering your diaphragm and by expanding your lungs as much as you can, before slowly exhaling out of your mouth. While doing this, your focus is directed only on your breathing and the movements of your body created from it. In this way, you should be able to achieve an awareness of your own inside and outside worlds. Later, when practice develops and your ability to focus attention improves, you can observe your thoughts and emotions as they arise. You can ask yourself where they come from, how they feel, and soon you will start noticing patterns in your thoughts and behaviour. A lot of people are afraid that mindfulness is quite complex, but in reality it is often much simpler than it seems. So, how do we start? Mindfulness is an ensemble of different exercises but, luckily, you can practice it at any moment during every-day activities, like eating… I can show you how this might feel by using something as simple as a raisin: Firstly, look at the raisin, lingering on every shape, colour and shadow. Secondly, smell it until you catch the different shades of the fragrance. Thirdly, after having closed your eyes, place the raisin in your mouth and roll it around with your tongue, noticing the taste and texture, what is happening and how your mouth reacts to it as you slowly chew and swallow the raisin. I am not for a moment expecting you to eat every mouthful of food in this way, but hopefully this activity demonstrated how much of a rich and deep your experience could be. By practicing it every day, then you can break through the glass wall between you and life itself. You can learn how to perceive and accept reality in the present moment, as it is, by looking at negative thoughts in a detached way — as if they were in a world separate from yours — and seeing them for what they are, that is, as a product of your mind. Thus, mindfulness could be helpful for those who suffer from anxiety, depression, experience burn-out and/or negative feelings that sometimes can be overwhelming, as mentioned when I spoke about mindfulness-based cognitive therapy. Remember that mindfulness is training, and like every training, it requires time and dedication. If after some sessions you don’t feel any changes and you feel like giving up, keep in mind to not to judge yourselves and remember that as Yoda said, “patience you must have my young padawan”. May the force be with you! header image source Deviant Art

The interplay between sex hormones and immune system: an undiscovered path in the affective disorder maze? For generations (until the ‘90s), males were considered as the ideal target population in clinical drug trials, triggering biased research and incomplete knowledge not only on the biological and psychological differences between males and females, but also on the treatment response of female patients. As a young contemporary PhD student in psychiatry, I feel I have a duty to study these differences, in order to help create multidisciplinary, sex-tailored precision medicine. In my previous blogs on Inspire the Mind, I published an initial reflection on sex differences in mental health with a particular focus on sex hormones, and a blog about mindfulness as a promising tool to handle stressful situations and to help improve mental wellbeing; but this time I want to talk about differences between male and female patients in the affective disorder population, focussing on sex hormones and inflammation, which is the main topic of my PhD. Sex differences in mental health are important, in particular in affective disorders Affective disorders (also known as “mood disorders”) are a set of psychiatric conditions such as for example major depressive disorder (MDD) and bipolar disorder (BD). There are important differences between male and female patients with these disorders. For example, as I wrote in my recently published paper, the risk of developing depression is higher in women than in men. But sex differences do not stop here, they spread out to other areas, such as the type of experienced symptoms and the response to medications. In fact, female patients tend to show a higher prevalence of atypical depression (an example of an atypical symptom is hypersomnia — that is, sleeping too much) and have a better response to selective serotonin reuptake inhibitors (SSRI), the newer and safer class of antidepressants that increases the amount of available serotonin in the brain and the serotonin activity. In comparison, male patients respond better to tricyclic antidepressants, which also act on the serotonin and norepinephrine reuptake, but they are older compounds and have more side effects and more risk of toxicity than SSRIs. Sex also plays a role in bipolar disorder, a condition characterised by mood swings (pathologically high and low mood, also called mania/hypomania episodes alternating with depressive episodes); female patients show later age of onset, more history of suicide attempts, and more frequent depressive episodes, mixed mania and rapid cycling (that is experiencing at least 4 mood episodes — depression, mania, hypomania — in a 12-month period) in comparison with male patients. What are the biological mechanisms that may explain the sex differences in affective disorders? Inflammation is one of the most studied biological mechanisms in depression. The immune system (that is the system that fights infections in your body) is, as previously discussed in this blog, hyperactivated in depressed patients. In fact, one of the signs telling us this system is activated is the increased levels of peripheral inflammation. Depressed patients present an over-activation of the immune system even though there is no ongoing infection in the body; moreover, we also see that those who do not respond to antidepressant treatments have even higher levels of inflammation in comparison with responders. This could truly be a turning point in helping those depressed individuals who cannot see the light at the end of the tunnel, going from one antidepressant treatment to another without significant improvement. Like in “Alice in Wonderland”, down the rabbit hole, one question leads to another. Why is this happening? Does the same mechanism affect the activation of the immune system in depression, in both males and females? Is out there a new possible sex-specific therapeutic approach for those patients who do not respond to antidepressant treatments? Answering these questions may give us the basis for the multidisciplinary sex-tailored precision medicine I mentioned earlier, with different treatments for male and female patients. Having seen the predominant role of inflammation in major depressive disorder, one of the possible answers may be a yet unexplored mechanism: the interaction between sex hormones and inflammation in affective disorders. It may seem strange that sex hormones, something that is commonly known as the regulator of processes such as our sexual development and reproduction, is also linked to a system that regulates stress response and that fights infections in our body. But let me take a little step back: what are sex hormones doing? Sex hormones (also known as gonadal hormones) can be divided into different classes such as androgens (for example testosterone), estrogens (for example estradiol), and progestogens (for example progesterone). They are known as the main actors of reproduction and development of secondary sex characteristics. To give you an overview, testosterone is involved, for instance, in the development of male reproductive organs in the fetal stage, the physical changes during puberty, and the production of sperm in adulthood. Estradiol is produced primarily by the ovaries in females and levels vary during the menstrual cycle, reaching the peak with ovulation (egg maturation and release), and the lowest levels during menstruation (also called “menses”). During pregnancy, the levels of estradiol increase exponentially, (also thanks to the cooperation of the placenta that produces estrogens and progesterone), with a drastic drop after the delivery and the expulsion of the placenta. Progesterone is also produced primarily by the ovaries in females and mainly in the luteal phase (second half of the menstrual cycle); furthermore, it maintains the early stages of pregnancy, inhibits gonadotrophin-releasing hormone (GnRH) and luteinising hormone (LH) liberation (with gonadotropins being essential for reproduction). If the egg is fertilised, this hormone also plays a significant role in pregnancy, by contributing for example to implanting the egg in the womb (uterus), to avoid contractions (which may cause miscarriages) and prevent milk production (through prolactin inhibition). However, sex hormones are also involved in a broader spectrum of functions throughout the whole life of an individual, with the ability also to affect mood and behaviour, as I described in my previous blog, and with potentially neuroprotective abilities. For example, testosterone is also implicated in the production of blood cells, in supporting the strength of the musculoskeletal system (specifically muscles and bones); and it shows anxiolytic and anti-depressant actions and the ability to improve cognitive functions, such as spatial memory (that is the memory which helps you to recover the locations of places and objects, and which is vital for survival). Moreover, estradiol improves the density of bones and cartilage (that is, the tissue that protects for example the extremities of long bones and is also a body component in your ears and nose) and improves cognitive functions (such as verbal fluency). But the story continues… Sex hormones also have immunoregulator proprieties. Inflammatory levels also vary accordingly to the hormonal environment, with testosterone showing anti-inflammatory effects and estrogen showing both, pro- and anti-inflammatory proprieties. Interestingly, pregnancy is generally characterised by a change towards an anti-inflammatory profile, whereas depressed pregnant women show increased inflammatory profiles in early pregnancy. Moreover, hormonal fluctuations and changes in physiology across the lifetime (for example puberty, pregnancy and menopause) can affect our mood and can be linked to sex differences in affective disorders. In fact, the risk of depression soars in puberty, and for females, it increases in particular after menarche (that is the first occurrence of menstruation), with testosterone being also linked to increased risk of suicide attempts in female patients with bipolar disorder. All these differences and links between mood, sex hormones and inflammation pushed me to explore this mechanism in affective disorders, by doing a systematic review. A systematic scientific review is a method used to understand what is already known about a topic, and what the key points are. This process allows us to select published articles that talk about the data of interest and thus understand the state of the art in your research question. It may bring new insights and/or an understanding of what is needed to be done in future research, and connects the dots between apparently disjointed pieces of evidence. However, when doing this review, the answer to the question was not so immediate, and I noticed that this interaction between inflammation, sex hormones, and affective disorders is quite understudied. In the published literature, we found only 20 articles that investigated our triad of factors — sex hormones, inflammation and depressive symptoms — in the same subjects; nevertheless, my systematic review finds some new insights that can be used for future research (and in the end, for potentially improving clinical practice). I have described this evidence in my paper “Sex hormones and immune system: a possible interplay in affective disorders? A systematic review”. Trying to put together these 20 articles was like walking through a maze! But I was able to find my way, at least a little. Testosterone may be protective in bipolar depression in men through anti-inflammatory effects. Bipolar disorder exhibits different mood states associated with different levels of sex hormones, such as higher testosterone levels in manic mood states than in depressive mood. Remarkably, a study found that male patients with bipolar disorder show decreased testosterone levels. Moreover, the lower the testosterone, the higher the inflammation, as measured by a protein in the blood called interleukin-17 (a pro-inflammatory biomarker). This suggests a possible protective role of testosterone as an anti-inflammatory agent in male patients. Basically, male patients with bipolar disorder tend to have increased inflammatory levels and decreased testosterone levels: perhaps increasing testosterone could have an anti-inflammatory effect in these patients, and help stabilise the mood? A study to be conducted in the future. Interestingly, this is relevant for male patients only, as testosterone is increased in female patients with bipolar disorder. Hormonal therapy may be protective in peri/postmenopausal women through anti-inflammatory effects. Menopause is an actual dilemma, requesting a balance of hormonal therapies to counteract the symptoms of hormonal deprivation and the increased risk of depression. Even though hormonal replacement therapy has some major benefits, such as improving mood and libido, it is associated with moderate side effects like headaches or feeling sick, and an increased risk of breast cancer. Studying the side effects of hormonal variations may help us to better understand the role of sex hormones in the interaction with the immune system. The studies focussing on menopause highlight a possible key role for hormonal therapies as protective factors in peri- and postmenopausal women, possibly through an effect on the immune system. For example, one study found that in women who are not taking hormonal therapy, higher inflammation is associated with more depressive symptoms. Another study showed that hormonal therapy improves depressive symptoms with a parallel decrease in pro-inflammatory biomarkers and increase of sex hormone levels. Thus, hormonal replacement therapy in peri-/postmenopausal women may be protective against depression through an anti-inflammatory action. The questions for the future One of the major findings of my systematic review is that… basically, we do not know much about the interaction between inflammation and sex hormones in affective disorders. We aim to study, and better understand, which patients with affective disorders would benefit from add-on hormonal therapies, with a view of targeting the immune system. In fact, if we can understand the underlying mechanisms associated with increased inflammatory levels or new ways to address these, we could reach a better understanding of new treatments or of the use of already existing compounds. For example, minocycline has been seen to be effective in those patients who do not respond to antidepressant treatment (defined as treatment-resistant depressed (TRD) patients) and who have higher inflammation in comparison with other TRD patients. We do not know if these effects are different in male and female TRD patients. Moreover, most of the studies did not analyse “female” sex hormones (such as estradiol) in male patients and “male” sex hormones (such as testosterone) in female patients. It would have been interesting to see the sex-crossed role of gonadal hormones and how they affect inflammatory response and depressive symptoms. We all have both sets of hormones, of course at different levels and with various effects, and it is another source of insufficient knowledge if we only measure female hormones in women and male hormones in men. All of these issues highlight the need to overcome the conceptual dualism of mind/body that has derailed the medical practice in the past decades, with the need to dig deep into the biological differences between males and females in order to detect new, tailored, therapeutic strategies that tap into these biological mechanisms. In conclusion, a better understanding of the modulating effect of sex hormones on the immune system will be a key point in prescribing hormonal add-on treatment for a sub-group of depressed patients with the aim of improving mood by regulating the immune system, with different interventions for men and women. If this will lead to an improvement in the mental health of people with affective disorders, then we will be finally out of the maze! Header Image Source: Victor Garcia on Unsplash

Beyond the Veil of a Male Phenomenon: Sex hormones & the immune system in suicide vulnerability Trigger warning: The following blog contains discussions about suicidal ideation and explicit descriptions of suicide itself. Some readers may find this distressing. “I used to think it utterly normal that I suffered from “suicidal ideation” on an almost daily basis. In other words, for as long as I can remember, the thought of ending my life came to me frequently and obsessively.” — Stephen Fry Losing someone to suicide can bring pervasive feelings of guilt, persistent questions about if anything could have helped them, and continuous scanning of their last days to understand the reasons behind their suicide. The feeling of helplessness can be disarming, and there are several support groups for the relatives and friends of suicide victims. Death by suicide is one of the leading causes of death worldwide, with more than 700,000 completed suicides every year (the World Health Organization (WHO)). Thus, early prevention is crucial for both sides, those at risk of suicide and those who remain. However, despite the high rates, this multi-stratified phenomenon is still taboo nowadays. There are a few definitions and degrees of ‘severity’ that you need to be familiar with before approaching this topic in the context of research. These are suicide itself (that is, “death caused by self-directed injurious behaviour with intent to die”), suicide attempt (“non-fatal, self-directed, potentially injurious behaviour with intent to die”), and suicidal ideation (“thinking about, considering, or planning suicide”). Suicide is such a delicate topic, and it can be viewed from different perspectives: personal, philosophical, political, cultural, psychological, and so on. In this blog, I will focus on my research, mainly exploring biological mechanisms and clinical aspects that are possibly relevant to increased suicide risk, which I recently described in my paper “New frontiers in suicide vulnerability: Immune system and sex hormones”. Approaching this topic from a biological perspective might feel quite dehumanising and detached, however, it might give us the possibility to unravel underlying factors which can increase suicidal vulnerability. I think it is essential to highlight new potential pathways in research that could help us identify those at high risk of suicide, detect new ways to help those who experience suicidal ideation, and perhaps even prevent suicide. I am a PhD student at King’s College London, and my main interest has always been the dialogue between biological and psychological aspects of mental health, especially major depressive disorder (MDD). I believe that the study of biological dynamics in psychiatric illnesses will help in creating a sex-specific medicine and tailored treatments to offer the best rehabilitation pathway for those patients in need. Suicidal ideation is one of the core symptoms of depression, and mood disorders such as MDD are the most common psychiatric conditions linked to suicide risk. Suicide has been linked with alterations in some of the brain areas involved in decision making, emotional regulation and behaviour control. However, some aspects of depression differ between sexes, so a priority in research is to detect and explore these dissimilarities. Even though women are at higher risk of both developing MDD and showing suicidal ideation than men, men are more likely to complete suicide. As a result, male sex has been identified as a suicide risk factor, along with previous suicide attempts and the degree of depressive symptoms (National Register Based analysis). Why does it happen? Can research help us understand increased rates of suicide among men? Immune system, sex hormones and suicide risk To understand why these biological factors are so important in depression and suicide, let’s look in more detail at this topic. The immune system plays a major role in some patients with depression. Briefly, patients with depression have increased levels of immune biomarkers (“a biomarker is a molecule, gene, or characteristic by which a particular pathological or physiological process, disease etc., can be identified.”) associated with increased immune system activity. Patients who do not respond to common antidepressants (i.e., treatment-resistant depression (TRD)) have even higher levels of these biomarkers than those who do respond, with TRD also being associated with increased suicide risk. As well as depression, increased inflammation seems to be a suicidal-specific biological trait. In fact, depressed patients who attempted suicide have increased inflammatory biomarkers than depressed patients without suicidal ideation. Furthermore, sex hormone levels are altered in patients with increased suicide risk. Increased androgen levels (e.g., testosterone) in both sexes and decreased estrogen levels in women are associated with increased rates of completed suicides and suicide attempts. Additionally, one of the possible immune-modulatory mechanisms might be played by sex hormones. In fact, estrogens can have both anti- and pro-inflammatory properties, whereas testosterone mainly has anti-inflammatory effects. Nevertheless, the balance between estrogen and testosterone might be important in regulating the immune system. Thus, an interplay between sex hormones and the immune system may be present in suicidal patients, and specifically in patients who attempted suicide. Some evidence suggests a possible role of these two systems in suicide. However, you are here to read about why these two systems may make suicide a “male phenomenon”, and why research should focus on them both. So, let’s continue. Where does the link between male sex and increased suicide risk lie? Violent methods of suicide show a link with increased inflammation, which is higher than in non-violent suicide attempts. Generally, men tend to use violent (and therefore more lethal) methods to complete suicide, while women tend to use non-violent methods. Other factors and sex differences must be considered when discussing suicide risk. For example, aggressive behaviour is linked to increased androgens, and impulsivity to increased inflammatory biomarkers. Interestingly, Mann and colleagues (2014) found an association between violent suicide attempts and both impulsivity and aggressive behaviour in men. However, we don’t have to fall into error and focus only on the biological aspects of suicide. In fact, there is more to reveal beyond the veil of this phenomenon. Clinical characteristics in males can help us understand further why men are at a higher risk of completing suicide. There is a need to increase awareness about sex differences in mood disorders and suicidal traits The time of intervention is crucial in these situations. However, it is not always possible to carry out rapid intervention, the chance of which dramatically decreases when the duration of the suicidal process (from the onset of the suicidal ideation to the act) is short. This suicidal process seems to be a male-specific risk factor, which is shorter in men than in women. Understandably, males with mood disorders can be more irritable, and importantly, they can have decreased impulse control. Furthermore, men tend to appear more hesitant than women in seeking help when they experience depression. Thus, there might be a delay in the diagnostic process, and the likelihood of therapeutic treatments is reduced. What can you do? I think there is an extreme need nowadays to learn and share as much information as possible about differences in clinical aspects of depression between men and women. Most of all, informing the public opinion about depression in men might help men to come forward, communicate their realities and thus, receive the support they need. Increased awareness may help us recognise when our loved ones need support, even if their presentation may not look like our typical understanding of depression. Consequently, this can enable us to help those in need feel understood and welcomed. The interaction between sex hormones, immune system, and behavioural aspects in males and females is worth investigating. However, although several studies investigate the interplay between these two biological systems, only a few focus on MDD and even fewer on suicidal patients. There are simple associations that are inadequate to reach causal conclusions, so more studies are needed to investigate the mechanisms behind suicide risk, particularly in men. The final aim of this research would be to offer new sex-specific therapeutic treatments and preventive strategies, and develop sex-sensitive services for patients who are at risk of suicide. “In the case of suicide, people think that no fight was involved they merely think that the person couldn’t take it and felt weak. They forget all the mental struggles the person faced because they were invisible and sometimes unspoken and unexposed to anyone. This attitude of society is wrong.” — Deeksha Arora If you are struggling and in need of support, below are a few incredibly helpful organisations that provide both resources and direct help: Shout Crisis Text Line — you can text Shout to 85258 if you are experiencing a personal crisis, are unable to cope and need support. Talk to the Samaritans — they offer 24-hour emotional support in full confidence. You can call them for free on 116 123 CALM (Campaign Against Living Miserably) offers a chat and hotlines service from 5pm to midnight Papyrus (Suicide Prevention Charity) offers similar service for adolescents and young adults under the age of 35 Mind — you can call the Mind Infoline on 0300 123 3393 / info@mind.org.uk, the Mind Legal Advice service on 0300 466 6463 / legal@mind.org.uk Talk to your GP

This is the third article of the brand-new series inspired by EU-PEARL (EUropean-Patient-cEntric clinicAl tRial pLatforms). The EU-PEARL project aims to shape the future of clinical trials, creating a framework for platform trials. I started my journey in psychiatric research a few years ago. My interest is understanding the biological aspects of psychiatric conditions. Thus, every alteration in the body that might be linked with abnormal mental functioning, both as a cause and a consequence. Here, I would like to share some thoughts on precision medicine and platform trials (which we have learned about in the previous articles in this series), and I wish to convey to you the importance of these two aspects in psychiatry. In psychiatry, we are dealing with complex disorders. It is therefore challenging to recognize the biological correlates of a disease, and to identify effective, tailored treatments to improve at best the well-being of patients. A clinical trial is an effective method to test how “good” a medication is for a certain disease, exploring new ways of treatment and prevention. However, it comes with a significant limitation. A clinical trial usually tests one drug at a time. This makes the process quite slow, and not very adaptive to new discoveries in terms of new potential treatments. The platform trial design can counteract this drawback as it can test various treatments at the same time. It is quite flexible in offering new medication under investigation to trial participants. However, this approach has not been used yet in psychiatry. I have recently joined the EUropean-Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project. It is a collaboration between different perspectives. For example, the pharmaceutical industry, research and clinical centres, and patient representatives. EU-PEARL aims to identify targeted treatments by innovating the clinical trial procedure. The EU-PEARL project focuses on four main disease areas among which is Major Depressive Disorder. The centrepiece of the project is to create a well-established network to develop an “integrated research platform” (IRP). To explain it a bit in detail, the IRP includes two types of study designs. A longitudinal natural history study (LNHS) and the aforementioned platform trial. An LNHS is an observational study. It simply observes what is happening to gather health data. This will help to explore the progression of a disease and to better identify effective treatments. This study combined with the platform trial will be a crucial pool of information to offer targeted treatments in a shorter period of time. “Why do we need targeted treatments and how can precision medicine come in to help?” The current state of medicine involves specific treatments for specific diagnoses. Yet, the matter is far more complex. The one-size-fits-all approach has several limitations. For example, we know that only a sub-group of patients with depression might show clinical improvement following antidepressant treatment. And we know that they have some particular clinical features which can help to develop better strategies for the clinical management of these individuals. Or again, a percentage of patients might exhibit different side effects than others, or even more severe. Thus, there is still the necessity to improve patient clinical care. The availability of tailored medications will help in enhancing the well-being of patients. A fundamental help in this process comes from precision medicine. But what is it? Precision medicine is an approach based on the core belief of patient centricity. The human genome project took the first step towards precision medicine around 20 years ago, by offering the possibility to improve clinical care based on genetic features (genes are information inherited from our parents which define our specific features). This has taken the research focus from the diagnosis to a patient’s individual characteristics. In fact, the primary concept of precision medicine is the study of individual variability (differences between patients) in “genes, environment, and lifestyle”. Individual variability is an integral part of the diagnosis and prevention processes in precision medicine. In other words, this approach puts the spotlight on individual differences to offer a targeted treatment reached after careful evaluation of patients’ characteristics. Oncological (cancer) research is an outstanding example of precision medicine and of the use of platform trials. Precision oncology identifies molecular profiles of a tumour. This research area produces specific treatments based on biological and molecular information. Thus, the analysis of biological samples (for instance, blood) helps in identifying specific markers. These markers could give information about who is more likely to respond to a specific treatment or which might be helpful in the assessment. It would be helpful to broaden this approach from the oncological field to other medical areas, such as psychiatry. This would improve screening procedures, diagnosis processes and prevention strategies. And the use of platform trials is highly valuable in speeding up the process. “So, what about precision medicine in psychiatry?” Adopting a precision approach in psychiatry would be a paradigm shift. A change of perspective. There have been relevant advances. Steps forward to get closer to precision psychiatry. A new perspective in psychiatry is the Research Domain Criteria (RDoC). This approach moves from a symptom-based diagnosis — what we routinely use in everyday conversations with a doctor — to a biological/genetic-based diagnosis. It will open new paths in the treatment of mental health conditions. And most of all, it will deepen the knowledge of psychological and biological alterations in psychiatric disorders. As the National Institute of Mental Health (NIHM) stated, RDoC’ s “goal is to foster new research approaches that will lead to better diagnosis, prevention, intervention, and cures” in mental health. Another step towards precision medicine in psychiatry is the detection of specific biomarkers (biological characteristics linked to biological and pathogenic processes, and that can be easily measured). For instance, inflammation is a mechanism that has recently drawn interest in psychiatry. As I explained in my previous blog, inflammation is an indication that the immune system (that is a defence line fighting infections and external intruders) in your body is over-activated. Inflammation has been studied in the context of depression, and in particular in treatment-resistant depression (TRD) (those patients who don’t respond to common antidepressants). In the MINocycline in DEPression (MINDEP) clinical trial, we investigated the efficacy of add-on minocycline treatment (an antibiotic that has also anti-inflammatory and antidepressant properties) in TRD patients. We found that only those patients with increased (above 3 mg/L) C-reactive protein (CRP), that is, a marker of inflammation, exhibit greater improvement in depressive symptoms, but not those patients with a CRP below that same cut-off. In simple terms, we identified a threshold that allows us to understand and possibly to predict which TRD patients best benefit from minocycline treatment alongside their antidepressant therapy. Per se, this is already an important discovery in the area of precision psychiatry. But, we wanted to take a further step in this direction. Thus, we decided to look at the role of sex in the same study (the MINDEP clinical trial). We detected sex-specific roles of inflammatory biomarkers in predicting treatment response. Our data found that CRP might be a relevant biomarker for female TRD patients, whereas interleukin (IL)-6 (that is another inflammatory biomarker) would be better for both sexes. These are just pilot data, but they well represent a model of how stratification of the population, biological data and sex differences can be leveraged towards a precision psychiatry. Psychiatry is a newbie in the field of precision medicine. However, psychiatric research and the mental health care system have started moving towards the development of specific patient-centric tailored care. This will contribute to better describing the phenotypes (observable features) of a specific diagnosis, and to better defining uncertain areas, such as the severity or duration cut-offs used in psychiatry to define a disorder. Moreover, it will help identify early markers (signs) of a disease and its risk factors. This approach side by side with the detection of specific biomarkers will be essential elements in precision psychiatry. The identification of specific biological profiles will speed up the diagnostic process and the identification of effective treatments in psychiatry. Precision medicine will guarantee improved prevention and clinical care. It will spare many patients from experiencing unwanted side effects, towards more precise and efficient therapeutic treatments. And it will bring improvement to all of those people who are not helped by our current therapeutic approaches.

Content warning: The following article contains language which some readers may find distressing. Reader discretion is advised. As with another one of my articles, on Francis Willis, the physician who took on the cases of monarchs George III of England and Mary I of Portugal, my subject for this piece is another historic healthcare provider with an even more infamous and challenging patient than two royals who nearly toppled over their own dynasties. Imagine, if you dare, being in charge of the care of a notorious, licentious writer whose idea of conducting research for his depraved novels is committing unspeakable sex crimes. François Simonet de Coulmier, otherwise known as the Abbé de Coulmier (1741-1818), had the twisted honour of treating Donatien Alphonse François de Sade, otherwise known as the Marquis de Sade (1740-1814). To save some time and space, they’ll be referred to from this point on as simply Sade and Coulmier, though there was nothing simple about either man. The two gentlemen in question couldn’t have been more of a mismatch. Coulmier hailed from a humble, middle-class Dijon background, while Sade — a titled marquis — was born straight into the French Parisian aristocracy. Coulmier was educated for the church, and eventually became a Catholic priest, while Sade devoted his life to the pursuit of church-forbidden pleasures (often at the expense of others). Coulmier was a staunch humanitarian who believed in people’s intrinsic goodness, while Sade was... Sade. The pair were brought together under one roof in 1803 when the French government decided France had had enough of Sadean scandals. Sade, at the age of sixty-three, was declared insane and placed under the jurisdiction of the Charenton Asylum in Charenton-Saint-Maurice (now Saint-Maurice, Val-de-Marne, France). Coulmier, at the time, was the institution’s head director, and Sade became his official charge, a daunting prospect for anyone, but most especially for a man of the cloth. Regardless, Coulmier was up for the challenge. His philosophy in running his asylum is (debatably) a kinder fate than Sade deserved. Coulmier’s psychotherapeutic methods were ground-breaking for Napoleonic France. Though the Revolution was over, there was a special Terror of its own hidden within the walls of "lunatic" asylums. Patients were treated more like animals than humans, and were rarely offered the opportunity for reformation. Coulmier subverted this standard regime by valuing creative expression and individuality. He encouraged his patients to occupy themselves with the arts and provided the materials they needed to channel their unused energies into something constructive. Under this overarching policy, his patient Sade was allowed an extraordinary privilege: he was given the space and resources to write his salacious stories, which Coulmier regarded as a safer alternative to Sade terrorizing real French women and men for sexual satisfaction. Even more extraordinarily, Sade was permitted to act as a director himself, penning and putting on plays with the other Charenton inmates. Brave theatregoers of the general public were allowed to enter the asylum to view these plays as part of the audience, for a fee. From an outsider’s perspective, it seems like an entirely practical arrangement. The inmates who participated in the production of Sade’s plays were kept busy, and the ones who didn’t had some entertainment to look forward to. Charenton as a whole benefitted, as the plays brought in much-needed extra income. And Sade himself was perhaps expelling some demons by being given permission to express himself in more harmless ways than what he was infamous for. However, Coulmier came under fire by both the medicinal community and the French government for his "too-humane" treatment of Sade and the other patients, leading to his eventual removal from the position of director by the ultraconservative and less forgiving Bourbon royal family, as soon as they came back into power. They wanted Sade under tighter reigns, so Coulmier's tenure came to an end. In the year 2000, director Philip Kaufman released the film Quills, a dramatisation of Sade’s final years at Charenton asylum in which Sade and Coulmier are played by Geoffrey Rush and Joaquin Phoenix, respectfully. The film exists as a base-breaker between those who adore it as a stand-alone work of art about Sade and those who remain more loyal to history than to cinema. The greatest critic of Quills, and its manhandling of Sade and Coulmier as characters, was the person Kaufman perhaps should have been trying his hardest to please. In 1999, Neil Schaeffer published his widely acclaimed The Marquis de Sade: A Life, which was used, very, very loosely, as the source material for Quills. Dates, events, and even the manner of Sade’s ultimate demise (no spoilers) were played around with by Kaufman like a directionless chef ignoring the instructions of a recipe book. Schaeffer was so outraged by this mismanagement of his research in the name of theatrics that he took a stand in an article in The Guardian shortly after the film’s release. “Perverting Sade,” Schaeffer calls his self-defence, and I admire him for his tenacity. As a historian myself, I feel obligated to take Schaeffer's side on the matter of his being entitled to justice for being unhappily associated with the film, and mistakenly credited as a writer-consultant. However, I’m torn. I’m a storyteller too, and I also understand what Kaufman was trying to do with his ingredients. It’s a complicated situation. It is known that Coulmier’s influence on Sade and the rest of the patients at Charenton was primarily positive, and that throughout his time as the asylum’s director, Coulmier remained a steady, reasonable, and reliable authority figure. Quills, however, reimagines Sade and Coulmier’s patient-therapist dynamic into a sinister game of wills, with the swashbuckling Sade’s predatory ways up against the vulnerable Coulmier’s crumbling moral high ground. It adds an element of contrived tension for the viewers. Who will win this dangerous game, the man wielding the devil’s pen, or the man clinging to his holy rosary, his grip slipping? In one scene, Sade attempts to seduce Coulmier and add the priest among his countless sexual conquests, and a tearful and reluctantly aroused Coulmier just barely resists him. And again, without spoilers, the ending of the film is considered by many to be the ultimate bastardisation of Coulmier’s legacy. According to Schaeffer, this portrayal of events is a gross misrepresentation — one can even go as far as to call it an insult — of the two men’s real relationship, which the historian maintains was the closest thing to a healthy bond Sade ever enjoyed in his seventy-four rampaging years. "Coulmier was perhaps the first true male friend Sade made in his life," Schaeffer insists. "And this may indicate that some improvement had taken place in his mental health. The movie sacrifices the truth of this relationship and of Coulmier's own fate to a surreal and didactic conclusion that has no connection with the truth". There is an argument here that Quills might have traded a fascinating chapter in Sade’s life, in which he might have flirted a bit with redemption, in favour of climatic melodrama. On the opposite end of the spectrum, there were the film critics who thoroughly enjoyed this racier take on history, preferring well-executed and entertaining inaccuracy over a more mundane reality. Perhaps not being a historian helps. Or not expecting a film about small successes in the history of mental health research. Roger Ebert in his approving review of Quills seemed to have appreciated the suspenseful subplot of Coulmier’s inevitable corruption by Sade, lightheartedly describing the scenario as the incongruity of the "young, handsome man forbidden by religion from pursuing fruits which fall into the hands of the scabrous old letch." Critic Chris Chang in his review takes a neutral stance, praising the actors’ performances while questioning its confusing messages. Chang in particular is critical of how the film depicted the rivalry between Coulmier and his critic/competitor Dr Royer-Collard (played by Michael Caine) who, to contrast Coulmier’s purity and goodness, is painted as a sadistic paedophile rapist who relishes torturing and exploiting his patients. Another Kauffman invention that strays far, far away from the truth. The real Dr Royer-Collard was thoroughly disgusted by Sade’s criminal record and reputation and assessed him as being fully in control of his decision-making, campaigning unsuccessfully to have Sade transported out of the asylum to a regular prison. This was precisely what the real Coulmier, who had developed a degree of affection for Sade, strove to avoid. For me, however, the Abbé de Coulmier is characterized in film, the real man represents a bright spot in what is otherwise a dark period in the history of mental health treatment. It’s a comfort to know that, like Francis Willis, there were carers in the eighteenth and nineteenth centuries who were actually trying, rather than just strapping their patients up in straight jackets, leaving them to wriggle around for hours in a cage, and calling it a day. Of course, Coulmier came nowhere close to "curing" Sade. Nothing stopped the Marquis’s heinous imagination or withheld him completely from his transgressions. But what Coulmier can take full credit for is his genuine attempt to foster a healthful environment at Charenton, which can be looked back upon as an early aspirational model for modern-day psychiatric institutions. Perhaps the next time the world encounters a Marquis de Sade, we’ll be better prepared. If you are interested in reading more about Sade, Coulmier, or Quills, see my list of resources below: Chang, C. (2000). [Review of QUILLS, by P. Kaufman]. Film Comment, 36(6), 73–74. Ebert, Roger (December 15, 2000). “Review of Quills.” RobertEbert.com. Perrottet, Tony (February 2015). "Who Was the Marquis de Sade?" Smithsonian Magazine. Quinlan, S. M. (2021). Medicine in the Boudoir: The Marquis de Sade and Medical Understanding after the Reign of Terror. In Morbid Undercurrents: Medical Subcultures in Postrevolutionary France (pp. 43–67). Cornell University Press. Schaeffer, Neil (1999). The Marquis de Sade: A Life. Knopf. Schaeffer, Neil (13 January 2001). "Perverting de Sade.” The Guardian.

Trigger warning: The following blog contains discussions about suicidal ideation and of suicide itself. Some readers may find this distressing. “Maybe we are not wired to ask for help.” From asking “When did you last cry?” to “What stops you from sharing your distress?”, this heartfelt confession from a guy friend left me speechless for a moment. “We have tear ducts too. It is just that instinctively they’re reserved for happy overwhelming moments.”, he added. Match wins, a long-awaited recognition, reunion with a long-lost beloved friend, a soulful music note that strums the heartstrings, holding your baby for the first time – what was your moment of happy tears? Mental health isn’t considered a gender-specific issue, but there is promising evidence to date – both experimental and anecdotal – where male-friendly approaches have been tried. Not enough attempts within mainstream services are done yet to design, deliver, and research gender-specific interventions for men in comparison with traditional approaches. It is important to comprehend that certain symptoms manifest differently in men than women. These men are our significant others, friends, fathers, brothers, sons, and people we care for. More than 6 million men suffer from depressive disorders and many remain undiagnosed; yet, they do not promptly seek help, irrespective of age, nationality, or ethnic or racial background. Possible reasons behind the reluctance to ask for help are the stigmas and the conditioning to internalise emotions. Statistics and Stigma We often associate sadness and hopelessness with depression. Men, more often, would be angry, aggressive or completely withdrawn with no interest in anything whilst undergoing depression, making it easier to misread the signs that something is wrong. Some men turn to drugs or alcohol as a coping mechanism. As per the WHO statistics, suicide rates for men are significantly higher in most countries. Male suicide methods are often more violent, making them more likely to be completed before anyone can intervene. I haven’t read a more apt explanation than David Wallace's: “The person in whom its invisible agony reaches a certain unendurable level will kill themselves the same way a trapped person will eventually jump from the window of a burning high-rise. It’s not desiring the fall; it’s terror of the flames. You’d have to have personally been trapped and felt flames to really understand a terror way beyond falling.” Research conducted by Mind in 2017 that consisted of 15,000 employees across 30 organisations showed that men are twice as likely to have mental health problems due to their job. In a survey done in the UK, 61% of men said they feel like they can’t discuss their mental health problems with their boss because they feel like their professional abilities would be questioned, their boss wouldn’t understand or their employer would judge them. Crisis Growing up between society’s expectations and stereotyped gender roles, it is considered a sign of weakness if men have emotional issues. Vulnerability is scary for all humans, and in particular for men. They are not supposed to show their fear; otherwise, how else would they be the main character who saves the world? Even though the boundaries of traditional gender roles seem to be blurring, research finds that it’s mostly a lip-service: “Yeah, yeah, we all go along with the whole touchy-feely 'men shouldn't be afraid to show their emotions' thing, but secretly when you see a man blubbing, you think 'wimp'!" This research is a decade old though. Has anything changed since then? Well, maybe if they cry in perceived masculine settings – a competitive sport, for example – then men are given a buffer from the negative consequences associated with violating gender stereotypes. When the war broke out between Ukraine and Russia a year ago, men between 18 and 60 years of age were not allowed to leave the country. Today, Ukraine is facing a mental health crisis among soldiers and civilians. Apart from anxiety, PTSD, and other war-related stress, some families are breaking up too. However, it doesn’t take a war to get mental health issues. A survey done in the UK revealed the biggest causes of mental health issues in men’s lives are work-related stress (32%), finances (31%) and their health (23%). Why would an ailment of the brain be treated less seriously than an illness of the heart? Self-Disclosure “Nobody believed me because I was a boy” – one of my close friends suffered sexual abuse at his home as a kid. Nobody believed him when he tried to tell how a close female relative was the perpetrator. Decades later, he still suffers from post-traumatic stress disorder (PTSD) and insomnia. However, that is veiled quite remarkably behind layers of his devil-may-care personality. “I stopped looking in mirrors and rage consumed me.” – another friend who recovered from a life-threatening illness. He lost a lot of weight and developed skin allergies. He couldn’t fathom how depression was expressing itself outwardly in the form of anger towards himself and others. Thankfully, counselling sessions and medications have helped him, to a large extent. There are many such real-life experiences that remind us that matters like body dysmorphia, body-image issues, intimate partner violence, and trauma inflicted by sexual violence also affect men. To some, it can be embarrassing to discuss the trauma because of the stigma in society. Being ostracised would only add to the misery so it's no wonder why the majority of men chose silence and self-repair over all the other seldom available sensitive alternatives. Suffering in silence isn’t a healthy option for the men in our lives. Required Measures Psychiatrists are using tailored approaches and interventions and not just talking therapies when it comes to treating men with mental health concerns. More research is needed but there are helpful resources available; for instance, a BPS research paper shares guidelines on psychological interventions to help male adults. Recent preliminary analyses of individual male-tailored mental health programs show promising results for the treatment of depressed men. Movements like Movember across the world help to raise awareness on the issues of men’s health. Get involved in awareness initiatives. Leaders at workplaces can take the baton of change by framing conversations that resonate with their male colleagues encouraging them to share their emotions around work challenges. Mental wellbeing should not just be a tokenism. Perhaps, offer confidential mental health counsellors as an added benefit instead of one-sided sessions. If a man in your life is undergoing mental health issues and is not willing to get professional treatment, maybe begin with getting help on their physical symptoms like exhaustion or ongoing headaches and alert the doctor about the mental health signs you notice. Offer a listening ear, support, patience and encouragement to open up. If you are struggling, reach out for help to mental health professionals, support groups, and helplines – wherever your comfort lies. Medications, psychotherapy, and counselling work. Dear Men… …if you feel exhausted and bullied by the constant misandry (and misogyny) of ‘man up’, please know that the issue isn’t your emotional ability. If the fear of being left out from the 'man's world' stops you from searching for answers, then know that the issue is with the misinterpretation of masculinity by most men around you and not your manliness. There are many safe spaces out there where you can and you should reach out. Rough patches hit all of us without discrimination. Seeking help, and showing emotions in public won’t make you anything else but human. And to be human in this world isn’t less of a feat. Wouldn’t you reach out for help when you fracture your leg? How is the brain splinter any less of a concern? Even when nothing is broken, you take care of your physical health. Include mental wellbeing too. Next time you see a little boy in distress, comfort him. Repeat for big boys too. May we see the world with nothing else but the lens of compassion! If you are struggling and in need of support, below are a few incredibly helpful organisations that provide both resources and direct help: Shout Crisis Text Line — you can text Shout to 85258 if you are experiencing a personal crisis, are unable to cope and need support. Talk to the Samaritans — they offer 24-hour emotional support in full confidence. You can call them for free on 116 123 CALM (Campaign Against Living Miserably) offers a chat and hotlines service from 5pm to midnight Papyrus (Suicide Prevention Charity) offers similar service for adolescents and young adults under the age of 35 Mind — you can call the Mind Infoline on 0300 123 3393 / info@mind.org.uk, the Mind Legal Advice service on 0300 466 6463 / legal@mind.org.uk Talk to your GP

I have broached the issue of climate anxiety previously and was inspired by the advice that one way of addressing our fears and despair is to take action. But what does taking action mean, other than separating our recycling and asking for takeaway coffee to be poured into our own reusable cups? I spoke to Abigail Woodman and Nathan Miller, Chair and Trustee of the East London Waterworks Park project, about how they are taking action to create a better world. I learnt that joining others with shared values in a grassroots community project can also fight despair, build resilience, and inspire hope. Celebrating a milestone East London Waterworks Park is celebrating a milestone. The project has raised over half a million pounds via their Crowdfunder campaign, to transform an industrial site in East London into a community-owned natural oasis and rainwater-fed swimming ponds. This represents a significant step on the journey towards purchasing the land and creating a new bio-diverse community space. It’s not hard to imagine the benefits for the community. Spending time in nature is good for us. Open-water swimming is beneficial for our mental health. But the unhealthy reality is that rivers such as the Lea River in East London, which swimmers flock to in hot weather, are polluted with raw sewage, carrying risks of disease. The mere image of an inclusive, free space for people to meet, spend time in nature, and bathe in clean rainwater ponds is soothing, and the concept of green therapy runs through it. Nature’s needs and people’s needs will be given equal priority in this microcosmic brave new world. It is clear that the end result will be of value and support the physical and mental health of the community. However, as I listen to Abigail and Nathan, it transpires that the journey towards this goal is an awe-inspiring tale of community empowerment and collaboration. From activism to world-building The project originated with a campaign to oppose a planning application for an ex-Thames Water depot site on metropolitan open land — which should be protected from development unless in very special circumstances. Having successfully blocked the development application, Abigail and others from the Campaign for Protection of Rural England London and Save Lea Marshes decided to shift towards creating a positive campaign. In 2019, a public meeting was held to ask the community, "If we could do anything we wanted, what would we want?". Abigail explains that this visionary, blue-sky thinking approach has become part of the essence of the project, and has attracted new people. "Everything we have done with this project has been asking what would we like to do first, and how do we do it second. And that’s how we’ve created something quite unique and special". As the group grew from a few people sitting in a pub to a project entirely made up of 174 volunteers, they adopted a system of governance called sociocracy, which suits organisations that want to self-govern with the values of equality. “We are all volunteers and it’s quite decentralised. People have working groups, and each working group has an area of responsibility and is empowered to make decisions in that area. Anyone can get involved at any level.” World-building, solar punk, and civic imagination Nathan Miller tells me about the concept of world-building, or "creating an imagined world", which he has brought to the project. World-building originated in the writing of fiction, with authors such as J.R.R. Tolkien describing the importance of creating an "inner consistency of reality" to make their stories believable. Now, the concept is crossing over into our world, and it can be good for our well-being as well as our creative thinking. Civic imagination involves imagining what a better world might look like, and seeing yourself as an agent for change. An example of this is Solarpunk, a hopeful movement that has sprung from the sci-fi genre and imagines equitable worlds with a sustainable future. For Nathan, this crossover brings his interest in sci-fi together with a call to action that reduces eco-anxiety. "East London Waterworks Park is a Solarpunk project in many ways. We are developing a vision for humans and nature coexisting in what is currently a fenced-in concrete-covered depot. This vision and the associated art has drawn people in, who volunteer to help build it with us. We used to think that 'the right volunteers just happened to arrive at the right time' when what has actually been happening is more a reciprocal process of worldbuilding the nature-connected world we want to live in, and aligned people joining us to help build out that vision". I can see how this open-minded and creative approach liberates people to contribute and dare to create their own vision of the future. Abigail imagines that the initial dream has become an "organic being" that evolves and grows over time, with the people that get involved and doesn’t belong to anyone. The idea has a power and life of its own, and a feeling of serendipity runs through the project. Abigail shares her vision with me: "What we want to do at its very highest level is create the world we want to live in. We want to create a new, biodiverse park, where nature is put first — which it isn’t in most decision-making scenarios. We want to show that the community is able to manage land and organise itself, and to reintegrate ourselves with nature, ourselves with land, ourselves with each other". Building agency, connection and resilience Just as Nathan found that building a better world was beneficial for addressing his own eco-anxiety, many have found that getting involved brings a sense of agency and hope, as well as opportunities for socialisation and connection. This is a stimulating, hopeful project, open to anyone anywhere. By helping to create a better world, we can help ourselves and each other. Abigail is convinced that involvement in the project is an antidote to loneliness, despair, and climate anxiety. "This is a way to say, 'I am doing something. And I am doing something substantial. And I am working with other people'. Knowing there are like-minded people out there and you can work together to create something helps. Hope is an incredibly powerful thing". She and other key volunteers like Nathan are working phenomenally hard on this project, usually fitting it around substantial day jobs. I ask Abigail how she has been able to persevere, and she explains that the process has been overwhelming at times but embodies and teaches resilience. "Sometimes, with any project, you just don’t know what to do, and just face an impenetrable brick wall. I see it like you get your little hammer, and you just start chipping away at the wall. And if you can keep chipping, the wall will collapse. And it does collapse, it always does, but you just have to keep chipping away".

Each year, on the 20th of June, the world honours everyone who was forced to flee their home country to escape conflict, climate, or persecution. This day is also one to celebrate their strengths and courage. My name is Lea Schmid. I am the deputy editor and dissemination coordinator at Inspire the Mind. I lived in Germany during the time it hosted and processed 1,404,550 Syrian and Afghan asylum seekers (2015-2017), making it the biggest host country for refugees in Europe. Living in Munich during that time, made it clear that the world was shifting, and people needed help. In 2015, I decided to get involved in the little ways I knew how. I started collecting sanitary items and cleaning supplies, and would go to temporary refugee centres to deliver these mere essentials. I was so dismayed by their living situation, and yet in such awe of their courage, that at 17 I wrote my final International Baccalaureate Extended Essay, an independent, self-directed piece of research, finishing with a 4,000-word paper, on the hardships they faced and the injustices of the system. Today, almost 8 years later, over half of them have found a job, and public support for immigration remains high. Still, as highlighted by Seku Keita and Helen Dempster, integration challenges continue to remain. Refugees typically work in lower-paid and more hazardous roles, which led them to be hit even harder by the COVID-19 pandemic. Germany, like many other host countries, still needs to introduce and enforce policies that target specific barriers to full labor and market integration such as staff training, certification of existing skills and diplomas. However, it is important to also consider that low-and-middle income countries, which have commendably hosted large numbers of refugees in the past years, still need a lot more assistance to provide sustainable, long-term homes. Almost seven million Ukrainians are sheltering in nearby countries and in 2022, hundreds of thousands of new Afghan refugees arrived in Pakistan following the government collapse, similar to the millions of Venezuelans that have been dispatched throughout the South American region. The World Bank has taken, and continuously will take, steps to provide more financial support and document the numbers in detail, but for some host countries, where policies, practices and regulations differ, it can be especially hard for the public to welcome immense numbers of asylum-seekers. Public Opinion and its Influence In Germany, I made connections, started to understand their struggles, and had the chance to gain some insight into their ways of living, before they inevitably had to leave their countries behind. I made friends with two individuals and the more I got to know them, the more I realised how truly difficult of a situation it is. Having to learn an entirely new language, having to fully immerse themselves into a different culture and secure opportunities for their future, lead to immense challenges and highlighted the true mental struggle of such a huge step into a hopeful future. When looking specifically at German public opinion, Germany has maintained high levels of support towards refugees. Initially, in 2015 a Polibarometer poll found that 66% felt that allowing large numbers of people to flow into the country was the right thing to do. This same survey consistently found that Germans felt they could cope with these flows (see graph below). Some 5 years later, in 2020, following the Moria refugee-camp fire in Greece and during the height of the pandemic, there was still widespread support for a more welcoming refugee policy, with only 9% being fully opposed to welcoming more asylum seekers. Mental Health after Fleeing According to the Mental Health Foundation , asylum seekers and refugees are more likely to experience poor mental health compared to the local population, including higher rates of depression, PTSD, and other anxiety disorders. The increased vulnerability to mental health problems is often linked to pre-migration experiences such as war trauma, and post-migration conditions, such as separation from family, difficulties with asylum procedures and poor housing. All displaced people experience the loss, in some form, of their social structures, cultural values and community rituals. However, it is important to remember that displaced people have varying countries of origin, cultures, levels of education, knowledge of English and levels of support available to them. Among these are also children (especially unaccompanied minors and those under 5), women (especially those pregnant and breastfeeding), elderly, disabled and LGBTQ+ people, who are at particular risk of developing mental illness. Research suggests that asylum seekers are five times more likely to have mental health needs than the general population, and more than 61% will experience severe mental distress. However, data shows that they are less likely to receive support than the general population. I found this to be especially striking during my visits. Often parents and children were separated and there was a clear divide between who would be offered the most help. People with less severe mental health conditions were prioritised. They were supported, counselled and given more opportunities than others, making integration into society even harder for those with poorer mental health. Future Challenges Despite the progress, I believe we still have a long way to go. It’s a tale of two trends. For millions of refugees and displaced people around this world, some things are continuously improving – such as laws enabling them to work, move and access services. But some things are getting worse – such as their opportunities for resettlement and asylum. Overall, refugee experiences and their stories allow us to not only shape and enhance our understanding of their hardships, but also allow us to analyse other socio-economic factors such as migration, displacement, and racism, to incentivise global decision makers to improve the lives of the millions of displaced people across our globe. Today, on June 20th, the world honours everyone who has had to flee and celebrates their strengths and courage. Support United Nations High Commissioner for Refugees: https://www.unhcr.org/uk/supporting-refugees-uk European Refugee Support: https://www.refugeesupporteu.com/ Psychological First Aid: https://www.rcpsych.ac.uk/international/humanitarian-resources/asylum-seeker-and-refugee-mental-health

It is easy to walk past homeless people and ignore them, convincing ourselves they are responsible for their own demise. Post-pandemic, with an increasing cost of living, rising rent prices and withdrawal of emergency measures, homelessness is on the rise. In 2022, 3,069 people were recorded as sleeping rough, on a single night in the UK. Yet, an often-overlooked factor in homelessness is the prevalence of mental health problems. In a 2014 study by the World Health Organisation, 80% of homeless people reported mental health issues. Richard's Sign The relationship between mental health and homelessness is two-way: mental health problems often precipitate homelessness, and homelessness further exacerbates mental health issues. As some of society’s most socially isolated individuals, loneliness can drastically impact homeless people’s mental health. By hearing their stories and giving them a voice, we can extend a hand, bringing them back from the fringes of society. And so, I want to introduce you to Richard. I first met Richard outside my local train station. As a woman and psychiatric researcher, I am often torn between personal safety and a desire to help when walking past a homeless person. However, the humanity of Richard's sign touched me, and I doubled back, asking if I could sit down for a chat. Richard told me that he is a keen reader and a lover of art, particularly favouring Gustav Klimt. He has liberal attitudes and a deep concern for the environment, he is a sports fan and a great dancer. But walking by, one may not give a second thought to the anonymous person behind the homelessness, nor the factors that led to it. Richard describes how in 1977, at age 12, he was taken aside by a concerned teacher who noticed his “bruises, broken arm, wrist and cheekbone that had been fractured in four places". Richard revealed his father had inflicted these injuries: "when he [the teacher] asked, I just told him". In 1973 Richard’s older brother died in car accident. Inexplicably, his father directed his grief at Richard. The logic behind this cruel treatment is something that mystifies Richard. "It’s something I have never understood", he tells me. Richard was placed in a children’s home. But, subject to intense bullying, he was miserable. He made repeated attempts to run away and was eventually moved to a remand house where the staff (he called them "ruthless") did not discriminate between young offenders and vulnerable children. According to Richard, "They tarred you all with the same brush", employing brutal tactics; "If you cried, they would hit you. If you didn't eat your food, they would hit you. They would condition you to their way of thinking, with continuous threats of violence". Thankfully, Richard had a brilliant care worker advocating for him, and in 1979 he was placed into a third children’s home. Here, the staff acted as his “new mothers and fathers”, empowering him to pursue his aspirations. He attended college, gaining his City and Guilds culinary qualification. This was also where he met his future partner Laura, who had also suffered terrible abuse from her father, becoming pregnant and enduring an abortion before age 13. Richard describes being “drawn” to Laura and their friendship eventually "grew into love". They moved in together at age 18. Richard continued to progress in his career, becoming a head chef and even went back to university, achieving a 2:1 in Psychology. Richard is utterly devoted to Laura, and he describes her as, “the love of my life”. Their “beautiful” relationship was one built on “trust, honesty, respect and love” and he says that they truly were “best friends”. But, on 12th February 2018, Laura suffered a sudden brain haemorrhage which caused a massive stroke. Tragically, she did not recover. Reeling from the shock of Laura’s death, Richard was left “confused”, “angry” and “totally heartbroken”. His “rock of 39 years” was gone. Richard describes how this affected him: “The pain of losing Laura seemed to increase day on day. I started to drink alcohol to blot out these feelings…but they were back in the morning. So, the cycle of alcohol dependency began. It totally consumed me". Richard explains that, "over the next two years or so I fell into a dark and deep alcoholic abyss. I lost my job, my home, and my respect for myself”. Thus, in 2020, having spent all his savings, Richard was left homeless. With no family to turn to he had no choice but to live on the street, where he continued to drink. In 2021, after 8 months, one couple who had been good friends with Laura, came to see him. They handed Richard £250 saying, “You can do one of two things: go and get drunk or use this money to seek help. Laura would not want you to do this to yourself". This was the push Richard needed. With the help of his GP, he started rehab, determined to quit drinking. He says, "I had enjoyed 39 happy years with Laura, and knew she wouldn’t want me to have another 39 unhappy years without her". Within 28 days Richard left rehab sober. He was subsequently offered social housing. But when he went to view it, the living room was littered with “empty beer cans, plastic cider bottles, empty spirit bottles". Richard was "gobsmacked". Certain that he had a better chance of remaining sober on the street, he handed back the keys. Having refused the accommodation, he was taken off the housing register and was only recently reinstated. Since becoming homeless Richard has faced further abuse. He has been urinated on whilst sleeping, dragged down the road in his sleeping bag, had three teeth kicked out, his hand stamped on and been "spat at, shouted at and told to 'get out of the area'". These attacks have been by strangers, typically at night when he is at his most vulnerable, 'cocooned in a sleeping bag'. These attacks make Richard fear people, isolating him. Richard’s mental health has also deteriorated, largely due to loneliness. Having to remain vigilant, with constant noise disruptions, he only sleeps between 12am and 5am. The other 19hrs of each day he spends alone. It is this loneliness that led Richard to put up his sign. When I asked Richard what he thinks passers-by can do to help the homeless, he suggested simply offering a smile, a “good morning” and stopping for a chat. Richard radiates positivity and warmth. Astonishingly, despite the lifelong abuse, neglect and stigma Richard has faced, he chooses to focus on the people who have advocated for and supported him. He is a beacon of hope and humanity. I am thrilled to finish this article with the news that Richard's hope paid off. On 8th June 2023, Richard was offered suitable housing in a quiet and comfortable estate. He plans to reconnect with his colleagues in the restaurant industry and is determined to return to work by the end of August. It shouldn’t have to take a sign to remind us that there is a person behind each nameless face. Offering social connection is free and the least we can do to try to help combat the loneliness of our unhoused neighbours. After all, as Richard says: “its good to talk”.

A psychiatrist’s view on how leaders should act as therapists to bring people together. This can truly be called an age of rage; everyone seems to be angry with one thing or the other. Following the outrageous behaviour of members of the House of Commons after the proroguing of parliament was declared unlawful by the supreme court, the behaviour of our leaders and representatives in the House was utterly shameful and disgraceful. British parliament had always prided itself being less partisan and more respectful towards each other. The leaders one would have liked to follow seem to be disappearing and instead, waves of abusive rage are surging. What would the next generation make of the current crop of leaders across the globe? Is the rage to do with the political situation? Economic or social discrimination? Or, is this something cyclical? In the USA, although, the differences between the two main political parties have always been obvious and strong, these have become even deeper and more pronounced. The UK, on the other hand, has always prided itself on having a reasonable level of civilised discourse, especially across the political divide. Whatever the rights or wrongs of the referendum to stay or leave the EU, it has been done. The past three years have been strange times living in the UK. The day after the referendum, for the first time, I felt worried about my safety in public. I have had racist experiences from patients and from colleagues at work many times, but this was a different feeling. Looking as an insider/outsider in the country which I have considered home for 40 years, it felt as if I do not recognise it anymore. The tribalism and the rigidity of opinions held by leaders and individuals have been truly astonishing. In common with the American experience, something that had been hidden was now unleashed and people felt that they could say whatever they wanted. However, the deep divisions that existed came to the surface and the feeling is that it is acceptable to be rude to people especially if you do not agree with their political views. The role of leaders to act as therapists to bring the warring couple together seems a distant dream. To my mind, this rage and division between the leavers and remainers can be seen as a discordant couple or family. Having worked with couples and families over the years, has the time now come to look at how these warring couples can be united for the sake of their children who are not only suffering now, but are likely to do so for generations to come? Furthermore, the parents need to stop squabbling and work towards better living together, as both parties have to live together whilst respecting each other’s view-points. However, a divorce, even if amicable, is not possible under these circumstances. Neither half of the population is likely to move out of the country, and the rage is making stress levels and strain palpable. Buried within this rage is a moral distress, where both sides perhaps want to do the right thing but are so stuck in their position that they cannot move or shift at all. Like warring couples, they still have to tolerate each other and live alongside one another in a mutually respectful and civil way. How does one resolve this situation where two individuals have to re-learn to live with each other having come close to separation which is theoretically not possible? Family and couple work teaches us to use a systems approach, which indicates that changes in one part of the system affect other aspects of the system. The rage has meant that people are losing control of their actions, and social and mainstream media seem to be feeding into this situation creating further tensions and stress. Thus, inevitable self-esteem and self-worth are affected, and individuals lose a sense of mastery of their actions and their inter-personal and communication skills are strongly and strangely influenced. In general, family and couples therapy looks at the individual context, suggesting suitable compromises while scrutinising the relationship between behaviour and environment between the patient and therapist; in this case, population and putative leader. Change and homeostasis become interchangeable forces within the system which may well protect the family from stressors and not exacerbate these. In this case, the country needs reconciliation and a healer leader who can bring the warring factions together, and not provoke further rage. Individual behaviour has to be understood within its relational and systems context. In a couple, at various times one individual holds the power, whereas the other individual does so at other times. It would appear that those who had previously felt powerless have grabbed the power from the establishment and are not likely to give it up readily. An interesting observation is that people who are saluting the people power are as ‘establishment’ as they come! In any family, if an individual acts out, there is a safe assumption that such behaviour is reflecting something else which may be obvious, or hidden, and may well be part of a larger drama with two parts affecting and influencing each other. Families or couples should be seen as a living open system composed of individuals connected in specific ways that mutually affect each other. Rules in family and couple relationships are both explicit and implicit. Explicit rules come into play early and clearly, but implicit rules can be observed in action — these emerge over time and are content specific for each family. In this age of rage, these rules are about Brexit and as they are implicit, neither side clearly knows what it means and thus, they can be interpreted in any which way. The family tensions were under the surface and the referendum brought these to surface. For the first time, the spouse who had felt hard done by but managed to hold on to their rage, has found it acceptable to let out this rage. The message from one half of the couple to the other was to say was that you have not been listening and political masters unleashed the rage with a vengeance. One half of the population is saying clearly to the other half: “you do not understand me and if you really loved me you will know how I feel’. The other half thus looks and behaves in a bewildered way — almost saying: “you know that I love you and if you loved me you would know that, I should not have to say it.” So, the bridging between the two is a task for a couples therapist — in this case, a visionary leader who can bring the two warring factions together, making sure that it is a win-win for both — but where are the therapists when you need them? It is possible to reach a level of reconciliation especially if both sides feel heard and listened to and appropriate compromises are suggested and carried out. The tone of political discourse especially with the use of social media is belligerent, loud and noisy, in that neither side is actually listening and has certainly taken a turn for the worset in the past few days. As in therapy, perhaps the first step will be to encourage communication in a civilised discourse — face to face rather than through social media — with a moderator or mediator. As the letter from the Bishops promotes. Boundaries in the families are both interpersonal and intergenerational with a continuum of permeability and these have rules which determine who participates in which situation and how. The rage that disengaged families feel and relate to a particular time or event needs to be clearly acknowledged and attempts made to mitigate these. Looking inwards and at each other with introjection of the rage is not a pragmatic way forward. A visionary leader who can mollify and reconcile warring factions is the need of the hour. What is needed is an outward looking approach, ascertaining positives and common ground upon which both parties can work in the context of building for next generations. It has to be recognised that the current disruption is not likely to be healed rapidly and may well last for a generation or two, and so the challenge to warring parents is how to protect and nurture the younger members of the society. Therapists, in the shape of leaders who can heal rather than divide, can provide maps or blueprints and needs to be both challenging and accommodating. No one is in listening mode, especially the leaders, so perhaps the first step may well be to bring together a group of leaders from a spectrum of views with clear instructions to listen, first and foremost. Perhaps a time-out may be needed to dampen the rage so that clear dialogue can begin. NOTE FROM THE EDITORS: We are honoured to have Professor Dinesh Bhugra, CBE, writing for InSPIre the Mind. Dinesh is an Emeritus Professor of Mental Health and Cultural Diversity at the Institute of Psychiatry, Psychology and Neuroscience at King’s College London, and an Honorary Consultant Psychiatrist at South London and Maudsley NHS Trust. Thank you, Dinesh for sharing your thoughts, expertise, and experience of BREXIT with us and our readers! HEADER IMAGE SOURCE TELETRAC NAVMAN

Medicine has been described as the second oldest profession: from caring to curing and prevention, doctors and medicine have played a major role in the lives of nations. But it is clear that in many countries, including the richest country on the planet, healthcare systems appear to be struggling. Covid-19 has been creating havoc around the globe and different national governments have responded in different ways . However, the mantra in the UK “Stay at home-Save the NHS and Save lives” is of interest. Saving the NHS is primary to saving lives. Every Thursday evening people show their appreciation by clapping for two minutes exactly at 8 pm. NHS is seemingly back in fashion but how long will it last we do not know — both Covid-19 and the NHS! History of establishing National Health Service is well known so will not repeat it. Suffice it to say that as a result of war, deprivation and poverty, it was the step that contributed to people living longer and it is not unfair to say that it has been a victim of its own success. NHS has carried on in almost the same way over the past 72 years in spite of societal changes, although structural reforms from both sides of the political divide have been a regular occurrence. Some of these reforms have been successful whereas others have decimated morale. So, what lessons can Covid-19 teach us? Were we to start from scratch and were establishing NHS today, will we do it the same way? There is no doubt that NHS is a success story and envy of the world, and we can learn and convey about primary and secondary care — but social care and public health need improvement. Repeated reforms and poor resources be they financial or human have led to healthcare professionals struggling to meet ever rising demands and expectations. With Covid-19 putting pressure on the NHS, is it any wonder that mantra from the government is to save the NHS. In recent times repeated studies have shown that the morale among NHS staff has been low which in turn has contributed to totally unacceptable levels of burnout and common mental disorders with high rates of alcohol and drug use among healthcare professionals. Disproportionate numbers of deaths of BAME doctors and nursing staff following exposure to Covid-19 adds another dimension. Societal changes, social media, changing patient expectations mean that stakeholders need to get together to explore what the Medicine’s Social contract is: when patients demand treatments as their right, which is fair and expected, they also need to recognise their responsibilities. The Social Contract is implicit and exists between medicine and patients and public, between medicine and government, and finally between government and public including patients. Once the Covid-19 pandemic is over, it is a critical time to explore with the stakeholders how such a contract can be reviewed and renewed by clearly exploring each group’s expectations of the others; how healthcare is funded and how it is designed, developed and delivered and then utilised. Right to free healthcare must come with responsibilities be they personal, familial or community based. Employers and regulators have a responsibility and a financial stake in ensuring that doctors are trained appropriately and keep up-to-date with advances in knowledge, new technologies and learning new skills. The government needs to revitalize the social contract with doctors by ensuring that they are listened to when informing the government policy, which is often made without any scientific evidence as is apparent in managing the Covid-19 pandemic. Doctors lack time with their patients which means the contract between them is also at risk especially in the face of changing public expectations, and that too when patients want to be a key part of the decision making process. There are three key inter-locking components in this social contract and each group has its own imperatives and expectations from each other. These three groups are: the government, represented by the employers, regulators and health care managers; patients, their families, their informal carers and the public; and finally the medical profession and its professional bodies as well as formal carers. This tri-partite contract is implicit but it needs periodic discussion and re-evaluation from time to time especially as society, societal expectations and more have changed over the past few decades. Social contract between medicine and society is of critical importance for a number of reasons. Doctors need to know what is expected of them by the patients and the government who are acting on behalf of the population. Patients need to know their responsibilities as well as their rights. And the government needs to be honest in helping identify what is needed to deliver what services. The role of the doctor in social contract: The key role of the doctor is to improve the health of individuals, extend life and improve the health of the community through a number of resources which need appropriate and adequate funding. If Covid-19 has shown us something it is that the tripartite relationship is the key to managing pandemics. The idea of doctors as healers has been lost possibly (hopefully temporarily) due to rapid advancements of science and technological innovations in medicine but also an increase in professional regulation and poor managerialism. The social determinants of health have as great an impact on health and healthcare as medical interventions do. Thus, doctors need to advocate more and speak on behalf of their patients. They need respect and suitable renumeration and acknowledgement. The role of the government: A major element of government’s responsibility under the social contract is to ensure adequate funding and resources for health services, so patients get the care they need when they need it, and doctors can do their jobs properly. The government has a responsibility to improve the health and wellbeing of the nation by using a number of means. This is the key component of the contract where a major role of the government is to ensure that population are looked after as is evident from the current state of affairs with Covid-19. The role of the patients: In the social contract patients too have a major role to play. Their expectations need to be manged but with their expectations come responsibilities in ensuring their wellbeing. Accessibility and availability of services require clear need not demand so their expectations of doctors and of the government need to be identified and managed carefully. A full, frank and transparent discussion and agreement is needed about what doctors and the NHS can and cannot provide. A major aspect has to be about funding-how it is provided and who provides it. Looking to the future 1. There has to be openness and clarity about what the NHS, and doctors, can and cannot deliver, and what patients and doctors expect of each other. Digital and e-health need to be assessed carefully to ensure that they are being used appropriately with clear ethical and moral imperatives. The government needs to move away from short-term objectives and take a more evidence-based approach to public policy. 2. The public should influence the government so that it upholds its part of the contract with adequate funding and resources, but there has to be honest debate about costs and actual resources rather than opaque hints. There needs to be an equity between physical and mental health and to look after the health and wellbeing of doctors and medical students among other health professionals so that they can look after the patients. 3. The medical students in these extraordinary circumstances have been thrown into the frontline and need a public acknowledgement and within any social contract, student healthcare professionals need to be looked after and their views into training and education taken into account by the government who need to prioritise the health and wellbeing of doctors. If you would like to read more about social contract you may find the following texts of interest: Williams DL(2014):Rousseau’s Social Contract: an introduction. Cambridge: CUP Bhugra (2013): Psychiatry’s Social contract. London: Mental Health Foundation Bhugra D, Malik A, Ikkos G (2011): Psychiatry’s contract with society, Oxford: OUP BMA(2019): Medicine’s Social Contract: report. London: BMA https://www.pelhammedicalgroup.nhs.uk/