This is Going to Hurt — But Shouldn’t Have to: An interview with Dr Ally Jaffee Trigger warning: This blog contains discussions of mental health struggles and suicidal thoughts. I am a postdoctoral researcher on arts and health and a writer for Inspire the Mind. Last year, I interviewed Dr Simon Ruffell on Ayahuasca, magic mushrooms and psychiatry. I now bring you the voice of another inspiring junior doctor, Dr Ally Jaffee, to discuss the controversial BBC show, “This is Going to Hurt”. The show has been criticised for triggering childbirth scenes and misogyny, although the lead female actor has rejected this criticism; it has also been applauded for highlighting the portrayal of the dedication and burnout of NHS staff. Dr Ally Jaffee (@drallyjaffee on all socials) is an NHS Junior doctor passionate about mental health and its intersecting fields — particularly the arts & nutrition. She is a mental health advocate and a champion for “You Okay Doc?”, the mental health and wellbeing charity for doctors. Ally is a Diana Award recipient (an award for 9–25-year-olds for social action or humanitarian work) and co-founder of Nutritank (a think tank and educational hub for nutrition). In this interview, we discuss “This Is Going To Hurt’”, her experience as a junior doctor in the NHS and her mental health journey. *Spoiler alert: this blog discloses details on the BBC show This Is Going to Hurt.* You have spoken before on the media about “This is Going to Hurt”, the book and now show by Adam Kay. For the readers that may not have watched this show, essentially it portrays Shruti, a junior doctor in Obstetrics and Gynaecology, and Adam the senior registrar doctor who is supervising her. Alongside her training, Shruti is studying for the Royal College of Obstetricians and Gynaecologists membership exams, while being apart from her family and being very lonely. Once you watch it, you can’t unsee certain things, and I’m not talking about the graphic obstetric scenes, I’m talking about the fluctuations in mental health in Adam and Shruti’s characters, like the flashbacks that Adam gets from the emergency C-section he performed on a young woman that he earlier had discharged home, or Shruti’s sleepless nights studying, alone, in hospital accommodation. Do you feel that that’s an accurate portrayal of what some junior doctors go through? I most related to Shruti’s character because she’s a junior doctor and I’m a junior doctor. These events were around 2010 when Adam was a registrar and we’re now in 2022. Now, legally we aren’t allowed to work over a certain number of hours a week and back then there was no regulation on that. One of the moments I resonated with the most is when she is in the early pregnancy clinic and she had her exams to revise for and she’s got patients queuing round the corner. Because of the pressure she was under, the way she broke that bad news on a couple miscarrying was very brash, without any empathy, and that wasn’t her fault. You could understand from Shruti’s position that it’s a systemic failure rather than an individual failure because she shouldn’t have been in a position where she was running on empty for so long. I also really sympathised with the scene where she was out for dinner with a senior female surgeon asking for advice and the surgeon says: “You just get on with it and maybe this isn’t a career for you, maybe you’re too sympathetic, too emotional”. I think that is one of the huge issues in Medicine. This kind of mask you have to wear. You just have to move on. You don’t have time to process grief, to reflect on what’s just happened. Move on to the next one. You’re constantly firefighting. That was apparent with all the flashbacks, consistent with post-traumatic stress disorder, that Adam experienced — it was just intrinsic to his everyday life. Are there pockets of support for doctors like Shruti and Adam, are they easily accessible? Are they useful? Do doctors have the time to engage with them? I think this system has got a bit better given the working hours aren’t as intense. When my registrar says, “Oh, you look a bit tired”, I’d be like, “Yeah, it’s, you know, it’s my fourth day on-call, I’m feeling it a bit, my back is feeling a bit”. Some senior doctors will say, “Well in my day we worked double this” and I find that very unhelpful. I do find it very unhelpful when your seniors essentially minimize your suffering and then you feel like you’re weak. That is very well portrayed in the show when the initially incompetent Shruti becomes more experienced and gets her junior doctor trainee, she becomes like Adam — she passes down bad behaviours that she learnt from him; verging on bullying. I am sure it’s still around, but I haven’t had any negative experiences like that. The way Shruti treated her junior, I haven’t had that. But it’s the minimisation of the challenges, the message that we should be resilient, that we should be able to carry on and carry on without complaining. Carry on without needing to take care of yourself. In aeroplanes, we know that you do need to put your oxygen mask on first before you help others, but this principle is not drilled into the kind of fabric of becoming a doctor and the socialisation process at Medical School. I’m an ambassador for “You Okay Doc?”, so there are incredible initiatives that are out there to assist doctors, there are pockets of mental health support for doctors, but it is still pretty unhelpful. When I started my first year of training, the only training we had around well-being was a 2–3 hour online workshop that was quite tokenistic. Luckily for me, I come from a privileged point of view: I’ve had private support from my mental health, and I’ve got an incredible support network, but obviously, for someone like Shruti, she was living alone in hospital accommodation, away from her loved ones. I’ve had one colleague saying that she disliked the fact that Shruti took her own life because it made the show leave a really bad taste in her mouth. My colleague was relating so strongly to Shruti being incompetent at the start, and then you see her increasing competency, but it was heart-breaking when Shruti takes her own life. For me, I think that was the most powerful thing because it just shows how high functioning depression can be and how prevalent it is in high achieving individuals, and how hidden it is. Systems need to change so that we can keep these brilliant minds going. The show is dark, not like the glamorous “Grey’s Anatomy” type. You are very vocal on social media about your journey with your mental health and junior doctors’ mental health. Can you tell me more? Essentially, at the end of my gap year before medical school, I started to suffer from panic attacks. It was quite debilitating. I had a lot of anxiety, but I never could put my finger on exactly what was going on. I didn’t have the literacy or the education. I know now that all these things are so normal, and everyone goes through them for a while. I kind of hid it and I didn’t really want to face it. When I did my intercalated year at Imperial College London, that was a huge, huge turning point in my mental health. I started to suffer from low mood, it wasn’t just anxiety anymore. It was just lack of motivation, suicidal ideation — the whole myriad of symptoms that come with clinical depression. A lot of self-doubts filled me at the time. Was I going to be able to care for patients, being so unwell? You know, doctors make terrible patients. It took a while for me to accept it to then seek help. I wasn’t sleeping, eating, so I finally went on medication. Over six weeks, I started to sleep better, to speak with a bit more lightness in my tone of voice, to have clearer thoughts. I got myself back to medical school and as the academic year started to progress, I became very open with talking about my experience. I realized how powerful that was because then I had really lovely people who opened up to me about their mental health. I just realized how much it helped me and the community I wanted to serve, by being open and authentic about my experience of poor mental health. I am doing, from a preventative point of view, a refresher course with iheart (Innate Health Education and Resilience Training), a not-for-profit organisation that offers resilience training, and that really helped me at the time. I needed structure for when I felt so unstructured and chaotic, and in each session you have you go through a different theme around the human condition. A new generation of doctors, I hope there’s more like you out there. Oh, it’s so lovely to chat with you. It was a really, really fun interview. Thank you for your time Ally, our conversation was raw and honest. Speaking to Ally has given me so much hope for the next generation of doctors being more supported than previous generations perhaps were, and that help is out there for anyone that needs it.

LGBTQ+ Mental Health: Revisiting the past to understand the present Recalling and naming the collective oppressed history of LGBTQ+ people is essential for understanding why mental health difficulties exist disproportionately for this group My name is Dr Brendan J Dunlop (he/him) and I am a Highly Specialist Clinical Psychologist and Clinical Lecturer in Clinical Psychology. I am motivated to reduce mental health inequalities for marginalised groups, especially LGBTQ+ (lesbian, gay, bisexual, transgender, queer/questioning, and others) people, with a consideration for wider systems, structures and stories that impact upon health and wellbeing. February is LGBTQ+ history month. Thinking about LGBTQ+ history is important for many reasons. These include understanding how marginalisation and victimisation previously operated, so that we can prevent it from happening again. Another equally important reason is to help us understand why LGBTQ+ people experience disproportionate levels of mental health difficulties and distress when compared to heterosexual and/or cisgender (i.e., those whose sense of personal identity and gender corresponds with their birth sex) people. To this end, we must recount the history of how people and groups, policies, institutions, and laws, as well as social stories, have influenced the mental health and wellbeing of LGBTQ+ folk. In this short blog, I will detail just a handful of historical events that have had a ‘trickle down’ influence on mental health and wellbeing today. I will include the implicit or explicit message this sent (or sends) to LGBTQ+ people, and in turn the potential mental health consequences. To start, let’s think about the criminalisation of homosexuality in the United Kingdom. Until partial decriminalisation in 1967, being gay was a crime. The explicit message this sent to gay people was that you, and what you do, are inherently and morally wrong. Imagine receiving the message that a central component of your identity was wrong? The mental health consequences of this law and the subsequent message it sent are that of internalised shame, reluctance to engage with authorities (e.g., not seeking medical attention) and difficulties with mood (such as feeling low, anxious or angry). Another example of a harmful law/policy that has a trickle-down effect is Section 28 of the Local Government Act (1988). This section of the Act stated that local authorities could not ‘promote’ homosexuality in schools or other learning environments. The implicit and explicit message here was that homosexuality is wrong and it should not be spoken about. The consequences here were multiple. Children and young people could not see themselves represented in others. Homophobia and bullying were rife. It is therefore no wonder that young LGBTQ+ people felt shame after experiencing such abuse, bullying and interpersonal trauma. In the 80s and 90s, the AIDS (acquired immune deficiency syndrome) crisis hit. This was dubbed by the media and other organisations as ‘the gay plague’, as HIV (human immunodeficiency virus) disproportionately affected gay men. This social story had far-reaching messages and implications. The prevailing narrative was that if you were gay, you were going to die. Furthermore, implicit and explicit messages were that, as someone on the ‘fringes’ of society, it was not in society’s interests to put effort into curing this disease and saving you. The mental health consequences of the AIDS crisis were wide ranging and included a reluctance to seek help due to shame and fear of rejection, anger, trauma, family rejection, grief from the death of friends and loved ones, and, for some, suicide. So-called ‘conversion therapies’ (any form of treatment or psychotherapy which aims to change a person’s sexual orientation or to suppress a person’s gender identity) have historically been used by some healthcare and religious groups to ‘cure’ homosexuality or gender identity differences. The banning of this is still being debated. Similar to my first example about the criminalisation of homosexuality, the message inherent within so-called ‘conversion therapies’ is that the very core of you needs to change. Shame, trauma, loss of trust in authorities, anger and self-harm/self-punishment are likely to have been mental health consequences of such a practice. For transgender (people whose gender does not match their sex-assigned at birth), non-binary (people whose gender identity is not ‘man’ or ‘woman’) and gender-diverse people (umbrella term for people that experience differences in expression and experience of gender), structures and systems perpetually retraumatise. Whether it is lack of legal recognition on state-issued documents, to ‘debating’ trans rights, to the endless waits for gender clinic appointments. The implicit message within these behaviours and lack of equity is that these folk are not worthy of attention. This marginalisation, rejection and erasure of gender-diverse people serves to maintain the ‘status quo’ of heteronormativity (where binary gender identity and heterosexuality are assumed to be the default position), and binary gender identity (i.e., those who identify as either man or woman). As you might be able to make a guess at by now, this has a very real impact on the mental health of these people within the LGBTQ+ community. Difficulties with mood, with trusting others, and with self-worth, could all be mental health consequences of oppressive and harmful systems and structures. The impact of such historical (and current) events and practices influence the way that both heterosexual/cisgender and LGBTQ+ people appraise the LGBTQ+ community. Implicit messages and stories over the years may have consciously or subconsciously influenced the way in which people respond to those that have a different sexuality and/or gender identity. This leads to present day discrimination, bullying, marginalisation, rejection, abuse, erasure, epistemic injustice, lack of legal protection and recognition, lack of healthcare awareness, unsupportive systems and actively harmful policies and laws. It is therefore no wonder that LGBTQ+ today experience disproportionate levels of mental health difficulties such as substance misuse, mood difficulties and suicidality when compared to other groups. For the purposes of this short blog, I have necessarily made the broad connection between history, messaging/social stories and mental health consequences. Of course, as humans, we are complicated people and there are often other mechanisms or factors that contribute to this picture. Understanding, however, how ‘minority stress’ related to people and groups, policies, institutions, and laws, as well as social stories, impacts upon the mental health and wellbeing of LGBTQ+ people is essential for identifying areas of change. Whether these changes are top-down policy changes, changes in the way systems operate so they are more inclusive, or challenging discrimination at an individual level, there are multiple things that can help to improve the mental health and wellbeing of this particular minoritised group of people. If you want to know more about how history and external influences play a part in impacting the mental health and wellbeing of LGBTQ+ people, including practical ways to improve mental health, you can find out more in The Queer Mental Health Workbook: A Creative Self-Help Guide Using CBT, CFT and DBT. This self-help resource can be used as your personal mental health resource and includes lots of activities tips, tricks and strategies to improve your mental health, or think about your identity and relationships in context. It isavailable now for pre-order here. Header image by Christian Lue on Unsplash

Clozapine: Knowing its flaws to optimize its potential When people find out what my job is, it is frequent that I hear jokes about me psychoanalyzing them or suggesting that their friends or relatives need a visit from me! I am an Italian psychiatrist and PhD student in Life Sciences at University Magna Graecia of Catanzaro (Italy), working in everyday clinical psychiatric practice, and am passionate about research and studying neurosciences, psychopharmacology, and mental health. Even if I have already heard similar jokes hundreds of times, this has not (yet) affected my desire to study the human mind and behavior, and to try to alleviate the suffering that psychiatric disorders bring to people. In this blog, I will briefly discuss schizophrenia and clozapine, the drug that is prescribed to patients who do not respond to other agents. I will also discuss my own research interests on this topic. What is Schizophrenia? Schizophrenia is one of the most severe disorders in psychiatry, and its diagnosis has a lot of impact and meaning for both clinicians and patients. Its name, deriving from ancient Greek, has a historical and descriptive value, and literally means “split mind”. However, its use over time has taken on a negative meaning and has often been the main synonymous with “madness” or mental illness in general, thus gaining an intrinsic stigma. In this regard, this has even led to the proposal to rename schizophrenia as something simpler and more descriptive such as “salience disorder”, “mind-split-disease” or “integration disorder”, or still as a more neutral version such as “Bleuler’s syndrome”. Managing schizophrenia involves a complex interplay between early diagnosis, family support, psycho-education, psychotherapy, and prompt rehabilitation, where a fundamental role is played by pharmacological treatment. The name of the entire category of drugs used to treat schizophrenia derives from the action against the most prominent symptoms, namely “antipsychotics”. Clozapine’s critical role The first antipsychotic drug, chlorpromazine, was synthesized in the ’50s, and initially used as an anaesthetic. Then, the French military surgeon Henri Laborit understood its antipsychotic properties in an attempt to prevent shock and noted that it produced a “euphoric quietude” in soldiers, thus transforming it into the first neuroleptic drug of history and the forefather of the following first-generation antipsychotics. Over the decades, many other antipsychotic molecules were developed, until clozapine made its appearance on the scene in the 1970s. Clozapine, the progenitor of the second generation of antipsychotics, has brought a breakthrough in the antipsychotic properties of the treatment of schizophrenia, being the first to control the symptoms of the disorder with a tangible clinical improvement, and a resumption of the patients’ overall functioning, even in patients who had not improved with other antipsychotic medications. Clozapine has thus conquered a unique role in the treatment of schizophrenia, also becoming the only drug with effect in “treatment-resistant schizophrenia”, which is when the other antipsychotics are not effective on the disease. However, despite its positive clinical impact, clozapine had a complicated fate, and it was even temporarily withdrawn from the market in the 1970s, due to a series of unforeseen deaths and after reports of agranulocytosis, a severe condition in which the bone marrow does not make enough of a certain type of white cell, most often neutrophils (a kind of white blood cells that protect from infections). That was the darkest period in its history, and we risked never using such an important drug in psychopharmacology. It was only thanks to important subsequent studies published in the late ’80s that it was understood that clozapine, while burdened with important and unpredictable side effects, shows an unmatched efficacy in treatment-resistant schizophrenia. Thus, it was finally approved by FDA in 1990. We also learnt that these unpredictable side effects could be identified early through regular blood tests. Since then, despite the important corollary of associated adverse events, the risk-benefit ratio of clozapine has been considered acceptable when using a specific protocol that includes a strict administration schedule and an extensive safety check, and especially full blood test (checking for white blood cells, associated with immune system functioning) that is mandatory in all countries but slightly different around the world. For example in the UK it is weekly for the first 18 weeks, then biweekly from 19 to 52 weeks, then monthly as long as taking clozapine, with temporary stop or discontinuation in case of neutropenia, that is a blood condition with low levels of neutrophils. Clozapine-related DRESS syndrome My research interest with clozapine is due to a rare but very interesting condition called “Drug reaction with eosinophilia and systemic symptoms” (DRESS). DRESS syndrome is a rare but potentially fatal condition associated with various drugs including antibiotics, allopurinol, other psychopharmacological agents such as carbamazepine, and, as identified more recently, clozapine. To date, this condition is not predictable and there are no definitive treatment guidelines, therefore its early recognition remains the main tool available. For a long time we did not know that clozapine could be implicated in this syndrome, since many of the symptoms used for diagnosis (e.g., eosinophilia, internal organ involvement, fever) are actually common adverse events that have already been associated with clozapine. Therefore, clozapine-related DRESS syndrome may have been oversighted and underestimated. Indeed, my research is mainly focused on better understanding clozapine's role in DRESS syndrome, and, to date, we already found 27 new cases of clozapine-related DRESS syndrome and the count is still ongoing through the screening of large international pharmacovigilance databases. However, the identification of this or other side effects should not discourage the use of such an important drug for schizophrenia treatment. Rather, knowing its characteristics, mechanisms and potential interventions should increase awareness and improve general management of clozapine to optimize its safe use despite its important side effects profile. Conclusion In conclusion, clozapine has had many ups and downs along its path, and it undoubtedly still remains fascinating and enigmatic in many ways. Its history, its effectiveness and the mystery of its unique action make it one of the most interesting medications in psychiatry. Until we have something safer and more effective to replace it, we need to understand how to best use it in the people who can benefit most from it.

Losing a Loved One Losing a parent is a grief-filled traumatic experience. We as humans understand that losing loved ones is inevitable. The NHS offer advice and support to anyone affected by losing a loved one, but despite all the advice and help that exists, nothing can prepare us for the gut-wrenching moment we lose or are about to lose a parent. On the 15th of August 2021, I woke up as a middle-aged man who was lucky enough to say I had two healthy parents. I woke up with the same ambitions, the same thoughts and feelings as when I went to bed the previous evening. But this day would change my life forever. The diagnosis Later that day, my mum called me to tell me the hospital had found a large tumour in my dad’s oesophagus. Receiving that news was a shock to my system. I feel like it’s an eventuality that every child refuses to acknowledge until it happens. The horror of potentially losing a parent is something so painful that our brains seemingly refuse to contemplate it. Even after this phone call, I refused to acknowledge that he might die. Many hospital appointments followed to distinguish if this tumour was benign or malignant. On the 11th of November, my mum called, and this dread came over my whole body, and I just knew it was bad news. Straight away, I could hear the distress in my mum’s voice, and she explained to me the diagnosis was terminal, and they couldn’t do anything to help dad due to his age (76). The rest of that conversation was a blur, and I couldn’t even say anything comforting to her. Memories At that moment and for the rest of that week, I went on a trip down memory lane. I kept thinking about how hard my dad used to work when I was younger. His work effort and desire to provide for us was unbelievable. It’s something I never appreciated until the last few years. One particular memory as a child that sticks out in my head was when he used to bounce me on his knee and sing this old World War I song to me, called Inky Pinky Parlez Vous! The lyrics to me as a child were hilarious. Honestly, I don’t think you would find many parents singing that to their son or daughter in this day and age. But it was a different time then, and it’s one of my most treasured memories of him and it paints a perfect picture of him. I have always viewed him as being perfectly imperfect. Growing up, I never saw him afraid of anything. He was always fearless. The only time I ever saw him cry was when my Grandad Roy passed away. I always felt he wished he was more like my Grandad, but they were both completely different but equally great. When my Grandad passed away after his brave battle with prostate cancer, I experienced that pain of losing someone you love. I saw how difficult it was for everyone, not just myself. It was a feeling I never want, to experience again. Family and Friends I think about my mum a lot and the impact my dad passing away will have on her. They have been married for 40+ years, and I cannot imagine being in someone’s presence for that long and then having to live on your own. She is the person that will need the most support in the long term, though it will be hard for family and friends to offer the right level of support. Everyone will want to be there for Mum with the best intentions, but we all have to get that balance right and not suffocate her. We as a family will have special occasions where we will all undoubtedly have to put on a brave face. But these occasions will be met with a twinge of sadness that my dad will not be there to crack an inappropriate joke or tell a relative how much he hates the football team they support. When I make a cup of tea, dad won’t be there to make sure I’m making it just the way he likes. My parents never really had friends. They adored their family, and that was all they needed. But in the last few years, they met another couple — Tony and Sandra. When they walk into a room, my dad’s face lights up. I am so thankful they have managed to forge a friendship with two of the kindest people I have ever met. The funeral is something I keep pondering. Standing in a line shaking peoples’ hands, some of whom I barely know, when all I want to do is sit there and watch football with Dad one last time. I can’t even imagine smiling or laughing anymore after he’s gone. I feel every person at some point has taken their parents for granted, me included — it’s not until the prospect of losing them is upon you that you truly appreciate everything that they have sacrificed for you. I have learned already that there is no blueprint for you to follow in this scenario. No one can tell you what to expect as grief impacts us all differently. You have to abide by that old cliché: ‘one day at a time’. Time has enabled me to forge a routine that helps me keep functioning — but I feel guilty that my life is continuing. People that have lost a parent will know there’s no clock on how long you should feel a certain way. Take each day as it comes and try to make yourself and your parents proud. The prospect of losing my dad terrifies me. I am thankful for every minute I have spent with him, and I will treasure every moment left. Dad is fighting every day and showing everyone just how tough he is. Christmas As I sit here at Christmas writing the ending to this article, I am remembering so many great Christmas memories involving my dad. The doctors think this could be the last Christmas he is alive. If this was the last Christmas, I want to thank him for being perfectly imperfect. As we celebrated Christmas day this year surrounded by friends, I kept looking at my dad, and his expressions were bittersweet. You could see how much he enjoyed himself, but when we all started to say we were tired, he heartbreakingly said he was ok and wasn’t tired — he didn’t want the day to end. Whatever happens from now, I hope dad continues to fight one day at a time. We are all incredibly proud of how he is handling his diagnosis, and personally, Dad has given me so many valuable lessons and great memories. I pray we have a few more years to make even more memories. I love you, dad.

Anxiety in families: Exploring the causes As a Research Associate at King’s College London, my work is focused on trying to understand how anxiety and other common forms of emotional problems run in families. When I tell people this, they often say: “you need to look at my family!”. It’s not surprising to hear that many people can identify intergenerational patterns (i.e., similarities between parents and children) of mental health problems in their families. Anxiety and related emotional problems constitute the most common forms of psychiatric impairment worldwide, and the children of parents who experience these problems are at higher risk for experiencing the same. But how does this intergenerational transmission happen? Was there something in the way your parents brought you up? My PhD thesis was dedicated to this question. Specifically, I focussed on efforts to disentangle the role of genetic from social transmission in families. We know that all mental health problems are influenced to some extent by genetics. We also know that children inherit their DNA from their biological parents. So, the genetic variants (i.e., DNA differences identified across people) influencing emotional problems in parents could be the same genetic variants influencing emotional problems in their offspring. That is, parents and children can be similar to one another in part because they share the same genes. However, genetics only explains part of the picture. Once we account for the role of genetics in families, then we can start to better understand what is going on in terms of social transmission (i.e., the result of direct interactions between parents and children). Here, it is important to recognise that social transmission is a two-way process. We often think about the ways in which parents can influence their children, but we must also remember to think about the ways in which children can influence their parents. There has been a wealth of research to show that parents and children are similar in their mental health. There has been less research that allows us to isolate the role of genetics and to determine the direction of social effects between parents and children. To really get to grips with what we do and don’t know, I conducted a systematic literature review (i.e., where you systematically search through literature databases for every single piece of research that addresses your research question) and a meta-analysis (i.e., where you collect all the results that exist already and merge them together to get an overall result). In collaboration with colleagues, I searched for published research that explored the association between parent anxiety and child emotional problems, while accounting for the influence of genetics. Evidence suggests that mothers who experience anxiety during pregnancy do not pass on similar emotional problems to their children, but later exposure to an anxious parent might have an impact. I found only eight studies on the association between parental anxiety and emotional problems in children. As specified by my search parameters, all these studies included techniques to account for and remove the role of genetics in how emotional problems can be passed on. These techniques involve comparing the likeness of family members who are differently related and/or exposed to one another (e.g., in adoptive families, where children are genetically unrelated to their rearing parents, any similarities between parents and children must be attributable to environmental effects). The studies that I found were all derived from Europe and the USA, published between 2010 and 2019. The first thing to note is that this is a very small literature base, from a very narrow sample of people, relative to the global population. This means that we have limited information on how well findings would generalise across different populations (i.e., across cultures, environments and societies). Data from three studies (which assessed >11,700 families with children aged 0.5 to 10 years) showed that exposure to mothers’ anxiety during pregnancy was not associated with emotional problems in children, after the effects of genetics on this association were accounted for and removed. In other words, there was no evidence to suggest that mothers’ anxiety during pregnancy increased the child’s risk for developing emotional problems. The association between mothers’ anxiety during pregnancy and child emotional problems was explained by their genetic relatedness. Meanwhile, six studies (which assessed >12,700 families with children aged 0.75 to 22 years) on parents’ anxiety after birth found a small association with emotional problems in children, after accounting for the role of genetics. This means that exposure to an anxious parent after birth might have an impact on child emotional problems, over and above the role of genetics. However, it wasn’t possible to tell whether this impact was parent or child driven (i.e., parents influencing children and/or children influencing parents), nor whether this effect would be long-lasting across time. So, although social exposure to your parent or child’s emotional problems could affect your own symptoms, we can’t say whether this effect is likely to stick around. When I tell people what I’ve been working on, and they want to know what it means for their families… what should I say? Our findings should be reassuring for parents. For pregnant mothers, we suggest that anxiety symptoms during pregnancy do not cause an increased risk of anxiety in the foetus. After birth, for parents of children and adolescents, our findings do not point to any large effects of parent anxiety on child emotional problems. There are three important points to consider: First, there is a striking need for new research. We are asking an important question about a topic that touches many people’s lives — how emotional problems run in families. But only eight studies have used robust methods for identifying the genetic and environmental pathways that exist in general populations. It is important that new research is conducted in this area, to help us develop better ways of preventing and supporting mental health from an early age. Second, we are not going to find a single cause. We cannot place all the ‘blame’ on our parents, just as we can’t solely ‘blame’ our genes or our wider environments (and I note here that wider environmental influence is not something we looked at in the research I described above — but could involve factors relating to wealth, pollution or crime levels, access to education and healthcare). The majority of existing literature focuses on mother-child relationships. Future research should take a more holistic view, considering the role of fathers, as well as siblings and broader environments. Third, a significant limitation across all mental health research is that it is conducted predominantly in Northern Europe and America, with participants who identify as white. In these areas, we have extremely limited information on the lived experiences of people from marginalised racial and ethnic groups, as well as those living elsewhere across the globe. Until this imbalance is addressed, mainstream evidence in mental health research will continue to perpetuate a cycle of evidence-based policy that excludes people who are not of white, European ancestry (i.e., excluding the global majority). We do not yet know whether our findings would hold true across different groups in different contexts, environments, and cultures.

LGBTQI+ mental health during the pandemic My name is Paul Gorczynski. I am a psychologist who conducts research relating to various topics including mental health and sport and exercise psychology. My work extends to mental health service delivery policy for LBGTQI+ (lesbian, gay, bisexual, transgender, queer, intersex, plus) people and I currently serve as a Parliamentary Fellow with the Women and Equalities Select Committee in UK Parliament. During the early weeks and months of the pandemic, I found myself engaged in thoughts about meaningful connections: what did it mean to be connected to someone? What did it mean to not feel that? In a sense, what did it feel like to be lonely? Loneliness can be described as an emotional state, one where individuals feel dissatisfied that their social needs are not being met by desired qualities and quantities of social interaction. These feelings of dissatisfaction, or loneliness, can be temporary and situational, or they can be chronic and last a very long time. Loneliness can lead to a variety of mental health symptoms and disorders. In the spring of 2020, many of us found ourselves disconnected from others. Closures and lockdowns meant that we could not see our friends or family, and socialising was highly restricted, limited in size, and often kept to brisk walks. As many of us may remember, benches were off-limits. During that time, I was fortunate enough to live close by to my dear friend, Fabio Fasoli, a lecturer of social psychology at the University of Surrey. Walk and talk As we looped our neighbourhood in south London, we often found ourselves lost in conversation about connection and what it meant for overall mental health. In particular, as gay men, we were concerned about the mental health of other LGBTQI+ people. News reports of LGBTQI+ people being trapped in hostile home environments; experiencing homophobia, biphobia, and transphobia; as well as mental health symptoms and disorders were beginning to emerge. However, as we read newly released scientific literature on mental health at that time we noticed an unsettling trend: that limited demographic data was being collected and disseminated about sexuality and gender identity in relation to mental health. This was a problem for a number of reasons. An absence of data meant that communities that have traditionally been marginalised and excluded from the research process were still being ignored and left out. Research prior to the pandemic had demonstrated that LGBTQI+ individuals experienced high rates of mental health symptoms and disorders, and that mental health services were not well designed or equipped to help these individuals. Limited data collection during the pandemic would not address mental health service challenges for LGBTQI+ people. An LGBTQI+ focused mental health research strategy So, we decided to act. On one of our walks we laid out a call-to-action to researchers of mental health: an LGBTQI+ focused mental health research strategy in response to COVID-19. Here we called for a participatory, collaborative, and multidisciplinary response to COVID-19. This response was rooted in equity, so that the mental health needs of LGBTQI+ people were better understood and took into account individual, environmental, and social determinants of health. Ultimately, we wanted to help lay the path to a culturally competent design of policies and mental health services. We also wanted to help end the invisibility of LGBTQI+ people in mental health-related research. Explorations of loneliness In addition to this call-to-action, we also embarked on another exploration: that of loneliness amongst sexual minority individuals. Research prior to the pandemic had shown that amongst those who identified as sexual minorities, loneliness ranged from 13 to 35%. Specifically, we wanted to examine levels of loneliness amongst sexual minorities in comparison to those who identified as heterosexual. Part of our research focus was to demonstrate a real need to take loneliness seriously, especially in relation to other mental health symptoms and disorders. We also wanted to help start a dialogue on future research and clinical practice to address loneliness amongst LGBTQI+ people. We believed that our research could meaningfully lay the groundwork for the exploration of enabling environments that could help foster feelings of safety and social connectedness. Our findings showed that sexual minority individuals experienced higher rates of loneliness in comparison to those who identify as heterosexual. Overall, these projects have spurred me on to try to help influence national policy and future mental healthcare services for LGBTQI+ people in the UK. Today, through a Parliamentary Office of Science and Technology Fellowship, I work with the Women and Equalities Select Committee in the UK Parliament on research that concerns the mental health needs of the LGBTQI+ community in the UK in relation to the pandemic. A prominent focus of my work is the exploration of connectedness and loneliness amongst LGBTQI+ people. Findings related to this project will be made available later this year. Connect with your community Now, two years into this pandemic, I find myself still thinking about meaningful connections. Thoughts of friends, family, and the broader communities that I am a part of occupy a great deal of my time. This February, as we celebrate LGBTQI+ history month, I would encourage everyone to connect, in whatever way you feel comfortable (and, of course, in accordance with required public health practice and policy). Connect with friends, family, and your communities. Embrace them. In London, there’s also plenty of community programming helping us celebrate this important month and helping us to see people and places we may not have seen in a very long time. For instance, my local council, Lambeth, has a lovely LGBTQI+ history month programme that creates space for important discussions of history, art, literature, film, health, and community building. Check it out!

When the name does matter The importance of definitions in treatment-resistant depression and a new published guideline for clinical studies Most, if not all, of us in our lives have experienced occasional sadness and low mood, or a lack of interests and motivation in daily activities. This is not necessarily depression. Short-lived mood fluctuations, mostly if clearly linked with a different range of challenging situations, can (and should) be considered as a normal and physiological component of an individual’s life experience. I am a Psychiatrist and a PhD Student in the Stress, Psychiatry and Immunology (SPI)-Lab at King’s College London, and my research focus is on major depression and specifically on treatment-resistant depression (TRD) and its biological correlates. I have written previous blogs for InSPIre the Mind, on the comorbidity between depression and cancer and on seasonal depression. In the present blog , I will discuss the importance of definitions in TRD-related research. I will start with an overview on TRD and core gaps in knowledge and I will then summarise the main recommendations of a newly published guideline for TRD clinical studies, which has been led by our research group. Depression, or more precisely ‘major depression’, is different from normal sadness. Major depression is, indeed, a complex and serious clinical condition in which a person experiences a depressed mood or a loss of pleasure in things and activities for most of the day, nearly every day, for at least two weeks, in addition to other specific physical, cognitive, and psychological symptoms. Currently, according to the World Health Organization, approximately 280 million people worldwide are living with depression. Notably, most people with depression have a chronic course of illness and recurrent episodes. Complicating matters, although a wide range of treatments are currently available and effective in a lot of people, they are not effective in all people. In fact, about one third of individuals with depression do not show any significant response after one or several antidepressant treatments. That means that almost 100 million people are suffering from a ‘not-effectively-treated’ depression all around the world. Given these premises, it is not surprising that depression is nowadays recognized as a leading contributor to the global burden of disease and as a major cause of disability worldwide. An important and fundamental step to tackle this dramatic evidence is to understand why the same treatments have different outcomes in different people. By focussing research on these individuals who ‘do not adequately respond’ to conventional treatments we may understand the reasons behind this non-response and how they could eventually respond or to which treatment, maybe targeting something different from standard antidepressants, as we have also previously discussed on InSPIre the Mind. When a treatment fails to eradicate or effectively improve depressive symptoms, we are conventionally referring to a condition named treatment-resistant depression, or TRD. Quite surprisingly considering this evidence, there is still uncertainty around concepts such as response, non-response, and partial response to treatments, and a clear and unequivocal definition of TRD is still missing. Correctly differentiating between different clinical phenotypes may lead to more tailored research, eventually allowing the discovery of novel treatments for selected group of individuals. Therefore, the name matters. A clear consensus on disease definitions is the necessary foundation to build reliable future research in psychiatry. Which are the main uncertainties and core gaps in knowledge? As discussed, there is still no clear consensus on what we mean by TRD. When we try, for example, to test the efficacy of a new treatment in individuals in whom conventional treatments failed to improve symptoms, a discordance in definitions may be reflected in a discrepancy in clinical populations between different studies, with potentially different results, generating confusion in TRD-related research. Now, let’s suppose we carry out five different clinical trials on people with TRD to test the efficacy of a new medication. Having ambiguous definitions for inclusion of participants in these trials may imply that different studies potentially analyse five different conditions — each of them equally defined as TRD. This is what has been happening. Only one in five TRD studies utilise the most consistently accepted definition of TRD in literature that is, a non-response to at least two previous antidepressant treatments, administered at an adequate dosage and for an adequate duration. If these definitions differ between the different theoretical and operational approaches, an unfortunate consequence may be to compare the same interventions — and to standardise outcomes — in clinically different populations, therefore raising the famous problem of ‘comparing oranges and apples’. Here, the issue may be even more complicated. In fact, the different TRD definitions usually only differ slightly between one another. This may imply we are not necessarily comparing oranges and apples, but we are probably not noticing important nuances, for example the difference that lies within different types of apples. Here lies the importance of the consensus guideline recently published on Molecular Psychiatry and coordinated by our research group. The original paper has been produced as part of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) project. The aim of the project is to design a protocol for platform trials in different diseases, including major depression. To develop the guideline, we followed an iterative consensus process involving over 60 experts in the treatment of depression, including clinicians, academicians, members of industry and regulatory agencies, and people with lived experience of depression. We aimed to gain consensus on the main uncertainties and gaps in knowledge in order to produce clear definitions of TRD for inclusion of participants in clinical studies and clinical trials. Future directions towards no more uncertainties Co-author on the report Fanni-Laura Mäntylä, who has experience of living with depression and has written a fascinating blog article about her own personal experience, said: “Personally, as a patient with a very difficult and lengthy path with the recovery from major depressive disorder, I feel a clearer definition would be very beneficial; as well as a more patient-centric and personalised approach to the treatment.” It was almost unanimous opinion that a better definition of TRD for clinical trials conducted for regulatory purposes is necessary. A definition of partially responsive depression (PRD), distinguished from TRD, has been also recommended. In more detail, we propose that to define TRD (and PRD) it is necessary to confirm a diagnosis of major depression and to document a non-response (or a partial response) to an antidepressant treatment. Non-response or partial response should be carefully assessed by examining number, type, dosage, and duration of current and past treatments. TRD should be defined after a minimum of two failed treatments (defined as an improvement less than 25% in clinical scores before and after treatment), with adequate dosing and duration (the minimal licensed dosage administered for at least four weeks) and different mechanisms of action. PRD can be defined even after a single treatment (improvement between 25 and 50%) with adequate dosing and duration. The improvement in depressive symptoms is usually measured prospectively, using the percentage reduction in clinical scales (pre- and post- treatment). However, it can also be evaluated retrospectively (only in the past two years), based on medical records. Still a lot must be discovered to correctly understand depression and treatment resistance. There are many different clinical phenotypes of depression and, probably, these are related to different biological and molecular profiles. Inflammation is certainly important in TRD, for example. Therefore, a depression that ‘does not respond’ (or ‘respond partially’) to treatments may have some intrinsic differences compared with ‘responsive’ depression, with peculiar clinical, biological, and molecular features. Understanding these features may allow a better characterization of TRD/PRD, ultimately leading to novel discoveries for diagnosis, prevention, and treatment.

International Day of Women & Girls in Science: My Journey and the Women Who Inspired It Author’s Note: This article is part of a collaboration between my colleague Amina Begum and I, both placement students studying immunopsychiatry at the Stress, Psychiatry, and Immunology Lab at King’s College London. As a woman in science, I find myself acutely aware of the fact that I wouldn’t have the ability to do what I do for a living if I had been born a few generations ago. It’s a privilege to be able to do what you love, a privilege that many — though sadly, not all — of us have only recently been afforded. As we celebrate International Women in Science Day, it’s important to remember those who came before us, who paved the way for women in science. I didn’t always know that I wanted to be a scientist, but I had an interest in science from a young age. I spent part of my childhood volunteering at the Sequoia Park Zoo in Eureka, California, where I was inspired by Dr. Jane Goodall and her work with chimpanzees. Dr. Goodall was the first female scientist I had ever heard of. She worked as a secretary until the age of 23 when she set sail for Tanzania to study chimpanzees, establishing her presence among them until she was able to make some of the most significant discoveries about primates and their behaviour. Her work changed how the world viewed chimpanzees and, by extension, how the world viewed species other than our own. As I progressed through my education, I learned about more female scientists and inventors, many of whom have been forgotten by history or remembered for the wrong reasons. Hedy Lamarr, who pioneered the technology that would lead to the invention of Bluetooth and WiFi is, for the most part, remembered simply for being beautiful. In collaboration with fellow innovator George Antheil, she developed a communication system that allowed the transmitter and receiver to “hop” frequencies simultaneously. The pair tried to offer their technology to the Navy during World War II; instead of commending her for the role that she had in this great work, Lamarr was told that she could do more for the war effort by using her beauty and celebrity to sell war bonds. The Navy later implemented the technology during the Cuban Missile Crisis. Lamarr and Antheil never saw a penny from it. When I was in my seventh-grade science class, we learned about Dr. Rosalind Franklin. Dr. Franklin and her graduate student Raymond Gosling took the now famous ‘Photograph 51’, an X-ray diffraction image showing the structure of DNA. One of her colleagues showed the image to scientists Watson and Crick without her awareness or consent. Using her work, they were able to confirmed their hypothesis and they are the ones often credited with the discovery of the molecular structure of DNA. When I landed a work placement at King’s College London, the same institution where Dr. Franklin made her discovery, it felt beyond surreal. I was living the wildest dream of my thirteen-year-old self. Entering the ivory tower of academia can be incredibly intimidating, but I was glad to find myself among colleagues with a variety of different backgrounds and experiences, so I didn’t feel like the odd one out. Unlike Dr. Franklin, I am not the only woman in the room. Interestingly, the word ‘scientist’ was first used to describe a woman, Mary Somerville. At the time, scientists were referred to by their disciplines and those with multiple disciplines were considered “men of science.” But Somerville refused to be confined to one area, studying everything from astronomy to chemistry to geology. Like so many women throughout history, her pursuit of science and mathematics was discouraged, to the point where she spent a great deal of her childhood studying secretly by candlelight. A scientific historian by the name of William Whewell was struggling to find a word to describe Somerville, writing that “We need very much a name to describe a cultivator of science in general. I should incline to call him a Scientist.” Although women have made an immense amount of progress in the sciences, there is still more that needs to be done to achieve parity. Today, less than one-third of scientists are women. Even though the number of female scientists is increasing, they are not always considered as valuable as their male counterparts. According to the United Nations, female researchers are paid less, receive less funding, and have shorter careers than their male counterparts. Female scientists are also more likely to experience imposter syndrome, feelings of inadequacy despite successes in one’s career. An immense amount of progress has been made around the world, but there are still many places where women are left out of science. In India, women are literally kept out of classrooms for wearing the hijab and discriminated against for seeking an education. So while it’s important to acknowledge the fact that things are changing, they aren’t changing everywhere, nor are they changing for everyone. As we each climb the ivory tower, we must remember that there is room at the table for all of us to have a seat. For more about international women in science day, be sure to check out Amina Begum’s blog: Are We There Yet? Challenges Women in Science and Academia Face Today.

How History Helped Us Grow into the Future I was astounded by the depth of my autistic son’s knowledge about naval history on a recent trip to Portsmouth’s Historic Dockyard. On the trip, a present for my son Charlie’s 20th birthday, I thought about how far we’ve come since he was diagnosed at the age of 7. I’m a middle-aged dad, living in Walthamstow with Cleo, my wife, and our kids, Charlie and Lola. While I work as a civil servant, my real passion is film, poetry, and writing. I’ve written about the challenges of raising a child with autism and had a chapter included in Dad: Untold Stories of Fatherhood. While I reflected, I realised that alongside the challenges there are many positives. As the theme for this year’s Children’s Mental Health Week is ‘Growing Together’ I decided to write a blog about those positives and in particular on what Charlie has taught me. I think, as with many parents, I’ve often focused on teaching my children and hopefully getting some messages through, Charlie is turning into a kind and considerate adult. Sometimes we forget how much our children can inspire and teach us. Past flights of fancy Charlie has severe, sometimes overwhelming anxiety and my wife and I have tried to help him as best we can. We battled to get him support over the years (now facing a new cliff-edge of entering adulthood and the children’s service support falling away). Like some people with autism, Charlie has ‘special interests’ about which he can talk at length and focusing on these is one of the tools we have used to help him with his anxiety. When he was younger one of Charlie’s special interests was birds. We have no idea where this came from, maybe because we live around the corner from Walthamstow Wetlands. We used feeding the geese as a way to get him up in time for his school bus. Some of his other special interests may have been slightly engineered by us, for example, his love of Star Wars was definitely initiated by me, although by the time he was 9 his knowledge of the Galaxy far, far away far exceeded my own. His love of birds was his first ‘special interest’ that actually taught me a lot. My own dad had for many years tried to get me interested in birds but by the age of ten I was far more interested in the world of punk rock than anything the young ornithologists had to offer. As I reached adulthood, I could probably identify pigeons, crows, ducks, and seagulls (hard not to growing up in Brighton), so my poor dad had miserably failed to teach me about birds. It was through Charlie’s enthusiasm for birds that I learnt all the things my dad wanted to teach me. Charlie’s incredible sense of hearing enables him to identify different types of bird from their song. He once told me there were some Greylag Geese approaching just by their sounds, I was sceptical until a whole gaggle of Greylags appeared. It was such a pleasure to be able to share and learn from Charlie’s passion. It took Charlie away from his anger and anxiety and transformed him into a calm and very happy child. And these days I can identify a much wider variety of birds, Dad would have been proud. Now It’s All History As he’s grown older, Charlie’s love of birds has waned somewhat and been replaced by other special interests. Some mean very little to me (the world of anime is completely alien) but others which have brought us together and taught me a lot. One is his love of history. Again, we have no idea where this came from, he went to a special school and they didn’t do a huge amount of history there, and he is currently studying media (like many of his generation his ambition is to be a YouTuber). One possibility is that it was initiated by playing a war game on his Xbox, he is particularly interested in military history, which contradicts the perception that gaming is just bad for kids. One of the great things about Charlie’s interest in history is his willingness to watch documentaries with us. Like many teens, Charlie spends an unhealthy amount of time in his room glued to his phone. Sometimes, when he is in the grip of an anxiety attack, I can distract him by putting on a documentary about something like the Second World War. The other wonderful thing is being able to have long, detailed discussions about a huge range of historical subjects from Genghis Khan to the morality of the British Empire. I find myself being regularly surprised at the level of Charlie’s knowledge, for someone who hardly ever reads books he has a really broad grasp of history. Aside from the documentaries we watch together, I’ve no idea where he gets all his information from, I assume it must be online. But wherever he does get it from, the really inspiring thing is that he’s taught himself. And by doing that he has been able to teach me. All Aboard My wife and I sometimes discuss how to nurture his special interest without putting him off, I’m sure if he had to study history, he would hate it. So, as the milestone of twenty approached, my wife came up with the idea of taking Charlie and a friend to Portsmouth. The trip was fascinating, for all of us, and we all really enjoyed it and learnt loads about life on a submarine, the Warrior and the Victory (although at 6’4” Charlie got backache from bending down). “That’s a Type 23 Frigate” Charlie informed me, before the guide said anything, as the tour boat took as around Portsmouth Harbour, and I had no doubt that it was indeed a Type 23 Frigate. As we travelled back to London, with heads full of Naval History, I remembered something we learnt on an autism training course from years before – ‘allow for the autism’. I’d always considered it in terms of Charlie’s behaviour, but it occurred to me that actually by nurturing his special interests we’d been allowing for his autism. Doing this had enabled us to grow strong relationships as a family through shared interests. And I felt hopeful about a future of growing together with Charlie through our shared interest in history.

“Stop being so difficult” — Why we need to rethink puberty Many mental health issues, like depression, bipolar disorder, or schizophrenia become apparent at an early age. Three out of four people diagnosed with a mental illness experience their first symptoms before they turn 18, with about half of them being younger than 15. Frequently, children in puberty are viewed as hard to deal with. In my teenage years, mental health wasn’t part of my family’s table talk. When my sister and I were expressing anger and were not in the mood to talk, we were “being difficult”. During seventh grade, my sister developed school anxiety. She refused to go to school, didn’t talk with anyone and escaped into the online world. Despite being close with my sister, we weren’t comfortable discussing this and I still don’t really know how she felt during that time. I remember the helplessness I felt. I was fed up with my daily struggles. At home, I often felt alone and misunderstood. Today, I’m a PhD student researching adolescent mental health and brain development within the eBRAIN study. I believe that it’s vital to talk about child and adolescent mental health, especially considering the extraordinary mental health challenges the pandemic imposes on young people. In the past two years, children and adolescents have been dealing with isolation, ongoing uncertainty, anxiety, and grief. This adds up to the usual struggles that young people face, and research has found that puberty is a particularly sensitive period for emerging psychopathologies. How does puberty work? Puberty is when our body matures from childhood to adulthood. Children in puberty commonly experience pronounced and fast physical changes. These are driven by hormones that essentially tell our bodies what to do. For example, to start developing breasts or pubic hair. Sometime between the age of 8 and 14, our body starts to produce steroid hormones like oestrogen, progesterone, and testosterone. This initiates pubertal development. Fast-changing hormone levels not only trigger visible bodily changes but also kick-start a highly exciting time for our brain! How your brain changes Brains are plastic. They are made up of billions of cells, called neurons, communicating through trillions of connections. As we learn something new, neurons that communicate to accomplish the task, form stronger connections. Let’s assume I’m learning to play Beethoven’s “Fur Elise” on the piano. As I attempt to play the song, neurons responsible for moving my fingers are activated in a certain pattern. With practice, their connections become stronger, making it easier for me to move my fingers in the right sequence to play “Fur Elise”. At the same time, connections we do not use weaken. Thus, our brain organises itself according to the functions that we use. Researchers refer to this amazing process as neuroplasticity. The pubertal brain In puberty, the developing brain is particularly plastic, which means it is highly adaptive to the demands of the environment. On the one hand, increased neuroplasticity enables learning and adapting to environmental demands easily. On the other hand, aversive experiences, like family conflict, or being rejected by your crush, are more likely to change the way your brain is organised. Thereby, painful experiences and failures can shape how we think, feel, and behave continuously. Thus, puberty is a sensitive period for maladaptive brain development and emerging psychopathologies. But why do some people get away fine with the struggles of puberty and others develop mental health difficulties? As usual in life, the answer is not that easy. Here, I consider a few factors that have been researched quite extensively. It’s all about timing According to multiple studies, children starting puberty earlier are more likely to develop depression, anxiety, eating disorders, or to use drugs. Why’s that? First, puberty that starts at a young age likely hits children unprepared. Children that go through puberty relatively early may feel like they are not ready yet and may have trouble coping with the physical changes they didn’t ask for. This likely elicits feelings of confusion, stress, or shame, which may become serious mental health challenges. Second, we commonly compare ourselves to others. When children that find themselves a bit off-time in their pubertal development compare themselves to same-aged peers, they may feel substantially different from the others. Not fitting the status quo within their age group, they may feel strange, excluded, and pressured to change. Lastly, physical changes during puberty affect not only how young people perceive themselves, but also how they are perceived by others. It’s always easy to pick up on something that stands out, or that looks somewhat strange or different from most others. Thus, children with early puberty may suffer from being bullied. Bullying has severe consequences for one’s mental and physical health. Being bullied likely triggers adverse feelings towards one’s body image, anxiety, and shame. Who’s particularly affected? Girls who start puberty at a young age are particularly at risk for psychopathologies. Maturing girls are likely to be exposed to sexualised comments and unwanted attention. Apart from being troublesome enough that women must learn to cope with this, young girls may be particularly unprepared to do so, making them feel ashamed and anxious in public. Puberty can be an equally stressful experience for boys. Research has shown that speedier progression through puberty puts boys at risk of developing mental health difficulties. When physical changes progress very fast, there is less time for getting used to one’s new bodily appearance and for adjusting one’s self-concept. Lastly, adultification may represent additional harm for Black children with relatively early puberty. This is when teachers and other authorities perceive Black children as being more mature and less innocent for their age as compared to their white peers. For example, a white child’s silly remark in school would be attributed to its young age, whereas a same-aged Black peer would more likely be held fully responsible for it. Let’s rethink puberty! To bring it all together, pubertal timing that deviates from the average makes it harder for children to deal with the challenges they are experiencing, and intensifies social risks, like bullying and social pressure. This is particularly true for early maturing girls and boys, and Black children. The increased distress during puberty can affect brain development, making it more likely to develop lasting mental health difficulties. To lessen this risk, one way forward would be to refrain from calling young people “difficult”, and instead, acknowledge that their bodies, including their brains, go through a rough time. We can start doing that by being aware of the mental health challenges children and adolescents are facing, and by attempting to talk with, and not about, them. Header image by Taylor Harding on Unsplash

“The Iron Forest” — building the walls to scar the nature If I could bring one thing from my hometown, it would be the fresh air of the conifers from “my” forest. This is the statement my friends have heard me say many times, in particular when I feel nostalgic about my hometown. Augustów, where I am from, lies in the midst of Augustów Primeval Forest, in the North-East of Poland — a region referred to as the “green lungs” of Poland. It is an enormous virgin forest complex stretching across the border with Lithuania and connecting with other forests in the region. When I was 10, I went on a school trip to a neighbouring Bialowieza forest — a UNESCO heritage site with its largest European bison population. I still remember the tranquillity and magnificence of its landscape including stoic bison. I never would have thought that some years later, the serenity of this place will face being destroyed by the wall built on the Polish and Belarusian border, following the recent events of the refugee crisis. Today, I am a mental health scientist with a background in Psychology and Psychological Medicine. I am also a Pole from the North-East of Poland. Embracing both identities, in this blog, I would like to talk about “building walls” and what it means from a psychological perspective. Building Walls and Social Identity Following the humanitarian crisis which recently took place on the border between Belarus and Poland, we are now witnessing Poland building a wall which would prevent asylum seekers from Syria, Iraqi Kurdistan and Afghanistan, to cross the border. The concept of building a wall to separate nations isn’t new. I am sure you have heard about the Berlin wall separating East and West Germany, the Israeli West Bank Barrier between Israel and Palestine, or more recently the wall between Mexico and the US. In fact, according to Elisabeth Vallet, a professor at the University of Quebec-Montreal, since World War II the number of border walls jumped from 7 to at least 70! So, how can we explain this need to separate? In her article for the New Yorker on “Do walls change how we think”, Jessica Wapner talks about the three main purposes of the walls which are “establishing peace, preventing smuggling, and terrorism”. It is based on the premises of keeping “the others” away, the others that are threatening to “us”, our safety, integrity and identity. These motivations form the basis for the political agenda of nationalism. Using the words of the famous psychologist, Elliot Aronson, humans are social animals, and we all have the need to belong to a group. This has been well described by the Social Identity Theory which claims that positive evaluation of the group we belong to helps us to maintain positive self-image and self-esteem. Negative evaluation of the “the other,” or the outgroup, further reaffirms the positive image of your own group — the intergroup bias. As such, strong social identity helps us feel safe and secure psychologically, which is handy in difficult times such as perceived threat posed by another nation or any other crisis. However, it often creates a “psychological illusion” as in attempt to seek that comfort, we distort the reality placing ourselves and our group in a more favourable light. This, in turn, only worsens the crisis, as described by Vamik Volkan, a psychiatrist and the president of the International Society of Political Psychology, in the article by Jessica Wapner. The disillusionment of walls In reality, history shows consistently that building walls have only, and many, negative consequences. The positive ones, well, are an illusion: based on the false sense of psychological protection. In 1973, a German psychiatrist Dietfried Müller-Hegemann, published a book, “Wall disease”, in which he talked about the surge of mental illness in people living “in the shadow” of the wall. Those who lived in the proximity of the Berlin wall showed higher rates of paranoia, psychosis, depression, alcoholism and other mental health difficulties. And the psychological consequences of the Iron Curtain lingered long after the actual wall was gone: in 2005, a group of scientists were interested in the mental representation of the distances between the cities in Germany among the German population. They demonstrated systematic overestimations of distances between German cities that were situated across the former Iron Curtain, compared with the estimated difference between cities all within the East or the West Germany. For example, people overestimated the distance between Dusseldorf and Magdeburg, but not between Dusseldorf and Hannover, or between Magdeburg and Leipzig. What was even more interesting is that this discrepancy was stronger in those who had a negative attitude towards the reintegration! These findings show that even when the physical separation is no longer present, the psychological distance persists. Building walls is a perfect strategy to prevent dialogue and cooperation and to turn the blind eye to what is happening on the other side — if I can’t see it, it doesn’t exist. It embodies two different ideologies that could not find the way to compromise and resorted to “sweeping the problem under the carpet”. From a psychoanalytical point of view, it refers to denial — a defence mechanism individuals experience and apply when struggling to cope with the demands of reality. It is important and comes to the rescue when we truly struggle, but, inevitably, it needs to be addressed for recovery to be possible. Perhaps this analogy applies to societies too. It goes without saying that the atmosphere created by putting the walls up is that of fear of “the other” and hostility. Jessica Wapner describes it very well in her article for the New Yorker, as she talks about the dystopian atmosphere of the looming surveillance and the mental illness that goes with it. And lastly, I wouldn’t want to miss a very important point related to the wall of interest in this blog — the Poland-Belarus wall. In this particular case, we will not only deal with the partition between people, but also between animals and within the ecosystem of the forest, which is likely to have a devastating effect on the environment and the local society. Bringing this blog to conclusion, I hope that we can take a step back and reflect on what history and psychology tell us about the needs and motivations to “build walls”, both physically and metaphorically, and the disillusionment and devastating consequences it might have: for people, for society, and for nature.

How our genes can help us to treat depression and an exciting new development Most of us know what depression is, but how many of us know that it is not only affecting the brain, but is a disorder of the body? It is believed that depression is a combination of genetic, environmental (such as economic status and education), and psychological (such as stressful and traumatic events) factors. Those factors not only can affect the biological system in the brain but also parts of the entire body. While pharmacological therapy with antidepressants is an important treatment for depression, there is still a significant number of patients who do not respond to it (called ‘treatment-resistant’), or experience serious side effects such as gastrointestinal disruptions, anxiety, agitation, and insomnia. Various research has been conducted to date in order to recognise and verify biomarkers involved in the response to antidepressant treatment that could be targeted in order to improve the treatment effectiveness and reduce side effects. A biomarker is a molecule, gene, or characteristic by which a particular pathological or physiological process, disease, etc. can be identified. Among others, gene expression is being used as an approach to understand the molecular mechanisms underlying depression… wait, too scientific, let’s take a step back for a second — what is gene expression and why it is important? As we all know, our traits (such as the colour of our eyes, our height or our risk for certain diseases) are determined by the genetic information contained in our DNA (DeoxyriboNucleic Acid). Genes are parts of the DNA that spell out specific instructions — much like in a cookbook recipe — for making proteins. Proteins are the building blocks for everything in your body. Bones and teeth, hair and earlobes, muscles and blood, are all made up of proteins. This “protein-making” process is called gene expression. Although every cell has two copies of each gene, each cell needs only certain genes to be switched on in order to perform its particular functions. The unnecessary genes are switched off. However, sometimes, a gene contains a change that disrupts the gene’s instructions. A change in a gene can occur spontaneously (no known cause), or it can be inherited. Changes in the coding that makes a gene function can lead to a wide range of conditions and diseases. It has now been a few years that we, and other researchers, have been trying to understand how the expression of genes can influence depression and how it can help to improve the way we treat it. In our recent review, we have presented several studies that looked at the expression levels of various genes in patients with depression. Altogether, these studies have discovered a pattern of altered expression in many genes related to different biological systems including inflammation. Does this mean that those who have certain genes that are less/more expressed could be less/more likely to respond to antidepressant therapy? To try to answer this question, our group has carried out the BIODEP study. This is the largest non-interventional study (meaning that, apart from their usual ongoing treatment, no drug was given to participants) conducted so far to investigate candidate gene expression in depressed patients, characterised by their current depressive symptoms and by their response to antidepressant treatment. Interestingly, what we have found is that there are similarities in the expression of some genes (most of which are related to inflammation) between treatment-resistant depressed patients and depressed patients that were not taking any medication, whereas the expression of the same genes in patients that were responding to the treatment (meaning that they saw an improvement in their symptoms), was alike participants without depression. You can find more details about this study in a previous blog written by Melisa Kose “Genes related to inflammation and stress may help tailor treatments for depression”. Knowing this, what can we do to improve the response to the antidepressant? I previously mentioned that some of the genes that are more expressed in patients with depression are related to inflammation. This confirms that there is a connection between inflammation and depression, as also previously discussed in a few of our blogs and papers. But what is inflammation in this context? There are two types of inflammation: acute and chronic. People are most familiar with acute inflammation which is the one that gives redness, warmth, swelling, and pain around tissues and joints and that occurs in response to an injury, like when you cut yourself or you twist your ankle. When the body is injured, your immune system releases white blood cells to surround and protect the area. It is also the one that helps fight infections, helps speed up the healing process. In contrast, when inflammation gets turned up too high and lingers for a long time, and the immune system continues to pump out white blood cells and chemical messengers that prolong the process, that’s known as chronic inflammation and this is what I will refer to as inflammation in this blog. This means that we could target inflammation and try to reduce it to improve the response to antidepressants. Our group, as part of the NIMA consortium founded by the Wellcome Trust, is running a clinical trial (ATP trial) that aims to test whether a new anti-inflammatory drug has the potential to treat patients suffering from depression and whose symptoms remain despite current medications. In particular, this trial (ATP) is based on the founding from the BIODEP study showing that one of the genes altered in depression is the P2X7 receptor (P2X7R). The P2X7 receptor is produced by immune cells in the brain. Laboratory experiments have shown that the P2X7 receptor can trigger inflammation and drugs that block the P2X7 receptor can reduce inflammatory activation of immune cells. We believe that inflammation of the brain can cause depression in some people and that a drug blocking this receptor may improve the response to the antidepressant by blocking the inflammatory response of immune cells in the brain. So, how can our genes help us to treat depression? The clinical practice continues to be a trial-and-error method that requires multiple treatment studies to reach adequate improvement of symptoms for a majority of MDD patients. Thus, there is an urgent need to personalize antidepressant treatment by maximizing the likelihood of improvement. The use of the measurement of gene expression levels could be particularly helpful in the clinical setting, for an early prediction of treatment response in depressed patients. In fact, it could help to develop personalized antidepressant treatment, maximizing the likelihood of improvement and minimizing the risk of adverse events. Header image source: Syda Productions on Adobe Stock