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We are excited to share that the SIRS 2020 Research Fund Awardee, Leandro Valiengo, has agreed to a SIRS Q&A. View our questions and his answers below!

What were you able to achieve with the SIRS Research Fund Award? 

The negative symptoms of schizophrenia are very hard to treat and very disabling. If photobiomodulation is demonstrated to be effective in future clinical trials, then it may help patients and their families to cope with the disease and improve their life quality.

How has your work shaped today's ongoing research?  

Today we are focusing on expanding the results of this pilot assessment by developing new clinical trials with new variables and more patients..

How has your work made an impact on patient's lives? 

The negative symptoms of schizophrenia are very hard to treat and very disabling. Giving them an option of treatment with favorable results, helps them and their families to cope with the disease and improves their life quality.

What is your ultimate goal in research? 

Now I want to explore the benefits of this technique (and maybe other types of noninvasive neuromodulation) in other symptoms of schizophrenia. My main objective is to improve the quality of life of patients with schizophrenia (and other severe mental disorders) through new treatments that have fewer side effects. I also intend to keep mentoring graduation and post-graduation students to initiate or expand their research skills.

What made you decide to pursue research into psychosis/schizophrenia? 

Treatment resistance in Schizophrenia is very common. This condition inputs a high rate of disability, and the negative symptoms are challenging to treat and limit the quality of life of the patients. So, the search for new treatments in this area, especially concerning the negative symptoms of the disorder, was imperative.

What made you pursue these specific research methods (i.e. genetics, neuroimaging, postmortem, etc.)?

I used brain photobiomodulation because there were other studies using this technique for Alzheimer's disease with promising results. My hypothesis was that if we used the same technique to stimulate the prefrontal cortex, known to be dysregulated in the negative symptoms of schizophrenia, the patients would have an improvement in symptom control.

 What researcher/scientist (doesn't have to be a SIRS member) has influenced your work the most and how?  

My mentor is Prof. Andre Brunoni, from the University of Sao Paulo, Brazil, who studies the use of neuromodulation techniques for humor disorders. He has a brief but extremely productive research career, with some impressive results, and has already published in highly prestigious periods, like NEJM and Lancet.

I am a medical graduate and PhD candidate in neuropsychiatry, aiming to pursue a career in clinical psychiatry and neuroscience. During my clinical training, I learned about the large impact of schizophrenia on the individual and community, which attracted me to the research of schizophrenia. I am impressed by the complex phenomenology of psychosis and how little we still know about it. In my research, I am particularly passionate about the biological underpinnings of psychiatric illnesses, including schizophrenia. I believe that by understanding the cellular- and network-level brain mechanisms that are associated with schizophrenia, we will be able to develop more effective treatment modalities to fill the gaps in our current therapeutic options. Advanced neuroimaging modalities allow us to study the brain in individuals with schizophrenia in real time, providing a unique opportunity to understand the brain as it functions. My PhD research focuses specifically on imaging of iron content in the brain in schizophrenia. Iron is closely linked to dopaminergic neurotransmission, one of the main neurotransmitter systems implicated in schizophrenia. At SIRS 2022, I presented the findings of our group that describes higher content of iron in specific brain regions accompanied by network wide alterations of iron distribution in people with schizophrenia. Excess iron leads to neural damage by generating oxidative stress. Therefore, it is possible that this iron accumulation could be associated with the structural brain changes and cognitive decline that are observed in individuals with schizophrenia. By attending SIRS 2022, I was able to present my study to research groups from around the world and learn about their scientific discoveries relevant to my work. This helped me reshape my research ideas and deepen my understanding of several pathologic cellular processes other than oxidative stress that are associated with iron burden. I met leaders in the field with whom I am hoping to collaborate to uncover more of the unknowns about biological processes in schizophrenia.

As my future direction, I am aiming to continue using advanced neuroimaging tools to understand brain changes in psychiatric illnesses with a primary focus on schizophrenia. Pending further studies and expanding our knowledge about oxidative stress and iron in schizophrenia, we can think about new therapeutic options to mitigate oxidative stress or reduce iron content in the brain, which could potentially alleviate the brain changes and symptoms of schizophrenia.

My interest in schizophrenia began already as a young university student and was motivated by a growing curiosity of how the human mind works. I am particularly interested in the developmental perspective on cognitive and brain maturation to examine trajectories leading to psychopathology. Currently, a precise understanding of the abnormal processes resulting in psychosis is lacking. I strongly believe that a better understanding of complex developmental trajectories may help progress the field in terms of more effective prevention programs, improved diagnosis, and individualised treatment strategies.

My presentation at the 2022 SIRS Annual Congress focused on this issue by examining how the combination of multiple early risk factors such as parental history of psychosis, low birth weight, premature birth, winter/spring birth, urbanicity, immigration status, paternal age, maternal smoking during pregnancy, and Apgar scores influence the age of illness onset in children, adolescents, and adults with psychosis. We conducted a nationwide register study of all individuals in Denmark receiving a schizophrenia spectrum diagnosis from 1973-2018 (N≈30.000) and a healthy control sample (N≈140.000). Here we found that parental history of psychosis, advanced paternal age, maternal smoking and low birth weight independently increased the risk of a schizophrenia spectrum disorder. Subgroup analyses based on sex revealed that advanced paternal age only increased the risk in females. Approximately 20% of the patients could be characterized as child-onset cases (<18 years) with female sex and parental history of psychosis as significant predictors of having an early onset. We also observed a cumulative effect of the early risk factors on age of illness onset with more risk exposures resulting in an earlier age of onset. These findings provide a basis for future treatment strategies in terms of individual risk stratification and early intervention, which from a health policy perspective is necessary in order to prevent, delay or attenuate the impact of schizophrenia spectrum disorders.

In ongoing studies, we relate the register data to our clinical cohorts and explore how these early risk factors influence cognitive performance at the time of illness onset. A better understanding of how multiple early risk factors acting in combination influence neurodevelopment may shed light on the mechanism underlying cognitive deficits in schizophrenia.

The inclusion of register data limits the effect of recall bias when examining exposures occurring many years prior to illness onset. The combination of clinical and register data is highly unique worldwide and will hopefully contribute with valuable knowledge to the field of psychosis.

Participating in SIRS 2022 and receiving the honour of an early career award was highly beneficial to further broaden my current knowledge and expertise, expand my international network, exchanging ideas and establishing new collaborations.

Finally, although we already know a lot about the development of the brain, we still have a lot to learn regarding the abnormal processes leading to cognitive impairments and emerging psychopathology. Much more research is needed to develop more effective treatments and improve the life of our patients. In this regard, I would like to express my deepest gratitude and appreciation towards all the patients in our studies for putting research before their own suffering, sharing a piece of their story and enduring long hours of psychiatric evaluation and neuropsychological testing.

One of the factors that has inspired me to work in psychosis and schizophrenia research is the challenge to improve the functional impairment of persons with schizophrenia and the current therapeutic approaches available. As a speech and language pathologist (SLP) I have a particular interest in the functionality, quality of life, and social inclusion of people, and as a researcher, I know that we must put efforts into generating evidence-based therapeutic mechanisms that help us to address these issues.  

In this context, my work so far has focused on finding meaningful patterns in the speech of people with schizophrenia and how the words they use relate to each other. Specifically, we observed that people within their first episode of psychosis used more words that are synonyms or are very similar to each other throughout their discourse, i.e., they had more inefficient discourse. This is a fundamental feature at the level of communication, but we went further and wanted to understand how these patterns relate to other cognitive domains, in particular interference control. Interference control is a cognitive function that allows us to select relevant information from irrelevant information for a particular context. Indeed, we observed that aberrant word selection is correlated with interference control. We then conducted a 6-month follow-up in a section of our sample and observed that neither speech inefficiency nor negative symptoms improved with pharmacological treatment. Finally, with an emphasis on unraveling how these patterns are associated with certain brain areas of the language network, we performed an analysis of resting-state effective connectivity with functional MRI in people with first episode of schizophrenia. We observed that there are two areas of great interest that are modulated by ineffective speech, i.e., these areas could be involved in this phenomenon and therefore could be possible targets for stimulation or treatment. These topics have been a priority for me as they have potential use in the implementation of language intervention programs in combination with brain neuromodulation for people with schizophrenia. There is still a lot of work to be done to understand the relationship between language and the brain language network.  

I believe it will be a significant and rewarding challenge for future researchers from translational cognitive neuroscience to incorporate this new knowledge and improve quality of life for people experiencing schizophrenia. This new knowledge can also be utilized to generate evidence-based intervention programs that are effective and efficient. Finally, I would like to remark that as an SLP we have another challenge, which is to be part of the mental health team to implement these interventions. However, this is not automatic and we need more people who specialize in the area because working with people with aphasia or dementia is not the same as working with persons with schizophrenia. I firmly believe that if we work on evidence-based programs and specialization in mental health, SLPs can provide a great contribution to the intervention and treatment process for people with schizophrenia.  

Psychotic disorders are complex, debilitating, and not very well understood. Symptoms are often debilitating, and the gaps in care are astonishing. Psychosis and severe mental illness take a toll on both an individual, and societal level. Though we experience the world on an individual level, structural, societal, and cultural features permeate everything that we do. In other words, our physical and social environments shape our every experience. Though our brains have evolved to be sensitive to the environments we inhabit, the degree of sensitivity varies by developmental stage and interacts with individual factors in ways that we do not yet fully understand. My research focuses on understanding the complex back and forth between individuals and their environments to inform prevention and intervention efforts to reduce risk for psychosis and severe mental illness.

My work so far, as a result, has aimed to understand psychosis vulnerability from both an individual and systemic lens.  Specifically, my first line of research aims to relate environmental exposures directly to vulnerability for developing a psychotic disorder. While individual-level environmental factors such as supportive parenting and childhood trauma have been extensively studied, local, regional, and country-level factors are relatively less understood within clinical science. Given that systemic inequities and environmental factors are not well understood, in a recent study I sought to establish distinct dimensions of types of structural environmental exposures. These included stimulation exposures conferring lack of safety and high attentional demands (e.g., neighborhood crime and population density), deprivation exposures constituting a lack of developmentally appropriate resources (e.g., neighborhood deprivation), and discrepancy exposures conferring feelings of social exclusion and lack of belonging (e.g., neighborhood income inequality and low ethnic density). I found evidence that these types of exposures could be meaningfully conceptualized as distinct (Vargas et al., 2021). Of note, all environmental exposure domains (measured by both objective measures such as Census-derived neighborhood characteristics, and self-report) related to psychosis vulnerability, with some exposures (e.g., deprivation) showing stronger associations relative to others. This work suggests that going beyond individual-level exposures, toward neighborhood, societal, and even cultural features, could be highly informative for psychosis vulnerability and resilience models.

My second line of research aims to dig further by identifying candidate neural and functional mechanisms through which environmental factors impact mental health across development. I have used MRI methods because I believe by allowing us a window into what is going on in our brains structurally, they allow us to understand possible lasting impacts of stress, environments, and systemic inequities. Interestingly, MRI allows us to identify relations between the brain, stress, and environments across different ages, which could help us understand how development plays a role. Particularly, I am interested in how biomarkers of types of environments and links to emergent behavior and health outcomes could aid early identification efforts. Identifying individuals who are most vulnerable to mental illness through environmental disadvantage could ultimately help us intervene earlier. At the population level, it could inform more effective allocation of prevention and intervention resources for vulnerable communities. In a recent study using a nationally representative United States sample of 9-11-year-old children, I found that these stimulation, deprivation, and discrepancy neighborhood-level features were associated with brain regions implicated in a host of cognitive, affective, and social functions (Vargas et al. 2022).  My previous work has shown that these relations hold even after accounting for more proximal, individual-level characteristics such as parental education and household income (Vargas et al., 2020). In my future research, I aim to clarify potential biomarkers and neural features that relate to different environmental factors across different developmental periods.

Understanding the systemic environmental factors that influence mental illness vulnerability is essential to the advancement of prevention and intervention-focused clinical research for vulnerable individuals, psychosis, and severe mental illness. In the future, I hope to apply my work to prevention, intervention, and health disparity-relevant translational research and advocacy. Being a SIRS Early Career Award recipient has been a highly rewarding and enriching experience, where I have had the opportunity to learn from brilliant scientists in the community as to how to achieve these goals in the service of helping individuals with psychosis, harnessing the power of collaboration to build bridges and further understanding.

My interest in mental health research spawned from my surroundings - many of my friends and family are living with various mental illnesses, so I became very sensible to these issues from a young age. Every day we are making progress in researching major mental illnesses, but we still do not know how they start or what can be done from early stages to delay its progress. To provide some insight, our lab starts from the very beginning - from cells itself and its proteins. We rely on previous genetic research to identify possible gene candidates and investigate proteins for which they encode and their possible disruption like protein aggregation. Our aims include dissecting proteins to their smallest bits to find which parts could be tipping the scale towards illness progression. Also, we are incorporating environmental factors like stress in our research to provide a bigger picture. My work mostly focuses on depression, which is highly prevalent in patients with schizophrenia, but still not talked about enough. In the future, I hope my work will bring awareness to the connection between schizophrenia (and other psychosis) and depression and how important it is to address both from early stages. On the bigger scale, I also hope research from our lab will provide more insight of specific proteins involved in major mental illnesses, thus leading towards more personalized treatment, but also more sensitive (and earlier) diagnostics. In spirit of this, I would like to emphasize how important conferences like SIRS are to the lives of people with psychosis. As an early career researcher, having an opportunity to learn from leading experts in different fields from across the globe, at one place, means a lot. Attending SIRS 2022 allowed me to meet many senior scientists, even people whose work I have read and relied on heavily in my research. But more importantly, being one of the Early Career Awardee allowed me to talk to my peers about challenges of working in academia and learn about new oportunities to learn outside of the lab.

Research on schizophrenia: an adventure not to be missed.

After finishing my residency in clinical psychology and training in psychological treatments for severe mental disorders, I decided to go behind the scenes of psychological treatment through research on schizophrenia, and that was the beginning of an incredible adventure!

It was not easy for me to move from clinical psychology to research, it required me to learn new skills from almost zero, until in my last year I started to integrate these two professional profiles. My main motivation for entering the world of psychosis research was to contribute to improving treatments so that as many people with psychosis as possible can have access to them as soon as possible. In addition to this, I discovered that new technologies will be my main interest for the following years of my career.

Undoubtedly, networking, meeting colleagues and references in the field of schizophrenia research is an important part of doing research. In that direction, being able to participate in the 2022 Annual SIRS Congress in Florence, exhibiting my poster in Florence was a unique opportunity to exchange contacts and get invaluable feedback from colleagues. Specifically, this year I presented part of my thesis work at the SIRS 2022 Congress, and it was one of the most enriching experiences of my career! This work explores how jumping to conclusions is related to and can influence how we interpret social information. We found that people with first episodes of psychosis who jump to conclusions are more likely to be impaired in their facial recognition of others' emotions, as well as to attribute the cause of negative events to themselves. However, these same people would not be impaired in decoding what others might be thinking. This new knowledge will allow us to refine psychological treatments that work with information processing biases and shape the topics of therapies toward those directions specifically.

For this work, I had the pleasure of receiving the Early Career Award, which was a unique impulse and a great motivation to continue exploring how to ameliorate the problems that living with psychosis can bring. Thanks to that possibility I was able to share time, exchange ideas and learn with my mentor, Dr. Matcheri Ketshavan. SIRS offers us a unique possibility to meet, exchange and learn from other researchers, both early career and long-time researchers.

How does this adventure continue? Considering the present and, above all, the future of research, I would like to highlight two points of particular interest to me. First, the possibility of developing treatments based on new technologies is a possibility to make them attractive, less expensive and simpler, which is why I am very motivated to continue in this direction after my doctorate. On the other hand, these years I learned that the wonderful thing about working in research lies in the need to generate collaborative work that includes people with psychosis and their families. I consider that first-person knowledge of the problems, as well as the need to generate solutions together, is the most appropriate way to build a research project. I have a lot to learn in this direction and it is very motivating for me. I recommend to colleagues clinical psychologists to enter into the world of schizophrenia research and above all to make community with colleagues through the SIRS. You will not come out the same as you went in!

People have diverse experiences of psychosis. As a physician training in psychiatry, I am taught to consider multiple factors to tailor my clinical approach and the choice of treatment: the personal history and values of patients, their culture, their social and physical environments, their family background, etc. But despite these considerations, one challenge that remains is to predict how a person’s psychotic disorder will evolve over time and during treatment. I believe this question, and its implications for personalizing our interventions, are important areas in psychosis research right now.

At the 2022 SIRS Congress, I presented research that aims to explore the diversity of symptom trajectories before and during psychosis. My research is based on data from PEPP-Montréal, an early intervention service for people with a first episode of psychosis. Under the mentorship of Dr Jai Shah and colleagues, I examined patterns of symptoms, including psychotic and non-psychotic symptoms, experienced by patients of PEPP-Montréal at different stages of their psychotic disorder. We found that some of the symptoms that preceded patients’ psychotic episodes were associated with the severity of their mental health problems later during treatment. My hope is that this type of research can help us better anticipate clinical needs and personalize services according to the unique symptom profiles of people with a first episode of psychosis.

After I complete my psychiatry training at McGill University, I hope to pursue a career in psychosis research as a clinician-scientist. Attending the SIRS Congress and receiving an Early Career Award have been incredible for my career journey. I was inspired by the research, clinical, and peer support initiatives that were presented. In addition to the opportunity of sharing my work, I had the chance to meet with mentors, to network, and to get new insights into the types of research questions I want to explore next.

I think a critical direction for future research is to understand how large-scale changes, at the societal and environmental levels, are influencing mental health across the spectrum of schizophrenia and psychosis. For example, climate change will impact several determinants of mental health relevant to psychosis, and it may exacerbate health inequalities related to people’s socioeconomic status, livelihoods, and geographical location. Another development to consider is the rise of immersive technologies like virtual reality and the metaverse: because these media can foster new forms of connections (and disconnections) between individuals, they seem to hold unique opportunities and risks for people with psychosis. As immersive digital media become more disseminated and accessible, I anticipate that there will be a need for clinical counselling and policymaking around their use, and to do so, we will need to study how they affect people with and without psychosis. I hope that we can harness some of that emerging knowledge to develop new treatment options. I am thinking for example of therapies delivered via virtual reality, which have the potential to address important therapeutic needs while tapping into people’s technological preferences. At the 2022 SIRS Congress, many scientific presentations illustrated the possibilities of digital treatment options, as well as the need to be mindful of technology-related addictions and distress.

I am excited to tackle these research areas and more as I move forward in my career, and I see multidisciplinary dialogues as central to my project. Importantly for the lives of people with psychosis, knowledge should be produced and shared in collaboration with people with lived experience, their families, health professionals, and researchers from various backgrounds. SIRS provides a space that facilitates these connections, and therefore I see SIRS as playing an important role in my future research endeavors.

A recent review by Torous and colleagues (2021) highlighted that detailed adverse events reporting is rare within the area of digital mental health, and as such, it is currently difficult to draw inferences about the safety of digital interventions. Evidence suggests that people with psychosis are willing and able to use or test digital health technologies (DHTs) to support their mental healthcare and recovery. DHTs present the unique opportunity for increased adverse events reporting and assessment of user experience due to the flexibility and adaptability of these technologies. For example, an app could have an in-built adverse event reporting function to allow users to self-report in real-time adverse events they might experience while taking part in a DHT research study. By providing participants with a range of options to report adverse events, we can record and report potential negative effects of DHTs and ensure these technologies are as safe as possible.

There is currently no consistent approach for reporting adverse events associated with digital health platforms for schizophrenia (DHPS). Convened by Professor Bucci and supported by the Schizophrenia International Research Society Research Harmonisation Award, our network is called the International Collaboration for Harmonising Adverse Events Reporting in Technology for Schizophrenia (iCHARTS). Our aim is to examine the full range of adverse events recorded and reported in DHPS trials, with a view to improving and standardising, where possible, adverse events and training procedures.

Over the past 12 months, we have successfully brought together 10 senior researchers, 14 Early Career Researchers, and three experts by experience across eight countries. During our proposed 2-year programme of work, we aim to produce a comprehensive adverse events reporting procedure, tool, and training resource to facilitate systematic reporting of adverse events in future DHPS studies. Our RHA draws on existing datasets, and members’ international expertise, to catalogue adverse events within DHPS internationally. This shared empirical data, along with an analysis of collated standard operating procedures (SOPs), will provide the basis for a harmonised reporting framework and procedure for reporting adverse events in DHPS.

The format of our iCHARTS Network has comprised wider network meetings as well as smaller Writing Group meetings (led by early career researcher members of our Network), to progress our planned programme of work. We recognise that any outputs from this Network are limited by the countries of members involved in the Network, but we look forward to producing an open-source document that can be updated and made globally relevant in due course. We also hope that the outputs from Writing Groups are “live” documents, open to feedback and additional content from experts, including experts by experience, around the world, to ensure the outputs from this Network reflect the most up-to-date global evidence.

A year into our SIRS RHA, we have collated how adverse event definitions and procedures differ across countries. We have analysed adverse events data from a wide range of DHPS studies to produce a comprehensive list of adverse events reported in 33 (so far) DHPS trials. We have also analysed over 36 Standard Operating Procedures used in DHPS trials and utilised our international collaboration Network to understand and harmonise these procedures.

We have been struck by how open many psychosis researchers have been for sharing data about adverse events that they have collected while trialling a whole range of digital interventions. We are deeply grateful for everyone’s efforts and especially Aansha (a research assistant who is assisting with the project) for making sure that they are fully anonymised. We are still welcoming datasets and hope more will come soon. Our writing group features psychiatrists, clinical psychologists, and service user researchers from across the world and we are conducting an inductive content analysis that includes all that diverse expertise. So far, we are noticing that adverse events reports vary in the amount of detail reported.

Collating the Standard Operating Procedures has brought to light how adverse events reporting differs across trials, study designs (particularly whether the study is investigating a medical device), and countries. Whilst anecdotally researchers clearly train research workers to record and report adverse events, these training procedures do not seem to be documented consistently in trials – one of our aims is to produce a training procedure that researchers can use to train research workers in sensitively asking service users about harm, and methods to record and report adverse events in the context of DHPS trials. This is where the group benefits from international collaboration to draw on the expertise of members, to understand more about these procedures.

As we move into Year 2 of the RHA Network, we will continue to harmonise our reporting procedures and would like to draw on the SIRS member community for input in how we can further develop adverse events procedures. The Network recognises and value the perspectives of our expert by experience members. Encouragement of mentor/mentee meetings between senior and early career researchers has also highlighted the value of mentorship and provided the opportunity to further collaborations between digital mental health researchers both nationally and internationally.

Psychiatry was the field of Medicine I chose after graduating medical school and performing field work in rural Northern New Mexico as a general practitioner for 3 years. Most of my patients would come into the clinic because of anxiety or depression and various kinds of emotional distress. So I chose to go back into training to be a psychiatrist. My interest in schizophrenia specifically goes back to the days of two movies —One Flew Over the Cuckoo’s Nest (1975) and I Never Promised you a Rose Garden (1977). The latter initiated my curiosity about the experiences people with schizophrenia have and their underlying basis. I then proceeded to read every book ever written by Frieda Fromm-Reichmann (the psychiatrist in the 1977 film) about the psychoanalysis of her patients. The former movie initiated my innate desire to change society for the better and certainly improve the quality of care in psychiatric inpatient units.  I chose a career in research, because it was clear to me that psychiatrists had no evidence-based knowledge for effectively, objectively and consistently treating their patients. The field seemed so primitive to me in the 1970’s that it was a welcomed challenge to think of being able to make some important contributions to our understanding of psychotic symptoms. There was so much yet to be done. When as a resident, I attended a lecture by Seymour Kety explaining how his adoption studies in Denmark had shown that biology and likely inheritance had far more influence on the development of schizophrenia than the environment, it was then that I decided to focus on biologic mechanisms for schizophrenia, and particularly genetic ones.

As I look back on these past 40+ years, I see that many biological findings came and then disappeared over and over again. Most depended heavily on the availability of (or lack of) advanced technology that allowed us to view them in debth. I followed many patients over the years by brain imaging to understand the progression of the schizophrenia process over time and I spent many years gathering data from large families with several members afflicted with the disorder. I hope that my research has contributed substantially to understanding the underlying progressive brain changes in schizophrenia and the heterogeneity of the possible genetic causes. Today I see those so called “multiplex families” I meticulously evaluated from all over the USA and other countries as a gold mine for further understanding of the disorder. I hope others will take off from where I left off in the quest for knowledge about schizophrenia. Currently I focus most of my time developing and expanding treatment programs for new onset cases of schizophrenia and their families. Each individual who comes to me for treatment is unique and gives me further insight into how we may improve the quality of all of their lives. I am now approaching an understanding of schizophrenia through them.