SIRS Research Stories

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.