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Julia Rodriguez-Sanchez, M.Sc., PhD Student, University College London

Julia Rodriguez-Sanchez, M.Sc.

I first became interested in psychosis spectrum disorders during the first year of my PhD at University College London. I had read about the work of Dr Rick Adams, who was using computational tools to study schizophrenia, and decided to pursue a rotation project with him. During the rotation, I learnt that we can investigate brain function without the need for invasive procedures by using mathematical models. This is crucial for two key reasons. First, it allows us to study psychosis directly in patients, accounting for important factors that cannot be fully captured in animal models. Second, it is more directly applicable to clinical practice, and could contribute to the development of new interventions.

As I delved into psychosis research, I also had to navigate the difficult experience of watching a loved one struggle with this condition. I became acutely aware of the stigma faced by those affected by psychosis, the difficulties associated with finding the right treatment, and the lack of guidance available for patients and their families. Indeed, despite the progress we have made over the past few decades in improving the understanding and treatment of psychosis, many important questions remain. What biological changes underlie the onset and progression of psychosis? How can we intervene earlier to improve outcomes? Can we develop more effective treatments with fewer side effects?

My research tries to tackle these questions by investigating biological changes in the early stages of psychosis. Specifically, I study the balance between excitatory and inhibitory activity in the brain – essentially, how different brain cells communicate to enable signal transmission whilst maintaining stability. This balance is crucial for brain function. It is altered, for example, in epilepsy, and it is also thought to become disrupted in psychosis spectrum disorders. My work focuses on individuals who are at a higher risk of developing psychosis, either due to a genetic predisposition or to experiencing symptoms, like unexplained sensory perceptions or odd thoughts, which do not meet the severity or frequency criteria for a psychosis spectrum disorder but are linked to higher conversion rates. Studying these early changes is important because it can help us understand how psychosis develops. It may also make it possible for doctors to tailor treatments for at-risk individuals before symptoms become severe.

At the SIRS 2024 congress, I presented results from my PhD research showing that both excitatory and inhibitory activity become altered in emerging psychosis. Using computational models and EEG, which measures electrical activity in the brain via small sensors placed on the scalp, I found evidence that changes affecting excitatory cells could be a primary cause of the illness. My findings also showed that reduced inhibition in the brain may contribute to the severity of symptoms. This is promising because it suggests that we could target these alterations using glutamatergic treatments. These treatments are not currently available for schizophrenia, but they have shown encouraging results in preclinical studies and have the potential to improve negative and cognitive symptoms – such as lack of motivation and difficulties with memory and attention – which are not addressed by current dopaminergic medications.

While there is still much to learn, this represents a first step toward more effective early interventions. Indeed, ongoing research is needed – for instance, to validate and improve the models that we use – but I am hopeful that we can make a meaningful impact by continuing to research excitation and inhibition in at-risk individuals. Attending the SIRS conference as an Early Career Awardee provided me with opportunities to learn about other advances and to receive feedback that inspired new research directions. Looking to the future, our goal is to explore how early interventions can be tailored based on individual brain function, and to study how brain changes relate to the development of specific symptoms. I believe that incorporating artificial intelligence into this research holds great promise for improving our understanding and enhancing treatment outcomes.

Recently, my loved one found a treatment that works for him, and has published a book sharing his experiences to raise awareness and inspire others facing similar challenges. I submitted my PhD thesis, and am looking forward to continuing investigating mental health as a postdoctoral researcher. I am confident that, with continued research and collaboration, we can achieve a better understanding of psychosis and offer hope to those affected by this condition.

Didenur Sahin Cevik, M.Sc., PhD Candidate Bilkent University, Turkey

Didenur Sahin Cevik, M.Sc.

I have always been captivated by understanding how the brain develops and how certain factors, such as genetics and life experiences, can shape a person’s vulnerability to mental health disorders such as schizophrenia. During my PhD studies under the supervision of Prof. Dr. Timothea Toulopoulou, I had the opportunity to work with both patients and healthy individuals, focusing on understanding the brain mechanisms involved in psychosis. Specifically, I am interested in how genetic and environmental factors like childhood trauma shape brain function. Psychosis, especially schizophrenia, is a complex disorder that affects how people think, feel, and behave. One way it impacts the brain is through changes in connectivity between different regions, particularly those involved in working memory—the ability to hold and manipulate information over short periods of time. By combining functional magnetic resonance imaging (fMRI) with twin data, I aim to better understand how brain connectivity is altered in people at risk for developing schizophrenia and how environmental and genetic factors affect these mechanisms. This research is important because it helps us understand not only the disruptions in the brain but also how some individuals seem to be more resilient to the effects of environmental stressors like trauma.

At the 2024 SIRS conference, I had the honor of receiving the Early Career Award, which provided a unique opportunity to present the findings of my latest study on the genetic resilience for schizophrenia and environmental risk on brain connectivity of adolescent twins. Schizophrenia is characterized by disruptions in the functional integration of working memory brain networks. Exposure to environmental risks during critical periods of brain development can disrupt the typical trajectory of brain maturation and increase the risk of schizophrenia. Investigating how genetic resilience, defined as a heritable measure of variation that increases resistance to disease by reducing the impact of risk loci, influences this link is critical to understanding the disorder’s causal mechanisms. To this aim, we collected fMRI data from 350 healthy twins oversampled for familiar schizophrenia risk. Functional connectivity indexes were calculated for each participant. We examined whether connectivity patterns in areas such as the paracingulate gyrus (PCG) and precentral area were predicted by environmental risks and how the polygenic resilience score for schizophrenia moderated this relationship. We found that genetic resilience moderated the relationship between environmental risk (discrimination and childhood trauma) and functional connectivity. For example, in individuals with lower levels of genetic resilience, childhood trauma reduced connectivity in the precentral region of the brain. Similarly, individuals who had lower levels of genetic risk discrimination decreased connectivity in the PCG. Individuals with higher genetic resilience did not show decreased connectivity in the same regions. Our findings underscore the interplay between genetics, environmental risk, and the neural mechanism in building resilience to schizophrenia. As PCG and precentral are relevant in schizophrenia, optimal connectivity in these regions may enhance a person’s ability to cope with adversity. The moderating role of genetic resilience highlights the importance of gene-environment interactions in investigating neural mechanisms responsible for genetic resilience to adversity.

Attending the SIRS conference as a young researcher was an invaluable opportunity. Not only was I able to share my findings with experts in the field, but I also had the opportunity to connect with researchers from all over the world. The chance to engage in discussions with other scientists and receive feedback on my research has been an invaluable experience.

Currently, I am in the final semester of my PhD and looking forward to continuing my research in the field of psychosis as a postdoc. I am passionate about continuing to work on how genetic and environmental risk factors shape brain development and may promote vulnerability to psychotic diseases by implicating brain mechanisms. Ultimately, my goal is to deepen the understanding of the neurobiological underpinnings of psychotic disorders to help develop early intervention strategies.

 

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