I became interested in psychosis in my first year studying undergraduate medicine. Like many people of that age, I began to think more philosophically than I had when younger. Questions such as “Do you perceive things the same way I do?”, “What is reality?”, “What makes us who we are?” and “Why do we behave the way we do?” were the subject of many debates between my friends and I at the time. If I’d been studying something other than medicine, my interest may have found a totally different outlet, but as a medical student, this most naturally aligned with schizophrenia, where perceptions, reality and identity are dramatically altered. I found learning about how the brain finds meaning much more profound and interesting than learning about medical diseases like heart failure.
I was initially attracted to the ideas of people like the psychotherapist and philosopher Carl Jung as I searched for answers to these questions. Later, as I read more about current schizophrenia research, I was excited to hear that modern brain imaging techniques were now being used to gain further insights. My desire to work in the field of schizophrenia was confirmed when I moved to London and began practicing as a doctor. Part of this was seeing first-hand that psychosis disproportionately affected young black men like myself, and the feedback I received from several patients that they valued having a peer as their doctor and felt more able to relate to me as a result.
Soon after qualifying, I got the opportunity to work with Professor Oliver Howes, a world expert on schizophrenia. I worked clinically as a psychiatrist in our outpatient service for people with treatment resistant schizophrenia (TREAT), based at the Maudsley hospital. I also started my PhD (“The neurobiology of negative and cognitive symptoms of schizophrenia”) at King’s College London, which aimed to understand the reasons that people with schizophrenia don’t recover full functioning even after the psychosis is successfully treated.
In my work presented at SIRS 2024, I showed that healthy volunteers who received amisulpride (a dopamine blocking antipsychotic) for 7 days at a dose used to treat schizophrenia developed negative symptoms (reduced motivation, emotional expression and enjoyment of activities) that we often see in schizophrenia. I also found a mechanism in the brain which might explain this, showing that amisulpride reduced the activation of an important part of the brain’s reward centre (the caudate) during an MRI task where people could win money whilst in the scanner, and that these two things were related to each other – so people who had more severe negative symptoms after receiving amisulpride also had greater reduction in their brain’s reward response to winning money. I showed that this was not a general effect of all antipsychotics; I found that another antipsychotic, aripiprazole, did not have these effects in healthy volunteers who also received it for 7 days. We included this experiment with aripiprazole because amisulpride blocks dopamine receptors to a greater extent than aripiprazole. Aripiprazole is a more flexible drug which acts in a similar way to amisulpride when dopamine levels are high, but can also have the opposite effect when dopamine levels are low. I like to think of it as a bit like the difference between a dimmer switch (aripiprazole) and a standard light switch (amisulpride).
Our study was designed to show cause and effect clearly, in that we compared both drugs to placebo (sugar pills), and neither the people taking the medications or us as the investigators knew who was taking what (double-blind). We chose to do our study in healthy volunteers, because there can be other factors which might confuse the interpretation of cause and effect on motivation after taking antipsychotics in people with schizophrenia. The most important thing to consider is that they usually reduce the distressing symptoms of psychosis, and so people are likely to be able to take part in activities more just because of this. But we screened the healthy volunteers in our study to be sure that they didn’t have any impairments at the start of the study for any reason, so we could be confident that any effects we saw were because of the drug.
This means that our results show quite clearly what many people with schizophrenia know first-hand, which is that receiving dopamine blocking drugs like amisulpride for a prolonged period can cause problems with motivation, emotional expression and enjoyment of activities. It’s important to note that negative symptoms are common in schizophrenia even in people not taking an antipsychotic, and that the evidence overall shows that antipsychotics improve negative symptoms in schizophrenia (probably because of the effect on improving psychosis). However, our work suggests that people who are experiencing negative symptoms caused by a drug like amisulpride might benefit from switching to a drug more like aripiprazole and also guides researchers towards developing future treatments for schizophrenia which don’t cause these problems with processing reward or motivation. If interested, you can find more information in the published article.
I was able to address some of the questions I had as a student, looking specifically at how the dopamine system relates to determining human behaviour. In future, I look forward to trying to answer more questions about how other neurotransmitters relate to changes in perception and understanding of reality. I am very grateful for the Early Career Award from SIRS that supported my conference attendance to present my work, as this gives me a great platform to address these and other questions, such as why black men are disproportionately affected by psychotic disorders, and how to improve outcomes for them and all people with schizophrenia.
Author Archive |
Enhancing Informed Consent in Schizophrenia Research by harnessing the power of lived experience perspectives.
Rebecca Soole1, 2, 3, Urska Arnautovska1, 2, 3, Nicole Korman1,2, Andrea Baker3, Dan Siskind1, 2, 3
1Faculty of Medicine, University of Queensland, Brisbane, Australia
2Metro South Addiction and Mental Health Services, Brisbane, Australia
3Queensland Centre for Mental Health Research, Brisbane, Australia
Informed consent is a cornerstone of self-determination of consumers receiving health and mental health services. Ensuring that potential participants understand the research study they are entering and voluntarily agree to participate is imperative to uphold ethical and regulatory standards of research activities. Patient Information and Consent Forms (PICFs) have faced criticism as potential barriers to valid consent due to their length and complexity. These barriers can be especially challenging for individuals with schizophrenia, who may face cognitive and motivational difficulties such as shorter attention and difficulties in executive functioning.
It is crucial that the very documents designed to facilitate informed consent are tailored to the unique needs of the population to ensure both ethical compliance and meaningful informed consent. To address these challenges, we conducted two participatory co-design sessions at a Brisbane psychosocial rehabilitation facility with individuals living with schizophrenia. The goal was to gather consumer insights on various aspects of our research teams current PICF—specifically its length, the use of visual prompts, and alternative ways to present content. This approach allowed us to gain invaluable insights from those who have firsthand experience with the challenges of navigating consent materials.
What we learned from consumers
The feedback from these sessions was clear: consumer representatives expressed preference for a shorter PICF, one that incorporated visual prompts as anchors to guide reading and facilitate initial discussions about the study. This approach was deemed more user-friendly, less overwhelming, and more motivating for individuals first learning about the research.
However, consumer representatives also recognised the need for a longer, more detailed text-based PICF for those who wanted or valued more in-depth information. To cater to this, our final design included both a short, icon-based PICF for initial conversations and a more detailed, text-based version for deeper engagement. To bridge these two versions, consumer representatives suggested the use of consistent visual icons to help readers navigate between the short and long PICFs.
To further enhance readability, a question-and-answer format was adopted for each paragraph in both versions. This format allows readers to quickly find the information that is most relevant to them. Additionally, consumer representatives provided valuable feedback on improving the overall aesthetics of the PICF, identifying jargon that could be simplified to improve accessibility, as well as language modifications to better emphasise autonomy.
Integrating consumer feedback into our practice
The insights gained from our co-design sessions have already begun to shape our research practices. The newly designed short and long-form PICFs received ethical clearance for use in our established schizophrenia platform trial. By incorporating lived experience into the design process, we are making strides toward more inclusive and accessible research practices.
Conclusion: Towards More Ethical and Effective Research
Traditional PICFs can inadvertently act as barriers to valid consent, particularly in populations with cognitive challenges. Our research underscores the importance of customising consent forms to meet the diverse needs of potential participants who may be interested in participating in research. By integrating the perspectives of those with lived experience, we made these materials more accessible and effective, promoting informed decision-making and enhancing the ethical conduct of schizophrenia research.
Impact and Future Directions
These adaptations are a critical step towards promoting informed decision-making in health-related research participation and meaningful and equitable engagement with individuals affected by schizophrenia. By tailoring PICFs to better serve individuals with schizophrenia, we empower this often-marginalised group to make informed choices, thus supporting their autonomy and reducing the stigma associated with schizophrenia. Our approach intends to not only facilitate greater access to research but also hopes to foster a more inclusive and respectful environment for participants of research studies and lived experience colleagues.
If you are interested in learning more about our co-designed PICFs or considering them for your research, please reach out to us at r.soole@uq.edu.au. Our dedicated team at the Physical and Mental Health Stream, University of Queensland, is committed to enhancing research accessibility for individuals living with schizophrenia, both in Australia and worldwide.
Samara Walpole, Ph.D.
Written by:
Samara Walpole, Ph.D.
Associate Research Fellow
University of Wollongong
I have always been fascinated by understanding how the brain works and exploring how the brain can change on a molecular level in the context of neuropsychiatric and neurological disorders. I first became interested in schizophrenia research during my undergraduate degree at the University of Wollongong, Australia, where I was fortunate to work with Professor Kelly Newell. Under her guidance, I explored molecular changes in the brain associated with schizophrenia using postmortem human brain tissue. This early exposure to research sparked my passion for understanding the biological foundations of psychiatric disorders and their complexity.
Building on this interest, I pursued a PhD with Professor Newell, focusing on the molecular changes in the brains of individuals with major depressive disorder. While my PhD work centred on depression, I explored mechanisms that are relevant across multiple psychiatric conditions, giving me a broader perspective on brain signalling and dysfunction. Now, in my postdoctoral research, I am returning to schizophrenia, applying the skills and knowledge I developed during my training to better understand the molecular and cellular changes that contribute to this disorder.
My research addresses several key questions that I believe are critical to advancing our understanding of schizophrenia. Specifically, I am to understand how several of the key biological pathways, such as inflammation and neurotransmitter signalling, contribute to the development and pathophysiology of schizophrenia as well as how these pathways could underpin the significant heterogeneity observed in schizophrenia.
At the 2024 SIRS congress, I was fortunate to be awarded the opportunity to present my latest findings on sex-specific alterations in glutamatergic receptors in schizophrenia. In this study, we explored the gene and protein levels of several receptors responsible for controlling the level of excitatory signalling that can occur in the nucleus accumbens, a brain region associated with reward processing, motivation and emotional regulation. We found that females with schizophrenia have increased levels of these receptors whilst males showed significantly decreased levels. Our findings reiterate the importance of investigating sex-specific differences in psychiatric disorders. Furthermore, addressing these changes would likely require distinct approaches for males and females with schizophrenia, highlighting the need for the development of sex-specific treatments.
As an emerging researcher in biological psychiatry, receiving an Early Career Award provided me with pivotal opportunities essential for my professional advancement in schizophrenia research. Attendance at the SIRS Congress in 2024 allowed me to meet researchers from around the world where I was able to have stimulating discussions around different techniques and approaches for best practice in my research. This award offered me the opportunity to connect with a mentor, Dr Sabina Berretta from Harvard Medical School. As an esteemed expert in postmortem research, Dr Berretta provided me invaluable guidance in refining my research direction and how to navigate the complex academic career path.
Currently, I am working as a postdoctoral researcher in the School of Medical, Indigenous and Health Sciences at the University of Wollongong, Australia. My research focus is now on exploring the impact of immune dysfunction as well as the impact of biological sex on changes to the molecular underpinnings of schizophrenia. Moving forward, I hope my research can provide a better understanding of subgroup-specific differences in schizophrenia to facilitate the better design and implementation of more targeted treatment options.
Felisa Maria Herrero, Dr. sc. nat.
Written by:
Felisa Herrero, M.Sc.
Ph.D. Student
University of Zurich
My journey into psychosis research began during my doctoral studies at the University of Zurich, Switzerland. Driven by a deep curiosity about the brain, I had the opportunity to work with Prof. Dr. Urs Meyer, whose research on the impact of maternal immune activation during pregnancy, and its implications for neuropsychiatric disorders, fascinated me. Through my work, I discovered the intriguing potential of endogenous retroviruses to explain patterns seen in psychiatric conditions.
Endogenous retroviruses (ERVs) are genetic elements in our DNA that come from viral infections that occurred throughout evolution. These viral remnants have shaped our biology, but growing evidence suggests they may also contribute to neuropsychiatric disorders. Specifically, I’m studying a family of these retroviruses called HERV-W, which may play a role in conditions like psychosis and other developmental disorders. For my research, I use a mouse model that expresses a human version of the HERV-W gene, particularly one that produces a viral protein involved in the infection process.
Our findings suggest that just expressing this gene causes significant changes in behavior and cognition in the mice, such as difficulties with memory, social interactions, and repetitive behaviors. These findings point to a potential link between this endogenous retrovirus and psychiatric conditions like schizophrenia.
We also observed that the expression of this viral gene altered the activity of many brain genes. Particularly, it affected genes related to cognition and brain development. For example, we found that genes linked to schizophrenia, such as Setd1a and Shank3, were turned down, along with genes that are crucial for the brain's synaptic development. This suggests that HERV-W may influence brain function in ways that contribute to these disorders.
One of the most interesting aspects of our findings was how the gene expression changes also affected the brain’s "epigenetic" profile. Epigenetics refers to the way environmental factors can turn genes on or off without changing the underlying DNA sequence of our genomes. We saw that in these mice, the altered expression of certain genes affected the way their brain cells were able to "read" other genes, which partially explain the cognitive and behavioral issues.
Nevertheless, we found promising results by using a drug that targeted the epigenetic changes in these mice, we were able to reverse some of the cognitive and behavioral deficits caused by the viral gene expression. This drug is currently being tested as a potential treatment for psychiatric disorders.
At the SIRS 2024 conference, I had the chance to share these findings and receive valuable feedback, which has inspired new directions for my research.
Although much remains to be discovered, I hope the field of endogenous retroviruses gains more attention. Understanding the role of these genes could improve our knowledge of psychosis development and individual differences. This research may pave the way for more personalized medical approaches, recognizing what we all already know: one-size-fits-all treatments are not effective for everyone.
As I move forward in my postdoctoral research, I am eager to deepen our understanding of how endogenous retroviruses contribute to schizophrenia. I hope to uncover new insights that not only enhance our scientific knowledge but also bring us closer to developing personalized treatments. By continuing to collaborate with fellow researchers and engaging with the wider scientific community, I am optimistic that we can make meaningful strides in improving the lives of individuals affected by psychosis.
Giulia Cattarinussi, M.D.’s SIRS Journey
Giulia Cattarinussi, M.D.
PhD Student, Research Assistant
Department of Neuroscience, University of Padova, Padova, Italy
I have always been interested in how the brain controls our thoughts and behaviors. When I started Medical School, from the very beginning I focused my target to become a psychiatrist, and I developed a deep interest in the brain mechanisms underlying psychosis. During my training in Psychiatry, alongside my clinical work with adolescents and young adults, I started exploring the brain abnormalities associated with the risk for psychosis. To do so, I employed functional magnetic resonance imaging, a non-invasive neuroimaging technique that allows to measure brain activity and connectivity. During my PhD in Neuroscience, I developed a deep interest in how changes in brain function correlate with clinical symptoms and cognitive functions in individuals with psychosis at different stages of the disorder. Understanding the neurobiology underlying symptoms and cognitive functioning in psychosis is crucial, as it could help facilitate earlier and personalized treatments, leading to better prognosis.
In 2024 I had the honor to win the SIRS Early Career Award and to attend the SIRS Congress. On that occasion, I was able to present the results of my latest study on the functional connectivity of the cerebellum, a region of the brain that helps coordinate a wide range of functions in the brain and the body. This study showed that altered connectivity of the cerebellum with rest of the brain was associated with more severe symptoms and greater cognitive impairments in individuals with psychosis. These results highlight the role of the cerebellum in the pathophysiology of psychosis and speak to the fact that therapeutic strategies targeting the cerebellum might represent promising interventions to reduce psychotic symptoms and to improve cognitive performance. The study has recently been published in Schizophrenia Research.
For a young researcher like me, attending the SIRS Congress gave me the opportunity to present my work to such a wide and highly specialized audience, to meet researchers from all around the world and to learn and discover the most updated notions in the field of schizophrenia research. I also had the chance to discuss my research with people with lived experience of psychosis, receiving invaluable feedback that substantially improved my work.
Currently, I am working as a post-doctoral researcher at the Department of Psychological Medicine at the Institute of Psychiatry, Psychology and Neuroscience at King’s College London. My research focuses on the brain changes associated with inflammation in psychosis, and how these correlate with symptoms and cognitive functioning. I am also involved in a multicentric study that aims to identify cognitive markers able to predict functioning in psychosis at the individual level.
Moving forward, I would like to establish my own research program dedicated to the study of brain abnormalities in individuals with psychosis and to the translation of these findings to clinical practice. I hope that my line of research will provide a clearer picture of the brain mechanisms underlying psychosis, ultimately helping the development of better diagnostic tools and therapeutic strategies.
Théo Korchia: Improving The Treatment Of Schizophrenia
My name is Théo KORCHIA, and I am a French psychiatrist, particularly involved in the treatment of early-onset schizophrenic disorders.
First of all, I'd like to thank the Schizophrenia International Research Society for honouring me with this prestigious award, as well as the Faculty of Medical and Paramedical Sciences at Aix-Marseille University (France) and the Assistance Publique des Hôpitaux de Marseille (APHM), which supported me and enabled me to spend a year at McGill University in Montreal.
Schizophrenia is a pathology often shrouded in mystery and prejudice, which profoundly affects the lives not only of those who suffer from it, but also those around them.
Management of the first psychotic episodes determines the outcome and prognosis of patients, and it is therefore necessary to improve it. Generally speaking, my work highlights the value of pharmacogenetics, adapting and personalizing the antipsychotic treatment to different genetic profiles for greater efficacy. Consequently, various side-effects of antipsychotic therapy, notably sexual dysfunction which is very disabling and leads to discontinuation of treatment, are drastically reduced. Patient motivation must also be strengthened by including them in therapeutic decisions to improve overall quality of life.
A particularly innovative aspect of my work concerns the impact of sexual dysfunction in patients suffering from schizophrenia. This issue, which has long remained on the fringes of psychiatric research, is crucial to patients' quality of life. Sexual dysfunction can be both a symptom of the illness and a side-effect of treatment, making it a dual challenge to overcome.
My perseverance on this issue has led to the publication of a meta-analysis of over 21,000 patients worldwide, in the journal JAMA Psychiatry.
Our study reveals with edifying clarity the high frequency of sexual dysfunction in individuals with schizophrenia spectrum disorders, showing an overall prevalence of 56.4%, with great variation in the types of dysfunction. This underlines the urgency of no longer neglecting adverse sexual effects in the treatment of schizophrenia. In the same way that weight gain or somnolence are side-effects commonly considered in the evaluation of antipsychotic treatments, it is crucial to include sexual dysfunction in our benefit-risk analysis. Recognizing and addressing these adverse effects goes beyond improving patients' quality of life; it represents a significant step forward in establishing a solid therapeutic alliance. Open communication about these issues, which are often stigmatized or played down, fosters a relationship of trust between doctor and patient, which is essential for effective management of schizophrenia. By taking these undesirable effects into account, we are improving not only adherence to treatment, but also the overall management of the patient, by recognising the importance of sexual health as a fundamental component of the patient's well-being.
This study therefore represents a significant advance, opening-up new prospects for treatments that are more respectful and tailored to patients' needs.
What drives my research is the conviction that innovation in psychiatry is not limited to the discovery of new drugs. It also lies in our ability to rethink the way we treat patients, by integrating dimensions of their experience that have been underestimated until now. The aim is twofold: to improve the quality of life of people suffering from schizophrenia and to reduce the obstacles to effective treatment, particularly those associated with the side effects of medication.
The implications of the studies I lead aim to have a direct impact on clinical practice by providing healthcare professionals with the tools they need to build a solid therapeutic alliance, thereby encouraging adherence to treatment and improving clinical outcomes. Considering sexual dysfunction, and more broadly the side effects of antipsychotics, is a concrete example of this influence.
My vision is of a dynamic psychiatry that is constantly evolving, where care is tailored to the uniqueness of each individual, and where each scientific advance lights the way towards better mental health.
I am therefore grateful to be able to share with you not only my research objectives, but also my vision of a future in which the management of schizophrenia is more enlightened, more effective and, above all, more humane. The road is long, the challenges many, but the passion that drives my quest is unshakeable. With determination and perseverance, we can provide meaningful answers to those struggling with mental suffering, and open up new horizons for the psychiatry of tomorrow.
Hyeon-Seung Lee: The Research Of An Early-Career Scientist On Schizophrenia & Self-Disturbance
Hyeon-Seung Lee
Individuals with depression often report their core belief of "I am worthless and unlovable." Individuals with anxiety disorders and OCD often report “what if” statement as a sign of excessive worry that leads to the thoughts of the worst-case scenario. Then, what would be a representative sign of schizophrenia? It is difficult to pick just one phenomenon given the multifaceted nature of the disorder, but I would pick "as if" statements related to the sense of self. Past research points out that self-disturbances are intertwined with the emergence of schizophrenia symptoms such as delusions and hallucinations. People at-risk often describe their experiences like this: “It feels 'as if' I am untuned to my body.” The anomalous feeling of altered self (agency, body ownership, self-boundary, and the experience of sensation, perception, and emotion) is a salient feature in the lives of those with schizophrenia. Bleuler’s original conceptualization of schizophrenia as that of the splitting of the mind and Kraepelin’s analogy of “an orchestra without a conductor” that indicates “a loss of inner unity”, both emphasize aberrations in the basic sense of self. These self-disturbances have been shown to be important for predicting functional outcomes.
Although the Research Domain Criteria (RDoC) of the National Institute of Mental Health (NIMH) and the International Classification of Diseases (ICD-11) include self-related features, self-disorder is not a prominent feature in either approach. Moreover, the sense of self has been ignored in the diagnosis, research, and treatment of schizophrenia due to lack of reliable and valid measures. With new methodological advances, it is now possible to empirically investigate the etiology and nature of self-disorders. As an early career researcher working with Dr. Sohee Park and multidisciplinary collaborators, I have developed and implemented novel experimental paradigms to elucidate and measure aspects of self-disturbances in schizophrenia. For instance, I have used virtual reality (VR) based measures to assess the neurocognitive representation of bodily space (i.e., peripersonal space) and how it is linked to schizophrenia symptoms. I also utilized VR-based social skills training to provide simulation and rehearsal of interpersonal interactions in realistic settings rather than explicitly teaching social cognitive skills to individuals with schizophrenia. In addition, I use computerized tools to visualize embodied emotions, manipulate cortical activities with brain stimulation, and assess the integrity of frontoparietal networks with neuroimaging to fully investigate the self-disturbances, symptoms, and social dysfunctions in schizophrenia.
Specifically, my master’s thesis focused on the abnormal spatial self-consciousness in schizophrenia formed through multisensory processing. As objects or people approach one’s personal space, multisensory neurons in the frontoparietal brain facilitate appropriate reactions. I used VR-based multisensory integration tasks to identify the inflection point where multisensory reaction time is facilitated, which estimates the size and slope of personal space. I found that individuals with schizophrenia generate small but unclearly-defined personal space boundaries relative to controls in the social context. The size or shape of personal space was associated with the severity of negative symptoms and hallucinations. In an ongoing review study, I further demonstrated how personal space is altered in various mental disorders (e.g., anxiety, post-traumatic stress disorder, autism spectrum disorders, etc.). The personal space size is enlarged in various disorders; however, the self-space is more solidly formed in individuals with anxiety and autism spectrum disorders, while the boundary is unclearly generated in those with schizophrenia. My dissertation research further examines the altered representation of personal space, investigating the effect of threat, social distress, and socioemotional factors.
Another line of research is investigating cross-cultural differences in the manifestation of psychosocial dysfunction. Previously, I examined the impact of the COVID-19 pandemic on the mental health of the general population from various cultures. Given the pandemic and social distancing were increasing feelings of social disconnection and loneliness, I expected that social disconnection and loneliness play a major role in poor physical and mental health. Delving into how cultural differences in public health strategies and compliance of the general population yield variances in reported stress, mood, anxiety, and psychotic experiences provided me with either a microscopic or a macroscopic view of psychosocial dysfunction. Moreover, I investigated culture-general and specific aspects of mental health symptoms and abnormal self-related experiences in schizophrenia. Previous cross-cultural works highlighted that though symptoms and self-disturbances are salient and prevalent in both Western and non-western cultures, there were culture-specific aspects such as relatively high tolerance for anomalous self-experiences and less attenuated embodied emotion in Koreans. I would like to continue to investigate cultural effects on psychosocial functions.
Psychiatric research is still mostly driven by researchers from Europe and North America. As a Korean scientist, I believe we have valuable contributions to make to this field and I hope to increase the representation of Korean and other Asian scientists in the field of schizophrenia research. Increased diversity of ideas and approaches will surely positively impact the future of the Schizophrenia International Research Society (SIRS).
Bobana Samardžija, mag. pharm. inv.: Our Research Holds Implications for the Future Diagnostics & Therapeutics
Bobana Samardžija, mag. pharm. inv.
Chronic mental illnesses, such as schizophrenia and major depressive disorder, are widespread and serious conditions that profoundly affect the lives of millions worldwide. Despite their prevalence, our comprehension of these disorders remains incomplete, and current therapeutic strategies often merely alleviate symptoms rather than target root causes. While extensive research has identified numerous genes associated with schizophrenia and major depressive disorder, their individual impacts tend to be marginal or specific to particular groups, underscoring the substantial influence of environmental factors alongside genetic predispositions.
Innovative approaches to unravel the complexities of these disorders are emerging, with a particular focus on disruptions in protein balance within the brain. This novel perspective draws inspiration from the realm of neurodegenerative diseases, where the accumulation of toxic protein aggregates significantly contributes to pathology.
At the University of Rijeka in Croatia, we examine post-mortem brain samples from individuals diagnosed with depression, Alzheimer's disease, those who have tragically died by suicide, as well as control subjects. We aim to elucidate the patterns of protein aggregation across diverse brain regions. Furthermore, we are investigating the possibility of multiple proteins aggregating together within the same individual and assess protein aggregation in cell cultures, all in hope to shed light on the intricate mechanisms underlying chronic mental illnesses.
Complementing these endeavors, we are also pioneering efforts to analyze aggregating proteins in blood samples obtained from living patients diagnosed with these challenging conditions, aiming to establish a non-invasive diagnostic tool that could revolutionize clinical practice.
By venturing beyond the genetic determinants, our research holds implications for the future of diagnostic methodologies and therapeutic interventions targeting chronic mental illnesses. This perspective empowers us to chart new paths towards understanding and addressing the multifaceted nature of these disorders, ultimately fostering hope for enhanced outcomes and improved quality of life for patients and their families.
Kirsten Borup Bojesen, MD, PhD: A Clinician-Scientist Studying Schizophrenia
Kirsten Borup Bojesen, MD, PhD
Residency trainee in psychiatry, postdoctoral researcher
Copenhagen University Hospital, Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Center Glostrup, Nordstjernevej 41, 2600 Glostrup
As a clinician-scientist, I have been struck by the large proportion of patients with schizophrenia insufficiently treated with antipsychotics and by the negative impact of cognitive deficits on everyday life. This has inspired me to explore the neurotransmitter aberrations underlying insufficient treatment response and cognitive deficits in patients with psychosis with a key focus on glutamate and GABA. My hope is that research on the impact of glutamatergic and GABAergic neurotransmitter disturbances on insufficient treatment outcome and cognition can pave the way for development of novel therapeutics.
My research has focused on glutamatergic and GABAergic aberrations in initially antipsychotic-naïve patients with first-episode psychosis and the impact of these disturbances on short- and long-term treatment outcome as well as cognitive performance. Specifically, we have found that higher levels of glutamate in thalamus and lower levels of GABA in dorsal Anterior Cingulate Cortex (dACC) are present from illness onset in antipsychotic-naïve first-episode patients and related to poor short-term treatment outcome after 6 and 26 weeks. Moreover, low GABA levels in dACC at illness onset are associated with poor functional outcome after two years of illness, and lower levels of glutamate in the dACC are associated with impaired cognitive function. Going further into the neurobiological underpinnings of insufficient treatment response, we investigated if brain glutamate and GABA levels were related to striatal dopaminergic function that is the main target of antipsychotic compounds. We observed that lower GABA levels in dACC were associated with higher striatal perfusion during the first two years of illness, suggesting that prefrontal GABA levels have a downregulatory effect on striatal activity and may be a novel treatment target. Furthermore, an aberrant interrelation between dACC levels of GABA and dopamine synthesis capacity in nucleus accumbens assessed with positron emission tomography could identify antipsychotic-naïve patients from healthy controls, whereas individual neurotransmitters were unable to do so, suggesting that aberrant interactions between neurotransmitters are more crucial for development of schizophrenia than single neurotransmitter disturbances. Currently, we examine the trajectory of glutamate levels in dACC and thalamus during the first two years of illness and relate neurotransmitter levels to long-term treatment outcome and cognitive function. Moreover, we investigate if a glutamatergic compound developed for neurological disorders is effective in patients with first-episode psychosis.
Our findings so far imply that treatment targeting glutamatergic and GABAergic disturbances can be beneficial in first-episode patients during the first two years of illness. As novel treatments are warranted not only during first-episode psychosis but also in the more chronic stage of the illness, we are currently preparing to re-examine brain levels of glutamate and GABA in the same cohort of patients and healthy controls after ten years.
I am always thrilled to attend the SIRS conference and get inspirated by both junior and senior researchers dedicating their time to improve the treatment and everyday life for patients with schizophrenia and psychotic disorders. The SIRS early career award 2023 and mentor program was very helpful in expanding my international network, and I especially gained from guidance on funding, publishing strategies, and life-work balance in academia. The program has supported me in developing my research career trajectory. It makes me believe that our combined international effort into unravelling the neurobiological and environmental factors underlying schizophrenia will lead to development of novel treatment options during the next decades.
Dr. Natalia Mansur Haddad’s Perspective & Experience as a Psychiatric Researcher
By: Dr. Natalia Mansur Haddad
I have enjoyed studying and understanding schizophrenia since the initial period of my first graduation, still in the field of psychology. Afterwards, I went to medical school to become a psychiatrist. Thereby, I have always been fascinated by psychosis in general as an area of study and research. During the last 10 years of clinical practice, I delved deeper into the care of chemically dependent patients and substance use disorders. At the confluence of these subjects, I have the privilege of studying the endocannabinoid system in a population with psychosis and how the impact of cannabis can influence its regulation.
In 2022 I had the great opportunity to win the SIRS Early Career Award. On that occasion, I was able to show the partial results of our study, which pointed to the use of cannabis as a factor that influences the reduction in endocannabinoid 2-AG values in plasma. In the following years, we continued to study the ECS and found an increase in peripheral CB2 receptors associated with the use of non-clozapine antipsychotics. The data complement the current literature, which is ambiguous and should be further studied.
It was very important for a young investigator like me to attend to an international meeting and it was a unique opportunity to establish international collaboration with important researchers in the field. It was a great honor and an encouragement to proceed with my research. I recently published an article with the findings of my thesis on changes in the endocannabinoid system of patients with schizophrenia in the European Archives of Psychiatry and Clinical Neuroscience Journal.
I have started my master's degree in February 2020, upgraded to doctorate degree and my thesis defense will take place next month.
All this development and career evolution in recent years gives me confidence to continue researching and sharing the results of my research with the international community. I believe that one of the main objectives is to align research results with clinical practice, thus contributing to the development of new screening methods for the disorder such as biomarkers, which can improve the diagnosis, treatment and prognosis of these individuals.
My research group is very diverse, we work at a Public Hospital and University in São Paulo - Brazil, and adverse situations are very frequent in an underrepresented country. However, year after year we prove that we can carry out quality research and talk to researchers from around the world, contributing relevant data from a large and diverse population sample with a major impact on global health. We intend to continue building knowledge and strengthening ties with the international community.
