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SIRS Research Stories

Sachin Nagendrappa, St. John’s Medical College Hospital

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Sachin Nagendrappa, St. John's Medical College Hospital

My interest in psychiatry started in medical school. I was fortunate to get a teacher Dr. Sanjay, a Psychiatrist who sparked my interest in the field of psychosis. As Dr. Sanjay knew my interest in psychiatry, he would take me to government-run mental health rehabilitation centers where most people with untreated psychosis were admitted. During the visits, he taught me about Schizophrenia in detail and I saw the majority of patients with severe symptoms whom he treated were getting better and also realized the stigma they face and several other social factors associated with the illness. I decided to pursue my passion in the field of psychiatry to learn more. I joined as a resident to pursue my post-graduation in Psychiatry at the National Institute of Mental Health and Neurosciences(NIMHANS), where I began my research in Schizophrenia. I was privileged to get mentors at NIMHANS who are stalwarts in the field of Schizophrenia who taught me the basics of research and continue to help me grow as a researcher in the field of Schizophrenia. My initial research began with treatment-resistant Schizophrenia and the factors leading to ultra-resistance. This led me to work on the Clinical, cognitive and neurobiological effects of clozapine in treatment-resistant Schizophrenia. I used a functional near-infrared spectroscopic study to evaluate the pre-post effects of clozapine in patients with treatment-resistant Schizophrenia. Later worked briefly on the tele consultation model for improving outcomes in Schizophrenia, in people who lack access to treatment in India. Currently, I am working as an Assistant Professor of Psychiatry at St Johns Medical College Hospital, Bengaluru, India, and will be beginning my journey as a Ph. D Scholar this month and continue to work in the field of Schizophrenia.

The journey as a researcher in the field of Schizophrenia is personally satisfying and made me more curious to learn and understand various aspects of treatment resistance in Schizophrenia. I am also involved in several other research collaborations including collaborations with UNICEF, ETH Switzerland, the University of Pittsburgh, Global mental health International, and several other national collaborations. The major studies in which I’m involved currently are RCT evaluating the efficacy of a repurposed drug in Schizophrenia, a study on neurophysiological correlates of self-other distinction in Schizophrenia, etc.

After I joined St Johns Medical College hospital, a general hospital,  I’m seeing numerous patients with chronic medical illnesses with comorbid psychiatric illnesses who are not taking adequate care of themselves. They come with varying knowledge of their illnesses and vary in their ability to monitor internal sensations and thoughts that can serve to improve self-care. This has intrigued me. I found it interesting to know the factors, and I have chosen to explore if low awareness of bodily sensation in chronic medical illnesses is similar to a lack of awareness of chronic psychotic illnesses. I believe this will potentially help broaden the concept of awareness of the illness and support cognitively informed interventions on the one hand, and radically alter the concept of awareness of illness on the other. I will use my research in understanding the treatment resistance in Schizophrenia, looking forward to developing cognitively informed intervention models to gain better insight in patients with Schizophrenia and thus improve the outcomes

I am ever grateful for the guidance of excellent mentors throughout my career and especially SIRS. SIRS has always motivated early-career researchers like me. SIRS stands at the forefront in providing support and the opportunity to interact with and gain knowledge from the esteemed and eminent faculty who are much more experienced in Schizophrenia research. I always look forward to attending SIRS annual conferences. The experience to gain as an early career researcher will be enormous and this will give a great fillip to early-career researchers' desire to set up an independent career in research.

Yours Sincerely,

Sachin Nagendrappa

The Global Schizophrenia Award is to support a SIRS member in a low and middle income country to attend the annual SIRS congress. The intent of the award is to widen diversity and to bring a member from under-represented countries to a state-of-the-art meeting to establish collaborations with other SIRS members. Sachin Nagendrappa was named the SIRS 2022 Global Schizophrenia Awardee.

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Matcheri Keshavan, Harvard University

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Matcheri Keshavan, Harvard University

I have always been interested in the nature of the self- questions such as who we are, and how an optimum knowledge of the self is critical for defining our health and happiness.  As I began learning to learn about the brain in medical school, I began asking- what in our brain determines our ability to distinguish the self from others. The young woman in my psychiatry rotation, diagnosed with schizophrenia, who was troubled by thoughts being stolen by, and feelings of her actions being controlled by an alien power, reflecting a blurred boundary between the self and other. This brilliant engineering student also had a substantive decline in her cognitive functions. She had been examined by neurologists, who felt there was no brain dysfunction they could identify; she was diagnosed with a “functional” psychosis. She questioned the diagnosis of schizophrenia, and I had no answer to her question as to how I can confirm her diagnosis. Her psychosis got better with medications, though she remained functionally impaired. Working with her crystallized my passion to study this illness. The fact that psychiatry was a field in which we could help change lives but still knew so little (which is true even now) drew me to pursue research.

It is hard to pinpoint a single mentor, but many remarkable individuals with illness, teachers and institutions were formative for my subsequent development as a clinician, teacher and researcher. Successive training experiences led me to learn about the various tools of understanding the brain, including imaging, EEG, neuroendocrine, genetic and cognitive neuroscience approaches. In parallel, as I began working with patients with a first psychotic episode, it became clear to me that studies in the early course is the best way to understanding these illnesses. It was also clear that treating psychosis was only part of the solution, and that addressing cognitive, and functional impairments early in the illness is critical. A series of controlled trials of cognitive enhancement therapy led to promising results for individuals in the early course of schizophrenia, and represents one of the most gratifying aspects of my work thus far.

As I continued to work with people with serious mental illnesses, it also became clear that no two individuals the same type of illness. Our symptom-based diagnostic labels were not neatly mapping on to what we saw in the clinic, with substantive overlaps in clinical presentation, treatment response and biomarkers across several psychotic illnesses, including bipolar disorders and schizophrenia. On the other hand, there appeared to be distinct groups of psychosis patients that appeared to differ in regard to the severity of cognitive impairments. This led us, as part of the bipolar-schizophrenia network for intermediate phenotypes (BSNIP) consortium, to propose a novel approach classification of psychotic disorders using cognition and electrophysiological biomarkers agnostic to DSM diagnoses.   This suggests that we may be in a position to predict outcomes in individuals in the early course of psychosis disorders, and also to identify which patients might respond best to specific psychosocial, or pharmacological interventions.  These questions shape my ongoing research which seek to translate research insights into clinical practice.

Looking back, it appears that understanding cognition and its impairments in psychoses, as well as improving these deficits is a theme that “connects the dots” in my career. It has also become clear that cognition may be the royal road to understanding this brain disease. More work needs to be done, that will hopefully steer our field toward a more precise way to understand, diagnose, and treat these highly enigmatic, and disabling illnesses.

Each year, the Society recognizes a SIRS member for an outstanding clinical/community contribution to schizophrenia research.  The contribution may be based on a single discovery or a cumulative body of work. The selection of the award recipient is based on the quality of the contribution(s) and its impact in advancing schizophrenia research. recognizes individuals in the field of schizophrenia research. Matcheri Keshavan was named the SIRS 2022 Outstanding Clinical and Community Research Awardee.

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Robin Emsley, Faculty of Medicine and Health Sciences, Stellenbosch University

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Robin Emsley, Faculty of Medicine and Health Sciences, Stellenbosch University

I have had the privilege of spending the major part of my professional career involved in researching the illness called schizophrenia. After qualifying as I psychiatrist and opting for an academic career in the early 1980’s I needed to choose a research area to focus on. This wasn’t a difficult choice because at the time I was working in a State psychiatric hospital and most of the hospital admissions were suffering from schizophrenia. Hospital beds were filled with acutely ill people requiring urgent attention. The impact of the illness on the afflicted individuals and their families was huge. Patients were being re-admitted over and over again – improving with treatment, being discharged and having to be readmitted a few weeks or months later. Together with a great team of research colleagues, we therefore focussed our research on identifying which factors are important in determining the outcome of illness. The most important issue that we identified was that patients were stopping their treatment soon after discharge. While various reasons are given for why they stopped taking the medication, the common denominator was that they were not convinced of the need for treatment. Illness unawareness and failure to recognise the need the treatment are core features of the illness and need to be kept in mind when discussing treatment options with patients and their families. The second most important factor that we identified was use of illicit drugs. In our setting here in Cape Town cannabis and crystal methamphetamine are the two most commonly used drugs, and both seem to be particularly important in increasing the risk of developing schizophrenia and worsening the outcome of the illness. Our work has highlighted the potentially grave consequences of illness relapse and consequently we have focussed on relapse prevention as a treatment priority.

Over the past years we have been pioneering the use of long-acting injectable antipsychotics as an early treatment option, as a way of providing assured, uninterrupted treatment during the critical period when the illness is at its most aggressive and relapses are most likely to occur.  We use a patient-centred, shared decision-making approach and involve family and carers as much as possible in the process. Using this approach, in which the advantages of continuous treatment and the risks of relapse are highlighted, patient acceptance is very good and overall outcomes are generally favourable.   Most patients achieve remission of the acute psychosis symptoms together with improvements in overall social and occupational functioning and better quality of life. While there are still many challenges that remain in our understanding and management of schizophrenia, impressive progress has been made, and the best use of available treatments can make a huge difference to the overall outcome. In keeping with modern public health principles, providing appropriate and continuous treatment as early as possible in the illness to prevent accruing morbidity, offers individuals the best chance of a favourable outcome.

About

Each year, the Society recognizes individuals in the field of schizophrenia research. Robin Emsley was named the SIRS 2022 Distinguished Service Awardee. SIRS recognizes a member who has provided extraordinary service to the Schizophrenia International Research Society. Their service has been a significant contribution to the society.

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E. Fuller Torrey, Stanley Medical Research Institute, Uniformed Services University of the Health Sciences, USA

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E. Fuller Torrey

When I was in college I was introduced to schizophrenia by my younger sister, Rhoda, who was so diagnosed at age 17. As a young psychiatrist I was introduced to infectious agents as a possible cause of schizophrenia by Dr. Carlton Gajdusek, who was subsequently awarded a Nobel Prize for his work on prion diseases of the brain. From the 1890s until the 1920s there had been some interest in infectious agents as a possible cause of schizophrenia, especially after the 1918-1919 influenza pandemic which was followed by many cases of a schizophrenia-like psychosis. However, for the next half-century interest in infectious agents in psychiatry virtually disappeared. Perhaps my major contribution to the schizophrenia research field has been to revive interest in an infectious hypothesis, beginning in 1973 with my paper in Lancet on “Slow and Latent Viruses in Schizophrenia”.

Since that time I have been continuously involved in research on infectious agents as possible causes for schizophrenia and bipolar disorder. The vast majority of this research has been done in collaboration with my friend and colleague, Dr. Robert Yolken, a specialist in pediatric infectious diseases at Johns Hopkins University Medical Center. Our research was enormously facilitated in 1989 when the late Ted and Vada Stanley generously offered to fund it. We therefore set up the Stanley Laboratory for Developmental Neurovirology under Dr. Yolken's direction, and it has become the world's leading laboratory for such research. Serological and CSF specimens for study have been obtained from St. Elizabeth’s hospital; the Stanley Research Unit under the direction of Dr. Faith Dickerson at Sheppard Pratt Hospital; and from a study of identical twins. Using the Stanley funds we also created The Stanley Brain Bank under the direction of Dr. Maree Webster, both to provide tissue for our own research as well as for researchers throughout the world.

In the intervening years we have examined a large number of infectious agents to see whether they might cause some cases of schizophrenia. Among the more interesting findings have been our studies on the endogenous retroviruses, especially HERV- W; the herpes family of viruses, especially cytomegalovirus; and the parasite Toxoplasma gondii. The latter is carried by cats and infects approximately 30% of Americans, most asymptomatically. Recent research has suggested that this parasite may be linked to approximate 20% of cases of schizophrenia; the evidence for this is summarized in my current book, Parasites, Pussycats and Psychosis: The Unknown Dangers of Human Toxoplasmosis (2021).

During the same years I have examined epidemiological aspects of schizophrenia to ascertain their compatibility with an infectious hypothesis. Schizophrenia has a clearly defined 6 to 8% birth excess in the winter and spring months, consistent with an infectious agent. Being born in, or raised in, an urban area compared to a rural area doubles your chances of later being diagnosed with the disease. Contrary to what is claimed in most textbooks, the incidence and prevalence of schizophrenia varies widely across the world, as summarized in my book Schizophrenia and Civilization (1980). Finally, there is good evidence that schizophrenia is a comparatively new disease and only became common within the past 300 years; this is summarized in my book The Invisible Plague: The Rise of Mental Illness from 1750 to the Present (2002). These epidemiological aspects are consistent with an infectious agent.

Finally, has research on infectious aspects of schizophrenia produced any new or improved treatments? Although it has opened up possibilities for new treatments using anti-infective and anti-inflammatory agents, the research has not yet led to any significant breakthroughs. Dr. Yolken's laboratory has shown that many standard antipsychotic drugs also suppress viruses. For example, some metabolites of clozapine suppress the growth of HIV in laboratory cultures. We have also supported research to identify drugs which are effective against brain cysts formed by Toxoplasma gondii; currently no effective drug exists. Perhaps most importantly, the infectious hypothesis raises the possibility of true prevention of schizophrenia if a vaccine could be developed against the causative infectious agent or agents.

 

About

Each year, the Society recognizes individuals in the field of schizophrenia research. E. Fuller Torrey was named the SIRS 2021 Lifetime Achievement Awardee. The Lifetime Achievement Award is SIRS most prestigious award, given to a scientist who has made a significant contribution to the advancement of the field of schizophrenia research. These individuals have:

– an established history in schizophrenia research
– exhibited leadership and provided mentoring to young investigators
– positively impacted the field of schizophrenia research

You can find more about E. Fuller Torrey's research and accomplishments by clicking on the button.

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