SIRS Research Stories

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.

As a psychiatrist and scientist, I see the devastating toll taken by psychotic illnesses and the almost overwhelming gap between available and needed remedies. In my view, we can only achieve major leaps forward as a field by approaching problems with fresh perspectives and novel solutions. That is why I have dedicated my career to leveraging innovations in technology to better understand psychotic disorders and optimize treatment outcomes.

My presentations at the 2022 SIRS Annual Congress addressed this issue through three approaches.

While schizophrenia is related to significant functional impairment for some individuals, others are able to thrive socially and occupationally. In our talk on “Biopsychosocial Contributions to Functional Outcomes in Schizophrenia: A Data-Driven Machine Learning Approach,” we used machine learning methods to identify different patterns of functional outcomes in schizophrenia, and to relate these in reliable ways to biopsychosocial characteristics. We found that, in addition to a group of individuals who are resilient across the board, and a group who are more impaired, there is a cluster of people with schizophrenia who function well socially and with regards to independent living, but are impaired in occupational functioning. We would not have found this pattern without the machine learning approach, because we would not have known to look for it. We also found that the functioning pattern for each person was highly related to their internal sense of motivation and enjoyment, as well as the volume of some brain structures and cognitive ability. Importantly, race, sex, and socioeconomic status were not strong contributors to the functioning pattern of individuals with schizophrenia.

We know that social cognition – or the ability to process social information – is very important to functioning for people with schizophrenia. In our talk, “Speech and Language Disturbance in Schizophrenia are Related to Social Processing,” we showed that social cognitive is also related to how people with schizophrenia communicate. In particular, the ability of individuals to correctly identify emotions was closely related to how their speech was organized. This was found using traditional clinical ratings for speech, as well as with automated speech analysis – computerized methods for objectively quantifying speech characteristics.

One major roadblock in psychiatry is that treatment is often a guessing game. We have a variety of effective treatments available, but we do not yet know who will respond to standard care, and who will not. In our poster presentation on “Predicting Treatment Outcomes with Computational Speech Features in Hospitalized Patients with Schizophrenia,” we used an app developed by Winterlight Labs to record speech from hospitalized patients with schizophrenia just after they were admitted to the inpatient facility. The speech samples underwent automated processing. We found that speech features soon after admission significantly contributed to predicting how symptomatic people were when they were discharged (2 weeks later, on average).

We still have much to do before our research can tangibly benefit people with schizophrenia and their loved ones. However, I believe that taking advantage of advances in technology and machine learning has enormous potential for understanding what goes wrong in schizophrenia and for guiding personalized medical treatment to improve outcomes.

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

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.