SIRS Research Stories

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.