KSKarthik V. Sarma

Karthik V. Sarma

*This is an algorithmically generated author record based on publicly available information.

Current Organizations / Institutes

The organizations/institutes from the scholar's latest article


Karthik V. Sarma has a total of 85 co-authors. Here are the top co-authors by number of shared publications:


Latest Publications

  • Open Access

    Yes, ChatGPT (and other models) need a psychiatrist: parallels between experimental neuropsychiatry and AI alignment science

    by Karthik V Sarma

    AI chatbots (such as ChatGPT or Claude) sometimes state false information with confidence, a behavior popularly termed “hallucination.” In their recent perspective, de Boer et al. [1] compared these errors to confabulation in patients with memory disorders, and asked whether ChatGPT needs a psychiatrist. I argue that it does, but for different reasons. False statements from chatbots may be better explained by how they are trained: first to produce contextually consistent text rather than true text, and later by being rewarded to produce answers. The more meaningful parallel lies elsewhere: because these systems learn to simulate human characters, they may also reproduce human personality traits and patterns resembling the symptoms of mental illness. Understanding them may require the methods of experimental psychiatry and psychology, and could advance our understanding of the human mind.

  • Open Access

    Simulated Reasoning and Self-Verification for Psychiatric Diagnosis in Generalist Large Language Models: Comparative Evaluation

    by Karthik V Sarma, Kaitlin E Hanss, Andrew J M Halls, Daniel F Becker, Anne L Glowinski, Andrew D Krystal

    Background: Large language models (LLMs) and, more recently, large reasoning models (LRMs) have rapidly garnered significant interest for application in psychiatry and behavioral health. However, recent studies have identified significant shortcomings and potential risks in the performance of LLM-based systems, complicating their application to psychiatric diagnosis. Two promising approaches to addressing these challenges and improving the efficacy of these models are simulated reasoning (SR) and self-verification (SV), in which additional “reasoning tokens” are used to guide model output, either during or after inference. Objective: We aimed to explore how the use of SR (via LRMs) and SV (via supplemental prompting) affects the psychiatric diagnostic performance of LLMs. Methods: 106 case vignettes and associated diagnoses were extracted from the DSM-5-TR (Diagnostic and Statistical Manual, Version 5, Text Revision) Clinical Cases book, with permission. Both an LLM and an LRM model were selected from the latest available model generation for each of the two vendors studied (OpenAI and Google). Two inference approaches were developed: a Basic approach that directly prompted models to provide diagnoses and a SV approach that augmented the Basic approach with additional prompts. All case vignettes were processed by the two LLMs, two LRMs, and two inference approaches, and diagnostic performance was evaluated using the sensitivity and positive predictive value (PPV). Binomial generalized linear mixed models were used to test for significant differences between the model vendors (OpenAI, Google), type (LLM, LRM), and the addition of an SV prompt. Results: All vignettes were successfully processed by each model and inference approach. Sensitivity ranged from 0.732 to 0.817, and PPV ranged from 0.534 to 0.779. The best overall performance was found in the o3-pro LRM using SV, with a sensitivity of 0.782 and a PPV of 0.779. No statistically significant fixed effects were found for sensitivity. For PPV, a statistically significant effect was found for prompt type (SV, P =.007) and model type (LRM, P =.009). No significant interaction effects were identified. Conclusions: We found that both SR and SV yielded statistically significant improvements in the PPV, without significant differences in the sensitivity. The addition of the manually specified SV prompt improved the PPV even when simulated reasoning was used. This suggests that future efforts to apply language models in behavioral health could benefit from manually crafted reasoning prompts and automated SR.

  • Open Access

    Integrating expert knowledge into large language models improves performance for psychiatric reasoning and diagnosis

    by Karthik V Sarma, Kaitlin E Hanss, Andrew J M Halls, Andrew Krystal, Daniel F Becker, Anne L Glowinski, Atul J Butte


  • Open Access

    Simulated Reasoning and Self-Verification for Psychiatric Diagnosis in Generalist Large Language Models: Comparative Evaluation

    by Karthik V Sarma, Kaitlin E Hanss, Andrew J M Halls, Daniel F Becker, Anne L Glowinski, Andrew Krystal

    Background: Large language models (LLMs), and, more recently, large reasoning models (LRMs) have rapidly garnered significant interest for application in psychiatry and behavioral health. However, recent studies have identified significant shortcomings and potential risks in the performance of LLM-based systems, complicating their application to psychiatric diagnosis. Two promising approaches to addressing these challenges and improving the efficacy of these models are simulated reasoning (SR) and self-verification (SV), in which additional “reasoning tokens” are used to guide model output, either during or after inference. Objectives: We aimed to explore how the use of SR (via LRMs) and SV (via supplemental prompting) affect the psychiatric diagnostic performance of LLMs. Methods: 106 case vignettes and associated diagnoses were extracted from the DSM-5-TR Clinical Cases book, with permission. Both an LLM and LRM model were selected from the latest available model generation for each of the two vendors studied (OpenAI and Google). Two inference approaches were developed, a Basic approach that directly prompted models to provide diagnoses, and a SV approach that augmented the Basic approach with additional prompts. All case vignettes were processed by the two LLMs, two LRMs, and two inference approaches, and diagnostic performance was evaluated using the sensitivity and positive predictive value (PPV). Binomial generalized linear mixed models were used to test for significant differences between the model vendors (OpenAI, Google), type (LLM, LRM), and addition of an SV prompt. Results: All vignettes were successfully processed by each model and inference approach. Sensitivity ranged from 0.732 to 0.817, and PPV ranged from 0.534 to 0.779. The best overall performance was found in the o3-pro LRM using SV, with a sensitivity of 0.782 and a PPV of 0.779. No statistically significant fixed effects were found for sensitivity. For PPV, a statistically significant effect was found for prompt type (SV, p=0.007), model type (LRM, p=0.009). No significant interaction effects were identified. Conclusions: We found that both SR and SV yielded statistically significant improvements in the PPV, without significant differences in the sensitivity. The addition of the manually specified SV prompt improved the PPV even when simulated reasoning was used. This suggests that future efforts to apply language models in behavioral health could benefit from manually crafted reasoning prompts and automated SR.


  • Open Access

    Integrating Expert Knowledge into Large Language Models Improves Performance for Psychiatric Reasoning and Diagnosis

    by Karthik V Sarma, Kaitlin E Hanss, Andrew J M Halls, Andrew Krystal, Daniel F Becker, Anne L Glowinski, Atul J Butte

    Purpose and Methods: The authors sought to evaluate the performance of common large language models (LLMs) in psychiatric diagnosis, and the impact of integrating expert-derived reasoning on their performance. Clinical case vignettes and associated diagnoses were retrieved from the DSM-5-TR Clinical Cases book. Diagnostic decision trees were retrieved from the DSM-5-TR Handbook of Differential Diagnosis and refined for LLM use. Three LLMs were prompted to provide diagnosis candidates for the vignettes either by directly prompting or using the decision trees. These candidates and diagnostic categories were compared against the correct diagnoses. The positive predictive value (PPV), sensitivity, and F 1 statistic were used to measure performance. Principal Results: When directly prompted to predict diagnoses, the best LLM by F 1 statistic (gpt-4o) had sensitivity of 77.6% and PPV of 43.3%. When making use of the refined decision trees, PPV was significantly increased (65.3%) without a significant reduction in sensitivity (71.8%). Across all experiments, the use of the decision trees statistically significantly increased the PPV, significantly increased the F 1 statistic in 5/6 experiments, and significantly reduced sensitivity only for the category-based evaluation in 2/3 experiments. Major Conclusions: When used to predict psychiatric diagnoses from case vignettes, direct prompting of the LLMs yielded most true positive diagnoses but had significant overdiagnosis. Integrating expert-derived reasoning into the process using decision trees improved LLM performance, primarily by suppressing overdiagnosis with minimal negative impact on sensitivity. This suggests that the integration of clinical expert-derived reasoning could improve the performance of LLM-based tools in the behavioral health setting.


  • Open Access

    Assessing the Accuracy and Reliability of Large Language Models in Psychiatry Using Standardized Multiple-Choice Questions: Cross-Sectional Study

    by Kaitlin Hanss, Karthik V Sarma, Anne L Glowinski, Andrew Krystal, Ramotse Saunders, Andrew Halls, Sasha Gorrell, Erin Reilly

    Background: Large language models (LLMs), such as OpenAI’s GPT-3.5, GPT-4, and GPT-4o, have garnered early and significant enthusiasm for their potential applications within mental health, ranging from documentation support to chat-bot therapy. Understanding the accuracy and reliability of the psychiatric “knowledge” stored within the parameters of these models and developing measures of confidence in their responses (ie, the likelihood that an LLM response is accurate) are crucial for the safe and effective integration of these tools into mental health settings. Objective: This study aimed to assess the accuracy, reliability, and predictors of accuracy of GPT-3.5 (175 billion parameters), GPT-4 (approximately 1.8 trillion parameters), and GPT-4o (an optimized version of GPT-4 with unknown parameters) with standardized psychiatry multiple-choice questions (MCQs). Methods: A cross-sectional study was conducted where 3 commonly available, commercial LLMs (GPT-3.5, GPT-4, and GPT-4o) were tested for their ability to provide answers to single-answer MCQs (N=150) extracted from the Psychiatry Test Preparation and Review Manual. Each model generated answers to every MCQ 10 times. We evaluated the accuracy and reliability of the answers and sought predictors of answer accuracy. Our primary outcome was the proportion of questions answered correctly by each LLM (accuracy). Secondary measures were (1) response consistency to MCQs across 10 trials (reliability), (2) the correlation between MCQ answer accuracy and response consistency, and (3) the correlation between MCQ answer accuracy and model self-reported confidence. Results: On the first attempt, GPT-3.5 answered 58.0% (87/150) of MCQs correctly, while GPT-4 and GPT-4o answered 84.0% (126/150) and 87.3% (131/150) correctly, respectively. GPT-4 and GPT-4o showed no difference in performance (P=.51), but they significantly outperformed GPT-3.5 (P<.001). GPT-3.5 exhibited less response consistency on average compared to the other models (P<.001). MCQ response consistency was positively correlated with MCQ accuracy across all models (r=0.340, 0.682, and 0.590 for GPT-3.5, GPT-4, and GPT-4o, respectively; all P<.001), whereas model self-reported confidence showed no correlation with accuracy in the models, except for GPT-3.5, where self-reported confidence was weakly inversely correlated with accuracy (P<.001). Conclusions: To our knowledge, this is the first comprehensive evaluation of the general psychiatric knowledge encoded in commercially available LLMs and the first study to assess their reliability and identify predictors of response accuracy within medical domains. The findings suggest that GPT-4 and GPT-4o encode accurate and reliable general psychiatric knowledge and that methods, such as repeated prompting, may provide a measure of LLM response confidence. This work supports the potential of LLMs in mental health settings and motivates further research to assess their performance in more open-ended clinical contexts.


  • Open Access

    Assessing the Accuracy and Reliability of Large Language Models in Psychiatry Using Standardized Multiple-Choice Questions: Cross-Sectional Study (Preprint)

    by Kaitlin Hanss, Karthik V Sarma, Anne L Glowinski, Andrew Krystal, Ramotse Saunders, Andrew Halls, Sasha Gorrell, Erin Reilly

    BACKGROUND Large language models (LLMs), such as OpenAI’s GPT-3.5, GPT-4, and GPT-4o, have garnered early and significant enthusiasm for their potential applications within mental health, ranging from documentation support to chat-bot therapy. Understanding the accuracy and reliability of the psychiatric “knowledge” stored within the parameters of these models and developing measures of confidence in their responses (ie, the likelihood that an LLM response is accurate) are crucial for the safe and effective integration of these tools into mental health settings. OBJECTIVE This study aimed to assess the accuracy, reliability, and predictors of accuracy of GPT-3.5 (175 billion parameters), GPT-4 (approximately 1.8 trillion parameters), and GPT-4o (an optimized version of GPT-4 with unknown parameters) with standardized psychiatry multiple-choice questions (MCQs). METHODS A cross-sectional study was conducted where 3 commonly available, commercial LLMs (GPT-3.5, GPT-4, and GPT-4o) were tested for their ability to provide answers to single-answer MCQs (N=150) extracted from the Psychiatry Test Preparation and Review Manual. Each model generated answers to every MCQ 10 times. We evaluated the accuracy and reliability of the answers and sought predictors of answer accuracy. Our primary outcome was the proportion of questions answered correctly by each LLM (accuracy). Secondary measures were (1) response consistency to MCQs across 10 trials (reliability), (2) the correlation between MCQ answer accuracy and response consistency, and (3) the correlation between MCQ answer accuracy and model self-reported confidence. RESULTS On the first attempt, GPT-3.5 answered 58.0% (87/150) of MCQs correctly, while GPT-4 and GPT-4o answered 84.0% (126/150) and 87.3% (131/150) correctly, respectively. GPT-4 and GPT-4o showed no difference in performance (P=.51), but they significantly outperformed GPT-3.5 (P<.001). GPT-3.5 exhibited less response consistency on average compared to the other models (P<.001). MCQ response consistency was positively correlated with MCQ accuracy across all models (r=0.340, 0.682, and 0.590 for GPT-3.5, GPT-4, and GPT-4o, respectively; all P<.001), whereas model self-reported confidence showed no correlation with accuracy in the models, except for GPT-3.5, where self-reported confidence was weakly inversely correlated with accuracy (P<.001). CONCLUSIONS To our knowledge, this is the first comprehensive evaluation of the general psychiatric knowledge encoded in commercially available LLMs and the first study to assess their reliability and identify predictors of response accuracy within medical domains. The findings suggest that GPT-4 and GPT-4o encode accurate and reliable general psychiatric knowledge and that methods, such as repeated prompting, may provide a measure of LLM response confidence. This work supports the potential of LLMs in mental health settings and motivates further research to assess their performance in more open-ended clinical contexts. CLINICALTRIAL

  • Open Access

    Integrating Battlefield Documentation into Virtual Reality Medical Simulation Training: Virtual Battlefield Assisted Trauma Distributed Observation Kit (BATDOK)

    by Karthik V Sarma, Michael G Barrie, John R Dorsch, Tanner W Andre, Jennifer S Polson, Rosie J Ribeira, Tyler B Andre

    Introduction: Clinical documentation is an essential component of the provision of medical care, enabling continuity of information across provider and site handoffs. This is particularly important in the combat casualty care setting when a single casualty may be treated by four or more or five completely disparate teams across the roles of care. The Battlefield Assisted Trauma Distributed Observation Kit (BATDOK) is a digital battlefield clinical documentation system developed by the Air Force Research Laboratory to address this need. To support the deployment of this tool, we integrated BATDOK into a commercially available virtual reality (VR) medical simulation platform used by the U.S. Air Force and Defense Health Agency personnel in order to provide an immersive simulation training experience which included battlefield documentation. Methods: A multidisciplinary team consisting of medical educators, VR simulation engineers, emergency physicians and pararescuemen, and BATDOK developers first developed a specification for a virtual BATDOK capability, including a detailed listing of learning objectives, critical interfaces and task plans, and sensor integrations. These specifications were then implemented into the commercially available Virtual Advancement of Learning for Operational Readiness VR Medical Simulation System and underwent developmental testing and evaluation during pararescueman training exercises at the Air Force Special Operations Command Special Operations Center for Medical Integration and Development. Results and Conclusions: The BATDOK capability was successfully implemented within the VR Medical Simulation System. The capability consisted of a virtual tablet with replicated interfaces and capabilities based on the developed specifications. These capabilities included integrated point-of-care ultrasound capability, multi-patient management, vitals sign monitoring with sensor pairing and continuous monitoring, mechanism of injury documentation (including injury pattern documentation), intervention logging (including tourniquets, dressing, airways, lines, tubes and drains, splints, fluids, and medications), and event logging. The capability was found to be operational and in alignment with learning objectives and user acceptance goals.


  • Open Access

    Harnessing clinical annotations to improve deep learning performance in prostate segmentation

    by Karthik V. Sarma, Alex G. Raman, Nikhil J. Dhinagar, Alan M. Priester, Stephanie Harmon, Thomas Sanford, Sherif Mehralivand, Baris Turkbey, Leonard S. Marks, Steven S. Raman, et al.

    Purpose: Developing large-scale datasets with research-quality annotations is challenging due to the high cost of refining clinically generated markup into high precision annotations. We evaluated the direct use of a large dataset with only clinically generated annotations in development of high-performance segmentation models for small research-quality challenge datasets. Materials and methods: We used a large retrospective dataset from our institution comprised of 1,620 clinically generated segmentations, and two challenge datasets (PROMISE12: 50 patients, ProstateX-2: 99 patients). We trained a 3D U-Net convolutional neural network (CNN) segmentation model using our entire dataset, and used that model as a template to train models on the challenge datasets. We also trained versions of the template model using ablated proportions of our dataset, and evaluated the relative benefit of those templates for the final models. Finally, we trained a version of the template model using an out-of-domain brain cancer dataset, and evaluated the relevant benefit of that template for the final models. We used five-fold cross-validation (CV) for all training and evaluation across our entire dataset. Results: Our model achieves state-of-the-art performance on our large dataset (mean overall Dice 0.916, average Hausdorff distance 0.135 across CV folds). Using this model as a pre-trained template for refining on two external datasets significantly enhanced performance (30% and 49% enhancement in Dice scores respectively). Mean overall Dice and mean average Hausdorff distance were 0.912 and 0.15 for the ProstateX-2 dataset, and 0.852 and 0.581 for the PROMISE12 dataset. Using even small quantities of data to train the template enhanced performance, with significant improvements using 5% or more of the data. Conclusion: We trained a state-of-the-art model using unrefined clinical prostate annotations and found that its use as a template model significantly improved performance in other prostate segmentation tasks, even when trained with only 5% of the original dataset.


  • Optimizing Spatial Biopsy Sampling for the Detection of Prostate Cancer

    by Alex G. Raman, Karthik V. Sarma, Steven S. Raman, Alan M. Priester, Sohrab Afshari Mirak, Hannah H. Riskin-Jones, Nikhil Dhinagar, William Speier, Ely Felker, Anthony E. Sisk, et al.

    Purpose:The appropriate number of systematic biopsy cores to retrieve during Magnetic Resonance Imaging (MRI)-targeted prostate biopsy is not well defined. We aimed to demonstrate a biopsy sampling...