Physician-Scientist Projects - Psychiatry Residency
Mark Kvarta, MD, PhD – 2021 PSTP Graduate
Assistant Professor of Psychiatry and Physiology
University of Maryland School of Medicine
PSTP Project: Stress, Genetics, and Neuroimaging of Depression in Serious Mental Illness
PSTP Faculty mentor: L. Elliot Hong, MD
Depression is a devastating, deadly, and costly burden of psychiatric disease. It is most commonly treated, often unsatisfactorily, by manipulating synaptic serotonergic tone, yet the key substrates that mediate antidepressant efficacy are largely unknown and a better understanding of the etiology and neurobiological pathophysiology is needed. One thing is clear, stress plays a role underlying depressive symptoms, with a stress-diathesis model of environment at critical time points interacting with genetic vulnerability to contribute to illness. Expanding on my doctoral thesis background in studying the role of chronic stress in perturbing synaptic function in key corticomesolimbic brain areas in depression, I worked with Dr. Hong to train in clinical and translational research in this area, gaining skills in genetics, functional neuroimaging, and stress-based tasks in human participants. I have continued to develop my research projects in these areas now as a faculty member at University of Maryland School of Medicine and the Maryland Psychiatric Research Center, while also attending in the academic outpatient clinic.
Gustavo C. Medeiros, MD
2021 PSTP Graduate / Mood Disorders Fellow at The Johns Hopkins University School of Medicine
- Impact of psychiatric comorbidities in antidepressant efficacy treatment with ketamine and esketamine: A meta-analysis; and
- Too much stress; a critical assessment of the use of animal models of stress to study depression.
Primary mentor: Todd D. Gould, MD
My first project is a meta-analysis assessing the impact of psychiatric comorbidities in antidepressant response with ketamine and esketamine. It is widely known that MDD is often accompanied by other psychiatric comorbidities, which tend to further complicate its treatment. There are some intriguing findings in the ketamine/esketamine literature suggesting a more substantial response in individuals with personal or family history of alcohol use disorder and anxiety comorbidities when compared to individuals without these comorbidities. However, it is still unclear if a broader and systematic review of the literature will support whether some patients may respond more favorably to one over the other. Therefore, our project will answer the following question: Does personal and/or a family history of psychiatric comorbidities (such as alcohol use disorder, substance use disorder, anxiety disorders, post-traumatic stress disorder, personality disorders, etc.) moderate the antidepressant efficacy of ketamine or esketamine?
Our second project is a review of current animal models of depression and the potential excessive reliance on stress-based models. Pre-clinical research is vital to improve the understanding of the physiopathology of MDD but it is surrounded by misconceptions regarding its strengths and limitations. A common misconception in the existence of animal models of MDD since MDD in humans is very unique and heterogeneous disorder that cannot to be fully replicated in other species. Animal paradigms model a specific aspect of MDD, and most of them are stress models where depression-like arise secondary to despair and hopelessness. Our review critically examines current animals used to study depression.
Eric Luria Goldwaser, DO, PhD
PGY-4 PSTP Resident
Project: Development stress and blood-brain barrier integrity in schizophrenia.
Primary mentor: Elliot Hong, MD and Peter Kochunov, PhD
Secondary mentor: Scott Aaronson, M.D.
Endothelial cell monolayers are shared within the body's many vascular systems. A peripheral assessment may provide surrogate information on the blood-brain barrier (BBB) endothelial function in schizophrenia. My doctoral research project was focused on the assessment of endothelial dysfunction in Alzheimer's disease at the molecular and cellular level of the BBB. This current project will extend my prior research experiences in BBB endothelial integrity to schizophrenia at the clinical biomarker level during my PSTP training.
The primary goals of this project are to:
- Test the central and peripheral endothelial integrity in schizophrenia which can be assessed with state-of-the-art neuroimaging for BBB integrity, ophthalmologic tools for blood-retina barrier function, and peripheral endothelial assays.
- Ascertain developmental insults as a significant contributor to the endothelial dysfunction in schizophrenia.
Neurocircuitry involved in aberrant processing and connectivity may further be explored at the junction between perfusion and metabolism utilizing various diffusion MRI sequences, and to carve out putative targets for non-invasive neuromodulation.
Andrew van der Vaart, MD, PhD
PGY2 PTSP Resident
Project: Neuroimaging of Delusions in Schizophrenia: Neural Circuits as a Bridge from Genes to Specific Clinical Subphenotypes
Primary mentor: Elliot Hong, MD
Secondary mentor: Seth Ament, PhD
Delusions are a prominent positive symptom of schizophrenia and other psychotic disorders, but the mechanism is not well understood. While it is theoretically possible that a single common pathway underlies all delusions and has merely escaped current detection methods, evidence to date points to the more likely scenario of distinct pathways underlying varied delusional states. To this end, my project seeks to empirically subcategorize delusions and identify corresponding neural circuits and genetic architecture. Among patients with schizophrenia spectrum disorders (SSD), we use the Peters Delusion Inventory (PDI) to assess delusions of multiple types (e.g. paranoid, grandiose, thought insertion/ broadcasting/ withdrawal). Delusion subtypes are then identified with principal component and cluster analyses of responses to the PDI. White matter changes corresponding to distinct delusion subtypes will be investigated via structural MRI. Subsequent task-based fMRI will allow for further delineation of functional connectivity during specific delusion-relevant perceptual tasks. Additionally, genotyping of schizophrenia risk-conferring polymorphisms will be used to assess differential association of individual genetic and polygenic risks with delusion subtypes, and potential genetic mediation of corresponding neuroimaging findings. I believe that mechanistic insights from these studies will contribute to resolving a major problem in psychiatric diagnosis and treatment: the likely etiological heterogeneity of broad diagnostic labels, i.e. "schizophrenia."