Philip R. Szeszko, PhD
Dr. Szeszko is Professor of Psychiatry and Neuroscience at the Icahn School of Medicine at Mount Sinai, and a VA clinical psychologist/researcher in the Mental Illness Research Education and Clinical Center at the James J. Peters VA Medical Center. He has received funding from the Brain and Behavior Research Foundation, Obsessive-Compulsive Foundation, American Foundation for Suicide Prevention, DANA Foundation, Veterans Health Administration Office of Research and Development and National Institute of Mental Health. Dr. Szeszko currently sits on the editorial board of Progress in Neuropsychopharmacology and Biological Psychiatry and has ~145 publications.
A major focus of his research has been the investigation of white matter abnormalities in the neurobiology of schizophrenia and associated psychotic disorders and how deviations in the normal trajectory of white matter may contribute to psychosis. His initial studies in this area focused on white matter abnormalities in patients with first-episode schizophrenia studied early in the course of illness prior to extensive pharmacologic intervention and among individuals with childhood onset schizophrenia. Subsequent work focused on understanding the clinical and neuropsychological significance of these abnormalities. Additional studies focused on how antipsychotic medications may influence white matter integrity and the use of a novel technique, free water imaging, to investigate the neuropsychological correlates of purported inflammation in the white matter early in the course of illness. More recent work has moved beyond the standard tensor framework by focusing on crossing white matter fibers and better understanding their potential contribution to risk for and protection against psychosis through an R01 study funded by the NIMH.
A long-standing research interest of his group has been the study of bipolar disorder and its relationship to suicidal behavior. Their early work demonstrated that abnormalities in the orbital frontal white matter play a role in the neurobiology of bipolar disorder and that abnormalities in this region are associated with a history of suicidal behavior. They have also demonstrated that individuals with bipolar disorder with a prior suicide attempt history are more impulsive compared to individuals with bipolar disorder and no suicide attempt history and healthy controls, which has been replicated in an independent sample. Their recent data indicate that individuals with bipolar disorder and a prior suicide attempt history have greater positive and negative urgency (i.e., the tendency to act impulsively when experiencing strong positive and negative emotions, respectively) compared to individuals with bipolar disorder and no prior suicide attempt history. These studies have now been extended to the VA where his team is examining the relationship between impulsivity and suicide in Veterans with bipolar disorder through a funded Merit study that is using functional magnetic resonance imaging tasks assessing cognitive and motor impulsivity.
A major recent focus of his work at the James J. Peters VA Medical Center has been the investigation of neurobiological abnormalities in PTSD and their relationship to treatment response. A recent review by his group emphasized the role of hippocampal abnormalities in the neurobiology of PTSD and it relationship to HPA functioning. Additional work in this area has focused on evidence of “accelerated aging” in PTSD given associations of less hippocampal volume and higher mean arterial pressure. Other studies are examining changes in resting state fMRI connectivity as predictors of treatment response to cognitive processing therapy in PTSD, which was funded by a grant from the Brain and Behavior Research Foundation. We have recently initiated a study to examine changes in brain functioning following MDMA-assisted psychotherapy for the treatment of chronic PTSD.
Research Interests
psychosis, white matter, schizophrenia, bipolar disorder, magnetic resonance imaging, PTSD
Grants
Longitudinal neuroimaging and neurocognitive assessment of risk and protective factors across the schizophrenia spectrum (2020-2024)
Role: Co-Principal Investigator. Funding source: NIMH
Predicting Suicidal Behavior in Veterans with Bipolar Disorder using Behavioral and Neuroimaging Based Impulsivity Phenotypes (2020-2024)
Role: Principal Investigator. Funding source: VA
Cognitive and Neural Mechanisms of the Accelerated Aging Phenotype in PTSD (2017-2022)
Role: Co-investigator. Funding source: NIMH.
Publications (Selected)
A full list of Dr. Szeszko’s publications can be found here.
Szeszko, PR, Bierer, LM, Bader, HN, Chu, KW, Tang, CY, Murphy, KM, Hazlett, EA, Flory, JD, & Yehuda, R. Cingulate and hippocampal subregion abnormalities in combat exposed veterans with PTSD. Journal of affective disorders, 2022.
Szeszko, PR, Gohel, S, Vaccaro, DH, Chu, KW, Tang, CY, Goldstein, KE, New, AS, Siever, LJ, McClure, M, Perez-Rodriguez, MM, Haznedar, MM, Byne, W, & Hazlett, EA. Frontotemporal thalamic connectivity in schizophrenia and schizotypal personality disorder. Psychiatry research. Neuroimaging, 2022.
Szeszko PR, McNamara RK, Gallego JA, Malhotra AK, Govindarajulu U, Peters BD, Robinson DG. Longitudinal investigation of the relationship between omega-3 polyunsaturated fatty acids and neuropsychological functioning in recent-onset psychosis: A randomized clinical trial. Schizophr Res. 2021.
Lyall AE, Nägele FL, Pasternak O, Gallego JA, Malhotra AK, McNamara RK, Kubicki M, Peters BD, Robinson DG, Szeszko PR. A 16-week randomized placebo-controlled trial investigating the effects of omega-3 polyunsaturated fatty acid treatment on white matter microstructure in recent-onset psychosis patients concurrently treated with risperidone. Psychiatry Res Neuroimaging. 2021.
Szeszko PR, Yehuda R. Magnetic resonance imaging predictors of psychotherapy treatment response in post-traumatic stress disorder: A role for the salience network. Psychiatry Res. 2019.
Reich R, Gilbert A, Clari R, Burdick KE, Szeszko PR. A preliminary investigation of impulsivity, aggression and white matter in patients with bipolar disorder and a suicide attempt history. J Affect Disord. 2019.
Gohel S, Gallego JA, Robinson DG, DeRosse P, Biswal B, Szeszko PR. Frequency specific resting state functional abnormalities in psychosis. Hum Brain Mapp. 2018.
Shafritz KM, Ikuta T, Greene A, Robinson DG, Gallego J, Lencz T, DeRosse P, Kingsley PB, Szeszko PR. Frontal lobe functioning during a simple response conflict task in first-episode psychosis and its relationship to treatment response. Brain Imaging Behav. 2019.
Szeszko PR, Lehrner A, Yehuda R. Glucocorticoids and Hippocampal Structure and Function in PTSD. Harv Rev Psychiatry. 2018.
Szeszko PR, Tan ET, Uluğ AM, Kingsley PB, Gallego JA, Rhindress K, Malhotra AK, Robinson DG, Marinelli L. Investigation of superior longitudinal fasciculus fiber complexity in recent onset psychosis. Progress in Neuropsychopharmacology and Biological Psychiatry, 2018.
Kafantaris V, Spritzer L, Doshi V, Saito E, Szeszko PR. Changes in white matter microstructure predict lithium response in adolescents with bipolar disorder. Bipolar Disord, 2017.
Lyall AE, Pasternak O, Robinson DG, Newell D, Trampush JW, Gallego JA, Fava M, Malhotra AK, Karlsgodt KH, Kubicki M, Szeszko PR. Greater extracellular free-water in first-episode psychosis predicts better neurocognitive functioning. Mol Psychiatry. 2018.
Schwehm A, Robinson DG, Gallego JA, Karlsgodt KH, Ikuta T, Peters BD, Malhotra AK, Szeszko PR. Age and Sex Effects on White Matter Tracts in Psychosis from Adolescence through Middle Adulthood. Neuropsychopharmacology, 2016.
Karlsgodt KH, John M, Ikuta T, Rigoard P, Peters BD, Derosse P, Malhotra AK, Szeszko PR. The accumbofrontal tract: Diffusion tensor imaging characterization and developmental change from childhood to adulthood. Hum Brain Mapp. 2015.
Prendergast DM, Ardekani B, Ikuta T, John M, Peters B, DeRosse P, Wellington R, Malhotra AK, Szeszko PR. Age and sex effects on corpus callosum morphology across the lifespan. Hum Brain Mapp. 2015.
Argyelan M, Gallego JA, Robinson DG, Ikuta T, Sarpal D, John M, Kingsley PB, Kane J, Malhotra AK, Szeszko PR. Abnormal resting state FMRI activity predicts processing speed deficits in first-episode psychosis. Neuropsychopharmacology. 2015.
Toteja N, Guvenek-Cokol P, Ikuta T, Kafantaris V, Peters BD, Burdick KE, John M, Malhotra AK, Szeszko PR. Age-associated alterations in corpus callosum white matter integrity in bipolar disorder assessed using probabilistic tractography. Bipolar Disord. 2015.
