Philip R. Szeszko, PhD

Thanks to modern in-vivo methods for neuroimaging, Dr. Szeszko’s lab is examining the brains of patients with neuropsychiatric disorders using magnetic resonance imaging.  The goal of this work is to identify the structural and functional abnormalities that play a role in the pathogenesis of disorders such as schizophrenia, obsessive-compulsive disorder and bipolar disorder and to relate these abnormalities to clinical and neuropsychological deficits.  In particular, Dr. Szeszko’s work has focused on the role of the anterior hippocampal formation in the pathophysiology of schizophrenia, and he has demonstrated that structural alterations in this region have a unique set of neuropsychological correlates, which implicate a defect in connectivity between the frontal and temporal lobes. In addition, his work has shown that this part of the hippocampus is particularly affected by stress, thus making it a potentially important target for environmental insults, which could lead to the manifestation of schizophrenia.

There is increasing evidence that disturbances in the brain white matter play a role in the pathophysiology of neuropsychiatric disorders and Dr. Szeszko is using a relatively novel technique called diffusion tensor imaging to examine this tissue. Specifically, diffusion tensor imaging provides a unique opportunity to identify and map the directionality of these white matter bundles. Work by Dr. Szeszko’s group has identified a pattern of white matter abnormalities in the left temporal lobe in patients with schizophrenia that correlate with increased symptom severity and neuropsychological deficits.

An additional focus of Dr. Szeszko’s work has been the examination of genetic factors that are associated with variation in brain structure. Prior work by his group suggests that the BDNF val66met polymorphism is associated with hippocampal volume in patients with schizophrenia and healthy volunteers.  In addition, more recent work provides evidence for an association between a DISC1 polymorphism, leu607phe, and prefrontal cortical gray matter volume and positive symptoms. Taken together, his data provide a potential mechanism through which DISC1 may confer increased risk for schizophrenia or schizo-affective disorder. Along these lines, a related goal of Dr. Szeszko’s research is to identify the genetic factors that contribute to variation in white matter integrity, as assessed using diffusion tensor imaging, in individuals with neuropsychiatric disorders and healthy humans. This work will have relevance for neurobiological models of schizophrenia and possibly other neurological disorders that have implicated white matter abnormalities in their pathogenesis.

Dr. Szeszko has received grant funding from the NIMH, DANA Foundation, NARSAD, Obsessive-Compulsive Foundation and American Foundation for Suicide Prevention and was a prior recipient of a Mentored Research Scientist development Award (K01).

Dr. Szeszko is a peer reviewer for 10 scientific journals and sits on the Editorial Board of Progress in Neuro-psychopharmacology and Biological Psychiatry and Psychiatry Research: Neuroimaging.

1. Mahon K, Wu J, Malhotra AK, Burdick KE, Derosse P, Ardekani BA, Szeszko PR. “A Voxel-Based Diffusion Tensor Imaging Study of White Matter in Bipolar Disorder.” Neuropsychopharmacology. 2009 Jan 14. [Epub ahead of print]
2. Kafantaris V, Kingsley P, Ardekani B, Saito E, Lencz T, Lim K, Szeszko PR. “Lower orbital frontal white matter integrity in adolescents with bipolar I disorder.” J Am Acad Child Adolesc Psychiatry. 2009 Jan;48(1):79-86.
3. Christian CJ, Lencz T, Robinson DG, Burdick KE, Ashtari M, Malhotra AK, Betensky JD, Szeszko PR. “Gray matter structural alterations in obsessive-compulsive disorder: relationship to neuropsychological functions.” Psychiatry Res. 2008 Nov 30;164(2):123-31. Epub 2008 Oct 19.
4. Narayan VM, Narr KL, Phillips OR, Thompson PM, Toga AW, Szeszko PR. “Greater regional cortical gray matter thickness in obsessive-compulsive disorder.” Neuroreport. 2008 Oct 8;19(15):1551-5.
5. Burdick KE, Robinson DG, Malhotra AK, Szeszko PR. “Neurocognitive profile analysis in obsessive-compulsive disorder.”  J Int Neuropsychol Soc. 2008 Jul;14(4):640-5.
6. Coscia DM, Narr KL, Robinson DG, Hamilton LS, Sevy S, Burdick KE, Gunduz-Bruce H, McCormack J, Bilder RM, Szeszko PR. “Volumetric and shape analysis of the thalamus in first-episode schizophrenia.” Hum Brain Mapp. 2008 Jun 20. [Epub ahead of print]
7. Betensky JD, Robinson DG, Gunduz-Bruce H, Sevy S, Lencz T, Kane JM, Malhotra AK, Miller R, McCormack J, Bilder RM, Szeszko PR. “Patterns of stress in schizophrenia.” Psychiatry Res. 2008 Jul 15;160(1):38-46. Epub 2008 Jun 2.
8. Szeszko PR, Christian C, Macmaster F, Lencz T, Mirza Y, Taormina SP, Easter P, Rose M, Michalopoulou GA, Rosenberg DR.  ”Gray matter structural alterations in psychotropic drug-naive pediatric obsessive-compulsive disorder: an optimized voxel-based morphometry study.” Am J Psychiatry. 2008 Oct;165(10):1299-307.
9. Szeszko PR, Hodgkinson CA, Robinson DG, Derosse P, Bilder RM, Lencz T, Burdick KE, Napolitano B, Betensky JD, Kane JM, Goldman D, Malhotra AK. “DISC1 is associated with prefrontal cortical gray matter and positive symptoms in schizophrenia.” Biol Psychol. 2008 Sep;79(1):103-10.
10. Szeszko PR, Robinson DG, Ashtari M, Vogel J, Betensky J, Sevy S, Ardekani BA, Lencz T, Malhotra AK, McCormack J, Miller R, Lim KO, Gunduz-Bruce H, Kane JM, Bilder RM. “Clinical and neuropsychological correlates of white matter abnormalities in recent onset schizophrenia.” Neuropsychopharmacology. 2008 Apr;33(5):976-84.

View more at PubMed