Yvette I. Sheline, M.D.

faculty photo
McLure Professor of Psychiatry and Behavioral Research
Department: Psychiatry
Graduate Group Affiliations

Contact information
Department of Psychiatry
University of Pennsylvania
Perelman School of Medicine
3700 Hamilton Walk
Richards Building Rm D307
Philadelphia, PA 19104
B.A. (Biology)
Harvard, 1974.
M.S. (Physiology)
Yale University, 1975.
Boston University, 1979.
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Description of Research Expertise

My overall research goal is to identify brain markers of depression and anxiety treatment response across disorders using structural and functional neuroimaging and to improve strategies for brain neuromodulation.

Funded grants include:

1.) "Novel neural circuit biomarkers of depression response to computer-augmented CBT"
We are using functional and structural magnetic resonance imaging (MRI) to determine novel neural circuit biomarkers of depression treatment response to cognitive behavioral therapy (CBT) augmented by actigraphy and computerized algorithms.

2.) "RECOVER: A PRospective, Multi-cEnter, Randomized Controlled Blinded Trial DemOnstrating
the Safety and Effectiveness of VNS Therapy® System as AdjunctivE Therapy Versus a No Stimulation
Control in Subjects With Treatment-Resistant Depression"
We are trying to determine whether active VNS Therapy treatment improves health outcomes for Treatment

3.) "Reducing neural perseveration through closed loop real time fMRI neurofeedback to alleviate
depressive symptoms"
We will test the efficacy of a new psychotherapeutic strategy to reduce depression severity, the first real-time fMRI feedback therapy to use cloud-based pattern classification to decode the patient’s attentional state and dynamically modulate task stimuli (in a “closed loop”) based on this state.

4.) "Intensive TMS for Rapid Relief of Bipolar Depression Symptoms"
In Bipolar depressed patients we are testing whether using high dose spaced theta-burst rTMS (HDS-TBS) produces a significant reduction in depressive symptoms compared with sham using a within-subjects design, maximizing power to detect differences and enabling all participants to receive active treatment.

5.) "Harmonization of Multi-Site Neuroimaging Data from Complex Study Designs"
In this project, we propose to develop, implement, and apply next-generation imaging harmonization methods for data acquired longitudinally or from more complex study designs, as well as appropriate harmonization methods for use in conjunction with popular multivariate pattern analysis techniques.

6.) "3/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)"
All MRI data will be processed and harmonized identically at a central imaging core to ensure
uniformity. We have three primary aims: 1) Investigate how the E-field achieves antidepressant effects, by
testing the causal paths on treatment responsive biomarkers expected to mediate effects on antidepressant outcomes; 2) Investigate how E-field produces cognitive effects, by testing causal paths on cognitive safety biomarkers expected to mediate effects on cognitive outcomes; and 3) through integration of methodologies, to determine localization and strength of optimal ECT

7.) "Novel electric-field modelling approach to quantify changes in resting state functional
connectivity following theta burst stimulation"
Build and validate a whole-brain, domain-general model of brain connectivity changes following transcranial magnetic stimulation (TMS), based on physical models of the current distribution at the cortex. This work will provide direct evidence that brain connectivity changes following neuromodulatory TMS vary as a function of the current density

8.) "Individualized brain biomarkers of late life depression: contributions to disease trajectory and
Determination of optimal brain and disease measures and with depression assessment for late life depression.

9.) "Depression and Alzheimer’s Disease: CaTAUstrophy?"
Dr. Sheline will assist with interpretation of clinical, neuroimaging and brain biomarker depression brain biomarker findings and provide input on determining life course and illness burden.

Selected Publications

Yang, Zhen, Oathes, Desmond, Linn, Kristin, Bruce, Steven D., Satterthwaite, Theodore, A. Cook, Philip K. Satchell, Emma Shou, Haochang Sheline, Yvette: Cognitive Behavioral Therapy Is Associated With Enhanced Cognitive Control Network Activity in Major Depression and Posttraumatic Stress Disorder. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging 2017.

Fortin, J. P., Cullen, N., Sheline, Y. I., Taylor, W. D., Aselcioglu, I., Cook, P. A., . . . Shinohara, R. T. : Harmonization of cortical thickness measurements across scanners and sites. Neuroimage, 167: 104-120, Feb 2017.

Satterthwaite, T. D., Cook, P. A., Bruce, S. E., Conway, C., Mikkelsen, E., Satchell, E., . . . Sheline, Y. I. : Dimensional depression severity in women with major depression and post-traumatic stress disorder correlates with fronto-amygdalar hypoconnectivty. Mol Psychiatry 21(7): 894-902, 2016.

Sheline YI, West T, Yarasheski K, Swarm R, Jasielec MS, Fisher JR, Ficker WD, Yan P, Xiong Z, Frederikson C, Grzelak MV, Chott R, Bateman R, Morris, J, Mintun M, Lee J, Cirrito JR: An antidepressant decreases CSF Aβ production in healthy individuals and in transgenic AD mice. Science Translational Medicine 6: 236, 2014.

Sheline YI, Disabato BM, Hranilovich J, Morris C, D’Angelo G, Pieper C, Tofanin T, Taylor WD, MacFall J, Wilkins C, Barch DM, Welsh-Bohmer KA, Steffens DC, Krishnan RR, Doraiswamy PM : Treatment course with antidepressant therapy in late-life depression. American Journal of Psychiatry 169(11): 1185-1193, 2013.

Sheline YI, Raichle ME : Resting state functional connectivity in preclinical Alzheimer's disease. Biological Psychiatry 5: 340-7, 2013.

Sheline YI, Pieper CF, Barch DM, Welsh-Boehmer K, McKinstry RC, MacFall JR, D’Angelo G, Garcia K, Gersing K, Wilkins C, Taylor W, Steffens DC, Krishnan RR, Doraiswamy PM : Support for the Vascular Depression Hypothesis in Late Life Depression: Results from a Two Site Prospective Antidepressant Treatment Trial. Archives of General Psychiatry 67: 277-85, 2010.

Sheline YI, Price JL, Yan Z, Mintun MA : Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proceeding of the National Academy of Sciences USA 107: 111020-5, 2010.

Sheline YI, Raichle ME, Snyder AZ, Morris JC, Head D, Wang S, Mintun MA : Amyloid plaques disrupt resting state default mode network connectivity in cognitively normal elderly. Biological Psychiatry 67: 584-7, 2010.

Sheline YI, Barch DM, Price JL, Rundle MM, Vaishnavi N, Snyder AZ, Mintun MA, Wang S, Coalson RS, Raichle ME : The Default Mode Network and Self-Referential Processes in Depression. Proceeding of the National Academy of Sciences 106: 1942-7, 2009.

Fales CL, Barch DM, Rundle MM, Mintun MA, Snyder AZ, Cohen JD, Mathews J, Sheline YI : Altered Emotional Interference Processing in Affective and Cognitive Control Brain Circuitry in Major Depression. Biological Psychiatry 63: 377-84, 2008.

Mintun MA, LaRossa GN, Sheline YI, Dence CS, Yoon Lee MS, Mach RH, Klunk WE, Mathis CA, DeKosky ST, Morris JC : PIB in a Nondemented Population Potential Antecedent Marker of Alzheimer Disease. Neurology. Neurology 67: 446-452, 2006.

Sheline YI, Barch DM, Garcia K, Gersing K, Pieper C, Welsh-Bohmer K, Steffens DC, Doraiswamy PM : Cognitive Function in Late Life Depression: Relationships to Depression Severity, Cerebrovascular Risk Factors and Processing Speed. Biological Psychiatry 60: 58-64, 2006.

Sheline YI, Gado MH, Kraemer HC : Untreated Depression and Hippocampal Volume Loss. American Journal of Psychiatry. American Journal of Psychiatry 160: 1516-1518, 2003.

Sheline YI : 3-D MRI Studies of Neuroanatomical Changes in Unipolar Major Depression: The Role of Stress and Medical Co-morbidity. Biological Psychiatry 48: 791-800, 2000.

Sheline YI, Wang PW, Gado MH, Csernansky JG, Vannier MW : Hippocampal Atrophy in Recurrent Major Depression. Proceedings of the National Academy of Sciences 93: 3908-3913, 1996.

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Last updated: 05/01/2023
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