Characterization of Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder Using Ketamine as an Experimental Medicine Probe-Journal of Psychiatry and Brain Science-CSCIED科技核心评价数据库-手机版

Characterization of Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder Using Ketamine as an Experimental Medicine Probe

Characterization of Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder Using Ketamine as an Experimental Medicine Probe

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DOI	10.20900/jpbs.20210012
刊名	Journal of Psychiatry and Brain Science JPBS
年，卷(期)	2021, 6(3)
作者	C. Sophia Albott*,Sey Lee,Kathryn R. Cullen,Paul Thuras,Shmuel Lissek,Joseph Wels,Katrina J. Friedrich,Alyssa M. Krueger,Kelvin O. Lim,
作者单位	Department of Psychiatry & Behavioral Sciences, University of Minnesota Medical School, Minneapolis, MN 55454, USA ; Minneapolis VA Health Care System, Minneapolis, MN 55417, USA ; Department of Psychology, University of Minnesota, Minneapolis, MN 55455, USA ;
Abstract	Comorbid posttraumatic stress disorder and major depressive disorder (PTSD + MDD) is the most common pathological response to trauma, yet despite their synergistic detriment to health, knowledge regarding the neurobiological mechanism underlying PTSD + MDD is extremely limited. This study proposes a novel model of PTSD + MDD that is built on biological systems shown to underlay PTSD + MDD and takes advantage of ketamine’s unique suitability to probe PTSD + MDD due to its rescue of stress-related neuroplasticity deficits. The central hypothesis is that changes in PTSD + MDD clinical symptoms are associated with functional connectivity changes and cognitive dysfunction and that ketamine infusions improve clinical symptoms by correction of functional connectivity changes and improvement in cognition. Participants with PTSD + MDD (n = 42) will be randomized to receive a series of six ketamine infusions or saline-placebo over three weeks. Pre/post-measures will include: (1) neuroimaging; (2) cognitive functioning task performance; and (3) PTSD, MDD, and rumination self-report measures. These measures will also be collected once in a trauma-exposed group including PTSD-only (n = 10), trauma-exposed-MDD (TE-MDD; n = 10), and healthy controls (HC, n = 21). Successful completion of the study will strongly support the concept of a biologically-based model of PTSD + MDD. The results will (1) identify functional imaging signatures of the mechanisms underpinning pathological responses to trauma, (2) shift focus from mono-diagnostic silos to unified biological and behavioral disease processes and, thus, (3) inform interventions to correct dysregulation of PTSD + MDD symptom clusters thereby supporting more precise treatments and better outcomes.
KeyWord	ketamine; stress disorders; stress biomarkers; trauma mechanism; post-traumatic stress disorders; treatment-resistant depressive disorder; magnetic resonance imaging; functional connectivity; neuroplasticity; pharmacologic actions
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C. Sophia Albott*,Sey Lee,Kathryn R. Cullen,Paul Thuras,Shmuel Lissek,Joseph Wels,Katrina J. Friedrich,Alyssa M. Krueger,Kelvin O. Lim. Characterization of Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder Using Ketamine as an Experimental Medicine Probe, Journal of Psychiatry and Brain Science. 2021; 6; (3). https://doi.org/10.20900/jpbs.20210012.

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