Abstract: To our knowledge, this is the first reported case demonstrating that both treatment-resistant major depression and its response to ketamine can occur in the absence of the basolateral amygdala. Influential reports regarding the neurobiological origin of depression have highlighted a central role for the amygdala in the pathogenesis of depression. While there are heterogeneous findings of amygdala activity in major depression, possibly as a result of differences in contrast selection, recent meta-analytic evidence indicates that major depression is associated with blunted amygdala responses to negative stimuli. Likewise, a meta-analysis found reduced amygdala volume in unmedicated patients, but there are also reports of amygdala enlargement in acutely depressed patients. Notably, pretreatment amygdala hyporeactivity has been identified as a general predictor of treatment response, and neurofeedback-based increases in amygdala hemodynamic activity can mitigate depressive symptoms. Furthermore, major depression has also been associated with dysfunctions in large-scale brain networks. One of the most consistent findings is hyperconnectivity of the default mode network (DMN), which encompasses the posterior and anterior cortical midline structures and shows increased activation during self-referential processing in the resting state. It has been suggested that the DMN assigns valence to internally represented stimuli, and the DMN has been linked to self-focused rumination in major depression. By contrast, patients with major depression have been found to exhibit hypoconnectivity within the frontoparietal network (FPN) and salience network (SAN). The FPN plays a pivotal role in cognitive control of emotional responses and the SAN, comprising the dorsal anterior cingulate cortex, fronto-insular cortex, and amygdala, is crucially involved in determining the biological significance of external stimuli. Interestingly, multiple depressive episodes may lead to a temporal decoupling of the amygdala from SAN regions.
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The participant will recognize the existence of depressive symptoms in a patient with basolateral amygdala damage and identify the profile of a ketamine-induced antidepressant effect.
This program is designed for all psychiatrists in clinical practice, residents in Graduate Medical Education programs, medical students interested in psychiatry, and other physicians who wish to advance their current knowledge of clinical medicine.
Estimated Time to Complete
Duration: 1 hour
Begin Date: December 1, 2019
End Date: November 30, 2021
How to Earn Credit
In order to earn CME credit, subscribers should read through the material presented in the article. After reading the article, complete the quiz and submit your evaluation and study hours (up to 1 AMA PRA Category 1 Credit™). A score of 60% or higher is required to receive credit.
The American Psychiatric Association (APA) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
The APA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Faculty and Planner Disclosures
Title: Treatment-Resistant Depression and Ketamine Response in a Patient With Bilateral Amygdala Damage
Authors: Dirk Scheele, Ph.D., Sophia Zimbal, Justin S. Feinstein, Ph.D., Achilles Delis, M.D., Claudia Neumann, M.D., Clemens Mielacher, Alexandra Philipsen, M.D., René Hurlemann, M.D., Ph.D.
Affiliations: Division of Medical Psychology (D.S., S.Z., C.M., R.H.), Department of Anesthesiology (A.D., C.N.), and Department of Psychiatry (A.P., R.H.), University Hospital, Bonn, Germany; Laureate Institute for Brain Research, Tulsa, Okla. (J.S.F.); and Department of Psychiatry, University of Oldenburg Medical Campus, Bad Zwischenahn, Germany (R.H.).
Disclosures: The authors report no financial relationships with commercial interests.
Discussion of unapproved or investigational use of products*: No.
*APA policy requires disclosure by CME authors of unapproved or investigational use of products discussed in CME programs. Off-label use of medications by individual physicians is permitted and common. Decisions about off-label use can be guided by scientific literature and clinical experience.
Ned H. Kalin, M.D. (Editor-in-Chief, AJP); Carolyn Rodriguez, M.D., Ph.D. (Deputy Editor, AJP); Michael D. Roy (Editorial Director, AJP); Michael A. Pogachar (Online Content Manager, Journals). Dr. Kalin has served as a consultant to the Board of Scientific Advisors, the Pritzker Neuropsychiatric Disorders Research Consortium, and the Skyland Trail Advisory Board and as Councilor, Society of Biological Psychiatry. Dr. Rodriguez has served as a consultant to Allergan, Blackthorn, Epiodyne, and Rugen. Mr. Roy and Mr. Pogachar report no financial relationships with commercial interests.
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