Shank3 as a potential biomarker of antidepressant response to ketamine and its neural correlates in bipolar depression
Shank3, a post-synaptic density protein involved in N-methyl-d-aspartate (NMDA) receptor tethering and dendritic spine rearrangement, is implicated in the pathophysiology of bipolar disorder. We hypothesized that elevated baseline plasma Shank3 levels might predict antidepressant response to the NMD...
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| Published in | Journal of affective disorders Vol. 172; pp. 307 - 311 |
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| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier B.V
01.02.2015
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0165-0327 1573-2517 1573-2517 |
| DOI | 10.1016/j.jad.2014.09.015 |
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| Abstract | Shank3, a post-synaptic density protein involved in N-methyl-d-aspartate (NMDA) receptor tethering and dendritic spine rearrangement, is implicated in the pathophysiology of bipolar disorder. We hypothesized that elevated baseline plasma Shank3 levels might predict antidepressant response to the NMDA receptor antagonist ketamine.
Twenty-nine subjects with bipolar depression received a double-blind, randomized, subanesthetic dose (.5mg/kg) ketamine infusion. Of the patients for whom Shank3 levels were collected, 15 completed baseline 3-Tesla MRI and 17 completed post-ketamine [18F]-FDG PET.
Higher baseline Shank3 levels predicted antidepressant response at Days 1 (r=−.39, p=.047), 2 (r=−.45, p=.02), and 3 (r=−.42, p=.03) and were associated with larger average (r=.58, p=.02) and right amygdala volume (r=.65, p=.009). Greater baseline Shank3 also predicted increased glucose metabolism in the hippocampus (r=.51, p=.04) and amygdala (r=.58, p=.02).
Limitations include the small sample size, inability to assess the source of peripheral Shank3, and the lack of a placebo group for baseline Shank3 levels and comparative structural/functional neuroimaging.
Shank3 is a potential biomarker of antidepressant response to ketamine that correlates with baseline amygdala volume and increased glucose metabolism in the amygdala and hippocampus. |
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| AbstractList | Shank3, a post-synaptic density protein involved in N-methyl-d-aspartate (NMDA) receptor tethering and dendritic spine rearrangement, is implicated in the pathophysiology of bipolar disorder. We hypothesized that elevated baseline plasma Shank3 levels might predict antidepressant response to the NMDA receptor antagonist ketamine.BACKGROUNDShank3, a post-synaptic density protein involved in N-methyl-d-aspartate (NMDA) receptor tethering and dendritic spine rearrangement, is implicated in the pathophysiology of bipolar disorder. We hypothesized that elevated baseline plasma Shank3 levels might predict antidepressant response to the NMDA receptor antagonist ketamine.Twenty-nine subjects with bipolar depression received a double-blind, randomized, subanesthetic dose (.5 mg/kg) ketamine infusion. Of the patients for whom Shank3 levels were collected, 15 completed baseline 3-Tesla MRI and 17 completed post-ketamine [(18)F]-FDG PET.METHODSTwenty-nine subjects with bipolar depression received a double-blind, randomized, subanesthetic dose (.5 mg/kg) ketamine infusion. Of the patients for whom Shank3 levels were collected, 15 completed baseline 3-Tesla MRI and 17 completed post-ketamine [(18)F]-FDG PET.Higher baseline Shank3 levels predicted antidepressant response at Days 1 (r=-.39, p=.047), 2 (r=-.45, p=.02), and 3 (r=-.42, p=.03) and were associated with larger average (r=.58, p=.02) and right amygdala volume (r=.65, p=.009). Greater baseline Shank3 also predicted increased glucose metabolism in the hippocampus (r=.51, p=.04) and amygdala (r=.58, p=.02).RESULTSHigher baseline Shank3 levels predicted antidepressant response at Days 1 (r=-.39, p=.047), 2 (r=-.45, p=.02), and 3 (r=-.42, p=.03) and were associated with larger average (r=.58, p=.02) and right amygdala volume (r=.65, p=.009). Greater baseline Shank3 also predicted increased glucose metabolism in the hippocampus (r=.51, p=.04) and amygdala (r=.58, p=.02).Limitations include the small sample size, inability to assess the source of peripheral Shank3, and the lack of a placebo group for baseline Shank3 levels and comparative structural/functional neuroimaging.LIMITATIONSLimitations include the small sample size, inability to assess the source of peripheral Shank3, and the lack of a placebo group for baseline Shank3 levels and comparative structural/functional neuroimaging.Shank3 is a potential biomarker of antidepressant response to ketamine that correlates with baseline amygdala volume and increased glucose metabolism in the amygdala and hippocampus.CONCLUSIONSShank3 is a potential biomarker of antidepressant response to ketamine that correlates with baseline amygdala volume and increased glucose metabolism in the amygdala and hippocampus. Abstract Background Shank3, a post-synaptic density protein involved in N-methyl- d -aspartate (NMDA) receptor tethering and dendritic spine rearrangement, is implicated in the pathophysiology of bipolar disorder. We hypothesized that elevated baseline plasma Shank3 levels might predict antidepressant response to the NMDA receptor antagonist ketamine. Methods Twenty-nine subjects with bipolar depression received a double-blind, randomized, subanesthetic dose (.5 mg/kg) ketamine infusion. Of the patients for whom Shank3 levels were collected, 15 completed baseline 3-Tesla MRI and 17 completed post-ketamine [18 F]-FDG PET. Results Higher baseline Shank3 levels predicted antidepressant response at Days 1 ( r =−.39, p =.047), 2 ( r =−.45, p =.02), and 3 ( r =−.42, p =.03) and were associated with larger average ( r =.58, p =.02) and right amygdala volume ( r =.65, p =.009). Greater baseline Shank3 also predicted increased glucose metabolism in the hippocampus ( r =.51, p =.04) and amygdala ( r =.58, p =.02). Limitations Limitations include the small sample size, inability to assess the source of peripheral Shank3, and the lack of a placebo group for baseline Shank3 levels and comparative structural/functional neuroimaging. Conclusions Shank3 is a potential biomarker of antidepressant response to ketamine that correlates with baseline amygdala volume and increased glucose metabolism in the amygdala and hippocampus. Background: Shank3, a post-synaptic density protein involved in N-methyl-d-aspartate (NMDA) receptor tethering and dendritic spine rearrangement, is implicated in the pathophysiology of bipolar disorder. We hypothesized that elevated baseline plasma Shank3 levels might predict antidepressant response to the NMDA receptor antagonist ketamine. Methods: Twenty-nine subjects with bipolar depression received a double-blind, randomized, subanesthetic dose (.5 mg/kg) ketamine infusion. Of the patients for whom Shank3 levels were collected, 15 completed baseline 3-Tesla MRI and 17 completed post-ketamine [ super(18)F]-FDG PET. Results: Higher baseline Shank3 levels predicted antidepressant response at Days 1 (r=-.39, p=.047), 2 (r=-.45, p=.02), and 3 (r=-.42, p=.03) and were associated with larger average (r=.58, p=.02) and right amygdala volume (r=.65, p=.009). Greater baseline Shank3 also predicted increased glucose metabolism in the hippocampus (r=.51, p=.04) and amygdala (r=.58, p=.02). Limitations Limitations include the small sample size, inability to assess the source of peripheral Shank3, and the lack of a placebo group for baseline Shank3 levels and comparative structural/functional neuroimaging. Conclusions: Shank3 is a potential biomarker of antidepressant response to ketamine that correlates with baseline amygdala volume and increased glucose metabolism in the amygdala and hippocampus. Shank3, a post-synaptic density protein involved in N-methyl-d-aspartate (NMDA) receptor tethering and dendritic spine rearrangement, is implicated in the pathophysiology of bipolar disorder. We hypothesized that elevated baseline plasma Shank3 levels might predict antidepressant response to the NMDA receptor antagonist ketamine. Twenty-nine subjects with bipolar depression received a double-blind, randomized, subanesthetic dose (.5 mg/kg) ketamine infusion. Of the patients for whom Shank3 levels were collected, 15 completed baseline 3-Tesla MRI and 17 completed post-ketamine [(18)F]-FDG PET. Higher baseline Shank3 levels predicted antidepressant response at Days 1 (r=-.39, p=.047), 2 (r=-.45, p=.02), and 3 (r=-.42, p=.03) and were associated with larger average (r=.58, p=.02) and right amygdala volume (r=.65, p=.009). Greater baseline Shank3 also predicted increased glucose metabolism in the hippocampus (r=.51, p=.04) and amygdala (r=.58, p=.02). Limitations include the small sample size, inability to assess the source of peripheral Shank3, and the lack of a placebo group for baseline Shank3 levels and comparative structural/functional neuroimaging. Shank3 is a potential biomarker of antidepressant response to ketamine that correlates with baseline amygdala volume and increased glucose metabolism in the amygdala and hippocampus. Shank3, a post-synaptic density protein involved in N-methyl-d-aspartate (NMDA) receptor tethering and dendritic spine rearrangement, is implicated in the pathophysiology of bipolar disorder. We hypothesized that elevated baseline plasma Shank3 levels might predict antidepressant response to the NMDA receptor antagonist ketamine. Twenty-nine subjects with bipolar depression received a double-blind, randomized, subanesthetic dose (.5mg/kg) ketamine infusion. Of the patients for whom Shank3 levels were collected, 15 completed baseline 3-Tesla MRI and 17 completed post-ketamine [18F]-FDG PET. Higher baseline Shank3 levels predicted antidepressant response at Days 1 (r=−.39, p=.047), 2 (r=−.45, p=.02), and 3 (r=−.42, p=.03) and were associated with larger average (r=.58, p=.02) and right amygdala volume (r=.65, p=.009). Greater baseline Shank3 also predicted increased glucose metabolism in the hippocampus (r=.51, p=.04) and amygdala (r=.58, p=.02). Limitations include the small sample size, inability to assess the source of peripheral Shank3, and the lack of a placebo group for baseline Shank3 levels and comparative structural/functional neuroimaging. Shank3 is a potential biomarker of antidepressant response to ketamine that correlates with baseline amygdala volume and increased glucose metabolism in the amygdala and hippocampus. |
| Author | Machado-Vieira, Rodrigo Ortiz, Robin Niciu, Mark J. Saligan, Leorey N. Luckenbaugh, David A. Zarate, Carlos A. Lukkahati, Nada Nugent, Allison C. |
| AuthorAffiliation | 3 School of Nursing, University of Nevada at Las Vegas, Las Vegas, NV, USA 2 National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, USA 1 National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Division of Intramural Research Programs, National Institutes of Health, Bethesda, MD, USA |
| AuthorAffiliation_xml | – name: 1 National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Division of Intramural Research Programs, National Institutes of Health, Bethesda, MD, USA – name: 3 School of Nursing, University of Nevada at Las Vegas, Las Vegas, NV, USA – name: 2 National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, USA |
| Author_xml | – sequence: 1 givenname: Robin surname: Ortiz fullname: Ortiz, Robin organization: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics & Pathophysiology Branch, Building 10/Clinical Research Center (CRC), 10 Center Dr., Room 7-5342, Bethesda, MD 20892, USA – sequence: 2 givenname: Mark J. surname: Niciu fullname: Niciu, Mark J. organization: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics & Pathophysiology Branch, Building 10/Clinical Research Center (CRC), 10 Center Dr., Room 7-5342, Bethesda, MD 20892, USA – sequence: 3 givenname: Nada surname: Lukkahati fullname: Lukkahati, Nada organization: National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, USA – sequence: 4 givenname: Leorey N. surname: Saligan fullname: Saligan, Leorey N. organization: National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, USA – sequence: 5 givenname: Allison C. surname: Nugent fullname: Nugent, Allison C. organization: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics & Pathophysiology Branch, Building 10/Clinical Research Center (CRC), 10 Center Dr., Room 7-5342, Bethesda, MD 20892, USA – sequence: 6 givenname: David A. surname: Luckenbaugh fullname: Luckenbaugh, David A. organization: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics & Pathophysiology Branch, Building 10/Clinical Research Center (CRC), 10 Center Dr., Room 7-5342, Bethesda, MD 20892, USA – sequence: 7 givenname: Rodrigo surname: Machado-Vieira fullname: Machado-Vieira, Rodrigo organization: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics & Pathophysiology Branch, Building 10/Clinical Research Center (CRC), 10 Center Dr., Room 7-5342, Bethesda, MD 20892, USA – sequence: 8 givenname: Carlos A. surname: Zarate fullname: Zarate, Carlos A. email: zaratec@mail.nih.gov organization: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics & Pathophysiology Branch, Building 10/Clinical Research Center (CRC), 10 Center Dr., Room 7-5342, Bethesda, MD 20892, USA |
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| Snippet | Shank3, a post-synaptic density protein involved in N-methyl-d-aspartate (NMDA) receptor tethering and dendritic spine rearrangement, is implicated in the... Abstract Background Shank3, a post-synaptic density protein involved in N-methyl- d -aspartate (NMDA) receptor tethering and dendritic spine rearrangement, is... Background: Shank3, a post-synaptic density protein involved in N-methyl-d-aspartate (NMDA) receptor tethering and dendritic spine rearrangement, is implicated... |
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| SubjectTerms | Adult Aged Amygdala - metabolism Antidepressive Agents - therapeutic use Biomarkers - blood Bipolar depression Bipolar Disorder - blood Bipolar Disorder - drug therapy Double-Blind Method Female Humans Ketamine Ketamine - therapeutic use Male MRI N-Methylaspartate - therapeutic use PET Psychiatry Receptors, N-Methyl-D-Aspartate - blood Shank3 Treatment Outcome |
| Title | Shank3 as a potential biomarker of antidepressant response to ketamine and its neural correlates in bipolar depression |
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