SHANK3 AS A POTENTIAL BIOMARKER OF ANTIDEPRESSANT RESPONSE TO KETAMINE AND ITS NEURAL CORRELATES IN BIPOLAR DEPRESSION

Robin Ortiz; Mark J Niciu; Nada Lukkahati; Leorey N Saligan; Allison C Nugent; David A Luckenbaugh; Rodrigo Machado-Vieira; Carlos A Zarate

doi:10.1016/j.jad.2014.09.015

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SHANK3 AS A POTENTIAL BIOMARKER OF ANTIDEPRESSANT RESPONSE TO KETAMINE AND ITS NEURAL CORRELATES IN BIPOLAR DEPRESSION

Journal article

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SHANK3 AS A POTENTIAL BIOMARKER OF ANTIDEPRESSANT RESPONSE TO KETAMINE AND ITS NEURAL CORRELATES IN BIPOLAR DEPRESSION

Robin Ortiz, Mark J Niciu, Nada Lukkahati, Leorey N Saligan, Allison C Nugent, David A Luckenbaugh, Rodrigo Machado-Vieira and Carlos A Zarate

Journal of affective disorders, Vol.172, pp.307-311

02/01/2015

DOI: 10.1016/j.jad.2014.09.015

PMCID: PMC4400209

PMID: 25451430

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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.

bipolar depression

Ketamine

Shank3

MRI

PET

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Title: Subtitle: SHANK3 AS A POTENTIAL BIOMARKER OF ANTIDEPRESSANT RESPONSE TO KETAMINE AND ITS NEURAL CORRELATES IN BIPOLAR DEPRESSION
Creators: Robin Ortiz - School of Nursing, University of Nevada at Las Vegas, Las Vegas, NV, USA
Mark J Niciu - School of Nursing, University of Nevada at Las Vegas, Las Vegas, NV, USA
Nada Lukkahati - School of Nursing, University of Nevada at Las Vegas, Las Vegas, NV, USA
Leorey N Saligan - School of Nursing, University of Nevada at Las Vegas, Las Vegas, NV, USA
Allison C Nugent - School of Nursing, University of Nevada at Las Vegas, Las Vegas, NV, USA
David A Luckenbaugh - School of Nursing, University of Nevada at Las Vegas, Las Vegas, NV, USA
Rodrigo Machado-Vieira - School of Nursing, University of Nevada at Las Vegas, Las Vegas, NV, USA
Carlos A Zarate - School of Nursing, University of Nevada at Las Vegas, Las Vegas, NV, USA
Resource Type: Journal article
Publication Details: Journal of affective disorders, Vol.172, pp.307-311
DOI: 10.1016/j.jad.2014.09.015
PMID: 25451430
PMCID: PMC4400209
NLM abbreviation: J Affect Disord
ISSN: 0165-0327
eISSN: 1573-2517
Grant note: name: IRP-NIMH-NIH, award: NCT00088699
Language: English
Date published: 02/01/2015
Academic Unit: Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9984003973702771

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