nih-gov/www.nimh.nih.gov/news/science-updates/2013/imaging-biomarker-predicts-response-to-rapid-antidepressant
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</style><div class="row feature-box m-0 mb-3"><div class="col-xl-12"><h5 class="mt-2 mb-0"><i class="fa-regular fa-box-archive"></i> &nbsp;Archived Content</h5><p><small>The National Institute of Mental Health archives materials that are over 4 years old and no longer being updated. The content on this page is provided for historical reference purposes only and may not reflect current knowledge or information.</small></p></div></div></div>
<div class="titleblock">
<h1 class="titleblock__title" id="title">Imaging Biomarker Predicts Response to Rapid Antidepressant</h1>
</div>
<p id="subtitle">Signals Dysfunction in Brain System Targeted by Scopolamine NIH Study</p>
<p class="pagestamp_news_wrap">
<time class="pagestamp_news_time" datetime="2013-02-04">February 4, 2013</time>
• <span class="pagestamp_news_type">Press Release</span></p>
<html><body><p>A telltale boost of activity at the back of the brain while processing emotional information predicted whether depressed patients would respond to an experimental rapid-acting antidepressant, a National Institutes of Health study has found.
</p>
<div><a href="http://www.youtube.com/watch?v=LYgOxldodeg" rel="external noreferrer">
<article class="media media--type-image media--view-mode-default">
<span class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <img loading="lazy" src="/sites/default/files/images/news-items/furey_scopalamine_video_thumbnail.png" width="240" height="134" alt="NIMHs Dr. Maura Furey talks about scopolamine research">
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&nbsp;<i class="fa-solid fa-arrow-up-right-from-square ext-link-icon"></i></a>
<br>
<!--<em>NIMH&#8217;s Dr. Maura Furey talks about scopolamine research</em>--></div>
<p>“We have discovered a potential neuroimaging biomarker that may eventually help to personalize treatment selection by revealing brain-based differences between patients,” explained Maura Furey, Ph.D., of NIHs National Institute of Mental Health (NIMH).
</p>
<p>Furey, NIMHs Carlos Zarate, M.D., and colleagues, reported on their functional magnetic resonance imaging (fMRI) study of a pre-treatment biomarker for the antidepressant response to scopolamine, Jan. 30, 2013, online in JAMA Psychiatry.
</p>
<p>Scopolamine, better known as a treatment for motion sickness, has been&nbsp;<a href="https://reporter.nih.gov/project-details/8556944" rel="external">under study&nbsp;<i class="fa-solid fa-arrow-up-right-from-square ext-link-icon"></i></a>&nbsp;since Furey and colleagues discovered its fast-acting antidepressant properties in 2006. Unlike&nbsp;<a data-entity-substitution="canonical" data-entity-type="node" data-entity-uuid="cfa023b3-e64e-402f-9f26-f142c639ac11" href="/news/science-updates/2012/brain-signal-ids-responders-to-fast-acting-antidepressant">ketamine</a>, scopolamine works through the brains acetylcholine chemical messenger system. The NIMH teams research has demonstrated that by blocking receptors for acetylcholine on neurons, scopolamine can lift depression in many patients within a few days; conventional antidepressants typically take weeks to work. But not all patients respond, spurring interest in a predictive biomarker.
</p>
<p>The acetylcholine system plays a pivotal role in working memory, holding information in mind temporarily, but appears to act by influencing the processing of information rather than through memory. Imaging studies suggest that visual working memory performance can be enhanced by modulating acetylcholine-induced activity in the brains visual processing area, called the visual cortex, when processing information that is important to the task. Since working memory performance can predict response to conventional antidepressants and ketamine, Furey and colleagues turned to a working memory task and imaging visual cortex activity as potential tools to identify a biomarker for scopolamine response.
</p>
<p>Depressed patients have a well-known tendency to process and remember negative emotional information. The researchers propose that this bias stems from dysregulated acetylcholine systems in some patients. They reasoned that such patients would show aberrant visual cortex activity in response to negative emotional features of a working memory task. They also expected to find that patients with more dysfunctional acetylcholine systems would respond better to scopolamine treatment.
</p>
<p>Before receiving scopolamine, participants performed a working memory task while their brain activity was monitored via fMRI. For some trials, it required that they pay attention to, and remember, the emotional expression (sad, happy, etc.) of faces flashing on a computer monitor. For other trials, they had to pay attention to only the identity, or non-emotional feature, of the faces. After scanning, and over the following several weeks, 15 patients with depression and 21 healthy participants randomly received infusions of a placebo (salt solution) and/or scopolamine. Mood changes were monitored with depression rating scales.
</p>
<p>Overall, scopolamine treatment reduced depression symptoms by 63 percent, with 11 of the patients showing a significant clinical response. The strength of this response correlated significantly with visual cortex activity during key phases of the working memory task while participants were paying attention to the emotional content of the faces. There was no such correlation for trials when they attended to the identity of the faces.
</p>
<p>The findings suggest that acetylcholine system activity drives visual cortex activity that predicts treatment response and that differences seen between depressed patients and controls may be traceable to acetylcholine dysfunction. Overall, patients showed lower visual cortex activity than controls during the emotion phase of the task. Patients showing activity levels most dissimilar to controls experienced the greatest antidepressant response to scopolamine treatment. Visual cortex activity in patients who didnt respond to scopolamine more closely resembled that of controls. As hypothesized, the pretreatment level of visual cortex activity appears to reflect the extent of patients acetylcholine system dysfunction and to predict their response to the experimental medication, say the researchers.
</p>
<p>Preliminary evidence suggests that such visual cortex activity in response to emotional stimuli may also apply to other treatments and may prove to be a shared biomarker of rapid antidepressant response, according to Furey.
</p>
<div class="image_middle_callout middle" data-cms-id="144045">
<div class="image_middle_callout_wrapper">
<article class="align-center media media--type-image media--view-mode-default">
<span class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <img loading="lazy" src="/sites/default/files/images/news-items/fureyscopolaminemidoccipital.png" width="252" height="220" alt="visual cortex activity">
</span>
</article>
<div class="image_middle_callout_callout">
<p><em>The level of increased activity in left and right visual cortex (blue), while attending to emotional faces in a working memory task, predicted depressed patients responsiveness to the experimental antidepressant scopolamine. View from the back of the brain shows fMRI data superimposed on anatomical MRI scan data.&nbsp;
<br>
<!--Source: Maura Furey, Ph.D., NIMH Experimental Therapeutics and Pathophysiology Branch</em>--></em>
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<div class="image_middle_callout middle" data-cms-id="144046">
<div class="image_middle_callout_wrapper">
<article class="align-center media media--type-image media--view-mode-default">
<span class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <img loading="lazy" src="/sites/default/files/images/news-items/fureyfaces1.png" width="526" height="409" alt="faces used in working memory task">
</span>
</article>
<div class="image_middle_callout_callout">
<p><em>Working memory task: Over several trials, participants were required to attend to either the identity (non-emotional feature) or the emotion of a face, remember it during a 9 second delay, and match the feature to a subsequent face. Neural activity in the visual cortex elicited by the emotion trials predicted a patients subsequent responsiveness to scopolamine treatment.</em>&nbsp;
<br>
<!--Source: Maura Furey, Ph.D., NIMH Experimental Therapeutics and Pathophysiology Branch--></p>
</div>
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<h2><em contenteditable="false" unselectable="on">References</em>
</h2>
<p><em contenteditable="false" unselectable="on"><a href="http://www.ncbi.nlm.nih.gov/pubmed/23364679" rel="external">Potential of Pretreatment Neural Activity in the Visual Cortex During Emotional Processing to Predict Treatment Response to Scopolamine in Major Depressive Disorder.&nbsp;<i class="fa-solid fa-arrow-up-right-from-square ext-link-icon"></i></a> Furey ML, Drevets WC, Hoffman EM, Frankel E, Speer AM, Zarate CA. JAMA Psychiatry. 2013 Jan 30:1-11. doi: 10.1001/2013.jamapsychiatry.60. [Epub ahead of print] PMID:23364679</em>
</p>
<p><em contenteditable="false" unselectable="on"><a href="https://reporter.nih.gov/project-details/8556944" rel="external">Cholinergic Modulation of Cognition and Emotion in Mood Disorders&nbsp;<i class="fa-solid fa-arrow-up-right-from-square ext-link-icon"></i></a></em>
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<html><body><p><strong>About the National Institute of Mental Health (NIMH):</strong> The mission of the
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