Effect of bupropion extended release on negative emotion processing in major depressive disorder: A pilot functional magnetic resonance imaging study

Brigitte Robertson, Lihong Wang, Michele Theresa Diaz, Marilyn Aiello, Kenneth Gersing, John Beyer, Srinivasan Mukundan, Gregory McCarthy, P. Murali Doraiswamy

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Background: Prior imaging studies suggest that patients with major depressive disorder have abnormalities in frontal and limbic neural circuitry including the amygdala, which is relatively more activated at rest and in response to negative emotional stimuli (sadness, fear, etc.) in depressed patients than in controls. Concurrently, patients with depression may have decreased activation of attentional executive regions in response to attentional stimuli. This study examined the effect of bupropion XL, an extended release formulation of the nonserotonergic antidepressant agent bupropion, using a paradigm that investigated both negative emotional response and attentional processing. Method: Functional magnetic resonance imaging (fMRI) scans and clinical ratings were obtained for 10 patients with DSM-IV-TR-defined major depressive disorder (mean [SD] age = 41 [± 7] years, mean [SD] Hamilton Rating Scale for Depression [HAM-D] score = 21 [± 4]) before and after 8 weeks of treatment with bupropion XL. The fMRI sessions were conducted during administration of the Emotional Oddball Task; scans were obtained while subjects viewed emotional distracters and performed an attentional executive function task. The primary outcome was fMRI activations evoked by the emotional distracters. The first baseline fMRI scan was performed in December 2004, and the last posttreatment scan was in March 2005. Results: Treatment with bupropion XL was associated with improvements in HAM-D and Clinical Global Impressions scale ratings (p < .05). Treatment reduced fMRI activation during emotional distracters in several regions including right orbital frontal cortex, left dorsomedial prefrontal cortex, right ventromedial prefrontal cortex, right anterior cingulate cortex, right inferior frontal cortex, right amygdala/parahippocampal area, right caudate, right fusiform gyrus, and left posterior cingulate. In addition, changes in fMRI activation in the amygdala correlated with improvements on the HAM-D (p < .05). Treatment increased activation to attentional targets in the following regions: right middle and inferior frontal gyri, right caudate, and bilateral precuneus. Conclusion: Despite the limitations of a small sample size and the lack of a placebo control group, this study demonstrated that bupropion XL therapy for 8 weeks may attenuate emotion-induced, blood-oxygen-level-dependent (BOLD) activation responses in the amygdala and related brain regions. Such attenuation may be associated with a positive clinical response in depression. Bupropion XL also improved activation in the executive-function neural network. These fMRI surrogate markers offer promise for studying anti-depressant and neurocognitive effects of existing and novel therapies.

Original languageEnglish (US)
Pages (from-to)261-267
Number of pages7
JournalJournal of Clinical Psychiatry
Volume68
Issue number2
DOIs
StatePublished - Jan 1 2007

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Bupropion
Major Depressive Disorder
Emotions
Magnetic Resonance Imaging
Amygdala
Prefrontal Cortex
Gyrus Cinguli
Executive Function
Frontal Lobe
Depression
Therapeutics
Parietal Lobe
Temporal Lobe
Diagnostic and Statistical Manual of Mental Disorders
Sample Size
Antidepressive Agents
Fear
Biomarkers
Placebos
Oxygen

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health

Cite this

Robertson, Brigitte ; Wang, Lihong ; Diaz, Michele Theresa ; Aiello, Marilyn ; Gersing, Kenneth ; Beyer, John ; Mukundan, Srinivasan ; McCarthy, Gregory ; Doraiswamy, P. Murali. / Effect of bupropion extended release on negative emotion processing in major depressive disorder : A pilot functional magnetic resonance imaging study. In: Journal of Clinical Psychiatry. 2007 ; Vol. 68, No. 2. pp. 261-267.
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abstract = "Background: Prior imaging studies suggest that patients with major depressive disorder have abnormalities in frontal and limbic neural circuitry including the amygdala, which is relatively more activated at rest and in response to negative emotional stimuli (sadness, fear, etc.) in depressed patients than in controls. Concurrently, patients with depression may have decreased activation of attentional executive regions in response to attentional stimuli. This study examined the effect of bupropion XL, an extended release formulation of the nonserotonergic antidepressant agent bupropion, using a paradigm that investigated both negative emotional response and attentional processing. Method: Functional magnetic resonance imaging (fMRI) scans and clinical ratings were obtained for 10 patients with DSM-IV-TR-defined major depressive disorder (mean [SD] age = 41 [± 7] years, mean [SD] Hamilton Rating Scale for Depression [HAM-D] score = 21 [± 4]) before and after 8 weeks of treatment with bupropion XL. The fMRI sessions were conducted during administration of the Emotional Oddball Task; scans were obtained while subjects viewed emotional distracters and performed an attentional executive function task. The primary outcome was fMRI activations evoked by the emotional distracters. The first baseline fMRI scan was performed in December 2004, and the last posttreatment scan was in March 2005. Results: Treatment with bupropion XL was associated with improvements in HAM-D and Clinical Global Impressions scale ratings (p < .05). Treatment reduced fMRI activation during emotional distracters in several regions including right orbital frontal cortex, left dorsomedial prefrontal cortex, right ventromedial prefrontal cortex, right anterior cingulate cortex, right inferior frontal cortex, right amygdala/parahippocampal area, right caudate, right fusiform gyrus, and left posterior cingulate. In addition, changes in fMRI activation in the amygdala correlated with improvements on the HAM-D (p < .05). Treatment increased activation to attentional targets in the following regions: right middle and inferior frontal gyri, right caudate, and bilateral precuneus. Conclusion: Despite the limitations of a small sample size and the lack of a placebo control group, this study demonstrated that bupropion XL therapy for 8 weeks may attenuate emotion-induced, blood-oxygen-level-dependent (BOLD) activation responses in the amygdala and related brain regions. Such attenuation may be associated with a positive clinical response in depression. Bupropion XL also improved activation in the executive-function neural network. These fMRI surrogate markers offer promise for studying anti-depressant and neurocognitive effects of existing and novel therapies.",
author = "Brigitte Robertson and Lihong Wang and Diaz, {Michele Theresa} and Marilyn Aiello and Kenneth Gersing and John Beyer and Srinivasan Mukundan and Gregory McCarthy and Doraiswamy, {P. Murali}",
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Effect of bupropion extended release on negative emotion processing in major depressive disorder : A pilot functional magnetic resonance imaging study. / Robertson, Brigitte; Wang, Lihong; Diaz, Michele Theresa; Aiello, Marilyn; Gersing, Kenneth; Beyer, John; Mukundan, Srinivasan; McCarthy, Gregory; Doraiswamy, P. Murali.

In: Journal of Clinical Psychiatry, Vol. 68, No. 2, 01.01.2007, p. 261-267.

Research output: Contribution to journalArticle

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T1 - Effect of bupropion extended release on negative emotion processing in major depressive disorder

T2 - A pilot functional magnetic resonance imaging study

AU - Robertson, Brigitte

AU - Wang, Lihong

AU - Diaz, Michele Theresa

AU - Aiello, Marilyn

AU - Gersing, Kenneth

AU - Beyer, John

AU - Mukundan, Srinivasan

AU - McCarthy, Gregory

AU - Doraiswamy, P. Murali

PY - 2007/1/1

Y1 - 2007/1/1

N2 - Background: Prior imaging studies suggest that patients with major depressive disorder have abnormalities in frontal and limbic neural circuitry including the amygdala, which is relatively more activated at rest and in response to negative emotional stimuli (sadness, fear, etc.) in depressed patients than in controls. Concurrently, patients with depression may have decreased activation of attentional executive regions in response to attentional stimuli. This study examined the effect of bupropion XL, an extended release formulation of the nonserotonergic antidepressant agent bupropion, using a paradigm that investigated both negative emotional response and attentional processing. Method: Functional magnetic resonance imaging (fMRI) scans and clinical ratings were obtained for 10 patients with DSM-IV-TR-defined major depressive disorder (mean [SD] age = 41 [± 7] years, mean [SD] Hamilton Rating Scale for Depression [HAM-D] score = 21 [± 4]) before and after 8 weeks of treatment with bupropion XL. The fMRI sessions were conducted during administration of the Emotional Oddball Task; scans were obtained while subjects viewed emotional distracters and performed an attentional executive function task. The primary outcome was fMRI activations evoked by the emotional distracters. The first baseline fMRI scan was performed in December 2004, and the last posttreatment scan was in March 2005. Results: Treatment with bupropion XL was associated with improvements in HAM-D and Clinical Global Impressions scale ratings (p < .05). Treatment reduced fMRI activation during emotional distracters in several regions including right orbital frontal cortex, left dorsomedial prefrontal cortex, right ventromedial prefrontal cortex, right anterior cingulate cortex, right inferior frontal cortex, right amygdala/parahippocampal area, right caudate, right fusiform gyrus, and left posterior cingulate. In addition, changes in fMRI activation in the amygdala correlated with improvements on the HAM-D (p < .05). Treatment increased activation to attentional targets in the following regions: right middle and inferior frontal gyri, right caudate, and bilateral precuneus. Conclusion: Despite the limitations of a small sample size and the lack of a placebo control group, this study demonstrated that bupropion XL therapy for 8 weeks may attenuate emotion-induced, blood-oxygen-level-dependent (BOLD) activation responses in the amygdala and related brain regions. Such attenuation may be associated with a positive clinical response in depression. Bupropion XL also improved activation in the executive-function neural network. These fMRI surrogate markers offer promise for studying anti-depressant and neurocognitive effects of existing and novel therapies.

AB - Background: Prior imaging studies suggest that patients with major depressive disorder have abnormalities in frontal and limbic neural circuitry including the amygdala, which is relatively more activated at rest and in response to negative emotional stimuli (sadness, fear, etc.) in depressed patients than in controls. Concurrently, patients with depression may have decreased activation of attentional executive regions in response to attentional stimuli. This study examined the effect of bupropion XL, an extended release formulation of the nonserotonergic antidepressant agent bupropion, using a paradigm that investigated both negative emotional response and attentional processing. Method: Functional magnetic resonance imaging (fMRI) scans and clinical ratings were obtained for 10 patients with DSM-IV-TR-defined major depressive disorder (mean [SD] age = 41 [± 7] years, mean [SD] Hamilton Rating Scale for Depression [HAM-D] score = 21 [± 4]) before and after 8 weeks of treatment with bupropion XL. The fMRI sessions were conducted during administration of the Emotional Oddball Task; scans were obtained while subjects viewed emotional distracters and performed an attentional executive function task. The primary outcome was fMRI activations evoked by the emotional distracters. The first baseline fMRI scan was performed in December 2004, and the last posttreatment scan was in March 2005. Results: Treatment with bupropion XL was associated with improvements in HAM-D and Clinical Global Impressions scale ratings (p < .05). Treatment reduced fMRI activation during emotional distracters in several regions including right orbital frontal cortex, left dorsomedial prefrontal cortex, right ventromedial prefrontal cortex, right anterior cingulate cortex, right inferior frontal cortex, right amygdala/parahippocampal area, right caudate, right fusiform gyrus, and left posterior cingulate. In addition, changes in fMRI activation in the amygdala correlated with improvements on the HAM-D (p < .05). Treatment increased activation to attentional targets in the following regions: right middle and inferior frontal gyri, right caudate, and bilateral precuneus. Conclusion: Despite the limitations of a small sample size and the lack of a placebo control group, this study demonstrated that bupropion XL therapy for 8 weeks may attenuate emotion-induced, blood-oxygen-level-dependent (BOLD) activation responses in the amygdala and related brain regions. Such attenuation may be associated with a positive clinical response in depression. Bupropion XL also improved activation in the executive-function neural network. These fMRI surrogate markers offer promise for studying anti-depressant and neurocognitive effects of existing and novel therapies.

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