Effects of an antidepressant on neural correlates of emotional processing in patients with major depression

Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, PR China.
Neuroscience Letters (Impact Factor: 2.03). 08/2012; 527(1):55-9. DOI: 10.1016/j.neulet.2012.08.034
Source: PubMed


We measured brain activation in patients with major depressive disorder when exposed to emotional pictures before and after antidepressant treatment. The participants included 18 first-episode unmedicated patients with current major depressive disorder and 18 age- and gender-matched control subjects. All subjects performed an emotional task during functional magnetic resonance imaging scanning at baseline and after 8 weeks of fluoxetine treatment. Unmedicated depressed patients showed lower accuracy rates (0.53±0.26) than did subjects in the control group (0.71±0.18) while viewing positive pictures. During exposure to positive stimuli, decreased activations were seen in the right insula (BA13) and left anterior cingulate cortex (BA32) in patients after antidepressant treatment. After antidepressant treatment, patients exhibited greater activation in the right middle frontal gyrus (BA8,9) in response to negative stimuli. Our results suggest that the prefrontal cortex, anterior cingulate cortex and insula may play key roles as biological markers for treatment response and as predictors of therapeutic success.

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    ABSTRACT: Major Depressive Disorder (MDD) is a leading cause of disability globally. Currently available treatments have limited efficacy and combination strategies are frequently used. Several lines of research have demonstrated that MDD patients experience impairments in various components of affective processing, including regulation of affective states. To identify baseline and 1-week neuroimaging predictors of response to a 6-week trial of fluoxetine/olanzapine combination treatment during an affective processing task. Twenty-one MDD patients and 18 healthy controls were enrolled in the study. MDD patients were treated for 6 weeks with fluoxetine (40-60mg/day) and olanzapine (5-12.5mg/day). All participants viewed images from the International Affective Picture Rating System during a functional magnetic resonance (fMRI) scan at baseline and 1 week. There was a 57% response rate (defined as a 50% decrease in Hamilton Rating Scale for Depression-17 item) at 6 weeks. At baseline, responders had increased premotor activity while viewing negative images compared to non-responders and healthy controls. Higher baseline premotor activity was also predictive of greater percent change on the HAMD-17 and improvement in negative disposition and behavioral drive. Non-responders exhibited increased insular activity at baseline compared to responders. Higher activity in the posterior cingulate cortex was also predictive of greater percent change on the HAMD-17. Change from baseline to 1 week did not produce any significant predictive findings. Treatment with fluoxetine/olanzapine demonstrated similar biomarkers of response to monotherapeutic strategies. In particular, posterior cingulate cortex, anterior insula, and premotor cortex may show predictive differences in their response to affective images prior to treatment. Further research needs to be conducted to determine the utility of early changes in emotion circuitry in predicting antidepressant response.
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    ABSTRACT: In the last two decades, neuroimaging research has reached a much deeper understanding of the neurobiological underpinnings of major depression (MD) and has converged on functional alterations in limbic and prefrontal neural networks, which are mainly linked to altered emotional processing observed in MD patients. To date, a considerable number of studies have sought to investigate how these neural networks change with pharmacological antidepressant treatment. In the current review, we therefore discuss results from a) pharmacological functional magnetic resonance imaging (fMRI) studies investigating the effects of selective serotonin or noradrenalin reuptake inhibitors on neural activation patterns in relation to emotional processing in healthy individuals, b) treatment studies in patients with unipolar depression assessing changes in neural activation patterns before and after antidepressant pharmacotherapy, and c) predictive neural biomarkers of clinical response in depression. Comparing results from pharmacological fMRI studies in healthy individuals and treatment studies in depressed patients nicely showed parallel findings, mainly for a reduction of limbic activation in response to negative stimuli. A thorough investigation of the empirical findings highlights the importance of the specific paradigm employed in every study which may account for some of the discrepant findings reported in treatment studies in depressed patients.
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