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Neural markers of symptomatic improvement during antidepressant therapy in severe depression: Subgenual cingulate and visual cortical responses to sad, but not happy, facial stimuli are correlated with changes in symptom score

Cardiff University, Psychological Medicine, Cardiff, UK.
Journal of Psychopharmacology (Impact Factor: 2.81). 09/2009; 23(7):775-88. DOI: 10.1177/0269881108093589
Source: PubMed

ABSTRACT Resting state activity in the ventral cingulate may be an important neural marker of symptomatic improvement in depression. The number of task related functional magnetic resonance imaging (fMRI) studies correlating blood oxygenation level dependent (BOLD) response with symptomatic improvement is limited and methodologies are still evolving. We measured BOLD responses to sad and happy facial stimuli in 12 severely depressed individuals in the early stages of antidepressant treatment (Time 1) and 12 weeks later (Time 2) using event-related fMRI. We calculated correlations between temporal changes in BOLD response and changes in symptom scores. Most subjects improved markedly by Time 2. At Time 1, depression severity correlated positively with responses to sad stimuli in the right visual cortex, subgenual cingulate, anterior temporal pole and hippocampus and correlated negatively with responses to happy stimuli in left visual cortex and right caudate. Decreases in individual effect sizes of right subgenual cingulate and right visual cortical responses to sad, but not happy, facial stimuli were correlated with decreases in symptom scores. There are contrasting cortical and subcortical responses to sad and happy stimuli in severe depression. Responses to sad stimuli show the strongest correlates of clinical improvement, particularly in the subgenual cingulate.

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    • "Evaluating antidepressant effects on emotion processing neurocircuitry can provide important insights into illness states, as well as potential biomarkers of response, all of which can contribute to improving selection of current therapies and development of future targeted therapeutics. A replicated outcome when employing emotional provocation techniques evaluated with fMRI in depressed states is overactivity in the subgenual cingulate, amygdala, insula, and prefrontal cortex (Anand et al., 2005; Harmer et al., 2009; Keedwell et al., 2009; Kalin et al., 1997; Sheline et al., 2001). These abnormalities are noted to normalize following successful treatment with selective Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/jad "
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    • "During the course of treatment, brain activity can change or " normalize " in these regions (Sheline et al. 2001; Davidson et al. 2003; Fu et al. 2004; Little et al. 2005; Keedwell et al. 2009; Frodl et al. 2011; meta-analysis— Fitzgerald et al. 2008). Thus, applying clinically effective treatments can influence brain activity in previously " dysfunctional " regions, corresponding to the clinical improvement. "
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