Toward Clinically Useful Neuroimaging in Depression Treatment Prognostic Utility of Subgenual Cingulate Activity for Determining Depression Outcome in Cognitive Therapy Across Studies, Scanners, and Patient Characteristics
Archives of general psychiatry (Impact Factor: 14.48). 09/2012; 69(9):913-24. DOI: 10.1001/archgenpsychiatry.2012.65
CONTEXT Among depressed individuals not receiving medication in controlled trials, 40% to 60% respond to cognitive therapy (CT). Multiple previous studies suggest that activity in the subgenual anterior cingulate cortex (sgACC; Brodmann area 25) predicts outcome in CT for depression, but these results have not been prospectively replicated. OBJECTIVE To examine whether sgACC activity is a reliable and robust prognostic outcome marker of CT for depression and whether sgACC activity changes in treatment. DESIGN Two inception cohorts underwent assessment with functional magnetic resonance imaging using different scanners on a task sensitive to sustained emotional information processing before and after 16 to 20 sessions of CT, along with a sample of control participants who underwent testing at comparable intervals. SETTING A hospital outpatient clinic. PATIENTS Forty-nine unmedicated depressed adults and 35 healthy controls. MAIN OUTCOME MEASURES Pretreatment sgACC activity in an a priori region in response to negative words was correlated with residual severity and used to classify response and remission. RESULTS As expected, in both samples, participants with the lowest pretreatment sustained sgACC reactivity in response to negative words displayed the most improvement after CT (R2 = 0.29, >75% correct classification of response, >70% correct classification of remission). Other a priori regions explained additional variance. Response/remission in cohort 2 was predicted based on thresholds from cohort 1. Subgenual anterior cingulate activity remained low for patients in remission after treatment. CONCLUSIONS Neuroimaging provides a quick, valid, and clinically applicable way of assessing neural systems associated with treatment response/remission. Subgenual anterior cingulate activity, in particular, may reflect processes that interfere with treatment (eg, emotion generation) in addition to its putative regulatory role; alternately, its absence may facilitate treatment response.
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- "Given the strong relationships between dmPFC and self-referential processing (Lemogne et al., 2012), we may hypothesize that cognitive behavior therapy (CBT), by addressing cognitive biases such as excessive self-focus, would target the dorsal part of the medial prefrontal cortex more specifically than antidepressant drugs. Indeed , while CBT influences both the ventral and dorsal medial frontal regions (Siegle et al., 2012; Yoshimura et al., 2013), a specific modulation by CBT on the dmPFC was described when compared with paroxetine (Goldapple et al., 2004) in the treatment of depression. Further studies comparing drugs and CBT (McGrath et al., 2013) are needed to test if reducing activity in the dmPFC during self-referential processing is a mechanism underlying clinical changes specific to CBT. "
ABSTRACT: Acute depression is associated with impaired self-referential processing. Antidepressant effects on the neural bases of self-referential processing in depression are unknown. This study aimed to assess short- and long-term effects of agomelatine on these neural bases in depressed patients and the association between pre-treatment brain activation and remission of depression 6 months later. We conducted a randomized double-blind, placebo-controlled, functional magnetic resonance imaging (fMRI) study during an emotional self-referential task, including three scanning sessions (baseline, after 1 week, and after 7 weeks). Twenty-five depressed outpatients were included, all treated with agomelatine or placebo for 1 week. Then, all patients received agomelatine for 24 weeks. Fourteen matched healthy volunteers (HV) who received placebo for 1 week were also included. After 7 days, only depressed patients receiving agomelatine significantly deactivated the ventrolateral prefrontal cortex during self-referential processing, as observed in HV at baseline. After 7 weeks, depressed patients significantly increased the activation of the ventral anterior cingulate cortex. Finally dorsomedial prefrontal cortex and precuneus activations at baseline significantly separated remitters from non-remitters at 24 weeks. In depressed patients, agomelatine had short- and long-term effects on brain structures involved in anhedonia and emotional regulation during self-referential processing. Activation of the dorsomedial prefrontal cortex and precuneus could be informative in the development of biomarker-based treatment of major depression.
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- "The most consistently reported cognitive feature of mood disorders is a negative emotion-processing bias where patients demonstrate a bias towards processing negative emotional stimuli over positive stimuli (Bradley et al., 1995, 1996; Mogg et al., 1995; Murphy et al., 1999; Erickson et al., 2005; Harmer, 2008; Koster et al., 2010). This bias is evident in behavioral studies (Bradley et al., 1995, 1996; Murphy et al., 1999; Erickson et al., 2005) as well as functional neuroimaging studies (Sheline et al., 2001; Fu et al., 2004; Gotlib et al., 2004; Victor et al., 2010, 2012), where patients demonstrate differential neural responses to sad and happy faces under implicit (Sheline et al., 2001; Victor et al., 2010) and explicit (Surguladze et al., 2005; Keedwell et al., 2010; Siegle et al., 2012) emotion-processing conditions. While these studies often focus on amygdala (Sheline et al., 2001; Victor et al., 2010), differential emotional processing in mood disorders also has been reported in prefrontal cortical regions (Davidson et al., 2003; Fu et al., 2004; Victor et al., 2012), including sgACC (Keedwell et al., 2009, 2010; Laxton et al., 2013), and visual processing areas (Surguladze et al., 2005; Keedwell et al., 2009, 2010). "
ABSTRACT: Faster acting antidepressants and biomarkers that predict treatment response are needed to facilitate the development of more effective treatments for patients with major depressive disorders (MDD). Here we evaluate implicitly and explicitly processed emotional faces using neuroimaging to identify potential biomarkers of treatment response to the antimuscarinic, scopolamine. Healthy participants (n=15) and unmedicated-depressed MDD patients (n=16) participated in a double-blind, placebo-controlled crossover infusion study using scopolamine (4ug/kg). Before and following scopolamine, blood oxygen-level dependent (BOLD) signal was measured using fMRI during a selective attention task. Two stimuli comprised of superimposed pictures of faces and houses were presented. Participants attended to one stimulus component and performed a matching task. Face emotion was modulated (happy/sad) creating implicit (attend-houses) and explicit (attend-faces) emotion processing conditions. The pre-treatment difference in BOLD response to happy and sad faces under implicit and explicit conditions (emotion processing biases) within a-priori regions-of-interest (ROIs), was correlated with subsequent treatment response in MDD. Correlations were observed exclusively during implicit emotion processing in the ROIs, which included the subgenual anterior cingulate (sgACC) (p<0.02) and middle occipital cortices (MOC) (p<0.02). The magnitude and direction of differential BOLD response to implicitly processed emotional faces prior to treatment reflect the potential to respond to scopolamine. These findings replicate earlier results, highlighting the potential for pre-treatment neural activity in the MOC and sgACC to inform us about the potential to respond clinically to scopolamine. Published by Oxford University Press on behalf of CINP 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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- "Because of the severe health-related consequences as well as societal costs of persistent AN (Golden et al., 2003; Arcelus et al., 2011; Crow and Nyman, 2004; Streigel-Moore et al., 2000) it is important to identify clinical markers or biomarkers to guide treatment selection. Recent studies suggest possible neuroimaging biomarkers for selecting treatment for other psychiatric disorders, including major depressive disorder, wherein subgenual cingulate activation predicts response to CBT (Siegle et al., 2012), visual cortex activation predicts response to scopolamine (Furey et al., 2013) and insula metabolism differentially predicts response to CBT versus escitalopram (McGrath et al., 2013). For patients suffering from panic disorder with agoraphobia, a negative functional connectivity between the anterior cingulate and amygdala at pretreatment predicts favorable response to CBT (Lueken et al., 2013). "
ABSTRACT: Background Patients with Anorexia Nervosa (AN) have neuropsychological deficits in Set-Shifting (SS) and central coherence (CC) consistent with an inflexible thinking style and overly detailed processing style, respectively. This study investigates brain activation during SS and CC tasks in patients with AN and tests whether this activation is a biomarker that predicts response to treatment.. Methods FMRI data were collected from 21 females with AN while performing an SS task (the Wisconsin Card Sort) and a CC task (embedded figures), and used to predict outcome following 16 weeks of treatment (either 16 weeks of cognitive behavioral therapy or 8 weeks cognitive remediation therapy followed by 8 weeks of cognitive behavioral therapy). Results Significant activation during the SS task included bilateral dorsolateral and ventrolateral prefrontal cortex and left anterior middle frontal gyrus. Higher scores on the neuropsychological test of SS (measured outside the scanner at baseline) were correlated with greater DLPFC and VLPFC/insula activation. Improvements in SS following treatment were significantly predicted by a combination of low VLPFC/insula and high anterior middle frontal activation (R squared = .68, p = .001). For the CC task, visual and parietal cortical areas were activated, but were not significantly correlated with neuropsychological measures of CC and did not predict outcome. Conclusion Cognitive flexibility requires the support of several prefrontal cortex resources. As previous studies suggest that the VLPFC is important for selecting context-appropriate responses, patients who have difficulties with this skill may benefit the most from cognitive therapy with or without cognitive remediation therapy. The ability to sustain inhibition of an unwanted response, subserved by the anterior middle frontal gyrus, is a cognitive feature that predicts favorable outcome to cognitive treatment. CC deficits may not be an effective predictor of clinical outcome.
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