Modulation of amygdala reactivity following rapidly acting interventions for major depression - PubMed (original) (raw)

. 2020 May;41(7):1699-1710.

doi: 10.1002/hbm.24895. Epub 2020 Mar 1.

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Modulation of amygdala reactivity following rapidly acting interventions for major depression

Joana R A Loureiro et al. Hum Brain Mapp. 2020 May.

Abstract

Electroconvulsive therapy (ECT) and ketamine treatment both induce rapidly acting antidepressant effects in patients with major depressive disorder unresponsive to standard treatments, yet their specific impact on emotion processing is unknown. Here, we examined the neural underpinnings of emotion processing within and across patients (N = 44) receiving either ECT (N = 17, mean age: 36.8, 11.0 SD) or repeated subanesthetic (0.5 mg/kg) intravenous ketamine therapy (N = 27, mean age: 37.3, 10.8 SD) using a naturalistic study design. MRI and clinical data were collected before (TP1) and after treatment (TP2); healthy controls (N = 31, mean age: 34.5, 13.5 SD) completed one MRI session (TP1). An fMRI face-matching task probed negative- and positive-valence systems. Whole-brain analysis, comparing neurofunctional changes within and across treatment groups, targeted brain regions involved in emotional facial processing, and included regions-of-interest analysis of amygdala responsivity. Main findings revealed a decrease in amygdalar reactivity after both ECT and ketamine for positive and negative emotional face processing (p < .05 family wise-error (FWE) corrected). Subthreshold changes were observed between treatments within the dorsolateral prefrontal cortex and insula (p < .005, uncorrected). BOLD change for positive faces in the inferior parietal cortex significantly correlated with overall symptom improvement, and BOLD change in frontal regions correlated with anxiety for negative faces, and anhedonia for positive faces (p < .05 FWE corrected). Both serial ketamine and ECT treatment modulate amygdala response, while more subtle treatment-specific changes occur in the larger functional network. Findings point to both common and differential mechanistic upstream systems-level effects relating to fast-acting antidepressant response, and symptoms of anxiety and anhedonia, for the processing of emotionally valenced stimuli.

Keywords: ECT; MDD; amygdala; emotion processing; ketamine; tfMRI.

© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.

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Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

Figure 1

Figure 1

Study design showing the MRI sessions and clinical scales acquired at each time point

Figure 2

Figure 2

FMRI task, mean activation, and processing pipeline. (a) face‐matching task example sequence showing the four stimulus conditions; (b) Mean activation map obtained from the one sample _t_‐test of both MDD patients and HC at baseline; (c) Flow diagram of preprocessing and first and second level postprocessing steps. HC, healthy control; MDD, major depressive disorder

Figure 3

Figure 3

Effects of treatment across modality (ECT + Ketamine) for the happy > objects contrast (a and c) and fearful > objects contrast (b and d). (a) Significant clusters for the happy > objects contrast (top) and %BOLD signal derived from the corresponding amygdala ROI at TP1 (baseline) and TP2 (post‐treatment) averaged across (bottom right) and within treatment groups (bottom left); (b) Significant clusters for the for fearful > objects contrast (top) and %BOLD signal derived from the corresponding amygdala ROI at TP1 and TP2 averaged across (bottom right) and within treatment groups (bottom left). (c) %BOLD signal within the amygdala ROI (cluster derived from happy > objects contrast as in panel a) plotted for happy face stimuli (top) and objects (bottom) separately, again shown across (right) and within treatment groups (left); (d) %BOLD signal within the amygdala ROI (cluster derived from fearful > objects contrast as in panel a) plotted for fearful faces stimuli (top) and objects (bottom) separately, again shown across (right) and within treatment groups (left). %BOLD for neutral stimuli were not shown to change over time and are not plotted. ECT, electroconvulsive therapy; FWE, family wise error correction; HC, health controls; MDD, major depressive disorder patients

Figure 4

Figure 4

Associations between %BOLD signal change (TP1–TP2) and %change in clinical measures (p < .05 FWE cluster corrected). Significant clusters are shown in the top panel and corresponding linear regressions are shown below. (a) Superior parietal cluster BOLD change showed significant positive correlation with %HDRS change; (b) Insula, DLPFC, and posterior central BOLD change showed significant negative correlation with %DASS change; (c) DLPFC cluster BOLD change showed significant positive correlation with %SHAPS change. DASS, depression anxiety stress scale; DLPFC, dorsolateral prefrontal cortex; HDRS, Hamilton depression rating scale; SHAPS, Snaith–Hamilton pleasure scale

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