Dataset Information

Relationship between amygdala responses to masked faces and mood state and treatment in major depressive disorder.

ABSTRACT: CONTEXT:Major depressive disorder (MDD) is associated with behavioral and neurophysiological evidence of mood-congruent processing biases toward explicitly presented, emotionally valenced stimuli. However, few studies have investigated such biases toward implicitly presented stimuli. OBJECTIVE:To investigate differential amygdala responses to sad, happy, and neutral faces presented below the level of explicit conscious awareness using a backward masking task in unmedicated participants with MDD and healthy controls (HCs). DESIGN:Initial cross-sectional design followed by a longitudinal treatment trial using functional magnetic resonance imaging. SETTING:Psychiatric outpatient clinic at the National Institute of Mental Health. PARTICIPANTS:We studied 22 unmedicated, currently depressed people with MDD (dMDD), 16 unmedicated individuals with MDD in full remission (rMDD), and 25 HCs. INTERVENTION:Ten dMDD participants underwent 8 weeks of antidepressant treatment with the selective serotonin reuptake inhibitor sertraline hydrochloride. MAIN OUTCOME MEASURES:Amygdala region-of-interest and whole-brain analyses evaluated the hemodynamic response during exposure to masked sad vs masked happy faces, to masked sad vs neutral faces, and to masked happy vs neutral faces. RESULTS:The dMDD participants showed greater amygdala responses than HCs to masked sad faces, whereas HCs showed greater amygdala responses to masked happy faces. The bias toward sad faces also was evident in rMDD participants relative to HCs and did not differ between dMDD and rMDD participants. This processing bias reversed toward the normative pattern in dMDD participants after sertraline treatment. CONCLUSIONS:Emotional-processing biases occur in amygdala responses to sad faces presented below the level of conscious awareness in dMDD or rMDD individuals and to happy faces in HCs. By influencing the salience of social stimuli, mood-congruent processing biases in the amygdala may contribute to dysfunction in conscious perceptions and social interactions in MDD. Our data suggest, however, that the negative bias resolves and a positive bias develops in patients with MDD during selective serotonin reuptake inhibitor treatment.

SUBMITTER: Victor TA

PROVIDER: S-EPMC3253452 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Relationship between amygdala responses to masked faces and mood state and treatment in major depressive disorder.

Victor Teresa A TA Furey Maura L ML Fromm Stephen J SJ Ohman Arne A Drevets Wayne C WC

Archives of general psychiatry 20101101 11

<h4>Context</h4>Major depressive disorder (MDD) is associated with behavioral and neurophysiological evidence of mood-congruent processing biases toward explicitly presented, emotionally valenced stimuli. However, few studies have investigated such biases toward implicitly presented stimuli.<h4>Objective</h4>To investigate differential amygdala responses to sad, happy, and neutral faces presented below the level of explicit conscious awareness using a backward masking task in unmedicated partici ...[more]

PMID: 21041614

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Project description:We have previously shown that in participants with major depressive disorder (MDD) trained to upregulate their amygdala hemodynamic response during positive autobiographical memory (AM) recall with real-time fMRI neurofeedback (rtfMRI-nf) training, depressive symptoms diminish. Here, we assessed the effect of rtfMRI-nf on amygdala functional connectivity during both positive AM recall and rest.The current manuscript consists of a secondary analysis on data from our published clinical trial of neurofeedback. Patients with MDD completed two rtfMRI-nf sessions (18 received amygdala rtfMRI-nf, 16 received control parietal rtfMRI-nf). One-week prior-to and following training participants also completed a resting-state fMRI scan. A GLM-based functional connectivity analysis was applied using a seed ROI in the left amygdala. We compared amygdala functional connectivity changes while recalling positive AMs from the baseline run to the final transfer run during rtfMRI-nf training, as well during rest from the baseline to the one-week follow-up visit. Finally, we assessed the correlation between change in depression scores and change in amygdala connectivity, as well as correlations between amygdala regulation success and connectivity changes.Following training, amygdala connectivity during positive AM recall increased with widespread regions in the frontal and limbic network. During rest, amygdala connectivity increased following training within the fronto-temporal-limbic network. During both task and resting-state analyses, amygdala-temporal pole connectivity decreased. We identified increased amygdala-precuneus and amygdala-inferior frontal gyrus connectivity during positive memory recall and increased amygdala-precuneus and amygdala-thalamus connectivity during rest as functional connectivity changes that explained significant variance in symptom improvement. Amygdala-precuneus connectivity changes also explain a significant amount of variance in neurofeedback regulation success.Neurofeedback training to increase amygdala hemodynamic activity during positive AM recall increased amygdala connectivity with regions involved in self-referential, salience, and reward processing. Results suggest future targets for neurofeedback interventions, particularly interventions involving the precuneus.

Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Project description:BACKGROUND:Although dysfunction of amygdala-related circuits is centrally implicated in major depressive disorder (MDD), little is known about how this dysfunction differs between adult and adolescent MDD patients. METHODS:Voxel-wise meta-analyses of abnormal amygdala resting-state functional connectivity (rsFC) were conducted in adult and adolescent groups separately, followed by a quantitative meta-analytic comparison of the two groups. FINDINGS:Nineteen studies that included 665 MDD patients (392 adults and 273 adolescents) and 546 controls (341 adults and 205 adolescents) were identified in the current study. Adult-specific abnormal amygdala rsFC in MDD patients compared to that in controls was located mainly within the affective network, including increased connectivity with the right hippocampus/parahippocampus and bilateral ventromedial orbitofrontal cortex and decreased connectivity with the bilateral insula and the left caudate. Adolescent MDD patients specifically demonstrated decreased amygdala rsFC within the cognitive control network encompassing the left dorsolateral prefrontal cortex and imbalanced amygdala rsFC within the default mode network, which was manifested as hyperconnectivity in the right precuneus and hypoconnectivity in the right inferior temporal gyrus. Additionally, direct comparison between the two groups showed that adult patients had strengthened amygdala rsFC with the right hippocampus/parahippocampus as well as the right inferior temporal gyrus and weakened amygdala rsFC with the bilateral insula compared to that in adolescent patients. INTERPRETATION:Distinct impairments of amygdala-centered rsFC in adult and adolescent patients were related to different network dysfunctions in MDD. Adult-specific amygdala rsFC dysfunction within the affective network presumably reflects emotional dysregulation in MDD, whereas adolescent-specific amygdala rsFC abnormalities in networks involved in cognitive control might reflect the neural basis of affective cognition deficiency that is characteristic of adolescent MDD. FUND: This study was supported by a grant from the National Natural Science Foundation of China (81671669) and by a Sichuan Provincial Youth Grant (2017JQ0001).

Project description:The endocannabinoid (eCB) system is implicated in the pathophysiology of depression and is responsive to acute exercise in healthy adults.PurposeWe aimed to describe acute changes in serum eCB across a prescribed moderate (MOD) and a self-selected/preferred (PREF) intensity exercise session in women with major depressive disorder (MDD) and determine relationships between changes in eCB and mood states.MethodsWomen with MDD (n = 17) exercised in separate sessions for 20 min on a cycle ergometer at both MOD or PREF in a within-subjects design. Blood was drawn before and within 10 min after exercise. Serum concentrations of eCB (anandamide [AEA], 2-arachidonoylglycerol) and related lipids (palmitoylethanolamine, oleoylethanolamine, 2-oleoylglycerol) were quantified using stable isotope-dilution, liquid chromatography/mass spectrometry/mass spectrometry. The profile of mood states and state-trait anxiety inventory (state only) were completed before, 10 min and 30 min postexercise.ResultsSignificant elevations in AEA (P = 0.013) and oleoylethanolamine (P = 0.024) occurred for MOD (moderate effect sizes: Cohen's d = 0.58 and 0.41, respectively). Significant (P < 0.05) moderate negative associations existed between changes in AEA and mood states for MOD at 10 min (depression, confusion, fatigue, total mood disturbance [TMD] and state anxiety) and 30 min postexercise (confusion, TMD and state anxiety). Significant (P < 0.05) moderate negative associations existed between 2-arachidonoylglycerol and mood states at 10 min (depression and confusion) and 30 min postexercise (confusion and TMD). Changes in eCB or related lipids or eCB-mood relationships were not found for PREF.ConclusionGiven the broad, moderate-strength relationships between improvements in mood states and eCB increases after MOD, it is plausible that the eCB system contributes to the mood-enhancing effects of prescribed acute exercise in MDD. Alternative mechanisms are likely involved in the positive mood state effects of preferred exercise.

Dataset Information

Relationship between amygdala responses to masked faces and mood state and treatment in major depressive disorder.

Publications

Relationship between amygdala responses to masked faces and mood state and treatment in major depressive disorder.

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