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Amygdala response to explicit sad face stimuli at baseline predicts antidepressant treatment response to scopolamine in major depressive disorder.

ABSTRACT: The muscarinic antagonist scopolamine produces rapid antidepressant effects in individuals with major depressive disorder (MDD). In healthy subjects, manipulation of acetyl-cholinergic transmission modulates attention in a stimulus-dependent manner. This study tested the hypothesis that baseline amygdalar activity in response to emotional stimuli correlates with antidepressant treatment response to scopolamine and could thus potentially predict treatment outcome. MDD patients and healthy controls performed an attention shifting task involving emotional faces while undergoing functional magnetic resonance imaging (fMRI). We found that blood oxygenation level dependent (BOLD) signal in the amygdala acquired while MDD patients processed sad face stimuli correlated positively with antidepressant response to scopolamine. Amygdalar response to sad faces in MDD patients who did not respond to scopolamine did not differ from that of healthy controls. This suggests that the pre-treatment task elicited amygdalar activity that may constitute a biomarker of antidepressant treatment response to scopolamine. Furthermore, in MDD patients who responded to scopolamine, we observed a post-scopolamine stimulus processing shift towards a pattern demonstrated by healthy controls, indicating a change in stimulus-dependent neural response potentially driven by attenuated cholinergic activity in the amygdala.

SUBMITTER: Szczepanik J

PROVIDER: S-EPMC6711385 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Amygdala response to explicit sad face stimuli at baseline predicts antidepressant treatment response to scopolamine in major depressive disorder.

Szczepanik Joanna J Nugent Allison C AC Drevets Wayne C WC Khanna Ashish A Zarate Carlos A CA Furey Maura L ML

Psychiatry research. Neuroimaging 20160620

The muscarinic antagonist scopolamine produces rapid antidepressant effects in individuals with major depressive disorder (MDD). In healthy subjects, manipulation of acetyl-cholinergic transmission modulates attention in a stimulus-dependent manner. This study tested the hypothesis that baseline amygdalar activity in response to emotional stimuli correlates with antidepressant treatment response to scopolamine and could thus potentially predict treatment outcome. MDD patients and healthy control ...[more]

PMID: 27366831

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Project description:BackgroundThis randomized, placebo-controlled, crossover trial examined the antidepressant efficacy of the muscarinic antagonist scopolamine in major depressive disorder subjects with more severe and refractory forms of major depressive disorder relative to previous reports.MethodsParticipants included 23 medication-free major depressive disorder subjects (12 F/11 M, 20-55 years) currently experiencing a major depressive episode. Subjects had scored ?20 on the Montgomery-Asberg Depression Rating Scale. Following a single-blind, placebo lead-in, participants were randomized to receive 2 counterbalanced blocks of 3 i.v. infusions of scopolamine (4 ?g/kg) and placebo in a double-blind manner. The primary and secondary outcomes were the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale, respectively. Magnetoencephalography and plasma brain-derived neurotrophic factor concentrations were obtained prior to and after each treatment phase.ResultsAs assessed by both the Montgomery-Asberg Depression Rating Scale and Hamilton Anxiety Rating Scale, scopolamine had no significant antidepressant or anxiolytic effects relative to placebo. No significant drug vs placebo effects were seen in magnetoencephalography gamma power or brain-derived neurotrophic factor plasma concentrations, and brain-derived neurotrophic factor changes did not correlate with change in Montgomery-Asberg Depression Rating Scale score in response to scopolamine.ConclusionsThese results do not support the efficacy of scopolamine for more severe or refractory forms of depression. No pre- to post-infusion changes in plasma brain-derived neurotrophic factor were detected, and magnetoencephalography gamma power changed only in the placebo lead-in, suggesting that these biomarker measures were not affected by scopolamine in this cohort. While difficult to interpret given the lack of antidepressant response, the findings suggest that the neurobiological effects of ketamine and scopolamine are at least partly distinct.

Project description:IntroductionConsiderable research has established a link between socioeconomic status (SES) and brain function. While studies have shown a link between poverty status and amygdala response to negative stimuli, a paucity of knowledge exists on whether neighborhood poverty is also independently associated with amygdala hyperactive response to negative stimuli.PurposeUsing functional brain imaging data, this study tested the association between neighborhood SES and the amygdala's response to negative stimuli. Considering race as a sociological rather than a biological construct, we also explored racial heterogeneity in this association between non-Hispanic Black and non-Hispanic White youth.MethodsWe borrowed the functional Magnetic Resonance Imaging (fMRI) data of the Adolescent Brain Cognitive Development (ABCD) study. The sample was 2,490 nine to ten year old non-Hispanic Black and non-Hispanic White adolescents. The independent variable was neighborhood income which was treated as a continuous measure. The primary outcomes were the right and left amygdala response to negative face during an N-Back task. Age, sex, race, marital status, and family SES were the covariates. To analyze the data, we used linear regression models.ResultsLow neighborhood income was independently associated with a higher level of amygdala response to negative face. Similar results were seen for the right and left amygdala. These effects were significant net of race, age, sex, marital status, and family SES. An association between low neighborhood SES and higher left but not right amygdala response to negative face could be observed for non-Hispanic Black youth. No association between neighborhood SES and left or right amygdala response to negative face could be observed for non-Hispanic White youth.ConclusionsFor American youth, particularly non-Hispanic Black youth, living in a poor neighborhood predicts the left amygdala reaction to negative face. This result suggested that Black youth who live in poor neighborhoods are at a high risk of poor emotion regulation. This finding has implications for policy making to reduce inequalities in undesired behavioral and emotional outcomes. Policy solutions to health inequalities should address inequalities in neighborhood SES.

Project description:Over the past two decades, evidence has accumulated that the human amygdala exerts some of its functions also when the observer is not aware of the content, or even presence, of the triggering emotional stimulus. Nevertheless, there is as of yet no consensus on the limits and conditions that affect the extent of amygdala's response without focused attention or awareness. Here we review past and recent studies on this subject, examining neuroimaging literature on healthy participants as well as brain-damaged patients, and we comment on their strengths and limits. We propose a theoretical distinction between processes involved in attentional unawareness, wherein the stimulus is potentially accessible to enter visual awareness but fails to do so because attention is diverted, and in sensory unawareness, wherein the stimulus fails to enter awareness because its normal processing in the visual cortex is suppressed. We argue this distinction, along with data sampling amygdala responses with high temporal resolution, helps to appreciate the multiplicity of functional and anatomical mechanisms centered on the amygdala and supporting its role in non-conscious emotion processing. Separate, but interacting, networks relay visual information to the amygdala exploiting different computational properties of subcortical and cortical routes, thereby supporting amygdala functions at different stages of emotion processing. This view reconciles some apparent contradictions in the literature, as well as seemingly contrasting proposals, such as the dual stage and the dual route model. We conclude that evidence in favor of the amygdala response without awareness is solid, albeit this response originates from different functional mechanisms and is driven by more complex neural networks than commonly assumed. Acknowledging the complexity of such mechanisms can foster new insights on the varieties of amygdala functions without awareness and their impact on human behavior.

Dataset Information

Amygdala response to explicit sad face stimuli at baseline predicts antidepressant treatment response to scopolamine in major depressive disorder.

Publications

Amygdala response to explicit sad face stimuli at baseline predicts antidepressant treatment response to scopolamine in major depressive disorder.

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