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Increased neural sensitivity to self-relevant stimuli in major depressive disorder.

ABSTRACT: The current research examined how individuals with depression process emotional, self-relevant stimuli. Across two studies, individuals with depression and healthy controls read stimuli that varied in self-relevance while EEG data were recorded. We examined the late positive potential (LPP), an ERP component that captures the dynamic allocation of attention to motivationally salient stimuli. In Study 1, participants read single words in a passive-viewing task. Participants viewed negative, positive, or neutral words that were either normative or self-generated. Exploratory analyses indicated that participants with depression exhibited affective modulation of the LPP for self-generated stimuli only (both positive and negative) and not for normative stimuli; healthy controls exhibited similar affective modulation of the LPP for both self-relevant and normative stimuli. In Study 2, using a separate sample and a different task, stimuli were provided within the context of sentence stems referring to the self or other people. Participants with depression were more likely to endorse negative self-referent sentences and reject positive ones compared to healthy controls. Depressed participants also exhibited an increased LPP to negative stimuli compared to positive or neutral stimuli. Together, these two studies suggest that depression is characterized by relatively increased sensitivity to affective self-relevant stimuli, perhaps in the context of a broader reduction in emotional reactivity to stimuli that are not self-relevant. Thus, depression may be characterized by a more nuanced pattern based on the degree of stimulus self-relevance than either a global decrease or increase in reactivity to affective stimuli.

SUBMITTER: Benau EM

PROVIDER: S-EPMC7066870 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Increased neural sensitivity to self-relevant stimuli in major depressive disorder.

Benau Erik M EM Hill Kaylin E KE Atchley Ruth Ann RA O'Hare Aminda J AJ Gibson Linzi J LJ Hajcak Greg G Ilardi Stephen S SS Foti Dan D

Psychophysiology 20190222 7

The current research examined how individuals with depression process emotional, self-relevant stimuli. Across two studies, individuals with depression and healthy controls read stimuli that varied in self-relevance while EEG data were recorded. We examined the late positive potential (LPP), an ERP component that captures the dynamic allocation of attention to motivationally salient stimuli. In Study 1, participants read single words in a passive-viewing task. Participants viewed negative, posit ...[more]

PMID: 30793773

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Project description:BackgroundSocial anxiety disorder (SAD) and major depressive disorder (MDD) are highly comorbid and share impairments in self-referential and social processing. Many naturalistic judgements activate these processes concurrently, which can be referred to as "self-other referential processing". We sought to examine its neural correlates in young people with SAD and MDD using a novel experimental task.MethodsFifty six young people aged 16 to 25 with diagnoses of SAD and/or MDD (15 with SAD [M = 20.3 years, 60% female], 17 with MDD [M = 19.8 years, 53% female], 24 with comorbid SAD and MDD [M = 19.8 years, 67% female]) and 76 age and gender-matched healthy controls (HCs; M = 20.7 years, 66% female) completed a novel self-other referential processing fMRI task that involved rating how much one related to emotional faces in active conditions and judging how far apart each person's eyes were in control conditions.ResultsParticipants with SAD had more and those with MDD had less activity in social cognitive areas than HCs when processing social information across all conditions and emotion types. Participants with comorbid SAD-MDD exhibited a distinct pattern of neural activity to patients with single diagnoses. Across the whole sample, the activation of reward system areas (the medial orbitofrontal cortex and caudate) in response to increasing relatedness correlated positively with a dimensional measure of social anxiety.ConclusionsYoung people with SAD, MDD and comorbid SAD-MDD showed deficits in social processing, but they were not specifically related to self-other referential processing. Dimensional social anxiety symptoms were correlated with reward system activation, suggesting that such symptoms are associated with an overestimation of the hedonic value of social stimuli. These novel findings have implications for our understanding of the neural correlates of SAD and MDD, suggesting that alterations in social processing and reward functioning underlie the impairments in self and social processing that characterize both disorders.

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: Major depressive disorder (MDD) is an affective disorder that is harmful to both physical and mental health. Abnormal self-knowledge, which refers to abnormal judgments about oneself, is a core symptom of depression. However, little research has summarized how and why patients with MDD differ from healthy individuals in terms of self-knowledge. Objective: To gain a better understanding of MDD, we reviewed previous studies that focused on the behavioral and neurological changes of self-knowledge in this illness. Main Findings: On the behavioral level, depressed individuals exhibited negative self-knowledge in an explicit way, while more heterogeneous patterns were reported in implicit results. On the neurological level, depressed individuals, as compared with non-depressed controls, showed abnormal self-referential processing in both early perception and higher cognitive processing phases during the Self-Referential Encoding Task. Furthermore, fMRI studies have reported aberrant activity in the medial prefrontal cortex area for negative self-related items in depression. These results revealed several behavioral features and brain mechanisms underlying abnormal self-knowledge in depression. Future Studies: The neural mechanism of implicit self-knowledge in MDD remains unclear. Future research should examine the importance of others' attitudes on the self-concept of individuals with MDD, and whether abnormal self-views may be modified through cognitive or pharmacological approaches. In addition, differences in abnormal self-knowledge due to genetic variation between depressed and non-depressed populations remain unconfirmed. Importantly, it remains unknown whether abnormal self-knowledge could be used as a specific marker to distinguish healthy individuals from those with MDD. Conclusion: This review extends our understanding of the relationship between self-knowledge and depression by indicating several abnormalities among individuals with MDD and those who are at risk for this illness.

Dataset Information

Increased neural sensitivity to self-relevant stimuli in major depressive disorder.

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Increased neural sensitivity to self-relevant stimuli in major depressive disorder.

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