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Review of Abnormal Self-Knowledge in Major Depressive Disorder.

ABSTRACT: 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.

SUBMITTER: Lou Y

PROVIDER: S-EPMC6447699 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Review of Abnormal Self-Knowledge in Major Depressive Disorder.

Lou Yixue Y Lei Yi Y Mei Ying Y Leppänen Paavo H T PHT Li Hong H

Frontiers in psychiatry 20190328

<b>Background:</b> 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. <b>Objective:</b> To gain a better understanding of MDD, we reviewed previous studies that focused on the behavioral and neurological ...[more]

PMID: 30984035

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Project description:Major depressive disorder (MDD) is a complex mental disorder featured by an increased focus on the self and emotion dysregulation whose interaction remains unclear, though. At the same time, various studies observed abnormal representation of global fMRI brain activity in specifically those regions, e.g., cortical midline structure (CMS) in MDD that are associated with the self. Are the self and its impact on emotion regulation related to global brain activity unevenly represented in CMS relative to non-CMS? Addressing this yet open question is the main goal of our study. We here investigate post-acute treatment responder MDD and healthy controls in fMRI during an emotion task involving both attention and reappraisal of negative and neutral stimuli. We first demonstrate abnormal emotion regulation with increased negative emotion severity on the behavioral level. Next, focusing on a recently established three-layer topography of self, we show increased representation of global fMRI brain activity in specifically those regions mediating the mental (CMS) and exteroceptive (Right temporo-parietal junction and mPFC) self in post-acute MDD during the emotion task. Applying a complex statistical model, namely multinomial regression analyses, we show that increased global infra-slow neural activity in the regions of the mental and exteroceptive self modulates the behavioral measures of specifically negative emotion regulation (emotion attention and reappraisal/suppression). Together, we demonstrate increased representation of global brain activity in regions of the mental and exteroceptive self, including their modulation of negative emotion dysregulation in specifically the infra-slow frequency range (0.01 to 0.1 Hz) of post-acute MDD. These findings support the assumption that the global infra-slow neural basis of the increased self-focus in MDD may take on the role as basic disturbance in that it generates the abnormal regulation of negative emotions.

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 Non-suicidal self-injury (NSSI) commonly occurs among adolescents with major depressive disorder (MDD), causing adverse effects on the physical and mental health of the patients. However, the underlying neurobiological mechanism of NSSI in adolescents with MDD (nsMDDs) remains unclear, and there are still challenges in the treatment. Studies have suggested that sertraline administration could be an effective way for treatment. Methods To verify the effectiveness and to explore the neurobiological processes, we treated a group of adolescents with nsMDDs with sertraline in this study. The brain spontaneous activity alteration was then investigated in fifteen unmedicated first-episode adolescent nsMDDs versus twenty-two healthy controls through the resting-state functional magnetic resonance imaging. Besides the baseline scanning for all participants, the nsMDDs group was scanned again after eight weeks of sertraline therapy to examine the changes after treatment. Results At pre-treatment, whole brain analysis of mean amplitude of low-frequency fluctuation (mALFF) was performed to examine the neuronal spontaneous activity alteration, and increased mALFF was found in the superior occipital extending to lingual gyrus in adolescent nsMDDs compared with controls. Meanwhile, decreased mALFF was found in the medial superior frontal in adolescent nsMDDs compared with controls. Compared with the pre-treatment, the nsMDDs group was found to have a trend of, respectively, decreased and increased functional neuronal activity at the two brain areas after treatment through the region of interest analysis. Further, whole brain comparison of mALFF at pre-treatment and post-treatment showed significantly decreased spontaneous activity in the orbital middle frontal and lingual gyrus in adolescent nsMDDs after treatment. Also, depression severity was significantly decreased after treatment. Conclusion The abnormal functional neuronal activity found at frontal and occipital cortex implied cognitive and affective disturbances in adolescent nsMDDs. The trend of upregulation of frontal neuronal activity and downregulation of occipital neuronal activity after sertraline treatment indicated that the therapy could be effective in regulating the abnormality. Notably, the significantly decreased neuronal activity in the decision related orbital middle frontal and anxiety-depression related lingual gyrus could be suggestive of reduced NSSI in adolescent MDD after therapy.

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.

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Review of Abnormal Self-Knowledge in Major Depressive Disorder.

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Review of Abnormal Self-Knowledge in Major Depressive Disorder.

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