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Orbito-frontal cortex mechanism of inhibition of return in current and remitted depression.

ABSTRACT: Deficient inhibition of return (IOR) for emotional materials is an important cognitive biomarker of depression. However, its neural mechanism and role in depression remission remain largely unknown. Using functional magnetic resonance imaging (fMRI), this study observed the neural foundation of inhibition of return in individuals with current (n?=?30) and remitted (n?=?27) depression and in healthy controls (n?=?33), by using a cue-target task. The results showed that individuals with remitted depression (RMD) possessed a nonavoidant attention model for sad faces, which indicated a cue validity and was correlated with enhanced task- and resting-state activation and function connectivity in orbitofrontal cortex (OFC). The patients with major depressive disorder (MDD), in contrast, displayed an IOR effect for all faces, which indicated a strategy of attention avoidance due to the high cognitive burden in the cue-target task, and was correlated with decreased resting-state activation and function connectivity in OFC. Moreover, the hippocampus, a less-known cortex in IOR, showed a contrary model, that is, lower activation in depression remission and higher task- and resting-state activation in depressive episodes. The results suggest the OFC mechanism of the IOR effect in remitted depression and the hippocampus mechanism of the IOR effect in depressive episodes, which offer potential biomarkers for the clinical treatment of depression.

SUBMITTER: Dai Q

PROVIDER: S-EPMC6866481 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Orbito-frontal cortex mechanism of inhibition of return in current and remitted depression.

Dai Qin Q Yin Xuntao X Li Hong H Feng Zhengzhi Z

Human brain mapping 20180325 7

Deficient inhibition of return (IOR) for emotional materials is an important cognitive biomarker of depression. However, its neural mechanism and role in depression remission remain largely unknown. Using functional magnetic resonance imaging (fMRI), this study observed the neural foundation of inhibition of return in individuals with current (n = 30) and remitted (n = 27) depression and in healthy controls (n = 33), by using a cue-target task. The results showed that individuals with remitted d ...[more]

PMID: 29575563

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Project description:Background: Major Depressive Disorder (MDD) is a highly prevalent, recurrent, and potentially chronic disorder. Identifying risk factors and underlying mechanisms to inform preventive and therapeutic interventions is therefore imperative. Emotion regulation is a proposed factor in the development and maintenance of MDD. The aim of the present review was to summarize and synthesize research on self-reported emotion regulation strategy use and emotion regulation abilities in adults diagnosed with current and remitted MDD. Methods: Seventy-two eligible studies were retrieved from databases through a systematic literature search. Group differences between individuals with current MDD, remitted MDD, and healthy controls were calculated using meta-analytic procedures. Meta-regression analyses investigated potential moderator effects on emotion regulation difficulties. Results: Results indicated that individuals with current MDD report higher maladaptive emotion regulation strategy use for avoidance (Hedges' g = 1.3), rumination (g = 2.1), and suppression (g = 1.1) compared to healthy controls. Also, they reported lower adaptive emotion regulation strategy use for acceptance (g = -1.0), problem solving (g = -1.0), and reappraisal (g = -0.7). Individuals with current MDD reported limited general emotion regulation abilities, indicated by higher alexithymia (g = 1.45), lower emotional awareness (g = -0.95), emotional clarity (g = -1.50) and emotional tolerance (g = -1.89). Similar results were found in individuals with remitted MDD for avoidance (g = 1.0), rumination (g = 1.1), suppression (g = 0.6), and general emotion regulation abilities. However, no difference was found between individuals with remitted MDD and healthy controls for adaptive emotion regulation strategies. Meta-regression analyses suggest that age of illness onset, comorbid anxiety and duration of remission influence emotion regulation. Conclusion: The present review and meta-analysis indicates that individuals with current and remitted MDD have difficulties with emotion regulation compared to individuals who have never been depressed. Although depressive symptoms improve, emotion regulation difficulties may continue, and could be a contributing factor to relapse. Our findings inform future research on emotion regulation and psychotherapeutic interventions.

Project description:BackgroundThe aim of this study was to improve our understanding of the underlying mechanisms in the maintenance of depression. We examined attentional bias (AB) for negative and positive adjectives and general threat words in strictly-defined clinical groups of participants with pure Major Depressive Disorder (MDD) without a history of anxiety disorders (AD), mixed MDD and AD, and remitted participants.MethodWe investigated both stimulus specificity and time course of AB in these groups, adopting a cross-sectional design. Data were drawn from the large scale Netherlands Study of Depression and Anxiety (NESDA), from which we selected all participants with pure current MDD without a history of AD (n = 29), all participants with current MDD and co-morbid AD(s) (n = 86), all remitted MDD participants (n = 294), and a comparison group without (a history of) MDD or ADs (n = 474). AB was measured with an Exogenous Cueing Task covering short and long presentation times (500 and 1250 ms) and 4 stimulus types (negative, positive, threat, neutral).ResultsBoth traditional and trial level (dynamic) AB scores failed to show an AB for negative adjectives in participants with MDD or mixed MDD/AD. Specifically for long duration trials (1250 ms), remitted participants showed a larger AB traditional score (albeit the actual score still being negative) than the comparison group. The mixed MDD/AD group showed a higher trial-level AB score away from positive adjectives (1250 ms) than the comparisons. In addition, the mixed MDD/AD group showed higher and more variable trial-level AB scores away from short and towards longer presented general threat words together with a non-significant tendency to show less negative traditional AB scores for threat trials (500 ms) than the comparison group.ConclusionsAll in all, the findings do not corroborate the view that an AB towards negative or away from positive adjectives is critically involved in currently depressed individuals. Yet, the relatively high (less negative) AB score for negative adjectives in remitted individuals points to the possibility that an AB for negative information may be involved as a risk factor in the recurrence of MDD.

Project description:ObjectivesRecently, the presence of a complete five subunit Kinase, Endopeptidase and Other Proteins of small Size (KEOPS) complex was confirmed in humans. The highly conserved KEOPS protein complex has established roles in tRNA modification, protein translation and telomere homeostasis in yeast, but little is known about KEOPS mRNA expression and function in human brain and disease. Here, we characterise KEOPS expression in post-mortem tissue from subjects diagnosed with major depression (MDD) and schizophrenia and assess whether KEOPS is associated with telomere length dysregulation in neuropsychiatric disorders.MethodsWe assessed mRNA expression of KEOPS complex subunits TP53RK, TPRKB, GON7, LAGE3, OSGEP, and OSGEP mitochondrial ortholog OSGEPL1 in the dorsolateral prefrontal cortex (DLPFC) of subjects with MDD, schizophrenia and matched non-psychiatrically ill controls (n = 20 per group) using qPCR. We conducted bioinformatic analysis using Kaleidoscope, data mining post-mortem transcriptomic datasets to characterise KEOPS expression in human brain. Finally, we assayed relative telomere length in the DLPFC using a qPCR-based assay and carried out correlation analysis with KEOPS subunit mRNA expression to determine if the KEOPS complex is associated with telomere length dysregulation in neuropsychiatric disorders.ResultsThere were no significant changes in KEOPS mRNA expression in the DLPFC in MDD or schizophrenia compared to non-psychiatrically ill controls. Relative telomere length was not significantly altered in MDD or schizophrenia, nor was there an association between relative telomere length and KEOPS subunit gene expression in these subjects.ConclusionsThis study is the first to describe KEOPS complex expression in post-mortem brain and neuropsychiatric disorders. KEOPS subunit mRNA expression is not significantly altered in the DLPFC in MDD or schizophrenia. Unlike in yeast, the KEOPS complex does not appear to play a role in telomere length regulation in humans or in neuropsychiatric disorders.

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Orbito-frontal cortex mechanism of inhibition of return in current and remitted depression.

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Orbito-frontal cortex mechanism of inhibition of return in current and remitted depression.

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