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Maladaptive blame-related action tendencies are associated with vulnerability to major depressive disorder.

ABSTRACT: Biases towards self-blaming emotions, such as self-contempt/disgust, were previously associated with vulnerability to major depressive disorder (MDD). Self-blaming emotions are thought to prompt specific action tendencies (e.g. "feeling like hiding"), which are likely to be more important for psychosocial functioning than the emotions themselves. Systematic investigations, however, of these action tendencies in MDD are lacking. Here, we investigated the role of blame-related action tendencies for MDD vulnerability and their relationship with blame-related emotions. 76 participants with medication-free remitted MDD and 44 healthy control (HC) participants without a history of MDD completed the value-related moral sentiment task, which measured their blame-related emotions during hypothetical social interactions and a novel task to assess their blame-related action tendencies (feeling like hiding, apologising, creating a distance from oneself, attacking oneself, creating a distance from other, attacking other, no action). As predicted, the MDD group showed a maladaptive profile of action tendencies: a higher proneness to feeling like hiding and creating a distance from themselves compared with the HC group. In contrast, feeling like apologising was less common in the MDD than the HC group. Apologising for one's wrongdoing was associated with all self-blaming emotions including shame, guilt, self-contempt/disgust and self-indignation. Hiding was associated with both shame and guilt. Our study shows that MDD vulnerability was associated with specific maladaptive action tendencies which were independent of the type of emotion, thus unveiling novel cognitive markers and neurocognitive treatment targets.

SUBMITTER: Duan S

PROVIDER: S-EPMC8756141 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIn major depressive disorder (MDD), self-blame-related fMRI measures have shown the potential to be used as prognostic markers for recurrence risk. Like most potential fMRI markers, however, their reliability is unclear. Here, we probed the internal reliability of self-blame-related fMRI measures, as well as the impact of different modelling approaches on reliability metrics and validity.MethodsInternal consistency (i.e. split-half reliability) was calculated for blood oxygen level-dependent (BOLD) responses and psychophysiological interactions (PPI) related to self-blame-related biases in medication-free remitted MDD participants (n = 81) and healthy controls (n = 41). Trial-length was modelled using three durations (0, 2 and 5 s), which was convolved with the haemodynamic response function (HRF) with and without time and dispersion derivatives. Intraclass correlation coefficients (ICCs) were calculated for simple contrasts examining activation to self-blaming emotions and other-blaming emotions and the more complex contrast of the subtraction-based difference between self- and other-blaming emotions within the following a priori ROIs: right superior anterior temporal lobe seed region, anterior subgenual cingulate cortex, posterior subgenual cortex and right striatum / pallidum.ResultsAcross ROIs, we obtained fair reliability (ICC ≥ 0.40) for simple, but poor reliability (ICC < 0.40) for more complex fMRI measures related to self-blame. Despite this low internal consistency of complex measures at the individual level, we observed robust activation at the group-level, reproducing previously published results.ConclusionsWhile simple BOLD contrasts had fair reliability, previously employed PPI models had poor reliability and simple connectivity measures lacked predictive validity. This calls for the development of functional connectivity measures that strike a better balance between reliability and validity for future clinical applications, which require robust measures at the individual rather than group-level.

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.

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Maladaptive blame-related action tendencies are associated with vulnerability to major depressive disorder.

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