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Childhood Adversity Impairs Theory of Mind Abilities in Adult Patients With Major Depressive Disorder.

ABSTRACT: Background: Patients with major depressive disorder (MDD) have various theory of mind (ToM) impairments which often predict a poor outcome. However, findings on ToM deficits in MDD are inconsistent and suggest the role of moderating factors. Child abuse and neglect are strong predictors of adult MDD and are often associated with a poorer clinical course trajectory. Objective: Because early-life adversities result in various forms of ToM deficits in clinical and nonclinical samples, our aim was to investigate if they are significant confounding factors of ToM impairments in MDD. Methods: We investigated 60 mildly or moderately depressed, nonpsychotic adult patients with MDD during an acute episode, and 32 matched healthy controls. The mental state decoding subdomain of ToM was examined with the Reading the Mind in the Eyes Test (RMET). Childhood adversities were assessed with the childhood trauma questionnaire (CTQ) and the early trauma inventory. Results: There was no difference between the control and MDD groups in RMET performance. However, when we divided the MDD group into two subgroups, one (N = 30) with high and the other (N = 30) with low levels of childhood adversities, a significant difference emerged between the controls and the highly maltreated MDD subgroup in RMET performance. A series of 3 (group) × 3 (valence) mixed-model analyses of covariance (ANCOVAs) revealed that childhood emotional and physical neglect had a significant negative impact on the response accuracy in RMET in general, whereas emotional abuse specifically interfered with the accuracy in the positive and negative valences if it co-occurred with early-life neglect. To test the dose-response relationship between the number of childhood adversities and RMET capacities, we subjected RMET data of the MDD group to multiple hierarchical regressions: the number of childhood adversities was a significant predictor of RMET total scores and RMET scores in the negative valence after controlling for age, sex, years of education, and the severity of current depression. Conclusion: Childhood adversities impair ToM capacities in MDD. Exposure to early-life emotional abuse and neglect have a negative impact on the performance in the emotional valences of RMET. Multiple early-life adversities have a dose-dependent association with mental state decoding deficits.

SUBMITTER: Simon M

PROVIDER: S-EPMC6928114 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Childhood Adversity Impairs Theory of Mind Abilities in Adult Patients With Major Depressive Disorder.

Simon Maria M Németh Nándor N Gálber Mónika M Lakner Elza E Csernela Eszter E Tényi Tamás T Czéh Boldizsár B

Frontiers in psychiatry 20191217

<b>Background:</b> Patients with major depressive disorder (MDD) have various theory of mind (ToM) impairments which often predict a poor outcome. However, findings on ToM deficits in MDD are inconsistent and suggest the role of moderating factors. Child abuse and neglect are strong predictors of adult MDD and are often associated with a poorer clinical course trajectory. <b>Objective:</b> Because early-life adversities result in various forms of ToM deficits in clinical and nonclinical samples, ...[more]

PMID: 31920739

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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.

Dataset Information

Childhood Adversity Impairs Theory of Mind Abilities in Adult Patients With Major Depressive Disorder.

Publications

Childhood Adversity Impairs Theory of Mind Abilities in Adult Patients With Major Depressive Disorder.

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