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COGNITION-CHILDHOOD MALTREATMENT INTERACTIONS IN THE PREDICTION OF ANTIDEPRESSANT OUTCOMES IN MAJOR DEPRESSIVE DISORDER PATIENTS: RESULTS FROM THE iSPOT-D TRIAL.

ABSTRACT: Childhood maltreatment (CM) history has been associated with poor treatment response in major depressive disorder (MDD), but the mechanisms underlying this relationship remain opaque. Dysfunction in the neural circuits for executive cognition is a putative neurobiological consequence of CM that may contribute importantly to adverse clinical outcomes. We used behavioral and neuroimaging measures of executive functioning to assess their contribution to the relationship between CM and antidepressant response in MDD patients.Ninety eight medication-free MDD outpatients participating in the International Study to Predict Optimized Treatment in Depression were assessed at baseline on behavioral neurocognitive measures and functional magnetic resonance imaging during tasks probing working memory (continuous performance task, CPT) and inhibition (Go/No-go). Seventy seven patients completed 8 weeks of antidepressant treatment. Baseline behavioral and neuroimaging measures were assessed in relation to CM (history of childhood physical, sexual, and/or emotional abuse) and posttreatment depression outcomes.Patients with maltreatment exhibited decreased modulation of right dorsolateral prefrontal cortex (DLPFC) activity during working memory updating on the CPT, and a corresponding impairment in CPT behavioral performance outside the scanner. No between-group differences were found for imaging or behavior on the Go/No-go test of inhibition. Greater DLPFC activity during CPT significantly predicted posttreatment symptom improvement in patients without maltreatment, whereas the relationship between DLPFC activity and symptom change was nonsignificant, and in the opposite direction, in patients with maltreatment.The effect of CM on prefrontal circuitry involved in executive function is a potential predictor of antidepressant outcomes.

SUBMITTER: Miller S

PROVIDER: S-EPMC4841677 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Project description:Gut microbiota and childhood maltreatment are closely related to depressive symptoms. This study aimed to analyze the characteristics of gut microbiota in major depressive disorder (MDD) patients with childhood maltreatment experience and explore the correlation between gut microbiota, childhood maltreatment, and depressive symptoms. A total of 37 healthy controls (HCs) and 53 patients with MDD were enrolled, including 18 MDD patients without childhood maltreatment experience and 35 MDD patients with childhood maltreatment experience. The Hamilton's Depression Scale (HAMD-24) and Childhood Trauma Questionnaire-Short Form (CTQ-SF) were used to evaluate their depressive symptoms and childhood maltreatment experience, respectively. The composition of gut microbiota was evaluated using 16S rRNA sequencing. Spearman's correlation analysis was used to evaluate the correlation between different gut microbiota, depressive symptoms and childhood maltreatment. The mediation analysis was used to evaluate the mediating effect of gut microbiota. In the α-diversity analysis, we found that the Simpson index and Pielou's Evenness index differed significantly between MDD patients without childhood maltreatment experience and HCs. In the β-diversity analysis, principal coordinate analysis (PCoA) showed significant differences between MDD patients without childhood maltreatment experience, MDD patients with childhood maltreatment experience and HCs. Twenty-seven different bacteria were identified through Linear discriminant analysis effect size (LEfSe) analysis at different levels of classification. The analysis of the correlation showed that Blautia, Bifidobacterium, Bacteroides, Roseburia, and Phascolarctobacterium were significantly correlated with HAMD and CTQ-SF scores. The mediation analysis showed that childhood maltreatment had a significant direct effect on the patients' depressive symptoms, and Blautia, Bifidobacterium, Roseburia had a significant mediating effect. The findings of this study suggested that MDD patients with childhood maltreatment experience had different gut microbiota, which might have a mediating effect on the influence of childhood maltreatment on depressive symptoms.

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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COGNITION-CHILDHOOD MALTREATMENT INTERACTIONS IN THE PREDICTION OF ANTIDEPRESSANT OUTCOMES IN MAJOR DEPRESSIVE DISORDER PATIENTS: RESULTS FROM THE iSPOT-D TRIAL.

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