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Do patients' resilience and subjective illness representation predict the outcome of a routine inpatient treatment program of major depressive disorder?

ABSTRACT: Adopting a personalized medicine approach beyond genetic/epigenetic profiling within psychiatric diagnostic and treatment is challenging. For the first time, we studied the influence of two patient resources (resilience and illness representation) on the success of an inpatient treatment of major depressive disorder (MDD). Using a 5-week observational real-world-study, the treatment- success was measured by the difference between the subjective depression- severity (according to the German short form of Beck's Depression-Inventory) at baseline (i.e., days four to six post-admission) and study- endpoint. In the intention-to-treat sample (n = 60, 47.3 ± 12.8 years old; 58% females), the patients' illness representation [measured by the "Krankheitskonzeptskala" (KK)] did not predict their treatment- success. The KK-dimension 'trust-in-doctors' was associated with resilience but not with the treatment-success. Albeit, the patients' resilience (determined by Resilience- Scale, 11-item-version (RS-11)) negatively predicted their positive treatment- success (b = - 0.09, p = 0.017, f² = 0.11). This influence of resilience on treatment- success was completely mediated by the baseline-depression- severity. This means, patients with low resilience reported high baseline-depression- levels which predicted a significant positive treatment- success. And, patients with high resilience reported low baseline-depression-levels which predicted no relevant or even negative inpatient treatment-success. The latter "high-resilience"- group (n = 27) was especially interesting. Remarkably, these patients appeared to have experienced within the first four-to-six inpatient treatment-days an "early sudden gain" against their considerable MDD- burden that initially had led to their admission. Thus, a stronger resilience might serve as a proxy of the development of an early MDD-relief as well as of lower baseline-depression- levels. Further studies are warranted to support the value of a patient's resilience to predict his treatment response and inpatient treatment duration.

SUBMITTER: Marschollek L

PROVIDER: S-EPMC8429153 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

Project description:Importance:Adolescence is a neurodevelopmental period during which experience-dependent plasticity in brain circuitry may confer vulnerability to depression as well as resilience to disorder. Little is known, however, about the neural mechanisms that underlie resilience during this critical period of brain development. Objective:To examine neural functional connectivity correlates of resilience in adolescent females at high and low familial risk for depression who did and did not develop the disorder. Design, Setting, and Participants:A longitudinal study was conducted at Stanford University from October 1, 2003, to January 31, 2017. Sixty-five female adolescents participated in the study: 20 at high risk in whom depression did not develop (resilient), 20 at high risk in whom depression developed (converted), and 25 at low risk with no history of psychopathology (control). Main Outcomes and Measures:We compared functional connectivity between resilient and converted, and between resilient and control, adolescent females using voxelwise 2-sided t tests to examine neural markers of resilience to depression as the main outcomes of interest. Specifically, we assessed differences in connectivity of the limbic (amygdala seed), salience (anterior insula seed), and executive control (dorsolateral prefrontal cortex seed) networks, implicated in emotion regulation. We also examined the association between functional connectivity and life events. Results:Of the 65 participants (mean [SD] age, 18.9 [2.5] years), adolescent females in the resilient group had greater connectivity between the amygdala and orbitofrontal cortex (z score?=?0.23; P?<?.001) and between the dorsolateral prefrontal cortex and frontotemporal regions (z score?=?0.24; P?<?.001) than did converted adolescent females. In adolescent females in the resilient group only, strength of amygdala-orbitofrontal cortex connectivity was correlated with positive life events (r18?=?0.48; P?=?.03). Resilient adolescent females had greater connectivity within frontal (z score?=?0.07; P?<?.001) and limbic (z score?=?0.21; P?<?.001) networks than did control individuals. Both high-risk groups had greater salience network connectivity: the converted group had greater intranetwork connectivity than did the resilient (z score?=?0.13; P?<?.001) and control (z score?=?0.10; P?<?.001) groups, and the adolescent females in the resilient group had greater salience network connectivity with the superior frontal gyrus than did the converted (z score?=?0.24; P?<?.001) adolescent females. Conclusions and Relevance:Resilient adolescent females have compensatory functional connectivity patterns in emotion regulatory networks that correlate with positive life events, suggesting that experience-dependent plasticity within these networks may confer resilience to depression. Further studies are warranted concerning connectivity-associated targets for promoting resilience in high-risk individuals.

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Do patients' resilience and subjective illness representation predict the outcome of a routine inpatient treatment program of major depressive disorder?

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