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The dynamical signature of anhedonia in major depressive disorder: positive emotion dynamics, reactivity, and recovery.

ABSTRACT: BACKGROUND:Major Depressive Disorder (MDD) is the leading cause of disability worldwide. The cardinal features of MDD are depressed mood and anhedonia. Anhedonia is defined as a "markedly diminished interest or pleasure in all, or almost all, activities of the day", and has generally been investigated on group-level using retrospective data (e.g. via questionnaire/interview). However, inferences based on group-level findings not necessarily generalize to daily life experiences within individuals. METHODS:We repeatedly sampled pleasurable experiences within individuals' daily lives by means of Experience Sampling Methods, and compared how positive affect unfolded in the daily life of healthy controls versus patients diagnosed with MDD and anhedonia. We sampled Positive Affect (PA) and reward experiences on 10 semi-random time points a day, for seven days in the daily lives of 47 MDD patients with anhedonia, and 40 controls. RESULTS:Multilevel models showed that anhedonia was associated with low PA, but not to differences in PA dynamics, nor reward frequency in daily life. In reaction to rewards, MDD patients with anhedonia showed no difference in their increase in PA (i.e., PA reactivity), and showed no signs of a faster return to baseline thereafter (i.e., PA recovery). CONCLUSIONS:Our results suggest that the dynamical signature of anhedonia in MDD can be described best as a lower average level of PA, and "normal" in terms of PA dynamics, daily reward reactivity and reward recovery. Preregistration: https://osf.io/gmfsc/register/565fb3678c5e4a66b5582f67 . Preprint: https://osf.io/cfkts.

SUBMITTER: Heininga VE

PROVIDER: S-EPMC6368777 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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The dynamical signature of anhedonia in major depressive disorder: positive emotion dynamics, reactivity, and recovery.

Heininga Vera E VE Dejonckheere Egon E Houben Marlies M Obbels Jasmien J Sienaert Pascal P Leroy Bart B van Roy Joris J Kuppens Peter P

BMC psychiatry 20190208 1

<h4>Background</h4>Major Depressive Disorder (MDD) is the leading cause of disability worldwide. The cardinal features of MDD are depressed mood and anhedonia. Anhedonia is defined as a "markedly diminished interest or pleasure in all, or almost all, activities of the day", and has generally been investigated on group-level using retrospective data (e.g. via questionnaire/interview). However, inferences based on group-level findings not necessarily generalize to daily life experiences within ind ...[more]

PMID: 30736751

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Project description:Background: Anhedonia is a common, persistent, and disabling phenomenon in treated adults with Major Depressive Disorder (MDD). Hitherto, relatively few antidepressant agents have been evaluated with respect to their effect on anhedonia in MDD. Methods: This is a post-hoc analysis of a primary study that sought to evaluate the sensitivity to change of the THINC-integrated tool (THINC-it) in MDD (ClinicalTrials.gov Identifier: NCT03053362). Adults meeting DSM-5 criteria for MDD with at least moderate depressive symptom severity [i.e., Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥20] were eligible. Subjects were recruited between October 2017 and August 2018 in Toronto, Ontario at the Brain and Cognition Discovery Foundation. All subjects received open-label vortioxetine (10-20 mg/day, flexibly-dosed) for 8 weeks. Herein, the primary outcome of interest was the change from baseline to endpoint in the Snaith-Hamilton Pleasure Scale (SHAPS) total score, as well as the MADRS anhedonia factor. The mediational effects of improvements in anhedonia on general function and quality of life, as measured by the Sheehan Disability Scale (SDS) and the 5-Item World Health Organization Well-Being Index (WHO-5), were secondarily assessed. Results: A total of 100 subjects with MDD were enrolled in the primary study and began treatment with vortioxetine. Vortioxetine significantly improved anhedonia as evidenced by significant baseline to endpoint improvements in SHAPS and MADRS anhedonia factor scores (p < 0.0001). Improvements in the SHAPS and the MADRS anhedonia factor correlated with improvements in general function (i.e., SDS) and quality of life (i.e., WHO-5) (p < 0.0001). Notably, improvements in anhedonia were found to mediate the association between improvements in overall depressive symptom severity (i.e., MADRS total score) and social functioning (i.e., social life component of the SDS) (p = 0.026). Conclusion: The unmet need in depression is to improve patient functioning and other patient-reported outcomes (e.g., quality of life). Antidepressant interventions capable of attenuating anhedonia as well as cognitive dysfunction in MDD may help in this regard, as improvement in these domains have been associated with improvement in psychosocial function and quality of life.

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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Dataset Information

The dynamical signature of anhedonia in major depressive disorder: positive emotion dynamics, reactivity, and recovery.

Publications

The dynamical signature of anhedonia in major depressive disorder: positive emotion dynamics, reactivity, and recovery.

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