A Data-Driven Clustering Method for Discovering Profiles in the Dynamics of Major Depressive Disorder Using a Smartphone-Based Ecological Momentary Assessment of Mood.

BACKGROUND: Although major depressive disorder (MDD) is characterized by a pervasive negative mood, research indicates that the mood of depressed patients is rarely entirely stagnant. It is often dynamic, distinguished by highs and lows, and it is highly responsive to external and internal regulatory processes. Mood dynamics can be defined as a combination of mood variability (the magnitude of the mood changes) and emotional inertia (the speed of mood shifts). The purpose of this study is to explore various distinctive profiles in real-time monitored mood dynamics among MDD patients in routine mental healthcare. METHODS: Ecological momentary assessment (EMA) data were collected as part of the cross-European E-COMPARED trial, in which approximately half of the patients were randomly assigned to receive the blended Cognitive Behavioral Therapy (bCBT). In this study a subsample of the bCBT group was included (n = 287). As part of bCBT, patients were prompted to rate their current mood (on a 1-10 scale) using a smartphone-based EMA application. During the first week of treatment, the patients were prompted to rate their mood on three separate occasions during the day. Latent profile analyses were subsequently applied to identify distinct profiles based on average mood, mood variability, and emotional inertia across the monitoring period. RESULTS: Overall, four profiles were identified, which we labeled as: (1) "very negative and least variable mood" (n = 14) (2) "negative and moderate variable mood" (n = 204), (3) "positive and moderate variable mood" (n = 41), and (4) "negative and highest variable mood" (n = 28). The degree of emotional inertia was virtually identical across the profiles. CONCLUSIONS: The real-time monitoring conducted in the present study provides some preliminary indications of different patterns of both average mood and mood variability among MDD patients in treatment in mental health settings. Such varying patterns were not found for emotional inertia

Examining the Theoretical Framework of Behavioral Activation for Major Depressive Disorder: Smartphone-Based Ecological Momentary Assessment Study.

BACKGROUND: Behavioral activation (BA), either as a stand-alone treatment or as part of cognitive behavioral therapy, has been shown to be effective for treating depression. The theoretical underpinnings of BA derive from Lewinsohn et al's theory of depression. The central premise of BA is that having patients engage in more pleasant activities leads to them experiencing more pleasure and elevates their mood, which, in turn, leads to further (behavioral) activation. However, there is a dearth of empirical evidence about the theoretical framework of BA. OBJECTIVE: This study aims to examine the assumed (temporal) associations of the 3 constructs in the theoretical framework of BA. METHODS: Data were collected as part of the "European Comparative Effectiveness Research on Internet-based Depression Treatment versus treatment-as-usual" trial among patients who were randomly assigned to receive blended cognitive behavioral therapy (bCBT). As part of bCBT, patients completed weekly assessments of their level of engagement in pleasant activities, the pleasure they experienced as a result of these activities, and their mood over the course of the treatment using a smartphone-based ecological momentary assessment (EMA) application. Longitudinal cross-lagged and cross-sectional associations of 240 patients were examined using random intercept cross-lagged panel models. RESULTS: The analyses did not reveal any statistically significant cross-lagged coefficients (all P>.05). Statistically significant cross-sectional positive associations between activities, pleasure, and mood levels were identified. Moreover, the levels of engagement in activities, pleasure, and mood slightly increased over the duration of the treatment. In addition, mood seemed to carry over, over time, while both levels of engagement in activities and pleasurable experiences did not. CONCLUSIONS: The results were partially in accordance with the theoretical framework of BA, insofar as the analyses revealed cross-sectional relationships between levels of engagement in activities, pleasurable experiences deriving from these activities, and enhanced mood. However, given that no statistically significant temporal relationships were revealed, no conclusions could be drawn about potential causality. A shorter measurement interval (eg, daily rather than weekly EMA reports) might be more attuned to detecting potential underlying temporal pathways. Future research should use an EMA methodology to further investigate temporal associations, based on theory and how treatments are presented to patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02542891, https://clinicaltrials.gov/ct2/show/NCT02542891; German Clinical Trials Register, DRKS00006866, https://tinyurl.com/ybja3xz7; Netherlands Trials Register, NTR4962, https://www.trialregister.nl/trial/4838; ClinicalTrials.Gov, NCT02389660, https://clinicaltrials.gov/ct2/show/NCT02389660; ClinicalTrials.gov, NCT02361684, https://clinicaltrials.gov/ct2/show/NCT02361684; ClinicalTrials.gov, NCT02449447, https://clinicaltrials.gov/ct2/show/NCT02449447; ClinicalTrials.gov, NCT02410616, https://clinicaltrials.gov/ct2/show/NCT02410616; ISRCTN registry, ISRCTN12388725, https://www.isrctn.com/ISRCTN12388725

Relationship between childhood physical abuse and clinical severity of treatment-resistant depression in a geriatric population

Introduction: We assessed the correlation between childhood maltreatment (CM) and severity of depression in an elderly unipolar Treatment-Resistant Depression (TRD) sample. Methods: Patients were enrolled from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centres. Results: Our sample included 96 patients (33% of the overall cohort) aged 60 years or above, with a mean age of 67.2 (SD = 5.7). The majority of the patients were female (62.5%). The Montgomery and Asberg Depression Rating Scale (MADRS) and Quick Inventory Depression Scale-Self Report (QIDS-SR) mean scores were high, 28.2 (SD = 7.49) [MADRS score range: 0–60; moderate severity≥20, high severity≥35] and 16.5 (SD = 4.94) [IDS-SR score range: 0–27; moderate severity≥11, high severity≥16], respectively. Mean self-esteem scores were 22.47 (SD = 6.26) [range 0–30]. In an age- and sex-adjusted model, we found a positive correlation between childhood trauma (CTQ scores) and depressive symptom severity [MADRS (β = 0.274; p = 0.07) and QIDS-SR (β = 0.302; p = 0.005) scores]. We detected a statistically significant correlation between physical abuse and depressive symptom severity [MADRS (β = 0.304; p = 0.03) and QIDS-SR (β = 0.362; p = 0.005) scores]. We did not observe any significant correlation between other types of trauma and depressive symptom severity. We showed that self-esteem (Rosenberg scale) mediated the effect of physical abuse (PA) on the intensity of depressive symptoms [MADRS: b = 0.318, 95% BCa C.I. [0.07, 0.62]; QIDS-SR: b = 0.177, 95% BCa C.I. [0.04, 0.37]]. Preacher & Kelly’s Kappa Squared values of 19.1% (k2 = 0.191) and 16% (k2 = 0.16), respectively for the two scales, indicate a moderate effect. Conclusion: To our knowledge, this is the first study conducted in a geriatric TRD population documenting an association between childhood trauma (mainly relating to PA) and the intensity of depressive symptoms

Effect of Sleep Disturbance Symptoms on Treatment Outcome in Blended Cognitive Behavioral Therapy for Depression (E-COMPARED Study): Secondary Analysis.

BACKGROUND: Sleep disturbance symptoms are common in major depressive disorder (MDD) and have been found to hamper the treatment effect of conventional face-to-face psychological treatments such as cognitive behavioral therapy. To increase the dissemination of evidence-based treatment, blended cognitive behavioral therapy (bCBT) consisting of web-based and face-to-face treatment is on the rise for patients with MDD. To date, no study has examined whether sleep disturbance symptoms have an impact on bCBT treatment outcomes and whether it affects bCBT and treatment-as-usual (TAU) equally. OBJECTIVE: The objectives of this study are to investigate whether baseline sleep disturbance symptoms have an impact on treatment outcomes independent of treatment modality and whether sleep disturbance symptoms impact bCBT and TAU in routine care equally. METHODS: The study was based on data from the E-COMPARED (European Comparative Effectiveness Research on Blended Depression Treatment Versus Treatment-as-Usual) study, a 2-arm, multisite, parallel randomized controlled, noninferiority trial. A total of 943 outpatients with MDD were randomized to either bCBT (476/943, 50.5%) or TAU consisting of routine clinical MDD treatment (467/943, 49.5%). The primary outcome of this study was the change in depression symptom severity at the 12-month follow-up. The secondary outcomes were the change in depression symptom severity at the 3- and 6-month follow-up and MDD diagnoses at the 12-month follow-up, assessed using the Patient Health Questionnaire-9 and Mini-International Neuropsychiatric Interview, respectively. Mixed effects models were used to examine the association of sleep disturbance symptoms with treatment outcome and treatment modality over time. RESULTS: Of the 943 patients recruited for the study, 558 (59.2%) completed the 12-month follow-up assessment. In the total sample, baseline sleep disturbance symptoms did not significantly affect change in depressive symptom severity at the 12-month follow-up (β=.16, 95% CI -0.04 to 0.36). However, baseline sleep disturbance symptoms were negatively associated with treatment outcome for bCBT (β=.49, 95% CI 0.22-0.76) but not for TAU (β=-.23, 95% CI -0.50 to 0.05) at the 12-month follow-up, even when adjusting for baseline depression symptom severity. The same result was seen for the effect of sleep disturbance symptoms on the presence of depression measured with Mini-International Neuropsychiatric Interview at the 12-month follow-up. However, for both treatment formats, baseline sleep disturbance symptoms were not associated with depression symptom severity at either the 3- (β=.06, 95% CI -0.11 to 0.23) or 6-month (β=.09, 95% CI -0.10 to 0.28) follow-up. CONCLUSIONS: Baseline sleep disturbance symptoms may have a negative impact on long-term treatment outcomes in bCBT for MDD. This effect was not observed for TAU. These findings suggest that special attention to sleep disturbance symptoms might be warranted when MDD is treated with bCBT. Future studies should investigate the effect of implementing modules specifically targeting sleep disturbance symptoms in bCBT for MDD to improve long-term prognosis

Élaboration d'un programme d'éducation thérapeutique du patient dans la dépression

Introduction - Le projet d élaborer un programme d éducation thérapeutique dans la dépression a été initié dans un service spécialisé dans la prise en charge des patients présentant des dépressions sévères et difficiles à traiter. La dépression est marquée chez ces patients par des complications évolutives : la rémission partielle, la rechute, la récurrence ou la chronicité. L adhésion au traitement médicamenteux apparait comme un élément déterminant dans la survenue de ces complications. L objectif de ce travail est de décrire les étapes ayant conduit à l élaboration du programme. Méthode - Dans l objectif d établir un référentiel de compétences spécifique de la dépression, nous avons analysé les besoins éducatifs auprès des patients et des soignants de l unité. Cette analyse a été complétée par les données de la littérature concernant l adhésion aux traitements médicamenteux. Résultats - Le programme est composé de quatre séances d une durée d 1h30, animées par un médecin et un infirmier. La première séance aborde la maladie, la seconde les traitements médicamenteux, la troisième la notion de balance bénéfice-risque, la dernière est une séance de synthèse. Dans l objectif d évaluer la faisabilité du programme, il a été mis en œuvre auprès de 22 patients hospitalisés. Un diagnostic éducatif, une auto-évaluation de l adhésion au traitement par la Medication Adherence Rating Scale ont été effectués chez ces patients. Conclusion - Pour être mis en œuvre, ce programme devra faire l objet d une demande d autorisation auprès de l Agence Régionale de Santé. Il devra également faire l objet d une évaluation visant à en mesurer les bénéfices sur la prise en charge des patients.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Sérotonine et gaba dans la dépression (évolution liée à l'électroconvulsivothérapie)

L électroconvulsivothérapie (ECT) est un des traitements de la dépression les plus efficaces et bien tolérée. Les mécanismes sous tendant son effet antidépresseur restent inconnus bien qu une hypothèse majeure concerne le rôle des mécanismes anticonvulsivants de l ECT. Afin d explorer cette hypothèse, nous avons inclus onze sujets présentant un état dépressif pour leur faire réaliser un examen par TEP, avant et 7 jours après une cure d ECT, comprenant une étude du récepteur aux benzodiazépines par le [11C]flumazénil et une étude du récepteur 5HT1A de la sérotonine par le [18F]MPPF. Les résultats chez les 6 patients ayant réalisé le protocole intégralement montre une augmentation significative de la densité des récepteurs aux benzodiazépines dans l hippocampe gauche suite à l ECT, alors qu avant le début du traitement, on trouve, par rapport aux sujets contrôles, une diminution significative dans l insula droite, le cortex cingulaire dorsal, le thalamus et une augmentation significative dans le cortex préfrontal dorsolatéral gauche. L étude du récepteur 5HT1A de la sérotonine trouve une diminution significative de son potentiel de liaison (BP) dans le système limbique avant l ECT. Cette diminution apparaît stable après ECT, laissant supposer qu il s agirait d un marqueur trait de la dépression. Bien que notre étude souffre de certains biais (hétérogénéité du diagnostic des patients, traitements médicamenteux, échantillon réduit), nos résultats permettent de faire un lien avec les données connues sur ce traitement (mécanismes anticonvulsivants ), une modification de la neurotransmission GABAergique, et son effet antidépresseur.GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Aborder la résistance des troubles unipolaires dans la pratique clinique (que faire de la théorie ?)

La résistance des troubles unipolaires est un concept vaste et encore mal défini. Actuellement aucune définition théorique ne permet au thérapeute de l'appréhender de manière objective dans la pratique quotidienne. Ce travail se propose donc de réfléchir sur le passage du concept théorique de résistance à son appréhension concrète dans la pratique quotidienne, selon quatre parties: Une première partie ayant pour vocation de délimiter le cadre théorique du propos. A cet effet, les notions d'unipolarité puis de résistance seront rappelées dans leurs généralités, suivies d'un bref chapitre exposant les obstacles d'une telle entreprise. Une seconde partie dans laquelle nous exposons les données théoriques nécessaires à l'élaboration secondaire d'une bonne démarche clinique, selon un modèle intégratif en 4 axes : ciblage des facteurs prédictifs d'une résistance ; définition de la résistance dans ses fondements ; intégration de la résistance dans l'évolution de la maladie dépressive ; et évaluation de sa sévérité et donc de l'arsenal thérapeutique à envisager pour le patient. Une troisième partie ensuite qui propose une conduite à tenir pratique reprenant chacun des axes abordés. Dans une dernière partie, nous discutons des limites et obstacles que pose l'application des connaissances actuelles à la pratique clinique. Nous tentons enfin, dans une dernière ouverture, de trouver quelques solutions à ces écueils.The resistance of unipolar disorder is a large and difficult to define concept. There is actually no theorical definition to help the clinician to identify it in his daily practice. We proposed to think about the link between the resistance's theory and its concrete application, according to 4 parts: In the first part, the theoritical limits of this concept are defined with a brief definitions of unipolar disorder and resistance, and a reminder of the main difficulties of the transposition between theory and practice. In the second part, we propose a model in 4 axes to help to this transposition. Each axe is reflecting one important aspect of the concept of resistance: targeting factors associated in the resistance; definition of resistance in its fundamental aspects; its integration in the evolution of the depressive disorder; and evaluation of its severity which is correlated to the type of therapeutic to choose. In the third part, this model is used to guide a systematic, light clinical and therapeutic demarche. We then discuss about the limits and obstacles of application of the current knowledge to the daily practice. Some solutions are finally proposed to resolve this problems.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Using the Personalized Advantage Index for Individual Treatment Allocation to Blended Treatment or Treatment as Usual for Depression in Secondary Care

A variety of effective psychotherapies for depression are available, but patients who suffer from depression vary in their treatment response. Combining face‐to‐face therapies with internet‐ based elements in the sense of blended treatment is a new approach to treatment for depression. The goal of this study was to answer the following research questions: (1) What are the most important predictors determining optimal treatment allocation to treatment as usual or blended treatment? and (2) Would model‐determined treatment allocation using this predictive information and the personalized advantage index (PAI)‐approach result in better treatment outcomes? Bayesian model averaging (BMA) was applied to the data of a randomized controlled trial (RCT) comparing the efficacy of treatment as usual and blended treatment in depressive outpatients. Pre‐ treatment symptomatology and treatment expectancy predicted outcomes irrespective of treatment condition, whereas different prescriptive predictors were found. A PAI of 2.33 PHQ‐9 points was found, meaning that patients who would have received the treatment that is optimal for them would have had a post‐treatment PHQ‐9 score that is two points lower than if they had received the treatment that is suboptimal for them. For 29% of the sample, the PAI was five or greater, which means that a substantial difference between the two treatments was predicted. The use of the PAI approach for clinical practice must be further confirmed in prospective research; the current study supports the identification of specific interventions favorable for specific patients

Short- and long-term efficacy of electroconvulsive stimulation in animal models of depression: The essential role of neuronal survival

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Quelle définition pour la dépression résistante ?

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