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We identified biologically relevant moderators of response to tumor necrosis factor (TNF)-α inhibitor, infliximab, among 60 individuals with bipolar depression. Data were derived from a 12-week, randomized, placebo-controlled clinical trial secondarily evaluating the efficacy of infliximab on a measure of anhedonia (i.e., Snaith-Hamilton Pleasure Scale). Three inflammatory biotypes were derived from peripheral cytokine measurements using an iterative, machine learning-based approach. Infliximab-randomized participants classified as biotype 3 exhibited lower baseline concentrations of pro- and anti-inflammatory cytokines and soluble TNF receptor-1 and reported greater pro-hedonic improvements, relative to those classified as biotype 1 or 2. Pretreatment biotypes also moderated changes in neuroinflammatory substrates relevant to infliximab's hypothesized mechanism of action. Neuronal origin-enriched extracellular vesicle (NEV) protein concentrations were reduced to two factors using principal axis factoring: phosphorylated nuclear factorκB (p-NFκB), Fas-associated death domain (p-FADD), and IκB kinase (p-IKKα/β) and TNF receptor-1 (TNFR1) comprised factor "NEV1," whereas phosphorylated insulin receptor substrate-1 (p-IRS1), p38 mitogen-activated protein kinase (p-p38), and c-Jun N-terminal kinase (p-JNK) constituted "NEV2". Among infliximab-randomized subjects classified as biotype 3, NEV1 scores were decreased at weeks 2 and 6 and increased at week 12, relative to baseline, and NEV2 scores increased over time. Decreases in NEV1 scores and increases in NEV2 scores were associated with greater reductions in anhedonic symptoms in our classification and regression tree model (r2 = 0.22, RMSE = 0.08). Our findings provide preliminary evidence supporting the hypothesis that the pro-hedonic effects of infliximab require modulation of multiple TNF-α signaling pathways, including NF-κB, IRS1, and MAPK.

Objective To evaluate the development and implementation of clinical practice guidelines for the management of depression globally. Methods We conducted a systematic review of existing guidelines for the management of depression in adults with major depressive or bipolar disorder. For each identified guideline, we assessed compliance with measures of guideline development quality (such as transparency in guideline development processes and funding, multidisciplinary author group composition, systematic review of comparative efficacy research) and implementation (such as quality indicators). We compared guidelines from low- and middle-income countries with those from high-income countries. Findings We identified 82 national and 13 international clinical practice guidelines from 83 countries in 27 languages. Guideline development processes and funding sources were explicitly specified in a smaller proportion of guidelines from low- and middle-income countries (8/29; 28%) relative to high-income countries (35/58; 60%). Fewer guidelines (2/29; 7%) from low- and middle-income countries, relative to high-income countries (22/58; 38%), were authored by a multidisciplinary development group. A systematic review of comparative effectiveness was conducted in 31% (9/29) of low- and middle-income country guidelines versus 71% (41/58) of high-income country guidelines. Only 10% (3/29) of low- and middle-income country and 19% (11/58) of high-income country guidelines described plans to assess quality indicators or recommendation adherence. Conclusion Globally, guideline implementation is inadequately planned, reported and measured. Narrowing disparities in the development and implementation of guidelines in low- and middle-income countries is a priority. Future guidelines should present strategies to implement recommendations and measure feasibility, cost-effectiveness and impact on health outcomes. [phrase omitted] [phrase omitted] Objectif Evaluer le developpement et la mise en reuvre des directives de pratique clinique pour la gestion de la depression dans le monde. Methodes Nous avons effectue une revue systematique des directives existantes en matiere de gestion de la depression chez les adultes souffrant de troubles depressifs majeurs ou de troubles bipolaires. Pour chaque directive identifiee, nous avons verifie le degre de conformite vis-a-vis des mesures de qualite du developpement des directives (transparence des processus d'elaboration des directives et de leur financement, composition multidisciplinaire du groupe d'auteurs, revue systematique des etudes d'efficacite comparative) ainsi que de la mise en reuvre (indicateurs de qualite). Nous avons confronte les directives des pays a faible et moyen revenu avec celles des pays a haut revenu. Resultats Nous avons identifie 82 directives de pratique clinique nationales et 13 directives de pratique clinique internationales dans 83 pays et en 27 langues. Les processus d'elaboration des directives et les sources de financement etaient explicitement indiquees dans une moindre proportion chez les pays a faible et moyen revenu (8/29; 28%) par rapport aux pays a haut revenu (35/58; 60%). Le nombre de directives redigees par un groupe d'auteurs multidisciplinaire etait moins eleve dans les pays a faible et moyen revenu (2/29; 7%) que dans les pays a haut revenu (22/58; 38%). Une revue systematique de l'efficacite comparative a ete menee pour 31% (9/29) des directives dans les pays a faible et moyen revenu, contre 71% (41/58) des directives dans les pays a haut revenu. Seulement 10% (3/29) des directives emises par les pays a faible et moyen revenu et 19% (11/58) de celles emises par les pays a haut revenu comprenaient un programme d'evaluation des indicateurs de qualite ou de l'adherence aux recommandations. Conclusion La mise en reuvre des directives est mal planifiee, mal analysee et mal mesuree. Reduire les disparites de developpement et de mise en reuvre des directives dans les pays a faible et moyen revenu est une priorite. A l'avenir, ces directives devraient prevoir des strategies d'execution des recommandations, mais aussi d'evaluation de la faisabilite, de la rentabilite et de l'impact sur l'etat de sante. [phrase omitted] Objetivo Evaluar la elaboracion e implementacion de las directrices de practica clinica para el tratamiento de la depresion a nivel mundial. Metodos Se realizo una revision sistematica de las directrices existentes para el tratamiento de la depresion en adultos con trastorno depresivo mayor o bipolar. Por cada directriz identificada, se evaluo el cumplimiento de las medidas de calidad de elaboracion de directrices (como la transparencia en los procesos de elaboracion de directrices y su financiamiento, la composicion del grupo multidisciplinario de autores, la revision sistematica del estudio de eficacia comparativo) y la implementacion (como los indicadores de calidad). En este contexto, se compararon las directrices de los paises de ingresos bajos y medios con las de los paises de ingresos altos. Resultados Se identificaron las directrices de practica clinica a nivel nacional (82) y a nivel internacional (13) de 83 paises en 27 idiomas. Los procesos de elaboracion de directrices y las fuentes de financiamiento se especificaron de manera explicita en un porcentaje menor de directrices de los paises de ingresos bajos y medios (8/29; 28 %) en relacion con las de los paises de ingresos altos (35/58; 60 %). Un grupo de desarrollo multidisciplinario elaboro menos directrices (2/29; 7 %) para los paises de ingresos bajos y medios, en relacion con las de los paises de ingresos altos (22/58; 38 %). Ademas, se realizo una revision sistematica sobre la efectividad comparativa en el 31 % (9/29) de las directrices de los paises de ingresos bajos y medios, frente al 71 % (41/58) de las directrices de los paises de ingresos altos. Solo el 10 % (3/29) de las directrices de los paises de ingresos bajos y medios y el 19 % (11/58) de las directrices de los paises de ingresos altos describieron planes para evaluar los indicadores de calidad o el cumplimiento de las recomendaciones. Conclusion La implementacion de las directrices no se planifica, notifica ni evalua de manera adecuada a nivel mundial. Es prioritario reducir las desigualdades en la elaboracion y la implementacion de las directrices en los paises de ingresos bajos y medios. Las directrices que se elaboren en el futuro deberan presentar estrategias para implementar las recomendaciones y evaluar la viabilidad, la rentabilidad y el impacto en los resultados sanitarios., Introduction The rising prevalence and burden of depression worldwide disproportionately affect low- and middle-income countries. (1-4) Major depressive and bipolar disorders independently increase the risk for other chronic diseases, including [...]

Background: The aim of this study was to examine the role of perceived sleep quality in predicting subjective as well as objective cognitive function in adults with major depressive disorder (MDD)., Methods: Adults with recurrent MDD (n = 100) experiencing a major depressive episode of at least moderate severity and age-, sex-, and education-matched healthy controls (HC) (n = 100) were recruited to participate in a clinical trial validating the THINC-integrated tool (THINC-it; NCT02508493) for cognitive function. The THINC-it includes subjective and objective measures of cognitive function. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI)., Results: Compared with HC, individuals with MDD reported significantly poorer sleep quality, as assessed by domain and global PSQI scores (all P values <.05). Both perceived sleep quality ( P < .001) and depression severity (P = .002) were found to independently predict impairments in subjective cognitive performance. Only perceived sleep quality predicted objective cognitive impairments (P = .017). Exploratory mediation analysis revealed depression severity to be a partial mediator of the relationship between perceived sleep quality and subjective cognitive performance (95% confidence interval [CI]: -0.56, -0.33)., Conclusions: The results indicate that the subjective and objective cognitive impairments are differentially related to perceived sleep quality and depression severity and emphasize the importance of treating sleep disturbances in MDD.

Background: Individuals with binge eating disorder (BED) are differentially affected by attention-deficit/hyperactivity disorder (ADHD), obesity, and substance use disorder. We have investigated to what extent cognitive deficits are relevant to binge eating behavior (BEB)., Methods: Data from the International Mood Disorders Collaborative Project were retrospectively and cross-sectionally analyzed to compare individuals with and without BEB on measures of anhedonia and general cognitive functions (n = 566). BEB was assessed using items from the Mini International Neuropsychiatric Interview Plus 5.0.0 for DSM-IV-TR that correspond with DSM-5-defined diagnostic criteria for BED. Individuals currently prescribed benzodiazepines were excluded from analyses., Results: Individuals with BEB were more likely to exhibit anhedonia (P = .044) and general cognitive (P = .005) symptoms, when compared to those without BEB. We also observed that individuals with BEB were more likely to have specific psychiatric (eg, ADHD) and medical (eg, obesity) disorders (P < .05)., Conclusions: Our results suggest that a central disturbance in cognitive processes may be mechanistically relevant to the cause and treatment of BEB in adults.

Phase stabilities of nanometer-sized materials are quite different from those of the corresponding bulk materials. Among the phase stabilities, melting point suppression is one of the most fundamentally important issues. In this work, real-time, atomic-scale direct observation of melting point suppression in nanometer-sized Au particles, along with simple size reduction, was carried out by means of in situ high resolution electron microscopy. Namely, it was confirmed in real space on an atomic scale that a solid-to-liquid transition occurred when the size of a particle, placed on a graphite substrate maintained at 1100 K, decreased to 5 nm during diminution. Furthermore, a monolayer-thick hole was formed on the substrate at the position of the liquid Au particle, probably due to carbon dissolution into the liquid Au particle.