Comparing Symptoms of Major Depression in Youth with Confirmed Versus Suspected Bipolar Disorder.

Background: While numerous studies have compared symptoms of major depressive episodes (MDEs) associated with bipolar disorder (BD; i.e., bipolar depression) versus major depressive disorder (MDD; i.e., unipolar depression), little is known about this topic in youth. We compared MDE symptoms in youth with BD with youth with suspected BD who have similar clinical and familial characteristics aside from having BD. Methods: MDE symptoms based on Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS) Depression Rating Scale items for the most severe past episode were compared in youth, ages 13-21 years, with BD (n = 208) versus suspected BD (n = 165). Diagnoses were confirmed via semistructured interviews. Symptoms with between-group differences (p < 0.05) in univariate analyses were evaluated in a multivariate forward stepwise regression. All analyses controlled for age and sex. Results: Youth with BD had significantly higher (more severe) ratings on depressed mood (p = 0.001, η2 = 0.05), irritability (p = 0.037, η2 = 0.02), anhedonia (p = 0.004, η2 = 0.04), negative self-image (p < 0.001, η2 = 0.07), hopelessness (p = 0.04, η2 = 0.02), fatigue (p = 0.001, η2 = 0.05), hypersomnia (p = 0.001, η2 = 0.05), suicidal ideation (p = 0.04, η2 = 0.02), and recurrent thoughts of death (p < 0.001, η2 = 0.05). In regression analyses, the only symptom that remained significant in the BD group was depressed mood (p = 0.002). Conclusions: These findings demonstrate greater severity of depressive symptoms in youth with BD versus MDD across mood, and cognitive and neurovegetative symptom domains. These differences are especially noteworthy given that the MDD group was highly similar to the BD group, aside from BD diagnosis. Present findings emphasize the need for novel treatment approaches to bipolar depression in youth, and for studies examining potential mechanisms underlying the increased severity of bipolar depression.

Exercise preference and tolerance in youth with bipolar disorder.

BACKGROUND: Despite the multiple potential benefits, individuals with bipolar disorder (BD) report lower levels of moderate-vigorous exercise. We examined the correlates of exercise preference and tolerance among youth with BD, to inform future exercise intervention studies. METHODS: In this cross-sectional study 107 adolescents (n = 54 BD, n = 53 healthy controls [HC]) completed the self-reported Preference for and Tolerance of the Intensity of Exercise Questionnaire, a 20-minute bout of moderate intensity aerobic exercise, and the Borg Rating of Perceived Exertion. Cardiorespiratory fitness (CRF) was calculated using a proxy measure. Variables associated with either exercise preference or tolerance at p < 0.01 in univariate analyses were entered into multivariable models. Significance was set at p < 0.05 for all analyses. RESULTS: Exercise tolerance and CRF were significantly lower in the BD group. There was no significant difference in exercise preference. Lower exercise preference among youth with BD was significantly associated with lower CRF (ß = 0.39, p = 0.006) and higher perceived exertion (ß = -0.33, p = 0.01), while higher exercise preference was associated with lifetime psychiatric hospitalization (ß = 0.29, p = 0.04). Female sex (ß = 0.31, p = 0.03), higher perceived exertion (ß = -0.37, p = 0.007), and non-Caucasian race (ß = 0.31, p = 0.02) were significantly associated with lower exercise tolerance in youth with BD. CONCLUSIONS: The current study adds to the limited literature examining exercise preference and tolerance in youth with BD and provides an avenue to examine these correlates further in clinical and exercise interventions.

Prevalence and correlates of childhood-onset bipolar disorder among adolescents.

AIM: Early-onset bipolar disorder (BD) is associated with a more severe illness as well as a number of clinical factors among adults. Early-onset can be categorized as childhood- (age < 13) or adolescent- (age ≥ 13) onset, with the two displaying different clinical profiles. We set out to examine differences in clinical, and familial characteristics among adolescents with childhood- versus adolescent-onset BD. METHODS: The study included 195 adolescents with BD, ages 14-18 years. Age of onset was determined retrospectively by self-report. Participants completed the semi-structured K-SADS-PL diagnostic interviews along with self-reported dimensional scales. Analyses examined between-group differences for clinical and familial variables. Variables associated with age of onset at p < 0.1 in univariate analyses were evaluated in a logistic regression model. RESULTS: Approximately one-fifth of participants had childhood-onset BD (n = 35; 17.9%). A number of clinical and familial factors were significantly associated with childhood-onset BD. However, there were no significant differences in depressive and manic symptom severity. In multivariate analyses, the variables most strongly associated with childhood-onset were police contact, and family history of suicidal ideation. Smoking and psychiatric hospitalization were associated with adolescent-onset. CONCLUSIONS: In this large clinical sample of adolescents with BD, one-fifth reported childhood-onset BD. Correlates of childhood-onset generally aligned with those observed in the literature. Future research is warranted to better understand the genetic and environmental implications of high familial loading of psychopathology associated with childhood-onset, and to integrate age-related treatment and prevention strategies.

Factors Associated With Sleep Disturbance Amongst Youth With Bipolar Disorder.

Background: While sleep disturbances and their impact on functioning are well-established in adults with bipolar disorder (BD), little is known about this topic in youth. Objective: This study investigates the prevalence and correlates of sleep disturbance among youth with BD. Methods: The study included 103 youth (72 BD, 31 healthy controls [HC]), ages 14-20 years. Study measures included a semi-structured diagnostic interview and the Pittsburgh Sleep Quality Index (PSQI). PSQI yields a global score and 7 subscale scores. Analyses examined between group differences in PSQI scores, and correlates of PSQI within BD. Results: BD youth had significantly higher (worse) global sleep scores, and higher scores on 5/7 subscales (quality, latency, disturbance, sleep medication use, daytime dysfunction). In univariate analyses, poorer sleep quality was associated with higher lifetime and current depression severity, mixed mood state, self-reported affective lability, and borderline personality traits. Lifetime lithium treatment and euthymic mood state were associated with better sleep scores. In multivariate analyses, greater current depression severity and self-reported affective lability were most robustly associated with poor sleep quality. Conclusions: Converging with data from adults, present findings indicate greater sleep disturbance among youth with BD versus HC. Also convergent with adults with BD, mood disturbance, whether depression severity or emotional lability, comprised the predominant correlates of sleep disturbance among youth with BD. Future research is warranted to better understand the temporal association between sleep disturbance and its correlates in youth with BD. Relatedly, interventions that address both mood and sleep disturbances may help improve overall functioning.

Contexte: Bien que les perturbations du sommeil et leur effet sur le fonctionnement soient bien établies chez les adultes souffrant du trouble bipolaire (TB). Nous en savons peu à ce sujet chez les jeunes. Objectif: La présente étude investigue la prévalence et les corrélats de la perturbation du sommeil chez les jeunes souffrant du TB. Méthodes: L'étude comprenait 103 jeunes (72 TB, 31 témoins en santé [TS]), âgés de 14 à 20 ans. Les mesures de l'étude étaient notamment une entrevue diagnostique semi-structurée et l'Index de Qualité du Sommeil de Pittsburgh (IQSP). L'IQSP donne un score global et 7 scores de sous-échelles. Les analyses ont examiné entre les différences de groupes dans les scores IQSP, et les corrélats d'IQSP dans le TB. Résultats: Les jeunes souffrant de TB avaient des scores de sommeil globaux significativement plus élevés (pires), et des scores plus élevés à 5/7 sous-échelles (qualité, latence, perturbation, utilisation de médicament pour dormir, dysfonction diurne). Dans les analyses univariées, la mauvaise qualité du sommeil était associée à la gravité de la dépression de durée de vie et actuelle, à l'état de l'humeur mixte, à la labilité affective auto-déclarée, et aux traits de la personnalité limite. Le traitement au lithium de durée de vie et l'état de l'humeur euthymique étaient associés avec de meilleurs scores de sommeil. Dans les analyses multivariées, une plus grande gravité de la dépression actuelle et de la labilité affective auto-déclarée étaient très robustement associées à une mauvaise qualité du sommeil. Conclusions: Convergeant avec les données des adultes, les résultats actuels indiquent une plus grande perturbation du sommeil chez les jeunes souffrant du TB contre les TS. Convergeant également avec les adultes souffrant de TB, la perturbation de l'humeur, que ce soit par la gravité de la dépression ou la labilité émotionnelle, comprenait les corrélats prédominants de la perturbation du sommeil chez les jeunes souffrant de TB. La future recherche est justifiée pour mieux comprendre l'association temporelle entre la perturbation du sommeil et ses corrélats chez les jeunes souffrant du TB. Étant liées, les interventions qui abordent l'humeur et les perturbations du sommeil peuvent aider à améliorer le fonctionnement général.

MASTREE+: Time-series of plant reproductive effort from six continents.

Significant gaps remain in understanding the response of plant reproduction to environmental change. This is partly because measuring reproduction in long-lived plants requires direct observation over many years and such datasets have rarely been made publicly available. Here we introduce MASTREE+, a data set that collates reproductive time-series data from across the globe and makes these data freely available to the community. MASTREE+ includes 73,828 georeferenced observations of annual reproduction (e.g. seed and fruit counts) in perennial plant populations worldwide. These observations consist of 5971 population-level time-series from 974 species in 66 countries. The mean and median time-series length is 12.4 and 10 years respectively, and the data set includes 1122 series that extend over at least two decades (≥20 years of observations). For a subset of well-studied species, MASTREE+ includes extensive replication of time-series across geographical and climatic gradients. Here we describe the open-access data set, available as a.csv file, and we introduce an associated web-based app for data exploration. MASTREE+ will provide the basis for improved understanding of the response of long-lived plant reproduction to environmental change. Additionally, MASTREE+ will enable investigation of the ecology and evolution of reproductive strategies in perennial plants, and the role of plant reproduction as a driver of ecosystem dynamics.

Aún existen importantes vacíos en la comprensión de la respuesta reproductiva de las plantas al cambio medioambiental, en parte, porque su monitoreo en especies de plantas longevas requiere una observación directa durante muchos años, y estos conjuntos de datos rara vez han estado disponibles. Aquí presentamos a MASTREE +, una base de datos que recopila series de tiempo de la reproducción de las plantas de todo el planeta, poniendo a disposición estos datos de libre acceso para la comunidad científica. MASTREE + incluye 73.828 puntos de observación de la reproducción anual georreferenciados (ej. conteos de semillas y frutos) en poblaciones de plantas perennes en todo el mundo. Estas observaciones consisten en 5971 series temporales a nivel de población provenientes de 974 especies en 66 países. La mediana de la duración de las series de tiempo es de 10 años (media = 12.4 años) y el conjunto de datos incluye 1.122 series de al menos dos décadas (≥20 años de observaciones). Para un subconjunto de especies bien estudiadas, MASTREE +incluye un amplio conjunto de series temporales replicadas en gradientes geográficos y climáticos. Describimos el conjunto de datos de acceso abierto disponible como un archivo.csv y presentamos una aplicación web asociada para la exploración de datos. MASTREE+ proporcionará la base para mejorar la comprensión sobre la respuesta reproductiva de plantas longevas al cambio medioambiental. Además, MASTREE+ facilitará los avances en la investigación de la ecología y la evolución de las estrategias reproductivas en plantas perennes y el papel de la reproducción vegetal como determinante de la dinámica de ecosistemas.

Five-Phase Replication of Behavioral Health Integration in Pediatric Primary Care.

BACKGROUND AND OBJECTIVES: Because of severe and protracted shortages of pediatric behavioral health (BH) specialists, collaboration between pediatric primary care practitioners (PCPs) and BH specialists has the potential to increase access to BH services by expanding the BH workforce. In a previous study, we demonstrated that phase 1 of a behavioral health integration program (BHIP) enrolling 13 independently owned, community-based pediatric practices was associated with increased access to BH services while averting substantial cost increases and achieving high provider self-efficacy and professional satisfaction. The current study was undertaken to assess whether the initial access findings were replicated over 4 subsequent implementation phases and to explore the practicality of broad dissemination of the BHIP model. METHODS: After phase 1, BHIP was extended over 4 subsequent phases in a stepped-wedge design to 46 additional pediatric practices, for a total cohort of 59 practices (354 PCPs serving >300 000 patients). Program components comprised BH education and consultation and support for integrated practice transformation; these components facilitated on-site BH services by an interprofessional BH team. Outcomes were assessed quarterly, preprogram and postprogram launch. RESULTS: Across combined phases 1 to 5, BHIP was associated with increased primary care access to BH services (screening, psychotherapy, PCP BH visits, psychotropic prescribing) and performed well across 7 standard implementation outcome domains (acceptability, appropriateness, feasibility, fidelity, adoption, penetration, and sustainability). Emergency BH visits and attention-deficit/hyperactivity disorder prescribing were unchanged. CONCLUSIONS: These findings provide further support for the potential of integrated care to increase access to BH services in pediatric primary care.

GroEL is an immunodominant surface-exposed antigen of Rickettsia typhi.

Rickettsioses are neglected and emerging potentially fatal febrile diseases that are caused by obligate intracellular bacteria, rickettsiae. Rickettsia (R.) typhi and R. prowazekii constitute the typhus group (TG) of rickettsiae and are the causative agents of endemic and epidemic typhus, respectively. We recently generated a monoclonal antibody (BNI52) against R. typhi. Characterization of BNI52 revealed that it specifically recognizes TG rickettsiae but not the members of the spotted fever group (SFG) rickettsiae. We further show that BNI52 binds to protein fragments of ±30 kDa that are exposed on the bacterial surface and also present in the periplasmic space. These protein fragments apparently derive from the cytosolic GroEL protein of R. typhi and are also recognized by antibodies in the sera from patients and infected mice. Furthermore, BNI52 opsonizes the bacteria for the uptake by antigen presenting cells (APC), indicating a contribution of GroEL-specific antibodies to protective immunity. Finally, it is interesting that the GroEL protein belongs to 32 proteins that are differentially downregulated by R. typhi after passage through immunodeficient BALB/c CB17 SCID mice. This could be a hint that the rickettsia GroEL protein may have immunomodulatory properties as shown for the homologous protein from several other bacteria, too. Overall, the results of this study provide evidence that GroEL represents an immunodominant antigen of TG rickettsiae that is recognized by the humoral immune response against these pathogens and that may be interesting as a vaccine candidate. Apart from that, the BNI52 antibody represents a new tool for specific detection of TG rickettsiae in various diagnostic and experimental setups.

Prevalence and correlates of police contact amongst youth with bipolar disorder.

OBJECTIVES: While multiple studies have examined prevalence and correlates of police contact in adults with bipolar disorder (BD), literature on this topic in youth is sparse. We therefore examined the prevalence and correlates of police contact amongst youth with BD. METHODS: The study included 197 youth with BD and 127 healthy controls, ages 14-20 years. Semi-structured interviews were used to determine diagnoses, treatment and police contact. The Life Problems Inventory examined self-reported trait impulsivity and emotional dysregulation. Analyses examined demographic and clinical variables among youth with versus without lifetime police contact. Variables that were associated with police contact at p<0.1 in univariate analyses were evaluated in a logistic regression model. Specific reasons for police contact, determined based on chart review, are reported descriptively. RESULTS: Lifetime prevalence of police contact was significantly higher amongst youth with BD versus healthy controls (36% versus. 3%; χ 2 = 47.58, p =<0.001). In multivariate analyses, age of BD onset, living with both natural parents, comorbid substance use disorder and conduct disorder, and psychiatric hospitalization were associated with police contact. Common reasons for police contact included shoplifting/theft and suicidality/self-harm . LIMITATIONS: The cross-sectional and retrospective study design precludes conclusions regarding directionality of the observed associations and/or causal inferences. CONCLUSIONS: One third of youth with BD experienced police contact. Correlates generally aligned with those observed with adults. Future longitudinal research is warranted to understand distal and proximal antecedents of police contact, with the goal of developing strategies to prevent police contact, incarceration, and related consequences.

Five-Year Outcomes of Behavioral Health Integration in Pediatric Primary Care.

BACKGROUND AND OBJECTIVES: In the context of protracted shortages of pediatric behavioral health (BH) specialists, BH integration in pediatric primary care can increase access to BH services. The objectives of this study were to assess the structure and process of pediatric BH integration and outcomes in patient experience (access and quality), cost, and provider satisfaction. METHODS: In 2013, we launched a multicomponent, transdiagnostic integrated BH model (Behavioral Health Integration Program [BHIP]) in a large pediatric primary care network in Massachusetts. Study participants comprised the first 13 practices to enroll in BHIP (Phase-1). Phase-1 practices are distributed across Greater Boston, with ∼105 primary care practitioners serving ∼114 000 patients. Intervention components comprised in-depth BH education, on-demand psychiatric consultation, operational support for integrated practice transformation, and on-site clinical BH service. RESULTS: Over 5 years, BHIP was associated with increased practice-level BH integration (P < .001), psychotherapy (P < .001), and medical (P = .04) BH visits and guideline-congruent medication prescriptions for anxiety and depression (P = .05) and attention-deficit/hyperactivity disorder (P = .05). Total ambulatory BH spending increased by 8% in constant dollars over 5 years, mainly attributable to task-shifting from specialty to primary care. Although an initial decline in emergency BH visits from BHIP practices was not sustained, total emergency BH spending decreased by 19%. BHIP providers reported high BH self-efficacy and professional satisfaction from BHIP participation. CONCLUSIONS: Findings from this study suggest that integrating BH in the pediatric setting can increase access to quality BH services while engendering provider confidence and satisfaction and averting substantial increases in cost.

The Binary Toxin CDT of Clostridium difficile as a Tool for Intracellular Delivery of Bacterial Glucosyltransferase Domains.

Binary toxins are produced by several pathogenic bacteria. Examples are the C2 toxin from Clostridium botulinum, the iota toxin from Clostridium perfringens, and the CDT from Clostridium difficile. All these binary toxins have ADP-ribosyltransferases (ADPRT) as their enzymatically active component that modify monomeric actin in their target cells. The binary C2 toxin was intensively described as a tool for intracellular delivery of allogenic ADPRTs. Here, we firstly describe the binary toxin CDT from C. difficile as an effective tool for heterologous intracellular delivery. Even 60 kDa glucosyltransferase domains of large clostridial glucosyltransferases can be delivered into cells. The glucosyltransferase domains of five tested large clostridial glucosyltransferases were successfully introduced into cells as chimeric fusions to the CDTa adapter domain (CDTaN). Cell uptake was demonstrated by the analysis of cell morphology, cytoskeleton staining, and intracellular substrate glucosylation. The fusion toxins were functional only when the adapter domain of CDTa was N-terminally located, according to its native orientation. Thus, like other binary toxins, the CDTaN/b system can be used for standardized delivery systems not only for bacterial ADPRTs but also for a variety of bacterial glucosyltransferase domains.

Processing of Alcohol-Related Health Threat in At-Risk Drinkers: An Online Study of Gender-Related Self-Affirmation Effects.

AIMS: Defensiveness in response to threatening health information related to excessive alcohol consumption prevents appropriate behaviour change. Alternatively, self-affirmation may improve cognitive-affective processing of threatening information, thus contributing to successful self-regulation. METHODS: Effects of an online self-affirmation procedure were examined in at-risk university student drinkers. Participants were randomly assigned to a self-affirmation (writing about personally relevant values) or control task (writing about values relevant to another person) prior to presentation of alcohol-related threatening information. Assessment of prosocial feelings (e.g. 'love') after the task served as a manipulation check. Generic and personalized information regarding the link between alcohol use and cancer was presented, followed by assessment of perceived threat, message avoidance and derogation. Page dwell-times served as indirect indices of message engagement. Alcohol consumption and intention to drink less were assessed during the first online session and at 1-week and 1-month follow-up. RESULTS: Although self-affirmation resulted in higher levels of prosocial feelings immediately after the task, there was no effect on behaviour in the self-affirmation group. Effects on intention were moderated by gender, such that men showed lower intention immediately after self-affirmation, but this increased at 1-week follow-up. Women's intention to reduce consumption in the self-affirmation group reduced over time. Trend-level effects on indices of derogation and message acceptance were in the predicted direction only in men. CONCLUSION: It is feasible to perform self-affirmation procedures in an online environment with at-risk drinkers. However, use of internet-based procedures with this population may give rise to (gender-dependent) effects that are substantially diluted compared with lab-based experiments.