Neurobiological theories of bipolar spectrum disorder (BSD) propose that the emotional dysregulation characteristic of BSD stems from disrupted prefrontal control over subcortical limbic structures (Strakowski et al., 2012; Depue & Iacono, 1989). However, existing neuroimaging research on functional connectivity between frontal and limbic brain regions remains inconclusive, and is unable to adequately characterize global functional network dynamics. Graph theoretical analysis provides a framework for understanding the local and global connections of the brain and comparing these connections between groups (Sporns et al., 2004). The purpose of this study was to investigate resting state functional connectivity in individuals at low and high risk for BSD based on moderate versus high reward sensitivity, both with and without a BSD diagnosis, using graph theoretical network analysis. Results demonstrated decreased connectivity in a cognitive control region (dorsolateral prefrontal cortex), but increased connectivity of a brain region involved in the detection and processing of reward (bilateral orbitofrontal cortex), among participants at high risk for BSD. Participants with BSD showed increased inter-module connectivity of the dorsal anterior cingulate cortex (ACC). Reward sensitivity was associated with decreased global and local efficiency, and interacted with BSD risk group status to predict inter-module connectivity. Findings are discussed in relation to neurobiological theories of BSD. / Psychology

Little to no research has evaluated factors that explain the manifestation and maintenance of bipolar disorder-anxiety disorder (BD-AD) comorbidity. The literature has shown that disruption of social and circadian rhythms is associated with mood episode onset. This association is especially pronounced among individuals who have a sensitive behavioral approach system (BAS). Inasmuch as anxiety sensitivity and trait anxiety have been associated both with BD and social rhythm disruption, it is worth examining whether anxiety sensitivity and trait anxiety confer risk for mood episode onset. The aims of this project were to: 1) evaluate trait anxiety and anxiety sensitivity as predictors of social rhythm disruption and BD-AD comorbidity, 2) examine social rhythm disruption (SRD) as a mediator of the association between trait anxiety and anxiety sensitivity and BD-AD comorbidity status, and 3) explore behavioral approach system sensitivity in these processes as contributing to the vulnerability to BD-AD comorbidity. A sample of 156 young adults participated in a multi-wave study in which they completed diagnostic interviews, symptom measures, and life event interviews which assessed the occurrence of positive and negative life events and the degree of SRD following these events every six months. Partial support for the hypotheses was found. Initial anxiety sensitivity, but not trait anxiety, positively predicted SRD for rewarding life events and follow-up bipolar symptoms. Additionally, SRD following positive life events predicted increases in depressive symptoms, but not hypomanic symptoms. SRD mediated the relationship between anxiety sensitivity and depressive symptoms. Furthermore, this relationship was stronger for healthy controls than for those with a bipolar disorder (BD) diagnosis or at-risk for developing BD. Moreover, individuals with a comorbid BD-AD diagnosis tended to have greater social rhythm disruption following negative life events than BD only or healthy individuals. Unexpectedly, individuals with comorbid BD-AD did not exhibit greater anxiety sensitivity or trait anxiety. Overall, the results suggest that anxiety sensitivity is a factor that may help to identify individuals who are vulnerable to bipolar symptoms. Furthermore, SRD is a mechanism that may partially explain this relationship. / Psychology

Yes / Current NHS policy encourages an integrated approach to provision of mental and physical care for individuals with long term mental health problems. The 'PARTNERS2' complex intervention is designed to support individuals with psychosis in a primary care setting. The trial will evaluate the clinical and cost-effectiveness of the PARTNERS2 intervention. This is a cluster randomised controlled superiority trial comparing collaborative care (PARTNERS2) with usual care, with an internal pilot to assess feasibility. The setting will be primary care within four trial recruitment areas: Birmingham & Solihull, Cornwall, Plymouth, and Somerset. GP practices are randomised 1:1 to either (a) the PARTNERS2 intervention plus modified standard care ('intervention'); or (b) standard care only ('control'). PARTNERS2 is a flexible, general practice-based, person-centred, coaching-based intervention aimed at addressing mental health, physical health, and social care needs. Two hundred eligible individuals from 39 GP practices are taking part. They were recruited through identification from secondary and primary care databases. The primary hypothesis is quality of life (QOL). Secondary outcomes include: mental wellbeing, time use, recovery, and process of physical care. A process evaluation will assess fidelity of intervention delivery, test hypothesised mechanisms of action, and look for unintended consequences. An economic evaluation will estimate its cost-effectiveness. Intervention delivery and follow-up have been modified during the COVID-19 pandemic. The overarching aim is to establish the clinical and cost-effectiveness of the model for adults with a diagnosis of schizophrenia, bipolar, or other types of psychoses. / PARTNERS2 is funded by the National Institute for Health Research (NIHR) under its Programme Grant for Applied Research Programme (grant number: RP-PG- 200625). This research was also supported by the NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula at the Royal Devon and Exeter NHS Foundation Trust.

Involviert in Netzwerke für das episodische Gedächtnis sowie als Bestandteil des Hypothalamus und des limbischen Systems stellen sich die im Zwischenhirn gelegenen Mamillarkörper als Zielstruktur im Kontext affektiver Störungen dar. Bislang waren die Mamillarkörper diesbezüglich lediglich in einer postmortem durchgeführten Studie Gegenstand der Forschung; es liegen keine Untersuchungen mit Hilfe der 7 Tesla-Magnetresonanztomografie vor. Um diese neuen Möglichkeiten der in vivo-Volumetrie im Submillimeterbereich auszuschöpfen, wurde auf Grundlage einer farbkodierten Darstellung ein detaillierter Algorithmus entwickelt, der sich als Hauptergebnis der vorliegenden Arbeit als hoch reliabel erwies. In der vorliegenden Pilotstudie wurde darüber hinaus das Mamillarkörper-Volumen von 14 Patientinnen und Patienten mit einer Bipolaren Störung und 20 gesunden Kontrollpersonen anhand von hochaufgelösten T1-gewichteten MRT-Bildern bestimmt. Ein signifikanter Unterschied zwischen den beiden Gruppen konnte nicht nachgewiesen werden, ebenso kein Unterschied zwischen den Geschlechtern. Es konnte gezeigt werden, dass das Volumen der Mamillarkörper signifikant invers mit dem Alter der ProbandInnen korreliert. Des Weiteren wurde eine signifikante positive Korrelation mit dem Gesamthirnvolumen der ProbandInnen festgestellt. Krankheitsschwere und Episodenzahl hingegen hatten keinen Einfluss auf das Mamillarkörper-Volumen. Die Ergebnisse dieser Pilotstudie sollten anhand einer größeren Stichprobe überprüft werden.

Objectives: Adherence to psychotropic medication is poor among individuals with bipolar disorder (BD). To understand treatment experiences and associated adherence among these individuals, we developed a novel construct of Clinical Net Benefit (CNB) using psychiatric symptoms, adverse effects and overall functioning assessments. We tested whether adherence differed across classes of CNB, whether individuals transitioned between classes over time, and whether these transitions were differentially associated with adherence. Methods: Data come from individuals aged 18+ during five years of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Latent class analysis identified groups of CNB. Latent transition analysis determined probabilities of transitioning between classes over time. Adherence was defined as taking 75%+ of medications as prescribed. Associations between CNB and adherence were tested using multiple logistic regression adjusting for sociodemographic characteristics. Results: Five classes of CNB were identified during the first two years (high, moderately high, moderate, moderately low, low), and four classes (removing moderately high) during the last three years. Adherence did not differ across classes or time points. Medication regimens differed by class; those with higher CNB taking fewer medications had lower odds of adherence while those with lower CNB taking more medications had higher odds of adherence compared with monotherapy. Probability of transitioning from higher to lower CNB, and lower to higher CNB was greatest over time. Conclusions: CNB is heterogeneous in individuals treated for BD, and movement between classes is not uncommon. Understanding why individuals adhere despite suboptimal CNB may provide novel insights into aspects influencing adherence.

Bipolare Störungen zählen zu den schwerwiegendsten psychiatrischen Erkrankungen, die sich bereits in der Adoleszenz und im frühen Erwachsenenalter manifestieren, jedoch aufgrund ihrer komplexen Symptomatologie oftmals erst mit deutlich zeitlicher Verzögerung korrekt diagnostiziert werden. Auf Patientenseite ist die Erkrankung mit schweren psychosozialen Beeinträchtigungen, Einbußen in der gesundheitsbezogenen Lebensqualität und einem deutlich erhöhten Suizidrisiko verbunden; eine bipolar-spezifische Behandlung setzt zumeist zu spät ein. Forschungsbemühungen auf dem Gebiet der Früherkennung Bipolarer Störungen zeigen, dass Personen in möglichen Vorstufen der Erkrankung bereits unter subsyndromalen Symptomen und Funktionseinschränkungen leiden. Der Bedarf nach frühzeitiger und adäquater Behandlung in Risikostadien kann in der klinischen Versorgung bis dato nicht abgedeckt werden, da spezifische Versorgungsstrukturen für junge Menschen vor Manifestation einer schweren psychischen Störung sowie evidenzbasierte Therapieprogramme nicht existieren. Frühe präventive Maßnahmen können hilfesuchenden Personen mit Risikokonstellation für eine bipolare Entwicklung aber die Chance bieten, die bestehende Symptomatik zu reduzieren, die Funktionsfähigkeit zu verbessern und Bewältigungsstrategien aufzubauen. Weitere Ziele einer frühen Intervention stellen die Verzögerung oder Abschwächung von drohenden Krankheitsphasen beziehungsweise bestenfalls die Verhinderung der Konversion in eine manifeste Bipolare Störung dar. Die Studienlage zur Effektivität von adäquaten Behandlungsansätzen für Personen mit erhöhtem Risiko für eine bipolare Entwicklung ist ausgesprochen begrenzt. Für psychotherapeutische Verfahren gibt es erste Hinweise auf die Wirksamkeit familienbasierter Verfahren, wobei die Aussagekraft der Befunde aufgrund methodischer Limitationen eingeschränkt ist. Trotz indirekter Evidenz, welche sich aus dem Wirksamkeitsnachweis von kognitiver Verhaltenstherapie bei bipolaren Patienten mit wenigen Krankheitsphasen ableiten lässt, wurden kognitiv-verhaltenstherapeutische Ansätze hinsichtlich der Effektivität bei jungen, noch nicht erkrankten Personen mit erhöhtem Bipolar-Risiko bislang nicht systematisch untersucht. Ziel der vorliegenden Arbeit war es, die beschriebene Forschungslücke zu schließen, indem die Wirksamkeit einer spezifischen kognitiv-verhaltenstherapeutischen Gruppenintervention bei Hochrisikopersonen für die Entwicklung einer Bipolaren Störung untersucht wurde. Aufgrund des bisherigen unzureichenden Kenntnisstands erfolgte zunächst eine Charakterisierung der untersuchten Hochrisikoklientel für die Entwicklung Bipolarer Störungen hinsichtlich des psychosozialen Funktionsniveaus, des Stresserlebens sowie Ressourcen und Selbstmanagementfähigkeiten. Ausgehend von ersten praktischen Erfahrungen aus spezialisierten Früherkennungszentren wurde postuliert, dass die teilnehmenden Hochrisikopersonen bereits Einschränkungen im psychosozialen Funktionsvermögen zeigen und ein hohes Ausmaß an chronischem Stress erleben, während ihre Bewältigungsmöglichkeiten begrenzt erscheinen. In der vorliegenden Arbeit wurde die zentrale Frage untersucht, inwieweit mittels einer spezifischen kognitiv-verhaltenstherapeutischen Intervention eine günstigere Beeinflussung des psychosozialen Funktionsvermögens, des Stresserlebens sowie von Ressourcen und Selbstmanagementfähigkeiten der Studienteilnehmer gelingen kann als bei einer unstrukturierten Kontrollbedingung. Wenngleich in der Interventionsbedingung eine stärkere Verbesserung in den untersuchten Outcome-Maßen erwartet wurde, sollte sich durch die Teilnahme an den unstrukturierten Sitzungen der Kontrollbedingung ebenfalls ein gewisser therapeutischer Nutzen ergeben, der sich in der Verbesserung der beschriebenen Parameter widerspiegeln sollte. Schließlich wurde die Hypothese geprüft, inwieweit sich die zu erwartenden positiven Effekte im psychosozialen Funktionsvermögen sowie in den stressassoziierten Parametern in beiden Versuchsgruppen auch als stabil über einen Verlauf von sechs Monaten erweisen. Die vorliegende Arbeit war eingebettet in die multizentrische, DFG-geförderte, randomisierte und kontrollierte klinische EarlyCBT-Studie, in der die Wirksamkeit eines innovativen Gruppentherapieprogramms für Hochrisikopersonen für die Entwicklung einer Bipolaren Störung im Vergleich zu unstrukturierten Sitzungen untersucht wird. Das Vorliegen einer positiven Familienanamnese für affektive und/oder schizoaffektive Störungen, gepaart mit zunehmenden Einschränkungen in der psychosozialen Funktionsfähigkeit und subsyndromaler affektiver Symptomatik, stellten die wesentlichen Einschlusskriterien zur Studienteilnahme dar. Die Stichprobe umfasste 74 hilfesuchende Probanden im Alter zwischen 15 und 30 Jahren, welche zu drei Erhebungszeitpunkten (Baseline, am Ende der Intervention und sechs Monate nach Beginn der Intervention) untersucht wurden. Das eigens für die Studie konzipierte Behandlungsmanual enthielt neben Elementen der kognitiven Verhaltenstherapie auch Achtsamkeits- und Entspannungsübungen sowie Interventionen zum Stressmanagement. Primäre Outcomes der vorliegenden Arbeit waren das psychosoziale Funktionsvermögen, das Erleben von chronischem Stress sowie die Ressourcen und Selbstmanagementfähigkeiten der Teilnehmer. Veränderungen im psychosozialen Funktionsniveau der Hochrisikopersonen wurden mittels eines semistrukturierten Interviews erhoben, während die Effektivität der therapeutischen Intervention in Bezug auf stressassoziierte Parameter anhand von Selbstreportfragebögen erfasst wurde. Die Auswertungen basierten auf dem intention-to-treat (ITT)-Ansatz; fehlende Werte wurden anhand des Expectation-Maximization (EM)-Algorithmus geschätzt. Als statistische Verfahren für die Prüfung der dargestellten Hypothesen kamen Varianzanalysen (einfaktoriell, mit und ohne Messwiederholung) zum Einsatz. Zur systematischen Analyse von Dropouts erfolgte eine Deskription der Zeitpunkte und Gründe für die Ausfälle sowie eine Prüfung von Unterschieden zwischen Probanden der Dropout-Gruppe und den vollständig an der Studie teilgenommenen Probanden mittels 2-Tests und einfaktoriellen Varianzanalysen. In der vorliegenden Studie konnte hypothesengemäß gezeigt werden, dass die untersuchten Hochrisikopersonen bereits deutliche psychosoziale Einschränkungen aufwiesen, chronischen Stress erlebten und nur über begrenzte Ressourcen und Strategien zum Umgang mit Stress und Belastungen verfügten. Am Ende der Intervention zeigten sich in der Gesamtstichprobe erwartungsgemäß signifikante Verbesserungen hinsichtlich des Stresserlebens sowie der Ressourcen und Selbstmanagementfähigkeiten. Entgegen der Hypothese erbrachten die Auswertungen zum psychosozialen Funktionsvermögen in der Gesamtstichprobe numerische, aber keine signifikanten Effekte am Ende der Intervention. Zwischen der Interventions- und Kontrollbedingung konnten entgegen den Hypothesen am Ende der Intervention keine bedeutsamen Unterschiede in den geprüften Zielgrößen psychosoziales Funktionsvermögen, Stresserleben und Ressourcen und Selbstmanagementfähigkeiten festgestellt werden. Sechs Monate nach Beginn der Gruppenteilnahme zeigten sich im Einklang mit den Hypothesen in beiden Versuchsgruppen signifikante Verbesserungen in den drei untersuchten Parametern. Die im Rahmen der vorliegenden Studie eingesetzte, spezifische kognitivverhaltenstherapeutische Gruppenintervention bietet Personen mit Hochrisikostatus für die Entwicklung einer Bipolaren Störung einen guten Einstieg in die psychotherapeutische Behandlung. Um der komplexen Symptomatologie, der häufigen Komorbidität sowie den individuellen Bedürfnissen der jungen, (noch) nicht bipolar erkrankten Hochrisikopersonen besser gerecht werden zu können, erscheint ein kombinierter, über einen längeren Zeitraum angelegter psychotherapeutischer Ansatz im Einzel- und Gruppensetting auch unter Einbeziehung der neuen Medien sinnvoll, dessen Entwicklung und Evidenzprüfung Ziel weiterer Forschungsbemühungen sein sollte. Eine zeitnahe Implementierung von präventiven, bedarfsgerechten Interventionsstrategien in die klinische Versorgung erscheint vor dem Hintergrund der bereits in Risikostadien Bipolarer Störungen existierenden erheblichen psychosozialen Belastungen, unter denen die Betroffenen leiden, erstrebenswert.

Background: Adolescence and young adulthood are particularly vulnerable periods for the development of mental health disorders, including bipolar disorder (BD). Mental health screening at universities could aid in the early identification of particularly at- risk individuals, with the long-term aim of providing early treatment interventions to improve clinical outcomes. However, further research into the identification of appropriate behavioral and biological markers for vulnerability to psychiatric disorders – as well as into the acceptability and efficacy of mental health screening - is warranted. Methods: Young adults were recruited via an already existing Internet-based mental health screening survey of undergraduate students at the University of Oxford. In Study 1, qualitative interviews of young adults with and without previous mental health problems were conducted to assess the acceptability and efficacy of mental health screening within a university setting. In Studies 2-5 we explored the hypotheses of altered emotional decision-making, reward processing and neurostructural integrity as behavioral and neurobiological markers for vulnerability to bipolar disorder via the study of young adults with a common bipolar phenotype (BPP) - some of whom meet diagnostic criteria for bipolar II or not-otherwise-specified disorder (BD II/NOS). To that end, we employed a diverse range of methodologies: alcohol challenge (Study 2); neuropsychological task performance (Study 3); functional magnetic resonance imaging (fMRI; Study 4); diffusion tensor imaging (DTI) and voxel-based morphometry (VBM; Study 5). Results: Findings from Study 1 suggest that young adults are willing to participate in mental health screening within a university setting, and that such screening may be used to offer subsequent treatment interventions. Taken together, findings from Studies 2 and 4 suggest a general blunted reward response among unmedicated young adults at increased risk for BD during euthymia, and additionally suggest pathophysiological similarities between BD and alcohol use disorders (AUDs) that may provide a causal link between the elevated co-occurrence rates of the two disorders. Finally, findings from Study 5 suggest widespread white matter microstructural alterations – which are likely to be neurodevelopmental in origin – among antipsychotic- and mood-stabilizer naïve young adults with BD II/NOS. Conclusions: These data support the hypothesis of neurodevelopmental alterations identifiable prior to significant clinical impairment among young adults at increased risk of – or already meeting DSM-IV criteria for – bipolar disorder. They also suggest that young adults in higher education are willing to participate in mental health screening. Future studies should aim to identify more specific markers for individual disorders such as BD.

Le trouble bipolaire est un trouble de l’humeur chronique marqué par l'alternance de dépressions, d'épisodes maniaques et de rémissions. La neuroimagerie permet l'étude de l'anatomie et du fonctionnement cérébral des patients bipolaires. Des études existantes avaient ainsi retrouvé des anomalies dans les aires du traitement des émotions chez les patients bipolaires. L'IRM anatomique avait permis de mettre en évidence certaines modifications morphométriques des régions associées (amygdale, gyrus cingulaire, thalamus) ainsi que des hypersignaux de la substance blanche. En imagerie fonctionnelle, lors du traitement d'informations émotionnelles, les patients bipolaires présentaient une hyperactivation d'un réseau ventro-limbique et une hypoactivation d'un réseau dorsal cognitif. Nous avons tout d’abord utilisé l'IRM de diffusion pour étudier la connectivité anatomique dans le trouble bipolaire. Dans une première étude, nous avons reconstruit le faisceau uncine, reliant le réseau dorsal cognitif au réseau ventro-limbique, chez 16 patients bipolaires et 16 contrôles en utilisant les techniques de suivi de fibres dites de tractographie exploitant les données d'IRM de diffusion. Les patients bipolaires avaient plus de fibres reconstruites dans le faisceau uncine gauche. Dans le même échantillon, en étudiant l'anisotropie du processus de diffusion dans tout le cerveau, nous avons également identifié une augmentation diffuse de la connectivité anatomique chez les patients. Enfin, nous avons réalisé une étude multicentrique internationale d’IRM de diffusion incluant 118 patients 10 bipolaires et 86 contrôles. Nous avons alors montré une diminution significative de l'anisotropie le long du corps calleux, du cingulum gauche et du faisceau arqué gauche chez les patients. Les patients bipolaires avec caractéristiques psychotiques avaient une anisotropie du corps calleux plus basse que les patients sans caractéristiques psychotiques. Dans une seconde partie de notre travail, nous avons étudié l'interférence produite par une information émotionnelle sur un traitement cognitif chez les patients. Nous avons comparé 17 patients bipolaires euthymiques à 17 sujets contrôles en IRM fonctionnelle lors d'un paradigme de type go/no-go émotionnel. Notre étude apporte des arguments tendant à démontrer l'existence d'une altération de la modulation par une information émotionnelle d’un traitement cognitif chez les patients avec une hyperactivation d’un réseau fronto-cingulo-striatal. Enfin, nous avons réalisé une synthèse quantitative de la littérature s'intéressant à l'imagerie anatomique, fonctionnelle et de diffusion dans le trouble bipolaire. Nous avons retrouvé chez les patients une diminution d’activation dans les tâches émotionnelles et une diminution du volume de substance grise dans des régions frontales et dorsales, tandis que sont présentes des hyperactivations dans des régions limbiques. L'ensemble de ces résultats a permis de préciser le modèle neural du trouble bipolaire avec les anomalies les plus importantes au niveau des zones impliquées dans la régulation automatique des émotions. Nos travaux ont significativement contribué à faire envisager le trouble bipolaire comme lié à des anomalies de la connectivité préfronto-limbique. Ils ouvrent aussi des perspectives de travail pour progresser dans la compréhension de sa physiopathologie. En particulier, le suivi prospectif d'une cohorte de patients permettra d'évaluer l'influence de l'évolution de la maladie bipolaire sur la structure cérébrale. Les techniques récentes d'IRM de diffusion permettront de mieux comprendre la signification physiopathologique des anomalies identifiées. Enfin, la reconceptualisation dimensionnelle proposée par le DSM-5 et le NIMH permettra probablement d'identifier des dimensions plus pertinentes que les catégories diagnostiques actuelles. / [Summary made by the web site Reverso] The bipolar disorder is a confusion of the chronic humor marked by the alternation of depressions, manic episodes and forgiveness. The neuroimaging allows the study of the anatomy and the cerebral functioning of the bipolar patients. Existing studies had so found anomalies in the areas of the treatment of the feelings at the bipolar patients. The anatomical MRI had allowed to highlight certain morphométriques modifications of the regions associated (tonsil, gyrus cingulaire, thalamus) as well as hypersignals of the white material. In functional imaging, during the processing of emotional information, the bipolar patients presented a hyperactivation of a network ventro-limbique and a hypoactivation of a cognitive dorsal network. We used first of all the MRI of distribution to study the anatomical connectivity in the bipolar disorder. In a first study, we reconstructed the beam uncine, connecting(binding) the cognitive dorsal network with the ventro-limbique network, at 16 bipolar patients and 16 controls by using the techniques of follow-up of said fibers of tractographie exploiting the data of MRI of distribution. The bipolar patients had more fibers reconstructed in the beam left uncine. In the same sample, by studying the anisotropie of the process of distribution in all the brain, we also identified a diffuse increase of the anatomical connectivity at the patients. In the same sample, by studying the anisotropie of the process of distribution in all the brain, we also identified a diffuse increase of the anatomical connectivity at the patients. Finally, we realized a study international multicentrique of MRI of distribution including 118 bipolar patients 10 and 86 controls. We then showed a significant decrease of the anisotropie along the corpus callusum, along the left(awkward) cingulum and along the left hooked beam at the patients. The bipolar patients with psychotic characteristics had an anisotropie of the corpus callusum lower than the patients without psychotic characteristics. In a second part of our work, we studied the interference produced by an emotional information about a cognitive treatment at the patients. We compared 17 bipolar patients euthymiques on 17 subjects controls in functional MRI during one paradigm of type emotional go / no-go. Our study brings arguments tending to demonstrate the existence of a change of the modulation by an emotional information of a cognitive treatment at the patients with a hyperactivation of a fronto-cingulo-striatal network. Finally, we realized a quantitative synthesis of the literature being interested in the anatomical, functional imaging and of distribution in the bipolar disorder. We found at the patient's a decrease of activation in the emotional tasks and a decrease of the volume of grey matter in frontal and dorsal regions, whereas are present hyperactivations in limbiques regions. All these results allowed to specify the neural model of the bipolar disorder with the most important anomalies at the level of zones implied in the self-regulation of the feelings. Our works significantly contributed to make envisage the bipolar disorder as bound to anomalies of the préfronto-limbique connectivity. They also open working perspectives to progress in the understanding of its physiopathology. In particular, the forward-looking follow-up of patients' troop will allow to estimate the influence of the evolution of the bipolar disease on the intellectual structure. The recent techniques of MRI of distribution will allow to understand better the physiopathological meaning of the identified anomalies. Finally, the dimensional reconceptualisation proposed by the DSM-5 and the NIMH will probably allow to identify dimensions more relevant than the current diagnostic categories.

O presente estudo descreveu as manifestações psicopatológicas do transtorno bipolar de início precoce, através da avaliação clínica de uma amostra de pacientes provenientes de um programa terciário de atendimento aos transtornos do humor. Os objetivos do estudo foram: (1) determinar o fluxo de atendimentos dos pacientes no programa, por meio do registro eletrônico dos casos ingressos, no período de janeiro de 2003 a dezembro de 2012; e, para a amostra final de pacientes bipolares (2) descrever as variáveis demográficas e antecedentes familiares de transtornos mentais; (3) estabelecer o intervalo de tempo entre os primeiros sintomas psicopatológicos e a procura por atendimento no programa; (4) investigar a frequência das comorbidades psiquiátricas e das comorbidades médicas gerais; (5) estimar a distribuição dos sintomas depressivos e maniformes e dos tipos clínicos de transtorno bipolar. A amostra inicial foi de 814 sujeitos, com idade entre 02 e 17 anos, encaminhados de serviços públicos e privados, agendados consecutivamente para a triagem. Os sujeitos elegíveis para a avaliação completa apresentaram um dos seguintes critérios diagnósticos: (a) diagnóstico provisório de transtornos do humor; ou (b) outros transtornos mentais mais a presença de oscilações do humor. Na avaliação completa, todas as informações coletadas foram avaliadas pela equipe do programa e o diagnóstico inicial foi realizado pelo método de melhor estimativa com base nos critérios do DSM-IV. No seguimento longitudinal, os pacientes foram atendidos mensalmente para tratamento clínico e confirmação diagnóstica. Nos resultados, a maioria dos 814 sujeitos era do sexo masculino (60%), brancos (83,5%) e com média de idade de 12,3 ± 3,8 anos, na triagem. Cerca de um terço do total de sujeitos não foi elegível para o programa. Dos pacientes restantes, após seguimento de 1,7 ± 1,7 anos, foi possível diagnosticar um terço deles como bipolar enquanto o último terço não preencheu os critérios para qualquer tipo de transtorno bipolar. Entre os pacientes que mudaram o diagnóstico inicial, durante o seguimento, menos de 10% eram falso positivos (diagnóstico bipolar para não bipolar) e cerca de 25% eram falso negativos (diagnóstico não bipolar para bipolar). 181 pacientes compuseram a amostra final de pacientes bipolares. 64,6% era bipolar tipo I, um em quatro tinha ao menos um dos pais bipolares ou deprimidos, 82,3% já haviam apresentado ao menos um episódio de depressão e 18,8% tinham pelo menos uma tentativa de suicídio. A média de tempo entre os primeiros sintomas psicopatológicos até o primeiro contato no programa foi de 4 anos. 50,5% tiveram o primeiro episódio do humor em idade escolar, sendo o tipo depressivo o mais frequente (47%). Dentre os pacientes que tiveram como primeiro episódio do humor os tipos depressivo, misto ou inespecífico, o intervalo de tempo para apresentar o primeiro episódio maniforme foi de 1 a 2 anos. As comorbidades psiquiátricas e médicas gerais ocorreram em, no mínimo, metade da amostra. Os pacientes foram altamente sintomáticos. Em relação aos sintomas depressivos, a grande maioria (>= 70%) apresentou tristeza, irritabilidade, ideias mórbidas, lentificação psicomotora, alterações da fala e do sono. Quanto aos sintomas maniformes, os sintomas mais frequentes (>= 70%) foram agitação psicomotora, explosão de raiva, aumento de energia, irritabilidade, euforia, distratibilidade, aceleração dos pensamentos, grandiosidade, logorréia e alterações do sono. Desse modo, o estudo mostra a importância do seguimento longitudinal não apenas das crianças e adolescentes, inicialmente diagnosticados como bipolares, mas também daqueles com oscilações do humor. A descrição de uma amostra de pacientes bipolares fora dos Estados Unidos pode ampliar as discussões atuais sobre as manifestações clínicas do transtorno bipolar de início precoce e incentivar a realização de trabalhos semelhantes em outros países / This study described the psychopathological manifestations of early onset bipolar disorder, using clinical assessment of a sample of patients from a tertiary care program for mood disorders. The study\'s objectives were: (1) to determine, based on electronic records of cases treated between January 2003 and December 2012, the flow of care of patients included in the program, from first contact to final diagnosis; and the final sample of bipolar patients (2) to describe demographic variables and family history of patients with psychiatric disorders; (3) to establish the time interval between the first psychopathological symptoms and the search for care in the program; (4) to investigate the frequency of psychiatric comorbidities and general medical comorbidities; (5) to estimate the distribution of depressive and manic symptoms and the clinical types of bipolar disorder. The initial sample included 814 subjects, aged 2-17 years, referred from public and private services, and scheduled consecutively for screening. Subjects eligible for complete evaluation showed one of the following diagnostic criteria: (a) provisional diagnosis of mood disorders; or (b) other mental disorders, plus the presence of mood disturbances. As part of a full evaluation, the program team analyzed the data, and an initial diagnosis was made according to the best-estimate method based on DSM-IV criteria. In the longitudinal follow-up, patients were seen monthly for clinical treatment and diagnostic confirmation. During screening, most of the 814 subjects were male (60%), white (83.5%), and had a mean age of 12.3 ± 3.8 years. About a third of the subjects were not eligible for the program. Of the remaining patients, after a mean follow-up of 1.7 ± 1.7 years, it was possible to diagnose a third of the sample as bipolar while the last third did not meet the criteria for any type of bipolar disorder. Among the patients who changed the initial diagnosis at follow-up, less than 10% were false positive (diagnosis changed from bipolar to not bipolar) and approximately 25% were false negative (diagnosis changed from not bipolar to bipolar). 181 patients comprised the final sample of bipolar patients. 64.6% were bipolar type I, one in four had at least one bipolar or depressed parent, 82.3% had already presented at least one episode of depression, and 18.8% had attempted suicide. The average time between the first psychopathological symptoms and the first referral to the program was 4 years. 50.5% had their first mood episode while in school age, more often of depressive type (47%). Patients, who had their first mood episode of depressive, mixed or non-specific types, presented their first manic episode 1-2 years after. General medical and psychiatric comorbidities occurred in at least half of the sample. Patients were highly symptomatic. In regard to depressive symptoms, the vast majority (>= 70%) had sadness, irritability, morbid ideas, psychomotor retardation, speech and sleep disorders. As for manic symptoms, the most common symptoms (>= 70%) were psychomotor agitation, outburst of anger, increased energy, irritability, euphoria, distractibility, racing thoughts, grandiosity, logorrhea and sleep disturbances. Thus, the study shows the importance of longitudinal follow-up not only of children and adolescents initially diagnosed as bipolar, but also of those with mood disturbances. The description of a sample of bipolar patients outside the United States may extend the current discussions about the clinical manifestations of early onset bipolar disorder and encourage the pursuit of similar studies in other countries

Os episódios mistos em pacientes portadores de Transtorno Bipolar são descritos freqüentemente como sendo mais graves que os episódios de mania aguda. Além disso, muitos trabalhos na literatura descrevem os pacientes com TB com história de episódios mistos, como um grupo distinto clínica e demograficamente do grupo com apresentação apenas de episódios de mania pura. Os objetivos deste estudo foram comparar clinicamente episódios agudos mistos versus episódios de mania pura e comparar clínica e demograficamente pacientes que apresentaram em algum momento do seguimento clínico pelo menos um episódio misto com pacientes que apresentaram apenas mania pura. Vinte pacientes apresentando episodio de mania pura foram comparados a 29 pacientes em estado misto de acordo com os critérios do DSM-IV. Não houve diferença na duração destes episódios, presença de hospitalização e tentativas de suicídio. Na comparação dos dados demográficos, não encontramos diferenças na idade, distribuição entre os sexos, classe sócio-econômica, estado civil e anos de escolaridade. Em relação ao curso, nosso estudo mostrou que pacientes com pelo menos um estado misto apresentaram maior freqüência de tentativas de suicídio e de episódios, mais comorbidades e idade de início da doença mais precoce. Foi realizada analise multivariada através de regressão logística para a identificação das variáveis clinicas que melhor distinguem um grupo do outro. Esta analise mostrou que a presença de comorbidades e de tentativas de suicídio foram as variáveis identificadas que mais fortemente estão associadas ao diagnóstico de pacientes com estado misto. / Mixed episodes in patients with bipolar disorder (BD) have been frequently described as more severe than acute manic episodes. Moreover, many papers in the literature have described the patients with BD with history of mixed episodes as a group that is clinically and demographically distinct from the group with clinical presentation of pure manic episodes. The purposes of this study were to compare clinically acute mixed episodes with pure manic episodes and compare clinically and demographically patients that present in any moment of their clinical follow-up at least one mixed episode with patients that present only pure mania. Twenty patients with pure manic episode were compared to 29 patients with mixed episodes according to DSM-IV criteria. There were no differences in episodes duration, presence of hospitalization and suicide attempts. Comparing the demographic data, we did not find differences in age, gender distribution, socio-economic status, marital status and years of education. Regarding the course of illness, our study showed that patients with at least one mixed state presented higher frequency of suicide attempts, younger age of illness onset, more co-morbidities, and higher index of impulsivity. A multi-variate analysis was performed with logistic regression to identify the clinical variables that better distinguish one group from the other. This analysis showed that the presence of co-morbidities and suicide attempts were the identified variables that are strongly associated with the diagnosis of patients with mixed state.