First episode schizophrenia and schizoaffective disorder: A psychiatric nosology

A nosological issue that has yet to be resolved relates to the diagnostic and clinical overlap of schizophrenia and schizoaffective disorder. Thus, the aim of this study was to compare, within a treated epidemiological cohort of first episode patients, the clinical characteristics of patients with schizophrenia (FES) or schizoaffective disorder (FESA). Medical fi le audit methodology was employed to collect information on 704 first episode psychosis patients (FEP), among which 283 patients had a fi nal diagnosis of FES and 64 patients with a fi nal diagnosis of FESA. These patients were treated at the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia. Patients with FES were signifi cantly more likely to have a longer prodrome (P = .020), longer duration of untreated psychosis (P < .001), and earlier age of onset (P = .004) compared to FESA. At service entry, FESA patients had more severe levels of psychopathology (P = .020), which was due to the presence of manic symptoms (P < .001); consequently, requiring a greater number of inpatient admissions (P = .017). At discharge, depressive symptoms were more severe in those with FESA (P = .011). There are signifi cant differences in the phenomenology of schizophrenia and schizoaffective disorder during early illness course; supporting the notion that these are two discernable disorders.

Prevention of major depression in complex medically ill patients: preliminary results from a randomized, controlled trial.

BACKGROUND: Depression is highly prevalent in patients with physical illness and is associated with a diminished quality of life and poorer medical outcomes. OBJECTIVE: The authors evaluated whether a multifaceted intervention conducted by a psychiatric consultation-liaison nurse could reduce the incidence of major depression in rheumatology inpatients and diabetes outpatients with a high level of case complexity. METHOD: Of 247 randomized patients, the authors identified 100 patients with a high level of case complexity at baseline and without major depression (65 rheumatology and 35 diabetes patients). Patients were randomized to usual care (N=53) or to a nurse-led intervention (N=47). Main outcomes were the incidence of major depression and severity of depressive symptoms during a 1-year follow-up, based on quarterly assessments with standardized psychiatric interviews. RESULTS: The incidence of major depression was 63% in usual-care patients and 36% in the intervention group. Effects of intervention on depressive symptoms were observed in outpatients with diabetes but not in rheumatology inpatients. CONCLUSION: These preliminary results based on subgroup analysis suggest that a multifaceted nurse-led intervention may prevent the occurrence of major depression in complex medically ill patients and reduce depressive symptoms in diabetes outpatients.

Genetics of narcolepsy and other major sleep disorders.

One third of the population is affected by a sleep disorder with a major social, medical, and economic impact. Although very little is known about the genetics of normal sleep, familial and twin studies indicate an important influence of genetic factors. Most sleep disorders run in families and in several of them the contribution of genetic factors is increasingly recognised. With recent advances in the genetics of narcolepsy and the role of the hypocretin/orexin system, the possibility that other gene defects may contribute to the pathophysiology of major sleep disorders is worth indepth investigation.

Redox dysregulation in the pathophysiology of schizophrenia and bipolar disorder: insights from animal models.

Abstract Significance: Schizophrenia (SZ) and bipolar disorder (BD) are classified as two distinct diseases. However, accumulating evidence shows that both disorders share genetic, pathological, and epidemiological characteristics. Based on genetic and functional findings, redox dysregulation due to an imbalance between pro-oxidants and antioxidant defense mechanisms has been proposed as a risk factor contributing to their pathophysiology. Recent Advances: Altered antioxidant systems and signs of increased oxidative stress are observed in peripheral tissues and brains of SZ and BD patients, including abnormal prefrontal levels of glutathione (GSH), the major cellular redox regulator and antioxidant. Here we review experimental data from rodent models demonstrating that permanent as well as transient GSH deficit results in behavioral, morphological, electrophysiological, and neurochemical alterations analogous to pathologies observed in patients. Mice with GSH deficit display increased stress reactivity, altered social behavior, impaired prepulse inhibition, and exaggerated locomotor responses to psychostimulant injection. These behavioral changes are accompanied by N-methyl-D-aspartate receptor hypofunction, elevated glutamate levels, impairment of parvalbumin GABA interneurons, abnormal neuronal synchronization, altered dopamine neurotransmission, and deficient myelination. Critical Issues: Treatment with the GSH precursor and antioxidant N-acetylcysteine normalizes some of those deficits in mice, but also improves SZ and BD symptoms when given as adjunct to antipsychotic medication. Future Directions: These data demonstrate the usefulness of GSH-deficient rodent models to identify the mechanisms by which a redox imbalance could contribute to the development of SZ and BD pathophysiologies, and to develop novel therapeutic approaches based on antioxidant and redox regulator compounds. Antioxid. Redox Signal. 18, 1428-1443.

Genome-wide association study of co-occurring anxiety in major depression.

OBJECTIVES: Co-morbidity between depression and anxiety disorders is common. In this study we define a quantitative measure of anxiety by summating four anxiety items from the SCAN interview in a large collection of major depression (MDD) cases to identify genes contributing to this complex phenotype. METHODS: A total of 1522 MDD cases dichotomised according to those with at least one anxiety item scored (n = 1080) and those without anxiety (n = 442) were analysed, and also compared to 1588 healthy controls at a genome-wide level, to identify genes that may contribute to anxiety in MDD. RESULTS: For the quantitative trait, suggestive evidence of association was detected for two SNPs, and for the dichotomous anxiety present/absent ratings for three SNPs at genome-wide level. In the genome-wide analysis of MDD cases with co-morbid anxiety and healthy controls, two SNPs attained P values of < 5 × 10⁻⁶. Analysing candidate genes, P values ≤ 0.0005 were found with three SNPs for the quantitative trait and three SNPs for the dichotomous trait. CONCLUSIONS: This study provides an initial genome-wide assessment of possible genetic contribution to anxiety in MDD. Although suggestive evidence of association was found for several SNPs, our findings suggest that there are no common variants strongly associated with anxious depression.

“IF ONLY I COULD�? ~ “THERE IS ALWAYS A LOOPHOLE"? Hope and hopelessness experienced by the severely depressive and nondepressive

The aim of this research was to structure a conceptual model of hope and hopelessness based on dictionary definitions, and to verify this model on the basis of the experiences of the severely depressive and non-depressive elderly. This research has produced a substantive theory of hope and hopelessness which is based on the experiences of the depressive and non-depressive elderly, and on the concept analysis of hope and hopelessness based on English dictionary definitions. The patients who participated in the research were 65 years old and older men and women (n=22) who had been admitted to a psychiatric hospital because of major depression, and another group: the non-depressive elderly (n=21), who were recruited from the pensioners’ clubs. The data were collected in interviews using the Clinical Assessment Tool, developed by Farran, Salloway and Clark (1990) and Farran, Wilken and Popovich (1992), and it produced 553 pages of written text, which were analysed using the ATLAS/ti programme. ATLAS/ti is a tool for analysing qualitative data and is based on Grounded Theory. The medical and nursing records of the depressive elderly completed source triangulation. The concept analysis of hope and hopelessness was made on the basis of the definitions of English dictionaries (n=103), using semantic analysis and the ATLAS/ti programme. The most important hope-promoting factors were human relations, health and managing in everyday living. Autonomy, self-determination and feeling of security were highly appreciated among the elderly. Hopelessness, on the other hand, was most often associated with the same factors: human relations, health and everyday living. Especially, losses of significant others were experienced as strongly hope-diminishing. Old age had brought freedom from duties concerning others, but now, when you finally had an opportunity to enjoy yourself, you could not accomplish anything; you were clasped in the arms of total inability, depression had come. The most obvious difference in the life course of the depressive and nondepressive elderly was the abundance of traumatic experiences in the childhood and youth of the depressive elderly. The continuous circulation of fearful thoughts was almost touchable, and suicidality was described in connection with these thoughts. You were afraid to be awake and also to go to sleep. Managing day by day was the goal. The research produced the Basic Social Process (BSP) of hope: achieving - maintaining - losing, which expresses a continuous balancing between Being without and Being with. The importance of the object of hope was combined with the amount of hope and disappointment. The process of approaching defined the realisation of hope and the process of withdrawal that of losing. Joy and security versus grief and insecurity defined the Being with and Being without. Two core categories were found. The first one “If only I could�? reflects lack of energy, lack of knowledge, lack of courage and lack of ability. The other one “There is always a loophole�? reflects deliberate tracing of possibilities and the belief in finding solutions, and managing.

Behavioral phenotyping of glutathione-deficient mice: Relevance to schizophrenia and bipolar disorder.

Redox-dysregulation represents a common pathogenic mechanism in schizophrenia (SZ) and bipolar disorder (BP). It may in part arise from a genetically compromised synthesis of glutathione (GSH), the major cellular antioxidant and redox-regulator. Allelic variants of the genes coding for the rate-limiting GSH synthesizing enzyme glutamate-cysteine-ligase modifier (GCLM) and/or catalytic (GCLC) subunit have been associated with SZ and BP. Using mice knockout (KO) for GCLM we have previously shown that impaired GSH synthesis is associated with morphological, functional and neurochemical anomalies similar to those in patients. Here we asked whether GSH deficit is also associated with SZ- and BP-relevant behavioral and cognitive anomalies. Accordingly, we subjected young adult GCLM-wildtype (WT), heterozygous and KO males to a battery of standard tests. Compared to WT, GCLM-KO mice displayed hyperlocomotion in the open field and forced swim test but normal activity in the home cage, suggesting that hyperlocomotion was selective to environmental novelty and mildly stressful situations. While spatial working memory and latent inhibition remained unaffected, KO mice showed a potentiated hyperlocomotor response to an acute amphetamine injection, impaired sensorymotor gating in the form of prepulse inhibition and altered social behavior compared to WT. These anomalies resemble important aspects of both SZ and the manic component of BP. As such our data support the notion that redox-dysregulation due to GSH deficit is implicated in both disorders. Moreover, our data propose the GCLM-KO mouse as a valuable model to study the behavioral and cognitive consequences of redox dysregulation in the context of psychiatric disease.

Combined analysis of grey matter voxel-based morphometry and white matter tract-based spatial statistics in late-life bipolar disorder.

Background: Previous magnetic resonance imaging (MRI) studies in young patients with bipolar disorder indicated the presence of grey matter concentration changes as well as microstructural alterations in white matter in various neocortical areas and the corpus callosum. Whether these structural changes are also present in elderly patients with bipolar disorder with long-lasting clinical evolution remains unclear. Methods: We performed a prospective MRI study of consecutive elderly, euthymic patients with bipolar disorder and healthy, elderly controls. We conducted a voxel-based morphometry (VBM) analysis and a tract-based spatial statistics (TBSS) analysis to assess fractional anisotropy and longitudinal, radial and mean diffusivity derived by diffusion tensor imaging (DTI). Results: We included 19 patients with bipolar disorder and 47 controls in our study. Fractional anisotropy was the most sensitive DTI marker and decreased significantly in the ventral part of the corpus callosum in patients with bipolar disorder. Longitudinal, radial and mean diffusivity showed no significant between-group differences. Grey matter concentration was reduced in patients with bipolar disorder in the right anterior insula, head of the caudate nucleus, nucleus accumbens, ventral putamen and frontal orbital cortex. Conversely, there was no grey matter concentration or fractional anisotropy increase in any brain region in patients with bipolar disorder compared with controls. Limitations: The major limitation of our study is the small number of patients with bipolar disorder. Conclusion: Our data document the concomitant presence of grey matter concentration decreases in the anterior limbic areas and the reduced fibre tract coherence in the corpus callosum of elderly patients with long-lasting bipolar disorder.

Mutations leading to X-linked hypohidrotic ectodermal dysplasia affect three major functional domains in the tumor necrosis factor family member ectodysplasin-A.

Mutations in the epithelial morphogen ectodysplasin-A (EDA), a member of the tumor necrosis factor (TNF) family, are responsible for the human disorder X-linked hypohidrotic ectodermal dysplasia (XLHED) characterized by impaired development of hair, eccrine sweat glands, and teeth. EDA-A1 and EDA-A2 are two splice variants of EDA, which bind distinct EDA-A1 and X-linked EDA-A2 receptors. We identified a series of novel EDA mutations in families with XLHED, allowing the identification of the following three functionally important regions in EDA: a C-terminal TNF homology domain, a collagen domain, and a furin protease recognition sequence. Mutations in the TNF homology domain impair binding of both splice variants to their receptors. Mutations in the collagen domain can inhibit multimerization of the TNF homology region, whereas those in the consensus furin recognition sequence prevent proteolytic cleavage of EDA. Finally, a mutation affecting an intron splice donor site is predicted to eliminate specifically the EDA-A1 but not the EDA-A2 splice variant. Thus a proteolytically processed, oligomeric form of EDA-A1 is required in vivo for proper morphogenesis.

One minute of grief: Emotional processing in short-term dynamic psychotherapy for adjustment disorder.

OBJECTIVE: Depth of emotional processing has shown to be related to outcome across approaches to psychotherapy. Moreover, a specific emotional sequence has been postulated and tested in several studies on experiential psychotherapy (Pascual-Leone & Greenberg, 2007). This process-outcome study aims at reproducing the sequential model of emotional processing in psychodynamic psychotherapy for adjustment disorder and linking these variables with ultimate therapeutic outcome. METHOD: In this study, 32 patients underwent short-term dynamic psychotherapy. On the basis of reliable clinical change statistics, a subgroup (n = 16) presented with good outcome and another subgroup (n = 16) had a poor outcome in the end of treatment. The strongest alliance session of each case was rated using the observer-rated system Classification of Affective Meaning States. Reliability coefficients for the measure were excellent (κ = .82). RESULTS: Using 1 min as the fine-grained unit of analysis, results showed that the experience of fundamentally adaptive grief was more common in the in-session process of patients with good outcome, compared with those with poor outcomes (χ2 = 6.56, p = .01, d = 1.23). This variable alone predicted 19% of the change in depressive symptoms as measured by the Beck Depression Inventory at the end of treatment. Moreover, sequences of the original model were supported and related to outcome. CONCLUSIONS: These results are discussed within the framework of the sequential model of emotional processing and its possible relevance for psychodynamic psychotherapy. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Anterior cingulate cortex pathology in schizophrenia and bipolar disorder.

To explore possible morphological abnormalities in the dorsal and subgenual parts of anterior cingulate cortex in mood disorders and schizophrenia, we performed a quantitative postmortem study of 44 schizophrenic patients, 21 patients with sporadic bipolar disorder, 20 patients with sporadic major depression, and 55 age- and sex-matched control cases. All individuals were drug naïve or had received psychotropic medication for less than 6 months, and had no history of substance abuse. Neuron densities and size were estimated on cresyl violet-stained sections using a stereological counting approach. The distribution and density of microtubule-associated (MAP2, MAP1b) and tau proteins were assessed by immunocytochemistry and quantitative immunodot assay. Mean total and laminar cortical thicknesses as well as mean pyramidal neuron size were significantly decreased in the dorsal and subgenual parts of areas 24 (24sg) in schizophrenic cases. Patients with bipolar disorder showed a substantial decrease in laminar thickness and neuron densities in layers III, V, and VI of the subgenual part of area 24, whereas patients with major depression were comparable to controls. Immunodot assay showed a significant decrease of both MAP2 and MAP1b proteins in bipolar patients but not in patients with schizophrenia and major depression. The neuroanatomical and functional significance of these findings are discussed in the light of current hypotheses regarding the role of areas 24 and 24sg in schizophrenia and bipolar disorder.

Cognitive errors assessed by observer ratings in bipolar affective disorder: relationship with symptoms and therapeutic alliance

The construct of cognitive errors is clinically relevant for cognitive therapy of mood disorders. Beck's universality hypothesis postulates the relevance of negative cognitions in all subtypes of mood disorders, as well as positive cognitions for manic states. This hypothesis has rarely been empirically addressed for patients presenting bipolar affective disorder (BD). In-patients (n = 30) presenting with BD were interviewed, as were 30 participants of a matched control group. Valid and reliable observer-rater methodology for cognitive errors was applied to the session transcripts. Overall, patients make more cognitive errors than controls. When manic and depressive patients were compared, parts of the universality hypothesis were confirmed. Manic symptoms are related to positive and negative cognitive errors. These results are discussed with regard to the main assumptions of the cognitive model for depression; thus adding an argument for extending it to the BD diagnostic group, taking into consideration specificities in terms of cognitive errors. Clinical implications for cognitive therapy of BD are suggested.

Community Policing in Switzerland's Major Urban Areas: An Observational Study of the Implementation and Impact Using Geospatial Data Mining

La présente étude est à la fois une évaluation du processus de la mise en oeuvre et des impacts de la police de proximité dans les cinq plus grandes zones urbaines de Suisse - Bâle, Berne, Genève, Lausanne et Zurich. La police de proximité (community policing) est à la fois une philosophie et une stratégie organisationnelle qui favorise un partenariat renouvelé entre la police et les communautés locales dans le but de résoudre les problèmes relatifs à la sécurité et à l'ordre public. L'évaluation de processus a analysé des données relatives aux réformes internes de la police qui ont été obtenues par l'intermédiaire d'entretiens semi-structurés avec des administrateurs clés des cinq départements de police, ainsi que dans des documents écrits de la police et d'autres sources publiques. L'évaluation des impacts, quant à elle, s'est basée sur des variables contextuelles telles que des statistiques policières et des données de recensement, ainsi que sur des indicateurs d'impacts construit à partir des données du Swiss Crime Survey (SCS) relatives au sentiment d'insécurité, à la perception du désordre public et à la satisfaction de la population à l'égard de la police. Le SCS est un sondage régulier qui a permis d'interroger des habitants des cinq grandes zones urbaines à plusieurs reprises depuis le milieu des années 1980. L'évaluation de processus a abouti à un « Calendrier des activités » visant à créer des données de panel permettant de mesurer les progrès réalisés dans la mise en oeuvre de la police de proximité à l'aide d'une grille d'évaluation à six dimensions à des intervalles de cinq ans entre 1990 et 2010. L'évaluation des impacts, effectuée ex post facto, a utilisé un concept de recherche non-expérimental (observational design) dans le but d'analyser les impacts de différents modèles de police de proximité dans des zones comparables à travers les cinq villes étudiées. Les quartiers urbains, délimités par zone de code postal, ont ainsi été regroupés par l'intermédiaire d'une typologie réalisée à l'aide d'algorithmes d'apprentissage automatique (machine learning). Des algorithmes supervisés et non supervisés ont été utilisés sur les données à haute dimensionnalité relatives à la criminalité, à la structure socio-économique et démographique et au cadre bâti dans le but de regrouper les quartiers urbains les plus similaires dans des clusters. D'abord, les cartes auto-organisatrices (self-organizing maps) ont été utilisées dans le but de réduire la variance intra-cluster des variables contextuelles et de maximiser simultanément la variance inter-cluster des réponses au sondage. Ensuite, l'algorithme des forêts d'arbres décisionnels (random forests) a permis à la fois d'évaluer la pertinence de la typologie de quartier élaborée et de sélectionner les variables contextuelles clés afin de construire un modèle parcimonieux faisant un minimum d'erreurs de classification. Enfin, pour l'analyse des impacts, la méthode des appariements des coefficients de propension (propensity score matching) a été utilisée pour équilibrer les échantillons prétest-posttest en termes d'âge, de sexe et de niveau d'éducation des répondants au sein de chaque type de quartier ainsi identifié dans chacune des villes, avant d'effectuer un test statistique de la différence observée dans les indicateurs d'impacts. De plus, tous les résultats statistiquement significatifs ont été soumis à une analyse de sensibilité (sensitivity analysis) afin d'évaluer leur robustesse face à un biais potentiel dû à des covariables non observées. L'étude relève qu'au cours des quinze dernières années, les cinq services de police ont entamé des réformes majeures de leur organisation ainsi que de leurs stratégies opérationnelles et qu'ils ont noué des partenariats stratégiques afin de mettre en oeuvre la police de proximité. La typologie de quartier développée a abouti à une réduction de la variance intra-cluster des variables contextuelles et permet d'expliquer une partie significative de la variance inter-cluster des indicateurs d'impacts avant la mise en oeuvre du traitement. Ceci semble suggérer que les méthodes de géocomputation aident à équilibrer les covariables observées et donc à réduire les menaces relatives à la validité interne d'un concept de recherche non-expérimental. Enfin, l'analyse des impacts a révélé que le sentiment d'insécurité a diminué de manière significative pendant la période 2000-2005 dans les quartiers se trouvant à l'intérieur et autour des centres-villes de Berne et de Zurich. Ces améliorations sont assez robustes face à des biais dus à des covariables inobservées et covarient dans le temps et l'espace avec la mise en oeuvre de la police de proximité. L'hypothèse alternative envisageant que les diminutions observées dans le sentiment d'insécurité soient, partiellement, un résultat des interventions policières de proximité semble donc être aussi plausible que l'hypothèse nulle considérant l'absence absolue d'effet. Ceci, même si le concept de recherche non-expérimental mis en oeuvre ne peut pas complètement exclure la sélection et la régression à la moyenne comme explications alternatives. The current research project is both a process and impact evaluation of community policing in Switzerland's five major urban areas - Basel, Bern, Geneva, Lausanne, and Zurich. Community policing is both a philosophy and an organizational strategy that promotes a renewed partnership between the police and the community to solve problems of crime and disorder. The process evaluation data on police internal reforms were obtained through semi-structured interviews with key administrators from the five police departments as well as from police internal documents and additional public sources. The impact evaluation uses official crime records and census statistics as contextual variables as well as Swiss Crime Survey (SCS) data on fear of crime, perceptions of disorder, and public attitudes towards the police as outcome measures. The SCS is a standing survey instrument that has polled residents of the five urban areas repeatedly since the mid-1980s. The process evaluation produced a "Calendar of Action" to create panel data to measure community policing implementation progress over six evaluative dimensions in intervals of five years between 1990 and 2010. The impact evaluation, carried out ex post facto, uses an observational design that analyzes the impact of the different community policing models between matched comparison areas across the five cities. Using ZIP code districts as proxies for urban neighborhoods, geospatial data mining algorithms serve to develop a neighborhood typology in order to match the comparison areas. To this end, both unsupervised and supervised algorithms are used to analyze high-dimensional data on crime, the socio-economic and demographic structure, and the built environment in order to classify urban neighborhoods into clusters of similar type. In a first step, self-organizing maps serve as tools to develop a clustering algorithm that reduces the within-cluster variance in the contextual variables and simultaneously maximizes the between-cluster variance in survey responses. The random forests algorithm then serves to assess the appropriateness of the resulting neighborhood typology and to select the key contextual variables in order to build a parsimonious model that makes a minimum of classification errors. Finally, for the impact analysis, propensity score matching methods are used to match the survey respondents of the pretest and posttest samples on age, gender, and their level of education for each neighborhood type identified within each city, before conducting a statistical test of the observed difference in the outcome measures. Moreover, all significant results were subjected to a sensitivity analysis to assess the robustness of these findings in the face of potential bias due to some unobserved covariates. The study finds that over the last fifteen years, all five police departments have undertaken major reforms of their internal organization and operating strategies and forged strategic partnerships in order to implement community policing. The resulting neighborhood typology reduced the within-cluster variance of the contextual variables and accounted for a significant share of the between-cluster variance in the outcome measures prior to treatment, suggesting that geocomputational methods help to balance the observed covariates and hence to reduce threats to the internal validity of an observational design. Finally, the impact analysis revealed that fear of crime dropped significantly over the 2000-2005 period in the neighborhoods in and around the urban centers of Bern and Zurich. These improvements are fairly robust in the face of bias due to some unobserved covariate and covary temporally and spatially with the implementation of community policing. The alternative hypothesis that the observed reductions in fear of crime were at least in part a result of community policing interventions thus appears at least as plausible as the null hypothesis of absolutely no effect, even if the observational design cannot completely rule out selection and regression to the mean as alternative explanations.

AMCHP Issue Brief: Environmental Scan: State Title V Program Response to Autism Spectrum Disorder and Other Developmental Disabilities, December 2009

The increasing incidence of children identified and diagnosed with Autism Spectrum Disorders (ASD) and other developmental disabilities (DD) poses a major challenge to Title V and other programs as they try to meet the diverse and sometimes complex needs of these children. However, those state that have initiated coordinated efforts to meet the needs of these children cross systems have had the opportunity to form and/or strengthen relationships with new partners. In addition, these coordinated efforts will allow states to develop new policies, programs and financing mechanisms addressing the health of children with ASD, which may also strengthen the system of care for all Children and Youth with Special Health Care Needs.

Public health significance of bipolar disorder: implications for early intervention and prevention.

OBJECTIVES: Early intervention and preventive strategies have become major targets of research and service development in psychiatry over the last few years. Compared to schizophrenia, bipolar disorder (BD) has received limited attention in this regard. In this paper, we review the available literature in order to explore the public health significance of BD and the extent to which this may justify the development of early intervention strategies for this disorder. METHODS: The main computerized psychiatric literature databases were accessed. This included Medline and PsychInfo, using the following keywords: bipolar, early intervention, staging model, burden, caregiver, public health, and manic depression. RESULTS: BD is often recurrent and has an impact that goes well beyond symptomatic pathology. The burden it incurs is linked not only to its cardinal clinical features, but also to cognitive dysfunction, poor functional outcome, poor physical health, high rate of comorbidities, and suicide. At a societal level, BD induces enormous direct and indirect costs and has a major impact on caregivers. The available literature reveals a usually long delay between illness onset and the start of treatment, and the absence of specific guidelines for the treatment of the early phase of BD. CONCLUSIONS: Considering the major impact of BD on patients and society, there is an urgent need for the development of early intervention strategies aimed at earlier detection and more specific treatment of the early phase of the disorder.