Can we predict a "tsunami"? Symptomatic and syndromal density, mood instability and treatment intensity in people with bipolar disorders under a strict and long lockdown.

BACKGROUND: Converging evidence supports the involvement of circadian rhythm disturbances in the course and morbidity of bipolar disorders (BD). During 2020, lockdown measures were introduced worldwide to contain the health crisis caused by the COVID-19 pandemic. As a result, chronobiological rhythms were critically disrupted and illness outcomes were expected to worsen. The current study aimed to explore changes in morbidity among BD patients living under lockdown. METHODS: Ninety BD outpatients under naturalistic treatment conditions were followed from March to September 2020 using a mood chart technique. Different treatment and illness variables, including mood instability, were assessed and compared with the outcomes obtained during the same 28-week period in 2019. RESULTS: For most clinical variables, no significant differences were observed between time periods. A slight decrease was found in symptom intensity (from 15.19 ± 20.62 to 10.34 ± 15.79, FDR-adjusted p = 0.04) and in the number of depressive episodes (from 0.39 ± 0.74 to 0.22 ± 0.63, FDR-adjusted p = 0.03), whereas the intensity of pharmacological treatment remained unchanged. Previous illness course predicted mood outcomes during the confinement. LIMITATIONS: Follow-up periods were relatively short. Further, actigraphy or other methods capable of ensuring significant changes in physical activity were not used. CONCLUSIONS: In line with other studies, our findings show no worsening in the clinical morbidity of BD patients during lockdown. This conspicuous contrast between our initial predictions and the observed findings highlights the fact that we are still far from being able to provide accurate predictive models for BD.

Update on the use and management of lithium in neuropsychiatry / Actualización en el uso y el manejo del litio en neuropsiquiatría.

Lithium is an alkaline metal, used for more than 60 years in psychiatry, and currently considered the gold standard in the treatment of bipolar disorder (BD). According to recent evidence, this active ingredient is useful for the treatment of a wide spectrum of clinical varieties of affective disorders. In addition, it is estimated that lithium reduces the risk of suicide and suicidal behavior in people with mood disorders. On the other hand, some novel studies have shown that the cation has a potential efficacy for the treatment of other neuropsychiatric processes, such as the likelihood of reducing the risk of dementia and slowing down the development of neurodegenerative diseases. Despite the enormous evidence in favor of the use of lithium, it is known that, in Argentina, medications containing it are prescribed less than expected. In view of all this, the Asociación Argentina de Psiquiatría Biológica (Argentine Association of Biological Psychiatry) (AAPB or AABP) convened a group of experts to review the available scientific literature and prepare an updated document on the management and use of lithium in neuropsychiatry. In addition to the use of the ion in daily clinical practice, the scope of this review includes other contents that have been considered of interest for the psychiatrist, such as certain pharmacological and pharmacogenetic aspects, possible clinical predictors of response to treatment with lithium, management of ion during perinatal period, management of lithium in child and adolescent population, management of adverse effects linked to cation and interactions with drugs and other substances.

El litio es un metal alcalino, usado hace más de 60 años en psiquiatría, y actualmente es considerado el estándar de oro en el tratamiento del trastorno bipolar (TB). De acuerdo con la evidencia reciente, este principio activo es útil para el tratamiento de un amplio espectro de variedades clínicas de los trastornos afectivos. Además, se estima que desde hace tiempo el litio reduce el riesgo de suicidio y de comportamiento suicida en personas con trastornos del estado de ánimo. Por otro lado, algunos estudios novedosos han demostrado que el catión posee una potencial eficacia para el tratamiento de otros procesos neuropsiquiátricos, tales como la probabilidad de disminuir el riesgo de demencia y la de ralentizar el desarrollo de enfermedades neurodegenerativas. A pesar de la enorme evidencia a favor de la utilización del litio, se sabe que, en la Argentina, las especialidades medicinales que lo contienen se prescriben menos de lo esperado. En virtud de todo lo mencionado, la Asociación Argentina de Psiquiatría Biológica (AAPB) convocó a un grupo de expertos para revisar la literatura científica disponible y elaborar un documento actualizado sobre el manejo y el uso del litio en neuropsiquiatría. Además de la utilización del ion en la práctica clínica diaria, el alcance de esta revisión incluye otros contenidos que se han considerado de interés para el médico psiquiatra, tales como ciertos aspectos farmacológicos y farmacogenéticos, posibles predictores clínicos de la respuesta al tratamiento con litio, el manejo del ion durante el período perinatal, el manejo de litio en la población infantojuvenil, el manejo de los efectos adversos vinculados con el catión y las interacciones con medicamentos y otras sustancias.

Third Argentine Consensus statement on management Bipolar Disorders. Section3: Bipolar Disorder in the context of special situations / Tercer Consenso Argentino sobre el manejo de los Trastornos Bipolares. Tercera parte: Manejo de los Trastornos Bipolares en el contexto de situaciones especiales.

This document constitutes the third and last part of the Third Argentine Consensus on the Management of Bipolar Disorders carried out by the Argentine Association of Biological Psychiatry (AAPB). Continuing with the initial objective, this section of the Consensus on the Management of Bipolar Disorders is focused on the management of bipolar disorders in special populations. This section constitutes a comprehensive review and expert consideration of the scientific evidence on: a) the management of bipolar disorders in treatment-resistant patients; b) the management of bipolar disorder in childhood and adolescence; c) the management of bipolar disorders in women during their perinatal period and, d) the management of bipolar disorders in older adults.

Este documento constituye la tercera y última parte del Tercer Consenso Argentino sobre el Manejo de los Trastornos Bipolares llevada a cabo por la Asociación Argentina de Psiquiatría Biológica (AAPB). Siguiendo con el objetivo propuesto por el comité de expertos, en la actual versión del Consenso sobre el manejo de los trastornos bipolares, esta sección está enfocada al abordaje de los Trastornos Bipolares en situaciones especiales. Esto configura una revisión exhaustiva de la evidencia científica  sobre: a) el manejo de los trastornos bipolares en pacientes resistentes al tratamiento, b) el manejo de los trastornos bipolares en la mujer en el período perinatal, c) el manejo del trastorno bipolar en la etapa infantojuvenil y d) el manejo de los trastornos bipolares en los adultos mayores.

Third Argentine Consensus statement on management Bipolar Disorders. Section 2 B / Tercer Consenso Argentino sobre el manejo de los Trastornos Bipolares. Segunda Parte B.

This document constitutes the second section B of the Third Argentine Consensus on the Management of Bipolar Disorders, focused on synthesizing the most updated evidence on therapeutic approaches for adult patients. The scope of this section is to provide therapeutic recommendations for managing bipolar disorders in adults, (i) acute mania (ii) bipolar depression (iii) mixed stated (iv) suicidality and (vi) psychological interventions. In addition, the current manuscript outlines the assessment and management of side effects of pharmacotherapeutic treatments.

Este documento constituye la segunda parte B del Tercer Consenso Argentino sobre el Manejo de los Trastornos Bipolares llevada a cabo por la Asociación Argentina de Psiquiatría Biológica (AAPB). Siguiendo con el direccionamiento iniciado en el parte 2A sobre el tratamiento integral de los trastornos bipolares, esta sección se ha enfocado en sintetizar la evidencia más actualizada sobre abordajes terapéuticos para pacientes adultos. El alcance de esta sección es proporcionar recomendaciones terapéuticas para el manejo de los trastornos bipolares en adultos, (i) manía aguda, (ii) depresión bipolar, (iii) estado mixto, (iv) el suicidio en el trastorno bipolar, (v) intervenciones psicológicas. Además, el presente manuscrito aborda la evaluación y el manejo de los efectos secundarios de los tratamientos farmacoterapéuticos.

Efficacy of cognitive remediation in bipolar disorder: systematic review and meta-analysis of randomized controlled trials.

A significant percentage of people with bipolar disorder (BD) exhibit suboptimal functional adjustment, even when appropriately treated and after symptomatic recovery is achieved. Given that cognitive impairment is one of the strongest correlates of socio-occupational outcomes and quality of life in BD, cognitive remediation (CR) is currently acknowledged as a promising treatment that could help bridge the gap between symptomatic and full functional recovery. The aim of this review was to explore the efficacy of CR approaches in improving cognitive and functional outcomes in BD patients. PubMed, PsycINFO, and CENTRAL were searched from inception to November 2022. Randomized controlled trials exploring the effects of CR on cognition and/or functional adjustment in adult BD patients were eligible. Ten studies based on seven independent trials (n = 586) were included. Change-score effect sizes (Hedges' g) were obtained for efficacy outcome measures and combined by means of meta-analytic procedures. Small but significant overall effects were observed for working memory (g = 0.32, 95% CI 0.11-0.52), planning (g = 0.30, 95% CI 0.03-0.56), and verbal learning (g = 0.40, 95% CI 0.15-0.66). However, CR was not found to exert any significant effects on functional outcomes at treatment completion or at follow-up assessment. Although CR may modestly enhance the cognitive performance of BD patients, this effect does not translate into an improvement at the functional level. The current data do not support the inclusion of CR as a treatment recommendation in clinical practice guidelines for the management of BD.

Clinicians' preferences and attitudes towards the use of lithium in the maintenance treatment of bipolar disorders around the world: a survey from the ISBD Lithium task force.

BACKGROUND: Lithium has long been considered the gold-standard pharmacological treatment for the maintenance treatment of bipolar disorders (BD) which is supported by a wide body of evidence. Prior research has shown a steady decline in lithium prescriptions during the last two decades. We aim to identify potential factors explaining this decline across the world with an anonymous worldwide survey developed by the International Society for Bipolar Disorders (ISBD) Task Force "Role of Lithium in Bipolar Disorders" and distributed by diverse academic and professional international channels. RESULTS: A total of 886 responses were received of which 606 completed the entire questionnaire while 206 completed it partially. Respondents were from 43 different countries comprising all continents. Lithium was the most preferred treatment option for the maintenance of BD patients (59%). The most relevant clinical circumstances in which lithium was the preferred option were in patients with BD I (53%), a family history of response (18%), and a prior response during acute treatment (17%). In contrast, Lithium was not the preferred option in case of patients´ negative beliefs and/or attitudes towards lithium (13%), acute side-effects or tolerability problems (10%) and intoxication risk (8%). Clinicians were less likely to prefer lithium as a first option in BD maintenance phase when practising in developing economy countries [X2 (1, N = 430) = 9465, p = 0.002) ] and private sectors [X2 (1, N = 434) = 8191, p = 0.004)]. CONCLUSIONS: Clinicians' preferences and attitudes towards the use of lithium in the maintenance treatment of bipolar disorders appear to be affected by both the patients' beliefs and the professional contexts where clinicians provide their services. More research involving patients is needed for identifying their attitudes toward lithium and factors affecting its use, particularly in developing economies.

Third Argentine Consensus statement on management Bipolar Disorders. Section 2 A: Comprehensive treatment of the bipolar disorders in adults / Tercer Consenso Argentino sobre el manejo de los Trastornos Bipolares. Segunda Parte A: Tratamiento integral de los trastornos bipolares en el adulto.

This document constitutes the second section A of the Third Argentine Consensus on the Management of Bipolar Disorders, focused on synthesizing the most updated evidence on therapeutic approaches for adult patients. The aim of this section (2A) is to provide therapeutic recommendations for managing bipolar disorders in adults. In addition, the scope of this current manuscript outlines recommendations on the use of treatment guidelines, levels of evidence available to support these recommendations, general considerations for the treatment of bipolar disorders, the so-called pseudoresistance and adherence to treatment, general considerations on psychological therapies, as well as long term treatment of bipolar disorders.

Este documento corresponde a la segunda parte del Tercer Consenso Argentino sobre el manejo de los trastornos bipolares, enfocada en sintetizar la evidencia actualizada sobre los abordajes terapéuticos de esta patología en los pacientes adultos. Siguiendo la metodología descripta en la primera parte del Consenso, el panel de expertos realizó una exhaustiva revisión de la bibliografía y, como consecuencia de un posterior debate sobre la información disponible, se generó esta sección A del segundo documento que abarca el tratamiento integral de las personas adultas que padecen este trastorno. Durante la etapa de debate y discusión de estas guías, se decidió incorporar algunos puntos que estimamos serán de gran utilidad para el equipo interdisciplinario encargado del manejo de pacientes con trastornos bipolares.  En tal sentido, en la sección A de la segunda parte de este documento, se podrán encontrar las recomendaciones generales para el uso de las guías de tratamiento, los niveles de evidencia disponibles para sustentar las recomendaciones, las consideraciones generales del tratamiento de los trastornos bipolares, el fenómeno de pseudorresistencia y adherencia al tratamiento, las consideraciones generales sobre el abordaje psicológico, así como el tratamiento a largo plazo de los trastornos bipolares.

Are all antidepressants the same? The consumer has a point.

BACKGROUND: Although a large variety of antidepressants agents (AD) with different mechanisms of action are available, no significant differences in efficacy and safety have been shown. However, there have been few attempts to incorporate data on subjective experiences under different AD. METHOD: We conducted a qualitative and quantitative analysis of the posts from the website www.askapatient.com from different AD. We reviewed a random sample of 1000 posts. RESULT: After applying the inclusion and exclusion criteria, we included a final sample of 450 posts, 50 on each of the most used AD: sertraline, citalopram, paroxetine, escitalopram, fluoxetine, venlafaxine, duloxetine, mirtazapine, and bupropion. Bupropion, citalopram, and venlafaxine had the higher overall satisfaction ratings. Sertraline, paroxetine, and fluoxetine had high reports of emotional blunting, while bupropion very few. Overall satisfaction with AD treatment was inversely associated with the presence of the following side-effects: suicidality, irritability, emotional blunting, cognitive disturbances, and withdrawal symptoms. After adjusting for confounders, only emotional blunting was shown to be more frequently reported by users of serotonergic agents, as compared to non-serotoninergic agents. CONCLUSION: This research points out that the subjective experience of patients under treatment should be taken into consideration when selecting an AD as differences between agents were evident. In contrast to the more frequent treatment decisions, users might prefer receiving a non-serotoninergic agent over a serotonergic one due to their lower propensity to produce emotional blunting.

Expert consensus recommendations on the use of randomized clinical trials for drug approval in psychiatry- comparing trial designs.

The use of randomized clinical trials, in particular placebo-controlled trials, for drug approval, is the subject of long-standing debate in the scientific community and beyond. This study offers consensus recommendations from clinical and academic experts to guide the selection of clinical trial design in psychiatry. Forty-one highly cited clinical psychiatrists and/or researchers participated in a Delphi survey. Consensus statements were developed based on the findings of a published, peer-reviewed systematic review. Participants evaluated statements in two survey rounds, following the Delphi method. The expert panel achieved consensus on 7 of 21 recommendations regarding the use of randomized clinical trials. The endorsed recommendations were: (i) Results from placebo-controlled trials are the most reliable and (ii) are necessary despite the growing placebo-effect; (iii) it is ethical to enroll patients in placebo-arms when established treatment is available, if there is no evidence of increased health risk; (iv) There is a need to approve new drugs with the same efficacy as existing treatments, but with different side-effect profiles; (v) Non-inferiority trials incur an increased risk of approving ineffective medications; (vi) The risk of approving an ineffective drug justifies trial designs that incur higher costs, and (vii) superiority trials incur the risk of rejecting potentially efficacious treatments. The endorsed recommendations inform the choice of trial-design appropriate for approval of psychopharmacological drugs. The recommendations strongly support the use of randomized clinical trials in general, and the use of placebo-controlled trials in particular.

Symptom Severity Mixity in Older-Age Bipolar Disorder: Analyses From the Global Aging and Geriatric Experiments in Bipolar Disorder Database (GAGE-BD).

OBJECTIVE: Some individuals with bipolar disorder (BD) experience manic and depressive symptoms concurrently, but data are limited on symptom mixity in older age bipolar disorder (OABD). Using the Global Aging & Geriatric Experiments in Bipolar Disorder Database, we characterized mixity in OABD and associations with everyday function. METHODS: The sample (n = 805), from 12 international studies, included cases with both mania and depression severity ratings at a single timepoint. Four mixity groups were created: asymptomatic (A), mixed (Mix), depressed only (Dep), and manic only (Man). Generalized linear mixed models used mixity group as the predictor variable; cohort was included as a random intercept. Everyday function was assessed with the Global Assessment of Functioning score. RESULTS: Group proportions were Mix (69.6%; n = 560), followed by Dep (18.4%; n = 148), then A (7.8%; n = 63), then Man (4.2%; n= 34); levels of depression and mania were similar in Mix compared to Dep and Man, respectively. Everyday function was lowest in Mix, highest in A, and intermediate in Man and Dep. Within Mix, severity of depression was the main driver of worse functioning. Groups differed in years of education, with A higher than all others, but did not differ by age, gender, employment status, BD subtype, or age of onset. CONCLUSIONS: Mixed features predominate in a cross-sectional, global OABD sample and are associated with worse everyday function. Among those with mixed symptoms, functional status relates strongly to current depression severity. Future studies should include cognitive and other biological variables as well as longitudinal designs to allow for evaluation of causal effects.

Bipolar symptoms, somatic burden, and functioning in older-age bipolar disorder: Analyses from the Global Aging & Geriatric Experiments in Bipolar Disorder Database project.

OBJECTIVE: Literature on older-age bipolar disorder (OABD) is limited. This first-ever analysis of the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) investigated associations among age, BD symptoms, comorbidity, and functioning. METHODS: This analysis used harmonized, baseline, cross-sectional data from 19 international studies (N = 1377). Standardized measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Global Assessment of Functioning (GAF). RESULTS: Mean sample age was 60.8 years (standard deviation [SD] 12.2 years), 55% female, 72% BD I. Mood symptom severity was low: mean total YMRS score of 4.3 (SD 5.4) and moderate-to-severe depression in only 22%. Controlled for sample effects, both manic and depressive symptom severity appeared lower among older individuals (p's < 0.0001). The negative relationship between older age and symptom severity was similar across sexes, but was stronger among those with lower education levels. GAF was mildly impaired (mean =62.0, SD = 13.3) and somatic burden was high (mean =2.42, SD = 1.97). Comorbidity burden was not associated with GAF. However, higher depressive (p < 0.0001) and manic (p < 0.0001) symptoms were associated with lower GAF, most strongly among older individuals. CONCLUSIONS: Findings suggest an attenuation of BD symptoms in OABD, despite extensive somatic burden. Depressive symptom severity was strongly associated with worse functioning in older individuals, underscoring the need for effective treatments of BD depression in older people. This international collaboration lays a path for the development of a better understanding of aging in BD.

The long-term course of cognition in bipolar disorder: a systematic review and meta-analysis of patient-control differences in test-score changes.

Neuropsychological impairment represents a key aspect of bipolar disorder (BD) that is evident even in early-course patients and is a strong predictor of functional outcomes among those affected. Previous meta-analyses of longitudinal studies suggest that BD-related cognitive deficits may not progress along the course of the disorder. However, short test-retest periods were used in most primary studies and comparisons with healthy controls were limited. The aim of this review was to synthesize the findings of research reports comparing long-term neurocognitive trajectories between BD patients and healthy individuals. PubMed, PsycINFO, and Scopus databases were searched from inception through July 2021. Publications were considered for inclusion if they reported cognitive test scores of BD patients and healthy controls at two different time points, with a minimum test-retest interval of 5 years. Fifteen studies compared the long-term course of cognition in BD patients with that of healthy controls. Ten of these were included in the quantitative analysis and involved 540 BD patients and 644 healthy individuals (mean follow-up period: 8.9 years). Patient-control effect sizes (standardized mean differences) were calculated for test-score changes in 24 neuropsychological variables and combined by means of meta-analytic procedures. No significant differences were found between patients and controls regarding long-term cognitive outcomes. These findings are consistent with previous shorter-term longitudinal meta-analyses and do not provide evidence for progressive cognitive deterioration in most bipolar individuals. Future studies should address the longitudinal course of cognition in different subgroups of BD patients and its prognostic and therapeutic value.

Third Argentine Consensus statement on management Bipolar Disorders. Section1: introduction and general concepts / Tercer Consenso Argentino sobre el manejo de los Trastornos Bipolares. Primera Parte: introducción, método de trabajo y generalidades.

The Third Argentine Consensus on the management of bipolar disorders (TB) is an initiative of the Argentine Association of Biological Psychiatry (AAPB). As a reference document, this consensus pursues two main objectives: on the one hand, to summarize and systematize the best available evidence on the comprehensive management of this pathology; on the other, to provide a useful, up-to-date instrument for psychiatrists, multidisciplinary teams dedicated to mental health, and government agencies. During a period of approximately six months of work -that is, from May to October 2022- a committee of experts made up of 18 professionals and representatives of the three most important Psychiatry and Mental Health associations in Argentina (that is, the AAPB, the Argentine Association of Psychiatrists, AAP, and the Association of Argentine Psychiatrists, APSA) have focused on updating the information regarding TB. Finally, this document was prepared as a result of an exhaustive review of the bibliography published to date, which was strategically divided into three parts: the first deals with the generalities of TB; the second deals with the comprehensive treatment of the pathology; finally, the third analyzes TB in the context of special situations.

El Tercer Consenso Argentino sobre el manejo de los Trastornos Bipolares (TB) es una iniciativa de la Asociación Argentina de Psiquiatría Biológica (AAPB). Como documento de referencia, este consenso persigue dos objetivos principales: por un lado, resumir y sistematizar la mejor evidencia disponible sobre el manejo integral de esta patología; por el otro, proporcionar un instrumento útil y actualizado a psiquiatras, a equipos multidisciplinarios abocados a la salud mental y a organismos gubernamentales. Durante un período de aproximadamente seis meses de trabajo -desde mayo a octubre de 2022- un comité de expertos integrado por 18 profesionales y por representantes de las tres asociaciones de Psiquiatría y Salud Mental más importantes de la Argentina: la AAPB, la Asociación Argentina de Psiquiatras, (AAP) y la Asociación de Psiquiatras Argentinos (APSA), se abocaron a actualizar la información respecto de los TB. Finalmente, y como resultado de una exhaustiva revisión de la bibliográfica publicada hasta la actualidad, se confeccionó este documento que fue dividido estratégicamente en tres partes: la primera versa acerca de las generalidades del TB; la segunda aborda el  tratamiento integral de la patología; y, por último, la tercera analiza los TB en el contexto de situaciones especiales.

[Adaptation of psychiatric practice in public and private mental health institutions of the City of Buenos Aires during the COVID-19 pandemic]. / Adaptación de la práctica psiquiátrica en instituciones de salud mental públicas y privadas de la Ciudad de Buenos Aires durante la pandemia de COVID-19.

BACKGROUND: One of the most significant indirect impacts of the COVID-19 pandemic will be seen on the mental health of the population. On this study, we will take into account the adapting capacity that the most representative mental health services (MHS) of Buenos Aires (BA) City have had as to this new situation. METHODS: We designed an online survey including 10 self-administered closed questions, strictly anonymous. It has been sent to targeted professionals who work in public and private MHS of BA after 2 months of the beginning of the lockdown. RESULTS: We got 38 answers. 2 professionals rejected to answer. 34% belonged to private institutions and 66% to public ones. 81% of the total were able to implement online assistance but only 24% had been trained on how to treat patients in this context. 69% of the private and 12% of the public sector professionals informed to have been trained on telemedicine tools. 69% of the private and 36% of the public sector professionals informed to have prepared materials for the users on telemedicine resources. 68% mentioned that their service was properly organized. 40% of the public sector professionals may have been reassigned to work on tasks related to the pandemic. 40% of the total informed a reduced capacity of assistance. CONCLUSIONS: The MHS of BA may have been able to migrate their assistance to telemedicine, however we have noticed differences in the training levels. A better capacity of training on this modality might be needed.

The Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project: Understanding older-age bipolar disorder by combining multiple datasets.

OBJECTIVE: There is a dearth of research about the aging process among individuals with bipolar disorder (BD). One potential strategy to overcome the challenge of interpreting findings from existing limited older-age bipolar disorder (OABD) research studies is to pool or integrate data, taking advantage of potential overlap or similarities in assessment methods and harmonizing or cross-walking measurements where different measurement tools are used to evaluate overlapping construct domains. This report describes the methods and initial start-up activities of a first-ever initiative to create an integrated OABD-focused database, the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project. METHODS: Building on preliminary work conducted by members of the International Society for Bipolar Disorders OABD taskforce, the GAGE-BD project will be operationalized in four stages intended to ready the dataset for hypothesis-driven analyses, establish a consortium of investigators to guide exploration, and set the stage for prospective investigation using a common dataset that will facilitate a high degree of generalizability. RESULTS: Initial efforts in GAGE-BD have brought together 14 international investigators representing a broad geographic distribution and data on over 1,000 OABD. Start-up efforts include communication and guidance on meeting regulatory requirements, establishing a Steering Committee to guide an incremental analysis strategy, and learning from existing multisite data collaborations and other support resources. DISCUSSION: The GAGE-BD project aims to advance understanding of associations between age, BD symptoms, medical burden, cognition and functioning across the life span and set the stage for future prospective research that can advance the understanding of OABD.

Episodic density, subsyndromic symptoms, and mood instability in late-life bipolar disorders: A 5-year follow-up study.

OBJECTIVES: Characterization of clinical course in old age bipolar disorder (OABD) is scarce and based solely on episode density (ED). The aim of this study was to explore mood instability (MI) and subsyndromal symptomatology (SS) in a prospective cohort of OABD. Further, we contrasted these measures with a cohort of young age bipolar disorder (YABD). METHODS: Life charts from weekly mood ratings were used to compute the number of weeks spent with subsyndromal symptoms (SD), the ED, and the MI during follow-up for a cohort of OABD (N = 38) that excluded late onset BD. Linear and logistic regression models were fitted to compare the clinical course of OABD with a cohort of YABD (N = 52) and to explore the relationship between these measures and functional outcomes. RESULTS: Median follow-up was 5 years (IQR: 3.6-7.9). OABD (61.6 years, SD: 8.3) spent 15%, 6%, and 3% of their follow-up with depressive, manic, and mixed symptoms, respectively, and suffered 4.2 mood changes per year (SD: 2.6). No significant differences between OABD and YABD regarding ED or MI emerged in multivariate analysis, while a higher subsyndromal manic symptom burden was observed in OABD (ß coefficient: 3.79, 95%CI: 0.4-7.2). Both SS and MI were associated with functional outcomes in OABD. CONCLUSIONS: The course of illness throughout OABD was similar to the one observed in YABD except for a higher subsyndromal manic burden. This study extended the association of MI and SD with global functioning to the late-life BD.