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La diabetes insípida (DI) es un síndrome caracterizado por poliuria y polidipsia asociado a la producción crónica de grandes volúmenes de orina diluida, secundario a una disminución de la secreción o acción de la hormona antidiurética (ADH) [1]. El litio es el principal fármaco implicado en la inducción de esta patología cuando se presenta de forma secundaria. [2]. Se presentan 2 reportes de casos de niños de 10 y 12 años con uso de litio por diagnóstico de trastorno del ánimo. Palabras Clave: Diabetes Melitus, trastornos del ánimo, nefrogénica, litio, hormona antidiurética

Diabetes insipidus (DI) is a syndrome characterized by polyuria and polydipsia associated with the production of large volumes of diluted urine, secondary to a decrease in the secretion or action of antidiuretic hormone (ADH) [1]. Lithium is the main drug involved in the induction of this pathology when it appears with a preventable cause [2]. Two case reports of children 10 and 12 years old with mood disorder and lithium use are presented with the intention of being alert to clinical manifestations and observation by caregivers.Key words: Diabetes insipidus, mood disorders, nephogenic, lithium, antidiuretic hormone.

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ABSTRACT Patients with Bipolar Disorder (BD) usually display cognitive deficits with aging. However, the correlation between BD and dementia syndromes is inconclusive, despite the similarity with behavioral variant frontotemporal dementia. We report a 78-year-old female patient who had bipolar type 1 disorder since adolescence. Her symptoms ranged from apathy to psychotic mania. She had had three hospitalizations, and since her last stay 10 years ago, her symptoms had remained stable. However, in the past 2 years, she displayed different symptoms, such as irritability manifested as verbal and physical aggression, cognitive impairment, repetitive pattern of behavior, perambulation, persecutory delusions, disorientation, and hyporexia. Treatment with anticholinesterases or mood stabilizers promoted no improvement. She scored 17/30 points on the Mini-Mental State Examination. Neuropsychological assessment suggested deficits in executive function, attention, and memory. Neuroimaging tests revealed frontotemporal degeneration and hypoperfusion. Diagnostic and therapeutic approaches for this type of patient represent a significant challenge for clinicians.

RESUMO Pacientes com Transtorno Bipolar (TB) costumam apresentardéficits cognitivosao envelhecer. No entanto, a correlação com síndromes demenciais é inconclusiva, apesar da similaridade com a variante comportamental da demência frontotemporal (bvFTD). Nósrelatamos uma paciente de 78 anos de idade com TB tipo 1 desde a adolescência. Seus sintomas variavam de apatia a mania psicótica. A paciente passou por 3 internações, sendo a última há 10 anos, seguida de estabilização clínica. No entanto, nos últimos 2 anos, ela apresentou sintomas diferentes, como irritabilidade expressada por agressões verbal e física, comprometimento cognitivo, padrão repetitivo de comportamento, perambulação, delírios persecutórios, desorientação e hiporexia. O tratamento com anticolinesterásicos ou estabilizadores de humor não revelou melhora. Apresentou 17/30 pontos no miniexame do estado mental, a avaliação neuropsicológica sugeriu déficit de função executiva, atenção e memória. Os exames de neuroimagem demonstraram atrofia e hipoperfusão fronto-temporal. Abordagens diagnósticas e terapêuticas para este tipo de paciente representam um desafio significativo para os clínicos.

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Objetivo: identificar os determinantes sociais de saúde dos pacientes com transtorno afetivo bipolar (TAB), sua distribuição espacial e a adesão ao tratamento. Métodos: estudo descritivo e transversal, com amostragem não probabilística, realizado no Centro de Atenção Psicossocial de Divinópolis/Minas Gerais, no período de fevereiro/2017 a fevereiro/2018 com 35 pacientes diagnosticados com TAB, submetidos a um questionário, escala clínica e telefonemas. Análise estatística realizada através de técnicas univariadas e multivariadas. Estudo aprovado por Comitê de Ética em Pesquisa. Resultados: a maioria da população estudada apresentou predição positiva à adesão ao tratamento, que se associou ao sexo, idade, estilo de vida saudável, apoio de redes sociais e comunitárias, saneamento básico, acesso a serviços sociais de saúde e benefício do governo. Conclusão: a adesão ao tratamento é um produto da interação entre as dimensões relacionadas ao paciente, ao serviço de saúde, aos fatores socioeconômicos e à terapêutica proposta.

Objective: to identify the health social determinants of patients with bipolar affective disorder (BAD), their spatial distribution and treatment adherence. Methods: a descriptive and cross-sectional study with non-probabilistic sampling, carried out at the Psychosocial Care Center of Divinópolis/Minas Gerais, from February/2017 to February/2018 with 35 patients diagnosed with BAD, submitted to a questionnaire, clinical scale and phone calls. Analysis performed through univariate and multivariate techniques. Study approved by the Research Ethics Committee. Results: most of the population studied had a positive prediction for treatment adherence, which was associated with gender, age, healthy lifestyle, support from social and community networks, basic sanitation, access to social health services and government benefit. Conclusion: adherence to treatment is a product of the interaction between the dimensions related to the patient, the health service, the socioeconomic factors and the proposed therapy.

Objetivo: identificar los determinantes sociales de la salud de pacientes con trastorno afectivo bipolar (TAB), su distribución espacial y la adherencia al tratamiento. Métodos: estudio descriptivo y transversal con muestreo no probabilístico, realizado en el Centro de Atención Psicosocial de Divinópolis/Minas Gerais, de febrero/2017 a febrero/2018 con 35 pacientes diagnosticados de TAB, sometidos a un cuestionario, escala clínica y llamadas telefónicas. Análisis realizado a través de técnicas univariadas y multivariadas. Estudio aprobado por Comité de Ética en Investigación. Resultados: La mayoría de la población estudiada tenía una predicción positiva para la adherencia al tratamiento, que se asoció con el género, la edad, el estilo de vida saludable, el apoyo de las redes sociales y comunitarias, el saneamiento básico, el acceso a los servicios de salud social y los beneficios del gobierno. Conclusión: la adherencia al tratamiento es producto de la interacción entre las dimensiones relacionadas con el paciente, el servicio de salud, los factores socioeconómicos y la terapia propuesta.

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Generar recomendaciones basadas en la mejor evidencia disponible acerca del manejo de personas con sospecha o diagnóstico de trastorno afectivo bipolar.

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BACKGROUND: Treatment of bipolar disorder (BD) usually requires drug combinations. Combinations of lithium plus valproic acid (Li/VPA) and lithium plus carbamazepine (Li/CBZ) are used in clinical practice but were not previously compared in a head-to-head trial. OBJECTIVE: The objective of this trial was to compare the efficacy and tolerability of Li/VPA versus Li/CBZ in treating type 1 BD in any phase of illness in young individuals. METHODS: LICAVAL was a randomized, unicenter, open-label, parallel-group trial that was conducted from January 2009 to December 2012 in a tertiary hospital in São Paulo, Brazil. Participants were between 18 and 35 years old and were followed up for 2 years. Our primary outcome was the number of participants achieving/maintaining response and remission during the acute and maintenance phases of BD treatment, respectively. Other outcomes assessed were symptom severity and adverse events throughout the study. In the analysis of the primary outcome, we compared groups by using a two-way repeated measures analysis of variance and estimated effect sizes by using Cohen's d. RESULTS: Of our 64 participants, 36 were allocated to Li/VPA and 28 to Li/CBZ. Our sample was composed predominantly of females (66.6%) and the average age was 27.8 years. A total of 27 (45.0%) participants had depression, 17 (28.3%) had mania/hypomania, and 16 (26.7%) had a mixed state. We found no between-group differences in CGI-BP (Clinical Global Impression Scale modified for use in bipolar disorder) scores (P = 0.326) or in any other outcome. Side effects differed significantly between groups only in the first week of treatment (P = 0.021), and there were more side effects in the Li/VPA group. Also, the Li/VPA group gained weight (+2.1 kg) whereas the Li/CBZ group presented slight weight loss (-0.2 kg). CONCLUSION: Our study suggests that Li/VPA and Li/CBZ have similar efficacy and tolerability in BD but that Li/CBZ might have metabolic advantages in the long term. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00976794 . Registered on September 9, 2009.

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INTRODUCTION: Epidemiological studies have described a high comorbidity of substance use disorders with another psychiatric disorder, which has been called dual pathology. However, the aetiological mechanisms underlying this association are still not fully understood. AIM: To carry out a preliminary study of the effect of polymorphism rs1051730 of the gene group CHRNA5-CHRNA3-CHRNB4 through a case-control study. SUBJECTS AND METHODS: A total of 225 subjects were selected and divided into three groups: those diagnosed with bipolar disorder, those with nicotine dependence, and subjects without nicotine dependence or any other psychiatric disorder. Genotyping was performed by real-time polymerase chain reaction. Genetic association analysis was performed using chi-square tests and multivariate logistic regressions. RESULTS: On comparing allelic frequencies with the control group, we found that polymorphism rs1051730 was associated with nicotine dependence (p = 0.03), but not with bipolar disorder (p = 0.94). CONCLUSION: Variant rs1051730 was associated with nicotine dependence in the Mexican population and showed the same effect in dual pathology. However, further studies are recommended to obtain conclusive results.

TITLE: Analisis del polimorfismo rs1051730 de CHRNA3 en pacientes con patologia dual en poblacion mexicana.Introduccion. Estudios epidemiologicos han descrito una alta comorbilidad de los trastornos de uso de sustancias con otro trastorno psiquiatrico, al cual se le ha llamado patologia dual. Sin embargo, los mecanismos etiologicos de esta asociacion continuan siendo dificiles de entender. Objetivo. Realizar un estudio preliminar del efecto del polimorfismo rs1051730 del grupo de genes CHRNA5-CHRNA3-CHRNB4 a traves de un estudio de casos y controles. Sujetos y metodos. Se selecciono a un total de 225 sujetos, divididos en tres grupos: con diagnostico de trastorno bipolar, con dependencia a la nicotina y sujetos sin dependencia a la nicotina o cualquier otro trastorno psiquiatrico. La genotipificacion se realizo mediante reaccion en cadena de la polimerasa en tiempo real. El analisis de asociacion genetica se realizo mediante pruebas de chi cuadrado y regresiones logisticas multivariables. Resultados. Al comparar las frecuencias alelicas con el grupo control, encontramos que el polimorfismo rs1051730 se asocio con el grupo de dependencia a la nicotina (p = 0,03), pero no con el de trastorno bipolar (p = 0,94). Conclusion. La variante rs1051730 se asocio con dependencia a la nicotina en la poblacion mexicana y mostro el mismo efecto en la patologia dual. Sin embargo, se recomiendan estudios adicionales para tener resultados concluyentes.

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BACKGROUND: Concurrence of substance use disorders (SUDs) is high in individuals with psychiatric illnesses; more importantly, individuals with both disorders (dual diagnosis) have more severe symptoms. Psychiatric disorders have been proposed to share a genetic susceptibility with SUDs. To explore this shared genetic susceptibility, we analyzed whether any of the polygenic risk scores (PRSs) for psychiatric disorders could be associated to dual diagnosis in patients with schizophrenia (SCZ) or bipolar disorder (BD). METHODS: We included 192 individuals of Mexican ancestry: 72 with SCZ, 53 with BD, and 67 unrelated controls without psychiatric disorders. We derived calculations of PRS for autism spectrum disorders, attention-deficit/hyperactive disorder, BD, major depression, and SCZ using summary genome-wide association statistics previously published. RESULTS: We found that dual diagnosis had a shared genetic susceptibility with major depressive disorder (MDD) and SCZ; furthermore, in individuals with BD, dual diagnosis could be predicted by PRS for MDD. CONCLUSIONS: Our results reinforce the notion that individuals with dual diagnosis have a higher genetic susceptibility to develop both disorders. However, analyses of larger sample sizes are required to further clarify how to predict risks through PRS within different populations.

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Background Concurrence of substance use disorders (SUDs) is high in individuals with psychiatric illnesses; more importantly, individuals with both disorders (dual diagnosis) have more severe symptoms. Psychiatric disorders have been proposed to share a genetic susceptibility with SUDs. To explore this shared genetic susceptibility, we analyzed whether any of the polygenic risk scores (PRSs) for psychiatric disorders could be associated to dual diagnosis in patients with schizophrenia (SCZ) or bipolar disorder (BD). Methods We included 192 individuals of Mexican ancestry: 72 with SCZ, 53 with BD, and 67 unrelated controls without psychiatric disorders. We derived calculations of PRS for autism spectrum disorders, attention-deficit/hyperactive disorder, BD, major depression, and SCZ using summary genome-wide association statistics previously published. Results We found that dual diagnosis had a shared genetic susceptibility with major depressive disorder (MDD) and SCZ; furthermore, in individuals with BD, dual diagnosis could be predicted by PRS for MDD. Conclusions Our results reinforce the notion that individuals with dual diagnosis have a higher genetic susceptibility to develop both disorders. However, analyses of larger sample sizes are required to further clarify how to predict risks through PRS within different populations.

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Abstract Introduction Although bipolar disorder (BD) is traditionally included among mood disorders, some authors believe that changes in energy and motor activity, rather than mood changes, represent the true cardinal symptoms in mania and depression. The aim of the current study was to identify which cluster of the Hamilton Depression Rating Scale (HAM-D) better distinguishes between mania, depression and euthymia. Method A group of 106 patients with BD were followed for 13 years and repeatedly assessed with the HAM-D as well as with other clinical scales. To perform a comparison, HAM-D items were classified according to clinical criteria into three clusters: energy/activity symptoms, mood symptoms, and other symptoms. Item response theory (IRT) analyses were performed to provide a test information curve for those three clusters. We measured the prevalence of one cluster of symptoms over the other two throughout the latent trait. Results Considering HAM-D items individually, the IRT analysis revealed that there was a mixture of mood and energy/activity symptoms among the most discriminative items, both in depression and in euthymia. However, in mania, only energy/activity symptoms - i.e., general somatic symptoms and retardation - were among the most informative items. Considering the classification of items, both in depression as in mania, the energy/activity cluster was more informative than the mood cluster according to the IRT analysis. Conclusion Our data reinforce the view of hyperactivity and motor retardation as cardinal changes of mania and depression, respectively.

Resumo Introdução Embora o transtorno bipolar (TB) seja tradicionalmente incluído entre os transtornos do humor, alguns autores acreditam que as alterações na energia e na atividade motora, em vez das alterações no humor, representam os verdadeiros sintomas cardinais na mania e na depressão. O objetivo do presente estudo foi identificar qual grupo da Escala de Depressão de Hamilton (HAM-D) distingue melhor entre mania, depressão e eutimia. Método Um grupo de 106 pacientes com TB foram acompanhados por 13 anos e avaliados repetidamente com a HAM-D e com outras escalas clínicas. Para realizar uma comparação, os itens da HAM-D foram classificados de acordo com critérios clínicos em três grupos: sintomas de energia/atividade, sintomas de humor e outros sintomas. Foram realizadas análises da teoria da resposta ao item (TRI) para fornecer uma curva de informações de teste para esses três grupos. Medimos a prevalência de um grupo de sintomas em comparação aos outros dois através do traço latente. Resultados Considerando os itens da HAM-D individualmente, a análise da TRI revelou que havia uma mistura de sintomas de humor e de energia/atividade entre os itens mais discriminativos, tanto na depressão quanto na eutimia. No entanto, na mania, apenas os sintomas de energia/atividade - ou seja, sintomas somáticos gerais e retardo - estavam entre os itens mais informativos. Considerando a classificação dos itens, tanto na depressão quanto na mania, o grupo energia/atividade foi mais informativo que o grupo humor, de acordo com a análise da TRI. Conclusão Nossos dados reforçam a visão da hiperatividade e do retardo motor como as alterações cardinais de mania e depressão, respectivamente.

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Abstract Background Optical coherence tomography (OCT) has been recently used to investigate neuropsychiatric disorders. Objective The aim of this study was to compare the retinal nerve fiber layer thickness (RNFLT) and the ganglion cell layer (GCL) volume in patients with type 1 bipolar disorder (BPD1, diagnosed according to DSM 5) to the values in healthy controls. Methods Eighty consecutive outpatients with a diagnosis of euthymic BPD1 and 80 healthy controls were enrolled in the study. Following assessment with the Sociodemographic Data Form, Structured Clinical Interview for DSM-IV (SCID-I), Hamilton Depression Scale and Young Mania Evaluation Scale, both groups underwent Optical coherence tomography (OCT). Results The mean RNFL thickness and mean GCL volume were significantly lower in the BPD1 group than in the controls (p < 0.05). The GCL global value had a significant and independent effect in distinguishing the BPD1 patients from the controls. A cut-off value of 101 mm3 for global GCL volume was proposed to distinguish BPD1 patients from controls with a sensitivity of 87.5%. Discussion Lower values of GCL volume and RNFLT in patients suffering from BPD1 suggest that neurodegeneration may occur during the course of BPD and that this degeneration can be characterized in particular by a thinning of the GCL volume.

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RESUMEN Objetivo: Describir y discutir la evidencia actual sobre la relación entre desempeño cognitivo, trastorno afectivo bipolar (TAB) y síndrome metabólico (SM). Métodos: Se buscaron artículos relacionados en distintas bases de datos bibliográficas (MEDLINE, EMBASE, Scielo), y con los artículos seleccionados se realizó una revisión narrativa de la literatura. Resultados: Hasta el momento no se ha estudiado ampliamente el SM en el TAB, pero sí hay datos importantes en la asociación con las variables metabólicas individuales. Se señala que la obesidad de los pacientes con TAB se asocia con peor desempeño en memoria verbal, velocidad de procesamiento psicomotor y atención sostenida. Parecería que la hipertrigliceridemia de los pacientes con TAB está en relación con deterioro en la función ejecutiva, y la hipertensión arterial, con el deterioro en la función cognitiva general. Conclusiones: Aunque algunas variables del SM se asocian con peor desempeño cognitivo en pacientes con TAB, faltan estudios para establecer con precisión la naturaleza de esta relación.

ABSTRACT Objective: To describe and discuss current evidence on the relationship between cognitive performance, Bipolar Affective Disorder (BAD) and Metabolic Syndrome (MS). Methods: We searched for related articles in different bibliographic databases (MEDLINE, EMBASE, Scielo) and performed a narrative review of the literature with the selected articles. Results: To date, evidence has not been conclusive and the effect of MS on BD has not been widely studied, but important correlations have been observed with individual metabolic variables. It is suggested that obesity in patients with BAD is associated wotj worse performance in verbal memory, psychomotor processing speed, and sustained attention. Hypertriglyceridemia in patients with BAD appears to be associated with a lower score in executive function tasks; hypertension appears to be associated with impairment in overall cognitive function. Conclusions: Despite the associations between MS and poor cognitive performance in patients suffering from BAD, more studies are required to precisely determine how these variables are related to each other.

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Introduction: The use of antidepressants (AD) in the treatment of bipolar depression is one of the most controversial issues in psychopharmacology. For some, AD are useful, but, for others, they should never be used in bipolar depression. Areas covered: This review examines published clinical studies on the use of ADs in bipolar depression, addressing their clinical efficacy and the occurrence of side effects, manic switches, cycle acceleration, and suicidal behavior. Meta-analyzes and review articles on the subject are also discussed. Expert opinion: Approved therapeutic options for bipolar depression are associated with not very high response rates and a high incidence of adverse effects. Patients with bipolar depression present very heterogeneous responses to the use of ADs. Some improve significantly, while others, especially those with concomitant manic symptoms, have had previous episodes of treatment-emergent mania or are rapid cyclers, exhibit manic switches or cycle acceleration. The authors conclude that the real question is not whether ADs should or should not be used in bipolar depression, but which patients benefit from these drugs and which ones are impaired. The concept of bipolar spectrum and a dimensional approach on bipolar/unipolar distinction may be useful for understanding the heterogeneity of responses to ADs.

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BACKGROUND: Studies aimed at understanding the higher risk profiles for self-inflicted violence in individuals with BD become essential as a possible predictive risk measure for the presence of suicidal behavior, corroborating the expressive reduction of suicide deaths in young people who are in psychic suffering. METHODS: The protocol was constructed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA-P) and the research question was constructed using guidelines from the Population Intervention Comparator Outcome Setting (PICOS) strategy. A third reviewer will be contacted, and two studies will be included in the selection, analysis and inclusion phases of the articles, in case of divergence, a third reviewer will be contacted. (1) methodological design studies of cohorts, case-control and cross-sectional; (2) Diagnosis of Bipolar disorder according to Diagnostic and statistical Manual of mental disorders V; (3) Studies with adult population and (4) Studies that consider at least one type of self-inflicted violence as a variable. The articles considered eligible will be analyzed by New Castle - Ottawa quality assessment scale/cross section studies (NOS) to evaluate the quality of the studies. RESULTS: The identification of the characteristics of self-harm may subsidize professionals who work in the treatment of bipolar disorder with greater attention to these practices and monitoring of possible suicidal behaviors. CONCLUSION: This study may represent one of the initial measures of evaluation on these correlations, which will allow to protocol the guidelines in the field of practice and contribute to improvements in public health indexes.

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OBJECTIVE: To describe and discuss current evidence on the relationship between cognitive performance, Bipolar Affective Disorder (BAD) and Metabolic Syndrome (MS). METHODS: We searched for related articles in different bibliographic databases (MEDLINE, EMBASE, Scielo) and performed a narrative review of the literature with the selected articles. RESULTS: To date, evidence has not been conclusive and the effect of MS on BD has not been widely studied, but important correlations have been observed with individual metabolic variables. It is suggested that obesity in patients with BAD is associated wotj worse performance in verbal memory, psychomotor processing speed, and sustained attention. Hypertriglyceridemia in patients with BAD appears to be associated with a lower score in executive function tasks; hypertension appears to be associated with impairment in overall cognitive function. CONCLUSIONS: Despite the associations between MS and poor cognitive performance in patients suffering from BAD, more studies are required to precisely determine how these variables are related to each other.

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OBJECTIVES: The International Society for Bipolar Disorders Big Data Task Force assembled leading researchers in the field of bipolar disorder (BD), machine learning, and big data with extensive experience to evaluate the rationale of machine learning and big data analytics strategies for BD. METHOD: A task force was convened to examine and integrate findings from the scientific literature related to machine learning and big data based studies to clarify terminology and to describe challenges and potential applications in the field of BD. We also systematically searched PubMed, Embase, and Web of Science for articles published up to January 2019 that used machine learning in BD. RESULTS: The results suggested that big data analytics has the potential to provide risk calculators to aid in treatment decisions and predict clinical prognosis, including suicidality, for individual patients. This approach can advance diagnosis by enabling discovery of more relevant data-driven phenotypes, as well as by predicting transition to the disorder in high-risk unaffected subjects. We also discuss the most frequent challenges that big data analytics applications can face, such as heterogeneity, lack of external validation and replication of some studies, cost and non-stationary distribution of the data, and lack of appropriate funding. CONCLUSION: Machine learning-based studies, including atheoretical data-driven big data approaches, provide an opportunity to more accurately detect those who are at risk, parse-relevant phenotypes as well as inform treatment selection and prognosis. However, several methodological challenges need to be addressed in order to translate research findings to clinical settings.

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Pediatric Bipolar Disorder (PBD) is a highly heritable condition responsible for 18% of all pediatric mental health hospitalizations. Despite the heritability of this disorder, few studies have assessed potential differences in the clinical manifestation of PBD among patients with a clear parental history of BD. Additionally, while recent studies suggest that attentional deficits are a potential endophenotypic marker of PBD, it is unclear whether heritability is a relevant contributor to these symptoms. In order to address this gap, the present study assessed 61 youth with PBD (6-17 years old), corresponding to 27 offspring of BD patients, and 31 PBD patients without a parental history of the disorder. All standardized assessments, including the K-SADS-PL-W were performed by trained child and adolescent psychiatrists. We performed a logistic multivariate model using the variables of ADHD, rapid cycling, and lifetime psychosis. Rates of ADHD comorbidity were significantly higher among PBD patients who had a parent with BD. Furthermore, PBD patients who had a parent with BD showed a trend toward significance of earlier symptom onset. PBD offspring did not show increased rates of suicide attempts, rapid cycling, or psychosis. Given these findings, it appears that PBD patients who have a parent with BD may represent a distinct endophenotype of the disorder. Future longitudinal and larger studies are required to confirm our findings.

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Introduction: Clinical and genetic study of psychiatric conditions has underscored the co-occurrence of complex phenotypes and the need to refine them. Bipolar Disorder (BD) and Binge Eating (BE) behavior are common psychiatric conditions that have high heritability and high co-occurrence, such that at least one quarter of BD patients have BE (BD + BE). Genetic studies of BD alone and of BE alone suggest complex polygenic risk models, with many genetic risk loci yet to be identified. Areas covered: We review studies of the epidemiology of BD+BE, its clinical features (cognitive traits, psychiatric comorbidity, and role of obesity), genomic studies (of BD, eating disorders (ED) defined by BE, and BD + BE), and therapeutic implications of BD + BE. Expert opinion: Subphenotyping of complex psychiatric disorders reduces heterogeneity and increases statistical power and effect size; thus, it enhances our capacity to find missing genetic (and other) risk factors. BD + BE has a severe clinical picture and genetic studies suggests a distinct genetic architecture. Differential therapeutic interventions may be needed for patients with BD + BE compared with BD patients without BE. Recognizing the BD + BE subphenotype is an example of moving towards more precise clinical and genetic entities.

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INTRODUCTION: The objective of this study was to identify whether mixed states in bipolar disorder (BD) are associated with more frequent suicidal behavior when compared to manic/hypomanic and depressive episodes. METHOD: We performed a systematic search of the scientific literature on the subject using the PubMed, ISI Web Of Science, PsycINFO and SciELO databases. The terms chosen for the search were (bipolar) AND (suicid*) AND (mixed). We selected original studies comparing suicidal behavior of patients in mixed states and suicidal behavior of patients in other BD phases. RESULTS: Sixteen papers fit the selection criteria. Twelve of the original 16 studies compared suicidal behavior in mixed states and pure mania, and the majority of these studies (n = 11) revealed that suicidal behavior was more frequent among individuals in mixed states. Five of the papers compared suicidal behavior between depressive and mixed phases of BD. One of these five papers reported more severe suicidal behavior in patients in mixed states and another described more frequent suicidal behavior in patients with pure depression. There were no significant statistical differences between groups in the remaining three of these five studies. CONCLUSION: During acute BD episodes, suicidal behavior is more strongly associated with mixed states than with pure mania or hypomania. However, it was not possible to demonstrate that the association between suicidal behavior and mixed states is stronger than the association between suicidal behavior and depressive phases. The results hereby presented are worth considering in clinical practice to better evaluate suicide risk and to prevent suicide.