While most patients with depression respond to pharmacotherapy and psychotherapy, about one-third will present treatment resistance to these interventions. For patients with treatment-resistant depression (TRD), invasive neurostimulation therapies such as vagus nerve stimulation, deep brain stimulation, and epidural cortical stimulation may be considered. We performed a narrative review of the published literature to identify papers discussing clinical studies with invasive neurostimulation therapies for TRD. After a database search and title and abstract screening, relevant English-language articles were analyzed. Vagus nerve stimulation, approved by the U.S. Food and Drug Administration as a TRD treatment, may take several months to show therapeutic benefits, and the average response rate varies from 15.2-83%. Deep brain stimulation studies have shown encouraging results, including rapid response rates (> 30%), despite conflicting findings from randomized controlled trials. Several brain regions, such as the subcallosal-cingulate gyrus, nucleus accumbens, ventral capsule/ventral striatum, anterior limb of the internal capsule, medial-forebrain bundle, lateral habenula, inferior-thalamic peduncle, and the bed-nucleus of the stria terminalis have been identified as key targets for TRD management. Epidural cortical stimulation, an invasive intervention with few reported cases, showed positive results (40-60% response), although more extensive trials are needed to confirm its potential in patients with TRD.

Treatment-resistant bipolar depression (TRBD) has been reported in about one-quarter of patients with bipolar disorders, and few interventions have shown clear and established effectiveness. We conducted a narrative review of the published medical literature to identify papers discussing treatment-resistant depression concepts and novel interventions for bipolar depression that focus on TRBD. We searched for potentially relevant English-language articles published in the last decade. Selected articles (based on the title and abstract) were retrieved for a more detailed evaluation. A number of promising new interventions, both pharmacological and non-pharmacological, are being investigated for TRBD treatment, including ketamine, lurasidone, D-cycloserine, pioglitazone, N-acetylcysteine, angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers, cyclooxygenase 2 inhibitors, magnetic seizure therapy, intermittent theta-burst stimulation, deep transcranial magnetic stimulation, vagus nerve stimulation therapy, and deep brain stimulation. Although there is no consensus about the concept of TRBD, better clarification of the neurobiology associated with treatment non-response could help identify novel strategies. More research is warranted, mainly focusing on personalizing current treatments to optimize response and remission rates.

Objective: Bipolar disorder (BD) is highly heritable. The present study aimed at identifying brain morphometric features that could represent markers of BD vulnerability in non-bipolar relatives of bipolar patients. Methods: In the present study, structural magnetic resonance imaging brain scans were acquired from a total of 93 subjects, including 31 patients with BD, 31 non-bipolar relatives of BD patients, and 31 healthy controls. Volumetric measurements of the anterior cingulate cortex (ACC), lateral ventricles, amygdala, and hippocampus were completed using the automated software FreeSurfer. Results: Analysis of covariance (with age, gender, and intracranial volume as covariates) indicated smaller left ACC volumes in unaffected relatives as compared to healthy controls and BD patients (p = 0.004 and p = 0.037, respectively). No additional statistically significant differences were detected for other brain structures. Conclusion: Our findings suggest smaller left ACC volume as a viable biomarker candidate for BD.

OBJETIVO: Comparar a eficácia da olanzapina, ziprasidona, haloperidol associado ao midazolam, haloperidol associado à prometazina e haloperidol isoladamente por via intramuscular como primeira escolha no tratamento de pacientes em agitação e agressividade. MÉTODO: Cento e cinquenta pacientes com agitação psicomotora por transtorno psicótico ou transtorno bipolar foram recrutados para estudo duplo-cego e receberam olanzapina, ziprasidona, haloperidol associado a midazolam, haloperidol associado a prometazina ou haloperidol isoladamente. Foram aplicadas as escalas Overt Agitation Severity Scale, Overt Aggression Scale e Ramsay Sedation Scale no período de 12 horas após a primeira aplicação. RESULTADOS: Todas as medicações foram capazes de acalmar os pacientes após uma hora da administração. Apenas a olanzapina e o haloperidol reduziram a agitação para menos de 10 pontos e apenas a olanzapina reduziu a agressividade para menos de quatro pontos nesse período. Doze horas depois, apenas o haloperidol com midazolam apresentou valores altos para a agitação e agressividade, e também esteve relacionado com maior proporção de efeitos colaterais. A ziprasidona, a olanzapina e o haloperidol apresentaram resultados mais estáveis para o controle da agitação e a ziprasidona, haloperidol associado a prometazina e olanzapina para o controle da agressividade. CONCLUSÃO: A olanzapina, a ziprasidona, o haloperidol associado a prometazina, o haloperidol associado ao midazolam e o haloperidol isoladamente foram efetivos no controle da agitação e da agressividade secundária a transtornos mentais dentro de 12 horas. Todas as drogas apresentaram vantagens e desvantagens, exceto pela associação haloperidol e midazolam que demonstrou os piores resultados em todos os parâmetros.

OBJECTIVE: To compare the effectiveness of intramuscular olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone as the first medication(s) used to treat patients with agitation and aggressive behavior. METHOD: One hundred fifty patients with agitation caused by psychotic or bipolar disorder were randomly assigned under double-blind conditions to receive olanzapine, ziprasidone, haloperidol plus midazolam, haloperidol plus promethazine or haloperidol alone. The Overt Agitation Severity Scale, Overt Aggression Scale and Ramsay Sedation Scale were applied within 12 hours after the first dosage. RESULTS: All medications produced a calming effect within one hour of administration, but only olanzapine and haloperidol reduced agitation by less than 10 points, and only olanzapine reduced aggression by less than four points in the first hour. After twelve hours, only patients treated with haloperidol plus midazolam had high levels of agitation and aggression and also more side effects. Ziprasidone, olanzapine and haloperidol alone had more stable results for agitation control, while ziprasidone, haloperidol plus promethazine and olanzapine had stable results for aggression control. CONCLUSION: Olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol were effective in controlling agitation and aggression caused by mental illness over 12 hours. Although all the drugs had advantages and disadvantages, haloperidol plus midazolam was associated with the worst results in all the observed parameters.

OBJETIVO: O objetivo do presente estudo foi descrever a análise perceptivo-auditiva e de psicodinâmica vocal de amostras de fala de personagens suicidas em filmes de cinema. MÉTODO: Foram analisadas amostras de fala de 48 personagens suicidas (27 homens, 21 mulheres), extraídas de 36 filmes produzidos no período de 1968 a 2006. As amostras foram analisadas utilizando-se um protocolo especificamente produzido para o registro das características da voz por meio da análise perceptivo-auditiva (qualidade vocal, ressonância, pitch, loudness, modulação, pausas, articulação e ritmo de fala) e da psicodinâmica vocal. RESULTADOS: 85,5% das amostras (n = 41) apresentaram alterações em ao menos cinco parâmetros da análise perceptivo-auditiva, com destaque para soprosidade (n = 42; 87,5% das amostras), rugosidade (n = 39; 81,2%) e tensão (n = 29; 60,4%), bem como ressonância laringofaríngea (n = 39; 81,2%), pitch agudo (n = 14; 29,2%) e loudness fraca (n = 31; 64,6%). A análise da psicodinâmica vocal revelou desânimo em 50% (n = 24) das amostras, desesperança em 47,9% (n = 23), resignação em 37,5% (n = 18) e tristeza em 33,3% (n = 16). CONCLUSÃO: Os achados do presente estudo apontam para padrões vocais característicos utilizados por atores na interpretação de personagens suicidas. Se replicados entre pacientes reais, estes achados podem contribuir para o aperfeiçoamento da avaliação do risco de suicídio e a instauração de medidas preventivas.

OBJECTIVE: The aim of this study was to describe the auditory-perceptive evaluation and the psychodynamic aspects of voice samples among suicidal movie characters. METHOD: Voice samples of 48 characters (27 male, 21 female), extracted from 36 movies produced between 1968 and 2006, were analyzed. The samples were evaluated through a specific protocol focusing on the auditory-perceptive evaluation (voice quality, resonance, pitch, loudness, modulation, pauses, articulation and rhythm) and the psychodynamic aspects of voice. RESULTS: 85.5% of the samples exhibited abnormal findings in at least five parameters of the auditory-perceptive analysis, such as breathiness (n = 42; 87.5% of the samples), hoarseness (n = 39; 81.2%) and strain (n = 29; 60.4%), as well as laryngopharingeal resonance (n = 39; 81.2%), either high pitch (n = 14; 29.2%), or decreased loudness (n = 31; 64.6%). With respect to the psychodynamic aspects, dismay was detected in 50% (n = 24) of the samples, hopelessness in 47.9% (n = 23), resignation in 37.5% (n = 18), and sadness in 33.3% (n = 16). CONCLUSION: Our findings suggest the existence of specific patterns used by actors during the interpretation of suicidal characters. The replication of these findings among real patients may contribute to improvement in the evaluation of potential suicidal patients, as well as the implementation of preventive measures.

CONTEXTO: Os conceitos de transtornos de humor e de personalidade sofreram diversas mudanças nas últimas décadas. Historicamente, esses conceitos foram construídos em paralelo, isto é, transtornos de humor e personalidade são considerados como transtornos independentes em relação ao diagnóstico, ao prognóstico e ao tratamento. Recentemente, entretanto, novas propostas na conceituação nosológica desses transtornos levantaram a questão de uma possível sobreposição dessas entidades, tornando o diagnóstico diferencial entre esses transtornos muitas vezes difícil. OBJETIVOS: Realizar uma revisão de literatura sobre a evolução dos conceitos de transtorno de humor e personalidade sob uma perspectiva histórica, focando em publicações relacionadas ao diagnóstico. MÉTODO: Revisão compreensiva da literatura utilizando o banco de dados MEDLINE (1990-2007). RESULTADOS: Ao contrário do conceito de transtorno de humor, que se apresenta estável e relativamente sem modificações desde suas primeiras descrições, o conceito de transtorno de personalidade mostra considerável variação ao longo dos diferentes achados de literatura. Assim, ambos os grupos de transtornos têm sido conceituados tanto categorial como dimensionalmente. Esta última abordagem pode ser, em parte, responsável pelas dificuldades algumas vezes encontradas no diagnóstico diferencial desses transtornos. CONCLUSÃO: O diagnóstico diferencial entre transtornos de humor e personalidade ainda representa um sério problema na prática clínica e não pode ser completamente esclarecido com base nas evidências disponíveis. O melhor entendimento da base fisiopatológica desses transtornos, bem como a identificação mais precisa de seus marcadores biológicos, pode ajudar a redefinir seus conceitos e seus status nosológicos atuais.

BACKGROUND: The concepts of mood and personality disorders have faced countless changes over the last decades. Historically, these concepts have been built in parallel, that is, mood and personality disorders have been considered as independent disorders with respect to diagnosis, prognosis and treatment. Recently, however, new proposes on the nosological conceptualization of these disorders have raised the question of a possible overlap between these nosological entities, making the differential diagnosis between these disorders difficult at times. OBJECTIVES: To carry out a literature review on the evolution of mood and personality disorders concepts under a historical perspective, focusing on diagnostic-related issues. METHOD: A comprehensive MEDLINE literature search (1990-2007) was conducted. RESULTS: Contrarily to the concept of mood disorder, which seems to be stable and relatively unchanged since its first description, the concept of personality disorder shows considerable variation over the different literature findings. Thus, both groups of disorders have been conceptualized not only in a categorical point of view but also according to a dimensional approach. The last one may be at least partially accountable for the difficulties sometimes observed in the differential diagnosis of these disorders. DISCUSSION: The differential diagnosis between mood and personality disorders may still represent a serious problem in clinical settings, and can not be completely clarified in light of available evidence. A better understanding of the pathophysiological basis of these disorders, as well as the more accurate identification of their biological markers can help redefining their concepts and their nosological current status.