Baicalin Ameliorates Corticosterone-Induced Depression by Promoting Neurodevelopment of Hippocampal via mTOR/GSK3β Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the role of hippocampal neurodevelopment in the antidepressant effect of baicalin.@*METHODS@#Forty male Institute of Cancer Research mice were divided into control, corticosterone (CORT, 40 mg/kg), CORT+baicalin-L (25 mg/kg), CORT+baicalin-H (50 mg/kg), and CORT+fluoxetine (10 mg/kg) groups according to a random number table. An animal model of depression was established by chronic CORT exposure. Behavioral tests were used to assess the reliability of depression model and the antidepressant effect of baicalin. In addition, Nissl staining and immunofluorescence were used to evaluate the effect of baicalin on hippocampal neurodevelopment in mice. The protein and mRNA expression levels of neurodevelopment-related factors were detected by Western blot analysis and real-time polymerase chain reaction, respectively.@*RESULTS@#Baicalin significantly ameliorated the depressive-like behavior of mice resulting from CORT exposure and promoted the development of dentate gyrus in hippocampus, thereby reversing the depressive-like pathological changes in hippocampal neurons caused by CORT neurotoxicity. Moreover, baicalin significantly decreased the protein and mRNA expression levels of glycogen synthase kinase 3β (GSK3β), and upregulated the expression levels of cell cycle protein D1, p-mammalian target of rapamycin (mTOR), doublecortin, and brain-derived neurotrophic factor (all P<0.01). There were no significant differences between baicalin and fluoxetine groups (P>0.05).@*CONCLUSION@#Baicalin can promote the development of hippocampal neurons via mTOR/GSK3β signaling pathway, thus protect mice against CORT-induced neurotoxicity and play an antidepressant role.

Dlg1 Knockout Inhibits Microglial Activation and Alleviates Lipopolysaccharide-Induced Depression-Like Behavior in Mice / 神经科学通报·英文版

Microglia-mediated neuroinflammation is widely perceived as a contributor to numerous neurological diseases and mental disorders including depression. Discs large homolog 1 (Dlg1), an adaptor protein, regulates cell polarization and the function of K

Occupational exposure to pesticides and health symptoms among family farmers in Brazil

ABSTRACT OBJECTIVE: To explore the association of occupational pesticide exposure with acute and mental health symptoms. METHODS: Cross-sectional survey carried out with 78 Brazilian family farmers, who were pesticide applicators and helpers conveniently selected. Symptoms and exposure data were collected by interviews, and mental health outcomes by the Self-Reporting Questionnaire. Blood samples were analyzed to assess cholinesterase levels. Exposure indicators and symptoms were compared between applicators and helpers, and Poisson regression was performed to estimate prevalence ratios. RESULTS: Farmers reported exposure to multiple pesticides from early ages; they worked without safety training, technical support, and full protective equipment, and they had a high prevalence of acute and mental health symptoms (e.g., headache, mucosal irritation, tachycardia, and depressive signs). Applicators had more cholinesterase changes than helpers, but less symptoms. Helpers used less personal protection and had significantly higher prevalence ratio of headache, dyspnea, wheezing, cough, poor digestion, tiredness, and feeling worthless, after adjustment. CONCLUSIONS: Acute and mental health symptoms were observed, both among farmers and helpers. Thus, surveillance actions must be reinforced in Brazil, technical support and safety training improved, focused on applicators and helpers, who are occupationally and environmentally exposed to pesticides. Agricultural practices of these groups with less pesticide use should receive incentive.

Emerging intervention of antidepressant with DMARD in non-cancerous nociceptive persistent pain associated depression in FCA induced rheumatoid arthritic rats

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that causes pain, systemic complications and premature mortality. Depression has also been identified as a problem for persons with RA. This association remaining significant even after the degree of disease activity is controlled. In the present study, the efficacy of combination therapeutic effect of antidepressant (amitriptyline) with Disease Modifying Anti rheumatoid drug (leflunomide) was determined in rheumatoid arthritis pain associated depression in Freund's complete adjuvant (FCA) induced arthritic rats. Drug treatment was started 9 days after induction of FCA induced arthritis in rats. The antiarthritic activity was assessed by measuring paw volume, weight-bearing, hematological, biochemical, serological parameters, Radiographic analysis and Histopathology of tibiotarsal joints. The antidepressant activity was assessed by Forced swimming test, Rota-rod test and confirmed by estimation of brain neuro transmitters (serotonin and norepinephrine) level. Results of this study revealed that leflunomide and amitriptyline combination showed more significant (p<0.001) antiarthritic and antidepressant action and leflunomide alone treatment showed significant (p<0.001) antiarthritic activity only as compared to arthritic control. The leflunomide and low dose amitriptyline combination found to be more effective in pain associated depression in rheumatoid arthritic rats

Depressive episode incidence in patients with chronic hepatitis c treated with pegylated interferon and ribavirin

ABSTRACT Background The effectiveness of antiviral therapy with pegylated interferon and ribavirin for chronic hepatitis C is far from ideal and presents several adverse events. Among such events, there is the depressive episode that can even lead to treatment discontinuity Objective Analyze the incidence of depressive episodes in patients with chronic hepatitis C treated with pegylated interferon (IFN-PEG) and ribavirin, as well as the possible factors associated with its occurrence and its impact on patients' sustained virological response. Methods People with chronic hepatitis C undergoing antiviral therapy were interviewed at the baseline, at the 4th, 12th, 24th and 48th treatment weeks and 4 weeks after the end of it, using the HADS scale for tracking the depressive episode. Patients with HADS ≥9 were subjected to Beck Depression Inventory (BDI-II) to grade the episode. Clinical, sociodemographic, laboratorial and histological variables were obtained to identify factors related to the onset of depression. The sustained virological response rate (negative HCV-RNA 6 months after end of therapy) was compared among patients with and without depressive symptoms. Results The study comprised 32 patients, most men (59%) with mean age of 54±11.13 years old. Genotype non-1 was prevalent (56%) and 81% of the patients were non-cirrhotic. The depressive episode was diagnosed in 25% of the patients and the peak incidence was found in the 12th treatment week. The depressive episode was moderate in 87% of the patients and only one patient abandoned the treatment. None of the analyzed factors was associated with depressive episode onset. A trend was observed in female patients ( P=0.08). The sustained virological response rate was of 75% and 67% in patients with and without depressive episode, respectively (P =0.66). Conclusion The incidence of depressive episodes in patients with chronic hepatitis C undergoing antiviral therapy was of 25% and the 12th treatment week was the most critical one. The presence of depressive episode did not affect the sustained virological response rate.

RESUMO Contexto A terapia antiviral para a hepatite C crônica com interferon peguilado e ribavirina tem eficácia longe do ideal e é repleta de eventos adversos. Entre estes, destaca-se o transtorno depressivo que pode inclusive levar a interrupção do tratamento. Objetivos Em pacientes com hepatite C crônica tratados com interferon peguilado (IFN-PEG) e ribavirina, verificar a incidência de episódio depressivo, os possíveis fatores associados ao seu surgimento e o impacto deste sobre a resposta virológica sustentada. Métodos Portadores de hepatite C crônica submetidos à terapia antiviral foram entrevistados no Baseline, nas semanas 4, 12, 24, 48 de tratamento e quatro semanas após o término do mesmo utilizando a escala HADS para rastreamento do episódio depressivo e naqueles com HADS ≥9 o Inventário de Depressão de Beck (BDI-II) para graduação do episódio. Variáveis clínicas, sociodemográficas, laboratoriais e histológicas foram obtidas com o objetivo de identificar os fatores relacionados ao surgimento da depressão. A taxa de resposta virológica sustentada (HCV-RNA negativo seis meses após a interrupção da terapia) foi comparada entre os pacientes com e sem sintomas depressivos. Resultados Foram incluídos 32 pacientes, a maioria do sexo masculino (59%) e com média de idade de 54±11,13 anos. Prevaleceu o genótipo não 1 (56%) e 81% dos pacientes foram não cirróticos. Episódio depressivo foi diagnosticado em 25% dos pacientes sendo o pico de incidência observado na semana 12 de tratamento. O episódio depressivo foi moderado em 87% dos pacientes e motivou a interrupção em somente 1 deles. Nenhum dos fatores analisados foi associado ao surgimento de episódio depressivo observando-se uma tendência com relação ao sexo feminino ( P =0,08). A taxa de resposta virológica sustentada foi 75% e 67% nos pacientes com e sem episódio depressivo, respectivamente ( P =0,66). Conclusão A incidência de episódio depressivo em pacientes com hepatite C crônica submetidos à terapia antiviral foi de 25% e a semana 12 é a mais crítica. A presença de episódio depressivo não interferiu na taxa de resposta virológica sustentada.

Correlation between depressive symptoms and quality of life in users of psychoactive substances / Relación entre los síntomas depresivos y la calidad de vida en los usuarios de sustancias psicoactivas / Correlação entre sintomas depressivos e qualidade de vida de usuários de substâncias psicoativas

Objectives: To evaluate the correlation between the presence of depressive symptoms and quality of life in users of psychoactive substances from Psychosocial Attention Centers in Mato Grosso. Method: A cross-sectional analytical study, conducted in Psychosocial Attention Centers, with 109 users. The instruments used were: Medical Outcomes Study 36, Beck Depression Inventory, socio-demographic variables and the use of psychoactive substances. A Tukey analysis and a Spearman correlation were conducted with a significance level of α<0,05. Results: The most affected domains of quality of life were emotional, social and mental health aspects, besides the strong correlation between depressive symptoms and quality of life. Conclusion: The use of psychoactive substances and the presence of symptoms significantly interfere in the life of users, which can compromise the motivation to the treatment, negatively affecting the quality of life in this population.

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Objetivo: Evaluar la relación de los síntomas depresivos y la calidad de vida en los usuarios de sustancias psicoactivas de los Centros de Atención Psicosocial de Mato Grosso. Método: Estudio transversal analítico realizado en los Centros de Atención Psicosocial con 109 usuarios. Se utilizaron los Instrumentos: Medical Outcomes Study 36, el Inventario de Depresión de Beck, de variables sociodemográficas y del uso de sustancias psicoactivas. Se realizó el análisis de Tukey y la correlación de Spearman con nivel de significancia de α<0,05. Resultados: Los dominios más afectados de la calidad de vida fueron los aspectos emocionales, sociales y de salud mental, además de una fuerte correlación entre los síntomas depresivos y la calidad de vida. Conclusión: El uso de sustancias psicoactivas y la presencia de síntomas depresivos interfieren significativamente en la vida de los usuarios, lo que puede comprometer la motivación para el tratamiento, afectando negativamente la calidad de vida de esta población.
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Objetivos: Avaliar a correlação entre a presença de sintomas depressivos e a qualidade de vida em usuários de substâncias psicoativas dos Centros de Atenção Psicossocial de Mato Grosso. Método: Estudo transversal analítico, realizado nos Centros de Atenção Psicossocial, com 109 usuários. Foram utilizados os instrumentos Medical Outcomes Study 36, Inventário de Depressão de Beck, variáveis sociodemográficas e do uso de substâncias psicoativas. Foi realizada a análise de Tukey e correlação de Spearman com nível de significância de α<0,05. Resultados: Os domínios mais afetados da qualidade de vida foram aspectos emocionais, sociais e de saúde mental, além de forte correlação entre sintomas depressivos e qualidade de vida. Conclusão: O uso de substâncias psicoativas e a presença de sintomas interferem significativamente na vida dos usuários, o que pode comprometer a motivação para o tratamento, afetando negativamente a qualidade de vida desta população.

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Interferon-induced depression in patients with hepatitis C: an epidemiologic study / Depressão induzida por interferon em pacientes com hepatite C: um estudo epidemiológico

Objective To assess the incidence rate and severity of depressive symptoms in different time points (12, 24 and 48 weeks) in Brazilian patients with HCV treated with PEG IFN plus ribavirin. Methods We conducted an observational prospective study using the Beck Depression Inventory (BDI) and the Center for Epidemiologic Studies Depression Scale (CES-D). Results Fifty patients were included. The assessments with either scale showed the highest score of depressive symptoms in the 24th week of treatment; the mean BDI score before treatment was 6.5 ± 5.3 and the mean CES-D was 10.9 ± 7.8. After 24 weeks, the mean BDI was 16.1 ± 10.2 and mean CES-D was 18.6 ± 13.0; 46% were diagnosed with depression according to combined BDI and CES-D scores. The somatic/psychomotor subscales were highly correlated with overall scale scores . Subjects with history of substance and alcohol abuse had higher risk for IFN-induced depression. Conclusion Treatment with PEG IFN was associated with a high incidence rate of depressive symptoms in this sample of Brazilian patients, as measured by CES-D and BDI. Alcohol and substance abuse increase the risk of PEG IFN-induced depression. .

Objetivo Avaliar a incidência e a gravidade de sintomas depressivos em diferentes intervalos (12, 24 e 48 semanas) em pacientes brasileiros com HCV tratados com PEG IFN mais ribavirina. Métodos Foi feito um estudo prospectivo observacional, usando o Inventário de Depressão de Beck (BDI) e a Escala de Rastreamento Populacional de Depressão (CES-D). Resultados Foram incluídos 50 pacientes. As avaliações com ambas as escalas mostraram os maiores escores de depressão na 24a semana de tratamento; o escore BDI médio antes do tratamento foi de 6,5 ± 5,3 e o CES-D foi 10,9 ± 7,8. Após 24 semanas, o BDI médio foi 16,1± 10,2 e o CES-D foi 18,6 ± 13,0; de acordo com os escores combinados BDI e CES-D, 46% receberam diagnóstico de depressão. As subescalas somática e psicomotora tiveram alta correlação. Indivíduos com história de abuso de substâncias e de álcool apresentaram maior risco de desenvolver depressão por PEG IFN. Conclusão O tratamento com PEG IFN associou-se a uma alta incidência de sintomas depressivos nessa população de pacientes brasileiros, de acordo com a BDI e CES-D. Abuso de álcool e substâncias aumentam o risco de depressão induzida por PEG IFN. .

Studying the effect of chronic glucocorticoide injection on the depressive behavior in mice

Chronic cortisol is considered to be a hallmark of neuroendocrine and psychiatric disorders, such as Cushing's disease and depression. It remains unclear whether cortisol directly contributes to the altered mood and behaviour seen in these diseases. To answer this question, a model of chronic cortisol was utilized, in which, male albinos mice were injected intraperitoneally with corticosterone [13 mg/kg] for 23 days. Locomoter Activity was measured during this period. The results show that Acute treatment with Corticosterone increased Total Activity, Mobile Time, Active time, Rearing Counts, however, Chronic but not acute treatment with Corticosterone decreased these activities. This study suggests that chronic corticosterone may contribute to at least part of the symptoms [i.e. locomoter activities] displayed by patients with depression

Prevalência de depressão e fadiga em um grupo de mulheres com câncer de mama / Prevalence of depression and fatigue in a group of women with breast cancer / Prevalencia de depresión y fatiga en un grupo de mujeres con cáncer de mama

Estudo transversal cujo objetivo foi identificar e avaliar a ocorrência de sintomas depressivos e de fadiga entre mulheres com até um ano de tratamento com radioterapia e/ou quimioterapia para o câncer de mama. Utilizou-se um instrumento com dados sociodemográficos, clínicos e terapêuticos. Para a avaliação da depressão foi aplicado Inventário de Depressão de Beck (BDI) e para a fadiga o Fatigue Questionnarie. Incluímos 31 mulheres atendidas em um núcleo de reabilitação de mastectomizadas. Os resultados mostram que 87,1% das mulheres apresentaram cansaço nas pernas, como sintoma de mal-estar relacionado à fadiga consequente ao tratamento. Em relação aos sintomas depressivos, 41,9% delas manifestaram sintomas entre leve e moderado. Os resultados apontam para a necessidade de abordagem e de condutas para o manejo dos sintomas depressivos e fadiga, além de auxiliar os profissionais da saúde a identificar as necessidades dos clientes e a desenvolver estratégias adequadas para o cuidado individualizado...

The objective of this cross-sectional study was to identify and evaluate the occurrence of symptoms of depression and fatigue in women undergoing radiotherapy and/or chemotherapy for breast cancer for one year or less. An instrument was used to collect the sociodemographic, clinical and therapeutic data. Depression was assessed using Beck's Depression Inventory (BDI), and the Fatigue Questionnaire was used to evaluate levels of fatigue. The participants were 31 women who were attending a rehabilitation center for mastectomy patients. Results show that 87.1% of the women report experiencing weakness of their legs as a symptom of fatigue-related malaise related to the treatment. Regarding depression symptoms, 41.9% reported experiencing mild to moderate symptoms. Results point to the need to develop approaches to manage symptoms of depression and fatigue, in addition to helping health professionals to identify their clients' needs and develop suitable strategies for individualized care...

Estudio transversal que objetivó identificar y evaluar la ocurrencia de síntomas depresivos y fatiga entre mujeres con hasta un año de tratamiento con radioterapia y/o quimioterapia para cáncer de mama. Se utilizó instrumento con datos sociodemográficos, clínicos y terapéuticos. Se aplicó Inventario de Depresión de Beck (BDI) para evaluación de depresión, y Fatigue Questionnaire para evaluación de fatiga. Incluimos 31 mujeres atendidas en núcleo de rehabilitación de mastectomizadas. Los resultados demuestran que 87,1% de las mujeres presentan cansancio en las piernas, como síntoma de malestar relacionado a la fatiga consecuente del tratamiento. Respecto a los síntomas depresivos, 41,9% de ellas manifestaron sintomatología de leve a moderada. Los resultados demuestran la necesidad de abordaje y conductas para el manejo de síntomas depresivos y fatiga, además de ayudar a los profesionales de salud a identificar las necesidades de las pacientes y desarrollar estrategias adecuadas para el cuidado personalizado...

Fisiopatología de los eventos psiquiátricos asociados al uso de interferón alfa / Pathophysiology of psychiatric events associated with alpha-interferon use

El uso de interferón para el tratamiento de la hepatitis C crónica activa, el melanoma y el carcinoma renal trajo aparejada la necesidad de asistir de modo adecuado los eventos adversos neuropsiquiátricos.Se han reportado con frecuencia eventos adversos psiquiátricos con el uso de interferón alfa, que pueden ocurrir al inicio del tratamiento o más tarde, como resultado de la continuidad del mismo.Los más comunes son: ánimo depresivo, anhedonia, ansiedad, irritabilidad, ideación suicida. También fatiga, insomnio, anorexia, dolor, enlentecimiento psicomotor y trastornos cognitivos.Estos síntomas limitan la adhesión al tratamiento y a veces precipitan su discontinuación, por lo cual está indicado el uso de antidepresivos, especialmente de los Inhibidores de la Recaptación de Serotonina, y de otros psicofármacos cuando se presenta hipomanía o psicosis. El objetivo de este trabajo es realizar una revisión de la fisiopatología de los eventos adversos psiquiátricos del tratamiento con interferón alfa, y de los diversos mecanismos que se han propuesto para explicarlos.Nuestra revisión incluye por su especial interés, el tema de la inmunomodulación producida a partir de la activación de la “vía de las kinureninas” por las citoquinas proinflamatorias, su importancia en las patologías autoinmunes y neurodegenerativas, y en la investigación de futuros blancos terapéuticos.

The use of interferon for the treatment of chronic active hepatitis, melanoma and renal cell carcinoma resulted in the need to adquately assist the neuropsychiatric adverse events. Psychiatric adverse events have been frequently reported with the use of interferon alpha, which can occur at the beginning of treatment or later, as a result of continuity. The most common are: depressed mood, anhedonia, anxiety, irritability, suicidal ideation. Also fatigue, insomnia, anorexia, pain, psychomotor retardation and cognitive disorders. These symptoms limit treatment adherence and sometimes precipitate its discontinuation, which is indicated by the use of antidepressants, especially inhibitors of serotonin reuptake, and the other psychotropic drugs when there is hypomania or psychosis. The aim of this paper is to review the pathophysiology of psychiatric adverse events of treatment with interferon alpha, and various mechanisms have been proposed to explain. Due to its special interest, our review includes the issue of Immunomodulation produced from the activation of the "way of kinureninas" by proinflammatory cytokines, its importance in autoimmune and neurodegenerative pathologies, and the research of therapeutic targets in future.

Cannabis e humor / Cannabis and mood

OBJETIVO: Avaliar as relações entre o uso agudo e crônico de cannabis e alterações do humor. MÉTODO: Os artigos foram selecionados por meio de busca eletrônica no indexador PubMed. Capítulos de livros e as listas de referências dos artigos selecionados também foram revisados. RESULTADOS: Observam-se elevados índices de comorbidade entre abuso/dependência de cannabis e transtornos afetivos em estudos transversais e em amostras clínicas. Estudos longitudinais indicam que, em longo prazo, o uso mais intenso de cannabis está relacionado com um risco maior de desenvolvimento de doença bipolar e, talvez, depressão maior em indivíduos inicialmente sem quadros afetivos; porém, os mesmos não encontraram maior risco de uso de cannabis entre aqueles com mania ou depressão sem esta comorbidade. Outra importante observação é que o uso de substâncias psicoativas em bipolares pode estar associado a uma série de características negativas, como dificuldade na recuperação dos sintomas afetivos, maior número de internações, piora na adesão ao tratamento, risco aumentado de suicídio, agressividade e a uma pobre resposta ao lítio. Tratamentos psicossociais e farmacológicos são indicados para o manejo da comorbidade entre cannabis e transtornos afetivos. CONCLUSÃO: As relações entre o uso de cannabis e alterações do humor são observadas tanto epidemiologicamente quanto nos contextos clínicos.

OBJECTIVE: Evaluate the relationship between acute and chronic use of cannabis and mood changes. METHOD: Articles were selected by electronic search in PubMed. Chapters in books and reference lists of selected articles were also reviewed. As the research did not involve humans, there was no evaluation by a Research Ethics Committee. RESULTS: High rates of comorbidity between use/abuse/dependence of cannabis and affective disorders in longitudinal studies and in clinical samples were observed. Longitudinal studies indicate that, in long-term, the higher use of cannabis is associated with an increased risk of developing bipolar disorder, and probably, major depression in subjects initially without affective disorder, but was not found increased risk of cannabis use among those initially only with mania or depression. Another important observation is that substance abuse in bipolar patients may be associated with a number of negative characteristics, such as difficulty in recovering the affective symptoms, more hospitalizations, poor compliance with treatment, increased risk of suicide, aggression and a poor response to lithium. Psychosocial and pharmacological treatments are indicated for the management of comorbidity between cannabis and affective disorders. CONCLUSION: The relationship between cannabis use and mood changes are observed both in the epidemiological research and in the clinical settings.

Novel insertion mutation of ABCB1 gene in an ivermectin-sensitive Border Collie

P-glycoprotein (P-gp) is encoded by the ABCB1 gene and acts as an efflux pump for xenobiotics. In the Border Collie, a nonsense mutation caused by a 4-base pair deletion in the ABCB1 gene is associated with a premature stop to P-gp synthesis. In this study, we examined the full-length coding sequence of the ABCB1 gene in an ivermectin-sensitive Border Collie that lacked the aforementioned deletion mutation. The sequence was compared to the corresponding sequences of a wild-type Beagle and seven ivermectin-tolerant family members of the Border Collie. When compared to the wild-type Beagle sequence, that of the ivermectin-sensitive Border Collie was found to have one insertion mutation and eight single nucleotide polymorphisms (SNPs) in the coding sequence of the ABCB1 gene. While the eight SNPs were also found in the family members' sequences, the insertion mutation was found only in the ivermectin-sensitive dog. These results suggest the possibility that the SNPs are species-specific features of the ABCB1 gene in Border Collies, and that the insertion mutation may be related to ivermectin intolerance.

Parkinsonism and other movement disorders in outpatients in chronic use of cinnarizine and flunarizine

O objetivo deste estudo foi determinar a prevalência e os padrões de distúrbios do movimento (DM) em pacientes ambulatoriais sob uso crônico de cinarizina (cz) ou flunarizina (fz), além de estabelecer os principais fatores de risco para o seu aparecimento. Durante três meses foram coletados dados de pacientes ambulatoriais em uso de cz ou fz. Todos esses pacientes foram submetidos a protocolo pré-estabelecido que incluía critérios diagnósticos do DSM-IV para distúrbios do movimento induzido por drogas e critérios para diagnostico de depressão maior. Parkinsonismo (PK) puro foi diagnosticado em 34% dos pacientes, PK com acatisia, PK com acatisia e síndrome mastigatória bucolingual (SMBL), SMBL isoladamente e distonia, foram encontrados em 4% dos pacientes. Os pacientes com SMBL apresentavam a média de idade mais avançada, o maior tempo médio de uso das drogas, configurando-se o grupo de maior risco ao aparecimento dos DM. O grupo dos pacientes com DM apresentou maior incidência de depressão quando comparados com os não afetados. O estudo demonstra uma relação direta entre o tempo de uso da droga, a idade avançada do paciente e o surgimento dos DM. Os resultados também sugerem que estas drogas aumentam a incidência de depressão.