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1.
Front Psychiatry ; 13: 1033816, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36545037

RESUMO

Introduction: The understanding of biological responses to psychedelics with antidepressant potential is imperative. Here we report how a set of acute parameters, namely emotional (depressive symptoms), cognitive (psychedelic experience), and physiological (salivary cortisol), recorded during an ayahuasca dosing session, modulated serum brain-derived neurotrophic factor (BDNF), serum cortisol (SC), serum interleukin 6 (IL-6), plasma C-reactive protein (CRP), and salivary cortisol awakening response (CAR). Methods: Results were analyzed 2 days after the psychedelic intervention (ayahuasca) versus placebo in both patients with treatment-resistant depression and healthy volunteers. These measures were assessed as part of a randomized double-blinded, placebo-controlled trial (n = 72). Results: Results revealed that larger reductions of depressive symptoms during the dosing session significantly moderated higher levels of SC in patients. Whereas lesser changes in salivary cortisol levels during the ayahuasca intervention were related to higher BDNF levels in patients with a larger clinical response in the reduction in depressive symptoms. No moderator was found for patient's CAR, IL-6, and CRP responses to ayahuasca and for all biomarker responses to ayahuasca in healthy controls and in the placebo group. Discussion: In summary, some specific emotional and physiological parameters during experimental ayahuasca session were revealed as critical moderators of the improvement of major depression biomarkers, mainly BDNF and SC two days after ayahuasca intake. These findings contribute to paving the way for future studies investigating the biological antidepressant response to psychedelic therapy.

2.
Rev. Ciênc. Plur ; 8(1): e25741, 2022. tab
Artigo em Português | LILACS, BBO - Odontologia | ID: biblio-1348355

RESUMO

Introdução:Pacientes com depressão maior geralmente respondem ao tratamento com medicamentos antidepressivos, no entanto em 10% a 30% dos casos há apenas uma resposta parcial ou nenhuma resposta, entre os fatores que podem influenciar encontra-se o perfil das enzimas hepáticas metabolizadoras dos antidepressivos, tal como a CYP2C19.Objetivo:Caracterizar os indivíduos quanto ao perfil genético dospolimorfismos CYP2C19*2 ou CYP2C19*17 em pacientes com transtorno depressivo maior (TDM) tratados com citalopram ou escitalopram e compará-los em relação a adesão ao tratamento, sintomas de depressão e qualidade de vida.Metodologia:Trata-se de um estudo transversal realizado com 29 pacientes com TDM. Amostras de sangue foram coletadas para genotipagem de CYP2C19 por discriminação alélica TaqMan®. Após caracterização do perfil genético, os indivíduos foram comparados quanto aos dados demográfico e socioeconômico, adesão ao tratamento (TestedeMorisky-Green),sintomas de depressão (escala de Hamilton) e qualidade de vida (WHOQoL-BREF).Resultados:Quatro pacientes (13.8%) apresentaram polimorfismo para CYP2C19*2 e 10 pacientes (34.4%) para CYP2C19*17, com maior prevalência de CYP2C19*17 (p>0.05). Nenhuma associação significativa de características socioeconômicas, demográficas e clínicas entre os genótipos do CYP2C19.No TestedeMorisky-Green, aadesão moderada ao tratamento foi predominante nos pacientes CYP2C19*2 e CYP2C19*17 (p>0.05). Não foi observada associação entre sintomas de depressão e polimorfismos genéticos (p>0.05). Uma associação significativa entre o genótipo polimórfico CC do CYP2C19*17 com a satisfação com a saúde, enquanto o genótipo CT foi associado ao estado "nem satisfeito/nem insatisfeito" (p<0.05). A maioria dos indivíduos CYP2C19*2 e CYP2C19*17 relatou "necessidade de melhorar" em relação aos domínios de qualidade de vida físico, psicológico, social e ambiental (p>0.05).Conclusões:Os pacientes apresentaram maior prevalência do polimorfismo CYP2C19*17, com moderada adesão ao tratamento. Alguns pacientes, mesmo sob efeito da medicação, apresentaram sintomas de depressão moderado a intenso e relataram uma indefinição na satisfação da sua qualidade de vida (AU).


Introduction:Patients with major depression usually respond to treatment with antidepressant drugs, however in 10% to 30% of cases there is only a partial response or no response, among the factors that can influence is the profile of liver enzymes metabolizing antidepressants, such as CYP2C19.Objective:To characterize the individuals regarding the genetic profile ofCYP2C19*2or CYP2C19*17 polymorphisms in patients with major depressive disorder (MDD) treated with citalopram or escitalopram, and to compare themaccording to treatment adherence, symptoms of depression and quality of life.Methodology:This is cross-sectionalstudy carried out with 29 patients with MDD. Blood samples were collected for CYP2C19 genotyping by TaqMan® allelic discrimination. After characterization of the genetic profile, the individuals were compared regarding the demographic and socioeconomic data, treatment adherence (Morisky-GreenTest), symptoms of depression (Hamilton scale) and quality of life (WHOQoL-BREF).Results:Four patients showed (13.8%) CYP219*2 and 10 patients (34.4%) CYP219*17 polymorphisms.,withhigher prevalence of CYP219*17 (p>0.05). No association between socioeconomic, demographic, and clinical features with CYP2C19 genotypes was observed. In Morisky-GreenTest, moderate adherence to treatment was predominant for CYP2C19*2 and CYP219*17 patients (p>0.05). No statistically significant association was observed between symptoms of depression and genetic polymorphisms (p>0.05). A significant association between polymorphic CC genotype of CYP219*17 with health satisfaction, while the CT genotype was associated with "neither satisfied/nor dissatisfied" status (p<0.05). Most of the CYP2C19*2 and CYP2C19*17 subjects reported "need to improve" or "regular" regarding physical, psychological, social, and environmental domainsof quality of life(p>0.05).Conclusions:The patients showed a higher prevalence of CYP219*17 polymorphism, with moderate treatment adherence. Some subjects, even under the effect of the medication, presented moderate to intense symptoms of depression, and reported a lack of definition in the satisfaction of their quality of life (AU).


Introducción:Los pacientes con depresión mayor responder al tratamiento con antidepresivos, en 10% al 30% de los casos existe una respuesta parcial o nula, entre los factores que pueden influir se encuentra el perfil de enzimas hepáticas metabolizadoras de antidepresivos, como CYP2C19.Objetivo: Caracterizar a los individuos en cuanto al perfil genético depolimorfismos CYP2C19 *2 o CYP2C19 * 17 en pacientes con trastorno depresivo mayor (TDM) tratados con citalopram o escitalopram y compararlos en relaciónpara la adherencia al tratamiento, síntomas de depresión y la calidad de vida.Metodología: Estudio transversalcon 29 pacientes con TDM. Se recogieron muestras de sangre para la determinación del genotipo CYP2C19 mediante discriminación alélica TaqMan®, los individuos fueron comparados en cuanto a los datosdemográficosy socioeconómicos, adherencia (Prueba de Morisky-Green), síntomas de depresión (escala de Hamilton) y calidad de vida (WHOQoL-BREF).Resultados: Cuatro pacientes (13,8%) con polimorfismo CYP2C19*2 y 10 (34,4%) con CYP2C19 * 17,(p> 0,05). No existe una asociación significativa de las características socioeconómicas, demográficas y clínicas con los genotipos CYP2C19. La adherencia moderada al tratamiento fue predominante en los pacientes con CYP2C19*2 y CYP2C19*17 (p> 0,05). No hubo asociación entre síntomas de depresión y polimorfismos genéticos (p> 0.05). Una asociación significativa entre el genotipo polimórfico CYP2C19 * 17 CC con la satisfacción con la salud, mientras que el genotipo CT se asoció con el estado "ni satisfecho / no insatisfecho" (p <0.05). La mayoría de CYP2C19 * 2 y CYP2C19 * 17 individuos informaron "necesidad de mejorar" en relación con los dominios físico, psicológico, social y ambientalde calidad de vida(p> 0,05).Conclusiones: Los pacients mostraron una mayor prevalencia del CYP2C19 * 17, con adherencia moderada al tratamiento, síntomas de depresión moderada a intensay informaron una falta de definición en la satisfacción de su calidad de vida (AU).


Assuntos
Humanos , Citalopram/farmacologia , Depressão/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Citocromo P-450 CYP2C19/farmacologia , Antidepressivos/farmacologia , Qualidade de Vida , Brasil , Estudos Transversais/métodos , Tratamento Farmacológico
3.
Front Psychol ; 12: 641779, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421705

RESUMO

The comprehension of the pathophysiology of the major depressive disorder (MDD) is essential to the strengthening of precision psychiatry. In order to determine the relationship between the pathophysiology of the MDD and its clinical progression, analyzed by severity of the depressive symptoms and sleep quality, we conducted a study assessing different peripheral molecular biomarkers, including the levels of plasma C-reactive protein (CRP), serum mature brain-derived neurotrophic factor (mBDNF), serum cortisol (SC), and salivary cortisol awakening response (CAR), of patients with MDD (n = 58) and a control group of healthy volunteers (n = 62). Patients with the first episode of MDD (n = 30) had significantly higher levels of CAR and SC than controls (n = 32) and similar levels of mBDNF of controls. Patients with treatment-resistant depression (TRD, n = 28) presented significantly lower levels of SC and CAR, and higher levels of mBDNF and CRP than controls (n = 30). An increased severity of depressive symptoms and worse sleep quality were correlated with levels low of SC and CAR, and with high levels of mBDNF. These results point out a strong relationship between the stages clinical of MDD and changes in a range of relevant biological markers. This can assist in the development of precision psychiatry and future research on the biological tests for depression.

4.
PLoS One ; 16(9): e0257251, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34587177

RESUMO

BACKGROUND: Molecular biomarkers are promising tools to be routinely used in clinical psychiatry. Among psychiatric diseases, major depression disorder (MDD) has gotten attention due to its growing prevalence and morbidity. METHODS: We tested some peripheral molecular parameters such as serum mature Brain-Derived Neurotrophic Factor (mBDNF), plasma C-Reactive Protein (CRP), serum cortisol (SC), and the salivary Cortisol Awakening Response (CAR), as well as the Pittsburgh sleep quality inventory (PSQI), as part of a multibiomarker panel for potential use in MDD diagnosis and evaluation of disease's chronicity using regression models, and ROC curve. RESULTS: For diagnosis model, two groups were analyzed: patients in the first episode of major depression (MD: n = 30) and a healthy control (CG: n = 32). None of those diagnosis models tested had greater power than Hamilton Depression Rating Scale-6. For MDD chronicity, a group of patients with treatment-resistant major depression (TRD: n = 28) was tested across the MD group. The best chronicity model (p < 0.05) that discriminated between MD and TRD included four parameters, namely PSQI, CAR, SC, and mBDNF (AUC ROC = 0.99), with 96% of sensitivity and 93% of specificity. CONCLUSION: These results indicate that changes in specific biomarkers (CAR, SC, mBDNF and PSQI) have potential on the evaluation of MDD chronicity, but not for its diagnosis. Therefore, these findings can contribute for further studies aiming the development of a stronger model to be commercially available and used in psychiatry clinical practice.


Assuntos
Biomarcadores/metabolismo , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/diagnóstico , Adulto , Algoritmos , Área Sob a Curva , Fator Neurotrófico Derivado do Encéfalo/sangue , Proteína C-Reativa/biossíntese , Estudos de Casos e Controles , Feminino , Humanos , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Prevalência , Escalas de Graduação Psiquiátrica , Psiquiatria/normas , Psicometria , Curva ROC , Análise de Regressão , Saliva/metabolismo , Sono , Fatores de Tempo , Adulto Jovem
5.
Rev. bras. educ. méd ; 44(4): e131, 2020. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1137547

RESUMO

Abstract: Introduction: To evaluate the self-confidence and knowledge of medical students when caring for patients at risk for suicide. Methods: A quantitative cross-sectional study was performed with a sample of 310 medical students from the campus of Universidade Federal do Rio Grande do Norte (UFRN) in Natal, Brazil. Data was collected through the application of the Suicide Behavior Attitude Questionnaire (QuACS, Questionário de Atitudes Frente ao Comportamento Suicida) in association with a sociodemographic questionnaire. The Spearman and Mann-Whitney correlation tests were used to analyze the data. Results: Students closer to the end of the course and those who had practical experience with suicide showed less negative feelings, more sense of professional capacity and less condemnatory attitudes towards suicide. Students in the beginning of the course showed more negative feelings towards suicide. There was no statistically significant influence of gender, having a friend or family member who attempted suicide or past experience of suicidal thoughts on the results. Conclusion: The study strengthens the correlation between the implementation of practical experience and capacitation activities with less negative feelings and increased sense of professional capacity to deal with suicidal behavior.


Resumo: Introdução: O objetivo deste estudo foi avaliar a autoconfiança e o conhecimento de estudantes de Medicina para que possam atuar no cuidado de paciente sob risco suicida. Método: Trata-se de estudo transversal quantitativo realizado com amostra de 310 estudantes de Medicina do câmpus da Universidade Federal do Rio Grande do Norte (UFRN), em Natal, no Brasil. Para coleta dos dados dos estudantes, aplicou-se o Questionário de Atitudes Frente ao Comportamento Suicida (QuACS) associado a um questionário sociodemográfico. Para análise dos dados, foram utilizados os testes de correlação de Mann-Whitney e Spearman. Resultados: Os estudantes mais próximos do final do curso e aqueles que já tinham experiência prática com o suicídio demonstraram menos sentimentos negativos, maior sensação de capacidade profissional e atitude menos condenatória com relação ao suicídio. Os alunos do início do curso demonstraram mais sentimentos negativos para com o suicídio. Não houve influência estatisticamente relevante de sexo, possuir amigo ou familiar que já tentou suicídio ou experiência prévia de pensamentos suicidas nos resultados obtidos. Conclusão: O estudo reforça a correlação da implementação de experiências práticas e atividades de capacitação dos alunos com redução de sentimentos negativos e aumento de percepção de capacidade profissional para lidar com o comportamento suicida.

8.
An. bras. dermatol ; 91(6): 791-798, Nov.-Dec. 2016. tab, graf
Artigo em Inglês | LILACS | ID: biblio-837980

RESUMO

Abstract Among the wide range of symptoms neglected or resistant to conventional treatments in clinical practice, itch is emerging gradually as a theme to be studied. Itch complaints and the negative effects in the quality of life are observed in several medical fields. Although the partially obscure pathophysiology, some researchers decided to check and test the use of psychotropic drugs in resistant itch to conventional topical treatments and antihistamines. The objective of this study was to evaluate scientific evidence in psychotropic use in the treatment of itch of various causes. This is a systematic review of scientific literature. The following databases were used: PubMed, Web of Science, Scopus and Scielo. Randomized controlled trials that should focus on treatment with psychotropic drugs of pruritus of various causes were the inclusion criteria. All articles were analyzed by the authors, and the consensus was reached in cases of disagreement. Fifteen articles were included after analysis and selection in databases, with the majority of clinical trials focusing on psychopharmacological treatment of itch on account of chronic kidney disease. Clinical trials with psychotropic drugs mostly indicated significant improvement in the itching. In most trials of chronic kidney disease as basal disease for itch, greater effectiveness was observed with the use of psychotropic drugs compared with placebo or other antipruritic. However, the small amount of controlled trials conducted precludes the generalization that psychiatric drugs are effective for itch of various causes.


Assuntos
Humanos , Prurido/tratamento farmacológico , Psicotrópicos/uso terapêutico , Prurido/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Resultado do Tratamento , Ácidos Cicloexanocarboxílicos/uso terapêutico , Doxepina/uso terapêutico , Ácido gama-Aminobutírico/uso terapêutico , Aminas/uso terapêutico , Nefropatias/complicações , Antipruriginosos/uso terapêutico
9.
Curr Med Chem ; 23(24): 2680-2691, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27450675

RESUMO

BACKGROUND: Recent findings suggest that dopaminergic abnormalities found in psychotic disorders may be secondary to nitric oxide dysfunctions. Nitric oxide seems to influence glutamatergic and dopaminergic neurotransmission, both of which have been associated with psychosis. OBJECTIVE: To search and review published works which examined the influence of nitric oxide in psychotic disorders subjects. METHODS: The research was executed in the on-line collections of Pubmed and ISI Web of Science. The key aspects utilized were "Psychotic Disorders AND Nitric Oxide", "Psychosis AND Nitric Oxide","Schizotypal Personality Disorder AND Nitric Oxide", "Delusional Disorder AND Nitric Oxide", "Brief Psychotic Disorder AND Nitric Oxide", "Schizophreniform Disorder AND Nitric Oxide", "Schizoaffective Disorder AND Nitric Oxide", and "Schizophrenia AND Nitric Oxide". Empirical works utilizing human subjects, published in the last 10 years, in English language were included. RESULTS: Initially, the search yielded a total of 95 studies. Then, 39 were elected according to the inclusion requirements. The selected articles were divided into five groups: biochemical studies (n=15; 38.5%), genetic studies (n=11; 28.2%), postmortem studies (n=6; 15.4%), clinical trials (n=6; 15.4%), and case reports (n=1; 2.5%). The studies evaluated only schizophrenic or schizoaffective disorder subjects. The great majority of them found evidence of nitric oxide dysfunctions in psychosis. CONCLUSIONS: The results of the review strengthen the idea that nitric oxide has a key participation in psychotic disorders and deserves deeper investigation as a target for future pharmacological intervention.


Assuntos
Óxido Nítrico/metabolismo , Transtornos Psicóticos/patologia , Antipsicóticos/uso terapêutico , Arginina/análogos & derivados , Arginina/uso terapêutico , Encéfalo/metabolismo , Ensaios Clínicos como Assunto , Humanos , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Inibidores da Fosfodiesterase 5/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/metabolismo , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo , Esquizofrenia/patologia , Citrato de Sildenafila/uso terapêutico
10.
CNS Neurol Disord Drug Targets ; 15(8): 976-986, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27450870

RESUMO

The prevalence of central nervous system trauma, neurodegenerative and psychiatric diseases has significantly increased in recent years. Most of these diseases show multifactorial causes and several progression mechanisms. The search for a medication which positively interferes in these mechanisms and thereby changes the course of these diseases is of great scientific interest. The aim of the present review is to assess current literature on the possible role of methylene blue (MB) in the central nervous system due to the increasing number of citations in spite of the few articles available on the subject which suggest growing interest in the protective effects of MB on the central nervous system. Searches were performed on PubMed and Thomson Reuters Web of Knowledge. Therefore, we provide an overview of existing articles concerning: 1) MB actions; 2) MB neuroprotection and cardiac arrest; 3) MB neuroprotection and degenerative brain diseases; 4) MB neuroprotection and psychiatric diseases. PubMed was chosen because it holds the highest number of articles on the subject, Thomson Reuters was chosen due to its functionality which evaluates citations through analytic graphs. We conclude that MB has a beneficial effect and acts through many mechanisms and pathways of the central nervous system, being a potential alternative for the treatment of many neurodegenerative and psychiatric diseases.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Transtornos Mentais/terapia , Azul de Metileno/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Animais , Humanos , PubMed
11.
An Bras Dermatol ; 91(6): 791-798, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28099602

RESUMO

Among the wide range of symptoms neglected or resistant to conventional treatments in clinical practice, itch is emerging gradually as a theme to be studied. Itch complaints and the negative effects in the quality of life are observed in several medical fields. Although the partially obscure pathophysiology, some researchers decided to check and test the use of psychotropic drugs in resistant itch to conventional topical treatments and antihistamines. The objective of this study was to evaluate scientific evidence in psychotropic use in the treatment of itch of various causes. This is a systematic review of scientific literature. The following databases were used: PubMed, Web of Science, Scopus and Scielo. Randomized controlled trials that should focus on treatment with psychotropic drugs of pruritus of various causes were the inclusion criteria. All articles were analyzed by the authors, and the consensus was reached in cases of disagreement. Fifteen articles were included after analysis and selection in databases, with the majority of clinical trials focusing on psychopharmacological treatment of itch on account of chronic kidney disease. Clinical trials with psychotropic drugs mostly indicated significant improvement in the itching. In most trials of chronic kidney disease as basal disease for itch, greater effectiveness was observed with the use of psychotropic drugs compared with placebo or other antipruritic. However, the small amount of controlled trials conducted precludes the generalization that psychiatric drugs are effective for itch of various causes.


Assuntos
Prurido/tratamento farmacológico , Psicotrópicos/uso terapêutico , Aminas/uso terapêutico , Antipruriginosos/uso terapêutico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Doxepina/uso terapêutico , Gabapentina , Humanos , Nefropatias/complicações , Prurido/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Resultado do Tratamento , Ácido gama-Aminobutírico/uso terapêutico
12.
J Neuropsychiatry Clin Neurosci ; 27(1): e14-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25716490

RESUMO

This is a report on two cases of refractory schizophrenia and two cases of clozapine-resistant schizophrenia successful treated with paliperidone palmitate. To the authors' knowledge, this is the first report of the successful use of paliperidone palmitate in such patients.


Assuntos
Antipsicóticos/uso terapêutico , Clozapina/efeitos adversos , Isoxazóis/uso terapêutico , Palmitatos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Palmitato de Paliperidona , Adulto Jovem
13.
Rev. latinoam. psicopatol. fundam ; 17(3): 528-543, Jul-Sep/2014.
Artigo em Português | Index Psicologia - Periódicos | ID: psi-63599

RESUMO

Objetivos: Discutir os avanços e limitações do uso dos modelos animais nos transtornos psiquiátricos. Método: Uma revisão narrativa de artigos. Resultados: Diferentes modelos animais atualmente demonstram validade adequada para características específicas de determinados transtornos mentais. Conclusão: Resguardadas as devidas limitações que impossibilitam mimetizar sintomas psicopatológicos complexos em modelos animais, estes seguem como úteis ferramentas de estudo na psiquiatria. .(AU)


Objectives: To discuss the advances and limitations of animal models in psychiatric disorders. Method: A narrative review of articles. Results: Different animal models currently demonstrate adequate validity for specific characteristics of certain mental disorders. Conclusion: Recognizing limitations that stay away from any mimicking of complex psychopathological symptoms in animal models, such models nonetheless represent useful tools in the study of psychiatry. .(AU)


Objectifs: Examiner les progrès et les limites des modèles animaux pour l'étude des troubles psychiatriques. Méthode: Révision narrative d'articles. Résultats: De différents modèles animaux possèdent actuellement une validité suffisante par rapport aux caractéristiques spécifiques de certains troubles mentaux. Conclusion: Malgré le fait des limites qui ne permettent pas de reproduire les symptômes psychopathologiques complexes dans les modèles animaux, ceux-ci restent néanmoins des outils utiles d'étude en psychiatrie. .(AU)


Objetivos: Discutir los avances y las limitaciones de los modelos animales en los trastornos psiquiátricos. Método: Una revisión narrativa de artículos. Resultados: Los diferentes modelos animales actualmente demuestran validez adecuada para las características específicas de determinados trastornos mentales. Conclusión: Guardadas las debidas limitaciones que imposibilitan mimetizar los síntomas psicopatológicos complejos en modelos animales, estes siguen siendo herramientas útiles en el estudio de la psiquiatría. .(AU)


Assuntos
Animais , Transtornos Mentais , Psicopatologia , Psiquiatria , Modelos Animais
14.
Rev. latinoam. psicopatol. fundam ; 17(3): 528-543, Jul-Sep/2014.
Artigo em Português | LILACS | ID: lil-725744

RESUMO

Objetivos: Discutir os avanços e limitações do uso dos modelos animais nos transtornos psiquiátricos. Método: Uma revisão narrativa de artigos. Resultados: Diferentes modelos animais atualmente demonstram validade adequada para características específicas de determinados transtornos mentais. Conclusão: Resguardadas as devidas limitações que impossibilitam mimetizar sintomas psicopatológicos complexos em modelos animais, estes seguem como úteis ferramentas de estudo na psiquiatria.


Objectives: To discuss the advances and limitations of animal models in psychiatric disorders. Method: A narrative review of articles. Results: Different animal models currently demonstrate adequate validity for specific characteristics of certain mental disorders. Conclusion: Recognizing limitations that stay away from any mimicking of complex psychopathological symptoms in animal models, such models nonetheless represent useful tools in the study of psychiatry.


Objectifs: Examiner les progrès et les limites des modèles animaux pour l'étude des troubles psychiatriques. Méthode: Révision narrative d'articles. Résultats: De différents modèles animaux possèdent actuellement une validité suffisante par rapport aux caractéristiques spécifiques de certains troubles mentaux. Conclusion: Malgré le fait des limites qui ne permettent pas de reproduire les symptômes psychopathologiques complexes dans les modèles animaux, ceux-ci restent néanmoins des outils utiles d'étude en psychiatrie.


Objetivos: Discutir los avances y las limitaciones de los modelos animales en los trastornos psiquiátricos. Método: Una revisión narrativa de artículos. Resultados: Los diferentes modelos animales actualmente demuestran validez adecuada para las características específicas de determinados trastornos mentales. Conclusión: Guardadas las debidas limitaciones que imposibilitan mimetizar los síntomas psicopatológicos complejos en modelos animales, estes siguen siendo herramientas útiles en el estudio de la psiquiatría.


Assuntos
Animais , Transtornos Mentais , Modelos Animais , Psiquiatria , Psicopatologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-24607770

RESUMO

Phenelzine, a non-selective irreversible inhibitor of monoamine oxidase (MAO), has been used in the treatment of depression and anxiety disorders for several decades. It is a unique inhibitor of MAO as it is also a substrate for MAO, with one of the metabolites being ß-phenylethylidenehydrazine (PEH), and it also inhibits several transaminases (e.g. GABA transaminase) in the brain when administered i.p. to rats. Administration of either phenelzine or PEH to rats has been reported to produce dramatic increases in rat brain levels of GABA and alanine while reducing levels of glutamine; these effects are abolished for phenelzine, but not for PEH, when the animals are pre-treated with another MAO inhibitor, suggesting that they are mediated by the MAO-catalyzed formation of PEH from phenelzine. In the present report, we have found that phenelzine and E- and Z-geometric isomers of PEH significantly increased rat whole brain concentrations of L-tyrosine. In a time-response study, acute administration of phenelzine, E-PEH and Z-PEH (30 mg/kg i.p.) elevated rat whole brain L-tyrosine levels at 3 and 6h following injection, reaching approximately 265-305% of vehicle-treated controls at 3h. To determine whether the effect on L-tyrosine is MAO-dependent, animals were pre-treated with the non-selective MAO inhibitor tranylcypromine (1mg/kg i.p.) prior to administration of phenelzine, racemic PEH or vehicle controls. This pre-treatment reversed the effects of phenelzine, but not of PEH, on brain L-tyrosine levels, suggesting that the tyrosine-elevating property of phenelzine is largely the result of its active metabolite PEH. These results are discussed in relation to possible therapeutic applications of these drugs.


Assuntos
Encéfalo/efeitos dos fármacos , Hidrazinas/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Fenelzina/farmacologia , Tirosina/metabolismo , Análise de Variância , Animais , Técnicas Eletroquímicas , Metacrilatos , Ratos , Fatores de Tempo
16.
Ther Adv Psychopharmacol ; 4(1): 30-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24490028

RESUMO

OBJECTIVE: Olanzapine is an atypical antipsychotic drug used to treat schizophrenia. Some of the adverse effects related to its use are obesity, hyperlipidemia, type 2 diabetes and hypertension, which may result in development of metabolic syndrome. This study aimed to investigate a possible increase in some anthropometric and biochemical parameters, and the existence of any correlation between them in Brazilian patients with schizophrenia treated with olanzapine in the mid term. METHODS: Thirty subjects with schizophrenia were evaluated, 16 women and 14 men, aged between 18 and 47 years. All patients underwent blood collection and anthropometric measurements at four different times during 12 months of follow up; thus each patient was his or her own control. RESULTS: Evaluation of some anthropometric measurements showed significant differences when comparing the mean values obtained in each of the different data collection times (p < 0.05). However, the biochemical indicators of development of metabolic syndrome measured in our study did not show the same rate of increment, with only the total cholesterol and glucose levels presenting statistically significant changes (p < 0.05), but without the same magnitude of weight change. CONCLUSION: We conclude that medium-term treatment with olanzapine promoted a substantial weight gain and increased visceral fat, while the metabolic profile did not show the same magnitude of change, suggesting a dissociation between weight gain and blood parameters, despite the severe weight gain observed among subjects evaluated.

17.
Ther Adv Psychopharmacol ; 3(2): 83-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24167679

RESUMO

BACKGROUND: Dengue is a febrile illness that is most common in tropical areas but is recognized worldwide as one of the most important arbovirus diseases of humans. This febrile illness generally has a course with mild alterations in white blood cell count, but there are also rare cases of severe neutropenia or agranulocytosis during dengue infection. Clozapine (CLZ) remains the most effective treatment for schizophrenia, but because of its poor side effect profile, in particular due to the increased risk of neutropenia and agranulocytosis, it is generally used for patients whose condition responds poorly to other antipsychotics. METHODS: We report three cases of dengue infection in patients with refractory schizophrenia who were using CLZ, and we discuss the implications of this infection on the continuation of CLZ treatment in these patients. RESULTS: Of these three cases with dengue infection and co-occurence of CLZ use, the first would be classified as severe neutropenia and the second as moderate leucopenia; the last case had a white blood cell (WBC) count inside the normal range, and had no need to change his antipsychotic. The first and the second patient presented a worsening in their schizophrenic psychopathologies, after CLZ withdrawal, evolving into catatonic states, that were reverted after the careful reintroduction of CLZ. DISCUSSION: It is very likely that during dengue epidemics many patients with schizophrenia and using CLZ have their treatment permanently discontinued given WBC count concerns, causing relapse of symptoms of schizophrenia and impairment of quality of life of these patients.This is the first report of neutropenia cases among CLZ-treated patients during dengue infection that describes the withdrawal of CLZ and its successful readministration.

18.
J Neural Transm (Vienna) ; 120(6): 987-96, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23392617

RESUMO

Phenelzine is a monoamine oxidase (MAO) inhibitor used in treatment of depression and anxiety disorders. It also elevates brain levels of γ-aminobutyric acid (GABA) and inhibits primary amine oxidase (PrAO), an enzyme whose activity and/or expression has been reported to be increased in diabetes mellitus, Alzheimer's disease and cardiovascular disorders. Phenelzine is not only an inhibitor of, but also a substrate for, MAO and it has been suggested that an active metabolite, namely ß-phenylethylidenehydrazine (PEH), is responsible for phenelzine's effects on amino acids. PEH is also a strong inhibitor of PrAO but has weak effects on MAO. PEH has a double bond and can thus exist as (E)- and (Z)-geometric isomers, but to date the two isomers have not been compared with regard to their neurochemical effects. We have investigated the effects of phenelzine, (E)- and (Z)-PEH on rat whole brain levels of amino acids, biogenic amine neurotransmitters and methylamine (an endogenous substrate of PrAO). Under the conditions used in the study, (E)- and (Z)-PEH appear to be equivalent in their neurochemical properties. Both PEH isomers and phenelzine produced marked increases in rat brain levels of GABA and alanine while decreasing brain levels of glutamine. Phenelzine increased brain levels of biogenic amine neurotransmitters (noradrenaline, dopamine and serotonin), whereas neither PEH isomer altered levels of these neurotransmitters to a considerable extent. All three drugs significantly increased rat brain levels of methylamine, with (E)- and (Z)-PEH causing a greater increase than phenelzine. These results are discussed in relation to the possible therapeutic applications of these drugs.


Assuntos
Aminoácidos/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , Hidrazinas/farmacologia , Metilaminas/metabolismo , Neurotransmissores/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Técnicas Eletroquímicas , Cromatografia Gasosa-Espectrometria de Massas , Isomerismo , Masculino , Morfolinas/farmacologia , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
20.
Expert Rev Neurother ; 12(7): 801-12, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22853788

RESUMO

Considering the lengthy history of pharmacological treatment of schizophrenia, the development of novel antipsychotic agents targeting the glutamatergic system is relatively new. A glutamatergic deficit has been proposed to underlie many of the symptoms typically observed in schizophrenia, particularly the negative and cognitive symptoms (which are less likely to respond to current treatments). D-serine is an important coagonist of the glutamate NMDA receptor, and accumulating evidence suggests that D-serine levels and/or activity may be dysfunctional in schizophrenia and that facilitation of D-serine transmission could provide a significant therapeutic breakthrough, especially where conventional treatments have fallen short. A summary of the relevant animal data, as well as genetic studies and clinical trials examining D-serine as an adjunct to standard antipsychotic therapy, is provided in this article. Together, the evidence suggests that research on the next generation of antipsychotic agents should include studies on increasing brain levels of D-serine or mimicking its action on the NMDA receptor.


Assuntos
Antipsicóticos/farmacologia , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo , Serina/metabolismo , Serina/farmacologia , Animais , Humanos , Esquizofrenia/fisiopatologia
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