Therapeutic effect and mechanism of Xiaoyao Kangai Jieyu Recipe on mice with breast cancer related depression through regulating COX pathway / 中国中药杂志

This study aimed to investigate the intervention effect and mechanism of Xiaoyao Kangai Jieyu Recipe(XKJR) on hip-pocampal microglia and neuronal damage in mice with breast cancer related depression. The mouse model of breast cancer related depression was established by inoculation of 4T1 breast cancer cells in axilla and subcutaneous injection of corticosterone(30 mg·kg~(-1)). The successfully modeled mice were randomly divided into a model group, a positive drug group(capecitabine 60 mg·kg~(-1)+fluoxetine 19.5 mg·kg~(-1)), and XKJR group(19.5 mg·kg~(-1) crude drug), with 6 in each group. Another 6 normal mice were taken as a normal group. The administration groups were given corresponding drugs by gavage, while the normal and model groups were given an equal volume of distilled water, once a day for 21 consecutive days. The depressive behavior of mice was assessed by glucose consumption test, open field test and novelty-suppressed feeding test. Hematoxylin and eosin(HE) staining and tumor suppression rate were used to evaluate the changes of axillary tumors. The mRNA expressions and the relative protein expressions of interleukin-1β(IL-1β), interleukin-18(IL-18), cyclooxyganese-2(COX-2) and glutamyl-prolyl-tRNA synthetase(EPRs) in the hippocampus of mice were determined by quantitative real-time polymerase chain reaction(qRT-PCR) and immunohistochemistry, respectively. Immunofluorescence was performed to detect the mean fluorescence intensity of CD11b, a marker of hippocampal microglia activation. Nissler staining and transmission electron microscopy were employed to observe the morphological changes and the ultramorphological changes of hippocampal neurons, respectively. The experimental results indicated that compared with the normal group, the model group had reduced glucose consumption and lowered number of total activities in open field test(P<0.05, P<0.01), prolonged first feeding latency in no-velty-suppressed feeding test(P<0.01), and significant depression-like behavior; the contents of IL-1β, IL-18, COX-2, and EPRs in hippocampus were increased(P<0.05, P<0.01), with hippocampal microglia activation and obvious neuronal damage. Compared with the model group, the positive drug group and the XKJR group presented an improvement in depressive behaviors, a decrease in the contents of IL-1β, IL-18, COX-2 and EPRs in hippocampus, and an alleviation in the activation of hippocampal microglia and neuronal damage; the tumor suppression rates of positive drug and XKJR were 40.32% and 48.83%, respectively, suggesting a lower tumor growth rate than that of the model group. In summary, XKJR may improve hippocampal microglia activation and neuronal damage in mice with breast cancer related depression through activating COX signaling pathway.

Antidepressant mechanism of Shenling Kaixin Granules based on BDNF/TrkB/CREB pathway / 中国中药杂志

To investigate the antidepressant mechanism of Shenling Kaixin Granules(SLKX) in treating chronic unpredictable mild stress(CUMS) model rats. Ninety male SD rats were randomly divided into control group, model group, Shugan Jieyu Capsules(110 mg·kg~(-1)) group and SLKX low-(90 mg·kg~(-1)), medium-(180 mg·kg~(-1)), and high-dose(360 mg·kg~(-1)) groups. Depression rat model was replicated by CUMS method. After treatment, the behavioral changes of rats were evaluated by sugar preference, open field, elevated cross maze and forced swimming experiments. The contents of interleukin 1 beta(IL-1β), tumor necrosis factor α(TNF-α), brain-derived neurotrophic factor(BDNF) and 5-hydroxytryptamine(5-HT) in serum were determined by enzyme linked immunosorbent assay(ELISA), and the activities of superoxide dismutase(SOD) and catalase(CAT) in hippocampal CA1 region were also detected. Pathological changes in hippocampal CA1 region were detected by hematoxylin-eosin(HE) staining, and Western blot was used to determine the expression of nerve growth factor(NGF), BDNF, phospho-tyrosine kinase receptor(p-TrkB)/TrkB, phospho-cAMP-response element binding protein(p-CREB)/CREB, nuclear factor E2 related factor 2(Nrf2), heme oxygenase 1(HO-1), B-cell lymphoma-2(Bcl-2)/Bcl-2 associated X protein(Bax) and caspase-3 in hippocampal CA1 region. RESULTS:: showed that compared with the control group, the model group had decreased sugar preference, reduced number of entries and time spent in the center of open field and shortened total distance of movement, reduced number of entries and proportion of time spent in open arm, and increased number and time of immobility in forced swimming experiment. Additionally, the serum contents of IL-1β and TNF-α and the expression of caspase-3 were higher, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1 and Bcl-2/Bax, and the Nrf2 nuclear translocation were lower in model group than in control group. Compared with the conditions in model group, the sugar preference, the number of entries and time spent in the center of open, total distance of movement, and the number of entries and proportion of time spent in open arm in treatment groups were increased while the number and time of immobility in forced swimming experiment were decreased; the serum contents of IL-1β and TNF-α and the expression of caspase-3 were down regulated, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1, Bcl-2/Bax, and Nrf2 nuclear translocation were enhanced. In conclusion, SLKX might regulate the Nrf2 nucleus translocation by activating BDNF/TrkB/CREB pathway, lower oxidative stress damage in hippocampus, inhibit caspase-3 activity, and reduce apoptosis of hippocampal nerve cells, thereby playing an antidepressant role.

Research progress of cross-disease miRNA molecular markers in schizophrenia, bipolar disorder and depression / 中华医学遗传学杂志

Micro non-coding RNA (microRNA, miRNA) is a small non-coding RNA involved in gene expression regulation that plays an important role in the onset and development of mental illness. Evidence suggests that several miRNAs are dysregulated in patients with mental illnesses. Because of its stability and quantitative detection in peripheral blood and cerebral fluid, miRNA is a particularly attractive biomarker. The objective of this research is to investigate the relationship between mental illness and miRNAs, as well as the potential processes through which miRNAs contribute to disease etiology. Schizophrenia, bipolar disorder, and depression are three major mental disorders with high disability and mortality. The study explored the particular dysregulated miRNAs for each condition as well as common dysregulated miRNAs across diseases. In this study, which analyzes the findings from relevant studies from 2016 to 2020, the authors discuss the functions of numerous severely dysfunctional miRNAs and their application potential in the field of psychiatry research.

The role and mechanism of SIRT1 gene in depression / 生理学报

As a kind of mental illness, depression produces great difficulties in clinical diagnosis and treatment, and has a high disability rate. It is urgent to clarify the mechanism of depression to find potential therapeutic targets and effective clinical treatment methods. As a deacetylase, silent mating type information regulator 2 homolog 1 (SIRT1) is involved in many biological processes such as cell aging, cancer, and cardiovascular disease. In recent years, more and more studies have found that SIRT1 gene plays an important role in the pathogenesis of depression, but the mechanism is still unclear. Therefore, this review mainly summarizes the relevant research progress on the role and mechanism of SIRT1 gene in the hippocampus, prefrontal cortex, amygdala, hypothalamic suprachiasmatic nucleus, and nucleus accumbens in depression, in order to provide new ideas for exploring the mechanism and prevention of depression.

Perfil genético del trastorno bipolar en Panamá: análisis de genes relacionados y otros factores determinantes en una región de alta prevalencia de episodios maníacos en la República de Panamá / Genetic profile of bipolar disorder in Panama: related gene analysis and other determi­ning factors in a high prevalence region of manic episodes in the Republic of Panama

Introducción El Trastorno Bipolar es una enfermedad que causa discapacidad física y cognitiva, afectando tanto a hombres como mujeres, con edad de inicio temprano y con un alto componente hereditario. Objetivo Estimar el comportamiento del Trastorno Bi­polar, variables sociodemográficas, antecedentes y su relación con los genes CACNA1­C (12p13.3) y DAOA (13q34) entre personas de 18 años y más en áreas específicas de la Región de Azuero de Panamá. Metodología La muestra calculada fue de 267 perso­nas de 18 años y más (IC 95%) utilizando un muestreo aleatorio, de distribución propor­cional según sexo. Se utilizaron las variables: "trastorno bipolar" medido a través del cuestionario de trastornos del estado de ánimo (Mood Disorder Questionnaire, MDQ por sus siglas en inglés); "genes asociados a la bipolaridad" (genes CACNA1­C (12p13.3) y DAOA (13q34)); y un cuestionario de datos sociodemográficos y antecedentes persona­les ­ familiares. El análisis genético se realizó con PCR (tiempo real). Se utilizaron por­centajes como medida de frecuencia relativa y se consideró significancia estadística para un valor de p ≤ 0.05. Resultados La prevalencia de bipolaridad en la muestra es­tudiada fue 3.7% (IC 95% 3.5 ­ 4.1), siendo mayor en mujeres, 6.0% (IC 95% 5.9 ­ 6.3). El 74.2% (IC 95% 73.9 ­ 74.4) de los participantes tenía presente el polimorfismo del gen CACNA1­C (12p13.3), y 19.1% (IC 95% 18.9 ­ 19.4) el del gen DAOA (13q34). Para todas las variables de estudio, la presencia del gen CACNA1­C (12p13.3) fue mayor que la del gen DAOA (13q34). De los 10 casos con MDQ+, 3 presentaron el gen CAC­NA1­C. Conclusión Esta es la primera investigación sobre bipolaridad, genes y otros factores asociados en Panamá. El gen CACNA1­C fue más prevalente que el DAOA y se asoció más al MDQ +.

Introduction Bipolar disorder is a disease that causes physical and cognitive disability, affecting both men and women, with an early onset age and a high hereditary compo­nent. Objective To estimate Bipolar Disorder demeanor, sociodemographic variables, antecedents and its relationship with CACNA1­C (12p13.3) and DAOA (13q34) genes among people aged 18 years and over in specific areas of the Azuero Region of Pana­ma. Methodology The calculated sample was 267 people aged 18 and over (95% CI) using random sampling, proportional distribution according to sex. The variables were used: "bipolar disorder" measured through the Mood Disorder Questionnaire (MDQ); "genes associated with bipolarity" (CACNA1­C (12p13.3) and DAOA (13q34) genes); and a sociodemographic data questionnaire and personal ­ family background. The ge­netic analysis was performed with PCR (real time). Percentages were used as a re of relative frequency and statistical significance was considered for a value of p ≤ 0.05. Results The prevalence of bipolarity in the studied sample was 3.7% (CI 95% 3.5 ­ 4.1), being higher in women, 6.0% (CI 95% 5.9 ­ 6.3). 74.2% (CI 95% 73.9 ­ 74.4) of the participants were aware of the polymorphism of the CACNA1­C gene (12p13.3), and 19.1% (CI 95% 18.9 ­ 19.4) of the DAOA gene (13q34). For all study variables, the pre­sence of the CACNA1­C gene (12p13.3) was greater than that of the DAOA gene (13q34). Of the 10 cases with MDQ +, 3 presented the CACNA1­C gene. ConclusionThis is the first research on bipolarity, genes and other associated factors in Panama. The CACNA1­C gene was more prevalent than DAOA and was more associated with MDQ +.

Familial misophonia or selective sound sensitivity syndrome: evidence for autosomal dominant inheritance? / Misofonia familiar ou síndrome da sensibilidade seletiva a sons: evidência de herança autossômica dominante?

Abstract Introduction: Misophonia is a recently described, poorly understood and neglected condition. It is characterized by strong negative reactions of hatred, anger or fear when subjects have to face some selective and low level repetitive sounds. The most common ones that trigger such aversive reactions are those elicited by the mouth (chewing gum or food, popping lips) or the nose (breathing, sniffing, and blowing) or by the fingers (typing, kneading paper, clicking pen, drumming on the table). Previous articles have cited that such individuals usually know at least one close relative with similar symptoms, suggesting a possible hereditary component. Objective: We found and described a family with 15 members having misophonia, detailing their common characteristics and the pattern of sounds that trigger such strong discomfort. Methods: All 15 members agreed to give us their epidemiological data, and 12 agreed to answer a specific questionnaire which investigated the symptoms, specific trigger sounds, main feelings evoked and attitudes adopted by each participant. Results: The 15 members belong to three generations of the family. Their age ranged from 9 to 73 years (mean 38.3 years; median 41 years) and 10 were females. Analysis of the 12 questionnaires showed that 10 subjects (83.3%) developed the first symptoms during childhood or adolescence. The mean annoyance score on the Visual Analog Scale from 0 to 10 was 7.3 (median 7.5). Individuals reported hatred/anger, irritability and anxiety in response to sounds, and faced the situation asking to stop the sound, leaving/avoiding the place and even fighting. The self-reported associated symptoms were anxiety (91.3%), tinnitus (50%), obsessive-compulsive disorder (41.6%), depression (33.3%), and hypersensitivity to sounds (25%). Conclusion: The high incidence of misophonia in this particular familial distribution suggests that it might be more common than expected and raises the possibility of having a hereditary etiology.

Resumo Introdução: A misofonia é uma condição recentemente descrita, mal compreendida e negligenciada. É caracterizada por fortes reações negativas de ódio, raiva ou medo quando os indivíduos precisam enfrentar alguns sons repetitivos seletivos e de baixa intensidade. Os mais comuns que desencadeiam tais reações aversivas são aqueles provocados pela boca (mascar goma ou mastigar comida, estalar os lábios) ou nariz (respirando, cheirando e soprando) ou pelos dedos (digitando, amassando papel, clicando a caneta, tamborilando na mesa). Artigos anteriores citam que esses indivíduos geralmente conhecem pelo menos um parente próximo com sintomas semelhantes, sugerindo um possível componente hereditário. Objetivo: Encontramos e descrevemos uma família com 15 membros com misofonia, detalhando suas características comuns e o padrão de sons que desencadeiam um desconforto tão forte. Método: Todos os 15 membros concordaram em nos fornecer seus dados epidemiológicos e 12 concordaram em responder a um questionário específico que investigou os sintomas, sons de gatilho específicos, principais sentimentos evocados e atitudes adotadas por cada participante. Resultados: Os 15 membros pertencem a três gerações da família. A idade variou de 9 a 73 anos (média de 38,3 anos, mediana de 41 anos) e 10 eram mulheres. A análise dos 12 questionários mostrou que 10 indivíduos (83,3%) desenvolveram os primeiros sintomas durante a infância ou a adolescência. A média do escore de irritação na Escala Visual Analógica de 0 a 10 foi de 7,3 (mediana 7,5). Os indivíduos relataram sentimentos de ódio/raiva, irritabilidade e ansiedade em resposta a sons, e enfrentaram a situação pedindo para interromper o som, deixando/evitando o lugar e até mesmo discutindo. Os sintomas associados auto-relatados foram ansiedade (91,3%), zumbido (50%), transtorno obsessivo-compulsivo (41,6%), depressão (33,3%) e hipersensibilidade aos sons (25%). Conclusão: A alta incidência de misofonia nessa distribuição familiar em particular sugere que possa ser mais comum do que o esperado e suscita a possibilidade de haver uma etiologia hereditária.

Asociación entre los polimorfismos 5HTTLPR, uMAOA y depresión en una cohorte de pacientes de atención primaria / Association between serotonin transporter and monoamine oxidase A gene polymorphisms and depression

Background: Serotonin plays a central role regulating mood and on the development of depressive disorders. Aim: To study whether 5HTTLPR functional polymorphisms in the serotonin transporter gene or the Monoamine oxidase A gene (uMAOA) were risk markers for depression. Material and Methods: The Composite International Diagnostic Interview (CIDI) was applied to 1,062 consultants in primary health care centers aged between 18 and 75 years to establish the diagnosis of depression. A sample of saliva was obtained for DNA extraction and genetic analyses. Results: No association between the presence of depressive disorders and 5HTTLPR (ss) or uMAOA (3/3) risk genotypes was found. Psychological abuse and the presence of two or more life events were found to be predictors of depression in the studied sample. Conclusions: In this study, 5HTTLPR and uMAOA polymorphisms were not risk factors for depression. However, psychological abuse and the presence of two or more life events were risk factors for depressive disorders.

Prueba de basculación (Tilt Table Testing): Comparación de dos protocolos: isoproterenol versus nitroglicerina / Comparison of the use of isoproterenol or nitroglycerine during the Tilt test

Background: There is debate about the advantages of different protocols usefulness of tilt test for the diagnosis of vasovagal collapse. Aim: To compare the sensitivity, specificity, adverse reactions, complications and time requirements of two different Tilt test protocols. Material and Methods: A Tilt test using isoproterenol in progressive doses (2 μg for 10 min and 5 μg for 5 min posteriorly was performed in 159 patients aged 9 to 84 years (59 males). Another Tilt test using sublingual nitroglycerine in doses of 0.3 mg was performed in 201 patients aged 8 to 87 years (62 males). Also, 20 healthy volunteers were tested. Results: The positivity rates of the tests using isoproterenol and nitroglycerin were 75.5 and 77.6% respectively (NS). The figures for sensitivity were 98.4 and 99.3% (NS). The figures for specificity were 93.2 and 98.4% (NS). The test using isoproterenol requires 15 more minutes. As adverse reactions, 38% of participants experienced palpitations with isoproterenol and 22% experienced headache with nitroglycerin. Conclusions: The Tilt test with nitroglycerin is shorter, simpler, painless, with less personnel involved and has the same diagnostic accuracy than the test with isoproterenol.

Genetic biomarkers of depression.

Depression is a term that has been used to describe a variety of ailments, ranging from minor to incapacitating. Clinically significant depression, termed as major depression, is a serious condition characterized not only by depressed mood but also by a cluster of somatic, cognitive, and motivational symptoms. Significant research efforts are aimed to understand the neurobiological as well as psychiatric disorders, and the evaluation of treatment of these disorders is still based solely on the assessment of symptoms. In order to identify the biological markers for depression, we have focused on gathering information on different factors responsible for depression including stress, genetic variations, neurotransmitters, and cytokines and chemokines previously suggested to be involved in the pathophysiology of depression. The present review illustrates the potential of biomarker profiling for psychiatric disorders, when conducted in large collections. The review highlighted the biomarker signatures for depression, warranting further investigation.

Serotonin Transporter Gene Polymorphisms and Chronic Illness of Depression

Clinical course of depression is variable. The serotonin transporter gene is one of the most studied genes for depression. We examined the association of serotonin transporter gene polymorphisms with chronicity and recurrent tendency of depression in Korean subjects. This cross-sectional study involved 252 patients with major depression. Patients were genotyped for s/l polymorphisms in 5-HTT promoter region (5-HTTLPR), s/l variation in second intron of the 5-HTT gene (5-HTT VNTR intron2). Chronicity was associated with 5-HTTLPR. Patients with l/l had higher rate of chronicity than the other patients (l/l vs s/l or s/s; odds ratio, 4.45; 95% confidence interval, 1.59-12.46; P=0.005; logistic regression analysis). Recurrent tendency was not associated with 5-HTTLPR. Chronicity and recurrent tendency were not associated with 5-HTT VNTR intron2. These results suggest that chronic depression is associated with 5-HTTLPR.

Depressão na mulher / Depression in women

A especial atenção que é dada à mulher quando se aborda a depressão justifica-se primordialmente pela maior prevalência deste transtorno no sexo feminino. As pacientes com transtornos depressivos habitualmente freqüentam os serviços de atendimento médico primário. Pode-se dizer, então, que a depressão na mulher faz parte do cotidiano clínico do médico em geral. Apesar disso, menos da metade dessas pacientes recebe tratamento mínimo adequado. Reconhecimento e tratamento adequados dos casos não só contribuem para a prevenção de complicações e novos episódios depressivos como para uma melhor resposta aos tratamentos clínicos e maior adesão terapêutica. Sendo assim, o estudo da depressão na mulher nos parece fundamental para a boa prática médica. Descreveremos neste artigo os aspectos clínicos particulares da mulher e as relações entre a depressão e o ciclo de vida feminino.

Hacia un modelo explicativo biopsicosocial de la relación entre depresión materna y psicopatología infantil / Towards an explanatory biopsychosocial model of the relation between maternal depression and childhood psychopathology

Este artículo describe los resultados de múltiples estudios de la relación entre la depresión materna y los problemas emocionales y conductuales en sus niños y presenta un modelo biopsicosocial de influencias mutuas. Las implicaciones prácticas de este modelo y líneas de investigaciones son discutidas.

This article presents a review of the relation-ship between maternal depression and emotional and conduct problems in their offspring, and also describes a mutual influences biopsychosocial model. Practical implications of this model and potential future researches are discussed.

Da herança à localização cerebral: sobre o determinismo biológico de condutas indesejadas / From heritage to cerebral localization: on the biological determinism of undesired conducts

Analisamos os argumentos utilizados, em dois momentos diferentes do século XX, para justificar o recurso a explicações biológicas de condutas consideradas como socialmente indesejadas. Referimo-nos, inicialmente, aos estudos realizados pelos higienistas de início do século, cujas explicações estavam centradas no caráter orgânico e inato dos desvios, para continuar logo com os recentes estudos da neurociência que se propõem a localizar as condutas nas sinapses inadequadas e nas explicações referidas a deficiências químicas do cérebro.

The article analyzes the arguments used in two distinct moments of the 20th century, to justify the use of biological explanations for conducts considered as socially undesirable. Firstly we refer to studies of hygienists in the early century, whose explanation were centered on the organic and innate character of deviations, then we analyze the recent studies in the neurosciences which try to locate these conducts in inadequate synapses and in explanations related to chemical cerebral deficiencies.

Polimorfismos genéticos del transportador de serotonina (SERT) y depresión / Serotonin transporter gene polymorphisms (SERT) and depression

Genetic studies on depression have focused on the polimorphisms of the serotonin system genes. It has been investigated the tryptophan hydroxylase and the serotonin receptor genes, specifically the serotonin transporter. Two alleles of the promoter for the serotonin transporter gene have been described: a long allele (L) and a short allele (S). Studies suggest that the presence of the short allele (S) is associated to a higher vulnerability for depression in the presence of adverse environmental factors. By the other hand, the presence of the long allele (L) gives resilience for stressful situations. It is believed that the acquisition of higher vulnerability for stress must occur during early stages of neurodevelopment.

Los estudios genéticos en depresión se han enfocado especialmente en los polimorfismos de los genes asociados al sistema serotoninérgico. Se han investigado los genes de la triptofano hidroxilasa, de algunos receptores de serotonina y particularmente del transportador de serotonina. Se han descrito dos alelos en la región promotora del transportador de serotonina: uno largo (L) y otro corto (S). Los estudios sugieren que la presencia del alelo corto (S) se asocia a una mayor vulnerabilidad a la depresión en presencia de factores ambientales adversos. A la inversa, la presencia del alelo largo (L) parece conferir resiliencia frente a las situaciones de estrés. Se cree que la adquisición de la mayor vulnerabilidad al estrés debe ocurrir en etapas tempranas del neurodesarrollo.

As bases neurobiológicas do transtorno bipolar / Neurobiological basis of bipolar disorder

Neste artigo, os autores revisam importantes aspectos associados às bases biológicas do transtorno de humor bipolar (THB). O THB está relacionado com o surgimento de diversas alterações bioquímicas e moleculares em sistemas de neurotransmissão e vias de segundos-mensageiros geradores de sinais intracelulares. Essas modificações em neurônios e glia parecem estar associadas com o surgimento de sintomas maníacos e depressivos. Ainda neste contexto, disfunções na homeostasia e no metabolismo energético cerebral tem sido associado com alterações comportamentais, na modulação do humor e ritmo circadiano em humanos e em modelos animais da doença. Assim, alterações metabólicas em neurônios e células gliais têm sido associadas com quadros depressivos e maníacos. Nos últimos anos, avanços nas técnicas de neuroimagem, genéticos e de biologia moleculares têm gerado novos conhecimentos acerca das bases biológicas da bipolaridade. Os autores destacam que a doença parece estar relacionada diretamente com disfunções em diferentes mecanismos adaptativos a estresse em células neurais, gerando perda na capacidade celular de induzir neuroplasticidade e neurotrofismo, facilitando assim o surgimento da doença.

Genética dos transtornos afetivos / Genetic of affective disorders

Os autores revisam neste artigo o conjunto de evidências genético-epidemiológicas que indicam a presença de fatores genéticos na vulnerabilidade para os transtornos afetivos. Apresentam também os dados obtidos até o momento, através de estratégias de genética molecular na busca de genes de susceptibilidade para o transtorno afetivo bipolar e para a depressão.

Farmacogenética do tratamento da depressão: busca de marcadores moleculares de boa resposta aos antidepressivos / Treatment pharmacogenetics of depression: the search after molecular markers with a good response to antidepressants

Os autores revisam os estudos que buscam determinantes genéticos para uma boa ou má resposta ao tratamento farmacológico da depressão, incluindo a verificação de diferenças interindividuais nos mecanismos farmacocinéticos - estudos de variantes gênicas das enzimas metabolizadoras das drogas - e farmacodinâmicos - estudos de variantes funcionais dos genes que codificam os sítios envolvidos no mecanismo de ação das drogas. Concluem que o conhecimento acerca da presença de variantes funcionais nos genes das isoformas envolvidas no metabolismo dos antidepressivos como o CYP2D6, ou nos genes codificando seus sítios de ação como a proteína transportadora de serotonina (5-HTT), podem fornecer importantes subsídios para a personalização da escolha de medicações e dosagens utilizadas no tratamento da depressão.

Depressão infantil: um fenômeno da contemporaniedade / Depression in childhood: a contemporary fenomena

A depressão infantil enquanto fenômeno contemporãneo apresenta-se de várias maneiras e exige uma intervenção sob o ponto de vista biológico, psicológico e social. Este trabalho aborda a depressão infantil de acordo com o referencial teorico, como a Teoria comportamental pode contribuir para lidar com estas questões.

A neurobiologia do suicídio: evidências do papel do sistema serotoninérgico / Neurobiology of suicide: evidences of the role of serotonergic system

O suicídio figura entre as principais causas de morte nos países industrializados e, a despeito de tentativas de prevenção, suas taxas são crescentes, o que tem estimulado as pesquisas na biologia do suicídio, com o objetivo de auxiliar o clínico na identificação do suicida em potencial. Existem hoje muitas evidências oriundas de estudos com diferentes metodologias (estudos postðmortem, estudos de concentrações liquóricas de 5ðHIAA, estudos neuroendocrinológicos) mostrando que anormalidades no sistema serotoninérgico estariam associadas ao comportamento suicida. Hoje, o foco principal das pesquisas, após as evidências dos estudos de epidemiologia genética de que o suicídio seria, pelo menos parcialmente, geneticamente determinado, são os estudos de genética molecular. Esta abordagem, apesar de estar ainda em fase inicial e de ter resultados às vêzes inconsistentes, é promissora, e seus resultados sugerem que, pelo menos em parte, fatores genéticos influenciam o comportamento suicida através do sistema serotoninérgico. As pesquisas devem continuar, principalmente focando a associação de características psicopatológicas básicas, potencialmente associadas ao comportamento suicida, como a impulsividade, e sua associação com genes ligados à função serotoninérgica, assim como estudos postðmortem que podem examinar a expressão gênica e suas proteínas