RESUMO
Mental health is vital to human well-being, and prevention strategies to address mental illness have a significant impact on the burden of disease and quality of life. With the recent developments in body-worn sensors, it is now possible to continuously collect data that can be used to gain insights into mental health states. This has the potential to optimize psychiatric assessment, thereby improving patient experiences and quality of life. However, access to high-quality medical data for research purposes is limited, especially regarding diagnosed psychiatric patients. To this extent, we present the OBF-Psychiatric dataset which comprises motor activity recordings of patients with bipolar and unipolar major depression, schizophrenia, and ADHD (attention deficit hyperactivity disorder). The dataset also contains data from a clinical sample diagnosed with various mood and anxiety disorders, as well as a healthy control group, making it suitable for building machine learning models and other analytical tools. It contains recordings from 162 individuals totalling 1565 days worth of motor activity data with a mean of 9.6 days per individual.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno Depressivo Maior , Atividade Motora , Esquizofrenia , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Esquizofrenia/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/diagnóstico , Qualidade de Vida , MasculinoRESUMO
Social comparisons are a core feature of human life. Theories posit that social comparisons play a critical role in depression and social anxiety triggering negative evaluations about the self, as well as negative emotions. We investigated the neural basis of social comparisons in participants with major depression and/or social anxiety (MD-SA, n = 56) and healthy controls (n = 47) using functional magnetic resonance imaging. While being scanned participants performed a social comparison task, during which they received feedback about their performance and the performance of a coplayer. Upward social comparisons (being worse than the coplayer) elicited high levels of negative emotions (shame, guilt, and nervousness) across participants, with this effect being enhanced in the MD-SA group. Notably, during upward comparison the MD-SA group showed greater activation than the control group in regions of the default mode network (DMN). Specifically, for upward comparison MD-SA participants demonstrated increased activation in the dorsomedial prefrontal cortex and reduced deactivation in the posteromedial cortex, regions linked to self-referential processing, inferences about other people's thoughts, and rumination. Findings suggest that people with depression and social anxiety react to upward comparisons with a more negative emotional response, which may be linked to introspective processes related to the DMN.
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Rede de Modo Padrão , Imageamento por Ressonância Magnética , Comparação Social , Humanos , Masculino , Imageamento por Ressonância Magnética/métodos , Feminino , Adulto , Adulto Jovem , Rede de Modo Padrão/fisiopatologia , Rede de Modo Padrão/diagnóstico por imagem , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Maior/diagnóstico por imagem , Ansiedade/fisiopatologia , Ansiedade/psicologia , Emoções/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Encéfalo/fisiologia , Mapeamento Encefálico , Depressão/fisiopatologia , Depressão/psicologia , Depressão/diagnóstico por imagem , Fobia Social/fisiopatologia , Fobia Social/psicologia , Fobia Social/diagnóstico por imagemRESUMO
This article analyzes the impact of psychotropic drug use on individuals diagnosed with schizophrenia, bipolar affective disorder, and severe depression in Chile. Using a qualitative narrative approach, the experiences of 25 patients from 2018 to 2021 are examined. Participants describe how these medications, while effective in symptom control, generate psychological suffering and a sense of coercion in daily life. The results reveal that prolonged use of psychotropic drugs leads to significant side effects, including physical, cognitive, and social deterioration, as well as a persistent sense of dependence on these medications. Furthermore, the article critiques the medicalization of mental disorders within modern psychiatry, where the biomedical approach predominates, reducing human distress to a neurochemical problem and disregarding social factors. The study concludes that while psychotropic drugs can stabilize patients, they also perpetuate forms of control and suffering.
Este artículo analiza el impacto del uso de psicofármacos en personas diagnosticadas con esquizofrenia, trastorno afectivo bipolar y depresión severa en Chile. A través de un enfoque cualitativo narrativo, se recogen las experiencias de 25 pacientes entre los 2018-2021, quienes describen cómo estos medicamentos, aunque efectivos para controlar los síntomas, generan sufrimiento psíquico y una sensación de coerción en su vida diaria. Los resultados muestran que el uso prolongado de psicofármacos provoca efectos secundarios significativos, como el deterioro físico, cognitivo y social, y que los pacientes sienten una dependencia constante hacia estos medicamentos. Además, el artículo critica la medicalización de los trastornos mentales en el contexto de la psiquiatría moderna, donde predomina el enfoque biomédico, reduciendo el malestar humano a un problema neuroquímico y desestimando factores sociales. Se concluye que, aunque los psicofármacos pueden estabilizar a los pacientes, también perpetúan formas de control y sufrimiento.
Assuntos
Transtorno Bipolar , Coerção , Psicotrópicos , Esquizofrenia , Humanos , Chile , Feminino , Masculino , Psicotrópicos/uso terapêutico , Adulto , Pessoa de Meia-Idade , Esquizofrenia/tratamento farmacológico , Transtorno Bipolar/tratamento farmacológico , Pesquisa Qualitativa , Transtorno Depressivo Maior/tratamento farmacológico , Adulto JovemRESUMO
Montanoa tomentosa is used in traditional Mexican medicine to treat reproductive and mood disorders. Preclinical studies support the idea that acute administration of M. tomentosa induces an antidepressant-like response that may be related to oxytocin activation in hypothalamic cells, however, it is unknown whether this behavioral and neuroendocrine effect is maintained when chronically administered. Here, 39 adults male Wistar rats were subjected to two conditions: without and with the forced swimming test (FST). Each group received for 28 consecutive days p.o., vehicle (1 mL/kg); fluoxetine (1 mg/kg); or M. tomentosa (50 mg/kg). M. tomentosa and fluoxetine treatments significantly decreased the total immobility time compared with that using vehicle without producing any significant change in locomotor activity. No significant between-treatment differences were found in the number of oxytocinergic neurons, indicating that chronic infusion of M. tomentosa exerts antidepressant-like effects, similar to those of Fluoxetine, independently of oxytocinergic activation.
Montanoa tomentosa es utilizada en la medicina tradicional mexicana para tratar trastornos reproductivos y de estado de ánimo. Estudios preclínicos, reportan que la administración aguda de M. tomentosa produce efectos tipo antidepresivo asociados con la activación de células hipotalámicas oxitocinérgicas, pero se desconoce si estos efectos conductual y neuroendocrino se mantienen después de un tratamiento crónico. Se incluyeron 39 ratas macho adultas Wistar bajo dos condiciones: sin y con inducción de estrés por nado forzado. Cada grupo recibió durante 28 días consecutivos p.o., vehículo (1mL/kg); fluoxetina (1 mg/kg); o M. tomentosa(Mt; 50 mg/kg). Los tratamientos con M. tomentosa y fluoxetina disminuyeron significativamente el tiempo total de inmovilidad comparado con vehículo, sin cambio significativo en la locomoción. No hubo diferencias significativas en el número de neuronas oxitocinérgicas entre tratamientos, lo que indica que la infusión crónica de M. tomentosa ejerce efectos tipo antidepresivos similares a Fluoxetina, independientemente de la activación oxitocinérgica.
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Animais , Ratos , Ocitocina/fisiologia , Montanoa , Transtorno Depressivo Maior/tratamento farmacológico , Neurônios/efeitos dos fármacos , Esquema de Medicação , Ocitocina/metabolismo , Ratos WistarRESUMO
Major depressive disorder is the psychiatric disease with the highest global prevalence, impacting social functioning and decreasing the quality of life. The partial pathophysiological knowledge of the disease, the economic burden and the low remission rates are sufficient justification to carry out an update on the subject in the search for new therapeutic approaches and targets. The endocannabinoid system has been linked to the development of depression, and its stimulation or antagonism is a promising approach in the treatment of major depressive disorder. Cannabidiol (CBD) and its properties have been widely studied recently; its analgesic, anti-inflammatory, antineoplastic and neuroprotective roles have even been reported in animal models and clinical trials, achieving its approved use for certain neurodegenerative pathologies. The use of CBD in depression biomodels and clinical trials has not been the exception, and here we contrast the current evidence of its administration and pharmacology against the pathological mechanisms of major depressive disorder.
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Antidepressivos , Canabidiol , Transtorno Depressivo Maior , Endocanabinoides , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Endocanabinoides/metabolismo , Animais , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Qualidade de VidaRESUMO
INTRODUCTION: The development of depression after myocardial infarction is associated with a 2- to 2.5-fold increased risk of all-cause mortality, cardiovascular mortality, and cardiovascular events. The objective of this study was to investigate, through a broad search of the literature, whether major depression is associated with worse psychiatric outcomes in middle-aged patients with myocardial ischemia. METHODS: An extensive search for studies on the association between major depression and myocardial ischemia was conducted in the PubMed, Embase, PsycINFO, and Web of Science databases. Randomized clinical trials of middle-aged patients with myocardial ischemia and concomitant depressive symptoms were included. RESULTS: The 14 articles included in this systematic review did not confirm an association between myocardial ischemia and depression with worse psychiatric outcomes in middle-aged patients. However, worse cardiovascular outcomes have been observed in patients with depression after myocardial infarction. CONCLUSIONS: The findings of this study suggest that major depression increases cardiovascular risk in patients after acute myocardial infarction, possibly because of a more pronounced increase in inflammatory markers. REGISTRATION: This systematic review was registered in the International Prospective Registry of Systematic Reviews (PROSPERO) under the number CRD: 511650.
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Transtorno Depressivo Maior , Infarto do Miocárdio , Isquemia Miocárdica , Humanos , Pessoa de Meia-Idade , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/psicologia , Infarto do Miocárdio/psicologia , Infarto do Miocárdio/epidemiologia , Isquemia Miocárdica/psicologia , Isquemia Miocárdica/epidemiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
We report the case of an older female patient suffering from a subacute qualitative and quantitative alteration in the state of consciousness secondary to a major depressive disorder with catatonic features. We discuss and review the clinical presentation, diagnosis, etiology, and treatment of catatonia in older adults from the internist's point of view.
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Catatonia , Transtorno Depressivo Maior , Humanos , Feminino , Transtorno Depressivo Maior/diagnóstico , Catatonia/diagnóstico , Diagnóstico Diferencial , Idoso , Transtornos da Consciência/etiologia , Transtornos da Consciência/diagnósticoRESUMO
The use of digital means of communication and socialization among young people brings with it new stressors, risks, and forms of ag- gression, such as cyberbullying. AIM: To evaluate the relationship between cyberbullying and major depressive symptoms in young Chileans between 15 and 29 years. METHODS: Survey through the StatKnows platform. Sampling was probabilistic and stratified with allocation proportional to the size of biphasic selection. The sample and the data were accessed virtually, respecting the bioethical standards of research with humans. RESULTS: At all ages studied, the probability of experiencing depressive symptoms increases as levels of cyber aggression do, especially in the group between 19 and 24 years. CONCLUSIONS: The results reflect various factors of emerging adulthood that make this group more vulnerable, emphasizing the importance of studying the phenomenon at non-school ages since this form of aggression is not exclusive to adolescence, and neither are its effects on mental health.
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Cyberbullying , Humanos , Chile/epidemiologia , Adolescente , Masculino , Feminino , Adulto Jovem , Cyberbullying/psicologia , Cyberbullying/estatística & dados numéricos , Adulto , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/psicologia , Fatores Etários , Fatores de Risco , Agressão/psicologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Major Depressive Disorder (MDD) is a global health issue, and a significant portion of individuals with MDD experience Treatment-Resistant Depression (TRD), characterized by the lack of response to adequately trialed antidepressant medication and therapy. This systematic review aims to investigate the effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) as an intervention for individuals with TRD. MATERIALS AND METHODS: We will conduct a thorough search for publications of randomized clinical trials and quasi-experimental studies in MEDLINE, Embase, PsycINFO, Web of Science databases, and ClinicalTrials.gov. Furthermore, reference lists of included studies will be manually screened for additional relevant articles, with no restrictions on language or publication date. The search will be conducted from the inception of the databases until June 2024. Our PICO-guided research questions are: (1) In adults with Treatment-Resistant Depression, is MBCT more effective than standard care or other active treatments in reducing depressive symptoms? (2) In adults with Treatment-Resistant Depression, does MBCT demonstrate a comparable safety profile to standard care or other active treatments? The quality of the included studies will be assessed independently using the Cochrane Risk of Bias Tool (RoB 2). This study seeks to evaluate the effectiveness and tolerability of Mindfulness-Based Cognitive Therapy as an intervention for Treatment-Resistant Depression, and will employ the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to appraise the confidence in the evidence. PROSPERO REGISTRATION: Prospero registration ID: CRD42023411978. Registered on April 07, 2023.
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Terapia Cognitivo-Comportamental , Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Atenção Plena , Humanos , Terapia Cognitivo-Comportamental/métodos , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Resistente a Tratamento/terapia , Metanálise como Assunto , Atenção Plena/métodos , Revisões Sistemáticas como Assunto , Resultado do TratamentoRESUMO
ABSTRACT: Lifetime history of suicide attempts is associated with inflammatory mechanisms, severity of depressive symptoms, and childhood trauma. This cross-sectional study enrolled 54 suicide attempters and 154 nonsuicide attempters. All individuals were assessed through a questionnaire, a structured clinical interview, scales, anthropometric measures, and laboratory biomarkers. Individuals with a history of lifetime suicide attempts showed significant positive correlations regarding soluble tumor necrosis factor receptor 1 and severity of depressive symptoms (p = 0.013), interleukin-1 receptor antagonist and severity of depressive symptoms (p = 0.04), and absenteeism from work and childhood physical abuse (p = 0.012). Suicide attempters also experienced more childhood trauma (sexual abuse, physical abuse, emotional abuse, emotional neglect, and physical neglect) compared with nonsuicide attempters. IL-4 levels were significantly lower in individuals who attempted suicide than in nonsuicidal individuals. Lifetime suicide attempts in major affective disorders were associated with childhood trauma and proinflammatory and anti-inflammatory cytokines.
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Sobreviventes Adultos de Maus-Tratos Infantis , Depressão , Inflamação , Tentativa de Suicídio , Humanos , Tentativa de Suicídio/estatística & dados numéricos , Tentativa de Suicídio/psicologia , Feminino , Masculino , Adulto , Estudos Transversais , Pessoa de Meia-Idade , Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Sobreviventes Adultos de Maus-Tratos Infantis/estatística & dados numéricos , Depressão/psicologia , Experiências Adversas da Infância/estatística & dados numéricos , Índice de Gravidade de Doença , Transtorno Depressivo Maior/psicologiaRESUMO
Major depressive disorder (MDD) is a significant cause of disability in adults worldwide. However, the underlying causes and mechanisms of MDD are not fully understood, and many patients are refractory to available therapeutic options. Impaired control of brain mRNA translation underlies several neurodevelopmental and neurodegenerative conditions, including autism spectrum disorders and Alzheimer's disease (AD). Nonetheless, a potential role for mechanisms associated with impaired translational control in depressive-like behavior remains elusive. A key pathway controlling translation initiation relies on the phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α-P) which, in turn, blocks the guanine exchange factor activity of eIF2B, thereby reducing global translation rates. Here we report that the expression of EIF2B5 (which codes for eIF2Bε, the catalytic subunit of eIF2B) is reduced in postmortem MDD prefrontal cortex from two distinct human cohorts and in the frontal cortex of social isolation-induced depressive-like behavior model mice. Further, pharmacological treatment with anisomycin or with salubrinal, an inhibitor of the eIF2α phosphatase GADD34, induces depressive-like behavior in adult C57BL/6J mice. Salubrinal-induced depressive-like behavior is blocked by ISRIB, a compound that directly activates eIF2B regardless of the phosphorylation status of eIF2α, suggesting that increased eIF2α-P promotes depressive-like states. Taken together, our results suggest that impaired eIF2-associated translational control may participate in the pathophysiology of MDD, and underscore eIF2-eIF2B translational axis as a potential target for the development of novel approaches for MDD and related mood disorders.
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Transtorno Depressivo Maior , Modelos Animais de Doenças , Fator de Iniciação 2B em Eucariotos , Fator de Iniciação 2 em Eucariotos , Córtex Pré-Frontal , Animais , Transtorno Depressivo Maior/metabolismo , Camundongos , Humanos , Fator de Iniciação 2B em Eucariotos/metabolismo , Fator de Iniciação 2B em Eucariotos/genética , Fator de Iniciação 2 em Eucariotos/metabolismo , Masculino , Córtex Pré-Frontal/metabolismo , Feminino , Camundongos Endogâmicos C57BL , Comportamento Animal , Pessoa de Meia-Idade , Cinamatos/farmacologia , Adulto , Biossíntese de Proteínas , Fosforilação , Anisomicina/farmacologia , Acetamidas , Cicloexilaminas , Tioureia/análogos & derivadosRESUMO
INTRODUCTION: Major depressive disorder is related to unfavourable outcomes in patients with severe comorbidities. In transplant patients, major depression is associated with worse clinical outcomes. CASE REPORT: We present the case of a 55-year-old man with a heart transplant due to heart failure of ischaemic origin. Six months after the transplant he developed depressed mood, anhedonia and suicidal ideation with a score of 20/27 on the PHQ-9 depression screening scale. After receiving mirtazapine 30â¯mg/night for a week and persisting with a high suicide risk, it was decided to administer ketamine infusion for 24â¯h, with which a significant improvement in mood was observed, and the disappearance of suicidal ideation 24â¯h after the infusion. DISCUSSION: Depression in transplant patients is a factor associated with graft loss and post-transplant mortality, in addition to favouring other negative outcomes such as deep vein thrombosis. CONCLUSIONS: Ketamine infusion was shown to be an effective and safe option to treat major depression with suicidal risk in a heart transplant patient.
Assuntos
Transtorno Depressivo Maior , Insuficiência Cardíaca , Transplante de Coração , Ketamina , Mirtazapina , Ideação Suicida , Humanos , Masculino , Pessoa de Meia-Idade , Ketamina/administração & dosagem , Mirtazapina/administração & dosagem , Resultado do Tratamento , Índice de Gravidade de DoençaRESUMO
Major depressive disorder (MDD) has demonstrated its negative impact on various aspects of the lives of those affected. Although several therapies have been developed over the years, it remains a challenge for mental health professionals. Thus, understanding the pathophysiology of MDD is necessary to improve existing treatment options or seek new therapeutic alternatives. Clinical and preclinical studies in animal models of depression have shown the involvement of synaptic plasticity in both the development of MDD and the response to available drugs. However, synaptic plasticity involves a cascade of events, including the action of presynaptic proteins such as synaptophysin and synapsins and postsynaptic proteins such as postsynaptic density-95 (PSD-95). Additionally, several factors can negatively impact the process of spinogenesis/neurogenesis, which are related to many outcomes, including MDD. Thus, this narrative review aims to deepen the understanding of the involvement of synaptic formations and their components in the pathophysiology and treatment of MDD.
Assuntos
Transtorno Depressivo Maior , Plasticidade Neuronal , Humanos , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/fisiopatologia , Animais , Plasticidade Neuronal/fisiologia , Plasticidade Neuronal/efeitos dos fármacos , Sinapses/metabolismo , Sinapses/efeitos dos fármacosRESUMO
Background: the aim of this study is to understand the diagnostic process undertaken by psychiatrists and psychologists regarding adjustment disorder (AD) in their clinical practice and how they differentiate it from major depressive episode (MDE).Methods: A hermeneutic study using grounded theory techniques was carried out. Semi-structured interviews were conducted with twelve psychiatrists and eight psychologists in Colombia, and transcribed verbatim. Initial line-by-line coding was performed, followed by focused and axial coding to construct categories explaining the professionals' reasoning process.Results: The clinical reasoning of professionals regarding AD was understood through four major categories. (1) Difficulty in addressing the experience of stressful events, as there is a risk of pathologizing and medicalizing them. (2) Mental health diagnoses are necessary but not apodictic. (3) The diagnostic category of AD allows for the description of a fluctuating depressive and anxious syndrome occurring in reaction to a stressful event, whose abnormality criteria are based on intersubjective knowledge of the patient's life history and consequential reasoning regarding the need for professional support. (4) The AD label could potentially protect against overdiagnosis of MDE and overuse of antidepressants. Many clinicians in their practice thus subordinate the diagnosis of MDE to ensuring it is not AD, contrary to what is outlined in diagnostic manuals.Conclusion: This study allowed us to understand the clinical reasoning of psychiatrists and psychologists about AD as a diagnosis that inherently indicates the need to work on coping and intervene in the stressor and should be considered as a diagnostic possibility in the same hierarchy as MDE in reactive syndromes, rather than a residual category.
Clinicians use consequential and intersubjective reasoning to diagnose Adjustment Disorder (AD).Systemic pressures lead to overdiagnosis of Major Depressive Episode (MDE) and excessive antidepressant use.AD should be recognized as a valid non-residual diagnostic category.
Assuntos
Transtornos de Adaptação , Raciocínio Clínico , Teoria Fundamentada , Psiquiatria , Humanos , Feminino , Transtornos de Adaptação/diagnóstico , Transtornos de Adaptação/psicologia , Masculino , Adulto , Transtorno Depressivo Maior/diagnóstico , Psicologia , Colômbia , Pessoa de Meia-Idade , Pesquisa Qualitativa , Entrevistas como Assunto , Diagnóstico Diferencial , PsiquiatrasRESUMO
Major depression disorder is an entity with high prevalence and worldwide impact. Current treatments present a non-response rate of 15-30%, and certain adverse effects are seen like apathy syndrome and lack of emotional response. It is stated that the treatment with psilocybin fungi allows the possibility of dose reduction and suspension of classic psychotropic drugs and entails changes on an emotional and behavioral level that result benefic in patients with major depressive syndrome. We present a case of a 19 years old patient with major depressive syndrome diagnosis. Accompaniment and patient advice was made appealing to the right of autonomy, on the psilocybin microdose self-administration process, aiming to reducing health risks and potentiate probable beneficial effects, with weekly evaluations, for a period of 7 months; using clinical anamnesis, laboratory tests and the Hamilton depression scale. As a result of this intervention, a symptomatic complete remission was proven, alongside with the suspension of conventional pharmacological treatment without discontinuation symptoms and improvements at the communicational level, social interaction and general well-being. These findings support the idea that psilocybin microdose treatments are promising tools in depression treatments. Scientific studies are needed in order to certify these findings.
La depresión mayor es una enfermedad de gran prevalencia e impacto mundial. Los tratamientos actuales presentan una tasa de no respuesta del 15 al 30 %, mientras que en casos de eficacia se suelen observar efectos adversos como el síndrome de apatía y la falta de respuesta emocional. Se postula que el tratamiento con hongos psilocibios genera la posibilidad de reducción de dosis y suspensión de psicofármacos clásicos y ocasiona cambios a nivel emocional y comportamental benéficos en pacientes con trastorno depresivo mayor. Este es un caso de un paciente no binario de 19 años de edad con diagnóstico de trastorno depresivo mayor. Se realizó unacompañamiento y asesoramiento del paciente apelando al derecho de autonomía, en el proceso de autoadministración de microdosis de psilocibina, para disminución de riesgos en salud y potenciar efectos benéficos probables, con evaluación semanal, durante un periodo de 7 meses; utilizando la anamnesis clínica, análisis de laboratorio y la escala validada de depresión de Hamilton. Como resultado de esta intervención se evidenció una remisión completa sintomática, la suspensión del tratamiento farmacológico convencional, sin síntomas de discontinuación y mejorías a nivel comunicacional, de interacción social y bienestar general. Estos hallazgos apoyan la idea de que los tratamientos con microdosis de psilocibina son una herramienta prometedora en los tratamientos de depresión. Se necesitan más estudios que aporten evidencia científica para comprobar dichos hallazgos.
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Transtorno Depressivo Maior , Alucinógenos , Psilocibina , Humanos , Psilocibina/uso terapêutico , Psilocibina/administração & dosagem , Transtorno Depressivo Maior/tratamento farmacológico , Adulto Jovem , Alucinógenos/uso terapêutico , Alucinógenos/administração & dosagem , Masculino , AgaricalesRESUMO
INTRODUCTION: Major Depressive Disorder (MDD) is a common mental health disorder marked by sadness, hopelessness, and anhedonia. Various therapies exist, but their effectiveness is limited. Dextromethorphan hydrobromide combined with bupropion hydrochloride (Auvelity®) is a recently approved alternative for treating this condition in adults. AREAS COVERED: This review summarizes the neurobiology of major depression and delves into the pharmacology, efficacy, safety, and tolerability of dextromethorphan plus bupropion in adult patients. It is based on observational studies, clinical trials, and other secondary studies obtained through systematic literature searches. EXPERT OPINION: The combination of bupropion and dextromethorphan as a new pharmacotherapy for mental health is an interesting addition to the treatment options that can be used for MDD. The combination can be used in a range of scenarios, including as a first line therapy, as a second option when a patient has failed to achieve remission with a serotonin targeting agent, and for treatment resistant depression. Further research for other indications, including addiction disorders, may provide exciting results. Although a new combination, clinicians will be very familiar with both agents, increasing their acceptability. This pharmacotherapy also may bring increased impetus for discovering other combinations that may have beneficial synergistic effects.
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Bupropiona , Transtorno Depressivo Maior , Dextrometorfano , Humanos , Bupropiona/uso terapêutico , Bupropiona/farmacologia , Dextrometorfano/uso terapêutico , Dextrometorfano/farmacologia , Transtorno Depressivo Maior/tratamento farmacológico , Quimioterapia Combinada , Antidepressivos de Segunda Geração/uso terapêutico , Combinação de MedicamentosRESUMO
BACKGROUND: Depression can be associated with increased mortality and morbidity, but no studies have investigated the specific causes of death based on autopsy reports. Autopsy studies can yield valuable and detailed information on pathological ailments or underreported conditions. This study aimed to compare autopsy-confirmed causes of death (CoD) between individuals diagnosed with major depressive disorder (MDD) and matched controls. We also analyzed subgroups within our MDD sample, including late-life depression and recurrent depression. We further investigated whether machine learning (ML) algorithms could distinguish MDD and each subgroup from controls based on their CoD. METHODS: We conducted a comprehensive analysis of CoD in individuals who died from nontraumatic causes. The diagnosis of lifetime MDD was ascertained based on the DSM-5 criteria using information from a structured interview with a knowledgeable informant. Eleven established ML algorithms were used to differentiate MDD individuals from controls by simultaneously analyzing different disease category groups to account for multiple tests. The McNemar test was further used to compare paired nominal data. RESULTS: The initial dataset included records of 1,102 individuals, among whom 232 (21.1%) had a lifetime diagnosis of MDD. Each MDD individual was strictly paired with a control non-psychiatric counterpart. In the MDD group, the most common CoD were circulatory (67.2%), respiratory (13.4%), digestive (6.0%), and cancer (5.6%). Despite employing a range of ML models, we could not find distinctive CoD patterns that could reliably distinguish individuals with MDD from individuals in the control group (average accuracy: 50.6%; accuracy range: 39-59%). These findings were consistent even when considering factors within the MDD group, such as late-life or recurrent MDD. When comparing groups with paired nominal tests, no differences were found for circulatory (p=0.450), respiratory (p=0.790), digestive (p=1.000), or cancer (p=0.855) CoD. CONCLUSIONS: Our analysis revealed that autopsy-confirmed CoD exhibited remarkable similarity between individuals with depression and their matched controls, underscoring the existing heterogeneity in the literature. Future research should prioritize more severe manifestations of depression and larger sample sizes, particularly in the context of CoD related to cancer.
Assuntos
Autopsia , Causas de Morte , Transtorno Depressivo Maior , Aprendizado de Máquina , Humanos , Transtorno Depressivo Maior/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Estudos de Casos e Controles , Idoso de 80 Anos ou maisRESUMO
Undergraduate students are frequently afflicted by major depressive disorder (MDD). Oxidative and nitrosative stress (O&NS) has been implicated in the pathophysiology of MDD. There is no information regarding whether mild outpatient MDD (SDMD) and first episode SDMD (FE-SDMD) are accompanied by O&NS. The current study compared lipid hydroperoxides (LOOH), malondialdehyde (MDA), advanced protein oxidation products, nitric oxide metabolites (NOx), thiol groups, plasma total antioxidant potential (TRAP), and paraoxonase 1 activities among SDMD and FE-SDMD patients versus healthy controls. We found that SDMD and FE-SDMD exhibit elevated MDA and NOx, and decreased TRAP and LOOH as compared with controls. There was a significant and positive correlation between O&NS biomarkers and adverse childhood experiences (ACEs), and negative life events (NLEs). O&NS pathways, NLEs and ACEs accounted for 51.7 % of the variance in the phenome of depression, and O&NS and NLS explained 42.9 % of the variance in brooding. Overall, these results indicate that SDMD and FE-SDMD are characterized by reduced total antioxidant defenses and increased aldehyde and NOx production. The combined effects of oxidative and psychological stressors are substantially associated with the manifestation of SDMD.
Assuntos
Malondialdeído , Óxido Nítrico , Estresse Oxidativo , Estresse Psicológico , Estudantes , Humanos , Masculino , Feminino , Óxido Nítrico/metabolismo , Malondialdeído/sangue , Malondialdeído/metabolismo , Adulto Jovem , Estresse Psicológico/metabolismo , Estudantes/psicologia , Estresse Oxidativo/fisiologia , Depressão/metabolismo , Depressão/psicologia , Adulto , Transtorno Depressivo Maior/metabolismo , Estresse Nitrosativo/fisiologia , Universidades , Biomarcadores/sangue , Adolescente , Experiências Adversas da InfânciaRESUMO
The biological mechanisms underlying the onset of major depressive disorder (MDD) have predominantly been studied in adult populations from high-income countries, despite the onset of depression typically occurring in adolescence and the majority of the world's adolescents living in low- and middle-income countries (LMIC). Taking advantage of a unique adolescent sample in an LMIC (Brazil), this study aimed to identify biological pathways characterizing the presence and increased risk of depression in adolescence, and sex-specific differences in such biological signatures. We collected blood samples from a risk-stratified cohort of 150 Brazilian adolescents (aged 14-16 years old) comprising 50 adolescents with MDD, 50 adolescents at high risk of developing MDD but without current MDD, and 50 adolescents at low risk of developing MDD and without MDD (25 females and 25 males in each group). We conducted RNA-Seq and pathway analysis on whole blood. Inflammatory-related biological pathways, such as role of hypercytokinemia/hyperchemokinemia in the pathogenesis of influenza (z-score = 3.464, p < 0.001), interferon signaling (z-score = 2.464, p < 0.001), interferon alpha/beta signaling (z-score = 3.873, p < 0.001), and complement signaling (z-score = 2, p = 0.002) were upregulated in adolescents with MDD compared with adolescents without MDD independently from their level of risk. The up-regulation of such inflammation-related pathways was observed in females but not in males. Inflammatory-related pathways involved in the production of cytokines and in interferon and complement signaling were identified as key indicators of adolescent depression, and this effect was present only in females.
Assuntos
Transtorno Depressivo Maior , Inflamação , Humanos , Adolescente , Masculino , Feminino , Transtorno Depressivo Maior/imunologia , Transtorno Depressivo Maior/sangue , Brasil/epidemiologia , Inflamação/imunologia , Inflamação/sangue , Fatores Sexuais , Sistema Imunitário , Citocinas/sangueRESUMO
Despite uncertainty about the specific molecular mechanisms driving major depressive disorder (MDD), the Wnt signaling pathway stands out as a potentially influential factor in the pathogenesis of MDD. Known for its role in intercellular communication, cell proliferation, and fate, Wnt signaling has been implicated in diverse biological phenomena associated with MDD, spanning neurodevelopmental to neurodegenerative processes. In this systematic review, we summarize the functional differences in protein and gene expression of the Wnt signaling pathway, and targeted genetic association studies, to provide an integrated synthesis of available human data examining Wnt signaling in MDD. Thirty-three studies evaluating protein expression (n = 15), gene expression (n = 9), or genetic associations (n = 9) were included. Only fifteen demonstrated a consistently low overall risk of bias in selection, comparability, and exposure. We found conflicting observations of limited and distinct Wnt signaling components across diverse tissue sources. These data do not demonstrate involvement of Wnt signaling dysregulation in MDD. Given the well-established role of Wnt signaling in antidepressant response, we propose that a more targeted and functional assessment of Wnt signaling is needed to understand its role in depression pathophysiology. Future studies should include more components, assess multiple tissues concurrently, and follow a standardized approach.