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1.
Expert Rev Cardiovasc Ther ; 22(9): 509-516, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-39350736

RÉSUMÉ

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.


Sujet(s)
Trouble dépressif majeur , Infarctus du myocarde , Ischémie myocardique , Essais contrôlés randomisés comme sujet , Humains , Infarctus du myocarde/psychologie , Infarctus du myocarde/épidémiologie , Ischémie myocardique/psychologie , Ischémie myocardique/épidémiologie , Adulte d'âge moyen , Maladies cardiovasculaires/psychologie
2.
PLoS One ; 19(10): e0306227, 2024.
Article de Anglais | MEDLINE | ID: mdl-39405311

RÉSUMÉ

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.


Sujet(s)
Thérapie cognitive , Trouble dépressif résistant aux traitements , Méta-analyse comme sujet , Pleine conscience , Revues systématiques comme sujet , Humains , Pleine conscience/méthodes , Trouble dépressif résistant aux traitements/thérapie , Thérapie cognitive/méthodes , Trouble dépressif majeur/thérapie , Résultat thérapeutique
3.
Transl Psychiatry ; 14(1): 397, 2024 Oct 01.
Article de Anglais | MEDLINE | ID: mdl-39349438

RÉSUMÉ

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.


Sujet(s)
Trouble dépressif majeur , Modèles animaux de maladie humaine , Facteur-2B d'initiation eucaryote , Facteur-2 d'initiation eucaryote , Cortex préfrontal , Animaux , Trouble dépressif majeur/métabolisme , Souris , Humains , Facteur-2B d'initiation eucaryote/métabolisme , Facteur-2B d'initiation eucaryote/génétique , Facteur-2 d'initiation eucaryote/métabolisme , Mâle , Cortex préfrontal/métabolisme , Femelle , Souris de lignée C57BL , Comportement animal , Adulte d'âge moyen , Cinnamates/pharmacologie , Adulte , Biosynthèse des protéines , Phosphorylation , Anisomycine/pharmacologie , Acétamides , Cyclohexylamines , Thiourée/analogues et dérivés
4.
Rev Colomb Psiquiatr (Engl Ed) ; 53(2): 210-216, 2024.
Article de Anglais, Espagnol | MEDLINE | ID: mdl-39127545

RÉSUMÉ

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 30 mg/night for a week and persisting with a high suicide risk, it was decided to administer ketamine infusion for 24 h, with which a significant improvement in mood was observed, and the disappearance of suicidal ideation 24 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.


Sujet(s)
Trouble dépressif majeur , Défaillance cardiaque , Transplantation cardiaque , Kétamine , Mirtazapine , Idéation suicidaire , Humains , Mâle , Adulte d'âge moyen , Kétamine/administration et posologie , Mirtazapine/administration et posologie , Résultat thérapeutique , Indice de gravité de la maladie
5.
Neuroscience ; 556: 14-24, 2024 Sep 25.
Article de Anglais | MEDLINE | ID: mdl-39103041

RÉSUMÉ

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.


Sujet(s)
Trouble dépressif majeur , Plasticité neuronale , Humains , Trouble dépressif majeur/métabolisme , Trouble dépressif majeur/traitement médicamenteux , Trouble dépressif majeur/physiopathologie , Animaux , Plasticité neuronale/physiologie , Plasticité neuronale/effets des médicaments et des substances chimiques , Synapses/métabolisme , Synapses/effets des médicaments et des substances chimiques
6.
Eur J Psychotraumatol ; 15(1): 2390332, 2024.
Article de Anglais | MEDLINE | ID: mdl-39166284

RÉSUMÉ

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.


Sujet(s)
Troubles de l'adaptation , Raisonnement clinique , Théorie ancrée , Psychiatrie , Humains , Femelle , Troubles de l'adaptation/diagnostic , Troubles de l'adaptation/psychologie , Mâle , Adulte , Trouble dépressif majeur/diagnostic , Psychologie , Colombie , Adulte d'âge moyen , Recherche qualitative , Entretiens comme sujet , Diagnostic différentiel , Psychiatres
7.
BMC Psychiatry ; 24(1): 531, 2024 Jul 24.
Article de Anglais | MEDLINE | ID: mdl-39048987

RÉSUMÉ

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.


Sujet(s)
Autopsie , Cause de décès , Trouble dépressif majeur , Apprentissage machine , Humains , Trouble dépressif majeur/diagnostic , Mâle , Femelle , Adulte d'âge moyen , Adulte , Sujet âgé , Études cas-témoins , Sujet âgé de 80 ans ou plus
8.
Neuroscience ; 554: 52-62, 2024 Aug 30.
Article de Anglais | MEDLINE | ID: mdl-38992564

RÉSUMÉ

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.


Sujet(s)
Malonaldéhyde , Monoxyde d'azote , Stress oxydatif , Stress psychologique , Étudiants , Humains , Mâle , Femelle , Monoxyde d'azote/métabolisme , Malonaldéhyde/sang , Malonaldéhyde/métabolisme , Jeune adulte , Stress psychologique/métabolisme , Étudiants/psychologie , Stress oxydatif/physiologie , Dépression/métabolisme , Dépression/psychologie , Adulte , Trouble dépressif majeur/métabolisme , Stress nitrosatif/physiologie , Universités , Marqueurs biologiques/sang , Adolescent , Expériences défavorables de l'enfance
9.
Expert Rev Neurother ; 24(9): 837-848, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-39039791

RÉSUMÉ

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.


Sujet(s)
Bupropion , Trouble dépressif majeur , Dextrométhorphane , Humains , Bupropion/usage thérapeutique , Bupropion/pharmacologie , Dextrométhorphane/usage thérapeutique , Dextrométhorphane/pharmacologie , Trouble dépressif majeur/traitement médicamenteux , Association de médicaments , Antidépresseurs de seconde génération/usage thérapeutique , Association médicamenteuse
10.
Vertex ; 35(164, abr.-jun.): 33-39, 2024 07 10.
Article de Espagnol | MEDLINE | ID: mdl-39024488

RÉSUMÉ

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.


Sujet(s)
Trouble dépressif majeur , Hallucinogènes , Psilocybine , Humains , Psilocybine/usage thérapeutique , Psilocybine/administration et posologie , Trouble dépressif majeur/traitement médicamenteux , Jeune adulte , Hallucinogènes/usage thérapeutique , Hallucinogènes/administration et posologie , Mâle , Agaricales
11.
Transl Psychiatry ; 14(1): 254, 2024 Jun 12.
Article de Anglais | MEDLINE | ID: mdl-38866753

RÉSUMÉ

Depression is a prevalent and incapacitating condition with a significant impact on global morbidity and mortality. Although the immune system's role in its pathogenesis is increasingly recognized, there is a lack of comprehensive understanding regarding the involvement of innate and adaptive immune cells. To address this gap, we conducted a multicenter case-control study involving 121 participants matched for sex and age. These participants had either an active (or current) major depressive episode (MDE) (39 cases) or a remitted MDE (40 cases), including individuals with major depressive disorder or bipolar disorder. We compared these 79 patients to 42 healthy controls (HC), analyzing their immunological profiles. In blood samples, we determined the complete cell count and the monocyte subtypes and lymphocyte T-cell populations using flow cytometry. Additionally, we measured a panel of cytokines, chemokines, and neurotrophic factors in the plasma. Compared with HC, people endorsing a current MDE showed monocytosis (p = 0.001), increased high-sensitivity C-reactive protein (p = 0.002), and erythrocyte sedimentation rate (p = 0.003), and an altered proportion of specific monocyte subsets. CD4 lymphocytes presented increased median percentages of activation markers CD69+ (p = 0.007) and exhaustion markers PD1+ (p = 0.013) and LAG3+ (p = 0.014), as well as a higher frequency of CD4+CD25+FOXP3+ regulatory T cells (p = 0.003). Additionally, patients showed increased plasma levels of sTREM2 (p = 0.0089). These changes are more likely state markers, indicating the presence of an ongoing inflammatory response during an active MDE. The Random Forest model achieved remarkable classification accuracies of 83.8% for MDE vs. HC and 70% for differentiating active and remitted MDE. Interestingly, the cluster analysis identified three distinct immunological profiles among MDE patients. Cluster 1 has the highest number of leukocytes, mainly given by the increment in lymphocyte count and the lowest proinflammatory cytokine levels. Cluster 3 displayed the most robust inflammatory pattern, with high levels of TNFα, CX3CL1, IL-12p70, IL-17A, IL-23, and IL-33, associated with the highest level of IL-10, as well as ß-NGF and the lowest level for BDNF. This profile is also associated with the highest absolute number and percentage of circulating monocytes and the lowest absolute number and percentage of circulating lymphocytes, denoting an active inflammatory process. Cluster 2 has some cardinal signs of more acute inflammation, such as elevated levels of CCL2 and increased levels of proinflammatory cytokines such as IL-1ß, IFNγ, and CXCL8. Similarly, the absolute number of monocytes is closer to a HC value, as well as the percentage of lymphocytes, suggesting a possible initiation of the inflammatory process. The study provides new insights into the immune system's role in MDE, paving the ground for replication prospective studies targeting the development of diagnostic and prognostic tools and new therapeutic targets.


Sujet(s)
Cytokines , Trouble dépressif majeur , Immunophénotypage , Monocytes , Humains , Femelle , Mâle , Études cas-témoins , Trouble dépressif majeur/immunologie , Trouble dépressif majeur/sang , Adulte , Adulte d'âge moyen , Cytokines/sang , Cytokines/immunologie , Monocytes/immunologie , Trouble bipolaire/immunologie , Trouble bipolaire/sang , Inflammation/immunologie , Inflammation/sang , Antigènes CD/sang , Antigènes CD/immunologie , Cytométrie en flux
12.
Expert Opin Ther Targets ; 28(5): 401-418, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38871633

RÉSUMÉ

INTRODUCTION: Inflammasome complexes, especially NLRP3, have gained great attention as a potential therapeutic target in mood disorders. NLRP3 triggers a caspase 1-dependent release of the inflammatory cytokines IL-1ß and IL-18, and seems to interact with purinergic and kynurenine pathways, all of which are implicated in mood disorders development and progression. AREAS COVERED: Emerging evidence supports NLRP3 inflammasome as a promising pharmacological target for mood disorders. We discussed the available evidence from animal models and human studies and provided a reflection on drawbacks and perspectives for this novel target. EXPERT OPINION: Several studies have supported the involvement of NLRP3 inflammasome in MDD. However, most of the evidence comes from animal models. The role of NLRP3 inflammasome in BD as well as its anti-manic properties is not very clear and requires further exploration. There is evidence of anti-manic effects of P2×R7 antagonists associated with reduction in the brain levels of IL-1ß and TNF-α in a murine model of mania. The involvement of other NLRP3 inflammasome expressing cells besides microglia, like astrocytes, and of other inflammasome complexes in mood disorders also deserves further investigation. Preclinical and clinical characterization of NLRP3 and other inflammasomes in mood disorders is needed before considering translational approaches, including clinical trials.


Sujet(s)
Modèles animaux de maladie humaine , Inflammasomes , Thérapie moléculaire ciblée , Troubles de l'humeur , Protéine-3 de la famille des NLR contenant un domaine pyrine , Animaux , Humains , Inflammasomes/métabolisme , Protéine-3 de la famille des NLR contenant un domaine pyrine/métabolisme , Troubles de l'humeur/traitement médicamenteux , Troubles de l'humeur/physiopathologie , Souris , Trouble bipolaire/traitement médicamenteux , Trouble bipolaire/physiopathologie , Antagonistes des récepteurs purinergiques P2X/pharmacologie , Antagonistes des récepteurs purinergiques P2X/administration et posologie , Trouble dépressif majeur/traitement médicamenteux , Trouble dépressif majeur/physiopathologie
13.
Transl Psychiatry ; 14(1): 230, 2024 Jun 01.
Article de Anglais | MEDLINE | ID: mdl-38824135

RÉSUMÉ

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.


Sujet(s)
Trouble dépressif majeur , Inflammation , Humains , Adolescent , Mâle , Femelle , Trouble dépressif majeur/immunologie , Trouble dépressif majeur/sang , Brésil/épidémiologie , Inflammation/immunologie , Inflammation/sang , Facteurs sexuels , Système immunitaire , Cytokines/sang
14.
Psychiatry Res ; 339: 115994, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-38865906

RÉSUMÉ

We conducted a systematic review and meta-analysis to investigate the comparative effectiveness of ketamine versus electroconvulsive therapy (ECT) for the treatment of major depressive episodes (MDEs). PubMed, EMBASE and Cochrane Library databases were systematically searched for randomized controlled trials (RCTs) comparing ketamine and ECT for MDE. The primary outcome was response rate, for which we prespecified a non-inferiority margin of -0.1, based on the largest and most recent RCT. Response was defined as a reduction of at least 50 % in the depression scale score. Six RCTs met the inclusion criteria, comprising 655 patients. In the overall population, ketamine was not non-inferior to ECT in response rate (RD -0.10; 95 % CI -0.26 to 0.05; p = 0.198; I2 = 72 %). The ECT group had a higher reduction in depression scores, but without difference in remission and relapse rates. Regarding safety outcomes, ketamine had better posttreatment cognition scores and reduced muscle pain rate compared with ECT, albeit with an increased rate of dissociative symptoms. In a subanalysis with only inpatients, ketamine was inferior to ECT in response rate (RD -0.15; 95 % CI -0.27 to -0.03; p = 0.014; I2 = 25 %), remission, and change in depression scores. These findings support the use of ECT over ketamine for inpatients. Further RCTs are warranted to clarify the comparative effect of these treatments for outpatients.


Sujet(s)
Trouble dépressif majeur , Électroconvulsivothérapie , Kétamine , Kétamine/usage thérapeutique , Kétamine/administration et posologie , Humains , Électroconvulsivothérapie/méthodes , Trouble dépressif majeur/thérapie , Trouble dépressif majeur/traitement médicamenteux , Résultat thérapeutique , Essais contrôlés randomisés comme sujet
15.
Psychiatry Res ; 339: 115983, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-38870775

RÉSUMÉ

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.


Sujet(s)
Trouble dépressif majeur , Voie de signalisation Wnt , Humains , Trouble dépressif majeur/métabolisme , Voie de signalisation Wnt/physiologie
16.
Eur Psychiatry ; 67(1): e50, 2024 May 23.
Article de Anglais | MEDLINE | ID: mdl-38778009

RÉSUMÉ

BACKGROUND: Depression is one of the most prevalent mental health conditions in the world. However, the heterogeneity of depression has presented obstacles for research concerning disease mechanisms, treatment indication, and personalization. The current study used network analysis to analyze and compare profiles of depressive symptoms present in community samples, considering the relationship between symptoms. METHODS: Cross-sectional measures of depression using the Patient Health Questionnaire - 9 items (PHQ-9) were collected from community samples using data from participants scoring above a clinical threshold of ≥10 points (N = 2,023; 73.9% female; mean age 49.87, SD = 17.40). Data analysis followed three steps. First, a profiling algorithm was implemented to identify all possible symptom profiles by dichotomizing each PHQ-9 item. Second, the most prevalent symptom profiles were identified in the sample. Third, network analysis for the most prevalent symptom profiles was carried out to identify the centrality and covariance of symptoms. RESULTS: Of 382 theoretically possible depression profiles, only 167 were present in the sample. Furthermore, 55.6% of the symptom profiles present in the sample were represented by only eight profiles. Network analysis showed that the network and symptoms' relationship varied across the profiles. CONCLUSIONS: Findings indicate that the vast number of theoretical possible ways to meet the criteria for major depressive disorder (MDD) is significantly reduced in empirical samples and that the most common profiles of symptoms have different networks and connectivity patterns. Scientific and clinical consequences of these findings are discussed in the context of the limitations of this study.


Sujet(s)
Dépression , Humains , Femelle , Mâle , Adulte d'âge moyen , Études transversales , Adulte , Dépression/diagnostic , Dépression/psychologie , Questionnaire de santé du patient , Sujet âgé , Échelles d'évaluation en psychiatrie/normes , Trouble dépressif majeur/diagnostic , Trouble dépressif majeur/psychologie , Trouble dépressif/diagnostic , Trouble dépressif/épidémiologie
17.
Psychiatry Res Neuroimaging ; 341: 111827, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38788296

RÉSUMÉ

Major Depressive Disorder (MDD) is a global problem. Currently, the most common diagnosis is based on criteria susceptible to the subjectivity of the patient and the clinician. A possible solution to this problem is to look for diagnostic biomarkers that can accurately and early detect this mental condition. Some researchers have focused on electroencephalogram (EEG) analysis to identify biomarkers. In this study we used a dataset composed of EEG recordings from 24 subjects with MDD and 29 healthy controls (HC), during the execution of affective priming tasks with three different emotional stimuli (images): fear, sadness, and happiness. We investigated abnormalities in depressed patients using a novel technique, by directly comparing Event-Related Potential (ERP) waveforms to find statistically significant differences between the MMD and HC groups. Compared to the control group (healthy subjects), we found out that for the emotions fear and happiness there is a decrease in cortical activity at temporal regions in MDD patients. Just the opposite, for the emotion sadness, an increase in MDD brain activity occurs in frontal and occipital regions. Our findings suggest that emotions regulate the attentional control of cognitive processing and are promising for clinical application in diagnosing patients with MDD more objectively.


Sujet(s)
Trouble dépressif majeur , Électroencéphalographie , Émotions , Potentiels évoqués , Humains , Trouble dépressif majeur/physiopathologie , Trouble dépressif majeur/psychologie , Trouble dépressif majeur/diagnostic , Mâle , Femelle , Potentiels évoqués/physiologie , Adulte , Émotions/physiologie , Jeune adulte , Adulte d'âge moyen , Encéphale/physiopathologie , Encéphale/imagerie diagnostique
18.
PLoS One ; 19(5): e0303967, 2024.
Article de Anglais | MEDLINE | ID: mdl-38776336

RÉSUMÉ

BACKGROUND: Major Depressive Disorder is a long-term, recurring, and very common illness that is associated with a significant decline in functional ability. The gold-standard method of treating depression is pharmacotherapy, which involves the use of antidepressant medications either alone or in various combinations. However, approximately 30% of Major Depressive Disorder patients suffer from Treatment Resistant Depression, a more severe condition that has a profound impact on patients' lives. Our study aims to conduct the first comprehensive review and meta-analysis to assess the effectiveness and safety of adding Dialectical Behavior Therapy to antidepressant medications compared to groups using pharmacotherapy alone as an intervention for adults with Treatment Resistant Depression. MATERIALS AND METHODS: We will search for publications in the following databases: Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Lilacs, Web of Science, and PsycINFO. We will manually review the reference lists of the included studies to identify potentially relevant studies. There will be no restrictions on the language or publication date. Quality assessment of the included studies will be performed independently according to the Cochrane Risk of Bias instrument. To assess the certainty of the findings' body of evidence, we will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. This study aims to determine the effectiveness and safety of Dialectical Behavior Therapy as an intervention for Treatment Resistant Depression in adults. ETHICS AND DISSEMINATION: Ethical approval was not required as individual patient data was not obtained. Our intention is to publish the systematic review in a medical journal that offers open access upon completion of the process. TRIAL REGISTRATION: PROSPERO registration number CRD42023406301. Registered on March 24, 2023.


Sujet(s)
Trouble dépressif résistant aux traitements , Thérapie comportementale dialectique , Méta-analyse comme sujet , Revues systématiques comme sujet , Humains , Trouble dépressif résistant aux traitements/thérapie , Adulte , Thérapie comportementale dialectique/méthodes , Trouble dépressif majeur/thérapie , Antidépresseurs/usage thérapeutique , Résultat thérapeutique
19.
Psychiatry Res ; 337: 115915, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38688118

RÉSUMÉ

This investigation explores the efficacy of subcutaneous ketamine for mitigating depressive symptoms and suicidal ideation, addressing a crucial need for rapid-onset treatments in severe depression cases. It introduces an innovative approach to administering an NMDA receptor antagonist, significantly advancing psychopharmacological methods for treating suicidal behaviors as distinct entities, even within depressive episodes. The study's objective is to assess the impact of subcutaneous ketamine on diminishing suicidal thoughts and mood symptoms during depressive episodes through a naturalistic, prospective observational design. Conducted at Hospital de Clínicas de Porto Alegre, Brazil, between 2021 and 2023, the study involved 26 patients undergoing a current depressive episode. Of these, 23 completed the acute phase of treatment, and 18 were followed up for 6 months. The treatment regimen commenced with a ketamine dose of 0.5 mg/kg, which was adjusted according to individual responses under psychiatric supervision. The findings revealed substantial decreases in Columbia Suicide Severity Rating Scale scores following multiple ketamine sessions, with most patients achieving remission after approximately eight sessions. A notable reduction in depressive symptoms was also observed. A clear dose-response relationship was established, indicating that higher doses of ketamine were associated with more significant improvements in depressive symptoms, suicidal ideation, and overall functionality. Follow-up assessments suggested that these improvements were sustained over time. The subcutaneous administration of ketamine was generally well-tolerated, with minor and short-lived side effects. The study posits that subcutaneous ketamine may present a promising solution for treating severe depression accompanied by suicidal tendencies, particularly considering its positive influence on patient functionality and well-being. This method could offer a cost-effective and accessible treatment alternative, especially relevant in settings with limited resources. Given its potential in reducing long-term disability and economic viability, the study advocates for its broader application and further validation through larger, controlled trials. Trial Registration: ClinicalTrials.gov NCT05249309.


Sujet(s)
Kétamine , Étude de validation de principe , Idéation suicidaire , Humains , Kétamine/administration et posologie , Kétamine/pharmacologie , Femelle , Mâle , Adulte , Adulte d'âge moyen , Études prospectives , Injections sous-cutanées , Dépression/traitement médicamenteux , Jeune adulte , Trouble dépressif majeur/traitement médicamenteux , Suicide/psychologie , Suicide/statistiques et données numériques , Prévention du suicide
20.
CNS Spectr ; 29(3): 197-205, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38685584

RÉSUMÉ

OBJECTIVE: To examine whether objective sleep parameters are associated with cognitive function (CF) in patients with major depressive disorder (MDD) with chronic insomnia (CI) and whether the severity of these disorders is related to CF. METHOD: Thirty patients with MDD with CI attending a tertiary care institution underwent two consecutive nights of polysomnographic (PSG) recording and a battery of neuropsychological tests, which included episodic memory, sustained attention, working memory, and executive function. The severity of MDD and CI was assessed by clinical scales. We examined the relationship between PSG parameters and CF, as well as whether the severity of the disorders is related to CF. RESULTS: Linear regression analysis revealed that total sleep time (TST) was positively associated with higher learning and recall of episodic memory, as well as better attention. Slow-wave sleep (SWS) showed a positive association with better working memory. Furthermore, wake after sleep onset (WASO) was negatively associated with episodic memory and lower attention. No significant relationships were found between the severity of MDD or CI with CF. CONCLUSION: Both sleep duration and depth are positively associated with several aspects of CF in patients with MDD with CI. Conversely, a lack of sleep maintenance is negatively related to CF in these patients. These findings could help identify modifiable therapeutic targets to reduce CF impairment.


Sujet(s)
Cognition , Trouble dépressif majeur , Polysomnographie , Troubles de l'endormissement et du maintien du sommeil , Adulte , Femelle , Humains , Mâle , Adulte d'âge moyen , Jeune adulte , Attention , Trouble dépressif majeur/complications , Trouble dépressif majeur/physiopathologie , Trouble dépressif majeur/psychologie , Mémoire épisodique , Mémoire à court terme , Acuité des besoins du patient , Troubles de l'endormissement et du maintien du sommeil/complications , Troubles de l'endormissement et du maintien du sommeil/physiopathologie , Troubles de l'endormissement et du maintien du sommeil/psychologie , Tests neuropsychologiques
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