An overview of major depression disorder: The endocannabinoid system as a potential target for therapy.

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.

Linking head and heart health: the association between psychiatric outcomes for patients with major depressive disorder and myocardial ischemia - a systematic review.

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.

Identifying genetic variants associated with side effects of antidepressant treatment: A systematic review.

Major Depressive Disorder (MDD) is one of the most prevalent neurobiological disorders globally. Antidepressant medications are the first-line treatment for managing symptoms. However, over time, pharmacotherapy has been linked to several challenges, primarily due to the wide array of side effects that often reduce patient adherence to treatment. The literature suggests that these side effects may be influenced by polymorphisms in genes related to the pharmacokinetics and pharmacodynamics of antidepressants. Thus, this systematic review aimed to identify studies that investigated the association between genetic variants and side effects resulting from antidepressant treatment in individuals with MDD. Original articles indexed in the electronic databases Cochrane Library, EMBASE, MEDLINE via PubMed, and Scopus were identified. A total of 55 studies were included in the review, and data regarding the outcomes of interest were extracted. Due to the exploratory nature of the review, a narrative/descriptive synthesis of the results was performed. The risk of bias was evaluated using the Joanna Briggs Institute's tools, tailored to the design of each study. Polymorphisms in 35 genes were statistically associated with the development of side effects. A subsequent Protein-Protein Interaction Network analysis helped elucidate the key biological pathways involved in antidepressant side effects, with a view toward exploring the potential application of pharmacogenetic markers in clinical practice.

Neurobiological mechanisms in the kynurenine pathway and major depressive disorder.

Major depressive disorder (MDD) is a prevalent psychiatric disorder that has damage to people's quality of life. Tryptophan is the precursor to serotonin, a critical neurotransmitter in mood modulation. In mammals, most free tryptophan is degraded by the kynurenine pathway (KP), resulting in a range of metabolites involved in inflammation, immune response, and neurotransmission. The imbalance between quinolinic acid (QA), a toxic metabolite, and kynurenic acid (KynA), a protective metabolite, is a relevant phenomenon involved in the pathophysiology of MDD. Proinflammatory cytokines increase the activity of the enzyme indoleamine 2,3-dioxygenase (IDO), leading to the degradation of tryptophan in the KP and an increase in the release of QA. IDO activates proinflammatory genes, potentiating neuroinflammation and deregulating other physiological mechanisms related to chronic stress and MDD. This review highlights the physiological mechanisms involved with stress and MDD, which are underlying an imbalance of the KP and discuss potential therapeutic targets.

Risk of Suicide in Association with Major Depressive Disorder among Patients with Dementia: A Population-based Nested Case-Control Study.

OBJECTIVE: This study aimed to explore the association between major depressive disorder (MDD) and suicide risk in dementia patients. METHODS: A cohort of 625,218 individuals aged ≥40 years with dementia between 2007 and 2018 was identified from Taiwan's National Health Insurance Research Database. After excluding prevalent cases in 2007. Subsequently, a nested case-control study enrolled 1,256 suicide cases and 5,022 matched controls was conducted. The frequencies of MDD-related outpatient or inpatient visits over a 7-year period preceding the event dates were calculated and analyzed for association using conditional logistic regression. RESULTS: Dementia comorbid with MDD was associated with increased suicide risk (adjusted odds ratio [AOR]: 2.67), particularly in individuals with ≤1.0 MDD episodes per year (AOR: 2.85). Similar association was observed only in individuals aged ≥65 years and males, with a pronounced risk of suicide in those ≤1.0 MDD episodes per year (AOR: 3.08 for individuals aged ≥65 years; AOR: 3.28 for males). Conversely, the risk increase was evident with >1.0 MDD episodes per year in those aged <65 years (AOR: 3.04) and females (AOR: 2.45). CONCLUSIONS: MDD is associated with suicide risk in dementia patients, with the strength of this association possibly varying by age and gender.

Prevalence of mental disorders among family members of individuals on the autism spectrum: systematic review and meta-analysis.

Parenting a child on the autism spectrum presents particular challenges that can lead to increased stress, anxiety, and depression among family members. Therefore, we aimed to investigate the prevalence of mental disorders in first-degree relatives of individuals on the autism spectrum. This article adheres to the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P) guidelines, including studies indexed in PubMed/Medline, Embase, PsycINFO, Biblioteca Virtual em Saúde (BVS), and SciELO. Nineteen articles met eligibility criteria for the systematic review. Using a random-effects model (N = 93,876), we found a pooled prevalence of affective disorders of 13% in mothers of people on the autism spectrum (95% CI 7-21%; I2 = 99%, p < 0.01). Additionally, another random-effects model pointed out that first-degree relatives of people on the autism spectrum (N = 93,263) were more likely to present affective disorders than relatives of people with neurotypical development (N = 152,455) (pooled OR: 2.17; 95% CI 1.81-2.61). Careful assessment for mental disorders in parents and siblings of individuals on the autism spectrum is crucial to ensure appropriate treatment for these family members. This approach can also contribute to optimizing care for the individuals on the autism spectrum.

Pre- and Post-Synaptic protein in the major depressive Disorder: From neurobiology to therapeutic targets.

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.

Is Nasal Dysbiosis a Required Component for Neuroinflammation in Major Depressive Disorder?

Human microbiota is known to influence immune and cerebral responses by direct and/or indirect mechanisms, including hypothalamic-pituitary-adrenal axis signaling, activation of neural afferent circuits to the brain, and by altering the peripheral immune responses (cellular and humoral immune function, circulatory inflammatory cells, and the production of several inflammatory mediators, such as cytokines, chemokines, and reactive oxygen species). The inflammatory responses in the nasal mucosa (rhinitis) or paranasal sinuses (chronic rhinosinusitis) are dual conditions related with a greater risk for developing depression. In the nasal cavity, anatomic components of the olfactive function are in direct contact with the CNS through the olfactory receptors, neurons, and axons that end in the olfactory bulb and the entorhinal cortex. Local microbiome alterations (dysbiosis) are linked to transepithelial translocation of microorganisms and their metabolites, which disrupts the epithelial barrier and favors vascular permeability, increasing the levels of several inflammatory molecules (both cytokines and non-cytokine mediators: extracellular vesicles (exosomes) and neuropeptides), triggering local inflammation (rhinitis) and the spread of these components into the central nervous system (neuroinflammation). In this review, we discuss the role of microbiota-related immunity in conditions affecting the nasal mucosa (chronic rhinosinusitis and allergic rhinitis) and their relevance in major depressive disorders, focusing on the few mechanisms known to be involved and providing some hypothetical proposals on the pathophysiology of depression.

The Antidepressant- and Anxiolytic-Like Effects of the Phosphodiesterase Type-5 Inhibitor Tadalafil are Associated with the Modulation of the Gut-Brain Axis During CNS Autoimmunity.

Multiple Sclerosis (MS) is a debilitating disease that severely affects the central nervous system (CNS). Apart from neurological symptoms, it is also characterized by neuropsychiatric comorbidities, such as anxiety and depression. Phosphodiesterase-5 inhibitors (PDE5Is) such as Sildenafil and Tadalafil have been shown to possess antidepressant-like effects, but the mechanisms underpinning such effects are not fully characterized. To address this question, we used the EAE model of MS, behavioral tests, immunofluorescence, immunohistochemistry, western blot, and 16 S rRNA sequencing. Here, we showed that depressive-like behavior in Experimental Autoimmune Encephalomyelitis (EAE) mice is due to neuroinflammation, reduced synaptic plasticity, dysfunction in glutamatergic neurotransmission, glucocorticoid receptor (GR) resistance, increased blood-brain barrier (BBB) permeability, and immune cell infiltration to the CNS, as well as inflammation, increased intestinal permeability, and immune cell infiltration in the distal colon. Furthermore, 16 S rRNA sequencing revealed that behavioral dysfunction in EAE mice is associated with changes in the gut microbiota, such as an increased abundance of Firmicutes and Saccharibacteria and a reduction in Proteobacteria, Parabacteroides, and Desulfovibrio. Moreover, we detected an increased abundance of Erysipelotrichaceae and Desulfovibrionaceae and a reduced abundance of Lactobacillus johnsonii. Surprisingly, we showed that Tadalafil likely exerts antidepressant-like effects by targeting all aforementioned disease aspects. In conclusion, our work demonstrated that anxiety- and depressive-like behavior in EAE is associated with a plethora of neuroimmune and gut microbiota-mediated mechanisms and that Tadalafil exerts antidepressant-like effects probably by targeting these mechanisms. Harnessing the knowledge of these mechanisms of action of Tadalafil is important to pave the way for future clinical trials with depressed patients.

Psilocybin fungi microdose treatment in major depressive disorder: a case report / Tratamiento con microdosis de hongos con psilocibina en trastorno depresivo mayor: reporte de un caso.

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.

Use of Extracellular Monomeric Ubiquitin as a Therapeutic Option for Major Depressive Disorder.

Major depressive disorder (MDD) is a mood disorder that has become a global health emergency according to the World Health Organization (WHO). It affects 280 million people worldwide and is a leading cause of disability and financial loss. Patients with MDD present immunoendocrine alterations like cortisol resistance and inflammation, which are associated with alterations in neurotransmitter metabolism. There are currently numerous therapeutic options for patients with MDD; however, some studies suggest a high rate of therapeutic failure. There are multiple hypotheses explaining the pathophysiological mechanisms of MDD, in which several systems are involved, including the neuroendocrine and immune systems. In recent years, inflammation has become an important target for the development of new therapeutic options. Extracellular monomeric ubiquitin (emUb) is a molecule that has been shown to have immunomodulatory properties through several mechanisms including cholinergic modulation and the generation of regulatory T cells. In this perspective article, we highlight the influence of the inflammatory response in MDD. In addition, we review and discuss the evidence for the use of emUb contained in Transferon as a concomitant treatment with selective serotonin reuptake inhibitors (SSRIs).

Profiling the combination of bupropion and dextromethorphan as a treatment option for major depressive disorder.

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.

Development and pharmacological evaluation of liposomes and nanocapsules containing paroxetine hydrochloride.

Depression is one of the most common psychiatric disorders. Nanotechnology has emerged to optimize the pharmacological response. Therefore, the aim of this work was to develop and characterize liposomes and nanocapsules containing paroxetine hydrochloride and evaluate their antidepressant-like effect using the open field and tail suspension tests in mice. Liposomes and nanocapsules were prepared using the reverse-phase evaporation and nanoprecipitation methods, respectively. The particle size of the formulation ranged from 121.81 to 310.73 nm, the polydispersity index from 0.096 to 0.303, the zeta potential from -11.94 to -34.50 mV, the pH from 5.31 to 7.38, the drug content from 80.82 to 94.36 %, and the association efficiency was 98 %. Paroxetine hydrochloride showed slower release when associated with liposomes (43.82 %) compared to nanocapsules (95.59 %) after 10 h. In Vero cells, in vitro toxicity showed a concentration-dependent effect for paroxetine hydrochloride nanostructures. Both nanostructures decreased the immobility time in the TST at 2.5 mg/kg without affecting the number of crossings in the open field test, suggesting the antidepressant-like effect of paroxetine. In addition, the nanocapsules decreased the number of groomings, reinforcing the anxiolytic effect of this drug. These results suggest that the nanostructures were effective in preserving the antidepressant-like effect of paroxetine hydrochloride even at low doses.

Ketamine versus electroconvulsive therapy for major depressive episode: An updated systematic review and non-inferiority meta-analysis.

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.

The Wnt signaling pathway in major depressive disorder: A systematic review of human studies.

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.

Hydroalcoholic Extract of Centella asiatica and Madecassic Acid Reverse Depressive-Like Behaviors, Inflammation and Oxidative Stress in Adult Rats Submitted to Stress in Early Life.

Major depressive disorder (MDD) is a severe disorder that causes enormous loss of quality of life, and among the factors underlying MDD is stress in maternal deprivation (MD). In addition, classic pharmacotherapy has presented severe adverse effects. Centella asiatica (C. asiatica) demonstrates a potential neuroprotective effect but has not yet been evaluated in MD models. This study aimed to evaluate the effect of C. asiatica extract and the active compound madecassic acid on possible depressive-like behavior, inflammation, and oxidative stress in the hippocampus and serum of young rats submitted to MD in the first days of life. Rats (after the first day of birth) were separated from the mother for 3 h a day for 10 days. When adults, these animals were divided into groups and submitted to treatment for 14 days. After subjecting the animals to protocols of locomotor activity in the open field and behavioral despair in the forced swimming test, researchers then euthanized the animals. The hippocampus and serum were collected and analyzed for the inflammatory cytokines and oxidative markers. The C. asiatica extract and active compound reversed or reduced depressive-like behaviors, inflammation in the hippocampus, and oxidative stress in serum and hippocampus. These results suggest that C. asiatica and madecassic acid have potential antidepressant action, at least partially, through anti-inflammatory and antioxidant profiles.

Clinical features and influencing factors of adolescent major depressive disorder with suicidal and self-injurious behaviour.

OBJECTIVE: To analyse the related influencing factors of adolescent major depressive disorder (MDD) with suicidal and self-injurious behaviour (SSIB). METHODS: A total of 299 adolescents with MDD who were admitted to the psychiatric department of the hospital between February 2022 and July 2023 were selected using the convenience sampling method. The participants were divided into the SSIB group (n = 110) and the non-SSIB group (n = 189) according to whether SSIB was present, and related indicators were collected and compared. RESULTS: The patients' ages at the time of their first SSIB ranged from 10 to 18 years old, with a mean age of 13.30 ± 1.74 years. The most commonly injured parts were the lower arm and wrist (42.13%), and the most common injury was cutting, accounting for 40.00% of the total patients. The most common type of self-injury differed by sex (X2 = 17.798, P = 0.006); for men, hitting was the most common, and for women, cutting was the most common. In 51.41% of the patients, the period between the initial thought and the actual committing of the SSIB was less than 5 minutes. The scores of the Eysenck Personality Questionnaire, the Barratt Impulsivity Scale, the Buss-Perry Aggression Questionnaire, the Symptom Checklist-90 (all P < 0.001), and the health-risk behaviour scale (67.47 ± 12.59 vs. 41.58 ± 11.36, t = 9.587, P < 0.001) were significantly increased in the SSIB group compared with the non-SSIB group. In addition, the total score of quality of life (QOL) (11.36 ± 4.32 vs. 16.43 ± 5.64, t = 5.496, P < 0.001) was decreased in the SSIB group compared with the non-SSIB group. CONCLUSION: The SSIB of adolescent patients with MDD is related to various factors, including impulsiveness, aggressiveness, personality traits, QOL, and mental health level.

Diagnosis support of major depressive disorder using event-related potentials during affective priming tasks.

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.

Exploring protective factors in a high-risk subsample: the pivotal role of paternal support in preventing depression in a cohort of young adults.

BACKGROUND: Major depressive disorder (MDD) is a global concern due to its widespread prevalence and morbidity. Identifying protective factors in high-risk individuals, including those with a familial predisposition, maltreatment history, and socio-economic vulnerabilities, is crucial. METHODS: We assessed a high-risk subsample within a young adult population cohort (n = 791; mean age = 31.94 [SD = 2.18]) across three waves. Using multiple regression models to analyse higher education, feeling supported, spirituality, psychotherapy access, higher socioeconomic status, involvement in activities, cohabitation, and family unity in Waves 1 and 2, and their association with MDD resilience at Wave 3. RESULTS: In the high-risk group, MDD incidence was 13.7% (n=24). Paternal support had a protective effect on MDD incidence (OR = 0.366; 95% CI [0.137 to 0.955], p = 0.040) and suicidal attempt risk (OR = 0.380; 95% CI [0.150 to 0.956], p = 0.038). Higher resilience scores were also protective (OR = 0.975; 95% CI [0.953 to 0.997], p = 0.030), correlating with reduced BDI (r = 0.0484; B = -0.2202; 95% CI [-0.3572 to -0.0738]; p = 0.003) and MADRS scores (r = 0.0485; B = -0.2204; 95% CI [-0.3574 to -0.0741]; p = 0.003). CONCLUSIONS: Our paper emphasizes reorienting the MDD approach, focusing on positive prevention strategies. It highlights fathers' crucial role in family-based interventions and promoting resilience in high-risk populations.

Effectiveness of short sprint interval training in women with major depressive disorder: a proof-of-concept study.

Background: High-intensity intermittent training has emerged as an option for treating major depressive disorder (MDD). However, short sprint training (sSIT), an efficient HIIT modality, has not been tested yet for this purpose. The sSIT has been proven to induce the same metabolic adaptations, with the advantage of promoting lower muscle fatigue than other HIIT protocols. Methods: Seventeen adult women diagnosed with moderate/severe MDD were randomly allocated into a sSIT group (n=9) or a control condition (n=8). The sSIT group completed, over two weeks, six 6-10-min sessions which consisted of 3-12 "all out" sprints of 5 s interspersed with low-intensity recovery of 30-45 s. The week before and after the intervention, both groups were evaluated with the Hamilton Depression Rating Scale of 21-itens (HAM-D21), and for physical fitness and incidental physical activity. Results: The sSIT group exhibited significant improvements for HAM-D21 scores (24.6±8.2 vs. 16.8±10.1), maximum aerobic power (140±15 vs. 155±15 W), countermovement jump (13.0±3.4 vs. 14.9±3.1 cm), % of body fatness (32.4±4.4 vs. 29.3±3.8%), and 4-days number of steps (13,626±11,309 vs. 16,643±15,371) after the training period when compared to the control group. Conclusion: Less than 1 hour of a sSIT protocol over two weeks have demonstrated to reduce depressive symptoms, while improving aerobic fitness and body composition, and increasing incidental physical activity in a sample of women diagnosed with MDD.