Despite its high prevalence, the precise mechanisms underlying major depressive disorder (MDD) remain incompletely understood. Growing evidence identifies mitochondrial dysfunction, including abnormalities in mitochondrial DNA, impaired bioenergetics, disrupted quality control, and redox imbalance, as a central pathological feature of MDD. Beyond deficits in energy production, mitochondria...
Objective This study evaluated whether intramuscular (IM) ketamine is non‐inferior to intranasal (IN) esketamine for treatment‐resistant depression (TRD) and assessed differences in safety and healthcare costs. Methods In a retrospective, observational sequential cohort at the VA San Diego, 179 Veterans with TRD received eight treatments of either IN esketamine ( n = 89) or IM ketamine ( n =...
Ketamine promotes spine growth on the apical dendrites of pyramidal neurons in the prefrontal cortex (PFC), which are critical for its behavioral effects. Follow-up studies show that brain-derived neurotrophic factor (BDNF) signaling is critical for these effects. In this context, we sought to determine if microglial BDNF contributes to the synaptic and behavioral effects of ketamine....
Health care workers (HCWs) faced unprecedented stress, anxiety, and burnout during the COVID-19 pandemic. Yoga, a mind-body practice combining physical postures, breathing, and meditation, has demonstrated benefits for mental and physical resilience. This systematic review evaluated the effectiveness of yoga interventions in addressing mental health challenges and promoting overall well-being...
Depression is a common mental health disorder affecting millions worldwide. Pharmacotherapies are partially effective, but numerous side effects often make them unfavorable. Recent investigations show that mindfulness meditation effectively mitigates depression-symptoms but the underlying mechanisms remain elusive. Here, we examined the sequential influence of emotion regulation (ER) and...
ABSTRACT: Introduction Ketamine and esketamine have reemerged as promising interventions for treatment-resistant depression (TRD), yet debate persists regarding the clinical relevance of acute dissociative experiences. This secondary exploratory analysis examined the relationship between dissociative experiences induced by subcutaneous esketamine and antidepressant response in patients with...
Neuroinflammation, particularly Toll-like receptor 4 (TLR4)-mediated signaling, plays a critical role in the pathophysiology of depression. This study aimed to investigate the mechanisms by which S-ketamine (S-ket) and S-hydroxynorketamine (S-HNK) modulate TLR4 and peroxisome proliferator-activated receptor alpha (PPARα) signaling in the prefrontal cortex (PFC) to exert antidepressant effects....
This paper explores whether some religious and spiritual experiences (RSEs) associated with depression resemble hypomania/mania. Content analysis and phenomenological analysis were used to characterize first-person RSE reports associated with depression (N = 249). Findings reveal that some RSEs that follow depression are characterized by long-duration states (lasting days to weeks) of positive...
Over the past two decades, ketamine has emerged as a rapid-acting antidepressant, especially among patients with treatment-resistant depression. As an N-methyl-d-aspartate glutamate receptor antagonist, ketamine has reshaped the understanding of the underlying neurobiological mechanisms of depression treatment. Ketamine induces a transient state of enhanced neuroplasticity and likely...
Summary Nitrous oxide is being investigated as a treatment for therapy-resistant depression, yet its environmental implications as a potent greenhouse gas are largely unaddressed. A single 1 h treatment generates ∼150 kg CO 2 -equivalents, rising to ∼7.8 t per patient-year, highlighting the need to incorporate environmental externalities into evaluation.
Pharmacological treatment for postpartum depression (PPD) have mainly involved conventional antidepressants, RCTs have also evaluated rapid-acting glutamatergic agents, neuroactive steroids, hormonal therapies, and botanical preparations. An updated comparative synthesis of these treatments is therefore needed. To synthesize RCT evidence and compare the efficacy, response, remission,...
Patients with treatment‐resistant depression who received psilocybin‐assisted psychotherapy showed clinically meaningful improvement in depressive symptoms relative to placebo, a Phase 2b trial has found. However, the study did not show a significant effect on the primary outcome of treatment response 6 weeks after the first of two doses of psilocybin. Study results were published online March...
Introduction Treatment-resistant major depressive disorder with high-risk suicidal ideation is a psychiatric emergency that requires rapid and effective intervention. Although intranasal esketamine and intermittent theta-burst stimulation (iTBS) are time-efficient therapeutic options, clinical reports describing their combined use in an accelerated inpatient schedule are limited, particularly...
Treatment-resistant depression (TRD) represents an unmet challenge, accounting for disproportionate morbidity, disability, and healthcare burden in depression. Limitations of monoaminergic antidepressants have prompted a conceptual shift toward models emphasizing impaired neuroplasticity, synaptic dysfunction, and network dysregulation. This expert review synthesizes preclinical, translational,...
NeuropharmacologyJuly 1, 2026Anne Nathalia De Sousa-Silva, Clarissa de Almeida Moura, Carina Ioná De Oliveira Torres et al.1 citation
N,N-dimethyltryptamine (DMT) is an naturally occurring indoleamine with hallucinogenic and antidepressant effects in humans. Here, we compared the effects of DMT and S-ketamine, a fast-acting antidepressant, in helpless mice. To induce helplessness, male single and group-housed mice were exposed to inescapable footshock stress; only helpless animals were subsequently treated with S-ketamine 10...
Background and Objective Ketamine and esketamine have emerged as effective and rapid-acting interventions for treatment-resistant depression. Nevertheless, the best-suited candidates for these treatments are not clear. As such, the ability to personalize treatment selection and parameters would likely improve therapeutic response. This systematic review synthesized the literature on clinical...
INTRODUCTION: The treatment of comorbid post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) is significantly more challenging than the treatment of either disorder alone. While gold standard evidence-based treatments exist for this comorbidity, clinically significant improvements are only observed in approximately half of clinical trial participants. The use of adjunctive...
Purpose: This study investigated the mediating roles of mindfulness and anxiety in the association between pregnancy stress and depression among hospitalized women with high-risk pregnancies. Methods: Employing a cross-sectional descriptive design, this study was guided by the Transactional Model of Stress and Coping. Data were collected from 109 high-risk pregnant women admitted to a...
IJNPJune 30, 2026Nurul Azizah, Rafhani Rosyidah, Widi Arti
Background: Postpartum women are vulnerable to pain and psychological disturbances such as stress, anxiety, and depression, which may affect maternal well-being and infant care. Mindfulness-Based Stress Reduction (MBSR) is a promising non-pharmacological intervention to enhance postpartum recovery. Objective: This study aimed to evaluate the effectiveness of MBSR in improving pain tolerance and...
BACKGROUND Anxiety and depression are prevalent and often co-occurring mental health disorders. While mindfulness training has shown efficacy in reducing symptoms, the underlying mechanisms, particularly the role of psychological resilience, remain underexplored. This study investigates whether mindfulness training alleviates anxiety and depression and hypothesizes that psychological resilience...