Psilocybin is a rapid-acting antidepressant, but its mechanism of action in major depressive disorder remains unclear. In this secondary analysis of randomized, placebo-controlled trial with multimodal CSF and blood biomarker measurements, psilocybin selectively reduced CSF galanin and noradrenaline, implicating that normalization of these co-transmitters is a key pharmacodynamic signature.
BACKGROUND: Longer-term outcome and safety data of repeated subcutaneous racemic ketamine for treatment-resistant depression (TRD) is lacking, as is knowledge of the impact of prior ketamine treatment on subsequent response. AIMS: To evaluate the effectiveness and safety of a 4-week course of subcutaneous racemic ketamine over 6 months and investigate whether prior ketamine treatment influences...
BACKGROUND: Neurotic disorders - major depressive disorder (MDD), panic disorder, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and specific phobia - have differing pharmaceutical profiles. But all, even when resistant to conventional treatment (TR), respond quickly to low dose (0.5-1.0 mg/kg I.M.) ketamine....
Treatment-resistant depression (TRD) remains a major clinical challenge, with highly variable responses to ketamine. Immune activation characterizes a subset of patients with TRD. The kynurenine pathway (KP), which integrates immunometabolic signals with glutamatergic neurotransmission, may provide candidate biomarkers to inform personalized treatment. We investigated whether KP metabolites and...
Ketamine is a fast-acting intervention for treatment-resistant depression (TRD), yet only a subset of patients show robust clinical response, and the underlying neural mechanisms remain unclear. High-order interactions (HOI) derived from multivariate information theory provide a framework for examining nonlinear dependencies among brain regions beyond pairwise connectivity. One such metric, the...
High Resolution Image Download MS PowerPoint Slide Provided herein are novel 6,5-bicyclic compounds as 5-HT2A receptor agonists, pharmaceutical compositions, use of such compounds in treating depression, anxiety, substance abuse, and headaches, and processes for preparing such compounds.
Treatment-resistant depression (TRD) remains a major clinical challenge. Intranasal esketamine, used adjunctively with an oral antidepressant, has been evaluated in randomized trials, but uncertainty persists regarding the magnitude and consistency of benefit, durability, and key harms. This systematic review and meta-analysis included randomized controlled trials comparing intranasal...
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...
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...
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....