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Ketamine has emerged as a promising rapid-acting antidepressant with distinct advantages for the treatment of treatment-resistant depression (TRD). Its therapeutic effects are mediated through multi-target modulation of the glutamatergic system. Unlike conventional antidepressants, ketamine exerts a markedly faster onset of action; however, its long-term safety profile and potential risk of dependence require rigorous evaluation. This scoping review aims to systematically summarize recent advances in research on ketamine's role in depression treatment. This review synthesizes current evidence regarding ketamine's molecular mechanisms of action, neuroimaging correlates, pharmacological characteristics, and associated ethical considerations. By primarily antagonizing N-methyl-D-aspartate (NMDA) receptors, ketamine rapidly disinhibits the mesolimbic dopamine reward pathway and upregulates brain-derived neurotrophic factor (BDNF) expression via eukaryotic elongation factor 2 kinase (eEF2K) suppression, thereby activating the mammalian target of rapamycin (mTOR) pathway and enhancing synaptic plasticity. Neuroimaging studies further reveal that ketamine induces rapid remodeling of prefrontal-limbic functional connectivity, modulates default mode network activity, and promotes the normalization of cerebral metabolism and structure. Pharmacologically, ketamine exhibits a rapid onset of action and a relatively broad therapeutic window, though notable pharmacodynamic and pharmacokinetic differences exist between its enantiomers and active metabolites, which warrants further investigation. Ketamine displays rapid onset and high efficacy in the management of TRD; nevertheless, its long-term safety, risk of dependence, and potential cognitive effects necessitate close clinical monitoring. Future research should prioritize the exploration of synergistic treatment regimens and the development of novel ketamine derivatives with improved target specificity and safety profiles to advance the application of precision psychiatry. Collectively, this review provides a foundational reference to guide clinical practice and inform subsequent mechanistic studies on ketamine-based antidepressant therapies. Show less

This research investigated the potential therapeutic role of α-(phenylselanyl) acetophenone (PSAP) in the comorbidity of chronic pain and depression triggered by partial sciatic nerve ligation (PSNL). Male Swiss mice underwent PSNL surgery, and after a four-week period, they received either PSAP (1-50 mg/kg, administered intragastrically) or imipramine (IMI) (50 mg/kg) 30 min prior to behavioral assessments. Both PSAP and IMI effectively alleviated PSNL-induced hypersensitivity to pain and depressive-like symptoms, as demonstrated in forced swim and allodynia tests. Additionally, PSAP counteracted the elevated levels of lipid peroxidation and reactive oxygen species observed in the cortex and hippocampus following PSNL. These neuroprotective effects appear to be linked to PSAP's anti-inflammatory properties, as it downregulated the expression of pro-inflammatory markers such as NF-κB p65, TNF-α, and IDO mRNA in the affected brain regions. Furthermore, PSAP restored hippocampal BDNF mRNA levels, which had been diminished by nerve injury. Since inflammation is a common pathway in both chronic pain and depression, the findings indicate that PSAP holds promise as a treatment for this comorbid condition. Show less

The global rise in mental health conditions has prompted interest in interventions that act beyond conventional psychopharmacology. Psychobiotics, broadly understood as live microorganisms or microbe-derived products that interact with the microbiota-gut-brain axis, have been suggested to exert neuroactive effects through neural, immune, endocrine and metabolic routes. This narrative review synthesizes recent preclinical, mechanistic and early clinical observations. Experimental studies show that selected strains can modulate cytokine signalling, influence stress-responsive systems such as the hypothalamic-pituitary-adrenal axis, and support synaptic plasticity via factors such as brain-derived neurotrophic factor. A limited number of human trials using well-characterized Lactobacillus and Bifidobacterium strains have reported improvements in affective and stress-related outcomes, but these effects are generally small to moderate, more apparent in adjunctive than stand-alone use, and dependent on strain, dose, population and intervention length (typically 4-12 weeks). Evidence on neurodevelopmental conditions (e.g., autism spectrum disorder, attention-deficit/hyperactivity disorder) remains preliminary, based on small and heterogeneous samples. Across studies, key constraints include methodological heterogeneity, incomplete strain-level reporting, and gaps in mechanistic resolution that make it difficult to link microbial shifts to psychiatric benefit. Emerging microbiome- and metabolomics-informed approaches may help identify likely responders and improve translational precision, but they are not yet ready for routine clinical application. Overall, psychobiotics should currently be viewed as a promising adjunct within integrative mental health care, warranting larger, standardized trials with clearly defined strains, doses and mechanistic endpoints. Show less