Brain Sciences

Background/Objectives: Esketamine-related dissociation is a transient, pharmacologically induced altered state that differs from the trait-like pathological dissociation typically observed in trauma-related conditions. While most studies have quantified these effects using the Clinician-Administered Dissociative States Scale (CADSS), patients’ subjective phenomenology and meaning-making remain underexplored. This qualitative exploratory study investigated how patients narrate, interpret, and integrate dissociative experiences occurring during intranasal esketamine treatment for treatment-resistant depression (TRD). Methods: We conducted semi-structured interviews with 36 adults with TRD who were receiving intranasal esketamine in outpatient settings in Northern Italy (2022–2024). Interviews focused on the most salient dissociative experiences during treatment. Transcripts were anonymized and analyzed using inductive thematic analysis. Two researchers coded the data independently; discrepancies were resolved by consensus, and recruitment continued until thematic saturation was reached. Results: Four experiential domains emerged: sensory alteration and perceptual flow (10/36, 27.8%), time suspension and chronological drift (21/36, 58.3%), body and space alteration (20/36, 55.6%), and psychic distance from suffering (30/36, 83.3%). While a minority described transient distress or loss of control, most narratives framed dissociation as neutral or subjectively meaningful, often associated with a temporary reduction in ruminative self-focus and depressive distress. Conclusions: A narrative, phenomenological lens complements quantitative research by clarifying what esketamine-induced dissociation feels like to patients and how it is appraised in context. The findings do not imply a causal or mediating role in antidepressant efficacy. Rather, they suggest that dissociation functions as a transitional subjective state, the clinical relevance of which depends on anticipation, framing, monitoring, and integration. These results support the use of structured psychoeducation, in-session support, and post-session integration within real-world esketamine programs.

While phosphatidylserine (PS) is recognized for its neuroprotective properties, the effects of PS purity on human cortical neurons remain unexplored. This study investigates the effects of three different PS purities (15 µM of 50%, 70%, and 80%) on neuronal health using human-embryonic-stem-cell-derived cortical neurons. Our findings reveal that higher PS purity enhances the expression of key regulatory proteins Sirtuin 1 (SIRT1) and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), known for their roles in neuroprotection and mitochondrial function. Specifically, 80% PS purity significantly increases SIRT1 and PGC-1α levels, suggesting that PS purity strengthens neuroprotective pathways and improves mitochondrial quality control. Through SIRT1 knockdown experiments, we demonstrate that PS-induced upregulation of PGC-1α is SIRT1 dependent, highlighting a SIRT1-PGC-1α regulatory axis that enhances mitochondrial health. In an amyloid-beta 1–42 (Aβ₄₂)-induced Alzheimer’s disease (AD) model, PS treatment reduced cytotoxicity and countered the Aβ₄₂-induced downregulation of SIRT1 and PGC-1α, particularly at 70% and 80% PS purity, indicating PS’s role in preserving neuronal viability and combating AD-like pathology. These results suggest that the biological activity of PS preparations in vitro can depend on purity, motivating future studies to define compositional determinants and bioavailability relevant to translational applications.

Background/Objectives: Neuromuscular fatigue (NMF) can impair manual dexterity and strength in healthcare professionals. Due to their high physical and cognitive workloads, physiotherapists (PTs) are particularly susceptible to NMF. This study investigated whether NMF, expressed as changes in manual dexterity and grip strength, occurs over a workday and across a workweek in PTs, and explored its relationship with stress and sleep quality. Methods: A total of 43 full-time PTs (25 female, mean age 37.72 ± 11.94 years) were recruited. Manual dexterity was assessed using the Functional Dexterity Test (FDT), while maximal grip strength (MGS) was measured by a hand dynamometer. Reliability was evaluated on a subgroup using Intraclass Correlation Coefficients (ICC_3,1) and Standard Error of Measurement (SEM). Evaluations were conducted at the beginning and at the end of the work shift, on Monday and Friday. Subjective fatigue, perceived stress, and sleep quality were also recorded. Results: The FDT showed excellent intra-rater reliability (ICC > 0.93; SEM < 0.94 s). FDT performance was significantly slower on Friday evening compared to all other time points (p < 0.01), exceeding the minimal detectable change thresholds. No significant changes were observed in MGS across the week. Perceived stress was strongly correlated with fatigue levels on Monday (ρ = 0.731) and Friday (ρ = 0.612) evenings. Sleep quality and professional experience did not correlate with performance changes. Conclusions: PTs experience a significant decline in manual dexterity by the end of the workweek, suggesting an accumulation of NMF. While MGS remains stable, fine motor control is more sensitive to fatigue. Psychosocial stress appears to be a major driver of perceived fatigue in this population.