Adolescent major depressive disorder is a leading cause of disability and a major risk factor for suicide. For 30% to 50% of patients who do not achieve remission after multiple treatments, consequences are substantial. Selective serotonin-reuptake inhibitors, though first-line, often take weeks to work and many adolescents do not respond, leaving a critical treatment gap. Esketamine, an NMDA receptor antagonist, may provide faster relief than conventional antidepressants, including as a monotherapy for treatment-resistant depression, but its neural mechanisms in the developing brain are not fully understood. Understanding these mechanisms is needed to guide clinical use and targeted prevention.
During propofol-induced unconsciousness, the brain's electrical activity patterns—EEG microstates—change in ways that can distinguish between resting, light, and deep anesthesia. Analyzing 60-channel EEG from 31 male subjects, the study identified 7 common and 2 anesthesia-specific microstate templates. Features such as the occurrence and duration of certain microstates decreased as consciousness suppression deepened. Machine learning models using these features classified the three consciousness levels with a mean accuracy of 85.6%. The findings suggest that microstate analysis may help reveal the neural mechanisms underlying propofol anesthesia and could provide useful markers for quantifying levels of consciousness.
During propofol-induced sedation, a distinct EEG microstate pattern—a posterior central maximum labeled microstate F—emerges and becomes prominent. Its coverage, occurrence, and power significantly increase in moderate sedation, and the transition from rest to sedation is accompanied by a significant rise in mean energy across all frequency bands in this microstate. The findings suggest that microstate F is closely linked to propofol-altered consciousness and may derive from the canonical anterior-posterior microstate C. The work also advances methods for analyzing microstates in the frequency domain using multivariate empirical mode decomposition and Hilbert-Huang transform.
Long-term methoxetamine, a ketamine analog used recreationally, causes bladder dysfunction and inflammation in rats. Female rats injected daily with 30 mg/kg methoxetamine or ketamine for 4 or 12 weeks showed increased urination frequency, damaged bladder lining, inflammatory cell infiltration, and fibrosis. Treated rats had elevated levels of pro-inflammatory cytokines and markers of fibrosis. Methoxetamine also directly damaged human urothelial cells and increased inflammatory signals. The findings suggest methoxetamine's bladder effects resemble ketamine-induced cystitis.