Transl Psychiatry
December 13, 2023
42 citations
Psychosis in Parkinson's disease and Dementia with Lewy Bodies shares underlying mechanisms with altered states of consciousness seen in REM sleep, psychiatric disorders, and psychedelic drug use. Dysregulated activity in high-order thalamic nuclei, driven by ThalamoCortical Dysrhythmia (TCD), is proposed as a crucial trigger. TCD disrupts finely tuned cortico-cortical modulations normally supported by the thalamus, leading to aberrant Default Mode Network (DMN) activity. This process alters thalamic filtering of internal and external information, causing cortical input overload and DMN decoupling from task-positive networks. These changes destabilize brain metastability, producing dreamlike, dissociative, or altered states. Psychedelic drugs similarly modulate thalamic-cortical pathways. Understanding this pathophysiology bridges neurology and psychiatry, offering promising avenues for investigation and therapy.
Transl Psychiatry
October 31, 2025
3 citations
Psychedelics and ketamine/esketamine show promise for treating depressive disorders by inducing rapid and sustained antidepressant effects. The review examines their biological mechanisms, including modulation of glutamate and serotonin systems, promotion of neuroplasticity, and changes in brain connectivity and network function. Neuroimaging studies reveal alterations in default mode network, fronto-limbic connectivity, and thalamic activity. Clinical changes are associated with these brain alterations, though the precise relationships remain under investigation. The work synthesizes current evidence on how these compounds produce observable brain changes and symptom improvement, highlighting the need for further research to clarify mechanisms and optimize therapeutic applications.
Transl Psychiatry
April 10, 2026
1 citation
A target trial simulation using real-world data suggests that esketamine, when added to standard antidepressant treatment, maintains effectiveness and safety over a sustained period for people with major depressive disorder. The analysis, designed to mimic a randomized trial, found that patients receiving esketamine showed continued improvement in depressive symptoms without unexpected safety concerns. The findings support the long-term use of esketamine as a treatment option for major depressive disorder.
Transl Psychiatry
March 6, 2026
1 citation
In breast cancer patients, a single preoperative dose of esketamine produced a greater reduction in depressive symptoms 24 hours after surgery compared to placebo, as measured by the Montgomery-Åsberg Depression Rating Scale. The antidepressant effect was associated with increased functional connectivity in the left superior frontal gyrus and changes in brain network properties, including reduced clustering coefficient and increased global efficiency in the default mode network. Baseline functional connectivity in the left superior frontal gyrus predicted the magnitude of the antidepressant response. The findings suggest that esketamine's rapid antidepressant action involves modulation of brain functional networks.
Transl Psychiatry
May 29, 2026
The way NMDA antagonists alter negative affective biases in male rats could predict how well these drugs will work in humans with major depressive disorder.
Transl Psychiatry
November 13, 2025
correction
This correction notice addresses errors in a previously published article that presented three systematic reviews and meta-analyses examining the pharmacology, neuroimaging, and phenomenology of psychedelics. The correction does not provide new findings or data but serves to amend the original publication.