European archives of psychiatry and clinical neuroscience
July 13, 2024
Jenessa N Johnston, Carlos A Zarate, Mark D Kvarta
18 citations
Esketamine, the (S)-enantiomer of racemic ketamine, is an FDA-approved rapid-acting antidepressant for treatment-resistant depression (TRD) that outperforms traditional oral antidepressants. Research on biomarkers predicting response to esketamine remains limited and mostly extrapolated from racemic ketamine studies. Genetic, proteomic, and metabolomic profiles suggest inflammation and mitochondrial function may contribute to its effects, but these findings require verification. Neuroimaging consistently implicates the prefrontal cortex, striatum, and anterior cingulate cortex. In perioperative settings, esketamine reduces depression and anxiety, correlating with increased brain-derived neurotrophic factor and serotonin. Better-designed biomarker-focused clinical trials are needed to clarify mechanisms and identify patients most likely to benefit.
Progress in neuro-psychopharmacology & biological psychiatry
June 8, 2024
Kaylene K A Scheil, Carla L Sánchez-Lafuente, Brady S Reive et al.
5 citations
Chronic stress reduces reelin, a brain protein, in the hippocampus and causes depression-like behavior. A single dose of reelin or ketamine each reversed these behavioral and molecular effects within one hour, and the benefit lasted at least one week. When given together, reelin and ketamine showed additive effects after one week. The findings suggest that reelin-based treatments could become a new class of rapid-acting antidepressants.
Translational psychiatry
November 18, 2025
Jenessa N Johnston, Peixiong Yuan, Bashkim Kadriu et al.
2 citations
In neurons derived from induced pluripotent stem cells of five women with treatment-resistant depression (average age 40.2 years), both the glycoprotein reelin and the ketamine metabolite (2R,6R)-hydroxynorketamine increased expression of several synaptic proteins (GluA1, PSD-95, Dab1, Synapsin I, and p-ERK) within one hour, with effects declining by 24 hours. Gene expression changes were similar for both compounds, though only reelin upregulated mTORC1 signaling. The findings suggest that iPSC-derived neurons may serve as a useful in vitro model for studying treatment-resistant depression and testing potential therapeutics.
Journal of neuroendocrinology
January 1, 2026
Hiroe Hu, Yoojin Lee, Alaina N Tillman et al.
1 citation
People with both major depression and post-traumatic stress disorder (PTSD) have lower baseline levels of copeptin, a stable marker of vasopressin secretion, and a blunted reduction in copeptin after a single low-dose ketamine infusion compared to those with depression alone. Copeptin levels were unrelated to depression diagnosis or symptom severity of depression, anxiety, PTSD, anhedonia, suicidal ideation, or childhood trauma, but higher copeptin was linked to verbal aggression, an association weakened by PTSD. These findings point to a possible biological subtype of reduced vasopressin activity in co-occurring depression and PTSD, suggesting copeptin may serve as a peripheral biomarker for central vasopressin-driven circuits in neuropsychiatric disorders.