Research Square
February 12, 2026
Jenessa N Johnston, Greg Jones, Shiyong Peng et al.
Rapid-acting antidepressants like ketamine and serotonergic psychedelics show promise for treatment-resistant depression (TRD), but the molecular mechanisms that contribute to their therapeutic effects remain unclear. Induced pluripotent stem cells (iPSCs) offer a platform to model human cortical neurons and investigate drug effects in a human-relevant system. Here, iPSCs from individuals with...
Journal of Neuroendocrinology
2026
Hiroe Hu, Yoojin Lee, Alaina N Tillman et al.
1 citation
Arginine vasopressin (AVP) modulates stress responsivity and social-affective behaviors, but its role in mood and trauma-related disorders remains poorly defined due to challenges in peripheral measurement. This study used copeptin, a stable, reliable, and well-validated surrogate marker of AVP secretion, to assess vasopressinergic function in a transdiagnostic sample of individuals...
Translational Psychiatry
November 18, 2025
Jenessa N Johnston, Peixiong Yuan, Bashkim Kadriu et al.
2 citations
Treatment-resistant depression (TRD) is associated with worse clinical outcomes and longer course of illness. However, TRD is more difficult to model in animal phenotypes, suggesting that other experimental and translational models must be considered to properly address and research novel therapeutics. Reelin, an endogenous glycoprotein downregulated in depression, has shown rapid...
Journal of Affective Disorders
March 15, 2025
Polymnia Georgiou, Cristan A Farmer, Gustavo C Medeiros et al.
24 citations
Subanesthetic doses of (R,S)-ketamine (ketamine) have demonstrated rapid and robust antidepressant effects in individuals with depression. However, individual variability in response to ketamine exists, and current biomarkers of ketamine treatment response are not entirely understood. Preclinical evidence suggests a link between hypothalamic-pituitary-adrenal (HPA) axis activation, a...
European Archives of Psychiatry and Clinical Neuroscience
July 13, 2024
Jenessa N Johnston, Carlos A. Zarate, Mark D Kvarta
18 citations
The discovery of racemic (R, S)-ketamine as a rapid-acting antidepressant and the subsequent FDA approval of its (S)-enantiomer, esketamine, for treatment-resistant depression (TRD) are significant advances in the development of novel neuropsychiatric therapeutics. Esketamine is now recognized as a powerful tool for addressing persistent symptoms of TRD compared to traditional oral...
Progress in neuro-psychopharmacology & biological psychiatry
June 8, 2024
Kaylene K A Scheil, Carla L Sánchez-Lafuente, Brady S Reive et al.
5 citations
There is an urgent need for novel antidepressants, given that approximately 30% of those diagnosed with depression do not respond adequately to first-line treatment. Additionally, monoaminergic-based antidepressants have a substantial therapeutic time-lag, often taking months to reach full therapeutic effect. Ketamine, an N-methyl-d-aspartate receptor (NMDAR) antagonist is the only current...
Neuropharmacology
January 13, 2023
Jenessa N Johnston, Bashkim Kadriu, Josh Allen et al.
64 citations
The discovery of ketamine as a rapid-acting antidepressant spurred significant research to understand its underlying mechanisms of action and to identify other novel compounds that may act similarly. Serotonergic psychedelics (SPs) have shown initial promise in treating depression, though the challenge of conducting randomized controlled trials with SPs and the necessity of long-term clinical...
Frontiers in Pharmacology
September 2, 2020
Jenessa N Johnston, Jonathan S. Thacker, Charissa Desjardins et al.
25 citations
Depression is the leading cause of disability worldwide, which necessitates novel therapeutics and biomarkers to approach treatment of this neuropsychiatric disorder. To assess potential mechanisms underlying the fast-acting antidepressant actions of ketamine we used a repeated corticosterone paradigm in adult male rats to assess the effects of ketamine on reelin-positive cells, a protein...