Translational Psychiatry
October 6, 2026
Nadia S. Hejazi, Mina Kheirkhah, Robin Chholak et al.
Insomnia and anxiety frequently co-occur with treatment-resistant depression (TRD). This study examined short-term changes in depression, anxiety, and insomnia symptoms post-ketamine in TRD and their inter-relationships. Seventy-one patients with TRD were assessed at baseline and 24 h after intravenous ketamine (0.5 mg/kg). Depression, anxiety, and insomnia were measured using the...
Translational Psychiatry
September 28, 2026
Johan Saelens, Franziska Stadler, Victoria Forschauer et al.
Obsessive-compulsive disorder (OCD) is a highly debilitating and often chronic condition. A large percentage of patients do not respond to first-line treatments with selective serotonin reuptake inhibitors (SSRIs) or cognitive behavioral therapy (CBT), underscoring the need for novel therapeutic approaches. In this context, promising innovative treatments have recently emerged for OCD; these...
Frontiers in Psychiatry
September 24, 2026
Franziska Stadler, Johan Saelens, Ioline D. Henter et al.
Background: The past few decades have seen a revived interest in psychedelic-assisted and ketamine-assisted therapy for mental health disorders, but data concerning the acute, subacute, and long-term effects of serotonergic psychedelics on cognitive functioning are scarce. This international, online study (N = 759) sought to investigate the potential acute, subacute, and long-term effects of...
Neuropsychopharmacology
September 21, 2026
Balwinder Singh, Hossam M Ali, Alessandro Miola et al.
Disrupted excitation-inhibition (E/I) balance involving GABA and glutamate (Glu) is implicated in the pathophysiology of depression. Ketamine, an NMDA receptor antagonist with rapid antidepressant properties, may modulate this balance, yet proton magnetic resonance spectroscopy (¹H-MRS) studies report inconsistent findings regarding the direction, magnitude, and timing of neurochemical effects....
JAMA Psychiatry
July 1, 2026
Sung Ryul Shim, Hye Su Jeong, Tanner J. Bommersbach et al.
1 citation
While intravenous ketamine is not approved by the US Food and Drug Administration, it is increasingly used with off-label indications as a novel treatment for suicidal and depressive symptoms. To systematically review and metasynthesize the efficacy and safety data for intravenous ketamine in treating major depressive episodes (MDEs). PubMed, PsycInfo, Cochrane Library, and Embase were...
Neuropsychopharmacology
June 16, 2026
Nadia S. Hejazi, Mina Kheirkhah, Brady A. Riedner et al.
Slow-wave activity (SWA), a key indicator of sleep homeostasis, is often diminished in individuals with treatment-resistant depression (TRD). Ketamine, a rapid-acting antidepressant, increases SWA during the first period of non-rapid eye movement (NREM1) sleep. However, research into how ketamine affects sleep and its connection to treatment outcomes in TRD has been limited by small sample...
General Hospital Psychiatry
February 25, 2026
Alan C. Courtes, Blake Myers, Noah Daly et al.
1 citation
Psychological stress not only undermines quality of life for people with cancer but also fuels tumor growth. Emerging evidence from the nascent field of cancer neuroscience suggests that adrenergic signaling from direct tumor-neuron interactions drives cancer progression, resistance to treatment, and worse outcomes. Cancer neuroscientists are increasingly seeking to repurpose psychoactive...
Research Square
February 12, 2026
Jenessa N Johnston, Greg Jones, Shiyong Peng et al.
preprint
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...
Pharmacological Reports
January 22, 2026
Taichi Goto, Joy D Kreskow, Alexander L R Ross et al.
Fatigue, a prevalent symptom of chronic illness, impacts quality of life. This proof-of-concept, randomized, double-blind, crossover trial assessed the anti-fatigue effects of ketamine (0.5 mg/kg) versus midazolam (0.045 mg/kg), the active comparator. Ten participants, who were cancer survivors, with fibromyalgia, myalgic encephalomyelitis/chronic fatigue syndrome, or systemic lupus...
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...
NPJ Digital Medicine
December 8, 2025
Joseph Geraci, Bessi Qorri, Mike Tsay et al.
Clinical trial failures are frequently driven by patient heterogeneity and limited sample sizes that obscure treatment effects by diluting statistical power. We introduce NetraAI, a novel explainable artificial intelligence (AI) platform that integrates dynamical-systems modeling, evolutionary long-range memory feature selection, and large-language model (LLM)-generated insights, to discover...
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...
Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition
September 16, 2025
Jen Evans, Carlos A. Zarate
Motivation: The exact mechanism of action of the rapid acting acting antidepressant ketamine is unknown. Goal(s): Investigation of the functional connectivity changes after acute ketamine in relation to receptor density. Approach: In a double blind placebo controlled clinical trial an infusion of ketamine or placebo was administered during resting state fMRI at 3T and functional connectivity...
Frontiers in Psychiatry
September 2, 2025
Mina Kheirkhah, Nastasia McDonald, Julia Aepfelbacher et al.
1 citation
Introduction: This is the first randomized controlled trial to use both qualitative and quantitative methods to evaluate the effects of a combined sensory intervention that included mindfulness, music, and a light-occluding eye mask during antidepressant-dose ketamine treatment for depression. Methods: Forty-three participants with unipolar depressive disorder enrolled in the study; 22...
medRxiv
August 28, 2025
Franziska Stadler, Johan Saelens, Ioline D. Henter et al.
preprint
This international online study (N=759) examined the acute, subacute, and long-term effects of psychedelic drug use on cognitive performance and mental health. Participants completed cognitive tasks assessing working memory, selective attention, and visual/spatial perception, as well as questionnaires assessing mental health outcomes and quality of life. Based on self-reported substance use,...
The American Journal of Drug and Alcohol Abuse
August 22, 2025
P. Manza, Annabelle M. Belcher, Heather Fitzsimons et al.
ABSTRACT Background: Opioid use disorder (OUD) is a chronic relapsing condition with a high mortality rate. While medications such as methadone are valuable first-line therapies, retention is poor, with the highest dropout rates early in a treatment attempt. Poor outcomes are due in part to the very high rates of co-morbid depression in people with OUD, as depression can drive opioid use....
Brain, Behavior, and Immunity
July 1, 2025
Brandi Quintanilla, Dede Greenstein, Ashutosh Tripathi et al.
7 citations
Recent evidence suggests that the rapid-acting antidepressant ketamine has immune regulatory functions. The complement system is an important component of the innate immune response and plays a key role in synaptic plasticity. An increase in complement component 3 (C3) expression was previously found in the prefrontal cortex of individuals with depression. Given the complement system's role in...
Psychiatry Research
July 1, 2025
Hiroe Hu, Alaina N Tillman, Miyu Fujita et al.
2 citations
Subanesthetic-dose ketamine has recently been reported to improve hedonic pleasures associated with social interactions and altruism in individuals with treatment-resistant depression. However, whether ketamine-among other glutamate receptor modulators-also improves empathy and/or prosocial behavior in humans remains unknown. Under a framework grounded in neurobiology that proposes that...
CNS Spectrums
June 30, 2025
Jose-Manuel Quintero, Rosa-Helena Bustos, Sharon Lechtig-Wassermann et al.
6 citations
Ketamine, originally synthesized in 1962, has gained increasing attention due to its rapid and sustained antidepressant effects in treatment-resistant depression (TRD). Unlike traditional antidepressants, ketamine acts on multiple neurotransmitter systems, including NMDA receptor antagonism and AMPA receptor potentiation, offering a novel mechanism for mood regulation. Beyond psychiatry,...
Neuron
May 7, 2025
Federica Lucantonio, Jacob Roeglin, Shuwen Li et al.
24 citations
Ketamine is recognized as a rapid and sustained antidepressant, particularly for major depression unresponsive to conventional treatments. Anhedonia is a common symptom of depression for which ketamine is highly efficacious, but the underlying circuits and synaptic changes are not well understood. Here, we show that the nucleus accumbens (NAc) is essential for ketamine's effect in rescuing...
Neuropsychopharmacology
May 1, 2025
Johan Saelens, Anna Gramser, Victoria Watzal et al.
47 citations
This systematic review and network meta-analysis (NMA) sought to compare different antidepressant treatments for treatment-resistant depression (TRD) in order to facilitate evidence-based choices. A literature search of PubMed, Cochrane Library, and Embase from inception until April 13th, 2023 identified randomized, controlled trials (RCTs) of adults with depression who had not responded to at...
Neuropsychopharmacology
May 1, 2025
Mina Kheirkhah, Wallace C. Duncan, Qiaoping Yuan et al.
6 citations
Abnormalities during rapid eye movement (REM) sleep contribute to the pathophysiology of major depressive disorder (MDD), but few studies have explored the relationship between REM sleep and treatment-resistant depression (TRD). In MDD, REM sleep abnormalities often manifest as alterations in total night REM Density (RD), RD in the first REM period (RD1), and REM Latency (RL). Among these, RD1...
Bipolar Disorders
April 2, 2025
Adam Fijtman, Mani Yavi, Abigail Vogeley et al.
2 citations
Treatment-resistant depression (TRD) remains a challenge, necessitating novel interventions that address associated cognitive deficits. The glutamatergic modulator ketamine exerts rapid antidepressant effects, prompting investigators to assess its impact on cognitive function, specifically working memory. This study explored ketamine's influence on working memory and magnetoencephalography...
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...
Biological Psychiatry
March 15, 2025
Anna Onisiforou, Andria Michael, Markos Apostolakis et al.
14 citations
Opioid use disorder (OUD) has reached epidemic proportions, with many countries facing high levels of opioid use and related fatalities. Although currently prescribed medications for OUD are considered lifesaving, they inadequately address negative affect and cognitive impairment, resulting in high relapse rates to nonmedical opioid use even years after drug cessation (protracted abstinence)....