Translational psychiatry
July 13, 2025
Xiaoqian Yu, Aki Tsuchiyagaito, Masaya Misaki et al.
4 citations
Adolescents who experienced early life adversity (ELA) show greater difficulty down-regulating the posterior cingulate cortex (PCC), a key node of the default mode network, compared to healthy controls. A neurofeedback-augmented mindfulness training combining breath focus with real-time fMRI neurofeedback targeting the PCC was tested in 43 ELA-exposed and 40 healthy adolescents. Those with ELA were randomly assigned to active or sham neurofeedback. Both active and sham groups showed similar PCC down-regulation, and all adolescents reported increased state mindfulness after training. ELA-exposed adolescents reported greater improvements in positive affect, negative affect, and stress at one-week follow-up relative to controls, but there was no difference between active and sham neurofeedback on self-reported measures. The approach was feasible and acceptable for ELA-exposed adolescents but may not enhance mindfulness training beyond sham.
Translational psychiatry
October 14, 2024
Marvin S Meiering, David Weigner, Matti Gärtner et al.
4 citations
In healthy adults, a single dose of ketamine reduced activity in the hippocampus and the default mode network (DMN) and increased connections between frontal and limbic brain regions while participants viewed emotional faces. These effects occurred both during the infusion and 24 hours later. Pretreatment with lamotrigine, which blocks glutamate release, prevented the increase in brain connectivity and the delayed reduction in DMN activity, but did not affect the acute drop in hippocampal and DMN activity. The findings suggest that ketamine's acute changes in brain connectivity and its sustained effects on DMN activity depend on glutamate transmission, whereas its immediate suppression of limbic and DMN activity does not.
Translational psychiatry
October 10, 2025
Wolfgang Emanuel Zürrer, Lionel Wettstein, Helena D Aicher et al.
3 citations
Salvinorin A, the main psychoactive compound in Salvia divinorum, shows therapeutic potential for pain, addiction, and stroke in animal models, but its side effects—including anxiety, motor and cognitive impairment—may limit clinical use. A systematic review and meta-analysis of 82 studies found anti-nociceptive, anti-inflammatory, neuroprotective, and anti-addictive effects, though depression results were inconsistent. Doses ranged from 0.1 to 10 mg/kg, with rapid onset and a half-life of about one hour. Sixteen structurally distinct analogues were identified with potentially improved safety and pharmacokinetic profiles. Findings support further development of analogues to overcome the side effect profile.
Translational psychiatry
February 6, 2025
Sumra Sajid, J John Mann, Michael F Grunebaum
3 citations
Ketamine and its enantiomers can reduce suicidal thoughts, but the effects are short-lived and vary by dose and route of administration. A systematic review of 16 clinical trials since 2020 found that multiple intravenous doses of ketamine or S-ketamine reduced suicidal ideation for several days to weeks, while single doses had shorter, less consistent effects. Intranasal and single intravenous doses produced less reliable results. R-ketamine showed fewer side effects but requires more research. No studies measured suicidal behavior as an outcome. The review highlights the need for personalized treatment and notes limitations such as small samples and study heterogeneity.
Translational psychiatry
July 25, 2024
Ariela S Buxbaum Grice, Laura Sloofman, Tess Levy et al.
3 citations
A single low-dose intravenous ketamine infusion (0.5 mg/kg) triggers immediate and profound changes in gene expression in the blood of individuals with ADNP syndrome, a rare neurodevelopmental disorder. These alterations include upregulation of immune and inflammatory processes and downregulation of RNA processing and metabolism, with specific enrichment in monocyte-related expression patterns. The changes are transient, returning to baseline within 24 hours to one week. The findings clarify ketamine's molecular effects and support further research into its therapeutic targets for ADNP syndrome and potentially autism spectrum disorder.
Translational psychiatry
January 29, 2026
Rafael V Lima Da Cruz, Rêmullo B G de Miranda Costa, Gabriel M De Queiroz et al.
2 citations
A single dose of the psychedelic DMT reversed depression-like behavior and restored cognitive performance in male mice exposed to chronic stress, outperforming chronic fluoxetine across most measures. When given during the stress period, DMT reduced anhedonia but did not rescue cognitive deficits, indicating domain-specific long-lasting effects. All DMT regimens increased the integration of adult-born granule cells and reduced abnormally integrated cells in the brain, suggesting structural circuit repair. The role of the psychedelic experience remains uncertain because isoflurane anesthesia may have confounded results.
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.
Translational psychiatry
October 31, 2025
Kristin L Dawson, Athena May Jean M Carangan, Jessica Klunder et al.
2 citations
Ketamine infusions reduced symptoms of depression and PTSD in 20 participants with major depressive disorder or posttraumatic stress disorder. The treatment also lowered biological age as measured by three epigenetic biomarkers (OMICmAge, GrimAge V2, and PhenoAge), indicating a potential reversal of accelerated aging linked to these conditions. Changes in underlying epigenetic biomarker proxies and surrogate protein markers accompanied the age reduction. The findings align with prior research on ketamine's effects and suggest that these epigenetic clocks can capture signals related to clinical improvements.
Translational psychiatry
May 26, 2026
Marvin M Urban, Lea Zillich, Nathalie M Rieser et al.
1 citation
In a pilot study of 37 detoxified patients with alcohol use disorder, psilocybin (25 mg) produced changes in DNA methylation across the genome compared to placebo. One methylation site in the TLE4 gene and a differentially methylated region in RASGRP4 were linked to psilocybin treatment. Co-methylation networks related to psilocybin were associated with reductions in depressive symptoms and drinking behavior, and gene analysis pointed to involvement in neuroplasticity and immune functions. The primary trial endpoints—duration of abstinence and mean alcohol use—were not reached, so the analysis focused on secondary psychometrics. The findings suggest immunomodulatory actions of psilocybin but are limited by the modest sample size.
Translational psychiatry
January 23, 2026
Stevan Nikolin, Clara Massaneda-Tuneu, Louise Brettell et al.
1 citation
Electroconvulsive therapy (ECT) leads to a faster reduction in depressive symptoms than ketamine for severe, medication-resistant depression. A meta-analysis of seven studies with 731 participants found that depression scores were slightly lower at baseline in the ketamine group. After adjusting for baseline differences, ECT produced an additional improvement of about 0.02 standardized mean difference per day, amounting to a predicted moderate advantage over ketamine after four weeks. This advantage falls within the range considered clinically meaningful.
Translational psychiatry
November 24, 2025
Xin-Yu Li, Di Qiu, Ni Du et al.
1 citation
Patients with preexisting sleep disorders are at higher risk for postoperative sleep disturbance (PSD). In a randomized trial of 130 patients, intraoperative esketamine (0.3 mg/kg/h) reduced the incidence of PSD on postoperative day 1 (43.1% vs. 64.6%; odds ratio, 0.414) and lowered hydromorphone use. Preoperative oral microbiota profiles differed between patients who later developed PSD and those who did not, with specific bacterial taxa linked to sleep disturbance. The findings suggest esketamine may help prevent postoperative sleep disruption, possibly by modulating the oral microbiota.
Translational psychiatry
November 17, 2025
Noah Stapper, Lindsay L Benster, Sahit Menon et al.
1 citation
A systematic review of 24 clinical trials examined neurophysiological biomarkers linked to treatment-induced changes in suicidal ideation. Most studies were published within the past five years but showed methodological heterogeneity, including non-randomized designs and concurrent interventions. Despite limitations, findings suggest that the anterior cingulate cortex is involved in the anti-suicidal effects of intravenous ketamine, an effect absent with oral ketamine, possibly explaining intravenous ketamine's superior clinical effects. Improvements in suicidal ideation following electroconvulsive therapy and magnetic seizure therapy were associated with activity in the prefrontal cortex. These patterns may indicate that acute effects of intravenous ketamine and sustained effects of seizure therapies involve differential modulation of these brain regions.
Translational psychiatry
October 6, 2025
Hanna J Szkudlarek, Rajkamalpreet Singh Mann, Krystyna Wieczerzak et al.
1 citation
Adolescent exposure to THC, the main psychoactive component of cannabis, increases the risk of later neuropsychiatric symptoms, and the medial prefrontal cortex is a key brain region involved. The antioxidant N-acetylcysteine (NAC) prevented cognitive, synaptic, neuronal, and neurochemical deficits caused by chronic adolescent THC exposure in a rodent model. This suggests that THC-induced oxidative stress contributes to neuropsychiatric risk and identifies NAC as a potential preventive treatment.
Translational psychiatry
March 8, 2025
Daiki Nakatsuka, Taro Suwa, Yuichi Deguchi et al.
1 citation
Aripiprazole, a partial dopamine receptor agonist, can suppress the dissociative side effects of the rapid-acting antidepressant ketamine without diminishing its antidepressant effects. Experiments in mice showed that aripiprazole blocked ketamine-induced psychotomimetic behaviors while preserving or enhancing antidepressant-like effects in the forced swim test, whereas the antagonist raclopride suppressed both. Brain mapping identified the ventral tegmental area as a key region. In a small clinical study of nine depressed patients, co-administering 12 mg of aripiprazole with ketamine reduced dissociative symptoms while maintaining antidepressant benefits. These findings suggest that combining aripiprazole with ketamine may offer a preferred therapy for treatment-resistant depression.
Translational psychiatry
June 18, 2024
Matti Gärtner, Anne Weigand, Marvin Sören Meiering et al.
1 citation
Ketamine reduces spontaneous brain activity in three subregions of the anterior cingulate cortex (ACC) during administration in healthy people. Lamotrigine, which inhibits glutamate release, attenuates this effect only in the ventral ACC subregions, suggesting glutamate involvement there. ACC activity returns to baseline 24 hours later, though group differences persist between the lamotrigine and ketamine groups. Trait negative emotionality is closely linked to activity changes in the subgenual ACC after ketamine. These findings clarify how ketamine affects different ACC subregions and may relate to its antidepressant mechanisms.
Translational psychiatry
June 5, 2026
Samaneh Ahmadian-Moghadam, Shiva Roshan-Milani, Ehsan Saboory
Psilocybin-induced neuroplasticity could theoretically modulate stress-related neurodevelopmental risk pathways relevant to ADHD, but this remains a speculative hypothesis rather than an evidence-based intervention. Preclinical studies in non-ADHD models show psilocybin can induce rapid synaptic plasticity, alter cortical excitatory-inhibitory dynamics, and reverse stress-associated alterations. Human clinical trials in mood, trauma-related, and substance use disorders demonstrate durable changes in emotional regulation, cognitive flexibility, and brain network organization—processes overlapping with ADHD neural systems. Emerging preliminary, largely self-reported studies suggest potential benefits for inattention, impulsivity, and emotional dysregulation. Key mechanistic uncertainties and ethical considerations, especially for vulnerable populations, are emphasized as critical constraints on translation.
Translational psychiatry
May 21, 2026
Francesco Bavato, Andrea Steuer, Anna M Jacobsen et al.
Chronic users of methamphetamine (METH) and MDMA (Ecstasy) show distinct alterations in blood levels of tryptophan-related metabolites, which may help explain their different clinical effects. In a study of 36 chronic MDMA users, 33 chronic METH users, and 71 healthy controls, METH use was linked to depleted serum tryptophan and serotonin and broad activation of kynurenine pathways, whereas MDMA use was associated with selective activation of the OH-kynurenine branch. These metabolite changes correlated with the severity of depression and psychosis symptoms. The findings suggest that persistent changes in peripheral tryptophan metabolism may contribute to the substances' contrasting addiction and psychiatric profiles.
Translational psychiatry
May 12, 2026
Linda Bryant, Laith Alexander, Sergio Mena et al.
A machine-learning model using structural brain scans predicted which adults with treatment-resistant depression would respond to a single ketamine infusion. The model, trained on 99 participants, achieved 72% balanced accuracy in the discovery sample and 60% in two independent groups, with performance dropping to chance in a saline-treated control group. Greater gray matter volume in frontal regions predicted response, while greater cerebellar volume predicted non-response. The findings suggest that pre-treatment brain structure may help guide personalized treatment decisions for ketamine therapy.
Translational psychiatry
April 21, 2026
Paul A Parcon, Amanda Bardhoshi, Amanda Olsen-Dufour et al.
Ketamine, a rapid-acting antidepressant, increases cyclic adenosine monophosphate (cAMP) activity in the brain within an hour of infusion, likely by affecting phosphodiesterase-4 (PDE4), an enzyme that normally terminates cAMP signaling. In rats given 10 mg/kg ketamine, binding of a radioligand to PDE4 increased by a mean of 24% (range 3%–42%); in rhesus macaques given 0.5 mg/kg, binding increased by a mean of 14% (range 12%–16%). A radioligand selective for the PDE4B subtype showed a mean increase of 28% (range 16%–37%) in monkeys. Control experiments ruled out blood-flow effects. The findings suggest that boosting cAMP activity through PDE4 inhibition, particularly the PDE4B subtype, may underlie ketamine's rapid antidepressant effects and point to a common pathway for antidepressant action.
Translational psychiatry
April 14, 2026
Ryan J Keenan, Rifa T Haque, Xiangjun Jin et al.
A single dose of psilocybin worsened diet-induced weight loss over four weeks in obese mice switched to low-fat chow, making them more likely to lose more weight. The effect came mainly from reducing food intake, not from changing energy expenditure. In obese mice kept on a high-fat diet, psilocybin did not affect body weight or food intake, suggesting it does not directly cause weight loss or reduce eating. Instead, it may help enable weight loss when combined with other weight-loss interventions. The findings support further research into psychedelic compounds as an add-on therapy for obesity, though more work is needed to understand the mechanisms.
Translational psychiatry
March 6, 2026
Ty Lees, Jason N Scott, Brian W Boyle et al.
A single low dose of ketamine (0.5 mg/kg) reduced depressive, anhedonic, and ruminative symptoms 24 hours later in 24 people with treatment-resistant depression. The symptom improvement was not linked to changes in brain connectivity but was associated with connectivity patterns present before the infusion. After ketamine, participants showed broad increases in resting-state functional connectivity within and between the default mode and frontoparietal networks, as measured by EEG. The authors suggest these connectivity increases may reflect ketamine's synaptogenic effects, which can be short-lived. The study included 34 healthy controls who did not receive ketamine.
Translational psychiatry
November 24, 2025
Assaf Oshri, Cullin J Howard, Steven M Kogan et al.
Socioeconomic hardship increases the risk of suicidal thoughts and behaviors in adolescents, partly through shorter sleep duration. A study of 11,878 youth from the Adolescent Brain Cognitive Development Study found that higher levels of hardship predicted more suicidal ideation and attempts. Shorter sleep acted as a pathway linking hardship to suicidal thoughts, but this indirect effect was weaker in adolescents with higher coherence in the brain's Default Mode Network. The findings suggest that sleep health is a mechanism connecting economic adversity to suicide risk, and that DMN coherence may serve as a neuroprotective factor supporting resilience.
Translational psychiatry
November 21, 2025
Andrea Francesco Carluccio, Georg Northoff
Auditory verbal hallucinations (AVH) in psychosis and schizophrenia involve changes in brain connectivity and organization, but how these relate to the structure of subjective experience is unclear. This review proposes two neurophenomenological hypotheses. First, disruptions in connections between sensory, bodily, and language brain regions may cause temporal fragmentation in perception and thought, leading to hyperreflexivity—abnormal attention to isolated objects. Second, a reduced distinction between unimodal and transmodal brain regions may blur the boundary between outer social and inner mental spaces, causing confusion between interpersonal and intrapersonal experience. These hypotheses link brain changes directly to the structure of experience in AVH.
Translational psychiatry
July 15, 2026
Annette Johansen, Pontus Plavén-sigray, Martin K Madsen et al.
A single dose of psilocybin (0.3 mg/kg) did not produce a statistically significant increase in synaptic density across all fifteen healthy participants. However, those who received psilocybin in a therapeutic-like room reported more intense mystical-type experiences, longer-lasting psychological benefits, and showed greater increases in synaptic density in the frontal cortex and hippocampus compared to those dosed inside an MRI scanner. The findings indicate that environmental context modulates psilocybin's neuroplastic effects, with implications for psychedelic-assisted therapies.