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Research papers

34,664 articles (and counting)

Trauma re-experiencing episodes during esketamine treatment in patients with treatment-resistant depression and comorbid PTSD: a retrospective case series.

European Journal of Psychotraumatology December 1, 2026 Maud Rothärmel, Lila Mekaoui, François Kazour et al. 1 citation

In a retrospective study of 22 adults with treatment-resistant depression and comorbid post-traumatic stress disorder who received esketamine nasal spray, trauma re-experiencing episodes occurred during treatment sessions. For 16 patients (72.7%) these episodes disappeared as sessions progressed. Treatment was stopped for 6 patients (27.3%) due to re-experiencing. Among those who continued esketamine, depression response rate was 45.5% and remission 22.7%; PTSD improvement rate was 45.5% and remission 18.2%. The findings suggest esketamine can be safely administered in this comorbid population and that trauma re-experiencing does not prevent clinical improvement.

The efficacy and mechanism of an integrated mindfulness-based programme on posttraumatic stress disorder among people with HIV: a randomized controlled trial with 3-month follow up.

European Journal of Psychotraumatology December 1, 2026 Chulei Tang, Ting Zhao, Simin Yu et al.

An integrated mindfulness-based programme combining the Community Resiliency Model and mindfulness-based stress reduction reduced posttraumatic stress disorder symptoms and improved antiretroviral therapy adherence in people with HIV. Eighty-two participants with HIV and PTSD were assigned to either the intervention or a control group. The intervention group showed significantly greater reductions in PTSD symptoms and improvements in ART adherence immediately after the programme and at a three-month follow-up. Increased mindfulness, enhanced resilience, and decreased rumination partially explained the effect on PTSD symptoms. The authors argue the programme offers a low-resource intervention for trauma and treatment adherence in HIV-positive populations.

Development and validation of a short-form (6-item) version of the clinician-administered dissociative states scale (CADSS-SF).

European Journal of Psychotraumatology December 1, 2026 V Ursule Taujanskaite, Sunjeev K. Kamboj

A 6-item short form of the Clinician Administered Dissociative States Scale (CADSS-SF) was developed using data from three studies of nitrous oxide in 229 healthy volunteers, then validated in 80 separate participants. The single-factor scale, composed of derealization and depersonalization items, showed excellent model fit and internal consistency (omega = 0.87), correlated strongly with the full 19-item CADSS (r ≥ 0.88), and moderately with a measure of psychotomimesis (r = 0.63). The CADSS-SF enables rapid, repeated assessment of dissociation during drug intoxication without disrupting the experience, but primarily captures derealization and depersonalization and requires further validation beyond drug-induced dissociation in healthy populations.

A neurocognitive account of complex PTSD: self-modelling, affective dysregulation, and implications for MDMA-assisted and targeted psychotherapies.

European Journal of Psychotraumatology December 1, 2026 Philip Gerrans, Hugh McGovern, Jakob Hohwy et al.

Complex post-traumatic stress disorder (C-PTSD) involves lasting difficulties with emotions, self-concept, and relationships, beyond typical PTSD symptoms. This review proposes a neurocognitive explanation based on predictive processing and self-modelling, focusing on how the brain's insula integrates bodily signals, emotions, and self-awareness. The authors suggest that C-PTSD arises from maladaptive predictions shaped by prolonged interpersonal trauma, leading to unstable self-regulation. They examine MDMA-assisted psychotherapy as one intervention that may temporarily alter emotional salience, trust, and self-related thinking. The framework generates testable hypotheses about self-modelling in C-PTSD and offers guidance for developing treatments that target affective regulation and self-referential processing.

Effects of sub-anesthetic doses of esketamine on immune function and postoperative negative emotions in acoustic neuroma patients: a randomized clinical trial.

Annals of medicine December 1, 2026 Zheping Chen, Yaozhu Wang, Peilin Cong et al.

A double-blind randomized trial found that perioperative sub-anesthetic esketamine reduced postoperative depression and anxiety and improved sleep quality in patients undergoing acoustic neuroma surgery. The incidence of depression on postoperative day 1 was 7.7% in the esketamine group versus 31.6% in the placebo group, and on day 3 it was 0.0% versus 15.8%. Anxiety and sleep disturbances also significantly decreased. No significant differences were observed in immune function, postoperative pain scores, or adverse events between groups.

Thalamic 5-HT2A receptor activation reduces GABA uptake, increases tonic GABAA inhibition and induces absence seizures in Wistar rats.

Neuropharmacology November 1, 2026 Vincenzo Crunelli, Tatiana P Morais, William M Connelly et al.

Serotonin 5-HT2A receptors (5-HT2ARs) in the thalamus increase in expression during development, shifting from interneurons to thalamocortical neurons in the ventrobasal region. Activating these receptors with the agonist TCB-2 reduces GABA uptake and enhances tonic GABAA currents in ventrobasal thalamocortical neurons, an effect absent in δ-subunit GABAA receptor knockout mice and independent of postsynaptic signaling. Bilateral injection of TCB-2 into the ventrobasal thalamus of freely moving rats induces spike-and-wave discharges and behavioral arrest, which are blocked by ethosuximide, indicating absence seizures. The findings suggest that 5-HT2AR signaling can shape thalamocortical dynamics and increase susceptibility to aberrant rhythmic activity.

Prescribing bias and adverse outcomes of esketamine in major depression comorbid substance.

Journal of Affective Disorders November 1, 2026 Dian‐jeng Li, Tien-Wei Hsu, Te-Chang Changchien et al.

Patients with major depressive disorder who are prescribed esketamine have higher rates of comorbid substance use disorders compared to those treated with antidepressants or repetitive transcranial magnetic stimulation. Among esketamine users, those with a substance use disorder face greater risks of self-harm, suicide attempt, emergency visits, hospitalization, and mortality. The findings indicate a prescription bias toward patients with comorbid substance use disorders and highlight the need for careful monitoring and specialized care for this population.

Changes in anxiety, quality of life, and functioning following psilocybin-assisted therapy in veterans with treatment-resistant depression.

Journal of Affective Disorders November 1, 2026 Carlton M Kelly, Mathieu Fradet, Catherine Bostian et al.

A single 25-mg dose of psilocybin with psychological support was associated with sustained improvements in anxiety, quality of life, functioning, and PTSD symptoms in 15 veterans with treatment-resistant depression. Anxiety scores dropped 59% from baseline at three weeks and remained lower through 12 months. Quality of life increased 24% and functional impairment decreased 46% at three weeks, though these effects were no longer statistically significant after accounting for concurrent improvements in depression. PTSD symptom reductions were observed at all timepoints. Acute subjective experiences did not correlate with treatment response. The study is limited by its small sample and open-label design.

Unpacking the role of psychopathology in the state-to-trait mindfulness transition: A longitudinal structural equation modeling study.

Journal of Affective Disorders November 1, 2026 Veronica L O'Brien, Nicolette P. Rickert

People with higher anxiety may find it harder to develop mindfulness through practice. A four-week online mindfulness course with 274 participants showed that previous mindfulness experience predicted higher starting state mindfulness, while baseline anxiety predicted higher starting state mindfulness but slower growth in state mindfulness over time. Growth in state mindfulness during the course predicted higher final levels of trait mindfulness. The findings suggest that anxiety can interfere with the benefits of mindfulness training.

Comparing transcranial magnetic stimulation and esketamine treatment response trajectories in resistant depression.

Journal of Affective Disorders November 1, 2026 Lindsay L Benster, Jordan N Kohn, Benjamin Wade et al.

In a real-world comparison of two FDA-approved treatments for treatment-resistant depression, intranasal esketamine led to faster improvement than repetitive transcranial magnetic stimulation (rTMS). Over 90 days, esketamine patients responded a median of 36 days versus 49 days for rTMS, and suicidal ideation resolved more quickly (median 9 vs. 26 days). However, by about 90 days, overall response and remission rates were similar between the groups (68.8% and 45.2% for esketamine; 59.4% and 40.1% for rTMS), suggesting a difference in speed rather than ultimate effectiveness. For rTMS, slower response was predicted by comorbid anxiety and benzodiazepine use, while former tobacco use predicted faster response. No such predictors were found for esketamine.

Increased morning cortisol after ketamine treatment for suicidal depression: Exploratory report from a randomized trial.

Journal of Affective Disorders November 1, 2026 Tse-Hwei Choo, Hanga C Galfalvy, John G Keilp et al.

A midazolam-controlled trial of intravenous ketamine for suicidal depressed patients found that ketamine rapidly reduced suicidal ideation within 24 hours. An exploratory analysis measured saliva cortisol awakening response at baseline and 24 hours after infusion. Waking cortisol significantly increased 24 hours after ketamine treatment. The increase in waking cortisol from baseline to post-infusion showed a small to medium, nonsignificant correlation with decreased suicidal ideation. These preliminary results, pending replication, align with evidence that moderate cortisol increases may enhance stress-resilience.

The effect of a mindfulness-based stress reduction program on stress and quality of life in mothers of children with physical disabilities: A single-blind randomized controlled trial.

Journal of Affective Disorders November 1, 2026 Cengiz Taşkaya, Leyla Sezgin, Necmettin Çiftci

An 8-week mindfulness-based stress reduction (MBSR) program for mothers of children with physical disabilities significantly reduced parental stress and increased mindfulness compared with no intervention. Significant improvements were observed in the psychological and environmental domains of quality of life, but not in the physical or social domains. The findings suggest MBSR can be a supportive approach in family-centered rehabilitation for these mothers.

Dream and nightmare alterations in patients presenting with suicidal crisis: A prospective study in psychiatric emergency department.

Sleep Medicine October 1, 2026 Emilie Gagneron, Katayoun Rezaei, Romain Perot et al.

In a psychiatric emergency department in Paris, 83% of patients experiencing a suicidal crisis reported at least one dream alteration. Bad dreams occurred in 61.9% of participants, nightmares in 52.4%, and suicidal scenarios within nightmares in 35.7%. Nightmares emerged on average 128 days before the crisis, while suicidal-themed nightmares appeared closer, about 16 days before the emergency visit. Over half of patients (54.8%) showed an evolutionary pattern of at least two successive dream alterations. Nightmare severity correlated with insomnia severity and anxiety symptoms. These findings suggest that nightmares may serve as early markers of suicide risk, with systematic assessment potentially enhancing clinical practice.

Olfactory bulb circuits drive ketamine-enhanced high-frequency oscillations via kainate and GABAergic mechanisms.

Neuropharmacology September 15, 2026 Taisiia Prosvirova, Wiktoria Podolecka, Jacek Wróbel et al.

Ketamine rapidly reorganizes fast brain rhythms differently across cortical networks. In freely moving rats, neocortical gamma power increased broadly, while the olfactory bulb showed suppressed gamma alongside robust high-frequency oscillations (HFO; 130-180 Hz). Local blockade of non-NMDA glutamate receptors in the olfactory bulb suppressed ketamine-enhanced HFO in the bulb, ventral striatum, and prefrontal cortex without affecting neocortical gamma, indicating separate circuit mechanisms. Within the bulb, a kainate receptor antagonist markedly reduced HFO, while AMPA receptor blockade had minimal effect. Blocking GABA-A receptors reduced HFO power while increasing gamma power, showing that fast inhibition is necessary for HFO expression. The findings suggest that tonic kainate-dependent depolarization recruits interneurons to generate an inhibitory network rhythm that drives HFO propagation through olfactory-limbic circuits.

Effects of ketamine on sleep and circadian rhythmicity in major depressive disorder and bipolar disorder: A systematic review.

Journal of Affective Disorders September 15, 2026 Rutger Boesjes, Claudia Oosterveld, Jeanine Kamphuis et al. 1 citation

Ketamine and its enantiomers show rapid antidepressant effects for major depressive disorder and bipolar disorder, but responses vary widely. This systematic review of 26 studies (1694 participants) found that ketamine treatment is linked to improved subjective sleep quality. Preliminary evidence suggests that baseline sleep disturbances and early sleep improvements may predict antidepressant response. Some studies also indicate beneficial effects on objective sleep and circadian rhythmicity, but this finding is tentative due to few published articles. The authors call for more research on objective circadian measures and potential synergy with chronotherapies.

Effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) on depression and anxiety in older adults: A systematic review and meta-analysis.

Journal of behavior therapy and experimental psychiatry September 1, 2026 Jieping Ding, Zafar Mehnaz Ali, Ateya Megahed Ibrahim et al.

Mindfulness-Based Cognitive Therapy (MBCT) may reduce depressive symptoms in adults aged 60 years and older compared with control conditions. A meta-analysis of three randomized controlled trials involving 178 participants found that MBCT was associated with significantly lower depressive symptom severity (pooled effect size Hedges g = -0.92, 95% confidence interval -1.30 to -0.55, with no heterogeneity). Evidence for anxiety and quality-of-life outcomes was limited and could not be pooled, and no trials reported relapse or recurrence. The authors note the evidence base remains small and heterogeneous, calling for larger, methodologically rigorous trials with standardized outcomes and longer follow-up.

Ketamine-related neural changes in treatment-resistant depression: A multimodal synthesis of fMRI and PET studies.

Journal of Affective Disorders September 1, 2026 Nesreen Sedeek, Carley Rivers, Lucas Williamson et al.

Ketamine's rapid antidepressant effects in treatment-resistant depression are linked to changes in brain activity, but previous studies have been hard to compare due to differences in imaging techniques, analysis methods, and timing. A review combining fMRI and PET studies found that ketamine-related effects commonly appear in subcortical brain regions, with more variable effects in cortical areas like the prefrontal and anterior cingulate cortices. Network-level patterns suggest involvement of the default-mode, ventral attention, and visual systems. These findings are hypothesis-generating and highlight the need for future studies that harmonize methods to directly connect circuit changes to molecular mechanisms and clinical outcomes.

Contribution of the Serotonin 5-HT2A Receptor to the Therapeutic Effect of Psilocin on Social Behavior Deficits in Mice Repeatedly Exposed to Social Defeat Stress.

Neuropsychopharmacol Rep September 1, 2026 Daisuke Ibi, Rika Takaba, Keisuke Yoshida et al.

In a mouse model of social defeat stress, the serotonin 5-HT2A receptor mediates the ability of psilocin to restore deficits in social behavior. Mice repeatedly subjected to social defeat stress showed reduced social interaction, and treatment with psilocin reversed this impairment. The therapeutic effect of psilocin was blocked by a 5-HT2A receptor antagonist and absent in mice lacking the 5-HT2A receptor, indicating that this receptor is necessary for the prosocial action of psilocin. These findings suggest that the 5-HT2A receptor is a key target for psilocin's effects on social behavior deficits caused by chronic stress.

Therapeutic properties of ayahuasca component N,N-Dimethyltryptamine in a pre-clinical model of Parkinson's disease.

Experimental Neurology September 1, 2026 Javier Calleja‐conde, Víctor Echeverry‐alzate, Marina Sanz-Sancristóbal et al.

In a preclinical model of Parkinson's disease, the compound N,N-dimethyltryptamine (DMT), the main psychoactive ingredient in ayahuasca, reduced neuroinflammation and preserved neurons in the nigrostriatal pathway. Treated animals also showed improvements in behavior. These results suggest DMT may have disease-modifying potential for Parkinson's disease, a progressive neurodegenerative disorder marked by loss of dopaminergic neurons and chronic inflammation, for which current treatments only relieve symptoms.

Functional recovery trajectories in cannabis-induced first-episode psychosis: The role of dissociative symptoms in the discrepancy between symptomatic improvement and functional outcomes.

Psychiatry Research September 1, 2026 Valerio Ricci, Andrea Paggi, Giovanni Martinotti et al.

In patients with cannabis-induced first-episode psychosis, dissociative symptoms—especially depersonalization and derealization—are strong independent predictors of poor functional recovery over 24 months. Among 72 patients, three recovery trajectories emerged: Rapid Recovery (34.7%, GAF +29.1 points), Gradual Recovery (40.3%, GAF +15.7 points), and Persistent Impairment (25.0%, GAF +4.7 points). A symptom-function discrepancy occurred in 31.9% of patients, where psychotic symptoms improved but functioning did not; these patients had higher baseline dissociation scores (33.8 vs. 18.1). Dissociation mediated 35% of cannabis's negative effect on functional outcomes. A high-risk subgroup (22%) with elevated dissociation, depression, and continued cannabis use showed minimal improvement despite treatment. Routine dissociation assessment and targeted interventions may improve outcomes.

Simultaneous LC-MS/MS determination of the emerging ketamine analogue 2F-2-oxo-PCPr and related compounds in human hair and application to forensic casework.

Forensic Science International September 1, 2026 Byungsuk Cho, Seonghoon Yeon, Sanghee Woo et al.

A white powder submitted to South Korea's National Forensic Service in early 2025 was identified as 2F-2-oxo-PCPr, a new ketamine analogue with fluorine replacing chlorine and a propyl group replacing the amine methyl group. Because ketamine produces hallucinogenic and dissociative effects by blocking NMDA receptors, this analogue may act similarly. To detect such substances in biological samples, researchers developed and validated a liquid chromatography-tandem mass spectrometry method for simultaneously measuring 2F-2-oxo-PCPr, 2F-2-oxo-PCE, 2F-deschloroketamine, ketamine, and their metabolites in human hair. The method met all validation criteria and was applied to hair from eight individuals suspected of using ketamine-related drugs. This is the first reported single hair-based workflow covering ketamine alongside three fluorinated analogues and their metabolites.

Ketamine and esketamine for the prevention of postpartum depression: A systematic review and network meta-analysis, with an integrated evidence synthesis.

Psychiatry Research September 1, 2026 Isis Lunsky, Gilmar Gutierrez, Xena Wang et al.

Postpartum depression (PPD) is common and harmful if untreated, with few effective prevention strategies. Ketamine and esketamine are rapid-acting antidepressants showing promise for PPD. This review searched five databases for peer-reviewed randomized controlled trials, pilot studies, and observational studies examining ketamine or esketamine for PPD prevention during pregnancy or postpartum, for both cesarean and vaginal deliveries. A network meta-analysis and narrative synthesis were used. Thirty-six studies were identified; five included vaginal delivery, thirty included cesarean section, and one did not specify delivery mode. Results suggested that ketamine and esketamine were well tolerated and may reduce PPD risk. However, data quality was low to very low, so results should be interpreted cautiously. More high-quality studies are needed.

Nightmares and cardiometabolic diseases in an adult population-based sample.

Journal of Psychosomatic Research September 1, 2026 Keyuan Liu, Geoffroy Solelhac, Nicola Andrea Marchi et al.

Frequent nightmares are linked to a higher risk of cardiometabolic diseases such as hypertension and diabetes. In a Swiss general-population study across three follow-ups, people with frequent nightmares had higher body mass index and greater prevalence of hypertension and diabetes than those without nightmares. Ecological momentary assessment confirmed a 2.53-fold higher odds of hypertension in the second follow-up. Polysomnography showed a lower pulse wave amplitude drops index in the frequent nightmare group, suggesting altered autonomic function, but salivary cortisol levels did not differ, indicating the stress hormone pathway alone does not explain the association. The findings suggest nightmares are associated with cardiometabolic risk, though the mechanisms remain unclear.

The subjective effects of △9-tetrahydrocannabinol: A systematic review and dose-response meta-regression.

Neuroscience and Biobehavioral Reviews September 1, 2026 Isabella Goodwin, Dominic Oliver, Edward Chesney et al.

A meta-analysis of 41 double-blind, placebo-controlled experiments involving 1,020 infrequent cannabis users found that acute THC administration increases feelings of high, anxiety, and tiredness, while decreasing alertness and contentedness, with no effect on calmness. Inhaled THC dose-dependently increased high and contentedness but decreased calmness, with greater consistency in high and contentedness at higher doses. On a 100-point scale, inhaling 5 mg THC increased high by 34.3 points, anxiety by 14.4, tiredness by 26.3, and calmness by 4.5, while decreasing alertness by 40.2 and contentedness by 71.0. Oral THC showed no significant subjective effects, though higher oral doses produced more consistent alertness. These findings can inform public health guidance on expected THC effects.