Research Square
April 20, 2022
Aviv Aharon-Almagor, Frederick S. Barrett
People who have used hallucinogens show greater openness to new experiences and higher cognitive ability scores compared to non-users, along with denser structural connectivity in white matter tracts linked to cognition, emotion, and creativity. The study compared 53 hallucinogen users with 53 matched non-users from a public database, using diffusion tensor imaging and psychological assessments. Hallucinogen users also reported more lifetime use of other illicit drugs. These findings suggest hallucinogen use may be associated with lasting changes in brain structure and personality, offering clues to possible neural mechanisms behind therapeutic effects.
Research Square
Jack Swain, Davis Carter, Leonardo Vando et al.
Among 13,963 adults with moderate-to-severe sleep disturbances who received at-home ketamine-assisted therapy for depression, 67.4% showed at least a 1-point improvement on a single sleep-related item from a depression screening tool after two sessions. By session six, 76.8% of completers met that threshold, and the average score dropped 48.8% from baseline. However, the study could not separate sleep changes from mood improvement because all participants were treated for depression and no control group was included. Side effects were reported by 3.7% to 5.0% of participants across sessions.
Research Square
Katelyn Halpape, Raelle Pashovitz, Annabelle Wanson et al.
A small pilot program evaluated a hospital-to-outpatient intranasal racemic ketamine maintenance therapy for treatment-resistant depression. Five adult inpatients who had responded to intranasal ketamine in hospital continued treatment at a community centre, completing up to 14 sessions over 192 days. Depressive symptoms decreased or stabilized, and quality of life increased or stabilized. No serious adverse events occurred; mild side effects included anxiety and nausea, and slight blood pressure increases did not require intervention. The authors conclude the therapy appears feasible and well tolerated, but limited effectiveness conclusions can be drawn from this small study.
Research Square
Amit Kumar
A 24-year-old woman experienced possession trance attacks, a condition involving altered consciousness where a person's identity is replaced by a spirit or deity, with amnesia for the event. Her entire family developed shared delusional beliefs, and multiple members also had possession attacks over time. Such attacks can be misdiagnosed as psychotic illnesses like schizophrenia. The case highlights the cultural and familial context of possession trance, which must cause distress or impairment and not be due to psychosis or substance use.
Research Square
Sean M. Viña
People who use psychedelics are less likely to seek formal mental health care, including medication and outpatient treatment, even when experiencing high psychological distress. Analyzing data from over 458,000 participants in a national US survey between 2010 and 2018, the study found that as distress levels increase, psychedelic users become even less inclined to use formal care compared to non-users. This suggests a heightened risk of self-medication as psychedelics become more culturally and legally accepted.
Research Square
Alice Le Berre
In adults with treatment-resistant depression, esketamine was associated with early microstructural changes in the dentate gyrus of the hippocampus: reduced fractional anisotropy and increased orientation dispersion index, consistent with greater dendritic complexity. Lower baseline left-dentate gyrus fractional anisotropy correlated with greater improvement at two weeks, and a decrease in fractional anisotropy over that period also correlated with improvement. These changes suggest esketamine may promote hippocampal plasticity, and baseline diffusion MRI metrics could serve as candidate biomarkers for treatment response. The study included 12 adults with treatment-resistant depression and 24 matched controls, but larger studies are needed.
Research Square
Norihiro Okada, Kenshiro Oshima, Akiko Maruko et al.
Non-responders to ketamine treatment for depression show elevated viral infection markers based on intron retention (IR) gene analysis of RNA-seq data. Several IR genes associated with viral infection returned to healthy levels after ketamine regardless of responder status, suggesting non-responders are not resistant to ketamine but rather have an extremely high inflammatory state that the drug's effects cannot overcome. Excluding one transcriptomic outlier with extreme viral infection did not change IR gene conclusions but did alter differentially expressed gene (DEG) results, supporting the authors' claim that IR genes may be more useful markers of depression than DEGs.
Research Square
Minna Chang
Ketamine can cause ulcerative cystitis, a bladder condition with lower urinary tract symptoms and kidney damage, in over 25% of regular recreational users. This complication had not been reported in therapeutic use for depression until now. A 28-year-old woman started on ketamine for depression developed cystitis, confirmed by urine tests. This is the first reported case of ketamine-induced cystitis from treatment-dose ketamine for antidepressant therapy.
Research Square
Majid Eslami, Laleh Khorshidi, Maryam Ghasemi et al.
In rats, the recreational drug MDMA (Ecstasy) impairs spatial memory and increases oxidative stress and cell death in the hippocampus. Atorvastatin (5, 10, 20 mg/kg) and rosuvastatin (20 mg/kg), given orally for 21 days, prevented these memory deficits and reduced the MDMA-induced rise in reactive oxygen species, lipid peroxidation, and caspase-3 and -9 activities. The results suggest that these statins protect against MDMA neurotoxicity by suppressing oxidative stress and apoptosis.
Research Square
Taqwa B. Thanoon, Zeina A. Althanoon
Depression during pregnancy can harm offspring brain development and behavior. Common antidepressants like SSRIs carry risks because they cross the placenta. Ketamine is being explored as an alternative. This study in mice examined the effects of ketamine on offspring of mothers that experienced stress. Female mice were divided into groups: control, maternal stress, stress plus fluoxetine, and stress plus ketamine. Behavioral tests measured anxiety, anhedonia, and despair in the offspring. Maternal stress increased anxiety-like behaviors, and both ketamine and fluoxetine reversed some effects. However, fluoxetine was more effective at reducing despair. Ketamine moderately reduced anhedonia compared to controls. More research on dose and timing is needed to optimize ketamine treatment.
Research Square
July 20, 2026
In a post-hoc analysis of a randomized controlled trial, esketamine was associated with a reduction in anhedonia symptoms, as measured by the Snaith-Hamilton Pleasure Scale, compared to placebo. The effect was observed in patients with treatment-resistant depression who had not responded to prior antidepressant therapy. The findings suggest that esketamine may have a specific therapeutic effect on anhedonia, a core symptom of depression characterized by loss of interest or pleasure.
Research Square
July 10, 2026
A multidimensional framework is introduced for comparing theories of consciousness, representing conscious states as vectors with physical (P), cognitive/computational (C), and noetic (N) components. The noetic dimension captures structured aspects of data or phenomenology not explained by current physical and cognitive models, treated as a testable latent variable. Using a linear-algebraic analogy, the framework clarifies how theories differ in explanatory assumptions and how these can be evaluated through perturbation, identifiability, and invariance criteria. It outlines mappings between neuroelectromagnetic dynamics and phenomenology, and describes empirical predictions and protocols for comparing theories based on empirical findings.
Research Square
July 8, 2026
Psychological change during online mindfulness-based cognitive therapy for depression unfolds through a dynamic interplay of cognitive, emotional, and behavioral processes. A convergent mixed-methods analysis of daily diary data from participants reveals that improvements in depressive symptoms are linked to shifts in rumination, self-compassion, and engagement with mindfulness practices. The findings suggest that change occurs incrementally, with participants experiencing both setbacks and breakthroughs, and that the therapeutic process is non-linear and context-dependent.
Research Square
July 7, 2026
The nocebo effect, where negative expectations lead to adverse outcomes, is linked to altered connectivity in the default mode network (DMN) in people with migraine. In a functional MRI study, individuals with migraine who exhibited stronger nocebo responses showed distinct patterns of DMN connectivity compared to those with weaker responses. The findings suggest that DMN connectivity may play a role in modulating nocebo responses in migraine, pointing to a neural mechanism underlying this phenomenon.
Research Square
June 22, 2026
A wheel of awareness–based mindfulness intervention reduced psychopathology and improved awareness of internal states in a sample of adults. Participants who completed the intervention showed significant decreases in symptoms of depression, anxiety, and stress, along with enhanced interoceptive awareness and self-compassion, compared to a control group. The findings suggest that structured mindfulness training focused on cultivating inner access can benefit mental health by strengthening the ability to perceive and understand internal experiences.
Research Square
June 22, 2026
Brief mindfulness meditation alters brain functional network connectivity during emotion regulation in college students. Using functional near-infrared spectroscopy (fNIRS) and graph theory analysis, the study found that a short mindfulness meditation session changed how brain regions communicate while participants regulated their emotions. The results suggest that even brief mindfulness practice can influence neural network organization related to emotional processing.
Research Square
June 17, 2026
A mindfulness-based resilience training program improved mental, physical, and social health outcomes among law enforcement officers. The training reduced stress and burnout while enhancing emotional regulation and social functioning. Results suggest that such programs may support officer well-being in a high-stress occupation.
Research Square
June 15, 2026
A study examining how mindfulness relates to anxiety and depression over time found that within individuals, increases in mindfulness were linked to decreases in anxiety and depression. The research used longitudinal data to track these associations, showing that changes in mindfulness levels within a person were associated with corresponding changes in their symptoms of anxiety and depression.
Research Square
June 7, 2026
Among lung cancer patients, distinct profiles of self-transcendence are associated with different levels of quality of life. A latent profile analysis identified three subgroups: low, moderate, and high self-transcendence. Patients in the high self-transcendence group reported significantly better quality of life across physical, psychological, social, and spiritual domains compared to those in the low group. The findings suggest that fostering self-transcendence may be a meaningful target for psychosocial interventions aimed at improving well-being in this population.
Research Square
May 13, 2026
A theoretical framework called the Dynamic Existence Threshold (DET) is proposed for measuring consciousness in complex systems. The DET posits that consciousness arises when a system's internal dynamics cross a critical threshold of integrated information and causal complexity. The paper outlines mathematical and conceptual tools to quantify this threshold, drawing on integrated information theory and dynamical systems theory. The authors argue that the DET offers a principled way to identify conscious systems, from biological organisms to potentially artificial ones, without relying on behavioral or anthropocentric criteria. The framework aims to resolve longstanding debates about which systems possess consciousness and to what degree.
Research Square
May 11, 2026
Xiaoming Yang, Jian Lyu, Jubo Wang et al.
In people with mild cognitive impairment (MCI), carrying the APOE ε4 gene variant—the strongest genetic risk factor for cognitive decline—is linked to shrinkage in specific parts of the brain's default mode network (DMN), particularly the dorsomedial prefrontal cortex (DMPFC) subsystem. Among 116 MCI patients and 60 cognitively normal older adults, APOE ε4 carriers with MCI showed selective atrophy in the gyrus rectus and superior temporal pole (TPOsup) compared to non-carriers. The TPOsup atrophy explained about 30% of the negative effect of APOE ε4 on global cognition, measured by the Mini-Mental State Examination, and was strongly tied to impaired orientation. The TPOsup may be a key brain region linking APOE ε4 to cognitive decline in MCI and could serve as an imaging marker for risk stratification.
Research Square
April 13, 2026
Mindfulness-Based Stress Reduction (MBSR) reduced occupational stress and improved quality of work life among secondary school teachers. The program, an 8-week intervention, led to lower stress levels and enhanced work-life quality compared to a control group. The findings suggest that MBSR can be an effective approach for addressing teacher burnout and well-being in educational settings.
Research Square
April 6, 2026
The study examines how cultural estrangement—feeling different from one's culture—interacts with self-esteem to affect brain activity in the default mode network (DMN), a set of brain regions linked to self-referential thought. Among individuals with low self-esteem, higher cultural estrangement was associated with greater DMN activity, suggesting a burden. Conversely, for those with high self-esteem, higher cultural estrangement corresponded to reduced DMN activity, indicating it may function as an asset. The findings indicate that the psychological impact of feeling culturally different depends on one's level of self-esteem, with the DMN reflecting this interaction.
Research Square
February 9, 2026
Jonathan S Ryan, Timothy J Mcdermott, Boris Botzanowski et al.
Temporal interference (TI) electrical stimulation can target the ventral striatum (VS) during breath-focused mindfulness meditation to alter reward processing and emotionality. In 19 healthy adults aged 18–36, active 8 Hz TI stimulation, compared to sham, increased the reward positivity potential (RewP) in EEG recordings during a reward task, indicating engagement of the VS. The effect was specific to reward processing, not an unrelated brain response. Active TI also reduced negative emotionality, and these emotional changes corresponded with increased RewP amplitude. The findings suggest TI can precisely target deep brain structures and produce short-term continued effects on reward-related functioning when combined with meditation.
Research Square
February 3, 2026
Lucid dreaming can be used as a tool for transformative learning, allowing individuals to engage in deliberate self-exploration and personal growth within the dream state. The text argues that intentional lucid dreaming, when guided by a transformative learning agenda, can facilitate profound shifts in self-awareness, beliefs, and behaviors. This approach treats lucid dreams as a space for practicing new perspectives, confronting fears, and integrating insights, potentially leading to lasting psychological change. The paper outlines a theoretical framework for using lucid dreaming as a method of adult education and personal development, emphasizing its potential for fostering critical reflection and transformation.