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Personalized Pharmaco-Lifestyle Interventions for Severe Mental Illnesses (LIFETRAIN)
Conditions: Severe Mental Illness; Depression / Major Depressive Disorder; Bipolar Disorder (BD); Schizophrenia
Interventions: Drug: Semaglutide (SEMA); Behavioral: Exercise module; Behavioral: Anti-inflammatory diet module; Behavioral: Sleep intervention module; Behavioral: Social prescribing module; Device: Closed-loop transcranial alternating current stimulation (CL-tACS); Behavioral: Structured lifestyle psychoeducation; Device: Sham CL-tACS
Sponsors: Ludwig-Maximilians – University of Munich
Not yet recruiting
Interventions: Drug: Semaglutide (SEMA); Behavioral: Exercise module; Behavioral: Anti-inflammatory diet module; Behavioral: Sleep intervention module; Behavioral: Social prescribing module; Device: Closed-loop transcranial alternating current stimulation (CL-tACS); Behavioral: Structured lifestyle psychoeducation; Device: Sham CL-tACS
Sponsors: Ludwig-Maximilians – University of Munich
Not yet recruiting
Reducing Intrusive Trauma Memories Using a Brief Mental Imagery Competing Task Intervention: Case Series of Trauma-Exposed Women in Iceland
Background: There is a need for scalable and simple interventions for trauma-exposed people. In this case series, we built on our previous case study and case series findings and further explored the use and potential effectiveness of a brief novel intervention to reduce the number of past intrusive memories of trauma. The imagery competing task intervention consists of a memory reminder and the visuospatial task Tetris played with mental rotation, targeting 1 intrusive memory at a time. Here, we test remote delivery of the intervention, including guidance from researchers without specialist mental health training, in a sample of women in Iceland with current intrusive memories from trauma. Objective: In a case series of trauma-exposed women, we aimed to explore whether this brief novel intervention reduces the number of established intrusive memories (primary outcome) and improves general functioning and symptom reduction in posttraumatic stress, depression, and anxiety (secondary outcomes). The acceptability of the intervention along with adaptations, that is, delivery by psychology students without specialist mental health training and digital delivery, was explored. Methods: Participants (N=8) monitored the number of intrusive memories from an index trauma (occurring 3‐16 years previously) in a daily diary at baseline, during the intervention, and postintervention at 1-month and 3-month follow-ups. The intervention was delivered digitally with guidance from clinical psychologists or psychology students. A repeated AB design was used (“A”: preintervention baseline, “B”: intervention phase). Intrusions were targeted one by one, creating repetitions of an AB design (ie, length of baseline “A” and intervention “B” varied for each memory). Results: The number of intrusive memories reduced for all participants from the baseline phase compared with the intervention phase, although the reduction was minimal for 2 participants (6.3%‐93%). The number of intrusive memories continued to reduce for 6 out of 8 participants (58%‐100% reduction at 1-month follow-up; 72%‐100% reduction at 3-month follow-up). Symptoms of posttraumatic stress, depression, and anxiety were reduced for most participants postintervention and continued to decrease during the follow-up periods. Functioning was improved for 7 of the 8 participants from baseline to postintervention and continued to improve at the follow-up assessments for 3 participants. The intervention delivered digitally and partly by students was perceived to be an acceptable way to reduce the frequency of intrusive memories by all participants (mean rating 9.5 out of 10). Conclusions: Data from this case series of traumatized women provide preliminary evidence for the effectiveness of this novel brief intervention in reducing intrusive memories of trauma occurring several years ago and in improving functioning and reducing core symptom burden. This study will inform a randomized controlled trial of this novel intervention, which may have considerable implications for large-scale clinical management of traumatized populations. Trial Registration: ClinicalTrials.gov NCT04209283; https://clinicaltrials.gov/study/NCT04209283 International Registered Report Identifier (IRRID): RR2-10.2196/29873
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Single Psilocybin Dose Relieves Depression for Over Three Months
Researchers in Sweden report that a single dose of psilocybin, a psychedelic compound found in mushrooms, can provide rapid relief from depressive symptoms. Results from a small-scale Phase II trial, published today in JAMA Network Open, show that patients experienced an improvement as soon as two days after treatment, with effects persisting for longer than three months.
”Our results suggest that psilocybin can provide rapid, clinically meaningful improvement in depression and may serve as an alternative to standard treatment when fast symptom reduction is important,” says Hampus Yngwe, MD, consultant psychiatrist and PhD student at the department of clinical neuroscience of the Karolinska Institutet in Stockholm.
Major depressive disorder is commonly treated with selective serotonin reuptake inhibitors (SSRIs), but most patients do not respond to this treatment or become resistant. In addition, their effects can typically take several weeks to be noticeable, and side effects are common.
Previous research had shown that a single dose of psilocybin can have antidepressant effects in people with treatment-resistant depression or anxiety disorders in patients with advanced cancer. The current study looked instead at the effects of this compound on “common” forms of major depressive disorder.
The study recruited a total of 35 people with moderate to severe recurrent depression, between 20 and 65 years of age. They were randomly assigned to receive either a single 25mg dose of psilocybin or niacin, an active placebo that causes a noticeable physical reaction. All patients received psychotherapeutic support before, during, and after treatment.
Participants were evaluated using the Montgomery–Åsberg depression rating scale (MADRS) to assess treatment effects at multiple time points after dosing. After a week, the group who received psilocybin saw an average MADRS score reduction of 9.7 points, compared to 2.4 points in the placebo group, and these effects persisted after two weeks and six weeks. At this point, 53% of participants who received psilocybin were in remission, compared to 6% in the placebo group.
A self-reported version of the MADRS revealed that patients saw antidepressant effects as early as day two after dosing, and continued to experience these positive effects for over three months.
A year after treatment, all patients who received psilocybin treatment remained in remission. However, many of the patients who received the placebo had also recovered at that point, showing no major statistical difference between both groups.
“The long-term effects are uncertain,” says Yngwe. “Repeated treatments may be needed to prevent relapse. This needs to be investigated in larger studies.”
Because the effects of psilocybin are strong and easily recognizable, many participants were able to tell whether they had received the treatment or the placebo. This is a common challenge scientists face when studying psychedelic treatments that can make it difficult for patients and researchers alike to separate the effects of the treatment from their expectations. “We want to understand how factors such as treatment expectations and lack of blinding affect the results, as previous studies may have exaggerated the treatment effects,” notes Yngwe.
Next, the researchers will analyze data from PET scans, blood, and cerebrospinal fluid samples collected from all patients before and after dosing. This will help them understand the physiological changes induced by psilocybin, and how these influence its observed antidepressant effects.
”Research suggests that the interaction between parts of the brain is impaired in depression and that this may be linked to changes in the connections between nerve cells, known as synapses,” says Yngwe. “In preclinical studies, psychedelics have been shown to stimulate synaptic growth. We therefore want to investigate whether psilocybin alters synaptic density in the brain.”
The post Single Psilocybin Dose Relieves Depression for Over Three Months appeared first on Inside Precision Medicine.
Large Language Models and Their Applications in Mental Health: Scoping Review
Background: Large language models (LLMs) are poised to transform mental health care, offering advanced capabilities in diagnosis, prognosis, and decision support. Since their inception, numerous mental health-focused LLMs have emerged in the scientific literature, reflecting the growing interest in leveraging these models across various clinical applications. With a broad range of models available, diverse optimization strategies, and multiple use cases, reviewing the current landscape is critical to understanding where future impact lies. Objective: This study aimed to conduct a scoping review investigating the use of LLMs in mental health across diagnostic, prognostic, and decision support tasks. Methods: We screened 3121 papers from PubMed, Scopus, and Web of Science for studies published between January 2023 and October 2025, using terms related to LLM and mental health. After removing duplicates, 2 reviewers (MCL and WWBG) independently screened the studies, with a third (JJK) to resolve conflicting opinions. We extracted and synthesized information on the models, use cases, datasets, and adaptation methods from selected papers. Results: In total, 41 papers were selected. Many studies included evaluations on OpenAI’s GPT series applications: GPT-4 (24 studies, 58.5%) and GPT-3.5 (16 studies, 39%). Others included Bidirectional Encoder Representations from Transformers-derived models (9 studies, 22%), LLaMA (8 studies, 19.5%), and RoBERTa-derived models (6 studies, 14.6%). While all studies initially applied out-of-the-box LLMs, several adapted them through few-shot learning or fine-tuning to better align with specific research goals. The most common use case was in diagnostics (31 studies, 75.6%), while the most common target condition was depression (11 studies, 26.8%). While many studies reported superior performance of LLMs, only a minority of studies (13 studies, 31.7%) validated LLM performance against clinician assessments using real patient data, with the majority relying on proxy outcomes such as clinical vignettes, examination questions, or social media posts. Conclusions: Despite rapid growth and diversity of LLM applications in mental health, the field remains nascent and exploratory. Future developments must emphasize consistent model adaptation procedures to ensure safety and clinical workflow alignment. Models must also be evaluated on robust evaluation criteria by using standardized protocols and real clinical outcome measures.
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A hierarchical machine learning model for predicting self-harm and suicidal behaviour in hospitalised patients with schizophrenia using clinical history and nursing observations
ObjectiveThis study aimed to develop and evaluate a two-layered machine learning framework that combines admission clinical information with longitudinal nursing observations to identify schizophrenia inpatients at high risk of self-harm or suicidal acts.MethodsWe retrospectively reviewed the records of 477 patients with schizophrenia hospitalised in Liaoning Province between July 2021 and July 2024. According to whether at least one self-injurious or suicidal episode was documented during the index admission, 159 individuals were assigned to a high-risk group and 318 to a non-high-risk group. At admission, 18 baseline variables (including age, sex, history of self-harm, hopelessness/depression, and educational attainment) were extracted from electronic medical records, and 39 nurse-rated behavioural items were scored weekly using the Psychiatric Patient Nursing Observation Scale. Static and dynamic feature sets were used to train six classifiers [regularized logistic regression (LR), support vector machine (SVM), extreme gradient boosting, random forest, multi-layer perceptron, and K-nearest neighbours]. The best static model (regularized LR) and the best dynamic model (SVM) were combined through probability-level weighted fusion to generate a hierarchical risk score.ResultsMultivariable analysis of admission features showed that previous self-harm [odds ratio (OR) = 4.323], hopelessness/depression (OR = 3.090), younger age (OR = 0.938), and higher educational level (OR = 1.357) were independent predictors of self-harm/suicidal behaviour. Among dynamic indicators, negative self-evaluation (OR = 2.303), self-reported depression (OR = 1.812), insomnia (OR = 1.768), talking to oneself (OR = 1.733), crying (OR = 1.700), and reduced conversation with others (OR = 1.422) remained significant. The optimised static LR model achieved an area under the curve (AUC) of 0.7564, and the dynamic SVM model reached an AUC of 0.8531. Their fusion further improved performance (AUC = 0.9048; sensitivity 0.8542; specificity 0.7789; accuracy 0.8042). This hierarchical model outperformed the best flat combined-feature model (SVM; AUC = 0.9022) in sensitivity (0.8542 vs. 0.6667), indicating a more clinically appropriate detection of high-risk patients.ConclusionA hierarchical machine learning approach that integrates baseline clinical history with repeated nursing assessments can effectively flag schizophrenia inpatients at high risk for self-harm and suicidal behaviour, supporting timely and individualised preventive strategies in psychiatric wards.
Context-dependent interaction between oxytocin gene polymorphisms and alcohol dependence in modulating negative emotions during acute alcohol withdrawal in adult males
ObjectiveThe importance of multiple gene-environment interaction (G × E) has been highlighted in understanding the etiology of negative emotions. This study examines the impact of oxytocin (OXT) polymorphisms (rs2740210, rs6133010, and rs2740209) in combination with alcohol dependence on anxiety and depression symptoms during acute alcohol withdrawal under different social and environmental contexts.MethodA total of 414 Chinese Han male adults undergoing acute alcohol withdrawal were recruited. Participants provided blood samples for genotyping, self-reported measures of depression and anxiety, assessments of alcohol dependence severity, and demographic information regarding social and environmental contexts.ResultsResults revealed a positive correlation between severity of alcohol dependence and symptoms of depression and anxiety, while oxytocin polymorphism did not have a direct effect on depressive and anxiety symptoms. A significant interaction between OXT polymorphism (rs2740210 and rs2740209) and alcohol dependence in relation to anxiety symptoms solely among adults living with family and/or those who were married was observed. Further analyses indicate that the GG and CC genotypes are risk genotypes, while the T allele (rs2740210) and G allele (rs2740209) are non-risk alleles in the interaction between OXT genotypes (rs2740210, rs2740209) and alcohol dependence on anxiety among the aforementioned participants.ConclusionsThese findings provide evidence for distinct G × E interaction effects on anxiety and depression symptoms during acute alcohol withdrawal, supporting the weak diathesis-stress model. Furthermore, the study highlights the importance of considering environmental factors when investigating the role of oxytocin as a biological substrate underlying social bonding and the regulation of negative emotions.
[Comment] Perinatal psychiatry: thinking in threes—before, during, and after pregnancy
Perinatal psychiatry is a recent specialty. Only a few countries offer specific training and specialised care, even though it is considered a major public health issue worldwide.1 Perinatal psychiatry remains ill-defined and has often been reduced to women’s mental health during pregnancy and postpartum. However, the World Psychiatric Association recognises that perinatal mental health is both a maternal (if not parental) and an infant mental health issue.2 Peripartum depression is considered the most common health risk for parents and their offspring.
[Editorial] Maternal depression: improving estimates and care
The first Wednesday of May marks World Maternal Mental Health Day, now celebrating a decade of advocacy to prioritise maternal mental health. Maternal depression is a prevalent illness that increases the risk of maternal morbidity and mortality, and contributes to adverse outcomes for offspring and family. Despite its substantial burden, maternal depression remains underdetected and undertreated.
Prior Heart Attack Linked to Faster Cognitive Decline Over Time
People who have experienced a heart attack, including those who had a “silent” heart attack that hadn’t been previously diagnosed, showed faster declines in memory and thinking skills over time, according to a study published in the journal Stroke. Researchers found that evidence of a previous myocardial infarction was associated with an accelerated rate of cognitive decline and a higher likelihood of developing cognitive impairment during more than a decade of follow-up, indicating this a cohort of patients who may need to take more proactive measures to retain cognitive acuity as they age.
“Having had a heart attack in the past may speed up the decline in memory and thinking over time,” said study lead author Mohamed Ridha, MD, an assistant professor of neurology at The Ohio State University. “Given the rising burden of dementia and cognitive decline among Americans, it is important to understand how cardiovascular disease affects their brain health. This knowledge can help heart attack survivors take steps to improve their brain health as they age.”
The research analyzed data from 20,923 adults enrolled in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study, a national cohort designed to examine racial and geographic disparities in stroke outcomes in the United States. Participants, who were enrolled between 2003 and 2007, had interpretable electrocardiograms and no evidence of cognitive impairment at the start of the study. Their average age was 63 years, with 62% identified as White adults and 38% as Black adults.
The team used a combination of self-reported medical history and electrocardiogram readings to determine if participants had evidence of a prior heart attack. The patients in the study were categorized into groups: those who had self-reported a heart attack, a clinically recognized heart attack confirmed by electrocardiogram, and silent heart attack, defined as electrocardiographic evidence of myocardial infarction without a prior diagnosis.
All participants took part in an annual telephone-based cognitive screening for a median of 10.1 years. The six-question assessment evaluated orientation and memory recall, with lower scores indicating poorer cognitive performance. Investigators adjusted for other factors that are known to be associated with cognitive decline including age, sex, race, education, exercise frequency, diabetes, smoking, blood pressure, depression, kidney function, and cardiovascular events that occurred during follow-up.
Among the study population, 2,183 participants had evidence of prior myocardial infarction at baseline. Of those cases, 1,098 were self-reported heart attacks, 281 were clinically recognized heart attacks confirmed by electrocardiogram, and 804 were silent heart attacks. Nearly 37% of all heart attacks identified in the study were clinically silent.
Compared with participants without a prior heart attack, heart attack survivors had an annual risk of developing cognitive impairment that was 5% higher that patients who had not suffered a heart attack. The accelerated decline was observed across all categories of prior heart attack, including silent myocardial infarction and was also consistent across races and sex.
The study adds to prior research that has linked cardiovascular disease and dementia risk and noted the importance of identifying such patients. “Previous investigations of incident coronary ischemic events have demonstrated that the impact on cognitive function is not immediate but manifests as a subsequent accelerated rate of long-term cognitive decline,” the researchers wrote. “Vascular contributions to cognitive impairment, including stroke, are prevalent and potentially modifiable factors underlying cognitive decline.”
The findings could help clinicians provide preventative care, since electrocardiograms and patient history are commonly available in routine practice. These tools could help clinicians identify patients who may benefit from counseling and monitoring related to cognitive health and Ridha noted that clinicians caring for heart attack survivors should discuss ways to reduce the risk of cognitive decline and dementia as patients age.
While the biological mechanisms linking heart attack and cognitive decline remain uncertain, the discussion proposed possible contributors, including microvascular disease, silent cerebral infarcts, systemic inflammation, reduced blood flow to the brain, and impaired amyloid clearance.
The post Prior Heart Attack Linked to Faster Cognitive Decline Over Time appeared first on Inside Precision Medicine.