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Hui Li,1– 3 Yanlong Liu,4– 6 Lifei Xing,7 Xiaoyu Yang,8 Jinzhong Xu,9 Qiushi Ren,1 Kuan-Pin Su,4,10,11 Yanye Lu,1 Fan Wang2,3,12 1Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, People’s Republic of China; 2Xinjiang Key Laboratory of Neurological Disorder Research, The Second Affiliated Hospital, Xinjiang Medical University, Urumqi 830063, People’s Republic of China; 3Psychosomatic Medicine Research Division, Inner Mongolia Medical University, Huhhot 010110, People’s Republic of China; 4Zhuji Institute of Biomedicine, School of Pharmaceutical Sciences, Wenzhou Medical University, Shaoxing 311800, People’s Republic of China; 5School of Mental Health, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 6The Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou 325035, People’s Republic of China; 7Department of Neurology, Inner Mongolia North Heavy Industries Group Corp. Ltd Hospital, Baotou 014030, People’s Republic of China; 8Beijing Jishuitan Hospital, Beijing 100035, People’s Republic of China; 9The Affiliated Wenling Hospital of Wenzhou Medical University, Wenling 317500, People’s Republic of China; 10An-Nan Hospital, China Medical University, Tainan, Taiwan; 11College of Medicine, China Medical University, Taichung, Taiwan; 12Beijing Hui-Long-Guan Hospital, Peking University, Beijing 100096, People’s Republic of ChinaCorrespondence: Fan WangBeijing Hui-Long-Guan Hospital, Peking University, Beijing 100096, People’s Republic of ChinaTel +86 10 62715511 ext. 6429Fax +86 10 62716285Email fanwang@bjmu.edu.cnBackground: Cigarette smoking has shown to be associated with sleep disturbance, especially prolonged sleep onset latency (SOL). Cigarette smoking stimulates the release of dopamine (DA) and serotonin (5-HT), which might promote awakening and inhibit rapid eye movement sleep. Dopamine transporter (DAT) and serotonin transporter play a key role in the reuptake of DA and 5-HT from the synaptic cleft into presynaptic neurons. However, the relationship among cigarette smoking, sleep disturbance and neurotransmitters has never been investigated in human cerebrospinal fluid (CSF).Methods: A total of 159 Chinese male subjects (81 active smokers and 78 non-smokers) who would undergo lumbar puncture before the surgery of anterior cruciate ligament reconstruction were recruited and 5mL-CSF samples were collected incidentally. CSF levels of DA, DAT, 5-HT, and serotonin transporter were measured using radioimmunoassay and ELISA. Sociodemographic data and the Pittsburgh Sleep Quality Index (PSQI) scale were collected before surgery.Results: PSQI global scores, SOL, and CSF DA levels were significantly higher in active smokers compared to non-smokers (2.00 [1.00– 4.75] scores vs 4.00 [3.00– 6.00] scores, p = 0.001; 10.00 [5.00– 15.00] minutes vs 15.00 [10.00– 30.00] minutes, p = 0.002; 87.20 [82.31– 96.06]ng/mL vs 107.45 [92.78– 114.38] ng/mL, p < 0.001), while CSF DAT levels were significantly lower in active smokers (0.35 [0.31– 0.39] ng/mL vs 0.29 [0.26– 0.34] ng/mL, p < 0.001).Conclusion: Cigarette smoking was indeed associated with sleep disturbance, shown by prolonged SOL, higher DA levels and lower DAT levels in CSF of active smokers.Keywords: sleep, cigarette smoking, dopamine, cerebrospinal fluid

Patients with depression have been extensively reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids (PUFAs), including significantly low eicosapentaenoic acid and docosahexaenoic acid in cell tissue [...]

The noninvasive brain and nerve stimulation (NIBNS) treatments had been widely applied in numerous psychiatric diseases. They exerted preferable efficacy and had been considered as an alternative or add-on treatment to the traditional pharmacotherapy. However, the risk of complication of seizure had seized the clinicians so that they feared about this potential complication. Actually, the NIBNS techniques have emerged as an alternative adjunctive treatment method for patients with epilepsy. However, the results of randomized controlled trials (RCTs) investigating the ability of NIBNS to reduce the frequency of seizures have been inconclusive. The aim of the current network meta-analysis (NMA) was to compare the efficacy and acceptability of various NIBNS techniques for reducing the frequency of seizures in patients with epilepsy. This frequentist model-based NMA included RCTs of NIBNS techniques for patients with epilepsy. The primary outcomes were seizure frequency change and acceptability (i.e., dropout rate). This NMA of 20 RCTs indicated that only 2-mA cathodal short-duration transcranial direct current stimulation (hc-sd-c-tDCS) was associated with significantly greater reduction in seizure frequency and significantly greater improvement in quality of life than the sham/control. Further, none of the investigated NIBNS techniques had significantly increased seizure frequency compared with the sham/control. In addition, all the investigated NIBNS techniques were associated with similar acceptability with the sham/control. Our results indicated that none of the investigated NIBNS techniques was associated with an increased risk of epileptic seizure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Purpose of Review: This review examines evidence from recent clinical trials on the therapeutic potential of omega-3 polyunsaturated fatty acids (PUFAs) in major depressive disorder (MDD). We focus on the effects in MDD with comorbidities, younger populations, and high-inflammation presentations., Recent Findings: PubMed, Cochrane, and Embase databases were systematically searched for studies published between May 2022 and May 2024. The search was conducted on randomized controlled trials using omega-3 PUFAs with participants with a clinical diagnosis of depression.Higher doses of eicosapentaenoic acid (EPA) (>1 g/day) improved measures of depression, particularly in MDD with elevated inflammation markers, comorbid cardiovascular diseases, late-life onset, and children and adolescent populations. Improvements in depressive symptoms were associated with increases in omega-3 PUFA-derived anti-inflammatory and proresolving lipid mediators. As adjuvant treatments, omega-3 PUFAs have potential benefits in mood, cognitive and metabolic functions, kynurenine and serotonin pathways, and alterations in corticolimbic functional connectivity., Summary: While evidence suggests promise, particularly for high-dose EPA and in inflammatory MDD subtypes, more research is needed to establish optimal dosing regimens, treatment duration, and patient subgroups most likely to benefit. Future studies should focus on sex differences, long-term effects, and potential synergies with other treatments., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Heart failure is a progressive condition associated with a high mortality rate. Despite advancements in treatment, many patients continue to experience less-than-ideal outcomes. ω-3 (n-3) polyunsaturated fatty acids (PUFAs) have been studied as a potential supplementary therapy for heart failure, but the optimal dosage and duration of supplementation remain unclear. This network meta-analysis (NMA) aimed to assess the efficacy of various n-3 PUFA supplementation regimens in patients with heart failure, focusing on dose-dependent and time-dependent effects. We conducted a systematic search for randomized controlled trials (RCTs) on n-3 PUFA supplementation in heart failure till 13 September, 2024. The primary outcome was the change in heart function, specifically left ventricular ejection fraction. Secondary outcomes included changes in peak oxygen consumption (VO 2 ), blood B-type natriuretic peptide concentrations, and quality of life. The safety analysis focused on dropout rates (i.e., patients leaving the study for any reason before completion) and all-cause mortality. A frequentist-based NMA was performed. This NMA, which included 14 RCTs with 9075 participants (mean age, 66.0 y; 23.3% female), found that high-dose n-3 PUFA supplementation (2000-4000 mg/d) over a duration of ≥1 y significantly improved left ventricular ejection fraction and peak VO 2 compared with those of control groups. Lower doses and shorter treatment periods did not produce the same benefits. No significant differences were found in dropout rates or all-cause mortality between the n-3 PUFAs and control groups. Long-term, high-dose n-3 PUFA supplementation, particularly with a predominance of docosahexaenoic acid or eicosapentaenoic acid, enhances cardiac function in patients with heart failure without increasing risk of adverse events. Further well-designed RCTs with long treatment durations (i.e., >1 y) and stringent heart failure inclusion criteria are necessary to confirm these findings and reduce potential biases. This trial was registered at PROSPERO as CRD42024590476., Competing Interests: Conflict of interest BS is supported by the NIHR Brendon Stubbs is part funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust. BS is also supported by the Maudsley Charity, King’s College London. All other authors report no conflicts of interest., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of the Review: Mounting evidence indicates that individuals with chronic obstructive pulmonary disease (COPD) face a heightened risk of severe outcomes upon contracting coronavirus disease 2019 (COVID-19). Current medications for COVID-19 often carry side effects, necessitating alternative therapies with improved tolerance. This review explores the biological mechanisms rendering COPD patients more susceptible to severe COVID-19 and investigates the potential of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in mitigating the severity of COVID-19 in COPD patients., Recent Findings: Current evidence indicates that COPD patients are at an increased risk of severe COVID-19 due to factors including compromised pulmonary function, dysregulated inflammation, weakened immune response, increased oxidative stress, elevated expression of angiotensin-converting enzyme (ACE2) receptors in the lungs, and genetic predispositions. Remarkably, n-3 PUFAs exhibit the potential in ameliorating the clinical outcomes of COPD patients with COVID-19 by modulating inflammation, reinforcing the body's antioxidant defenses, reducing viral entry and replication, and enhancing immunity. N-3 PUFAs hold potential for improving COVID-19 outcomes in patients with COPD. However, there has been limited investigation into the therapeutic effects of n-3 PUFAs in enhancing clinical outcomes for COPD patients. Rigorous clinical studies are essential to evaluate the impact of n-3 PUFAs on COPD patients with concurrent COVID-19 infection., Competing Interests: Declarations. Competing interest: The authors declare no competing interests. Human and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

There is no multi-country/multi-language study testing a-priori multivariable associations between non-modifiable/modifiable factors and validated wellbeing/multidimensional mental health outcomes before/during the COVID-19 pandemic. Moreover, studies during COVID-19 pandemic generally do not report on representative/weighted non-probability samples. The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is a multi-country/multi-language survey conducting multivariable/LASSO-regularized regression models and network analyses to identify modifiable/non-modifiable factors associated with wellbeing (WHO-5)/composite psychopathology (P-score) change. It enrolled general population-representative/weighted-non-probability samples (26/04/2020-19/06/2022). Participants included 121,066 adults (age=42±15.9 years, females=64 %, representative sample=29 %) WHO-5/P-score worsened (SMD=0.53/SMD=0.74), especially initially during the pandemic. We identified 15 modifiable/nine non-modifiable risk and 13 modifiable/three non-modifiable protective factors for WHO-5, 16 modifiable/11 non-modifiable risk and 10 modifiable/six non-modifiable protective factors for P-score. The 12 shared risk/protective factors with highest centrality (network-analysis) were, for non-modifiable factors, country income, ethnicity, age, gender, education, mental disorder history, COVID-19-related restrictions, urbanicity, physical disorder history, household room numbers and green space, and socioeconomic status. For modifiable factors, we identified medications, learning, internet, pet-ownership, working and religion as coping strategies, plus pre-pandemic levels of stress, fear, TV, social media or reading time, and COVID-19 information. In multivariable models, for WHO-5, additional non-modifiable factors with |B|>1 were income loss, COVID-19 deaths. For modifiable factors we identified pre-pandemic levels of social functioning, hobbies, frustration and loneliness, and social interactions as coping strategy. For P-scores, additional non-modifiable/modifiable factors were income loss, pre-pandemic infection fear, and social interactions as coping strategy. COH-FIT identified vulnerable sub-populations and actionable individual/environmental factors to protect well-being/mental health during crisis times. Results inform public health policies, and clinical practice., Competing Interests: Conflict of interest Conflict of interest statements of all authors are detailed in eTable 12., (Copyright © 2024. Published by Elsevier B.V.)

Neurodegenerative diseases (NDs) demonstrate a complex interaction with the immune system, challenging the traditional view of the brain as an "immune-privileged" organ. Microglia were once considered the sole guardians of the brain's immune response. However, recent research has revealed the critical role of peripheral immune cells located in key brain regions like the meninges, choroid plexus, and perivascular spaces. These previously overlooked cells are now recognized as contributors to the development and progression of NDs. This newfound understanding opens doors for pioneering therapeutic strategies. By targeting these peripheral immune cells, we may be able to modulate the brain's immune environment, offering an alternative approach to treat NDs and circumvent the challenges posed by the blood-brain barrier. This comprehensive review will scrutinize the latest findings on the complex interactions between these peripheral immune cells and NDs. It will also critically assess the prospects of targeting these cells as a ground-breaking therapeutic avenue for these debilitating disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The comorbidity of obesity and depression has major public health impacts, highlighting the need to understand their shared mechanisms. This study explored the connection between obesity and depression through the transient receptor potential V1 (TRPV1) signaling pathway, using obese/depressed murine models and clinical data. Mice fed a high-fat diet showed altered TRPV1 pathway expression in brain regions of the mice: downregulated in the medial prefrontal cortex (mPFC) and hippocampus, and upregulated in the hypothalamus and amygdala, influencing depression-like behaviors and inflammation. Treatments like eicosapentaenoic acid (EPA) and acupoint catgut embedding (ACE) reversed these effects, similar to observations in Trpv1 -/- mice. Furthermore, chemogenetic activation in the ventral mPFC also alleviated depression via TRPV1. In our clinical validation, single nucleotide polymorphisms (SNPs) in TRPV1-related genes (PIK3C2A and PRKCA) were linked to interferon-induced depression. These findings underscore the potential of targeting TRPV1 as a therapeutic approach for obesity-related depression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The high incidence and mortality rates of postoperative delirium (POD) among elderly patients highlights the pressing need for tailored prophylactic strategies. Despite various pharmacologic prophylactic strategies have been reported effective, their overall benefit and safety remain unclear in the geriatric population. Our network meta-analysis (NMA) aimed to systematically evaluate and rank the effectiveness of various pharmacological interventions in preventing POD in elderly patients., Methods: We conducted an extensive search of PubMed, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and Google Scholar for randomized controlled trials (RCTs) published up to August 1, 2023. We included RCTs examining pharmacological prophylactic effects of POD in elderly patients. To extract data in alignment with predefined areas of interest, we employed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The primary outcome was the incidence of POD. For secondary outcomes, we evaluated tolerability through all-cause discontinuation or drop-out rates, as well as all-cause mortality., Results: Our analysis encompassed a total of 44 RCTs involving 11,178 patients. Out of these, 26 RCTs involved comparisons with placebo only. For delirium prevention, the treatment groups receiving atypical antipsychotics (odds ratio (OR) of 0.27 and 95% confidence interval (CI) of 0.12-0.58), haloperidol (OR of 0.42; 95% CI of 0.25-0.71), dexmedetomidine (OR of 0.51 and 95% CI of 0.37-0.71 and melatonergic agents (MMA) (OR of 0.57 and 95% CI of 0.33-0.98) had significantly lower rates of delirium compared to the placebo group. Notably, the atypical antipsychotics ranked as the most effective treatment. For tolerability, no statistically differences in rates of dropout discontinuation and all-cause mortality among groups allocated to the placebo or individual pharmacological treatments., Conclusions: Based on indirect evidence, our network meta-analysis identified atypical antipsychotics, dexmedetomidine, MMA, and haloperidol as effective in preventing POD in the elderly, with atypical antipsychotics ranking highest. However, it is essential to note that these findings should be confirmed through further RCTs., Competing Interests: Declaration of Competing interest We have no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Essential hypertension (EH) with secondary insomnia is associated with increased risks of neuroinflammation, neuronal damage, and Alzheimer's disease (AD). However, its relationship with specific cerebrospinal fluid (CSF) biomarkers of neuronal damage and neuroinflammation remains unclear. This case-control study compared CSF biomarker levels across three groups: healthy controls (HC, n = 64), hypertension-controlled (HTN-C, n = 54), and hypertension-uncontrolled (HTN-U, n = 107) groups, all EH participants experiencing secondary insomnia. CSF samples from knee replacement patients were analyzed for key biomarkers, and sleep quality was assessed via the Pittsburgh Sleep Quality Index (PSQI). Our findings showed that the HTN-U group had significantly higher CSF levels of proinflammatory cytokines IL-6, TNF-α, and IL-17 than the HC and HTN-C groups (all p < 0.01). These cytokines correlated positively with secondary insomnia measures, with IL-6 (r = 0.285, p = 0.003), IL-17 (r = 0.324, p = 0.001), and TNF-α (r = 0.274, p = 0.005) linked to PSQI scores. In the HTN-U group, elevated IL-6, TNF-α, and IL-17 levels were also positively associated with neurofilament light (NF-L) and negatively with β-amyloid 42 (Aβ42), both key AD markers (all p < 0.05). Additionally, secondary insomnia was negatively correlated with Aβ42 (r = -0.225, p = 0.021) and positively with NF-L (r = 0.261, p = 0.007). Higher CSF palmitic acid (PA) levels observed in the HTN-U group were linked to poorer sleep quality (r = 0.208, p = 0.033). In conclusion, EH with secondary insomnia is associated with CSF biomarkers of neuronal damage, neuroinflammation, and neurodegeneration, suggesting a potential increase in AD risk among this population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose of Review: This review explores the intersection of urbanization, stress, inflammation, diet, lifestyle changes, and digital evolution as key factors influencing depression, emphasizing the necessity for integrative and evolutionary perspectives in mental health and intervention., Recent Findings: Epidemiological studies reveal a dramatic increase in common mental disorders, particularly depression, alongside parallel increases in suicide, unemployment, and divorce rates. Evolutionary perspectives suggest that mechanisms once advantageous for survival, such as stress responses and inflammatory processes, may contribute to mental health challenges in modern urban environments. Moreover, the mental health crisis among generation Z underscores the impact of digital evolution, where the shift from play-based to phone-based childhood contributes significantly to rising depression rates. Recent research highlights the significant role of omega-3 fatty acids, circadian rhythm regulation, mindfulness, and anti-inflammatory lifestyle interventions in mitigating depressive symptoms., Summary: The interplay between our evolutionary heritage and rapid societal changes has created a "symphony" of factors contributing to depression. Understanding these evolutionary mismatches in stress responses, inflammatory processes, dietary shifts, circadian disruptions, and digitalization provides new insights into the etiology of depression. This holistic approach, conceptualized as "harmonizing the inner orchestra," offers promising avenues for prevention and treatment strategies that address the multifaceted nature of depression in our modern world., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The rate of suicide attempts by patients with bipolar disorder is high. In addition to patient and country specific factors, environmental factors may contribute to suicidal behavior. Sunlight has multiple diverse impacts on human physiology and behavior. Solar insolation is defined as the electromagnetic energy from the sun striking a surface area on earth. We previously found that a large change in solar insolation between the minimum and maximum monthly values was associated with an increased risk of suicide attempts in patients with bipolar I disorder., Methods: The association between solar insolation and a history of suicide attempts in bipolar disorder was again investigated using an international database with 15% more data and more sites at diverse locations and countries., Results: Data were available from 5641 patients with bipolar I disorder living at a wide range of latitudes in 41 countries in both hemispheres. A large change in solar insolation between the minimum and maximum monthly values was associated with a history of suicide attempts in patients with bipolar I disorder, a replication of our prior analysis. The estimated model also associated state sponsored religion in the onset country, female gender, a history of alcohol or substance abuse, and being part of a younger birth cohort with a history of suicide attempts., Conclusions: A large change between the minimum and maximum monthly values of solar insolation was associated with a history of suicide attempts in bipolar I disorder, replicating our prior research. Physicians should be aware that daylight has wide ranging physiological and psychiatric impacts, and that living with large changes in solar insolation may be associated with an increased suicide risk., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki. Human Ethics and Consent to Participate declarations: not applicable. Competing interests: Eduard Vieta has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, AbbVie, Adamed, Alcediag, Angelini, Biogen, Beckley-Psytech, Biohaven, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, HMNC, Idorsia, Johnson & Johnson, Lundbeck, Luye Pharma, Medincell, Merck, Newron, Novartis, Orion Corporation, Organon, Otsuka, Roche, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, Teva, and Viatris, outside the submitted work., (© 2024. The Author(s).)

Background: Device-based treatments exist in psychiatry for decades, but are usually operated by clinicians and require multiple office visits. Near-infrared transcranial photobiomodulation (tPBM) is a safe neurostimulation modality with potential antidepressant and hypnotic effects. We investigated the feasibility and efficacy of adjunctive tPBM treatment, self-administered by a wearable headband., Methods: We randomized 48 outpatients with major depressive disorder (MDD) into tPBM or sham with 1:1 ratio. All participants were advised to receive the device-based intervention for at least 20 min daily at their preferred time and place for 8 weeks. The compliance and adverse events were monitored throughout the trial. The Hamilton Depression Rating Scale (HAMD), Beck's Depression Inventory (BDI) and Pittsburgh Sleep Quality Index (PSQI) were used to evaluate the symptoms from baseline until week-12., Results: Participants reported this self-administered intervention well-tolerated. Treatment compliance was equally good between various group-comparisons, and the adverse effects were minimal and transient. Post-treatment, the HAMD and BDI scores of patients in both tPBM group and sham group significantly decreased compared to baseline, with no between-group difference. However, a significant PSQI score reduction was only found in tPBM group from week-2 onward compared with baseline, with significant between-group difference lasting until week-12 (F 1,46  = 6.16, p = 0.017)., Limitations: This smaller sample size and short treatment and follow-up durations., Conclusions: Self-administered wearable tPBM appears to be a feasible and well-tolerated in MDD patients. The low-level dosimetry appeared insufficient to produce an antidepressant effect but effective in improving sleep quality. Further studies should investigate different dosimetry and intervention time. CLINICAL TRIALS REGISTRATION NUMBER IN CLINICALTRIAL.GOV: NCT04619121., (Copyright © 2024. Published by Elsevier B.V.)

Research on nutraceutical and dietary interventions in psychiatry has grown substantially, but progress is hindered by methodological inconsistencies and limited reporting standards. To address this, the International Society for Nutritional Psychiatry Research presents the first guidelines on clinical trial design, conduct, and reporting for future clinical trials in this area. Recommendations were developed using a Delphi process including eighteen researchers with considerable clinical trial expertise and experience in either methodology, nutraceutical, or dietary interventions in psychiatry. These guidelines provide forty-nine recommendations for clinical trial design and outcomes, five for trial reporting, and seven for future research priorities. The recommendations included in these guidelines are designed to inform both nutraceutical and dietary clinical trial interventions in Nutritional Psychiatry. Common themes include an emphasis on the importance of a multidisciplinary research team and integration of co-design processes into the conduct and design of clinical research, methods to improve transparency and replicability of trial outcomes, and measures to address common biases in nutrition trials. Furthermore, we provide recommendations for future research including examining a greater variety of nutraceutical and dietary interventions, scalable delivery models, effectiveness and implementation studies, and the need to investigate these interventions in the prevention and management of less studied psychiatric conditions (e.g. schizophrenia and bipolar disorder). Recommendations included within these guidelines are intended to improve the rigor and clinical relevance of ongoing and future clinical trials in Nutritional Psychiatry.

International studies measuring wellbeing/multidimensional mental health before/ during the COVID-19 pandemic, including representative samples for >2 years, identifying risk groups and coping strategies are lacking. COH-FIT is an online, international, anonymous survey measuring changes in well-being (WHO-5) and a composite psychopathology P-score, and their associations with COVID-19 deaths/restrictions, 12 a-priori defined risk individual/cumulative factors, and coping strategies during COVID-19 pandemic (26/04/2020-26/06/2022) in 30 languages (representative, weighted non-representative, adults). T-test, χ 2 , penalized cubic splines, linear regression, correlation analyses were conducted. Analyzing 121,066/142,364 initiated surveys, WHO-5/P-score worsened intra-pandemic by 11.1±21.1/13.2±17.9 points (effect size d=0.50/0.60) (comparable results in representative/weighted non-probability samples). Persons with WHO-5 scores indicative of depression screening (<50, 13% to 32%) and major depression (<29, 3% to 12%) significantly increased. WHO-5 worsened from those with mental disorders, female sex, COVID-19-related loss, low-income country location, physical disorders, healthcare worker occupations, large city location, COVID-19 infection, unemployment, first-generation immigration, to age=18-29 with a cumulative effect. Similar findings emerged for P-score. Changes were significantly but minimally related to COVID-19 deaths, returning to near-pre-pandemic values after >2 years. The most subjectively effective coping strategies were exercise and walking, internet use, social contacts. Identified risk groups, coping strategies and outcome trajectories can inform global public health strategies., Competing Interests: Declaration of competing interest Conflict of interest statements of all authors are detailed in eTable 8., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To identify the COVID-19 pandemic impact on well-being/mental health, coping strategies, and risk factors in adolescents worldwide., Method: This study was based on an anonymous online multi-national/multi-language survey in the general population (representative/weighted non-representative samples, 14-17 years of age), measuring change in well-being (World Health Organization-Five Well-Being Index [WHO-5]/range = 0-100) and psychopathology (validated composite P-score/range = 0-100), WHO-5 <50 and <29, pre- vs during COVID-19 pandemic (April 26, 2020-June 26, 2022). Coping strategies and 9 a priori- defined individual/cumulative risk factors were measured. A χ 2 , penalized cubic splines, linear regression, and correlation analyses were conducted., Results: Analyzing 8,115 of 8,762 initiated surveys (representative = 75.1%), the pre-pandemic WHO-5 and P-score remained stable during the study (excluding relevant recall bias/drift), but worsened during the pandemic by 5.55 ± 17.13 (SD) and 6.74 ± 16.06 points, respectively (effect size d = 0.27 and d = 0.28). The proportion of adolescents with WHO-5 scores suggesting depression screening (<50) and major depression (<29) increased from 9% to 17% and 2% to 6%. WHO-5 worsened (descending magnitude, with cumulative effect) in adolescents with a mental or physical disorder, female gender, and with school closure. Results were similar for the P-score, with the exception of school closure (not significant) and living in a low-income country, as well as not living in a large city (significant). Changes were significantly but minimally related to COVID-19 deaths/restrictions, returning to near-pre-pandemic values after >2 years. The 3 most subjectively effective coping strategies were Internet use, exercise/walking, and social contacts., Conclusion: Overall, well-being/mental health worsened (small effect sizes) during the early stages of the COVID-19 pandemic, especially in vulnerable subpopulations. Identified at-risk groups, association with pandemic-related measures, and coping strategies can inform individual behaviors and global public health strategies., Study Preregistration Information: Physical and mental health impact of COVID-19 on children, adolescents, and their families: The Collaborative Outcomes study on Health and Functioning during Infection Times - Children and Adolescents (COH-FIT-C&A); https://doi.org/10.1016/j.jad.2021.09.090 DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. We actively worked to promote sex and gender balance in our author group. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science., (Copyright © 2024 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

This study aimed to assess the ability of an artificial intelligence (AI)-based chatbot to generate abstracts from academic psychiatric articles. We provided 30 full-text psychiatric papers to ChatPDF (based on ChatGPT) and prompted generating a similar style structured or unstructured abstract. We further used 10 papers from Psychiatry Research as active comparators (unstructured format). We compared the quality of the ChatPDF-generated abstracts with the original human-written abstracts and examined the similarity, plagiarism, detected AI-content, and correctness of the AI-generated abstracts. Five experts evaluated the quality of the abstracts using a blinded approach. They also identified the abstracts written by the original authors and validated the conclusions produced by ChatPDF. We found that the similarity and plagiarism were relatively low (only 14.07% and 8.34%, respectively). The detected AI-content was 31.48% for generated structure-abstracts, 75.58% for unstructured-abstracts, and 66.48% for active comparators abstracts. For quality, generated structured-abstracts were rated similarly to originals, but unstructured ones received significantly lower scores. Experts rated 40% accuracy with structured abstracts, 73% with unstructured ones, and 77% for active comparators. However, 30% of AI-generated abstract conclusions were incorrect. In conclusion, the data organization capabilities of AI language models hold significant potential for applications to summarize information in clinical psychiatry. However, the use of ChatPDF to summarize psychiatric papers requires caution concerning accuracy., Competing Interests: Declaration of competing interest Declaration of interests All authors declared no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Major Depressive Disorder (MDD) is a prevalent mental health condition with a complex pathophysiology involving neuroinflammation, neurodegeneration, and disruptions in neuronal and glial cell function. Microglia, the innate immune cells of the central nervous system, release inflammatory cytokines in response to pathological changes associated with MDD. Damage-associated molecular patterns (DAMPs) act as alarms, triggering microglial activation and subsequent inflammatory cytokine release. This review examines the cellular mechanisms underlying MDD pathophysiology, focusing on the lipid-mediated modulation of neuroinflammation. We explore the intricate roles of microglia and astrocytes in propagating inflammatory cascades and discuss how these processes affect neuronal integrity at the cellular level. Central to our analysis are three key molecules: High Mobility Group Box 1 (HMGB1) and S100 Calcium Binding Protein β (S100β) as alarmins, and Neuron-Specific Enolase (NSE) as an indicator of neuronal stress. We present evidence from in vitro and ex vivo studies demonstrating how these molecules reflect and contribute to the neuroinflammatory milieu characteristic of MDD. The review then explores the potential of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) as neuroinflammation modulators, examining their effects on microglial activation, cytokine production, and neuronal resilience in cellular models of depression. We critically analyze experimental data on how ω-3 PUFA supplementation influences the expression and release of HMGB1, S100β, and NSE in neuronal and glial cultures. By integrating findings from lipidomic and cellular neurobiology, this review aims to elucidate the mechanisms by which ω-3 PUFAs may exert their antidepressant effects through modulation of neuroinflammatory markers. These insights contribute to our understanding of lipid-mediated neuroprotection in MDD and may inform the development of targeted, lipid-based therapies for both depression and neurodegenerative disorders.

Objective: Omega-3 polyunsaturated fatty acids ( n -3 PUFAs) have demonstrated protective effects in major depressive disorder (MDD) patients receiving antidepressant treatment. However, there have been a few double-blind randomized controlled trials focused on n -3 PUFAs as monotherapy in MDD, and the outcomes have been mixed. This study aimed to assess the clinical effects of n -3 PUFAs monotherapy in patients with MDD., Methods: A total of 60 patients with MDD participated in this 12-week double-blind randomized controlled trial. They were randomized to either the n -3 PUFAs group (n = 30; 3.2 g of eicosapentaenoic acid, EPA and docosahexaenoic acid, DHA per day) or the placebo group (n = 30; 3.2 g of soybean oil per day). The severity of depression was evaluated using the Hamilton Rating Scale for Depression (HRSD)., Results: The n -3 PUFAs group had a significantly lower HRSD score compared with the placebo group at week 4 ( p = 0.004), week 6 ( p = 0.006), week 8 ( p = 0.004), and week 12 ( p = 0.01). The n -3 PUFAs group showed slightly higher rates for both remission (26.7% vs. 10%, p = 0.095) and response (23.3% vs. 6.7%, p = 0.145) compared with the placebo group at week 12, but these differences did not reach statistical significance., Conclusions: These findings suggested that monotherapy of n -3 PUFAs could improve depression and potentially serve as an alternative option for MDD patients.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Major depressive disorder (MDD), affecting over 264 million individuals globally, is associated with immune system dysregulation and chronic neuroinflammation, potentially linked to neurodegenerative processes. This review examines blood-brain barrier (BBB) dysfunction in MDD, focusing on key regulators like matrix metalloproteinase 9 (MMP9), aquaporin-4 (AQP4), and ATP-binding cassette subfamily B member 1 (ABCB1). We explore potential mechanisms by which compromised BBB integrity in MDD may contribute to neuroinflammation and discuss the therapeutic potential of omega-3 polyunsaturated fatty acids (n-3 PUFAs). n-3 PUFAs have demonstrated anti-inflammatory and neuroprotective effects, and potential ability to modulate MMP9, AQP4, and ABCB1, thereby restoring BBB integrity in MDD. This review aims to elucidate these potential mechanisms and evaluate the evidence for n-3 PUFAs as a strategy to mitigate BBB dysfunction and neuroinflammation in MDD., (Copyright ©2024, Yale Journal of Biology and Medicine.)

Inflammation is a potential risk factor of voriconazole (VCZ) overdose, procalcitonin (PCT) is reported to act as a diagnostic marker for bacterial infections. However, the association of PCT with VCZ trough serum concentrations (VCZ-C min ) is not fully clear. Our study aims to investigate the associations between PCT and VCZ-C min . In this retrospective cohort study, we collected the clinical data of 147 patients who received VCZ and monitored the VCZ concentration of them in our hospital from August 2017 to August 2021. All patients underwent routine clinical examinations on the day or the day before VCZ administration. General information and clinical symptoms of these patients were recorded. Multivariate liner analysis showed that PCT was significantly associated with VCZ-C min (p < 0.001). Overall, it was shown that VCZ-C min was significantly increased by 0.32 µg/mL for each fold increment in PCT in crude model. In the minor adjusted model (Model 1, adjustment for sex, age, albumin, direct bi1irubin, WBC) and fully adjusted model (Model 2, adjustment for sex, age, albumin, direct bilirubin, WBC, AST and ALT), VCZ-C min was significantly increased by 0.23 µg/mL and 0.21 µg/mL, respectively, for each fold increment in PCT. In conclusion, this research reveals the correlation between PCT and VCZ-C min , indicating that PCT has the potential to serve as a valuable biomarker for drug monitoring in the treatment of VCZ., (© 2024. The Author(s).)

Observational studies suggest a potential correlation between antidepressants and increased lung cancer risks. However, existing studies are limited to small sample sizes, unadjusted covariates especially smoking status, and unclear exposure duration. We performed a large-scale retrospective cohort study to re-examine the association. We analyzed non-smokers and smokers separately to eliminate the confounding effect of smoking status. We found patients with long-term antidepressant use were at a lower risk of lung cancer in both smokers and non-smokers (odds ratio (OR), 0.61; 95% CI: 0.46-0.80, OR: 0.75; 95% CI: 0.65-0.86). None of the antidepressants was associated with an increased lung cancer risk., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Benzodiazepines (BZDs) are widely prescribed for anxiety disorders. However, the long-term implications on mental health remain uncertain, especially the potential association between chronic BZD use and subsequent diagnosis of mood and substance use disorders (SUDs)., Method: We conducted a 5-year retrospective cohort study by analyzing the TriNetX database, a real-time electronic medical record network. The study population was defined as patients aged 18-65 with anxiety disorders (ICD-10-CM: F40-F48). We employed propensity score matching to pair a BZD-exposed cohort (≥12 BZD prescriptions) with a BZD-unexposed control cohort. The outcomes were defined as depressive disorders, bipolar disorders, and SUDs. We employed Kaplan-Meier analyses to assess the survival probability over five years following diagnosis and BZD exposure; log-rank test to obtain the hazard ratio (HR) with 95 % confidence interval (CI)., Results: We identified and matched 76,137 patients in the study and control cohorts. Compared to the control cohort, the BZD-exposed group exhibited significantly higher risks of being diagnosed with depressive disorders (HR, 2.64; 95 % CI, 2.59-2.68), bipolar disorders (HR, 4.39; 95 % CI, 4.15-4.64), overall substance use disorders (HR, 3.00; 95 % CI, 2.92-3.08), alcohol use disorder (HR, 3.38; 95 % CI, 3.20-3.57), stimulant use disorder (HR, 3.24; 95 % CI, 2.95, 3.55), cannabis use disorder (HR, 2.93; 95 % CI, 2.75-3.11), inhalant use disorder (HR, 4.14; 95 % CI, 3.38-5.06), and nicotine use disorder (HR, 2.72; 95 % CI, 2.63-2.81)., Conclusion: Our findings demonstrate a concerning association between BZD use and an increased risk of being diagnosed with various mood disorders and SUDs., Competing Interests: We declare no conflict of interest by any authors., (© 2024 Published by Elsevier B.V.)

The prevalence of pediatric constipation ranges from 0.7 to 29.6% across different countries. Functional constipation accounts for 95% of pediatric constipation, and the efficacy of pharmacotherapy is limited, with a success rate of 60%. Several randomized controlled trials (RCTs) have shown the benefits of probiotic supplements in treating this condition. However, the reported strains of probiotics varied among the RCTs. We aimed to compare the efficacy and acceptability of different probiotic supplements for pediatric functional constipation. The current frequentist model-based network meta-analysis (NMA) included RCTs of probiotic supplements for functional constipation in children. The primary outcome was changes in bowel movement or stool frequency; acceptability outcome was all-cause discontinuation. Nine RCTs were included (N = 710; mean age = 5.5 years; 49.4% girls). Most probiotic products, used either alone or combined with laxatives, were associated with significantly better improvement in bowel movement or stool frequency than placebo/control. Protexin plus laxatives (standardized mean difference (SMD) = 1.87, 95% confidence interval (95% CI) = 0.85 to 2.90) were associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products. For the single probiotic interventions, only Lactobacillus casei rhamnosus Lcr35 was associated with significant efficacy compared to placebo/control treatments (SMD = 1.37, 95% CI: 0.32 to 2.43). All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments.  Conclusion: The results of our NMA support the application of an advanced combination of probiotics and laxatives for pediatric functional constipation if there is no concurrent contraindication.  Registration: PROSPERO (CRD42022298724). What is Known: • Despite of the high prevalence of pediatric constipation, which ranges from 0.7% to 29.6%, the efficacy of pharmacotherapy is limited, with a success rate of 60%. Several randomized controlled trials (RCTs) have shown the benefits of probiotic supplements in treating this condition. However, the reported strains of probiotics varied among the RCTs. The widely heterogeneous strains of probiotics let the traditional meta-analysis, which pooled all different strains into one group, be nonsense and insignificant. What is New: • By conducting a comprehensive network meta-analysis, we aimed to compare the efficacy and acceptability of different strains of probiotic supplements for pediatric functional constipation. Network meta-analysis of nine randomized controlled trials revealed that the most probiotic products, used either alone or combined with laxatives, were associated with significantly better improvement in bowel movement or stool frequency than placebo/control. Protexin plus laxatives was associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products. For the single probiotic interventions, only Lactobacillus casei rhamnosus Lcr35 was associated with significant efficacy compared to placebo/control treatments. All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments., (© 2024. The Author(s).)

Introduction: Despite its high lifetime prevalence rate and the elevated disability caused by posttraumatic stress disorder (PTSD), treatments exhibit modest efficacy. In consideration of the abnormal connectivity between the dorsolateral prefrontal cortex (DLPFC) and amygdala in PTSD, several randomized controlled trials (RCTs) addressing the efficacy of different noninvasive brain stimulation (NIBS) modalities for PTSD management have been undertaken. However, previous RCTs have reported inconsistent results. The current network meta-analysis (NMA) aimed to compare the efficacy and acceptability of various NIBS protocols in PTSD management., Methods: We systematically searched ClinicalKey, Cochrane Central Register of Controlled Trials, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov to identify relevant RCTs. The targeted RCTs was those comparing the efficacy of NIBS interventions, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and transcutaneous cervical vagal nerve stimulation, in patients with PTSD. The NMA was conducted using a frequentist model. The primary outcomes were changes in the overall severity of PTSD and acceptability (to be specific, rates of dropouts for any reason)., Results: We identified 14 RCTs that enrolled 686 participants. The NMA demonstrated that among the investigated NIBS types, high-frequency rTMS over bilateral DLPFCs was associated with the greatest reduction in overall PTSD severity. Further, in comparison with the sham controls, excitatory stimulation over the right DLPFC with/without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms, including depression and anxiety symptoms, and overall PTSD severity., Conclusions: This NMA demonstrated that excitatory stimulation over the right DLPFC with or without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms., Trial Registration: PROSPERO CRD42023391562., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The long-term mental health consequences of COVID-19 in children and adolescents remain unclear. We investigated the impact of COVID-19 infection on mental health after China's zero-COVID policy relaxation, focusing on symptom-specific and social-family risk factors for mental health issues in children and adolescents. In a longitudinal study, 8348 youths (aged 10-18) were assessed twice (T1: September to October 2022 and T2: April to May 2023). Mental health changes (Δ=T1-T2) were compared between COVID-19-infected (COVID+, n = 4108) and non-infected (COVID-, n = 4240). After balancing social-family confounding factors at T1 with propensity score-based inverse probability weights, multivariable logistic regression was employed to assess associations between COVID-19 infection and the onset/worsening of mental health symptoms. Multivariable logistic regression was conducted to explore specific acute COVID-19 symptoms and social-family risk factors associated with the onset/worsening of mental health symptoms in COVID + group. Compared to COVID- group, COVID + group exhibited lower overall mental health improvement (Δ). COVID + group was associated with increased risks of depression worsening (OR 1.20, 95 % CI 1.04-1.39), anxiety worsening (OR 1.30, 95 % CI 1.15-1.47), stress worsening (OR 1.23, 95 % CI 1.03-1.46), insomnia worsening (OR 1.21, 95 % CI 1.05-1.39), and emotional symptoms worsening (OR 1.72, 95 % CI 1.27-2.33). Moderate-to-severe difficulty thinking, breathlessness, and gastrointestinal symptoms were specific COVID-19 symptoms associated with worsening of various mental health outcomes. Furthermore, academic difficulties, economic disadvantages, family conflicts, food addiction, and alcohol consumption were identified as social-family risk factors for worsening mental health symptoms in COVID + youths. COVID-19 infection leaves lasting mental health scars in youths, extending beyond the acute phase. Specific symptoms, particularly cognitive dysfunction and respiratory/gastrointestinal distress play a significant role in this vulnerability. Social-family factors further modulate these effects, highlighting the need for comprehensive interventions that address both biological and psychosocial aspects. This study provides valuable insights for tailoring mental health support to youths navigating the consequences of the COVID-19 pandemic., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: Large language models (LLMs) have been suggested to play a role in medical education and medical practice. However, the potential of their application in the psychiatric domain has not been well-studied., Method: In the first step, we compared the performance of ChatGPT GPT-4, Bard, and Llama-2 in the 2022 Taiwan Psychiatric Licensing Examination conducted in traditional Mandarin. In the second step, we compared the scores of these three LLMs with those of 24 experienced psychiatrists in 10 advanced clinical scenario questions designed for psychiatric differential diagnosis., Result: Only GPT-4 passed the 2022 Taiwan Psychiatric Licensing Examination (scoring 69 and ≥ 60 being considered a passing grade), while Bard scored 36 and Llama-2 scored 25. GPT-4 outperformed Bard and Llama-2, especially in the areas of 'Pathophysiology & Epidemiology' (χ 2  = 22.4, P < 0.001) and 'Psychopharmacology & Other therapies' (χ 2  = 15.8, P < 0.001). In the differential diagnosis, the mean score of the 24 experienced psychiatrists (mean 6.1, standard deviation 1.9) was higher than that of GPT-4 (5), Bard (3), and Llama-2 (1)., Conclusion: Compared to Bard and Llama-2, GPT-4 demonstrated superior abilities in identifying psychiatric symptoms and making clinical judgments. Besides, GPT-4's ability for differential diagnosis closely approached that of the experienced psychiatrists. GPT-4 revealed a promising potential as a valuable tool in psychiatric practice among the three LLMs., (© 2024 The Authors. Psychiatry and Clinical Neurosciences © 2024 Japanese Society of Psychiatry and Neurology.)

Omega-3 polyunsaturated fatty acids (PUFAs) may benefit migraine improvement, though prior studies are inconclusive. This study evaluated the effect of eicosapentaenoic acid (EPA) on episodic migraine (EM) prevention. Seventy individuals with EM participated in a 12-week randomized, double-blind, placebo-controlled trial from March 2020 and May 2022. They were randomly assigned to either the EPA (N = 35, 2 g fish oil with 1.8 g of EPA as a stand-alone treatment daily), or the placebo group (N = 35, 2 g soybean oil daily). Migraine frequency and headache severity were assessed using the monthly migraine days, visual analog scale (VAS), Migraine Disability Assessment (MIDAS), Hospital Anxiety and Depression Scale (HADS), Migraine-Specific Quality-of-Life Questionnaire (MSQ), and Pittsburgh Sleep Quality Index (PSQI) in comparison to baseline measurements. The EPA group significantly outperformed the placebo in reducing monthly migraine days (-4.4 ± 5.1 days vs. - 0.6 ± 3.5 days, p = 0.001), days using acute headache medication (-1.3 ± 3.0 days vs. 0.1 ± 2.3 days, p = 0.035), improving scores for headache severity (ΔVAS score: -1.3 ± 2.4 vs. 0.0 ± 2.2, p = 0.030), disability (ΔMIDAS score: -13.1 ± 16.2 vs. 2.6 ± 20.2, p = 0.001), anxiety and depression (ΔHADS score: -3.9 ± 9.4 vs. 1.1 ± 9.1, p = 0.025), and quality of life (ΔMSQ score: -11.4 ± 19.0 vs. 3.1 ± 24.6, p = 0.007). Notably, female particularly benefited from EPA, underscoring its potential in migraine management. In conclusion, high-dose EPA has significantly reduced migraine frequency and severity, improved psychological symptoms and quality of life in EM patients, and shown no major adverse events, suggesting its potential as a prophylactic for EM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The prevalence of postoperative emergence delirium in paediatric patients (pedED) following desflurane anaesthesia is considerably high at 50-80%. Although several pharmacological prophylactic strategies have been introduced to reduce the risk of pedED, conclusive evidence about the superiority of these individual regimens is lacking. The aim of the current study was to assess the potential prophylactic effect and safety of individual pharmacotherapies in the prevention of pedED following desflurane anaesthesia., Methods: This frequentist model network meta-analysis (NMA) of randomized controlled trials (RCTs) included peer-reviewed RCTs of either placebo-controlled or active-controlled design in paediatric patients under desflurane anaesthesia., Results: Seven studies comprising 573 participants were included. Overall, the ketamine + propofol administration [odds ratio (OR) = 0.05, 95% confidence intervals (95%CIs) 0.01-0.33], dexmedetomidine alone (OR = 0.13, 95%CIs 0.05-0.31), and propofol administration (OR = 0.30, 95%CIs 0.10-0.91) were associated with a significantly lower incidence of pedED than the placebo/control groups. In addition, only gabapentin and dexmedetomidine were associated with a significantly higher improvement in the severity of emergence delirium than the placebo/control groups. Finally, the ketamine + propofol administration was associated with the lowest incidence of pedED, whereas gabapentin was associated with the lowest severity of pedED among all of the pharmacologic interventions studied., Conclusions: The current NMA showed that ketamine + propofol administration was associated with the lowest incidence of pedED among all of the pharmacologic interventions studied. Future large-scale trials to more fully elucidate the comparative benefits of different combination regimens are warranted., Trial Registration: PROSPERO CRD42021285200., (© 2023. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Parkinson's disease (PD) is intricately linked to abnormal gut microbiota, yet the specific microbiota influencing clinical outcomes remain poorly understood. Our study identified a deficiency in the microbiota genus Blautia and a reduction in fecal short-chain fatty acid (SCFA) butyrate level in PD patients compared to healthy controls. The abundance of Blautia correlated with the clinical severity of PD. Supplementation with butyrate-producing bacterium B. producta demonstrated neuroprotective effects, attenuating neuroinflammation and dopaminergic neuronal death in mice, consequently ameliorating motor dysfunction. A pivotal inflammatory signaling pathway, the RAS-related pathway, modulated by butyrate, emerged as a key mechanism inhibiting microglial activation in PD. The change of RAS-NF-κB pathway in PD patients was observed. Furthermore, B. producta-derived butyrate demonstrated the inhibition of microglial activation in PD through regulation of the RAS-NF-κB pathway. These findings elucidate the causal relationship between specific gut microbiota and PD, presenting a novel microbiota-based treatment perspective for PD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Sepsis is a critical medical condition associated with high mortality for patients. Current pharmacological strategies for sepsis management or prevention had not achieved satisfactory results. The omega-3 fatty acids, with anti-inflammatory benefits, are considered to be promising agents for sepsis management/prevention. The aim of this network meta-analysis (NMA) is to compare the efficacy of various dosages and formulations of fish oil supplements for sepsis management and sepsis prevention. The current NMA consisted of two parts: (1) sepsis management and (2) sepsis prevention. The PubMed, ClinicalKey, Embase, ProQuest, Cochrane CENTRAL, ScienceDirect, Web of Science, and ClinicalTrials.gov databases were systematically searched to date of February 22 nd , 2024 for relevant randomized controlled trials (RCTs). RCTs were eligible for inclusion if they enrolled participants with a diagnosis of sepsis or who with high risk for sepsis. All NMA procedures were conducted under the frequentist model. The primary outcomes assessed are (1) mortality rate in sepsis treatment or (2) incidence of sepsis in sepsis prevention. Our NMA, based on 28 RCTs and 1718 participants (mean age=51.6 years, mean female proportion=35.6 %), showed that (1) high dose parenteral fish oil supplement yield the lowest mortality rate in sepsis management in adult patients, and (2) high dose enteral fish oil supplement yield the lowest incidence of sepsis in pediatric patients. This study provides compelling evidence that high-dose fish oil supplements provide beneficial effects for both sepsis management and sepsis prevention. Our findings provide a preliminary rationale for future large-scale RCTs to investigate the role of fish oil supplementation in sepsis management or prevention., Competing Interests: Declaration of competing interest Ping-Tao Tseng, Bing-Yan Zeng, Pin-Yang Yeh, Bing-Syuan Zeng, Brendon Stubbs, John S. Kuo, Cheuk-Kwan Sun, Yu-Shian Cheng, Yen-Wen Chen, Tien-Yu Chen, Yi-Cheng Wu, Yu-Kang Tu, Pao-Yen Lin, Dian-Jeng Li, Chih-Sung Liang, Mein-Woei Suen, Yi-Che Lee, Wei-Chieh Yang, Chih-Wei Hsu, Yow-Ling Shiue, and Kuan-Pin Su declared that there were no any competing interests existed., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Patients with bipolar disorder (BD) receive traditional Chinese medicine (TCM) for clinical needs unmet with psychotropic medications. However, the clinical characteristics of practices and outcomes of TCM in BD are not fully understood. This cohort study investigated the clinical characteristics, principal diagnoses, TCM interventions, and TCM prescriptions in patients with BD., Methods: Data for a total of 12,113 patients with BD between 1996 and 2013 were withdrawn from Taiwan's longitudinal health insurance database 2000 (LHID 2000). The chi-square test was used for categorical variables, and the independent t -test was used for continuous variables. A p -value less than 0.05 indicated significance., Results: One thousand three hundred nineteen patients who visited TCM clinics after the diagnosis of BD were in the TCM group, while those who never visited TCM were in the non-TCM group ( n = 1053). Compared to the non-TCM group, patients in the TCM group had younger average age, a higher percentage of female individuals, more comorbidities of anxiety and alcohol use disorders, and higher mood stabilizer usage rates. The TCM group exhibited pain-related indications, including joint pain, myalgia, myositis, headache, and sleep disturbances. Corydalis yanhusuo and Shu-Jing-Huo-Xue-Tang were the most useful single herbs and herbal formulae., Conclusions: Physicians need to be aware of the use of TCM in patients with BD.

Aim: This study aimed to examine dose-effects of total pulses on improvement of depressive symptoms in patients with treatment-resistant depression (TRD) receiving repetitive transcranial magnetic stimulation (rTMS) over the left dorsal lateral prefrontal cortex (DLPFC)., Materials and Methods: The MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, PsycINFO, and ClinicalTrial.gov databases were systematically searched. We included randomized, double-blind, placebo-controlled trials (RCT) that used rTMS over left DLPFC in patients with TRD. Excluded studies were non-TRD, non-RCTs, or combined other brain stimulation interventions. The outcome of interest was the difference between rTMS arms and sham controls in improvement of depressive symptoms in a dose-response manner. A random-effects meta-analysis and dose-response meta-analysis(DRMA) was used to examine antidepressant efficacy of rTMS and association with total pulses., Results: We found that rTMS over left DLPFC is superior to sham controls (reported as standardized mean difference[SMD] with 95% confidence interval: 0.77; 0.56-0.98). The best-fitting model of DRMA was bell-shaped (estimated using restricted cubic spline model; R 2 =0.42), indicating that higher doses (>26,660 total pulses) were not associated with increased improvement of depressive symptoms. Stimulation frequency(R 2 =0.53) and age(R 2 =0.51) were significant moderators for the dose-response curve. Furthermore, 15-20 Hz rTMS was superior to 10 Hz rTMS (0.61, 0.15-1.10) when combining all doses., Conclusions: Our findings suggest higher doses(total pulses) of rTMS were not always associated with increased improvement of depressive symptoms in patients with TRD, and that the dose-response relationship was moderated by stimulation frequency and age. These associations emphasize the importance of determining dosing parameters to achieve maximum efficacy., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: The aim of this network meta-analysis (NMA) was to assess whether participants assigned to a placebo and standard of care (SoC) group had different major coronavirus disease 2019 (COVID-19)-related outcomes than those assigned to SoC alone., Design: Frequentist model-based NMA., Setting: We searched for randomised controlled trials (RCTs) of Janus kinase/Bruton tyrosine kinase inhibitors for the management of COVID-19., Participants: Patients with COVID-19 infection., Main Outcome Measures: The primary outcome was the 28-day all-cause mortality, and secondary outcomes were: (1) use of mechanical ventilation; (2) secondary bacterial infection; (3) acceptability (i.e. drop-out rate); and (4) safety (i.e. serious adverse events). We conducted an NMA using the frequentist model. Effect sizes were estimated using odds ratios (ORs) with 95% confidence intervals (95% CIs)., Results: We identified 14 eligible RCTs enrolling a total of 13,568 participants with COVID-19. Participants assigned to placebo plus SoC had a significantly higher risk of 28-day all-cause mortality than those receiving SoC alone (OR = 1.39, 95% CI = 1.07-1.79). This finding did not change substantially by subgroup analysis stratified by epidemiology factor, pandemic history progression and statistical methodologic consideration. In addition, none of the treatments investigated were associated with a significantly different risk of secondary bacterial infection, acceptability or safety compared with the SoC group., Conclusions: This NMA suggested a higher all-cause mortality in patients treated with placebo plus SoC compared with those treated with SoC alone. However, caution is advised in interpreting these results due to the absence of a direct head-to-head comparison. Future research should critically evaluate the necessity of placebo administration in COVID-19 RCTs and consider alternative study designs to minimise potential biases. Trial registration: The current study was approved by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (TSGHIRB No. B-109-29) and registered in PROSPERO (CRD42022376217).

This clinical practice guideline on the supply of the omega-3 docosahexaenoic acid and eicosapentaenoic acid in pregnant women for risk reduction of preterm birth and early preterm birth was developed with support from several medical-scientific organizations, and is based on a review of the available strong evidence from randomized clinical trials and a formal consensus process. We concluded the following. Women of childbearing age should obtain a supply of at least 250 mg/d of docosahexaenoic+eicosapentaenoic acid from diet or supplements, and in pregnancy an additional intake of ≥100 to 200 mg/d of docosahexaenoic acid. Pregnant women with a low docosahexaenoic acid intake and/or low docosahexaenoic acid blood levels have an increased risk of preterm birth and early preterm birth. Thus, they should receive a supply of approximately 600 to 1000 mg/d of docosahexaenoic+eicosapentaenoic acid, or docosahexaenoic acid alone, given that this dosage showed significant reduction of preterm birth and early preterm birth in randomized controlled trials. This additional supply should preferably begin in the second trimester of pregnancy (not later than approximately 20 weeks' gestation) and continue until approximately 37 weeks' gestation or until childbirth if before 37 weeks' gestation. Identification of women with inadequate omega-3 supply is achievable by a set of standardized questions on intake. Docosahexaenoic acid measurement from blood is another option to identify women with low status, but further standardization of laboratory methods and appropriate cutoff values is needed. Information on how to achieve an appropriate intake of docosahexaenoic acid or docosahexaenoic+eicosapentaenoic acid for women of childbearing age and pregnant women should be provided to women and their partners., (Copyright © 2023. Published by Elsevier Inc.)

Migraine is a highly prevalent neurologic disorder with prevalence rates ranging from 9% to 18% worldwide. Current pharmacologic prophylactic strategies for migraine have limited efficacy and acceptability, with relatively low response rates of 40% to 50% and limited safety profiles. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are considered promising therapeutic agents for migraine prophylaxis. The aim of this network meta-analysis (NMA) was to compare the efficacy and acceptability of various dosages of EPA/DHA and other current Food and Drug Administration-approved or guideline-recommended prophylactic pharmacologic interventions for migraine. Randomized controlled trials (RCTs) were eligible for inclusion if they enrolled participants with a diagnosis of either episodic or chronic migraine. All NMA procedures were conducted under the frequentist model. The primary outcomes assessed were 1) changes in migraine frequency and 2) acceptability (i.e., dropout for any reason). Secondary outcomes included response rates, changes in migraine severity, changes in the frequency of using rescue medications, and frequency of any adverse events. Forty RCTs were included (N = 6616; mean age = 35.0 y; 78.9% women). Our analysis showed that supplementation with high dosage EPA/DHA yields the highest decrease in migraine frequency [standardized mean difference (SMD): -1.36; 95% confidence interval (CI): -2.32, -0.39 compared with placebo] and the largest decrease in migraine severity (SMD: -2.23; 95% CI: -3.17, -1.30 compared with placebo) in all studied interventions. Furthermore, supplementation with high dosage EPA/DHA showed the most favorable acceptability rates (odds ratio: 1.00; 95% CI: 0.06, 17.41 compared with placebo) of all examined prophylactic treatments. This study provides compelling evidence that high dosage EPA/DHA supplementation can be considered a first-choice treatment of migraine prophylaxis because this treatment displayed the highest efficacy and highest acceptability of all studied treatments. This study was registered in PROSPERO as CRD42022319577., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Cigarette smoking increases both the risk for insulin resistance and amyloid-β (Aβ) aggregation, and impaired brain insulin/insulin-like growth factor 1 (IGF1) signaling might increase risk factors for Alzheimer's disease (AD). We aimed to investigate the association among cerebrospinal fluid (CSF) insulin sensitivity/IGF1, glucose/lactate, and Aβ42 and further explore whether insulin sensitivity contributed to the risk for AD in active smokers., Methods: In this cross-sectional study, levels of insulin, IGF1, and lactate/glucose of 75 active smokers and 78 nonsmokers in CSF were measured. Three polymorphisms regulating IGF1 were genotyped. Analysis of variance was used to compare differences of variables between groups. Partial correlation was performed to test the relationship between CSF biomarkers and smoking status. General linear models were applied to test the interaction of the effect of single nucleotide polymorphisms and cigarette smoking on CSF IGF1 levels., Results: In the CSF from active smokers, IGF1 and lactate levels were significantly lower (p = .016 and p = .010, respectively), whereas Aβ42 (derived from our earlier research) and insulin levels were significantly higher (p < .001 and p = .022, respectively) as compared to the CSF from nonsmokers. The AG + GG genotype of rs6218 in active smokers had a significant effect on lower CSF IGF1 levels (p = .004) and lower CSF insulin levels in nonsmokers (p = .016)., Conclusions: Cigarette smoking as the "at-risk" factor for AD might be due to lower cerebral insulin sensitivity in CSF, and the subjects with rs6218G allele seem to be more susceptible to the neurodegenerative risks for cigarette smoking., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

This study investigated the efficacy and safety of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in relapse prevention of bipolar disorder (BD), addressing the shortcomings of current medications. Thirty-one stable BD patients were randomized to receive n-3 PUFAs or placebo for 6 months and intergroup differences in the incidence of the recurrence of bipolar depression were assessed. Differences in depression severity, manic symptoms, and routine biochemical parameters were also assessed. Interestingly, n-3 PUFAs demonstrated a favorable preventive effect on bipolar depression recurrence (p=0.005; Log-Rank) and reduced depression severity compared to placebo, and were well-tolerated, suggesting their potential as a safe prophylactic therapy for BD., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) and other forms of dementia represent major public health challenges but effective therapeutic options are limited. Pathological brain aging is associated with microvascular changes and impaired clearance systems. The application of omega-3 polyunsaturated fatty acids (n-3 or omega-3 PUFAs) is one of the most promising nutritional interventions in neurodegenerative disorders from epidemiological data, clinical and pre-clinical studies. As essential components of neuronal membranes, n-3 PUFAs have shown neuroprotection and anti-inflammatory effects, as well as modulatory effects through microvascular pathophysiology, amyloid-beta (Aβ) clearance and glymphatic pathways. This review meticulously explores these underlying mechanisms that contribute to the beneficial effects of n-3 PUFAs against AD and dementia, synthesizing evidence from both animal and interventional studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: ChatGPT may act as a research assistant to help organize the direction of thinking and summarize research findings. However, few studies have examined the quality, similarity (abstracts being similar to the original one), and accuracy of the abstracts generated by ChatGPT when researchers provide full-text basic research papers., Objective: We aimed to assess the applicability of an artificial intelligence (AI) model in generating abstracts for basic preclinical research., Methods: We selected 30 basic research papers from Nature, Genome Biology, and Biological Psychiatry. Excluding abstracts, we inputted the full text into ChatPDF, an application of a language model based on ChatGPT, and we prompted it to generate abstracts with the same style as used in the original papers. A total of 8 experts were invited to evaluate the quality of these abstracts (based on a Likert scale of 0-10) and identify which abstracts were generated by ChatPDF, using a blind approach. These abstracts were also evaluated for their similarity to the original abstracts and the accuracy of the AI content., Results: The quality of ChatGPT-generated abstracts was lower than that of the actual abstracts (10-point Likert scale: mean 4.72, SD 2.09 vs mean 8.09, SD 1.03; P<.001). The difference in quality was significant in the unstructured format (mean difference -4.33; 95% CI -4.79 to -3.86; P<.001) but minimal in the 4-subheading structured format (mean difference -2.33; 95% CI -2.79 to -1.86). Among the 30 ChatGPT-generated abstracts, 3 showed wrong conclusions, and 10 were identified as AI content. The mean percentage of similarity between the original and the generated abstracts was not high (2.10%-4.40%). The blinded reviewers achieved a 93% (224/240) accuracy rate in guessing which abstracts were written using ChatGPT., Conclusions: Using ChatGPT to generate a scientific abstract may not lead to issues of similarity when using real full texts written by humans. However, the quality of the ChatGPT-generated abstracts was suboptimal, and their accuracy was not 100%., (©Shu-Li Cheng, Shih-Jen Tsai, Ya-Mei Bai, Chih-Hung Ko, Chih-Wei Hsu, Fu-Chi Yang, Chia-Kuang Tsai, Yu-Kang Tu, Szu-Nian Yang, Ping-Tao Tseng, Tien-Wei Hsu, Chih-Sung Liang, Kuan-Pin Su. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 25.12.2023.)

Background: Moderate-to-severe cancer related fatigue occurs in 45% of patients with cancer and interferes with many aspects of quality of life. Although physical exercise has level 1 evidence for improvement of cancer related fatigue, it has a relatively high behavioural demand compared with other non-pharmacological interventions. The aim of this updated meta-analysis was to address the efficacy of light therapy in improving cancer related fatigue in patients with cancer., Methods: We included randomised controlled trials investigating the efficacy of bright white light (BWL) therapy in ameliorating cancer related fatigue in patients with cancer. This meta-analysis was conducted using a random-effects model. The target outcomes were changes in cancer related fatigue associated with BWL or dim red light (DRL)., Results: There were 9 articles with 231 participants included. The main results revealed that daily morning BWL for 30 min was associated with significantly better improvement in fatigue severity compared with DRL ( k =5, Hedges' g =-0.414, 95% CI -0.740 to -0.087, p=0.013). The subgroup without psychiatric comorbidities ( k =4, Hedges' g =-0.479, 95% CI -0.801 to -0.156, p=0.004) was associated with significantly better improvement in fatigue severity with BWL than with DRL. In contrary, BWL was not associated with significantly different changes in depression severity or quality of life compared with DRL. Finally, BWL was associated with similar acceptability (ie, dropout rate) and safety profile (ie, any discomfort) as those of DRL., Conclusions: This meta-analysis provides an updated evidence on the rationale for application of BWL in ameliorating cancer related fatigue in patients with different types of cancer., Trial Registration Number: INPLASY202140090., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)