bluuebunny/crossref_metadata_2025_split huggingface dataset:
MITOCHONDRIAL DYSFUNCTION IN BONE DENSITY METABOLISM IN PATIENTS WITH OPIOID USE DISORDER UNDER METHADONE MAINTENANCE TREATMENT
Authors: Hsu *Wenyu 
Published: February 2025

Abstract

Background
Recent studies have also shown that mitochondrial function and oxidative stress might play important roles in bone metabolism. Whether patients with opioid use disorder (OUD) experienced a decrease in bone density and an increased risk of osteoporosis and fractures through this mechanism is still unknown. Therefore, we examined the mitochondrial function between health control subjects the OUD patients under methadone maintenance treatment.

Methods
We conducted a cross-sectional cohort study. Patients with OUD receiving methadone maintenance treatment in Changhua Christian Hospital in Taiwan were recruited. We compared the difference between patients with OUD and without OUD in Mitochondrial DNA (mtDNA) copy number, oxidative modification of mtDNA index(mtDNA(DeltaCT)), and 8-hydroxy-2'-deoxyguanosine.

Results
Finally, 29 patients from MMT were allocated in opioid group. 37 health control subjects were allocated in control group. Patients in opioid group had significantly lower mtDNA than those in control group. Besides, patients in opioid group also had significantly lower DeltaCT and 8-hydroxy-2'-deoxyguanosine than those in control group.

Conclusions
Mitochondrial dysfunction was found in patients with OUD in our study. The precise role of mitochondrial dysfunction in bone density metabolism in this population should be further investigated.

References
Wen-Yu Hsu, et al. (2019) Association between opioid use disorder and fractures: a population-based study. Addiction. 114(11):2008-2015.
Wen-Yu Hsu, et al. (2018) Medications Used for Cognitive Enhancement in Patients With Schizophrenia, Bipolar Disorder, Alzheimer's Disease, and Parkinson's Disease. Frontiers in Psychiatry. 9:91.
ASSOCIATION OF NEUROFILAMENT LIGHT CHAIN WITH THE ANTIDEPRESSANT EFFECTS OF LOW-DOSE KETAMINE INFUSION AMONG PATIENTS WITH TREATMENT-RESISTANT DEPRESSION
Authors: Wu Hui-Ju , Chen *Mu-Hong , Lin Wei-Chen 
Published: February 2025

Abstract

Background
The role of neurofilament light chain (NFL) in treatment-resistant depression (TRD) is unclear. Whether baseline NFL concentrations are associated with the antidepressant effects of low- dose ketamine infusion has not been determined.

Methods
The NFL concentrations of 71 patients with TRD and 17 healthy controls were assessed. Patients with TRD were randomly administered a single infusion of 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, or normal saline. Depressive symptoms were assessed prior to infusion and sequentially at postinfusion timepoints (after 240 min and 2–7 and 14 days after infusion) using the Hamilton Depression Rating Scale (HDRS).

Results
After adjustment for age, sex, and body mass index, patients with TRD were more likely to have higher concentrations of NFL than healthy controls (p &lt;0.001). A generalized estimating equation model with adjustments for infusion group, age, sex, body mass index, and baseline HDRS scores showed that baseline NFL concentrations were positively associated with subsequent HDRS scores following low-dose ketamine infusion (p = 0.038).

Discussion
Higher concentrations of NFL were observed among patients with TRD compared with healthy controls. Baseline NFL concentrations may predict the antidepressant effects of low-dose ketamine infusion.

References
1.Chen et al. Int J Neuropsychopharmacol 25(2): 99-105.
2.Lin et al. Int J Neuropsychopharmacol. 2023 Jul 25;pyad045.
MODULATION OF THE ANTIDEPRESSANT RESPONSE OF KETAMINE BY AN IMMUNOSUPPRESSANT RAPAMYCIN: A PROSPECTIVE RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED STUDY IN THE PATIENTS WITH REFRACTORY DEPRESSION
Authors: Su *Tungping , Chen Mu-Hong 
Published: February 2025

Abstract

Background
Our ketamine studies on the refractory depression (TRD) in the past 10 years have observed a short effect of a single dose of ketamine infusion lasting less than14 days. The antidepressant effect of ketamine was believed to activate the mechanistic target of rapamycin complex 1 (mTORC1), and produce synaptogenesis. Theoretically, inhibition of mTORC1 by an immunosuppressant rapamycin, prior to ketamine infusion, its antidepressant effect by ketamine would be diminished. However, in a comparison study using rapamycin plus ketamine vs. placebo plus ketamine, Abdallah found the antidepressant effect of the former was 47% whereas the later was 13 %, indicating that rapamycin might have other mechanisms beyond activation of mTORC1. To assess the role of rapamycin in ketamine treatment of TRD patients and to test if rapamycin might enhance and prolong the antidepressant effect of ketamine, we will conduct a parallel, randomized, double blind and placebo controlled study.

Method
The clinical trial has two study phases: in phase 1 study, 48 subjects with TRD will be enrolled. Two group of patients with each 24 subjects, randomly sampled, will receive either oral rapamycin 6 mg or placebo 2 hours before ketamine (0.5mg/kg) infusion once every two weeks for three times. Ratings for depression, anxiety and suicidality will be assessed at baseline, 2nd week, 4th week and 6th week.
Response is defined by 50% reduction of the baseline mood symptoms at each timepoint and 2 out of 3 - timepoint response is defined as clinical responder. The outcome is to compare the number of responder between these two parallel trial groups. The responder obtained from phase 1 trial will be enrolled for the phase 2 open-label study. These subjects will continue to receive oral rapamycin 6 mg, 2 hours prior to a single dose of ketamine 0.5mg/kg infusion at the timepoint of the end of 6th week.

Result
Our initial results revealed 24 subjects (50%) received oral rapamycin 6mg + ketamine (0.5mg/kg) infusion while another 24 subjects received oral placebo + ketamine (0.5mg/kg) infusion. Response rate was found equally in the rapamycin ketamine group and placebo ketamine group. The effect of rapamycin ketamine group was not superior to that of the placebo ketamine group.

Conclusion
The initial finding was not compatible with the previous result from Abdallah’ s study, and did not show that rapamycin might prolong the duration of efficacy of ketamine.. Further detailed analysis might answer the differences.
PREDICTING RELAPSE FROM THE TIME TO REMISSION DURING THE ACUTE TREATMENT OF DEPRESSION: A RE-ANALYSIS OF THE STAR*D DATA
Authors: Kubo *Kaoruhiko , Sakurai Hitoshi , Tani Hideaki , Watanabe Koichiro , Uchida Hiroyuki 
Published: February 2025

Abstract

Background
Major depressive disorder (MDD) is a recurrent illness. However, there is still lack of clinical data to predict relapse at an early point in patients with depression.

Aims and Objectives
The objective of this analysis was to investigate the association between the time taken to achieve remission in the acute phase, and the subsequent relapse rate or time to relapse using the Sequenced Treatment Alternatives to Relieve Depression dataset.

Method
Data of 1,296 outpatients with nonpsychotic depression who entered a 12-month naturalistic follow-up period after achieving remission with citalopram for up to 14 weeks were analyzed. One-way analysis of variance and the Jonckheere-Terpstra trend test were performed to compare the relapse rates and days to relapse during the follow-up period among those who achieved remission at weeks 2, 4, 6, 9, 12, and 14. Remission and relapse were defined as scores of &lt;=5 and &gt;=11, respectively, on the 16- Item Quick Inventory of Depressive Symptomatology and Self-Report. Multivariate logistic regression analysis was also performed in order to examine other demographic and clinical characteristics which are associated with subsequent relapse.

Results
A total of 1,093 participants achieved remission during Step 1 treatment and received at least one assessment during the follow-up period. The mean± SD weeks taken to achieve remission were 6.4±3.8. Among them, 362 (33.1%) patients relapsed during the follow-up period. The mean± SD days to subsequent relapse after remission were 160.0±99.8. The relapse rates were significantly different among those who achieved remission each week (F(5, 1087)=4.995, p &lt;0.001). The lowest and highest relapse rates were observed in those who achieved remission at weeks 4 (25.7%) and 12 (42.4%), respectively, with a significant difference (p =0.006). There was also a significant negative trend between the weeks taken to achieve remission and the days to relapse (z=-6.13, p &lt;0.001). In the multivariate logistic regression analysis, weeks at achieving remission status were associated subsequent relapse in the follow-up phase (OR=1.05±0.03, p=0.02). Older age, longer current episodes and baseline severity of depression were also significantly associated with subsequent relapses during the follow-up period.

Discussion & Conclusions
The present findings demonstrated that achieving remission at earlier weeks during treatment was associated with a lower relapse rate and a longer time to relapse during the one- year follow-up period. These results indicate that patients with depression who show a faster response to antidepressant treatment are more likely to maintain remission in the long term. Thus, to prevent relapse, it is critical to closely monitor patients who take a longer time to achieve remission.
NEURAL MECHANISMS OF ACCELERATED ITBS FOR TREATMENT- RESISTANT DEPRESSION: A DOUBLE-BLIND SHAM-CONTROLLED NEUROIMAGING STUDY
Authors: Li *Cheng-Ta , Cheng Chih-Ming , Wu Hui-Ting , Bai Ya-Mei , Su Tung-Ping 
Published: February 2025

Abstract

Background
Intermittent theta-burst stimulation (iTBS), as an updated form of repetitive transcranial magnetic stimulation (rTMS), was effective in treating treatment-resistant depression (TRD)1,2,3. 10-Hz rTMS at left prefrontal cortex (PFC) was reported to have antidepressant effects by modulating the activities in bilateral frontal-cingulo-temporal circuit2. Although both 10-Hz rTMS and iTBS were found to be effective, iTBS (80% motor threshold, 1800 pulses) acted differently by modulating the activities in midline structures, such as cingulate cortex and precuneus. Although the clinical effects were not enhanced compared to single session of iTBS treatment per day, we recently reported that 2 uninterrupted sessions of iTBS were also effective4. However, it remains elusive whether accelerated protocols (i.e., two uninterrupted sessions per day: prolonged iTBS x 2, piTBS*2) may also be effective through modulation in the midline structures.

Methods
Patients with antidepressant-resistant major depressive disorder were randomly assigned and to the piTBS*2 group, rTMS*2 group (10Hz, 120% motor threshold, 3000pulses/session, 2 sessions/day), and sham treatment group. Before and after the trials, 18F-FDG PET was applied and depression severity by 17-item Hamilton Depression Rating Scale (HDRS- 17) was evaluated.

Results
HDRS-17 scores decreased significantly in all three groups. Voxel-based analysis revealed that the piTBS*2 group showed increased activities after treatment in the midline structures including anterior and middle cingulate cortex and precuneus. By contrast, rTMS increased the bilateral frontal and temporal lobe activities.

Conclusion
Accelerated iTBS modulated the metabolism in the midline structures, but the direction of modulation is opposite to the findings reported in the singles-session iTBS protocol. Findings in the rTMS*2 group were similarr with past studies. Our results suggested that neural mechanisms of iTBS was not linear and dose-dependent.

References
Cheng-Ta Li* et al. Efficacy of Prefrontal Theta-Burst Stimulation in Refractory Depression: A Randomized Sham-Controlled Study. Brain, 2014 Jul;137(Pt 7):2088-98. Cheng-Ta Li* et al. Effects of prefrontal theta-burst stimulation on brain function in treatment-resistant depression. Brain Stimulation. 2018;11(5):1054-1062.
Cheng-Ta Li* et al. Antidepressant Efficacy of Prolonged Intermittent Theta Burst Stimulation Monotherapy for Recurrent Depression and Comparison of Methods for Coil Positioning: A Randomized, Double-Blind, Sham-controlled Study. Biological Psychiatry, Mar. 2020
Cheng-Ta Li* et al. The longer, the better ? Longer left-sided prolonged intermittent theta burst stimulation in patients with major depressive disorder. Asian J Psychiatry. 2023
BEHAVIORAL ANALYSES OF ANTIDEPRESSANT-LIKE EFFECT OF SEROTONERGIC PSYCHEDELICS IN MICE
Authors: Ibi *Daisuke , Takaba Rika , Yoshida Keisuke , Mamiya Takayoshi , Kitagaki Shinji , Hiramatsu Masayuki 
Published: February 2025

Abstract

Background
Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide, and DOI exert a hallucinatory effect through the serotonin 5-HT2A receptor (5-HT2A). Recent studies have revealed that serotonergic psychedelics have therapeutic potential for neuropsychiatric disorders, including major depressive and anxiety-related disorders.

Aims & Objectives
The involvement of 5-HT2A in mediating the therapeutic effects of serotonergic psychedelics remains unclear. In this study, we analyzed the role of 5-HT2A in the occurrence of anxiolytic- and antidepressant-like effects of serotonergic psychedelics such as psilocin, an active metabolite of psilocybin, DOI, and TCB-2 in mice 24 h after treatment.

Method
Male C57BL/6J mice (7–9 weeks old) were utilized in this study. The forced-swimming test (FST) and tail-suspension test (TST) were performed to investigate the antidepressant-like effect of psychedelics in mice. The anxiolytic-like effect of psychedelics was assessed using the novelty-suppressed feeding test (NSFT). Mice subjected to either chronic unpredictable mild stress (CUMS) or chronic corticosterone (CORT) treatment were employed as animal models of depression. All drugs were administered intraperitoneally.

Results
Mice with acute psychedelic treatment exhibited significantly shorter immobility times in the FST and TST than vehicle-treated control mice. These effects were eliminated by pretreatment with volinanserin, a 5-HT2A antagonist. Surprisingly, the decreasing immobility time in the FST in response to acute psilocin treatment was sustained for at least three weeks. In the NSFT, the latency to feed, an indicator of anxiety-like behavior, was decreased by acute administration of psilocin; however, pretreatment with volinanserin did not antagonize this effect. In contrast, DOI and TCB-2 did not affect the NSFT performance in mice. Furthermore, psilocin, DOI, and TCB-2 treatment did not affect the spontaneous locomotor activity or head-twitch response, a hallucination-like behavior in rodents. Lastly, we observed that mice subjected to either CUMS or CORT treatment exhibited a decrease in immobility time in the FST, which was reversed by a single dose of DOI.

Discussion & Conclusion
These results suggest that 5-HT2A plays a central role in the antidepressant effects of serotonergic psychedelics, which may contribute to the therapeutic effects of psychedelics in animal models of depression.
USING MULTI-SCALE ENTROPY ANALYSIS IN FMRI DATA TO EXAMINE THE COGNITIVE FUNCTION IN PATIENTS OF LATE-LIFE DEPRESSION AFTER ONE-YEAR FISH OIL SUPPLEMENT
Authors: Lin *Chemin , Lee Shwu-Hua , Huang Chih-Mao , Wu Yu-Wen , Chang You-Xun , Liu Ho-Ling , Ng Shu-Hang , Cheng Ying-Chih , Chiu Chih-Chiang , Wu Shun-Chi Wu 
Published: February 2025

Abstract

Background
Late-life depression (LLD) is a risk factor for dementia and cognitive decline. Fish oil supplement is efficacious for depressive symptoms with cognitive protective benefits. While there is limited strategy to deter cognitive decline in older adults, examining the cognitive protection in LLD by using fish oil can potentially provide a new promise.

Aims & Objectives
In addition to using double-blind randomized controlled trial to examine the clinical effects of fish oil in LLD, we also explore the neural mechanism by using pre-and post fMRI scans.

Method
A 52-week trial was conducted. Complexity analysis (multi-scale sample entropy) was employed to analyze rs-fMRI data. We also correlate the MRI changes with changes in cognitive function and inflammatory profiles.

Results
Limited by the pandemic, we only included 20 patients with 11 u nder fish oil and nine under placebo. Only marginal improvement in processing speed was found in fish oil group. We found decreased brain entropy in left posterior cingulate gyrus (PCG), multiple visual areas, the orbital part of the right middle frontal gyrus, and the left Rolandic operculum. Brain entropy changes in PCG in the fish oil group was associated with language function improvement and decrease in interleukin-6 levels.

Discussion & Conclusion
Our results confirm the anti-inflammatory effects of fish oil in LLD could be the underlying mechanism of cognitive protective effects. Also, fish oil may exert its function through modulation of brain entropy changes in key area in default-mode network, a network strategic both in depression and dementia.
EXPLORING MOLECULAR CHANGES IN THE EXTENDED AMYGDALA INDUCED BY CHRONIC CORTICOSTERONE ADMINISTRATION
Authors: Ueda *Shuhei , Hosokawa Masahito , Kakita Manami , Arikawa Koji , Matsunaga Hiroko , Takeyama Haruko , Takemoto-Kimura Sayaka 
Published: February 2025

Abstract
Chronic stress is a significant risk factor for multiple psychiatric disorders, including depression. When exposed to social and/or environmental stressors, the hypothalamic-pituitary-adrenal (HPA) axis becomes activated, leading to the release of glucocorticoids (cortisol in humans, corticosterone in rodents) from the adrenal glands into the blood. This activation works to regulate various physiological processes such as metabolism, blood pressure, and immunity, allowing the body to cope with stress.
Subsequently, negative feedback on the HPA axis lead to its deactivation and terminates the stress response. While, severe chronic stress can disrupt the normal functioning of the HPA axis and is believed to contribute to the development of psychiatric disorders. However, it is still unclear what kind of changes at molecular level occur in the brain due to dysfunction of the HPA axis, leading to various psychiatric symptoms. In the present study, we employed mice that were continuously administered corticosterone for 24 days as a model of chronic stress-induced HPA axis dysfunction. These mice exhibited depression-like symptoms, including body weight loss, decreased spontaneous activity, diminished sucrose preference (anhedonia), and increased immobility time during the forced swim test (despair). Next, we focused on the extended amygdala, a pivotal brain region of emotions and stress responses, and performed subnuclei-targeted tissue collection using microdissection punching system, followed by gene expression analysis by RNA-seq. As a result, we found that in the extended amygdala with complex subnuclear structures, different molecular changes were observed in each subnucleus due to chronic corticosterone administration. These findings represent a significant step toward elucidating the neural circuit alterations induced by chronic stress.
BRAIN PH IS DECREASED IN PATIENTS WITH MAJOR DEPRESSIVE DISORDER: A META-ANALYSIS OF POSTMORTEM STUDIES
Authors: Hagihara *Hideo , Miyakawa Tsuyoshi 
Published: February 2025

Abstract

Background
Major depressive disorder (MDD) is a prevalent and debilitating mental disorder that shares symptoms, genetics, and molecular changes in the brain with other psychiatric disorders, such as schizophrenia and bipolar disorder. Decreased brain pH, associated with increased lactate levels due to altered energy metabolism and neuronal hyperexcitation, has consistently been observed in individuals with schizophrenia and bipolar disorder compared with healthy controls. We have recently demonstrated that similar brain alterations are common in a wide range of animal models of neuropsychiatric disorders, including MDD. However, our understanding of brain pH alterations in human patients with MDD remains limited.

Aims & Objectives
In this study, we aimed to evaluate postmortem brain pH in patients with MDD in comparison to control subjects.

Method
We utilized publicly available data on brain pH to conduct a quantitative meta-analysis.

Results
The results of the random effects model, using 43 available datasets, indicated a decrease in brain pH in patients with MDD (Hedges’ g = -0.22, p = 0.0056). We also conducted a two-way analysis of covariance, with the dataset and diagnosis as the main factors, and postmortem interval, age at death, and sex as covariates. While significant effects were observed for the covariates, the effect of diagnosis remained significant.

Discussion & Conclusion
This study suggests a decrease in brain pH in patients with MDD, which could be a potential clue in understanding the pathophysiology. When combined with insights from animal model studies, it suggests that altered brain energy metabolism leading to decreased brain pH may serve as a potential transdiagnostic endophenotype for MDD and other neuropsychiatric disorders.
UTILIZING STRUCTURAL EQUATION MODELING TO ANALYZE POLYGENIC RISK AND ENVIRONMENTAL INFLUENCES ON LATE-LIFE DEPRESSION
Authors: Elsheikh *Samar Salah Mohamedahmed , Marshe Victoria , Kennedy James , Paré Guillaume , Fischer Corinne , Felsky Daniel , Mueller Daniel 
Published: February 2025

Abstract

Background
Our understanding of the interplay between genetic and environmental factors (Gene x Environment Interaction, or GxE) determining mental health disorders has improved through the proliferation of genome-wide interaction association studies (GWIAS) and targeted GxE analyses.
Moreover, multivariate modelling approaches, such as structural equation modelling (SEM) and polygenic risk scores (PRS), offer opportunities for the integration of clinical and genome-wide genotype data in building improved biopsychosocial models of mental illness aetiology and their response to treatment.

Aims & Objectives
We propose to construct a SEM framework to uncover the inter-correlation and directed structure of mental health phenotypes by leveraging the joint predictive capacity of PRS for comorbid traits that share underlying biological and environmental risk pathways. The proposed model will be capable of linking latent constructs to their observed measurements; these will include disease severity, comorbidities and clinical histories, and behaviours and lifestyle factors such as physical and social activity.

Method
Our gene-by-environment SEM (GESEM) will be initially developed and tested using four well- characterized clinical cohorts for older adults diagnosed with late-life depression and treated with antidepressants (CAN-BIND, IRL-GREY, STOP-PD II and IMPACT; n =1,238). The primary outcome will be antidepressant remission. Multiple PRS will be calculated to capture underlying genetic risk across vulnerable pathways which contribute to comorbidities. This selection will be made based on new, largely unpublished work from our group on the impact of PRS and targeted GxE studies on psychiatric outcomes across the lifespan. Each PRS will be calculated using both clumping and thresholding (PRSice-2) and continuous shrinkage (PRS-CS-auto) methods across selected cohorts using well-powered publicly available GWAS summary statistics. The multilevel GESEM model will include interactions between symptoms and comorbidities (i.e., observed measurements), which are caused by unobserved factors (i.e.,latent constructs), and are subject to modification by background PRS. We will compare our GESEM model against existing SEM-based approaches to GxE, including local SEM (LOSEM).

Discussion & Conclusion
An open-source R package of the analytical code will be created and shared with the research community. This work has the potential to improve upon existing PRS-based predictive models in a clinical setting.