bluuebunny/crossref_metadata_2025_split huggingface dataset:
AGE OF ONSET AFFECTS RELAPSE OF ALCOHOL USE DISORDER: A 7- YEAR RETROSPECTIVE COHORT STUDY
Authors: Zhang *Kai , Yao Yitan , Wu Yuanxiong , Ma Qianru , Yang Qiongyao , Chen Chuanchuan , Wang Yue , Luo Bei , Yuan Xiaoping 
Published: February 2025

Abstract

Background
Age of onset(AOO) influences the prognosis of many diseases and even serves as potential driver. But in Alcohol Use Disorders(AUD), there is no consensus regarding the effect of AOO on the course.

Objectives
We thus retrospectively investigated a large-scale cohort to explore the effect of AOO on the course of AUD.

Method
In this study, a total of 14,357 inpatients with alcohol use disorders were recruited over a 7- year time span, and after applying rigorous data criteria, 2,176 inpatients were ultimately included in the statistical analysis. Patients were divided into three age subgroups according to their age of onset, which were early adult onset(EAO), middle adult onset(MAO) and late adult onset(LAO).

Results
The proportion of recurrence was statistically different in the subgroups with different age of onset (X2=9.819, df=3, P=0.007), the Bonferroni post hoc test suggested a higher proportion of recurrence in the EAO than that in the MAO subgroup (66.1% vs 59.5%, P&lt;0.05). We then performed a Binary logistic regression. Taking patients in the EAO subgroup as a reference, patients with MAO had a lower risk of recurrence (OR=0.75, 95%CI=0.63-0.90, P=0.002), however, the risk of recurrence in the LAO subgroup was not statistically different from the EAO (OR=0.78, 95%CI=0.54-1.11, P=0.17).
Subsequently, a survival analysis for recurrence within one year was performed. There were statistically differences in Kaplan-Meier method estimates of the probability of disease-free survival (DFS) at day 365 between the three age of onset subgroups (33.9%, 40.5%, 39.7%, respectively; P=0.03).
Specifically, post hoc tests suggested that DFS was lower in the EAO subgroup than in the other two groups (median DFS=197, 95%CI=172.10-221.90, P=0.012). Finally, we follow-up all patients for 5 years for cerebral atrophy onset, and the results suggest that the incidence of cerebral atrophy during the follow-up period was lower in the EAO subgroup than that in the other two subgroups (OR=1.42, 95%CI=1.19-1.70, P&lt;0.001; OR=1.62, 95%CI=1.14-2.31, P=0.007, respectively), but this difference was no longer statistically significant after controlling for the age factor (both P&gt;0.05).

Conclusion
This is the first large sample size study to explore the influence of age of onset on alcohol use disorders in a Chinese population. Our study found that alcohol use disorders with onset in early adult are associated with more recurrences. These findings will help explore risk factors for alcohol use disorders and provide preliminary evidence for clinical development of prevention strategies.
NERVE GROWTH FACTOR GENE POLYMORPHISMS MAY BE ASSOCIATED WITH HEROIN DEPENDENCE IN WOMEN BUT DO NOT MEDIATE IMPULSIVITY AND SPECIFIC PERSONALITY TRAITS
Authors: Huang *San-Yuan , Shih Mei-Jen 
Published: February 2025

Abstract

Objective
Heroin use disorder (HUD) is a complex disease with substantial genetic contribution, and patients with HUD have been associated with traits of impulsivity. Nerve growth factor (NGF) is a neurotrophic factor and may mediate the reward processes in HUD. We performed this study to investigate whether NGF gene polymorphisms are associated with the occurrence of HUD and the impulsive personality traits of patients with HUD.

Method
We selected a homogeneous Han Chinese population to overcome possible confounding effects of population. For the study, 1364 participants (831 HUD patients and 533 healthy controls) were recruited. In addition, 185 female patients with HUD completed the Chinese version of Barratt Impulsiveness Scale Version 11 (BIS-11) to assess impulsive personality traits for subsequent analysis.

Results
Three polymorphisms exhibited a difference in allele and genotype frequency between HUD patients and controls (p = 0.035 for rs2254527; p = 0.005 for rs6678788; p = 0.006 for rs7523654), especially in the female subgroup. In haplotype analysis, four associations were found in the female subgroup (p = 0.003 for the T-T-A haplotype p = 0.002 for the C-C-A haplotype in block 1; p = 0.011 for the T-T haplotype, and p = 0.009 for C-T haplotypes in block 2), but not in the male subgroup. However, there was no significant association between the selected NGF polymorphisms and BIS scores in female patients with HUD.

Conclusion
The NGF gene may contribute to the risk in the development of female HUD, but not mediate the relationship between impulsive personality traits and HUD in the female population.
ANXIETY-LIKE BEHAVIOUR STUDY IN ADULT RAT STRESS MODEL INDUCED BY LIGHT DOMINANT EXPOSURE IN CIRCADIAN RHYTHM DISRUPTION
Authors: Kusumawardani *Shanty Rahayu , Yoshida Sachiko , Terui Kiki 
Published: February 2025

Abstract
The breakdown of biobehavioural adaptive mechanisms with stress response and vulnerability may result from circadian rhythm disruption driven by an internal timing system that enables numerous fundamental features from gene expression to behaviour. Previous study showed the difference length of the exposure in circadian cycle caused behaviour abnormality. However, the light dominant exposure as a stressor in circadian disruption affects behaviour still remain unclear. Using a rat model, we investigated the stress-related mechanisms susceptible to chrono disruption manifested in anxiety-like behaviour. We evaluated the effect of light-dominant exposure of adult male rats to white light-emitting diodes (LED) with 300 lux light intensity. The experimental groups consisted of three conditioned light-dominant exposures. Group 1 (16 h light: 8h dark); Group 2 (20 h light: 4 h dark); Group 3 (24 h light) compared to the control group (12 h light: 12 h dark) in 4 weeks of intense light exposure. By the end of the exposure time, we assessed their behaviour using Open Field Test instruments. Additionally, body weight and food consumption amounts were measured by the end of each week to indicate the effect of chrono disruption on the eating behaviour of the rats. ANOVA and Tukey post-hoc test were applied to determine the significant value among the groups of the treatments. Behaviour study revealed that 24-hour light exposure showed increased time spent in the centre and total travelled distance, which showed less anxiety than all groups. Meanwhile, rats exposed to 20h light had the lowest activity to interact with the recognized and novel object, which indicates anxiety toward the stimulus. Similarly, 20h light exposure rats showed the least interaction with the social partner and increased duration and frequency of grooming, which exhibited anxiety-like behaviour. Other than that, 24-hour light exposure showed less anxiety, indicated by increased social interaction and decreased grooming time. In body weight change, there was no significant difference (P &gt;0.05) between all groups; meanwhile, the 24-hour light exposure showed the lowest food consumption. The disruption of circadian rhythm by exposure to chronic light induces stress and anxiety by altering serotonin regulation in the brain. The light dominant exposure lengthens the inactive phase of the rat’ s biological clock that influence serotonin release which is the highest serotonin release is during the active phase under circadian control. Decreased serotonergic activity has been implicated in anxiety and depression. The low serotonin activity might inhibit melatonin hormone release as the essential factor in sleep regulation, which underlies the circadian rhythm. Therefore, light-dominant exposure to rats has marked an anxiety-like behaviour on the circadian rhythm dysregulation.
A RHO-KINASE 2 SELECTIVE INHIBITOR KD025 AMELIORATES SCHIZOPHRENIA-LIKE BEHAVIORS IN MK-801-TREATED MICE
Authors: Tanaka *Rinako , Liu Yue , Liao Jingzhu , Mouri Akihiro , Nagai Taku , Nabeshima Toshitaka , Kaibuchi Kozo , Tachibana Daiki , Kobayashi Yohei , Ozaki Norio , Mizoguchi Hiroyuki , Yamada Kiyofumi 
Published: February 2025

Abstract

Background
Rho-kinase is a serine/threonine kinase and regulates actin dynamics. There are two subtypes: Rho-kinase 1 and Rho-kinase 2. Recently, we found that a Rho-kinase1/2 inhibitor, fasudil, ameliorated schizophrenia-like behaviors in MK-801-treated mice (Takase et al., 2022). However, fasudil has been shown side effects, such as hypotension, which may hinder its clinical application for schizophrenia. Since Rho-kinase 2 is predominantly expressed in brain, we hypothesized that selective inhibition of Rho-kinase 2 might exhibit antipsychotic-like effects with fewer cardiovascular side effects.

Aims & Objectives
To investigate the potential of a Rho-kinase 2 inhibitor as a therapeutic agent for schizophrenia, we evaluated the effect of a selective Rho-kinase 2 inhibitor, belumosudil (KD025), on MK-801-indued schizophrenia-like behaviors and blood pressure in mice.

Method
Effects of KD025 on schizophrenia-like behaviors in MK-801-treated mice were evaluated by locomotor activity test, novel object recognition test (NORT), and visual discrimination test (VD). KD025 (100-200 mg/kg) was orally administered 120 min before the behavioral tests. The blood pressure was also measured after KD025 treatment by tail-cuff method. Furthermore, we evaluated the depolarization-evoked extracellular dopamine and serotonin levels in the nucleus accumbens (NAc) using an in vivo microdialysis method.

Results
KD025 (100 or 200 mg/kg) restored MK-801-induced hyperlocomotion and the cognitive impairments in the NORT and VD, while KD025 showed little effect on systolic blood pressure, not like fasudil. In addition, local perfusion of KD025 (10-20 μ M) in the NAc suppressed the depolarization- evoked serotonin-, but not dopamine-release in the NAc.

Discussion & Conclusion
Our findings indicate that Rho-kinase 2 has potential as a therapeutic target for schizophrenia and KD025 may be a candidate as an antipsychotic for schizophrenia.

References
TAKASE, S., LIAO, J., LIU, Y., TANAKA, R., MIYAGAWA, Y., SAWAHATA, M., SOBUE, A., MIZOGUCHI, H., NAGAI, T., KAIBUCHI, K., OZAKI, N. &YAMADA, K. 2022. Antipsychotic-like effects of fasudil, a Rho- kinase inhibitor, in a pharmacologic animal model of schizophrenia. Eur J Pharmacol, 931, 175207.
THE EFFECTS OF ACUTE CANNABIS WITH AND WITHOUT CANNABIDIOL ON NEURAL REWARD ANTICIPATION IN ADULTS AND ADOLESCENTS
Authors: Skumlien *Martine , Freeman Tom P , Hall Daniel , Mokrysz Claire , Wall Matthew B , Ofori Shelan , Petrilli Kat , Trinci Katie , Borissova Anna , Fernandez-Vinson Natalia , Langley Christelle , Sahakian Barbara J , Curran H Valerie , Lawn Will 
Published: February 2025

Abstract

Background
Cannabis, and its main psychoactive compound tetrahydrocannabinol (THC), may alter the brain’ s reward system both acutely and over time. The endocannabinoid and reward systems mature during adolescence and adolescents may therefore respond differently to acute cannabis exposure compared with adults. Despite this, no previous functional magnetic resonance imaging (fMRI) study has examined the acute effects of cannabis in this age group. Aims & Objectives. The aims of this study were to investigate the neural correlates of reward anticipation after acute exposure to THC with and without cannabidiol (CBD), and whether the effect of cannabis differed in adolescents and adults.

Method
This double-blind, placebo-controlled, randomised, crossover design used data from the 'CannTeen’ study, collected between March 11, 2019, and June 16, 2021. Twenty-three adults (26-29 years) and 24 adolescents (16-17 years), matched on gender and cannabis use frequency (0.5-3 days/week) performed the Monetary Incentive Delay task after inhaling cannabis with 0.107 mg/kg THC ('THC’) (8 mg THC for a 75-kg person) or with THC plus 0.320 mg/kg CBD ('THC+CBD’) (24 mg CBD for a 75-kg person), or placebo cannabis. We investigated neural responses to reward anticipation with whole-brain analyses and region of interest analyses in the right and left ventral striatum, right and left anterior cingulate cortex, and right insula. All analyses and hypotheses were pre-registered to the Open Science Framework.

Results
THC acutely reduced reward anticipation activity in the right (p =.005, d = 0.49) and left (p =.003, d = 0.50) ventral striatum and the right insula (p =.01, d = 0.42) compared with placebo. THC+CBD also reduced activity in the right ventral striatum (p =.01, d = 0.41) and the right insula (p =.002, d = 0.49) compared with placebo. The effects of active cannabis were the same in adolescents and adults and there were no differences between the THC and THC+CBD conditions.
Bayesian analyses supported these null findings. There were no significant effects in the whole-brain analyses.

Discussion & Conclusion
In weekly cannabis users, cannabis suppresses the brain’ s anticipatory reward response to money and CBD does not moderate this effect. Furthermore, the adolescent reward circuitry is not differentially sensitive to acute effects of cannabis on reward anticipation. This is the first study to investigate the acute effects of cannabis on the adolescent brain using fMRI and future studies of other cognitive and psychological processes are needed.
THE IMPACT OF SLEEP JET LAG ON DEPRESSION DIFFERED BY SEX AND AGE ~ EVIDENCE FROM 27,916 TAIWAN BIOBANK PARTICIPANTS
Authors: Chen *Shaw-Ji 
Published: February 2025

Abstract

Introduction
Sleep jet lag (SJL) means difference of sleep time between weekdays and weekend consumption. The influence of SJL on depression was controversial in previous studies. Therefore, this study analyzed the influence of SJL on depression y by using data from the Taiwan Biobank (TWB), established in 2012.

Methods
Participants in TWB were included in our study, with a total of 41,290 respondents included for analysis. To investigate SJL on the influence of depression and anxiety, we surveyed their SJL and depression byPHQ-4. To estimate more precise risk, we also collected their other covariate data such as age, sex in the study.

Results
We found that participants in the group of SJL more than one hour with more risk to develop depression than participants in the group of SJL fewer than one hour (OR=1.84 95% CI: (1.35-2.51), p&lt;0.001). Participants with age. 65 years old and female were found to be significantly protective on depression. (Age &gt;65 year old: OR=1.70 95% CI: (1.37- 2.11), p&lt;0.001:female: OR=1.86 95% CI: (1.53-2.26), p&lt;0.001) The other covariates such as alcohol, tobacco, coffee or tea use will be assessed latter.

Conclusions
The influence of SJLon depression and anxiety was noticed. More detail subgroup analysis more than age and sex would be presented in the conference. The interactions between SJL on depression will be performed latter in the conference.
IRON DEPOSITIONS IN PREFRONTAL CORTEX INFLUENCES THE EFFECTIVENESS OF CORTICAL PAIRED ASSOCIATIVE STIMULATION IN HEROIN-DEPENDENT PATIENTS: A RANDOMIZED SHAM-CONTROLLED STUDY
Authors: Chen *Tianzhen , Tan Haoye , Su Hang , Jiang Haifeng , Zhao Min 
Published: February 2025

Abstract

Background
Brain iron homeostasis, which may be disrupted in substance dependence, will cause cell death and influence the neural plasticity function when out of balance. Transcranial magnetic stimulation (TMS) protocols in paired associative stimulation (PAS) are increasingly used to influence spike-timing-dependent plasticity and behaviors. The use of heroin causes severe brain damage; however, it is unclear whether PAS protocols in healthy people can benefit heroin patients’ cognitive behaviors and mechanisms.

Aims & Objectives
The aim of this study was to explore the role of a PAS stimulation protocol based on dorsolateral prefrontal-medial prefrontal cortex in modulating cognitive function in patients with heroin dependence, as well as the role of brain iron deposition levels in modulating the intervention effects.

Methods
A total of forty heroin patients were randomized to accept one of the following PAS protocols for 100 trials: left dorsolateral prefrontal cortex (DLPFC) stimulation preceding left ventromedial prefrontal cortex (VMPFC) stimulation by 4 ms (DLPFC+4ms), reverse the order (VMPFC+4ms), or placebo stimulation setting (DLPFC+100ms/VMPFC+100ms). Subjects were tested on the Quantitative susceptibility mapping and two cognitive tasks (i.e., stop signal task and two-back task) at baseline and after stimulation. Thirty healthy controls also accepted the DLPFC+4ms or VMPFC+4ms stimulation and finished two cognitive tasks during the PAS setting.

Results
Among the healthy controls, DLPFC+4ms stimulation significantly improved the accuracy rate of the two-back task (TWOB-ACC) than the VMPFC+4ms setting (p=0.01), while the VMPFC+4ms significantly increase the stop signal reaction time (SSRT) than DLPFC+4ms (p=0.03). However, three stimulation groups of heroin patients did not show a difference in two cognitive tasks during the PAS stimulation. Magnetic susceptibility of left DLPFC has positive predictive effect in the change of TWOB- ACC in the DLPFC+4ms group of heroin patients (p=0.002). In contrast, the magnetic susceptibility of left DLPFC has positive predictive effect in the change of SSRT in the VMPFC+4ms group of heroin patients (p=0.04).

Discussion & Conclusion
The brain magnetic susceptibility influences the functional plasticity induced by PAS, and the stimulus parameters applicable to the healthy controls cannot cause cognitive changes in the heroin-dependent population. Brain magnetic susceptibility should be considered an important modulating factor in TMS studies.
ASSOCIATIONS BETWEEN GENETIC LIABILITY TO ATTENTION DEFICIT HYPERACTIVITY DISORDER AND METHAMPHETAMINE ABUSE
Authors: Chung *Annie , Lin Yen-Feng , Huang Ming-Chyi 
Published: February 2025

Abstract

Background
Attention deficit hyperactivity disorder (ADHD) and substance use disorder co-occurs frequently. Both methamphetamine abuse and ADHD is heritable and probably highly polygenic. Shared genetic factors may explain the high comorbidity between methamphetamine abuse and ADHD. In this study, we hypothesize methamphetamine abuse may be genetically correlated with ADHD.

Aims & Objectives
The aim of the study was to examine the association of common genetic variants (i.e., single nucleotide polymorphisms [SNPs]) across the whole genome with methamphetamine abuse and to examine the genetic overlap between ADHD and methamphetamine abuse as well as other methamphetamine use variables.

Method
143 treatment-seeking patients with methamphetamine abuse were recruited in Taipei City Hospital and 77,520 healthy individuals were Taiwan Biobank’ s participants with no prior history of psychiatric or substance use disorders. Genome-wide single nucleotide polymorphism genotyping, demographics, and clinical information were obtained. We conducted an exploratory genome-wide association analysis (GWAS) for methamphetamine abuse vs. healthy individuals. ADHD GWAS summary statistics from Psychiatric Genomics Consortium were utilized as the discovery datasets to compute a polygenic risk score (PRS) of ADHD for each subject in our study sample. We also examined the relationship between ADHD-PRS and methamphetamine use characteristics among the patients with methamphetamine abuse.

Results
Preliminary genome wide analysis revealed a significant SNP rs66510859 on chromosome 7 (P-value= 2.04E-09) associated with methamphetamine abuse. Methamphetamine abuse was significantly associated with ADHD-PRS with a P-value threshold of 0.05. ADHD-PRS with P-value threshold of 0.5 was associated with log-transformed earlier age of first use (beta=-6.1, p=0.02) and log-transformed regular use (beta=-6.0, p=0.01) after adjustment for covariates.

Discussion & Conclusion
Methamphetamine abuse may be genetically correlated with ADHD. Further study will examine the causal relationships between the genetic liability to ADHD, the Adult ADHD Self-Report Scale score, and clinical characteristics of methamphetamine abuse by using causal mediation analysis and Mendelian randomization.
CAUSAL RELATIONSHIP BETWEEN SUBSTANCE USE AND INSOMNIA: A BIDIRECTIONAL MENDELIAN RANDOMIZATION STUDY
Authors: Guo *Lei , Su Hang , Chen Tianzhen , Du Jiang , Jiang Haifeng , Zhao Min 
Published: February 2025

Abstract

Background
Insomnia is a significant factor that affects both physical and mental health and may increase the risk of various mental disorders, causing a considerable burden on mental health. Substance use, particularly tobacco and alcohol use, is a significant health issue affecting the Chinese population. Previous studies have suggested a correlation between substance use, such as tobacco and alcohol, and the occurrence of insomnia, and insomnia may further aggravate substance use problems. However, the causal relationship between the two is still unclear.

Aims & Objectives
This study aimed to use a bidirectional Mendelian randomization approach to explore the causal relationship between substance use and insomnia.

Method
The Mendelian randomization (MR) method used genome-wide association study (GWAS) summary data to study the causal relationship between exposure and outcome. Bidirectional MR tested the bidirectional effects of the two factors and determined the bidirectional causal relationship between the two factors. This study used GWAS data on alcohol addiction (N = 6514), weekly alcohol consumption (N = 335394), smoking initiation (N = 607291), daily smoking quantity (N = 249752), and two insomnia traits (N = 462341; N = 336965) to conduct bidirectional MR analysis and confirmed the robustness of the analysis using sensitivity analysis.

Results
The bidirectional MR results indicated that weekly alcohol consumption (IVW: P = 0.017, b = 0.063; Weighted median: P = 0.025, b = 0.048) and smoking initiation (IVW: P = 0.008, b = 0.036; Weighted median: P = 0.04, b = 0.023) had promoting effects on insomnia. However, although IVW suggested that insomnia had an effect on alcohol addiction (P = 0.036) and daily smoking quantity (P = 0.016), sensitivity analysis using methods such as Weighted median and Weighted mode did not support this.

Discussion & Conclusion
This study, through bidirectional MR analysis, found that tobacco use and alcohol consumption have a promoting effect on insomnia, which is consistent with previous reports. However, this study's results do not support the speculation that insomnia itself promotes alcohol and tobacco use. Insomnia caused by alcohol and tobacco use may be related to the neural excitability and awakening function abnormalities caused by substance use, and patients with insomnia may be less likely to seek relief through tobacco and alcohol. This study reveals the potential causal relationship between substance use and insomnia through Mendelian randomization analysis based on large-scale GWAS data, providing new evidence for clinical diagnosis and treatment. Future large-scale cohort studies are needed to further explore the causal relationship between substance use and insomnia.