bluuebunny/crossref_metadata_2025_split huggingface dataset:
CAUSAL ASSOCIATIONS BETWEEN SCHIZOPHRENIA AND CANCERS: MENDELIAN RANDOMIZATION ANALYSES
Authors: Shao *Jun X , Zhu Gang 
Published: February 2025

Abstract

Background
Schizophrenia is one of the most prevalent neurological disorders that affect the physical, cognitive, behavioral, and emotional functioning of an individual. Cancer as a chronic disease is closely related to shorten lifespan in patients with schizophrenia.

Aims & Objectives
At present, the associations between these two diseases still remains unclear. So we preformed Mendelian randomization (MR) methodological approach to address whether this association is causal using genetic variants identified in genome-wide association studies (GWAS).

Methods
GWAS statistics data, including schizophrenia (n =533,86) from the Psychiatric Genomics Consortium and cancer patients (n = 12,409,533) from the GWAS Catalog of European ancestry, was analyzed. In this study, a two-sample MR method was used to determine the causality between schizophrenia and cancer and two-step MR design to explore whether some (including smoking and sex hormone levels) mediates the causal pathway from schizophrenia to specific cancer outcome. The inverse-variance weighted approach was used as the principal analysis, complemented with weighted median, weighted mode, simple median method, and MR- Egger analyses, while several sensitivity analyses were applied to evaluate heterogeneity and pleiotropy.

Results
In total, we obtained instrumental variables of schizophrenia and 20 major site-specific cancers using 38 summary association statistics. Two-sample MR analysis revealed a significant positive causal influence for schizophrenia on increased cancer risk, including breast cancer, subtype oestrogen receptor (ER) positive breast cancer, subtype ER negative breast cancer,bowel cancer if ever had screening, lung cancer, lung cancer with illnesses of mother, cancer in upper lobe, bronchus or lung and myeloid leukaemia. Two-step MR analysis showed smoking was a mediator of the positive cause-effect relationship between schizophrenia and cancer of lung.

Discussion & Conclusion
Our present MR study identified a causal relationship between schizophrenia and cancer. Smoking is a confounder when evaluating the association between schizophrenia and lung cancer. Further research is needed on additional risk factors as potential mediators.
PSYCHOTROPIC DRUGS AND THEIR EFFECTS ON SEIZURE DURATION IN PATIENTS RECEIVING ELECTROCONVULSIVE THERAPY
Authors: Pariwatcharakul *Pornjira , Homhual Patipon , Prachgosin Punyisa , Sa-Guanpanich Naratip , Liao Pitchaporn , Suansanae Thanarat 
Published: February 2025

Abstract

Objective
To examine the effects of psychotropic drugs on seizure duration in patients receiving electroconvulsive therapy (ECT).

Methods
The medical records of patients who received ECT at a university hospital in Bangkok from March 2014 to February 2017 were retrospectively reviewed. Demographic data, psychotropic drug use, ECT stimulus parameters, and motor seizure duration were recorded. The daily dose of drugs with antipsychotic properties and benzodiazepine in each patient was converted into a risperidone equivalent dose and a diazepam equivalent dose, respectively. Beside descriptive statistics, regression analyses were performed with SPSS using a generalized estimating equation to examine the association between seizure duration and the use and daily dose of psychotropic drugs.

Results
All 647 ECT sessions were delivered in a general psychiatry ward in 249 patients, 99.1% (n = 641) in which thiopental was used for anesthesia induction. After 7 ECT sessions with anesthesia induction agents other than thiopental were excluded, 641 ECT sessions remained for statistical analysis; 436 (68.0%) and 205 (32.0%) sessions were in the acute phase and maintenance phase, respectively. Most ECT treatments achieved adequate EEG seizures (n = 581; 90.6%) as well as motor seizure duration (n = 509; 79.4%). Seizure duration was associated with the benzodiazepine equivalent dose (p = 0.001), especially when the daily diazepam equivalent dose was 20 mg or higher (p = 0.035). Risperidone equivalent dose and clozapine use did not show any significant association with seizure duration. Doses of anesthetic agents for the ECT procedure, thiopental (p &lt;0.001) and succinylcholine (p = 0.027), and ECT stimulus parameters (i.e., charge (p &lt;0.001), frequency (p &lt;0.001), and train duration (p = 0.002) were significantly associated with seizure duration. After adjustment for those, the benzodiazepine equivalent dose (OR 0.921, p = 0.001) and the diazepam equivalent dose of 20 mg or higher (p = 0.014) remained significantly associated with seizure duration.

Conclusion
The benzodiazepine dose was associated with seizure duration in patients receiving ECT, particularly at a diazepam equivalent dose of 20 mg or higher. Clinicians should be cautious when prescribing benzodiazepine to patients receiving ECT.
EFFECTS OF TESTOSTERONE ON AVERSIVE LEARNING: A DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY
Authors: Wu *Yin 
Published: February 2025

Abstract

Objective
Testosterone, a male sex hormone, is found to influence a broad range of human social behavior, but whether it affects people's pro-social decision-making is unclear. The purpose of this study was to examine the effects of testosterone on pro-social decision-making tendencies.

Methods
This study used a 2 group (testosterone vs. placebo, between-groups) × 2 recipient (self vs. other, within- groups) experimental design in which 120 healthy male university student subjects were recruited and randomly assigned to either testosterone or placebo groups. Three hours after testosterone or placebo administration, participants were required to perform to a task of avoiding electroshock harms for themselves and others, respectively. The task was a probabilistic learning task in which participants were required to choose between a pair of symbols. Each symbol is associated with a lower or higher probability of getting an electric shock.

Results
Behavioral analyses in this study were conducted using generalized linear mixed models, and the optimal model revealed a main effect of receiver and number of trials, where participants would have a higher probability of selecting the correct symbol (i.e., the symbol with the lower probability of receiving a shock) when performing the task for themselves, and the probability of selecting the correct option increased with the number of trials, demonstrating a learning trend; at the same time, there was a marginal-significant receiver condition versus number of trials effect, i.e., the probability of participants choosing the correct option when performing the task for another person tended to increase more with the number of trials, and this effect was present in both the testosterone and placebo groups. Further analyses using a positive and negative reinforcement learning model of aversion learning revealed that there were higher learning rates when a better-than- expected outcome was encountered; positive learning rates were lower and negative learning rates were higher in the testosterone group relative to the placebo group, suggesting that the testosterone administration reduced positive bias in decision making. Consistent with the mixed-effects linear modeling results, participants generally learned quicker in the others condition. However, in the receiver-as-self condition, the testosterone group presented more unbiased learning, i.e., lower positive learning rates and higher negative learning rates. The testosterone group focused less on worse-than- expected negative outcomes when avoiding harm for others, i.e., lower negative learning rates.

Conclusion
Testosterone may influence learning about avoiding harm for oneself, leading to a tendency towards more unbiased learning; and less concern for negative consequences when learning to avoid harm for others.
LATENT CLASSES BASED ON CLINICAL SYMPTOMS OF MILITARY RECRUITS WITH MENTAL HEALTH ISSUES AND THEIR CLINICAL RESPONSES TO TREATMENT OVER 12 MONTHS
Authors: Jon *Duk-In , Eo Jeongwon , Park Eun Hee , Hong Hyun Ju 
Published: February 2025

Abstract

Background
In South Korea, all men at the age of 18 or older are required to serve at military for a certain period as an obligation. These recruits should be able to withstand psychological stress and pressures of rapid adaptation of the unique and new environment in military. The number of military recruits facing adaptation issues has been on the rise, necessitating an evaluation for active service. In our previous study (Park et al., in press 2023), we classified the military recruits with mental issues according to latent profile analysis (LPA) and examined the treatment response during six months.

Aims
In this study, we further examined clinical characteristics over the next six months.

Methods
Ninety- two participants were analyzed with LPA using MMPI-2 clinical profiles in the previous study. The three classes were identified: mild maladjustment (Class 1, n=14), neurotic depression and anxiety (Class 2, n=36), high vulnerability and hypervigilance (Class 3, n=42). At 12 months, Clinical Global Impression- Severity and Global Assessment of Functioning were assessed to test their long-term changes.

Results
While Class 1 and 2 significantly improved over 6 months, Class 3 showed little or no improvement even with more medications in our previous study. During the 6-month follow-up period, 50% of Class 1, 38.9% of Class 2, and 41.5% of Class 3 were dropped. It was during this period that their level of military service was decided. Class 1 and 2 which showed marked improvement up to initial 6 months, did not demonstrate substantial further improvement during follow-up period with a considerable portion stopped visiting hospital. Subjects in Class 3, who showed little or no improvement during initial 6 months, demonstrated continued improvement in this study, although their symptoms still appeared relatively severe.

Conclusion
This study suggests clinical implications for treatment plan and intervention of each subgroup classified based on MMPI-2 clinical profiles of military recruits who might show maladjustment to serve. The long-term continuous treatment for Class 3 patients will be needed, even after exemption from active duty.
FAT LOSS AND MUSCLE GAIN: THE POSSIBLE ROLE OF CORTICAL GLUTAMATE IN DETERMINING THE EFFICACY OF PHYSICAL EXERCISE
Authors: Abdullah Muhammad , Lin Shih-Hsien , Huang Li-Chung , Chen Po See , Tseng Huai-Hsuan , Yang *Yen Kuang 
Published: February 2025

Abstract

Background
Physical exercise effectiveness in treating obesity remains contentious.

Aims & Objectives
Owing to the roles of glutamate in appetite, food addiction and impulsivity, this study aimed to identify medial prefrontal cortex (mPFC) glutamate as a predictor of variability in exercise response, specifically in terms of fat loss and muscle gain.

Method
Healthy non-exercising adult men (n=21) underwent an 8- week supervised exercise program. Baseline glutamate levels in the mPFC were measured through magnetic resonance spectroscopy. For exercise-dependent changes in fat, muscle, basal metabolic rate (BMR), and blood metabolic biomarkers were obtained, respectively.

Results
The exercise program resulted in significant improvements in most of the index (Table1). Interestingly, lower baseline glutamate levels were associated with greater loss in percentage body fat mass (r = 0.58, p = 0.01, Fig 1), body fat mass (r = 0.53, p = 0.02), and increase in muscle mass (r = −0.50, p = 0.03).

Discussion & Conclusion
The results highlight cortical glutamate as a potential predictor of exercise-induced fat loss and muscle gain.
REVEALING BRAIN CHOLESTEROL DYNAMICS AND ITS RELATIONSHIP WITH AGGRESSION IN PSYCHIATRIC PATIENTS
Authors: Degmecic *Dunja , Jelinčić Ivana , Balog Marta , Korade Zeljka , Mirnics Karoly , Heffer Marija , Šantić Andrijana 
Published: February 2025

Abstract

Background
It is known that cholesterol is essential for the normal functioning of the brain. Sterol metabolism dysfunction contributes to many psychiatric and neurodegenerative disorders. Cholesterol intermediates, such as lathosterol and desmosterol, are considered better markers of endogenous cholesterol biosynthesis than cholesterol itself; thus, they are reliable markers of cholesterol metabolism dysfunction.

Methods
To gain insight into cholesterol metabolism, we conducted a study to determine the levels of cholesterol intermediates in blood samples from a population of psychiatric patients. Participants were recruited over a 6-month period from hospitalized patients at the Psychiatry Clinic in Osijek. Patients underwent a comprehensive clinical psychiatric examination, accompanied by a questionnaire specifically designed for this research. Special attention was focused on clinical determinants of aggression symptoms. Blood samples were collected from the patients in serum tubes, and these samples were analyzed by LC-MS/MS.

Results
Through the analysis of collected data using the χ2 test and Fisher's exact test, 34% of participants reported engaging in or carrying out self-harming behaviors in the past, 7.8% of participants reported having self-harming thoughts during hospitalization, 4.9% of participants exhibited heteroaggressive behavior before hospital treatment (N=205). Among participants with elevated oxysterol levels (7DHC), 31.8% reported engaging in or carrying out self-harming behaviors in the past, 4.5% reported having self-harming thoughts during hospitalization, and none of the selected population exhibited heteroaggressive behavior before hospital treatment.

Conclusion
Detailed analysis of the available literature reveals a connection between symptoms of depression and elevated oxysterol levels. While suicidality and self- or other-directed aggression are potential symptoms of depressive disorders, it is not possible to definitively conclude that there is a biological association between them. Our results did not demonstrate statistical significance regarding the association between elevated oxysterol levels and the manifestation of aggressive behaviors throughout life.
UNLOCKING THE BRAIN'S CHOLESTEROL SECRETS: MEDICATION EFFECTS ON LIVER HEALTH IN PSYCHIATRIC PATIENTS
Authors: Šantić Andrijana , Jelinčić Ivana , Balog Marta , Korade Zeljka , Mirnics Karoly , Heffer Marija , Degmecic *Dunja 
Published: February 2025

Abstract

Background
Cholesterol is necessary for the proper functioning of the brain. The brain, although it makes up about 2% of the total body weight, contains approximately 25% of cholesterol and its derivatives. Following critical observations, over the course of several years, we have confirmed that aripiprazole, trazodone, cariprazine, and haloperidol are strong inhibitors of sterol biosynthesis, each with profound biochemical effects on the developing brain. These are drugs believed to lead to the accumulation of 7DHC oxysterols, an important marker of oxidative stress. Oxidative stress has detrimental effects on most cellular structures; an excess of hydroxyl radicals and peroxynitrite will cause lipid peroxidation, resulting in damage to cell membranes and lipoproteins. In clinical practice, liver activity is monitored by measuring the concentrations of liver enzymes in blood serum. Gamma-glutamyl transferase is the one of most sensitive indicators of liver damage, particularly if the damage is caused by toxic substances (e.g., alcohol, drugs).

Methods
We conducted a study to assess the levels of cholesterol intermediates in blood samples from a population of psychiatric patients, which we further examined through a biochemical analysis of their blood serum. Participants were recruited for the study over a 6-month period from hospitalized patients at the Psychiatry Clinic in Osijek. Patients underwent a comprehensive clinical psychiatric examination, accompanied by a questionnaire designed specifically for this research. Blood samples were collected from the patients into serum tubes, and these samples were analyzed by LC-MS/MS, followed by biochemical processing.

Results
From the collected results through the implementation of the χ2 test and Fisher's exact test, elevated AST levels were identified in 15.1% of patients; elevated GGT levels in 25.4%, and reduced Che levels in 72.2% (N=205). Among patients with elevated oxysterols (7DHC), elevated AST levels were identified in 13.6% of patients, elevated GGT levels in 22.7%, and Che values were reduced in 75% of patients, with a statistically almost significant change primarily in the GGT concentration, which is the most sensitive indicator of liver damage.

Conclusion
In clinical practice, it is well-known that many drugs have hepatotoxic effects due to their metabolism. Considering that the liver is the primary organ responsible for storing exogenous cholesterol, among other functions, it is expected that the use of drugs that indirectly increase the concentration of 7DHC will lead to more significant damage. However, our research did not demonstrate statistical significance in the greater impact of the selected drugs compared to other psychopharmacotherapeutic medications.
CHARACTERISTICS OF PHARMACOTHERAPY DURING PREGNANCY AND NON-PREGNANCY IN PATIENTS WITH PSYCHIATRIC DISORDERS: A PRELIMINARY COMPARISON
Authors: Kobayashi *Tamayo , Kodaka Fumitoshi , Ishii Junpei , Mori Keisuke , Saeki Chihiro , Sakai Yoshiyuki , Shigeta Masahiro 
Published: February 2025

Abstract

Background
"The Guide for the Care of Pregnant Women with or Potentially With Psychiatric Disorders" developed by the Japanese Society of Psychiatry and Neurology recommends that the number of perinatal mother's prescriptions should be kept to a minimum one, but in real-world practice, it is not known which classes of medication are more likely to be changed after pregnancy in patients with psychiatric disorders after pregnancy.

Aims & Objectives
In this study, we used a prescription database to compare the medication regimens of patients who became pregnant / were pregnant with those of non-pregnant patients. The study was approved by the Ethics Committee of the Jikei University School of Medicine.

Methods
This database study was conducted using the prescription database (JP4DR) of patients who visited the outpatient section of the Department of Psychiatry, The Jikei University Hospital as outpatients between January 1, 2018 and December 31, 2021. Fifty-two patients who became pregnant/were pregnant during the study periods were selected, and 52 non-pregnant patients were selected from the same database according to propensity scores matching for age, sex, and diagnosis. We then compared the prescriptions of antipsychotics, antidepressants, anxiolytic hypnotics, and mood stabilizers between the pregnant and nonpregnant patient groups, as well as the imipramine equivalent, chlorpromazine equivalent, and diazepam equivalent of the anxiolytics and hypnotics. A t-test was used to compare continuous amounts, and a chi-square test was used for categorical variables, both at a 5% level of significance.

Results
Among all patients, the pregnant patient group had a significantly lower prescription rate for anxiolytics and hypnotics than the non-pregnant group(p=4.0×10-3), but there was no significant difference in the diazepam equivalents among those taking the medications(p=9.22×10-1). Subgroup analysis showed a significant difference in the prescription rate of anxiolytics and hypnotics in patients with depressive disorders(N=20), and showed a lower prescription rates of antidepressants in the pregnant group, although this did not reach significance(p=5.5×10-2). There were no significant differences in the prescription rate of mood stabilizers (p=2.0×10-1 for lithium carbamate, p=6.3×10-2 for mood stabilizers).

Discussion & Conclusion
The study suggests that psychiatrists could discontinue anxiolytics and hypnotics after pregnancy. Further research on the low prescription rate of antidepressants would be needed from the perspective of the appropriate use of psychotropic medications in pregnant women as recommended in the "The Guide for the Care of Pregnant Women with or Potentially with Psychiatric Disorders".
STRESS-RELATED COMPOUND BLOCKS NEUTROPHIL MOBILIZATION AND BEHAVIORAL IMPAIRMENT INDUCED BY CHRONIC SOCIAL STRESS IN MICE
Authors: Zhu *Qing , Hisasue Toshihiro , Yamaguchi Yuta , Taniguchi Masayuki , Ishii Shinichi , Katayama Yoshio , Shinohara Ryota , Furuyashiki Tomoyuki 
Published: February 2025

Abstract

Background
Excessive stress due to adverse and demanding conditions induces emotional and cognitive abnormalities and precipitates mental illnesses such as depression. Clinical and preclinical studies have linked systemic inflammation with depression. Thus, neutrophils and monocytes have been reported to increase in the circulating blood of depressive patients and mice subjected to chronic social stress as a model of depression. Altered levels of compounds have been reported in depressive patients. However, how these changes are related to stress-induced systemic inflammation and its behavioral consequences remains unexplored.

Aims & Objectives
In this study, using a mouse model of repeated social defeat stress (R-SDS), we aim to investigate whether one of the compounds downregulated in the blood of depressive patients (hereafter referred to as ‘Compound X’) affects stress-induced leukocyte mobilization and its behavioral consequences.

Methods
Male C57BL/6 mice were exposed to aggression from a male ICR mouse for two hours daily for six consecutive days. Control mice were left undisturbed for the same six days. Depression-related behaviors were then assessed for multiple behavioral tests, including the social interaction test, the elevated plus maze test, the female urine sniffing test, the sucrose splash test, the novel object recognition test, and the tail suspension test. Compound X (10 mg/kg) was administered to mice via two routes, intraperitoneally or orally, during R-SDS and subsequent behavioral testing. After the mice were sacrificed, leukocytes in the bone marrow, circulating blood, spleen, and brain were collected and analyzed by flow cytometry.

Results
R-SDS induced the mobilization of myeloid cells, especially neutrophils, in the blood, spleen, and brain, which was sustained for at least one week, along with depression-related behaviors. Systemic administration of Compound X blocked R-SDS-induced neutrophil mobilization to the blood, spleen, and brain and alleviated depression-related behaviors, such as social avoidance, increased passive coping behavior, and cognitive deficits.

Discussion & Conclusion
These results demonstrate that Compound X blocks stress- induced neutrophil mobilization into the circulation and behavioral disturbances. Thus, we propose that the reduction of this compound may promote stress-related pathology and provide a novel therapeutic target for depression.