bluuebunny/crossref_metadata_2025 huggingface dataset:
THE FATTY ACID AMIDE HYDROLASE ENZYME INHIBITION IN GLOBUS PALLIDUS CAUSES PANICOLYTIC LIKE EFFECT IN PREY THREATNED BY BOTHROPS JARARACA
Authors: Da Silva Juliana Almeida , Falconi-Sobrinho Luiz Luciano , De Paiva Yara Bezerra , Almada Rafael Carvalho , Coimbra *Norberto Cysne
Published: February 2025

The endocannabinoid modulation of fear and anxiety due to their on-demand synthesis and degradation is supported by a large body of research. Although it has been proposed that the anandamide (AEA) in the globus pallidus (GP) seems to be important for the modulation of innate fear-related behaviours, a role for endogenous AEA has yet to be clarified. Rats were treated with the fatty acid amide hydrolase (FAAH) selective inhibitor URB597 at different concentrations (0.01, 0.1, 1 nmol/ 0.1 µL) in the GP followed by bicuculline microinjections in dlSC and confronted by a lancehead pit viper (Bothrops jararaca) in the enriched polygonal arena for snake panic test. The most effective dose of URB597 (1 nmol) was also preceded by microinjections of the CB1 receptor antagonist AM251 (0.1 nmol) in the GP, and rats were then confronted by venomous snakes. URB597 (0.1 and 1 nmol) in the GP decreased the expression of defensive behaviours such as defensive attention, escape, and time spent inside the burrow of animals confronted by pit vipers. Moreover, the pretreatment of the GP with AM251 suppressed these antiaversive effects of URB597 in such midbrain structure. Overall, these data clearly indicate that the panicolytic consequences of the endogenous AEA enhancement in the GP are mediated by CB1 receptors signalling.
IGFBP2 ATTENUATES RESTRAIN STRESS-INDUCED ANXIETY-LIKE BEHAVIOR VIA MODULATING THE MYELINATION AND SYNAPTIC PLASTICITY IN THE MEDIAL PREFRONTAL CORTEX
Authors: Zhang *Ying-Dan , Shi Dong-Dong , Zhang Sen , Wang Zhen
Published: February 2025

Background

Exposure to stress markedly impairs the emotional functions of the highly evolved prefrontal association cortex (PFC). However, the underlying molecular mechanisms are poorly understood and limited options for treatment. Our previous study has found that the level of IGFBP2 in serum is related to stress resilience in individuals. Insulin-like growth factor binding protein 2 (IGFBP2), a neurotrophic factor, has been associated with neurite outgrowth and synaptic plasticity in central nervous system, enhancing stress resilience.

Aim

To examine the protective effects of IGFBP-2 on stress related disorder and explore its mechanism in SD rats and provide new targets for the intervention.

Method

Here, using a model of restrain stress (RS), we found that RS induces obvious anxiety-like behavior in the open field (OFT) and elevated plus maze test (EPM). RNA-sequencing was further applied to analyze the molecular mechanisms of mPFC following RS. Then we injected IGFBP2 by tail vein administrations to evaluate the anxiolytic effect of IGFBP2. Immunofluorescence and electron microscopy experiments were applied to verify the effect of IGFBP2 on RS-induced brain structural and functional abnormalities.

Result

RS enhances susceptibility to anxiety-like behavior in rats, with injured myelination in mPFC. Systemic delivery of IGFBP2 significantly attenuated anxiety-like behavior in OFT and EPM. Besides, IGFBP2 treatment rats showed enhanced myelination of axons compared to controls. To further confirm the pro-myelinating function of IGFBP2, lysolecithin-induced rat model of focal demyelination was used. Our results showed that IGFBP2 treatment was sufficient to attenuate anxiety-like behaviors and promote remyelination in lysolecithin-induced rat model of focal demyelination. In addition, the RS rats treated with IGFBP2 significant increase in the thickness and length of PSD.

Discussion & Conclusion

Collectively, our results demonstrate that the ultrastructural and functional changes of myelin and synaptic alterations in mPFC could be involved in stress-induced anxiety-like behavior. Notably, our study provides the first evidence that systemic delivery of IGFBP2 produced rapid-acting effects in rescuing the anxiety like behavior in RS rat models, which provides a critical rationale about IGFBP2 may has therapeutic potential for the treatment of anxiety disorders from a translational perspective clinically and deserves further study to provide more evidence for the treatment of anxiety disorder in the future.
THE LONGITUDINAL IMPACT OF COVID-19 LOCKDOWNS ON COGNITIVE FUNCTION IN INDIVIDUALS WITH ALZHEIMER’ S DISEASE AND MILD COGNITIVE IMPAIRMENT
Authors: Lee *Hahyun , Lee Jun-Young
Published: February 2025

Objective

This study aims to comprehensively assess the longitudinal repercussions of the COVID-19 lockdowns on individuals diagnosed with Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI).

Methods

The study involved a cohort of 130 individuals (50 MCI, 80 AD) who underwent cognitive assessments in Korea from 2018 to 2021. Longitudinal data were collected to assess the impact of COVID-19 lockdowns. Linear mixed-effects models were employed to assess changes in cognitive, psychological, and behavioral functioning in people with MCI/AD. Path analysis was used to explore the relationships between various cognitive measures(MMSE, CERAD, ADL, IADL, SGDS, NPI) and the Clinical Dementia Rating Scale Sum of Boxes (CDR_SUM)

Results

The findings revealed a statistically significant decline in cognitive function among AD patients during the lockdown period. In contrast, individuals with MCI exhibited comparatively milder deterioration. In the path analysis, MMSE, ADL, and IADL exhibited strong negative associations with CDR_SUM, emphasizing their predictive value in determining the severity of clinical dementia.

Discussion & Conclusion

This study underscores the disproportionate vulnerability of AD individuals to the cognitive consequences of lockdown measures. Our findings highlight the profound impact of social isolation on cognitive functions in individuals with MCI and AD. The integration of linear mixed-effects models and path analysis offers a comprehensive understanding of the dynamic cognitive changes occurring over time. Future interventions and support systems should prioritize addressing specific cognitive domains, such as memory, activities of daily living, and instrumental activities of daily living, to effectively mitigate the adverse effects of social isolation on dementia progression.
ADMINISTRATION OF SSRI DURING PREGNANCY AFFECTED BEHAVIORAL CHANGES AND HIPPOCAMPAL NEUROGENESIS IN OFFSPRING IN RATS
Authors: Horie *Junko , Kinjo Tomoya , Ito Masanobu , Suzuki Toshihito
Published: February 2025

Background

Approximately 10 - 20 % pregnant women have been diagnosed with depression, and 3 - 6% pregnant women receive SSRI treatment. In Japan, it reported that approximately 1% of pregnant women (105 out of 10,000 births) were prescribed SSRIs during the perinatal period. Importantly, SSRIs crossed the placenta and may affect perinatal outcomes in infants exposed to these drugs during pregnancy in human. Several large cohort studies have been conducted, some finding significant differences in the risk of ASD and others not. In the present study, we created an animal model of a patient receiving medication during pregnancy and examined changes in the offspring`s behavior and brain structure.

Aims & Objectives

We created an animal model of a patient receiving medication during pregnancy and examined changes in the offspring`s behavior and brain structure in rats.

Methods

We used pregnant female Wistar rats. Paroxetine was administered daily from ED12.5 to ED21.5, covering the last 9–12 days of pregnancy. Oral sondes were used to keep rodents at a constant daily dose, and paroxetine 1 mg / kg / day or paroxetine 2.5 mg / kg / day or saline was given to the control group. The control group received saline daily. We evaluated spontaneous locomotor activity using the open field test (OF), spontaneous alternation behavior using the Y-maze test, and anxiety behavior using the elevated plus maze test (EPM) in male offspring at PD30. BrdU-positive cells in hippocampus were counted by fluorescence microscope.

Results

Locomotor activities significantly increase in paroxetine 2.5 mg group compare to a control group. The paroxetine 2.5 mg group spent less time in the closed arm compared to the control and paroxetine 1 mg groups in EPM. The number of BrdU-positive cells was significantly increased in the paroxetine 2.5 mg group compared to the control group. There was tendency to be a positive correlation between spontaneous activity and the number of BrdU-positive cells.

Discussion & Conclusions

In this study, it was revealed that oral administration of paroxetine during pregnancy induces hyperactivities and impulsivities in offspring, and increased neurogenesis in hippocampus of rats. There was a positive correlation between locomotor activity and the amount of neurogenesis. SSRI administration during pregnancy may affect the neurodevelopment of the newborn infant.
THE RECOVERY EFFECT OF STEM CELLS AND KAMPO MEDICINE KAMIKIHITO ON SOCIAL BEHAVIOR DYSFUNCTIONS IN REFRACTORY PSYCHIATRIC DISORDERS
Authors: Ukai *Wataru , Deriha Kenta , Nishimura Emi , Hashimoto Eri , Yamada Misa , Hashiguchi Hanako , Hirose Shoma , Mochizuki Marina , Momoki Yukihiko , Furuse Kengo , Ishii Takao , Nagaishi Kanna , Riva Marco A , Kawanishi Chiaki
Published: February 2025

Background

The brain pathophysiology of social dysfunctions in depression and autism spectrum disorder are complex, and there is a growing need to understand the relevant neuronal circuit alterations and to find direct and effective treatments for their recoveries.

Aims & Objectives

In this study, we have investigated the influences of bone marrow-derived mesenchymal stem cell (MSC) transplantation and Japanese Kampo medicine, Kamikihito on social behaviors as a novel treatment options for intractable psychiatric disorders, using refractory depression animal model related to stress vulnerability, we had preliminary established, induced by dual stress during embryonic/juvenile period (Furuse et al., 2019).

Method

We explored the possibility that MSC transplantation, which we have demonstrated the recovery effect on behavioral abnormalities in refractory depression model (Kigawa et al., 2014), and Kamikihito that has been used for anxiety and nervousness in clinics and recently reported to induce changes in emotional and social functions via oxytocinergic neuron enhancement (Tsukada et al., 2021), may promote neural repair and regeneration in brain regions related to social cognition and empathy, which in turn may enhance recovery for social dysfunctions.

Results

In the refractory depression model, active social interaction behavior, as indicated in the social interaction test, was reduced by approximately 50%. In contrast, treatments of MSC alone or MSC and kamikihito significantly improved social interaction behavior, which was reduced in the model animal. On the other hand, no such effects were observed in the group treated with kamikihito alone. In the model group, contact time with the restrained individual and empathy-like voluntary behavior as indicated by rescue behavior were reduced by approximately 40%. Interestingly, the reduction of empathy-like behavior in the model group was significantly improved in the groups treated with kamikihito alone and in the group treated with kamikihito and MSC. On the other hand, MSC monotreatment group could not show any effect.

Discussion & Conclusion

We would add some data of analyzing changes of dynamics of oxytocinergic neurons from the hypothalamic paraventricular nucleus, Parvalbumin (PV)/somatostatin (SS) positive GABA interneuron changes in brain regions including the cingulate cortex, amygdala, and hippocampus in each animal group, and identify brain circuit mutations that lead to social cognitive behavioral abnormalities for revealing the mechanisms of their recoveries.
VITAMIN D AND DEPRESSION
Authors: Suryani *Puji Rizki , Zulissetiana Eka Febri , Prananjaya Bintang Arroyantri , Aini Syarifah , Ikhsan Diyaz Syauki
Published: February 2025

Background

Depression is one of the mood disorders that is often found today. The cause of depression has not yet been determined, but it is believed that genetic, biological and psychosocial factors play an important role. One of them that was found was vitamin D deficiency.1 However, the effect of administering vitamin D in depressed patients has not been determined. Several studies have not found a link between giving vitamin D and improving patients depressive symptoms. Some studies show a positive relationship, but several other studies show a negative or even inconsistent relationship.2

Aims and Objective

This is the basis on which this research was conducted, to determine blood serotonin levels in mice treated with vitamin D.

Method

By using mice induced depression by immobilization, giving Fluoxetine as a standard drug used to treat depression and vitamin D as a comparison, serotonin levels in the mice's blood will be seen. Four groups were divided by the given treatment. No intervention in the first group, while the second group was given Fluoxetine, the third group was given vitamin D, and the last group was given Fluoxetine and vitamin D.

Results

The average serotonin levels in the four groups respectively are 0.031557 pg/ml, 0.031560 pg/ml, 0.031529 pg/ml, and 0.031614 pg/ml. Based on statistical analysis, there were no significant differences between the four groups.

Discussion and Conclusion

In this study, administration of vitamin D and Fluoxetine showed the highest serotonin levels. Fluoxetine is an antidepressant that is often used for depression. Vitamin D metabolites can penetrate the brain barrier and are believed to have an effect as neuroprotector. This may lead the suggests that it also has an effect on depressive symptoms.3A number of studies have found that single administration of vitamin D has an effect on depressive symptoms, while other studies have shown no effect. In this study, serotonin levels in the third group were the lowest which means it shows no effect on depression. 3It can be concluded that giving vitamin D does not have a significant effect on depressive symptoms.

References

Rebecca E S Anglin, Zainab Samaan, Stephen D Walter, Sarah D McDonald. 2018. Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry. https://pubmed.ncbi.nlm.nih.gov/23377209/. Guowei Li, Lawrence Mbuagbaw, Zainab Samaan et al. 2013. Efficacy of Vitamin D supplementation in depression in adults: a systematic review protocol. Biomed Central. http://ncbi.nlm.nih.gov. Vikas Menon,Sujita Kumar Kar, Navratan Suthar, and Naresh Nebhinani. 2020. Vitamin D and Depression: A Critical Appraisal of the Evidence and Future Directions. Indian J Psychol Med. 42(1): 11–21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970300/
INVOLVEMENT OF PGE2-EP1 SIGNALING IN THE PTZ-INDUCED EPILEPTIC SEIZURE AND ITS NEUROINFLAMATION-ASSOCIATED EXACERBATION
Authors: Ishizaka *Yukino , Mouri Akihiro , Kunisawa Kazuo , Nishikawa Takaya , Furuyashiki Tomoyuki , Narumiya Shuh , Nabeshima Toshitaka
Published: February 2025

Background

Epilepsy is one of the most common neurological disorders. Neuroinflammation and an enhanced excitability via NMDA receptor are known to be involved in the pathophysiology of epilepsy. The cyclooxygenase (COX)/prostaglandin E2 (PGE2) signaling pathway plays a critical role in the neuroinflammation. Among PGE2 receptors (EP1-4), EP1 contributes to NMDA receptor-mediated neuronal excitability.

Aims & Objectives

We aimed to investigate whether the PGE2-EP1 signaling is involved in the epileptic seizures induced by pentylenetetrazol (PTZ) in mice.

Method

Pentylenetetrazol (PTZ) was administered to mice every other consecutive day and seizures were evaluated. Co-administration of lipopolysaccharide (LPS) with PTZ and seizure scores were evaluated. Brains were removed and PGE2-related gene mRNA was measured by real-time PCR.

Results

Chronic administration of PTZ exacerbated epileptic seizures and increased expression of EP1 but not cyclooxygenases (COXs) and microsomal prostaglandin E synthases (mPGESs). The exacerbation of seizure was attenuated in the EP1-knockout mice. Co-administration of lipopolysaccharide (LPS) with PTZ increased body-temperature associated with enhanced expression of COX-2 and mPGES-1 and exacerbated epileptic seizures. This exacerbated seizure was also attenuated in the EP1- knockout mice.

Discussion & Conclusion

These data suggested that PGE2-EP1 signaling may have critical roles in the pathophysiology of epilepsy and its exacerbation with neuroinflammation. In conclusion, EP1 receptors may be attractive therapeutic target for epileptic seizure.
CAUSAL ASSOCIATIONS BETWEEN SCHIZOPHRENIA AND CANCERS: MENDELIAN RANDOMIZATION ANALYSES
Authors: Shao *Jun X , Zhu Gang
Published: February 2025

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

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 <0.001) and succinylcholine (p = 0.027), and ECT stimulus parameters (i.e., charge (p <0.001), frequency (p <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

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

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

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

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

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

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

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.
THE SUCROSE INTAKE CHANGES STRESS-INDUCED BEHAVIOR VIA GLUCOSE METABOLISM AND NORADRENERGIC NEURONAL SYSTEM
Authors: Sakata *Takatoshi , Mouri Akihiro , Kazuo Kunisawa , Hasegawa Masaya , Takemura Masao , Matunami Hidetoshi , Saito Kuniaki , Nabeshima Toshitaka
Published: February 2025

Background

322 million people globally are suffering from major depressive disorder (MDD). MDD is projected to become the primary cause of disease burden by 2030. Lifestyle habits have attracted attention as potential environmental factors for MDD. However, it remains unclear how lifestyle habits affect pathophysiology of depression.

Aims & Objectives

In this study, we analyzed lifestyle habits in high-risk subjects of major depressive disorder (HRMDD) by using the clinical database from Resource Center for Health Science (RECHS). A notable observation from our analysis revealed that sucrose intake was elevated among HRMDD subjects.

Method

To investigate whether sucrose intake affects stress-induced depression-like behaviors, we observed the behaviors of mice took freely sucrose via water bottle under the chronic unpredictable mild stress (CUMS).

Results

Our findings revealed that sucrose intake attenuated CUMS-induced hyperactivity and aggressive behavior but not social deficit. Unexpectedly, the sucrose intake under CUMS impaired recognition memory. Furthermore, sucrose intake under stress increased serum corticosterone levels and blood glucose levels. In association with high blood glucose level, CUMS changed expression of mRNA related to glucose and lactate metabolism such as glucose transporter, lactate dehydrogenase, and monocarboxylate transporter in the prefrontal cortex (PFC). Further, CUMS reduced noradrenaline (NA) levels in the PFC. Sucrose intake under CUMS ameliorated reduction in NA levels, although it decreased the turnover of NA, which associated with expression of decrease in adrenergic α1 receptors, but of an increase in of adrenergic α2 receptors. Antidepressants targeting noradrenergic neuronal system alleviated these depression-like behaviors and cognitive dysfunction.

Discussion & Conclusion

In conclusion, our data suggest that high sucrose intake in HRMDD may cope stress-induced aggression and hyperactivity. However, this comes with the unintended consequence of impairment of cognition. These contradictory findings may be associated with changes of glucose and lactate metabolism and noradrenergic system in the PFC.
DYSFUNCTIONAL INTERACTIONS OF SALIENCE NETWORK IN EARLY PSYCHOSIS
Authors: Zhao *Lei , Bo Qijing , Wang Chuanyue
Published: February 2025

Background

Currently, there is increasing attention paid to early psychiatric populations such as first episode of schizophrenia (FES) and clinical high risk for schizophrenia (CHR). Research based on static functional connectivity (FC) has unanimously recognized functional abnormalities in the salience network (SN) of schizophrenia, but there is still controversy over whether these abnormalities will fully extend to the early stages of mental illness.

Aims

The aim of this study is to evaluate the functional interaction characteristics of early psychiatric salience networks based on network level assessment.

Methods

This study focuses on data from 26 cases of FES, 20 cases of CHR, and 37 healthy controls (HC). Based on network level, static FC analysis method is used to explore the functional connectivity characteristics within the early mental patient population's saliency network and with advanced cognitive networks (DMN, CEN) and sensory networks (SMN, AN, VN). Use analysis of variance or Kruskal Wallis H-test to compare the intergroup differences of the above indicators, and Spearman correlation analysis to explore the brain behavioral correlation between intergroup difference indicators and clinical and cognitive data of early psychiatric patients.

Results

Static functional connectivity analysis found that compared to HC, the FC between FES salient network and default network, auditory network decreased or showed a decreasing trend (PSN-DMN=0.038, PSN-AN=0.066).

Conclusion

Abnormal functional interaction between early psychiatric prominence networks, advanced cognitive networks, and sensory networks in a resting state.
THE EFFECT OF STATE-TRAIT ANGER EXPRESSION ON VIOLENCE POTENTIAL INDEX IN CRIMINAL SUBJECTS WITH SCHIZOPHRENIA
Authors: Chee *Hyun Seung , Han Solee
Published: February 2025

Background

Anger is defined as a psycho-biological emotional state that consists of feelings varying in intensity from mild irritation or annoyance to intense fury and rage. And, anger is a species-typical response to either: perceived threat, frustration or social provocation. The most important point about anger regulation by the individuals is how to express anger and control it. Dysfunction in anger regulation is a marker of most psychiatric disorders. Assessing risk of harm to self and others is a very important element in the evaluation and treatment of subjects with psychiatric disorder. The Violence Potential Index(VPI) have been found to be most associated with violence and dangerousness.

Aims & Objectives

The authors examined the effect of state-trait anger expression on violence potential index(VPI) in criminal subjects with schizophrenia.

Methods

The sample consisted of 177 criminal subjects with schizophrenia. First, We investigated whether there was a difference in state-trait anger expression between male and female group. After that, we investigated the effect of state-trait anger expression on VPI in the entire subjects with criminal schizophrenia, and the effect of state-trait anger expression on VPI was examined for male and female groups respectively. State-trait anger expression was assessed with Korean State-Trait Anger Expression Inventory(STAXI-K). Assessment of Violence Potential Index(VPI) was performed using the Personality Assessment Inventory(PAI).

Results

In comparison of male and female group, there were no differences in current age, age of onset, age at time of crime, or education level, and state anger was higher in the male group(t=2.620, p=0.011). However, there were no differences in trait anger, anger in, anger out, and anger control. The factor affecting VPI for the entire subject group was trait anger(B=0.164, ß=0.317, t=4.419, p=0.000). The factor affecting VPI in the male group was anger out(B=0.232, ß=0.294, t=3.688, P=0.000), and in the female group, trait anger was found to affect VPI(B=0.213, ß=0.469, t=2.856, p=0.008).

Discussion & Conclusion

It was shown that anger out in the male group and trait anger in the female group influenced VPI. It was suggested that there may be a difference in state-trait anger expression on VPI between male and female groups. In the future, a comparative study including non-criminal subjects with schizophrenia and the general population is needed to determine the impact of state-trait anger expression on crime in patients with schizophrenia.