bluuebunny/crossref_metadata_2025 huggingface dataset:
RELATIONSHIP BETWEEN ALCOHOL -RELATED BRAIN DYSFUNCTION AND BRAIN PERFUSION SPECT
Authors: Shirasaka *Tomohiro
Published: February 2025

Background

In Japan, the nationwide survey for assessing the prevalence of alcohol dependence syndrome per the ICD-10 criteria estimated that the number of individuals with alcohol dependence syndrome was 1.09 million. One notable finding is the steep increase in alcohol consumption among the elder person. Alcohol-related brain dysfunction has become a serious social problem in Japan. It is a form of dementia caused by long-term, excessive consumption of alcoholic beverages, resulting in neurological damage and impaired cognitive function. Certain individuals with alcohol-related brain dysfunction present with damage to the frontal lobes of their brain causing disinhibition, loss of planning and executive functions. In this time focus on the Alcoholics, we conducted a survey of alcohol-related cognitive dysfunction and related cerebral blood flow(CBF) by the RI scintigraphy.

Method

Subjects were 11 alcoholics and 34 healthy controls. To evaluate regional patterns of CBF, Z-score analysis was carried. To evaluate regional patterns of CBF alterations, two-sample t-test values were calculated on a pixel- by-pixel basis between Alcoholics and normal control. To evaluate their correlation between the CBF and Frontal Assessment Battery(FAB) was examined using Pearson's correlation coefficient.

Results

Compare with the normal control, we found that alcoholics have a significant reduction of the blood flow at the medial frontal lobe and we found a significant correlation between the FAB scale and the CBF decreasing (r=0.683, p<0.05) suggesting that frontal dysfunction and frontal blood flow are associated with each other. We will show the detail contents in this presentation.
LONG-ACTING INJECTABLE ANTIPSYCHOTIC USE IN PATIENTS WITH BIPOLAR DISORDER: FINDINGS FROM REAP-BD STUDY
Authors: Lin *Shih-Ku , Lin Chun
Published: February 2025

Background

Bipolar disorder is a mental illness characterized by significant mood fluctuations and extreme mood swings. The standard treatment for bipolar disorder includes oral medication therapy and psychotherapy. For oral medications, a combination of mood stabilizers and antipsychotic medications is commonly prescribed, and may be supplemented with other psychotropics such as antidepressants, anxiolytics, and sedative-hypnotics. However, in recent years, long-acting injectable antipsychotics (LAIA) have emerged as a promising therapeutic option. Aims: To survey the use of LAIA in bipolar disorder across Asian countries, including China, Hong Kong, India, Indonesia, Japan, Korea, Pakistan, Malaysia, Myanmar, Singapore, Sri Lanka, Thailand, and Taiwan. Method: Data including demographics and medications of patients with bipolar disorder were collected through an online website-based system.

Results

A total of 2,121 prescription records were collected, and among them, 104 (4.9%) patients were prescribed LAIA, with the majority (76.9%) receiving first-generation antipsychotics. India, Myanmar, and Japan do not prescribe LAIA at all. The highest rate is Sri Lanka (20.0%), followed by Malaysia (16.9%), and Singapore (15.8%). Other countries had prescription rates of less than 10%. Compared with the group of oral medications, the LAIA group has a younger age, a higher psychotropic drug load, more male sex, and a higher body mass index.

Discussion &Conclusion

An extensive variation in the utilization of LAIA among patients with bipolar disorder was observed across different Asian countries, with the majority using FGA. This variation in prescription patterns warrants further investigation.
MODULATION OF THE DOPAMINERGIC NEUROTRANSMISSION BY CONTROLLING THE ACTIVITY OF TYROSINE HYDROXYLASE
Authors: Ichinose *Hiroshi , Aida Rina , Nago-Iwashita Yuka , Moriya Yuki , Ide Soichiro , Ikeda Kazutaka
Published: February 2025

Background

Dopaminergic neurotransmission is involved in several important issues for determination of our behaviour including motivation, decision-making, and motor-control. Therefore, its dysfunction is deeply involved in movement disorders and neuro-psychiatric disorders.

Aims & Objectives

Dopamine is synthesized from tyrosine by the action of tyrosine hydroxylase (TH). While TH is known to be a rate-limiting enzyme for the dopamine synthesis, we found that the metabolism of dopamine in the nerve terminal was different from that in the cell body (1,2). Besides, the mice overexpressing the active-form of TH using a micro-injection of AAV-Th into the midbrain showed a dramatically enhanced locomotor activity induced by methamphetamine (METH), while the dopamine levels in the nucleus accumbens (NAc) were almost unchanged. Our findings suggest that the levels of the TH activity rather than the dopamine contents would affect the METH responses.

Results

Here, we examined the locomotor activity induced by METH in heterozygous Th-knockout mice, in which the TH expression levels are about half of the wild-type while the dopamine levels were not decreased in the brain. We found that the locomotor activities of the heterozygous Th-knockout mice were less than that of the wild-type. Next, we administered a TH inhibitor, a-methyl-p-tyrosine (AMPT) to the mice. Administration of AMPT dose-dependently reduced the locomotor activities to METH.

Discussion & Conclusion

These results showed that the METH responses were affected by the TH activity and expression levels, and suggest that the TH activity would be a drug-target for patients suffered from addiction disorders by altering the metabolism of dopamine.

References

1)TOKUOKA, H., MURAMATSU, S., SUMI-ICHINOSE, C., SAKANE, H., KOJIMA, M., ASO, Y., NOMURA, T., METZGER, D. &ICHINOSE, H. 2011. Compensatory regulation of dopamine after ablation of the tyrosine hydroxylase gene in the nigrostriatal projection. J Biol Chem, 286, 43549-58.

2)NAGO-IWASHITA, Y., MORIYA, Y., HARA, S., OGAWA, R., AIDA, R., MIYAJIMA, K., SHIMURA, T., MURAMATSU, S. I., IDE, S., IKEDA, K. &ICHINOSE, H. 2023. Overexpression of tyrosine hydroxylase in dopaminergic neurons increased sensitivity to methamphetamine. Neurochem Int, 164,105491.
GXE INTERACTION EFFECTS OF HCRTR2 SINGLE NUCLEOTIDE POLYMORPHISM AND ADVERSE CHILDHOOD EXPERIENCES ON METHAMPHETAMINE USE DISORDER
Authors: Chen *Kai-Ting , Huang Ming-Chyi , Lin Chun , Chang Hu-Ming , Kao Chung-Feng
Published: February 2025

Background

Methamphetamine (METH) use disorder (MUD) is a major global health concern. The hypothalamic orexin system regulates stress response and addictive behaviors. The genetic variation in the hypocretin receptor 2 (HCRTR2), rs2653349, is associated with substance dependence. We explored the gene- environment (GxE) interaction of SNP rs2653349 and adverse childhood experiences (ACEs) in relation to MUD susceptibility. We explored the gene-environment (GxE) interaction involving SNP rs2653349 and early-life stress factors, adverse childhood experiences (ACEs), in relation to MUD susceptibility.

Methods

Four hundred and one individuals with MUD and 348 healthy controls completed a self-report questionnaire evaluating ACEs, encompassing childhood abuse and household dysfunction categories, and were genotyped for SNP rs2653349. METH use variables were collected using the Diagnostic Interview for Genetic Studies. We used regression analyses to assess the GxE effect on MUD risk.

Results

The MUD group had a comparable genotypic distribution for rs2653349 to the control group, albeit with a higher prevalence and number of types of ACEs, which was linked to an increased MUD risk (p <0.05). No significant genetic impact of rs2653349 on MUD risk was found. However, we observed a GxE interaction effect between the minor allele of rs2653349 and the number of childhood abuse or household dysfunction types, correlating with a reduced MUD risk (OR = -0.71, p = 0.04, adjusted p = 0.08 and OR = -0.59, p = 0.045, adjusted p = 0.09, respectively).

Conclusion

HCRTR2 SNP rs2653349 has no significant impact on MUD risk, but ACEs might increase this risk. GxE results suggest that rs2653349 could offer protection against developing MUD in individuals experiencing multiple types of ACEs.
NAVIGATING BIPOLAR DISORDERS: ADDRESSING CHALLENGES IN TREATMENT-RESISTANT DEPRESSION AND RAPID CYCLING
Authors: Dines *Micaela
Published: February 2025

Bipolar disorders present complex and debilitating mental disorder, characterized by extreme mood swings ranging from manic to depressive episodes and mixed symptoms in between (Tondo et al 2017). Despite significant advancements in understanding and managing bipolar disorders, certain treatment aspects of the illness remain challenging to address (Baldessarini et al 2019a). This oral presentation focuses on two critical topics in the field: treatment-resistant depression, rapid cycling in individuals with bipolar disorders.The first section of this oral presentation aims to discuss treatment-resistant depression in bipolar disorders. Despite the availability of various treatment options, a subset of patients experiences persistent depressive symptoms that do not respond adequately to standard interventions (Baldessarini et al 2020). The presenter will discuss the importance of recognizing treatment-resistant depression early in the course of the illness to prevent long-term disability, exploring potential pharmacological options, and improve overall outcomes for affected individuals (Bahji et al 2021; Vazquez et al 2017, Vazquez et al 2023).The second session is dedicated to understanding and managing rapid cycling in bipolar disorders. Rapid cycling refers to the phenomenon of frequent and distinct shifts between manic and depressive states within a year (Miola et al 2023a). This condition poses unique challenges, as it can lead to increased disability and reduced response to traditional treatments. By reviewing the current knowledge on the topic the session aims to facilitate the identification, management and prevention strategies that can help stabilize mood fluctuations in rapid cycling patients (Miola et al 2023b).
COMBINING PHARMACOTHERAPY AND COGNITIVE TRAINING IN SCHIZOPHRENIA: EFFECTS ON COGNITION AND FUNCTIONAL OUTCOME
Authors: Sachs *Gabriele , Erfurth Andreas
Published: February 2025

Objectives

Cognitive impairment is a common feature of psychiatric disorders. The Screen for Cognitive Impairment in Psychiatry (SCIP) has been developed for routine screening of psychiatric patients and is available in several languages. The German version (SCIP-G) was used in 3 studies: 1. to investigate the feasibility, reliability and validity of the SCIP-G [Sachs et al. Schizophr. Res. Cogn. 2021: 25, 100197], 2. to perform a confirmatory factor analysis [Sachs et al. Schizophr. Res. Cogn. 2022: 29, 100259], and 3. to assess patients before and after standard inpatient treatment including cognitive training.

Methods

Study 1 included patients with schizophrenia or schizoaffective psychosis and thirty healthy controls matched for sex, age and education. In study 3, all patients received modern pharmacotherapy plus cognitive remediation using the COGPACK® software package version 6.06; 54 patients were diagnosed with F2 (schizophrenia, schizotypal and delusional disorder) based on ICD-10 research criteria. They were compared with 39 patients meeting criteria for bipolar disorder (F30 and F31) and 50 for depression (F32 and F33).

Results

In Study 1, significant differences in cognitive performance were found between patients and healthy controls on both versions of the SCIP. The SCIP discriminated effectively between patients and controls. In Study 2, a two-factor solution yielded a good model fit (χ² = 6.7, df = 3, p =.08, χ²/df = 2.2). In study 3, the total SCIP score showed significant improvement after treatment in all three diagnostic groups (p<.001), with no statistically significant interaction between total SCIP score and diagnostic group (p =.860).

Conclusion

Our data suggest that the SCIP-G is a valid and reliable instrument for the assessment of cognitive impairment. Good model fit can be achieved with a two-factor solution for the SCIP. Inpatient treatment consisting of pharmacotherapy and cognitive training improved cognitive deficits. This improvement in cognitive performance was observed to a similar extent in patients with schizophrenia, bipolar disorder and major depression and were accompanied by improvements in functional outcome.
SERUM EXTRACELLULAR VESICLE-DERIVED HSA-MIR-2277-3P AND HSA-MIR-6813-3P ARE POTENTIAL BIOMARKERS FOR MAJOR DEPRESSION
Authors: Yoshimura *Reiji , Seki Issei , Izumi Hiroto , Okamoto Naomichi , Ikenouchi Atsuko , Morimoto Yasuo , Horie Seichi
Published: February 2025

The aim of the present study was to investigate the association between miRNA levels in extracellular vesicles (EVs) from serum and the severity of Major Depression (MD). Patient sera from 16 MD cases were collected at our university hospital. The miRNAs contained in EVs were extracted using a nanofiltration method, and their expression levels were analyzed using miRNA microarrays. Intergroup comparisons were performed to validate the diagnostic performance of miRNAs in EVs. In addition, candidate miRNAs in EVs were added to neural progenitor cells, astrocytes, and microglial cells in vitro, and the predicted target genes of the candidate miRNAs were extracted. The predicted target genes underwent enrichment analysis. The expression levels of hsa-miR-6813-3p and hsa-miR-2277-3p were significantly downregulated with increasing depression severity of MD. The pathway enrichment analysis suggests that hsa-miR-6813-3p may be involved in glucocorticoid receptor and gamma-aminobutyric acid receptor signaling. Additionally, hsa-miR-2277-3p was found to be involved in the dopaminergic neural pathway. The analysis of serum miRNAs in EVs suggests that hsa-miR-6813-3p and hsa-miR-2277-3p could serve as novel biomarkers for MD, reflecting its severity. Moreover, these miRNAs in EVs could help understand MD pathophysiology. This preliminary srudy may shed light on the role for these two miRNA on pathophysiology for MD. We are reconfirming the results with larger MD samples.
PLASMA GLIAL FIBRILLARY ACIDIC PROTEIN (GFAP) IN ASTROCYTES CONTRIBUTES TO INCREASES IN THE PREVALENCE OF AUTISM SPECTRUM DISORDERS (ASD)
Authors: Yui *Kunio
Published: February 2025

Background

Increased prevalence of autism spectrum disorders (ASD) [1] and appearance of nanoparticle production [2] occurred at 2005. Therefore, exposure to nanoparticle may contribute to increase of prevalence of ASD. Astroglia plays an important role in the synaptic circuits, and dysfunction of astrocyte increase serum glial fibrillary acidic protein (GFAP). Exposure of carbon black nanoparticle (CB-NP) may related to increased ASD prevalence

Aims and Objectives

To study examine the effects of exposure of CB-NP on increased ASD prevalence, plasma GFAP levels were measured. We studied the asociation between plasma CB-NP levels, and urinary antioxidant capacity and nutrient intake.

Methods

Assessment of plasma GFAP levels and urinary antioxidant capacity in the 23 individuals with ASD (mean age 12.1years) and 15 healthy controls (mean age 17.1 years), using ELISA Enzyme Immunoassay kit and Total Antioxidant Power Kit, respectively. Nutrient intake was assessed using a semi-constructive questionnaire of DHQ15 (Tokyo, Japan)

Results

ASD group significantly increased plasma GFAP levels than control group Plasma GFAP levels were significantly associated with the total scores of Aberrant Behavioral Checklist and Social Responsiveness Scale but no association of urinary antioxidant capacity and nutrient intake.

Discussion and Conclusion

Astrocytes elucidate the signaling networks [4], exposure to CB-NP increased plasma GFAP levels due to astrogliosis and signaling dysfunction via sphingosine 1-phosphate (SIP) metabolism, NLRP3 inflamasome or Mmp3 expression, and then might contribute to increased prevalence of ASD.

References

1. Lewandowski, T.A., Bartell, S.M., Yager, J.W., Levin, L. (2009) An evaluation of surrogate chemical exposure measures and autism prevalence in Texas. J Toxicol Environ Health A. 72(24), pp. 1592-603. doi: 10.1080/ 15287390903232483.

2. Liu, Y.Y., Chang, B.M., Chang, H.C. (2020) Nanodiamond-enabled biomedical imaging. Nanomedicine (Lond). 15(16), pp. 1599-1616. doi: 10.2217/nnm-2020-0091.

3. Onoda, A., Hagiwara, S., Kubota, N., Yanagita, S., Takeda, K., Umezawa, M. (2022) A Novel Staining Method for Detection of Brain Perivascular Injuries Induced by Nanoparticle: Periodic Acid-Schiff and Immunohistochemical Double-Staining. Front Toxicol. 825984. doi: 10.3389/ftox.2022.825984

4. Soto, J.S., Jami-Alahmadi, Y., Chacon, J., Moye, S.L., Diaz-Castro, B., Wohlschlegel, J.A,. Khakh, B.S. (2023). Astrocyte-neuron subproteomes and obsessive-compulsive disorder mechanisms. Nature. 2023 616 (7958). pp. 764-773. doi: 10.1038/s41586-023-05927-7.
MEMORY RELATED STRUCTURAL AND FUNCTIONAL NEURAL CHANGES FOLLOWING A SINGLE INFUSION OF KETAMINE IN PTSD
Authors: Harpaz-Rotem *Ilan , Duek Or , Korem Nachshon , Krystal John
Published: February 2025

Background

NMDA receptor antagonists play a vital role in new fear memory learning and extinction. Crucial to post-retrieval extinction processes is the reconsolidation window, where memories are activated into a labile state and then reconsolidated in an altered form into the hippocampus. This concept might have significant clinical implications for the treatment of PTSD.

Aims & Objectives

we tested the potential of a single subanesthetic intravenous infusion of ketamine (NMDA receptor antagonist) after recall, to enhance post-retrieval extinction of PTSD trauma memories.

Method

28 participants suffering from PTSD were randomly assigned to receive either ketamine (0.5mg/kg 40 minutes; N=14) or midazolam (0.045mg/kg; N=14) after retrieval of the traumatic memory. 24 hours following infusion, participants received a four-day retrieval and processing trauma-focused psychotherapy. They were assessed before treatment, at the end of treatment, and at 30-day follow-up. Using amygdala activity as a major biomarker of fear response, we tested the potential of a single subanesthetic intravenous infusion of ketamine (NMDA receptor antagonist) after recall, to enhance post-retrieval extinction of PTSD trauma memories. We also tested changes in white matters pre-post treatment.

Results

Post-treatment, ketamine recipients showed a lower amygdala (-0.33, sd=0.13, 95%HDI [-0.56,-0.04])and hippocampus (-0.3 (sd=0.19), 95%HDI [-0.65, 0.04]; marginal effect) reactivation to trauma memories, compared to midazolam recipients. Post-retrieval ketamine administration was also associated with decreased connectivity between the amygdala and hippocampus (-0.28, sd=.11, 95%HDI [-0.46, -0.11]), with no change in amygdala-vmPFC connectivity. Moreover, reduction in fractional anisotropy in bi-lateral uncinate fasciculus was seen in the Ketamine recipients compared with the midazolam recipients (right: post-treatment: -0.01108, 95% HDI [-0.0184,-0.003]; follow-up: -0.0183, 95% HDI [-0.02719,-0.0107]; left: post-treatment: -0.019, 95% HDI [-0.028,-0.011]; follow-up: -0.017, 95% HDI [-0.026,-0.007])

Discussion & Conclusion

Taken together it is possible that ketamine may enhance post-retrieval extinction of trauma memories in humans. These preliminary findings show promising direction toward the capacity to rewrite human traumatic memories and modulate the fear response for at least 30 days post-extinction. The naturalistic stimuli used here promote an ecological measurement of the brain’ s response to traumatic memories.
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

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<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<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>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

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

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 >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

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

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

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<0.001). Participants with age. 65 years old and female were found to be significantly protective on depression. (Age >65 year old: OR=1.70 95% CI: (1.37- 2.11), p<0.001:female: OR=1.86 95% CI: (1.53-2.26), p<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

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

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

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.
NEUROFILAMENT LIGHT CHAIN AS A POTENTIAL INDICATOR OF DELIRIUM TREMENS AMONG PATIENTS WITH ALCOHOL DEPENDENCE
Authors: Hou *Yu Chi , Huang Ming Chyi , Liu Tung Hsia , Liu Yu Li
Published: February 2025

Background

Delirium tremens (DTs) is the most serious complication of alcohol withdrawal syndrome in patients with alcohol dependence (AD) as it is associated with high risk of mortality rate if not recognized promptly and treated adequately. Neurofilament light chain (NFL), as a measure of neuroaxonal injury, has recently gained attention in AD(Huang et al., 2023). However, whether NFL level differs between patients with and without DTs has not been explored yet.

Aims & Objectives

We compared the blood NFL levels between patients with AD who had experience of DTs and those did not to test the hypothesis that NFL can identify the patients with AD to develop DTs.

Methods

224 inpatients fulfilled the DSM-IV-TR criteria for AD and 116 healthy controls were enrolled. Patients with AD were divided by the appearance of DTs into the DT group (n = 25) and non-DT group (n = 199). Blood levels of NFL were measured by Ella microfluid platform analysis. We performed the receiver operating characteristic (ROC) analysis to determine the possibility of NFL level to discriminate individuals with DTs.

Results

Serum NFL levels differed significantly among the three groups, with highest in the DT group (63.1 ± 47.2 pg/mL), followed by non-DT group (24.0 ± 22.4 pg/mL) and then control group (11.8 ± 6.1 pg/mL) (p <0.0001). In addition, the ROC curve revealed that an NFL level of 31.2 pg/mL could significantly differentiate DTs group from non-DT group (sensitivity: 80.0%; specificity: 76.9%; area under the curve: 0.84; p <0.001; 95% Confidence Intervals for the AUC: 0.77-0.91).

Discussion & Conclusion

Our study revealed the patients with AD experiencing DTs had a significantly higher NFL level, compared to those without such experiences. This result indicate the NFL can be an indicator of delirium tremens in patients with alcohol dependence.Furthermore, the pronounced increase of NFL levels in the patients with AD warrants further investigation of a potential neuroaxonal vulnerability of patients with AD to the development of DTs.

References

HUANG, M. C., TU, H. Y., CHUNG, R. H., KUO, H. W., LIU, T. H., CHEN, C. H., MOCHLY-ROSEN, D. &LIU, Y. L. 2023. Changes of neurofilament light chain in patients with alcohol dependence following withdrawal and the genetic effect from ALDH2 Polymorphism. Eur Arch Psychiatry Clin Neurosci.
NEUROPSYCHOLOGICAL FEATURES AS MEDIATORS BETWEEN PSYCHOPATHOLOGIES AND HEART RATE VARIABILITY: THE SEX DEFFERENCES
Authors: Huang *Wei-Lieh , Liao Shih-Cheng , Wu Chi-Shin , Chiu Yi-Ting
Published: February 2025

Background

Heart rate variability (HRV), as an index of parasympathetic activity, has been reported to be lower in individuals with common mental disorders (depression, anxiety, and somatic symptoms) than in healthy individuals in previous studies. Several meta-analyses have supported this result, but the effect sizes of the differences between patients and healthy individuals are mostly low to moderate, making it difficult for small sample studies to demonstrate between-group differences. Therefore, the mechanisms underlying the link between the psychopathologies of common mental disorders and HRV require further investigation. In recent years, the theory of the frontal-vagal network has gained increasing attention. Furthermore, the relationship between psychopathologies and HRV has been reported to differ between sexes.

Aims & Objectives

Under the hypothesis that disorder status affects cognitive function, we examined whether neuropsychological features can be mediators between psychopathologies and HRV and possible sex differences.

Method

We recruited 359 individuals with and without common mental disorders. Questionnaires were used to measure their psychopathologies. Eight tests from the Cambridge Neuropsychological Test Automated Battery were selected to measure neuropsychological functions. Resting-state HRV measurements were obtained for 5 min. The associations among these constructs were analyzed using multiple linear regression analysis and structural equation modelling.

Results

When psychopathologies and neuropsychological features were simultaneously included as independent variables, most psychopathologies did not exhibit significant associations with HRV. Among women, Reaction Time (RTI, a task of psychomotor speed) indicator mediated the relationship between depression and low-frequency power (LF); Emotion Recognition Task (ERT, a task of emotional regulation) indicator mediated the relationship between health anxiety and high-frequency power (HF). Among men, Intra-Extra Dimensional Set Shift (IED, a task of shifting) indicator mediated the relationship between depression and LF; Match to Sample Visual Search (MTS, a task of selective attention) indicator mediated the relationship between health cognition and HF. The depression-RTI-LF pathway in women tended to lower HRV; whereas health anxiety-ERT-HF in women, depression-IED-LF and health cognition-MTS-HF in men tended to increase HRV.

Discussion & Conclusion

Our findings support the notion that neuropsychological features mediate the relationship between psychopathologies and HRV, and that sex differences exist.