bluuebunny/crossref_metadata_2025_split huggingface dataset:
TAAR1 AGONISTS AS POTENTIAL ANTI-ADDICTION CANDIDATES: PRECLINICAL EVIDENCE
Authors: Li *Jun-Xu 
Published: February 2025

Abstract

Background
TAAR1 represents an exciting new drug target for the development of medications to treat neuropsychiatric disorders, with most exciting discoveries coming from the positive clinical trials of TAAR1 agonist for the treatment of schizophrenia 1.

Aim & Objectives
The objective of this presentation is to provide emerging preclinical findings that TAAR1 functions as a modulating “brake” of central dopaminergic system excitability and as such TAAR1 agonists can counter addiction-related effects of a number of commonly abused drugs with cocaine as an example.

Methods
Commonly used behavioral paradigms designed to measure different aspects of drugs of abuse were employed to examine the reinforcing, motivational and relapse effects of cocaine in rats. Genetic, pharmacological and molecular approaches were used to delineate the underlying mechanisms of TAAR1 agonist-induced anti- addiction effects.

Results
TAAR1 partial agonist RO-5263397 reduced cocaine intake and cocaine reinforcing efficacy as well as cue, drug and stress-induced reinstatement of cocaine-seeking behavior 2. TAAR1 agonist RO5166017 recapitulated the similar efficacy as RO-5263397. RO5166017 attenuated drug-induced reinstatement of cocaine-seeking and prevented drug priming-induced CaMKIIα activity in the NAc shell. Activation of TAAR1 dampened the CaMKIIα/GluR1 signaling pathway in the NAc shell and reduced AMPAR-EPSCs on the NAc slice. Microinjection of the selective TAAR1 antagonist EPPTB into the NAc shell enhanced drug-induced reinstatement as well as potentiated CaMKIIα activity in the NAc shell. Furthermore, viral-mediated expression of CaMKIIα in the NAc shell prevented the behavioral effects of TAAR1 activation 3.

Discussion & Conclusion
TAAR1 agonists reduced different aspects of cocaine addiction, and the effects may be mediated via CaMKIIα/GluR1 signaling pathway in the NAc shell. These results provide strong preclinical evidence that TAAR1 agonists have potential as anti- addiction medications against cocaine use disorder.

References
1. Achtyes ED, Hopkins SC, Dedic N, Dworak H, Zeni C, Koblan K (2023) Ulotaront: review of preliminary evidence for the efficacy and safety of a TAAR1 agonist in schizophrenia. Eur Arch Psychiatry Clin Neurosci, 273(7): 1543-56.
2. Thorn DA, Jing L, Qiu Y, Gancarz-Kausch AM, Galuska CM, Dietz DM, Zhang Y, Li JX. (2014) Effects of the trace amine-associated receptor 1 agonist RO5263397 on abuse-related effects of cocaine in rats. Neuropsychopharmacology, 39(10):2309-16.
3. Liu J, Wu R, Seaman R Jr, Manz KM, Johnson B, Vu J, Huang Y, Zhang Y, Robison AJ, Neve R, Grueter BA, Dietz D, Li JX. (2022) TAAR1 regulates drug-induced reinstatement of cocaine-seeking via negatively modulating CaMKIIα activity in the NAc. Mol Psychiatry, 27(4):2136-2145.
RELATIONSHIP BETWEEN ALCOHOL -RELATED BRAIN DYSFUNCTION AND BRAIN PERFUSION SPECT
Authors: Shirasaka *Tomohiro 
Published: February 2025

Abstract

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&lt;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

Abstract

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

Abstract

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

Abstract

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 &lt;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

Abstract
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

Abstract

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&lt;.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

Abstract
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

Abstract

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

Abstract

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.