bluuebunny/crossref_metadata_2025_split huggingface dataset:
DOES COCAINE-INDUCED AGGRAVATION OF DEPRESSION ALTER MATE ATTRACTIVENESS IN MALES?
Authors: Ohnishi *Yoshinori N , Kawahara Yukie , Ohnishi Yoko , Nishi Akinori 
Published: February 2025

Abstract
Social defeat stress is a recognized method to induce depressive-like behaviors in mice. Our study found that when mice subjected to social defeat stress were later administered with cocaine, their depressive state significantly worsened. Notably, the typical anti-depressive effects gained from overexpressing DFosB in the nucleus accumbens (NAc), a region known for mediating anti-depressive states, failed to counteract the exacerbating effects of cocaine. Interestingly, a pre-treatment involving electrical shocks to the brain triggered the induction of endogenous DFosB, generating an anti-depressive effect.
Nevertheless, even in this mitigated state, subsequent cocaine administration reinstated the depressive behaviors. To robustly verify the intensification of the depressive state, behavioral paradigms like the elevated plus maze and forced swim test were conducted both before and after cocaine treatment. A notable deterioration in performance was observed specifically in the forced swim test post-cocaine administration. Given our understanding that male attractiveness in mice is influenced by physical appearance and perceived confidence, we postulated how this intensified depressive state might affect a male's attractiveness. Observations revealed that during the depressive state induced by social defeat, dopaminergic neurons in the ventral tegmental area (VTA) exhibit hyperactivity. Building on this, we employed a retrograde AAV DIO Gi and Gq injection into the NAc of TH-cre mice. The objective is to delineate the impact of dopaminergic neuron activity on both male attractiveness and the depressive state under the combined influence of social defeat and cocaine. In conclusion, this study illuminates the intricate relationship between cocaine, social defeat-induced depression, and male attractiveness, providing crucial insights into the underlying neurobiological mechanisms and potential therapeutic interventions.
N,N-DIMETHYLTRYPTAMINE, A NATURAL HALLUCINOGEN, AMELIORATES ALZHEIMER’ S DISEASE BY RESTORING NEURONAL SIGMA-1 RECEPTOR- MEDIATED ENDOPLASMIC RETICULUM-MITOCHONDRIA CROSSTALK
Authors: Cheng Dan , Zhang *Zhang-Jin 
Published: February 2025

Abstract

Background
Aberrant neuronal Sigma-1 receptor (Sig-1r)-mediated signaling between the endoplasmic reticulum (ER) and mitochondria plays an essential role in neuronal cytopathology of Alzheimer’ s disease (AD). The natural hallucinogen N,N-dimethyltryptamine (DMT) is a Sig-1r agonist that may have the anti- AD potential by protecting neuronal ER-mitochondrial interplay.

Aim and Objectives
The purpose of this study was to systematically investigate the anti-AD effects of DMT and the association with its restoration of neuronal ER-mitochondria signaling.

Methods
Effects of chronic DMT (2 mg/kg) for 3 weeks on cognitive impairment and Aβ deposits were examined in 3× TG-AD transgenic mouse model of AD. The effects of DMT on the expression of Sig-1r and mitochondria-associated membranes (MAM)-associated proteins, physical contact, and calcium dynamic between ER and mitochondria were detected in in vitro and in vivo paradigms, with the utilization of Sig-1r knockdown mice and the Sig-1r antagonist BD1063.

Results
Chronic DMT markedly alleviated cognitive impairment in water maze of 3× TG-AD transgenic mice. In parallel, it largely diminished Aβ deposits in the hippocampus and prefrontal cortex. DMT restored the decreased Sig-1r levels of the transgenic and knockdown mice and in cultured hippocampal neurons co-treated with BD1063. DMT prevented physical contact and calcium dynamic between the two organelles in in vitro and in vivo pathological circumstances. The hallucinogen also reinstated the expression of multiple mitochondria-associated membrane (MAM)-associated proteins in 3× TG-AD mice.

Discussion and Conclusions
These results suggest that the anti-AD effects of DMT are associated with its protection of neuronal ER-mitochondria crosstalk via the Sig-1r activation. DMT may serve as a novel preventive and therapeutic agent against AD.
REGULATION OF THE TRANSITION BETWEEN MEMORY RECALL AND NON- RECALL BY HISTAMINE NEURON ACTIVITY
Authors: Takamura *Yuki , Morishita Yoshikazu , Nishimura Kyoka , Hitora(Imamura) Natsuko , Minami Masabumi , Nomura Hiroshi 
Published: February 2025

Abstract

Background
The spontaneous recollection of forgotten memories remains a puzzling aspect of cognitive function, with uncertain mechanistic underpinnings. Brain histamine is produced in the tuberomammillary nucleus (TMN) and is involved in various functions, including learning and memory. In our previous work, we demonstrated that upregulating histamine release by administrating histamine H3 receptor inverse agonists promotes the recall of forgotten memories.

Aims & Objectives
The purpose of this study is to examine whether and how histamine neuronal activity regulates the transition between recall and non-recall.

Method
To probe the dynamics of histaminergic neuronal activity during associative tone-reward learning, we employed fiber photometry. Specifically, a genetically encoded fluorescent calcium sensor GCaMP6s was expressed in histamine neurons within the mouse TMN, and its fluorescence was monitored through implanted optical fibers. We assessed the impact of histamine neuronal activity on associative memory recall by optogenetically inhibiting these neurons. We expressed a light-sensitive chloride ion pump, NpHR, in TMN histamine neurons and utilized green light illumination to modulate their activity.

Results
After several days of tone-reward conditioning, the mice exhibited predictive licking responses following tone presentations in some trials (recall trials), whereas such responses were absent in other trials (non-recall trials). We compared the histamine neuronal activity between the recall and non-recall and found that the histaminergic neuronal activity preceding the conditioned stimulus (CS) correlated with memory recall performance. To test whether elevated histamine neuron activity preceding the CS fosters associative memory recall, we employed closed-loop CS presentation contingent on histaminergic neuronal activity. The recall performance was enhanced when the CS was presented during elevated histaminergic neuronal activity as opposed to constant activity levels. Furthermore, optogenetic inhibition of histaminergic neurons prior to the CS attenuated associative memory recall.

Discussion & Conclusion
These results suggest that the activity of histamine neurons preceding the presentation of a memory recall cue is a key regulator in determining the accessibility of stored memories.
EXPLORE THE ASSOCIATION OF SWEET PREFERENCE WITH THE TREATMENT RESPONSE TO NALTREXONE IN PATIENTS WITH ALCOHOL USE DISORDER
Authors: Chang *Min Chiao , Meng Shih-Chun , Huang Ming-Chyi 
Published: February 2025

Abstract

Background
Alcohol use disorder (AUD) is a prevalent psychiatric issue worldwide, contributing to the global burden of morbidity and mortality. While pharmacological interventions have been developed to manage AUD, the efficacy of Naltrexone, the first-line treatment, varies among individuals. Identifying phenotypes associated with naltrexone response is essential for optimizing treatment plans. Naltrexone functions by attenuating the reward signals from the endogenous opioid system, which is also linked to the hedonic response to sweet tastes. Naltrexone has been observed to have a better response in patients with a preference for sweet tastes in Western populations. However, it remains unknown whether sweet preference serves as a predictive phenotype for therapeutic response in Taiwan.

Aim and Objective
The study aimed to examine the association between sweet preference and naltrexone response in Taiwanese patients with AUD.

Method
A total of 56 patients diagnosed with AUD as per DSM-5 criteria participated in this study. They underwent a sweet preference test, rating their pleasurableness of various concentrations of sucrose. Following the preference test, they underwent a 12-week treatment, with evaluations at the end of weeks 2, 4, 8, and 12 to assess drinking outcomes. The drinking outcomes were measured by days to first drink after treatment initiation, maximum daily drinks, average daily drinks, and craving severity measured by Visual Analogue Scale (VAS). The generalized estimating equation and the Mann-Whitney test were applied to investigate the difference in drinking outcomes between sweet-liking and sweet- disliking groups.

Result
Participants were dichotomously classified into the sweet-liking (SL) group (n =28) and the sweet- disliking (SDL) group (n = 28) by comparing their pleasurableness ratings at 0.2M to the median pleasurableness ratings of all participants at 0.2M. We observed no significant differences in demographics between the SL and SDL groups. The time to their first drink was significantly longer in the SL group compared to the SDL group (57.8 days vs. 42 days, p = 0.03). Participants in the SL group also reported a lower daily drinking amount, both maximal (1.1 drinks vs. 5.4 drinks, p = 0.02) and average (1.5 drinks vs. 5.8 drinks, p = 0.01), after four weeks of treatment. By the end of the 12-week period, the SL group also exhibited lower VAS scores compared to the SDL group.

Discussion and Conclusion
Ours is the first study in Taiwan to indicate that patients with AUD with a preference for sweet taste responded better to naltrexone treatment in terms of drinking outcomes, specifically, a longer period of abstinence, reduced craving, and an earlier reduction in drinking amount. Future studies should focus on expanding the understanding of precision medicine in AUD treatment.
DISRUPTION OF IMPULSIVITY BEHAVIORS IN CANNABIS USERS IN ADOLESCENTS AND YOUNG ADULTS: A META-ANALYSIS OF FUNCTIONAL NEUROIMAGING STUDIES
Authors: Zhang *Yuxin , Liu Xiao-Xing , Li Ming-Zhe , Li Peng , Bao Yan-Ping , Lu Lin 
Published: February 2025

Abstract

Background
Cannabis is a widely used controlled psychoactive substance. Increased dopamine excitation transmission reduced the capacity of controlling impulsivity behaviors which contributed to their growing desire to drugs, especially teenager and young adults. In cannabis users, the effect of cannabis on impulsivity control behaviors mainly reflected in impulsivity control, inhibitory control and delayed reward discounting, however no unified conclusion has made.

Aims & Objectives
We sought to perform a meta-analysis to clarify the effect of cannabis use on impulsivity control behaviors and dynamic changes of brain regions during impulsivity control process of cannabis users in teenage and early adulthood.

Method
A systematic search of the PubMed, Embase and Web of Science was performed to identify fMRI studies that were published from the inception up to August 20th, 2023, which reported the brain activation during impulsivity control process of cannabis users in teenage and early adulthood. Backward citation tracking was also performed. Seed-Based d Mapping (SDM) was applied to combine the statistical maps, coordinates and t-values of the peaks in each study. We concerned the sources of heterogeneity by subgroups and meta-regression.

Results
28 studies with 1381 individuals were included in the analysis. Compared to healthy controls, cannabis users in adolescents and early adulthood showed weakened impulsivity control capacity. Besides, cannabis users during abstinence period showed increased responses in bilateral anterior thalamic projections and cingulate cortex during impulsivity control process compared with healthy controls. Further, cannabis users with early onset age showed worse inhibition capacity in cingulate cortex and medial prefrontal cortex. Increased activation in cingulate cortex and better inhibition in striatum were correlated with better performance in impulsivity control tasks.

Discussion & Conclusion
This review and meta-analysis indicates attenuation in impulsivity control behaviors in teenage and early adulthood cannabis users. During impulsivity control process, increased activation in cingulate cortex was shown in adolescents and early adulthood cannabis users. Earlier cannabis intake could cause dysregulation of cingulate cortex and medial prefrontal cortex in impulsivity control process. Protective measures should be taken to reduce the possibility of adolescents' exposure to cannabis and attenuate the damage of cannabis to the brain.
GENOMIC AND IMMUNOLOGICAL BIOMARKERS FOR PREDICTING TREATMENT OUTCOME IN DEPRESSION
Authors: Ising *Marcus , Belcredi Petra , Lucae Susanne , Tontsch Alina , Namendorf Christian , Uhr Manfred , Holsboer Florian , Rex-Haffner Monika , Simulionyte Egle , Hebib Sandi , Gruber Oliver , Behler Nora , Nenov-Matt Tabea , Schüle Cornelius , Manook André , Heckel Barbara , Baghai Thomas , Rupprecht Rainer 
Published: February 2025

Abstract
The aim of this project is the validation of genomic and non-genomic biomarkers for predicting antidepressant treatment outcome to identify biologically more homogenous subgroups of patients that might benefit from specific treatments targeting the identified biomarker system. Based on previous findings, we focused on the stress regulation gene FKBP5 for the selection of the genomic biomarkers and on a set of 41 cytokines/chemokines for defining immunological biomarkers. 307 inpatients hospitalized for treating a major depressive episode were included, who participated in the MARS/OptiMD study. MARS/OptiMD is an open-label multicentric treatment study conducted at four clinical centers in Germany. Biomarkers were extracted from DNA, RNA, and serum samples collected after study inclusion. Antidepressant treatment outcome was evaluated weekly by trained personal with the 21-items Hamilton Depression Rating scale (HAMD-21). Primary endpoint in this analysis was response after six weeks of treatment defined as a 50% HAMD-21 reduction compared with baseline.
Replicating our previous findings with suggestive evidence, we observed that reduced FKBP5 expression was associated with response with approaching significance, and this trend was moderated by the FKBP5 genotype (rs1360780). Using Illumina EPIC Methylation BeadChips, we identified 67 DNA methylation markers located within the boundaries of the FKBP5 gene. A principal component analysis revealed five vectors with two (vector 1 and vector 2) showing a robust positive association between higher methylation levels and antidepressant treatment response. Again, these effects were moderated by the rs1360780 genotype. Among 41 cytokines/chemokines, six markers showed an association with treatment response with the strongest effect observed for interleukin 13. For interleukin 3, a trend was found towards an association with treatment response that was moderated by the individual CRP level as marker of the inflammation status. A combined analysis of both types of biomarkers, genomic and immunological, suggests that the observed effects on treatment outcome are independently from each other. Our results confirm and extend previous findings on the prominent role of genomic FKBP5 biomarkers, and partly also of cytokines/chemokine biomarkers, for predicting antidepressant treatment outcome in depression. Importantly, these effects are moderated by person factors like the FKBP5 genotype and the individual inflammation status, pointing to a suitability of these markers in identifying subgroups of patients that might benefit from personalized treatments targeting the associated biomarker systems.
EFFECT MODIFICATION OF TUMOR NECROSIS FACTOR-α ON THE KYNURENINE AND SEROTONIN PATHWAYS IN MAJOR DEPRESSIVE DISORDER ON TYPE 2 DIABETES MELLITUS
Authors: Okamoto *Naomichi , Hoshikawa Takashi , Honma Yuichi , Chibaatar Enkhmurun , Ikenouchi Atsuko , Harada Masaru , Yoshimura Reiji 
Published: February 2025

Abstract

Background
Major depressive disorder (MDD) is strongly associated with type 2 diabetes mellitus (T2DM). The kynurenine and serotonin pathways, as well as chronic low-grade inflammation, are being considered potential links between them. MDD associated with T2DM is less responsive to antidepressants than that without T2DM; however, the underlying mechanism remains unknown.

Aims & Objectives
We aimed to investigate the effects of inflammatory cytokines on the kynurenine and serotonin pathways in patients with comorbid MDD and T2DM and those with only MDD.

Method
We recruited 13 patients with comorbid MDD and T2DM and 40 patients with MDD. We measured interleukin- 6 and tumor necrosis factor-α (TNF-α) levels as inflammatory cytokines and metabolites of the kynurenine pathway and examined the relationship between the two.

Results
TNF-α levels were significantly higher in patients with comorbid MDD and T2DM than in those with only MDD in univariate (p = 0.044) and multivariate (adjusted p = 0.036) analyses. TNF-α showed a statistically significant effect modification (interaction) with quinolinic acid/tryptophan and serotonin in patients from both groups (β = 1.029, adjusted p &lt;0.001; β = −1.444, adjusted p = 0.047, respectively). Limitations attributed to the study design and number of samples may be present. All patients were Japanese with mild to moderate MDD; therefore, the generalizability of our findings may be limited.

Discussion & Conclusion
MDD with T2DM has more inflammatory depression components and activations of the kynurenine pathway by inflammatory cytokines than MDD without T2DM. Hence, administering antidepressants and anti-inflammatory drugs in combination may be more effective in patients with comorbid MDD and T2DM.
EFFICACY AND SAFETY OF ADJUNCTIVE LURASIDONE IN TREATMENT RESISTANT UNIPOLAR DEPRESSION : AN OPEN-LABEL SINGLE-ARM PILOT STUDY
Authors: Chiu *Nan-Ying , Chang Cheng-Ju 
Published: February 2025

Abstract

Background
Major depressive disorder (MDD) is a recurrent, chronic, and disabling disorder worldwide. Antidepressant treatment is an important evidence-based therapy. However, the response rate of antidepressant therapy is unsatisfied. Lots of evidence indicates atypical antipsychotic is an efficient choice for adjunctive therapy for patient with treatment resistant depression (TRD), but only aripiprazole, quetiapine and brexpiprazole are indicated. Lurasidone is a novel atypical antipsychotic as a serotonin-dopamine modulator. Its pharmacological mechanism may be beneficial for depressed mood with few notable adverse effects. The efficacy and safety of lurasidone adjunctive therapy in MDD is not yet well established.

Objectives
This clinical study aimed to explore efficacy and safety of lurasidone as adjunctive therapy for TRD patients.

Methods
This is an 8-week open-label single-arm study, enrolled TRD cases. Use lurasidone as adjunctive drug treated with antidepressant. We select Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impression- severity (CGI-S), Clinical Global Impression- Improvement (CGI-I) as assessment tools. Evaluation were done at baseline, week 2, week 4, and week 8, included efficacy and safety.

Results
This is an interim report. Totally 17 patients enrolled, 7 males and 10 females, mean age was 39.0 (SD: 10.2) year-old, 58.8% were married, 35.3% were single, 47.1% employed, 41.2% were housewife, 58.8% were college/university graduated, 23.5% had suicide attempt history, mean number of previous MDE was 2.7 (SD: 1.9), mean duration of current MDE was 18.4 (SD: 4.3) weeks. Preliminary results indicated a trend of reduction of MADRS, and CGI (MADRS: P=0.001; CGI-S: P=0.002; CGI-I: P=0.004). The score of MADRS reduced from 32.6 (SD: 3.0) to 23.0 (SD: 2.62). The response rate was 52.9%, but the remission rate was 0%. Mean maximal dose of lurasidone was 35.3 (SD: 8.8) mg/day. Three mild adverse events were observed: sedation, nausea, weight gain.

Discussion & Conclusion
This pilot study found in a sample of TRD patients, suggest that lurasidone may be an effective and safe adjunctive drug. Our 8-week study found a response rate of 52.9%. The observed effect size on reducing depressive symptoms is substantial and clinically relevant. The findings should be interpreted with caution, as this is a single-arm small sample size study. Further double- blinded, randomized, placebo-controlled study is needed.

References
Trisha S, Robert S, Josephine C, et al. Lurasidone for the treatment of Major depressive disorder with mixed features: A Randomized, Double-Blind, Placebo-Controlled Study. Am J Psychiatry 2016; 173:400- 407.
TRANSLATIONAL ANIMAL MODELS OF ANTIDEPRESSANT EFFECTS, LONGITUDINAL BIOMARKER MONITORING IN RESPONDER/ NON RESPONDER MALE AND FEMALE MICE
Authors: Gorgievski *Victor , Ibrahim El Cherif , Le Marois Marguerite , Belzeaux Raoul , Tzavara Eleni 
Published: February 2025

Abstract

Background
Predictive biomarkers of antidepressant (AD) response, as well as ADs with novel mechanisms of action are an unmet medical need. Translational models that encompass both sexes, multiple ADs, and longitudinal monitoring are urgently needed to identify biomarkers that could inform new AD mechanisms and allow to test pharmacological hypotheses. Here we present two such models in male (M) and female (F) mice.

Aim and Objectives
We have previously shown that the transcription factor Elk1 is a mediator of the stress response in M mice. We expand these findings in F and test Elk1 expression as a novel biomarker differentiating ad hoc responders from non responders in both sexes.

Methods
We use M and F C57Bl6 mice in the unpredictable chronic mild stress (UCMS; n=107M, 113F) and the vicarious social defeat (vSD; n=60M, 60F) to longitudinally assess stress and fluoxetine (FL) or desipramine (DM) effects. We determine responders (R) and non-responders (NR) with principal component analysis across multiple behavioral tests. We perform transcriptomics in whole blood (sampled longitudinally) and RT-qPCR to validate candidate blood biomarkers (including Elk1) translated from previous and current (ANTaRES; ERANET Neuron) clinical trials.

Results
UCMS and vSD precipitate a depressive-like phenotype in both sexes with different trajectories in M and F (interaction p=0.016 UCMS; p=0.007 vSD). In R (which account for approximately 30% of AD treated M and F mice) AD treatment overall reverses this phenotype with effects varying across behavioral test, sex and drug. RT-qPCR confirms Elk1 as a blood biomarker for stress and AD also in females (main effect p=0.003).

Conclusions
We validate two mouse models of AD action in M and F mice. Longitudinal behavioral and molecular (biomarker) monitoring reveals sex-dependent differences in stress and AD effects over time. We confirm Elk1 as a novel target and putative blood biomarker in both sexes.