bluuebunny/crossref_metadata_2025 huggingface dataset:
SAFETY AND EFFICACY OF KARXT IN PATIENTS WITH SCHIZOPHRENIA IN THE RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED EMERGENT TRIALS
Authors: Kramer *Kenneth , Brannan Stephen K , Sauder Colin , Kaul Inder
Published: February 2025

Background

A high unmet medical need exists for more effective, better tolerated treatments for schizophrenia with novel mechanisms of action. All currently approved treatments for schizophrenia have dopamine D2 receptor blocking activity; the efficacy and tolerability limitations of these therapies are well known. KarXT is a novel combination of the dual M1/M4 preferring muscarinic receptor agonist xanomeline and the peripherally restricted anticholinergic trospium chloride. KarXT is designed to preserve the beneficial central nervous system effects of xanomeline, while mitigating the adverse events observed previously due to peripheral muscarinic receptor activation. In a 5-week, randomized, double-blind, placebo-controlled, phase 2 study (EMERGENT-1; NCT03697252), KarXT met the primary endpoint of a significant reduction in Positive and Negative Syndrome Scale (PANSS), improved other key secondary efficacy measures, and was generally well tolerated.

Methods

EMERGENT-2 (NCT04659161) and EMERGENT-3 (NCT04738123) were 5-week, randomized, double-blind, placebo-controlled phase 3 trials of KarXT in people with schizophrenia with acute psychosis in an inpatient setting. Key inclusion criteria were recent worsening of positive symptoms warranting hospitalization, Positive and Negative Syndrome Scale (PANSS) total score >80, and Clinical Global Impression– Severity (CGI-S) score >4. Eligible participants were randomized 1:1 to KarXT or placebo. KarXT dosing (mg xanomeline/mg trospium) started at 50 mg/20 mg twice daily (BID) and increased to a maximum of 125 mg/30 mg BID. The primary efficacy endpoint was change from baseline to week 5 in PANSS total score. Other efficacy endpoints included change from baseline to week 5 in PANSS positive, PANSS negative, and PANSS Marder negative factor subscale scores.

Results

In the EMERGENT trials, KarXT consistently demonstrated significant and clinically meaningful reductions in Positive and Negative Syndrome Scale (PANSS) score and was generally well tolerated. KarXT demonstrated a significant improvement in other secondary outcome measures, including CGI and PANSS positive subscales, across clinical trials. PANSS negative subscale and PANSS Marder negative factor achieved statistical significance compared with placebo at study endpoint in EMERGENT-1 and 2 and only at week 4 in EMERGENT-3. The most common (>5%) treatment-emergent adverse events with KarXT were all mild to moderate in severity and were not associated with common problematic side effects of current therapies such as motor symptoms, weight gain, prolactin elevation, or somnolence.

Conclusions

If approved, KarXT has the potential to be first in a new class of schizophrenia treatments based on muscarinic receptor agonism and a promising alternative to direct dopamine D2 receptor antagonists and partial agonists.
PROLACTIN LEVEL CHANGES ACCORDING TO ATYPICAL ANTIPSYCHOTICS USE
Authors: Jeong *Jong-Hyun , Sohn Inki , Kim Suhyung , Um Yoo Hyun , Kim Tae Won , Seo Ho-Jun
Published: February 2025

Background

Antipsychotic drugs are known as the major cause of non-neoplastic hyperprolactinemia.

Aims & Objectives

This study aimed to investigate the levels of serum prolactin elevation depending on the use of antipsychotic drugs in patients through the Clinical Data Warehouse.(CDW)

Method

We conducted a cohort search in the CDW application with the following condition. The subjects who aged more than 18 years old and visited from March 1, 2017, to May 31, 2022 at the Department of St. Vincent’ s Hospital, The Catholic University of Korea. The subjects were diagnosed according to ICD- 10 for schizophrenia, schizotypal and delusional disorders, manic episodes, and bipolar affective disorders. And the subjects who was taking one of risperidone, blonanserin, amisulpride, and olanzapine. The subjects also conducted serum prolactin level tests. After that, we reviewed the medical data.

Results

Among the 117 subjects included in the analysis, the mean serum prolactin level was 64.654.6ng/ml. Serum prolactin levels were significantly higher in subjects taking risperidone or amisulpride compared to blonanserin and olanzapine. The female subjects who took blonanserin, olanzapine, and risperidone had significantly higher prolactin levels, but there was no difference in serum prolactin levels between the sex in the subjects who took amisulpride.

Discussion & Conclusion

This study suggests the need for regular monitoring of serum prolactin levels in patients who are taking antipsychotics, especially in female patients. And we showed that there is a possibility to conduct more effective and simpler big data research using the CDW. Further studies on the subjects with controlled confounding variables and larger sample groups are needed.
BERBERINE REDUCES ANTIPSYCHOTIC-ASSOCIATED WEIGHT GAIN IN SCHIZOPHRENIA PATIENTS WITH LOW-LEVEL LDL: A POOLED ANALYSIS OF RANDOMIZED CONTROLLED TRIAL
Authors: Qin *Zongshi , Wu Jiani
Published: February 2025

Background

MetS thus has become a major concern in the long-term prescription of antipsychotics, as its prevalence is as high as 33.4% in patients with schizophrenia, and it increases diabetic and cardiovascular morbidity and mortality. Berberine is a naturally occurring alkaloid mainly extracted from the Chinese herbal medicine Coptis chinensis. Although berberine has not been licensed for the treatment of metabolic disorders, in vitro and in vivo experimental evidence confirms that berberine has body weight-lowering effects.

Objective

To evaluate the efficacy and safety of berberine as an adjuvant in treating antipsychotic- associated weight gain.

Method

One hundred and thirteen participants with schizophrenia spectrum disorders who had developed metabolic syndrome (MetS) were recruited. They were randomly assigned to berberine (600 mg/day, n=58) or placebo (n=55) groups for 12 weeks. The primary outcome was the change from baseline to week 12 in net weight.

Results

Compared with the placebo group, the berberine group showed a significantly greater reduction in weight gain at 9 weeks (mean difference [MD]=-0.75, 95% confidence interval [CI]: -1.42 to -0.07, P =0.031, d=0.41) and 12 weeks (MD=-1.08, 95% CI: -1.76 to -0.40, P=0.002, d=0.59) in all patients. In the subgroup patients with low-level LDL at baseline (<2.9 mmol/L), there is a larger effect regarding weight gain at 12 weeks (MD=-2.0, 95%CI: -2.8 to -1.0) compared with high-level LDL (MD=-0.3, 95%CI: -1.3 to 0.7). Berberine was well tolerated without serious adverse events and aggravation of psychotic symptoms compared with placebo.

Conclusions

Findings suggest that berberine is effective in attenuating antipsychotic-associated weight gain and MetS, especially for patients with low-level LDL.
GENOME-WIDE DNA METHYLATION RISK SCORES FOR SCHIZOPHRENIA DERIVED FROM BLOOD AND BRAIN TISSUES FURTHER EXPLAIN THE GENETIC RISK IN PATIENTS STRATIFIED BY POLYGENIC RISK SCORES FOR SCHIZOPHRENIA AND BIPOLAR DISORDER
Authors: Ohi *Kazutaka , Shimada Mihoko , Soda Midori , Nishizawa Daisuke , Fujikane Daisuke , Takai Kentaro , Kuramitsu Ayumi , Muto Yukimasa , Sugiyama Shunsuke , Hasegawa Junko , Kitaichi Kiyoyuki , Ikeda Kazutaka , Shioiri Toshiki
Published: February 2025

Background

Genetic and environmental factors contribute to the pathogenesis of schizophrenia (SZ) and bipolar disorder (BD). Among genetic risk groups stratified by combinations of polygenic risk score (PRS) deciles for SZ, BD, and SZ vs. BD, genetic SZ risk groups had high SZ risk and prominent cognitive impairments. Furthermore, epigenetic alterations are implicated in these disorders.

Aims & Objectives

However, it was unclear whether DNA methylation risk scores (MRSs) for SZ risk derived from blood and brain tissues were associated with SZ risk, particularly the PRS-stratified genetic SZ risk group.

Method

Epigenome-wide association studies (EWASs) of SZ risk in whole blood were preliminarily conducted between 66 SZ patients and 30 healthy controls (HCs) and among genetic risk groups [individuals with low genetic risk for SZ and BD in HCs (n=30) and in SZ patients (n=11), genetic BD risk in SZ patients (n=25), and genetic SZ risk in SZ patients (n=30)] stratified by combinations of PRSs for SZ, BD, and SZ vs. BD. Next, differences in MRSs based on independent EWASs of SZ risk in whole blood, postmortem frontal cortex (FC), and superior temporal gyrus (STG) were investigated among our case- control and PRS-stratified genetic risk status groups.

Results

Among case-control and genetic risk status groups, 33 and 351 genome-wide significant differentially methylated positions (DMPs) associated with SZ were identified, respectively, many of which were hypermethylated. Compared with the low genetic risk in HCs group, the genetic SZ risk in SZ group had 39 genome-wide significant DMPs, while the genetic BD risk in SZ group had only six genome- wide significant DMPs. The MRSs for SZ risk derived from whole blood, FC, and STG were higher in our SZ patients than in HCs in whole blood and were particularly higher in the genetic SZ risk in SZ group than in the low genetic risk in HCs and genetic BD risk in SZ groups. Conversely, the MRSs for SZ risk based on our whole-blood EWASs among genetic risk groups were also associated with SZ in the FC and STG. There were no correlations between the MRSs and PRSs.

Discussion & Conclusion

These findings suggest that the MRS is a potential genetic marker in understanding SZ, particularly in patients with a genetic SZ risk.
NASAL EPITHELIAL INPUT DRIVES KETAMINE-ENHANCED HIGH- FREQUENCY OSCILLATIONS IN FREELY MOVING RATS
Authors: Hunt *Mark Jeremy , Podolecka Wiktoria
Published: February 2025

Background

Subanesthetic doses of ketamine are used to model psychoses and for the treatment of depression. The mechanism though which ketamine achieves its effects are not fully understood. Ketamine is known to significantly increase the power of high-frequency oscillations (HFO, 130-180 Hz) in many rodent brain regions. Our previous findings have shown that the olfactory bulb is an important generator of ketamine-enhanced HFO, and may orchestrate this activity in other areas.

Aims & Objectives

The nasal epithelia houses olfactory sensory neurons whose axons directly innervate the olfactory bulb. Here we tested that the enhancement of HFO, after ketamine, is dependent on input from the nasal epithelia.

Method

Local field potentials were recorded from the olfactory bulb, ventral striatum and prefrontal cortex of freely moving rats. Damage to the nasal epithelia was induced by intranasal gadolinium infusion. Rats received intraperitoneal ketamine 25 mg/kg injection before and at different time points up to two weeks after nasal infusion.

Results

Gadolinium nasal infusion, but not saline, was associated with a reduction in respiration rhythm recorded in the olfactory bulb. Ketamine-enhanced HFO power were significantly reduced in all regions we recorded. This effect lasted at least 7 days and was associated with a gradual recovery thereafter. Ketamine-enhanced locomotion was not affected by intranasal gadolinium.

Discussion And Conclusion

These findings show that ketamine-enhanced HFO in the olfactory bulb, and other brain regions, are dependent on input from the nasal epithelium.

The authors wish to thank NCN (grant 2021/41/B/NZ4/03882) for funding this project.
VISUAL HALLUCINATIONS IN PARKINSON’ S DISEASE WERE ASSOCIATED WITH DECREASING BLOOD FLOW IN THE BILATERAL POSTERIOR CINGULATE CORTEX ON 123I-IMP-SPECT
Authors: Ito *Masanobu , Hatano Taku , Horie Junko , Katsuta Narimasa , Oyama Genko , Takeshige-Amano Haruka , Ogawa Takashi , Sasaki Fuyuko , Shimo Yasushi , Umemura Atsushi , Iwamuro Hirokazu , Kamagata Koji , Nakanishi Atsushi , Aoki Shigeki , Hattori Nobutaka , Kato Takafumi
Published: February 2025

Background

Psychosis is known as one of the non-motor symptoms of Parkinson’ s disease (PD). Psychosis is typically associated with an increased burden regarding living activities in PD and thus constitutes a serious public health problem.

Aims & Objectives

We hypothesized that the visual hallucinations associated with PD would be predicted by neurodegeneration of specific regions. We consecutively enrolled 228 patients with PD between October 2016 and March 2021 at Juntendo University Hospital in Japan.

Method

All patients were assessed for motor function, cognition, mental state, and REM sleep-related events using the REM sleep behavior disorder (RBD) Single-Question Screen (RBD1Q), and for regional cerebral blood flow (rCBF) using N-isopropyl-p-123I-iodoamphetamine single photon emission tomography.

Results

The patients were divided into two groups: one with a history of visual hallucinations (Hal-PD; n = 119) and one without (nHal-PD; n = 109). Three factors were associated with Hal-PD: sex and scores on both the RBD1Q and Odor Stick Identification Test for Japanese (OSIT-J). In single photon emission tomography data, rCBF in the bilateral posterior cingulate (PC) and right cuneus were significantly lower in the Hal-PD than in the nHal-PD group. RBD1Q scores were associated with rCBF in the bilateral PC.

Discussion & Conclusions

Visual hallucinations were associated with rCBF in the bilateral PC and OSIT-J scores. Especially, rCBF in the left PC was an independent risk factor. RBD1Q scores were significantly associated with Hal-PD. RBD1Q scores may be an easy surrogate factor for visual hallucinations in settings where rCBF cannot be measured.
DRUG CONCENTRATIONS IN BLOOD AND BREAST MILK WHILE TAKING PSYCHOTROPIC DRUGS-PRELIMINARY STUDY-
Authors: Fujii *Kumiko , Maekawa Masamitsu , Tsuji Shunichiro , Sumi Yukiyoshi , Fujikawa Ryoko , Murakami Takashi , Ozeki Yuji
Published: February 2025

Background

The perinatal period is a time when psychiatric disorders frequently occur. Promotion of breastfeeding is recommended by WHO and other organizations, and is considered important for mother-infant attachment formation, but expectant mothers taking psychotropic drugs tend to avoid breastfeeding due to less accurate information. Currently, scientific and empirical data on breastfeeding are available, but these data are limited. We report here the results of a study to determine drug concentrations in the blood and breast milk of lactating women taking psychotropic drugs.

Aims & Objectives

This study was approved by the Ethics Committee of Shiga University of Medical Science. The subjects were lactating women undergoing treatment at the Department of Psychiatry, Shiga University Hospital, and consent for the study was obtained in writing before the study was conducted. Blood levels of medications were measured by liquid chromatography/tandem mass spectrometry at the Department of Pharmaceutical Sciences, Tohoku University Hospital. Blood samples were taken at 6:00 in the morning, and breast milk was collected on the same day as the blood samples.

Results

The subjects were those who had been taking brocizolam before pregnancy and those who had been taking lorazepam 0.5 mg as an abortive dose. The blood concentration of brocizolam was 5.12 ng/ml, which was within the therapeutic range. However, it was not detected in breast milk. As for lorazepam, it was lower than the recommended concentration from Therapeutic Drug Monitoring for blood levels (1), and it is also low in breast milk. We will present the results of other psychotropic medications at the meeting.

Discussion & Conclusion

The blood and breast milk concentrations of patients taking psychotropic drugs were measured. The data of brotizolam is not listed on Hale's Medications Mother's Milk2023 which is often used to determine the acceptability of breastfeeding. The package inserts for many benzodiazepines state that they may pass into human milk and cause lethargy, weight loss, etc. in newborns. In fact, the package insert for brotizolam also states that breastfeeding should be avoided, but it was suggested that the effect on the infant might be low. Lorazepam was also detected, but at low levels. Both of these medications might appear to be safe to administer to nursing mothers. We will increase the number of cases and measure multiple psychotropic drugs in the future.

References

(1)Hiemke C, Bergemann N, Clement HW, et al. 2018. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017. Pharmacopsychiatry. 51(1-02):9-62
CLINICAL IMPLICATION OF MAUMGYEOL BASIC BIOTYPES – EEG- AND PPG-BASED BWAVE STATE INVENTORY (EBSI)
Authors: Kwon *Hyesun , Kim Yunsu , Kim Jeongin , Lee Seung-Hwan
Published: February 2025

Background

The development of individual subtypes based on biomarkers offers an intriguing and timely avenue for capturing individual factors pertaining to mental health independent from individuals’ insights.

Aims & Objectives

Incorporating 2-channel electroencephalography (EEG) and photoplethysmogram (PPG), we sought to develop subtype classification system with clinical relevance.

Method

One hundred healthy participants and 99 patients with psychiatric disorders were recruited. Classification thresholds were established using the EEG and PPG data from 2,278 individuals without mental disorders, which used to classify subtypes of 199 participants. MANOVA (Multiple Analysis of Variance) was applied to examine psychological differences between the subtypes. K-means clustering was employed to verify the classification system.

Results

The distribution of subtypes differed between healthy participants and those with psychiatric disorders. Cognitive ability differed depending on brain subtypes, whereas mind subtypes showed significant differences in symptom severity, overall health, and cognitive stress. K-means clustering revealed that the results of our theory-based classification and data-driven classification are comparable.

Discussion & Conclusion

The utilization of EEG and PPG signals for subtype classification offers potential for the future of digital mental healthcare.
OMEGA-3 FATTY ACIDS FOR INFLAMED DEPRESSION – A MATCH/MISMATCH STUDY
Authors: Lindahl *Jesper , Suneson Klara , Söderberg Gustav , Tjernberg Johanna , Ståhl Darya , Ventorp Simon , Ängeby Filip , Lundblad Karl , Wolkowitz Owen M , Lindqvist Daniel
Published: February 2025

Background

Despite decades of research on the pathophysiology of depression, the development of new therapeutic interventions has been slow, and no biomarkers of treatment response have been clinically implemented. Several lines of evidence suggets that the clinical and biological heterogeneity among patients with major depressive disorder (MDD) has hampered progress in this field. MDD with low-grade inflammation - "inflamed depression" - is a subtype of depression that may be associated with the superior antidepressant treatment response to anti-inflammatory compounds. Omega-3 fatty acoid eicosapentaenoic acid (EPA) has anti-inflammatory properties, and preliminary data suggest that it may be particulary efficacious in inflamed depression.

Aims And Objectives

In this study we tested the hypothesis that add-on EPA has greater antidepressant efficacy in MDD patients with high baseline high-sensititivity C-reactive protein (hs-CRP) compared to MDD patients with low hs-CRP.

Method

All subjects recevied 2.2 g EPA/day for 8 weeks, added to stable ongoing antidepressant treatment. The primary outcome was change in the 17-item Hamilton Depression Rating Scale (HAM-17). Patients and raters were blind to baseline hs-CRP status.

Results

In an intention-to-treat analysis including all subjects with at least one post baseline visit (n=101), a hs- CRP cut-off of >=1 mg/L, bot not >=3 mg/L, was associated with a greater improvement in HAMD-17 total score. In addition to a general antidepressant effect among patients with hs-CRP >= 1 mg/L, adjuvant EPA treatment improved symptoms putatively related to inflamed depression such as fatigue and sleep difficulties.

Discussion And Conclusion

The results suggests that EPA supplementation has a greater antidepressant effect in patients with mildy-moderately elevated hs-CRP compared to patients with lower hs-CRP. These findings add to the mounting evidence that stratificaton of MDD-subgroups based on inflammatory markers may be relevant to predict response to anti-inflammator interventions. Altough more studies are needed to confirm the most optimal cut-off to define these subgroups, this and other similar studies have the potential to facilitate the developement of targeted interventions and thereby break ground for precision medicine in psychiatry.
APELIN AS A NOVEL MEDIATOR OF ANTIDEPRESSANT EFFECTS OF PHYSICAL EXERCISE
Authors: Yu *Jiasui , Yau Suk-Yu
Published: February 2025

Physical exercise is known to be the best effective antidepressant for depression; however, its underlying mechanism is still largely unknown. Identifying the molecular mechanisms underlying the antidepressant effect of physical exercise can provide therapeutic targets for treating depression. Apelin, a novel myokine linked to sarcopenia, can elicit antidepressant effects and influence hippocampal neuroplasticity in rodent studies. Physical exercise in humans is effective in preventing both sarcopenia and depression. A recent study has shown that physical exercise counteracts sarcopenia by restoring decrease in apelin levels of aged mice and humans, suggesting the important role of apelin in both sarcopenia and depression. By using a mouse model of depression induced by chronic unpredictable stress (CUS), here we found that stressed mice showed significantly decreased protein expression of apelin and its receptor (APJ) in the hippocampus, whereas 4-weeks voluntary exercise rescued depression-like behaviour in association with increased Apelin/APJ levels and neurogenesis in the hippocampus, and lower limb muscles including gastrocnemius (Gas), and tibialis anterior (TA) of stressed mice. Specific knockout of Apelin in skeletal muscle attenuated the antidepressant effect of voluntary exercise, suggesting the key role of apelin in mediating the antidepressant effect of physical exercise. In contrast, overexpression of apelin in Gas and TA muscles mimicked antidepressant effects of physical exercise in the CUS mouse model. These data suggest that the potential role of apelin mediating the crosstalk of the muscle-brain axis on sarcopenia-associated depression, and provide a novel potential therapeutic target for treating geriatric depression.
TRANSCRANIAL PULSE STIMULATION (TPS) OPENS UP NEW HORIZONS IN THE TREATMENT OF PSYCHIATRIC PATIENTS
Authors: Ziegenbein *Marc , Sprick Ulrich , Cheng Calvin , Cheung Teris
Published: February 2025

Background

With transcranial pulse stimulation (TPS), a new, non-invasive brain stimulation procedure has been available since 2019 that, unlike previous methods, is based on the principle of mechanotransduction using shock waves.

Aims & Objectives

Individual MRI data sets form the basis for the infrared-assisted neuronavigation of the TPS and thus enable personalized neuromodulation. Various neurophysiological factors are discussed with regard to the specific mechanisms of action. Mechanical effects of TPS on the cell membrane, both in neurons and in glial cells, influence ion channels and lead to a change in cell membrane permeability. Changes in the levels of various neurotransmitters were observed after TPS treatment: In addition to increases in extracellular dopamine and serotonin levels, a reduction in GABA levels was noticeable. In addition, TPS treatment could lead to an increase in the levels of trophic factors (e.g. brain derived neurotrophic factor - BDNF and vacular endothelial growth factor - VEGF). Depending on the site of stimulation, there is also a reversible opening of the blood-brain barrier.

Method, Results & Discussion

CE certification for the treatment of patients with Alzheimer's disease (AD) has now been obtained in Europe and the first promising publications are available. The participants of this symposium are leading psychiatrists and psychologists and share their interdisciplinary expertise on TPS from the fields of science, research and practice. In addition to experiences from the practical application of TPS through real-word data from patients with AD, the speakers will also present results on off-label indications, such as TPS treatment with psychiatric (MDD, autism and ADHD) and post-Covid patients. The aim is to discuss the opportunities, risks and limitations of TPS and to venture an outlook on AI-supported innovative screening and monitoring tools.
TRANSCRANIAL PULSE STIMULATION (TPS) – NEW PERSPECTIVES IN TREATMENT OF DEMENTIA IN ALZHEIMER’S DISEASE?
Authors: Ziegenbein *Marc , Penkov Cassandra , Rößner-Ruff Vanessa , Friedrich Kathrin , Clark Daniel
Published: February 2025

Background

Dementia is one of the most common mental illnesses. The impairment of a normal symptom-free life according to DALY is, next to depression, the second most pronounced with deficits in social and everyday behaviour. Early and adequate treatment is of high relevance. Dementia in Alzheimer's disease is often associated with depressive symptoms. A psychiatric clinic in Lower Saxony (Wahrendorff clinic, Germany) has focused on treating patients with this diagnosis as early as possible on an outpatient basis. For this purpose TPS is used. With the aim of releasing growth factors and contributing an improvement in cerebral blood flow, low-frequency sound pulses are introduced into brain regions in order to promote and maintain cognitive performance. Some studies have found positive effects, although more research is needed. The aim of the current study is to investigate the development of cognitive performance and depressive symptom severity over the course of treatment with TPS, focus on the question if there is an improvement.

Methods

Cognitive performance (Montreal Cognitive Assessment, MOCA) and depressive symptom severity (Geriatric Depression Scale, GDS) are assessed at the beginning of the treatment (t1) and every three months during the course of treatment from patients with a diagnosis of Dementia in Alzheimer's disease who have undergone treatment with TPS since june 2021 (n = 80) in the outpatient setting of Wahrendorff clinic. In this study a follow-up until 9 months of treatment (t3) should be considered.

Results

Analysis of variance with repeated measurement show a minimal increase in mean values of MOCA from the different measurement points, without statistical significance (mean value MOCA t1 = 12.94 vs. t2 = 13.05, p n.s.). Analysis of variance with repeated measurement show that there is a statistical significant difference in the mean values of GDS from the different measurement points with a decrease of depressive symptom severity (mean value GDS t1 = 8.91 vs. t2 = 6.72, p less than 0.05).

Conclusion

Results suggest that TPS could lead to maintaining the cognitive performance of patients with Dementia in Alzheimer's disease over the course of treatment. Futhermore treatment with TPS could lead to an improvement of depressive symptom severity. The TPS might be helpful in the treatment of Dementia in Alzheimer's disease and its symptoms and might give new perspectives in the treatment, especially as patients report high treatment tolerance and few side effects. Further data should be collected so the study is being continued and not yet concluded.
ASSOCIATION BETWEEN CHANGE IN SLEEP DURATION AND POSTTRAUMATIC STRESS SYMPTOMS IN NATURAL DISASTER VICTIMS: THE MEDIATING ROLE OF RESILIENCE
Authors: Ho *Dham , Park Mina , Lim Weon-Jeong
Published: February 2025

Aims & Objectives

This study investigated the association between changes in sleep duration after disaster and post-traumatic stress disorder (PTSD) symptoms and the mediating role of resilience on the association.

Method

Data were collected from 2,951 Korean adults who were victims of a natural disaster and did not have any mental or medical illnesses before the event. They completed a long-term survey on changes in life for disaster victims using computer-aided personal interviews. Changes in sleep duration before and one month after experiencing a disaster were assessed using a self-reported questionnaire.

Resilience levels and PTSD symptoms were measured using the Brief Resilience Scale and the Impact of Event Scale – Revised, respectively, and more than 33 of the IES-R score items were defined as significant PTSD symptoms. Multivariate logistic regression was used to examine the associations between changes in sleep duration and PTSD symptoms. Additionally, mediating studies were conducted to identify the role of resilience on the association.

Results

Compared with participants without significant PTSD symptoms, those with PTSD symptoms were more likely to be older and female (group without significant PTSD symptom: mean age=56.12± 18.70 years, female sex=49.24%; group with significant PTSD symptoms: mean age=60.88±15.66 years, female sex=59.52%). Compared with disaster victims without changes in sleep duration, those who had shorter sleep duration after disaster had a higher risk of significant PTSD symptoms (OR=2.89, 95% Cl=2.31– 3.62, p<0.001). In the mediating study, resilience level significantly mediated the relationship between reduced sleep duration and PTSD symptoms

Discussion &Conclusion

This study revealed that individuals with reduced sleep duration after disaster had a higher risk of PTSD symptoms, while those with increased sleep duration did not. In addition, mediating effects of resilience level on the relationship between reduced sleep duration and significant PTSD symptoms were observed.
IMPAIRED RESTING-STATE ANTERIOR PREFRONTAL FUNCTIONAL CONNECTIVITY ASSOCIATED WITH PROSPECTIVE MEMORY DEFICITS IN SCHIZOPHRENIA
Authors: Zhou *Fuchun , Wang Nan , Li Hang , Zhang Zhifang , Wang Chuanyue
Published: February 2025

Background

Prospective memory (PM) deficit is one of the most common cognitive impairments of patients with schizophrenia spectrum disorders (SSDs). PM deficits have been associated with social functioning impairment, poor adherence to drugs and adverse clinical outcome. Previous studies have atributed the PM deficits in schizophrenia to the failure of cue detection and intention retrieval. In healthy people, these cognitive processes reflect the ability of strategic monitoring, which heavily rely on the functional network of anterior prefrontal cortex (aPFC) and related brain regions. This suggests that PM deficits in SSDs patients may be due to aPFC functional connectivity impairments.

Aims & Objectives

The aim of the present study is to compare the resting-state aPFC functional connectivity between patients with SSDs and healthy controls, and to examine whether the PM deficits in SSDs patients are due to aPFC functional connectivity impairments.

Method

Sixty-three SSDs patients and 32 healthy controls (HCs) formed the study sample. Time- and event-based PM (TBPM and EBPM) performance were measured with the Chinese version of the Cambridge Prospective Memory Test (C-CAMPROMPT). Patients' clinical symptoms were evaluated with the Positive and Negative Symptom Scale (PANSS). All participants underwent resting-state functional magnetic resonance imaging (fMRI). Left and right BA 10 were chosen as seeds to perform seed-based whole brain voxels resting-state functional connectivity analyses.

Results

Compared to HCs, SSDs patients demonstrated significantly worse PM performance and attenuated functional connectivity between right aPFC and precuneus (x= -9, y= -51, z=45), a key hub of the default mode. The correlation analysis results showed that the aforementioned functional connectivity in the SSDs group was significantly positively correlated with EBPM parformance (r= 0.319, P=0.013). No significant correlation analysis results were found between the functional connectivity and EBPM within the HC group.

Discussion & Conclusion

The results indicate that aPFC resting-state networks are affected in SSDs patients. The reduced magnitude of resting state functional connectivity between right aPFC and precuneus is a key marker of information processing failure underlying PM impairments in SSDs patients.
WHITE MATTER ABNORMALITIES OF THE FRONTAL-STRIATAL-THALAMIC CIRCUITS IN INDIVIDUALS WITH ATTENUATED POSITIVE SYMPTOM SYNDROMES A PROBABILISTIC TRACTOGRAPHY STUDY
Authors: Bo *Qijing , Chen Zhenzhu , Wang Chuanyue
Published: February 2025

Background

Attenuated positive symptoms syndrome (APSS) is a risk state preceding psychosis. Disturbances in the frontal-striatal-thalamic circuit have been implicated in the neuropathology of APSS. This study aimed to systematically investigate white matter (WM) alterations in the frontal -striatal- thalamic circuit in APSS.

Methods

Diffusion magnetic resonance imaging (dMRI) and T1-weighted images were acquired from 43 individuals with APSS and 50 healthy controls (HCs). The dMRI data were preprocessed using FSL software. Brainnetome Atlas (BNA) was utilized to extract regions of interest (ROIs) in the frontal lobe, striatum, and thalamus. Bidirectional probabilistic tractography was performed to construct the frontal-striatal-thalamic circuit. Multiple linear regression was employed to compare the connectivity probability (CP) and diffusion index values between the APSS and HC groups.

Results

Compared to HCs, individuals with APSS exhibited significantly lower CP values in right Orbital gyrus_area 13- right nucleus accumbens (R: OrG_A13-NAC) fiber tract. Higher mean diffusivity values were observed in the L: OrG_A13-NAC and left ventral caudate– left caudal temporal thalamus (L: vCa- cTtha) fiber tract. Additionally, higher radial diffusivity values were found in the R: NAC-OrG_A13 fiber tract, while higher axial diffusivity values were observed in multiple frontal lobe ROIs-striatum ROIs and striatum ROIs-thalamus ROIs fiber tracts. No significant differences were found in fractional anisotropy values.

Conclusions

Individuals with APSS demonstrated reduced fiber connection strength, impaired myelin and inflammatory changes in the R: NAC-OrG_A13 fiber tract, and possible inflammatory changes in the L: vCa-cTtha fiber tract. These alterations may contribute to the neuropathology of APSS. Additionally, increased fiber coherence in multiple fiber tracts suggests potential compensatory mechanisms.
OXYTOCIN-INDUCED INCREASES IN CYTOKINES AND CLINICAL EFFECT ON THE CORE SOCIAL SYMPTOMS OF AUTISM
Authors: Wakuda *Tomoyasu , Benner Seico , Uemura Yukari , Kojima Masaki , Kameno Yosuke , Kuwabara Hitoshi , Yamasue Hidenori ,   +32 Co-Authors
Published: February 2025

Background

Oxytocin may provide a novel treatment for the core symptoms of autism spectrum disorder (ASD). However, previous results regarding the efficacy of repeated or higher dose oxytocin are controversial, and the underlying mechanisms including interactions with other molecules remain unclear.

Aims & Objectives

The current study is aimed to clarify whether repeated oxytocin alter plasma cytokine levels in relation to clinical improvements of autism social core symptom.

Method

We analyzed cytokine concentrations using comprehensive proteomics of plasmas of 207 adult males with high-functioning ASD collected from two independent multi-center large-scale randomized controlled trials (RCTs): Testing effects of 4-week intranasal administrations of TTA-121 (A novel oxytocin spray with enhanced bioavailability: 3U, 6U, 10U, or 20U/day) and placebo in the crossover discovery RCT; 48U/day Syntocinon or placebo in the parallel-group verification RCT.

Results

Among the successfully quantified 17 cytokines, 4 weeks TTA-121 6U (the peak dose for clinical effects) significantly elevated IL-7 (9.74, 95% confidence interval [CI] 3.59 to 15.90, False discovery rate corrected P (PFDR) = 0.009), IL-9 (56.64, 20.46 to 92.82, PFDR = 0.017) and MIP-1b (18.27, 4.96 to 31.57, PFDR = 0.017) compared with placebo. Inverted U-shape dose-response relationships peaking at TTA-121 6U were consistently observed for all these cytokines (IL-7: P = 0.025; IL-9: P = 0.002; MIP- 1b: P = 0.010). Increased IL-7 in participants with ASD after 6 weeks oxytocin administration compared with placebo was verified in the confirmatory Syntocinon trial dataset (19.74, 0.31 to 39.18, P = 0.047). Furthermore, the changes in all these cytokines during 4 weeks of TTA-121 10U administration revealed correlations with changes in reciprocity score, the original primary outcome, observed during the same period (IL-7: r = −.347, P = 0.089; IL-9: r = −.489, P = 0.013; MIP-1b: r = −.527, P = 0.007).

Discussion & Conclusion

These findings provide the first evidence for the role of interaction between oxytocin and neuroinflammation in the treatment of ASD core social symptoms, and support the potential role of this interaction as a novel therapeutic seed.
THE PHARMACOLOGICALLY DIVERSE HUMAN BRAIN: HOW NEUROSIGNALLING SYSTEMS REGULATE NEUROTYPICAL AND NEURODIVERGENT RESTING-STATE NETWORKS
Authors: Whelan *Tobias Patrick , Franca Lucas G S , Dimitrov Mihail , Mulcrone Naoise , Puts Nicolaas A , Daly Eileen , Murphy Declan G M , Mcalonan Grainne M
Published: February 2025

Background

Functionally inter-connected large-scale brain networks underpin complex human behaviour and a wide range of alterations in this landscape have been consistently reported in psychiatric and neurodevelopmental conditions, including autism. Evidence from preclinical and correlational human studies suggest that these differences arise from underlying differences in neurotransmitter systems. However, to directly assess how a given neurotransmitter system modulates functional connectivity, we need to change it and observe a shift in network connectivity.

Aims & Objectives

To report on how resting-state connectivity is differentially modulated by different drug classes and how responses differ between autistic and non-autistic individuals.

Methods

Here we establish a common framework to capture the modulation of functional connectivity within and between brain functional networks by neurosignalling systems targeted by a range of pharmacological probes. Alterations in functional connectivity are reported for seven cortical networks following activation of the serotonin, dopamine, opioid, cannabinoid and glutamate-GABA systems in neurodiverse (autistic and non-autistic) individuals. Reproducible differences in resting-state network functional connectivity, including both hyper- and hypoconnectivity of within- and between-network interactions, are reported in autism. Thus, we also assessed whether there are group-level network responsivity differences between autistic and non-autistic participants to drug challenge, or whether the response profile was primarily individual/ heterogeneous in either group.

Results

One common finding across pharmacological probes was that networks with reproducible baseline differences in autism (e.g. sensory and attentional networks) were also those that respond differently to drug challenge. Broadly, the cannabinoid compounds (cannabidiol and cannabidivarin) decreased functional connectivity in autistic individuals compared to non-autistic controls. By contrast, the other compounds such as the GABAergic drugs AZD7325 & arbaclofen (which activate GABAA and GABAB receptors, respectively), increased functional connectivity in autistic individuals relative to non-autistic controls.

Discussion & Conclusion

This is important to not only to advance our understanding of how neurotransmitter systems regulate fundamental functional networks in both the neurotypical and neurodivergent brain, but to provide a common framework for evaluating pre-existing and novel neuro-active compounds in the living human brain. We hope this work can be extended to form the basis of a human neuropharmacological reference library of neuro-active compounds across individuals and diagnoses.
RELATIONSHIP BETWEEN CEREBELLAR VOLUME AND PSYCHOLOGICAL FACTORS OF NORMAL YOUNG ADULTS
Authors: Moon *Seok Woo
Published: February 2025

Aims & Objectives

There have been no studies about the relationship between cerebellar volume and various psychological factors for normal subjects. This study analyzed the relationship between the cerebellar volume of normal adults in the third decade of life (20-29 years) and various psychological factors.

Methods

The cerebellar volume of 118 subjects (mean age, 23 ± 2.6 years), including 58 males (mean age, 24 ± 2.8 years) and 60 females (mean age, 21.9 ± 2.1 years), was measured using magnetic resonance imaging (MRI). The following tests were performed on all subjects: the Symptom Checklist-90-R (SCL-90-R), the Component of Type A Behavior, the State Anxiety Inventory from Korean YZ, the Sixteen Personality Factor (16PF), and the Self-rating Depression Scale (SDS). Using linear regression analysis, the relationship between cerebellar volume and psychological factors was analyzed.

Results

Without considering gender differences, as the tendency toward type A personality increased and the state of anxiety and superego strength increased, cerebellar volume decreased. As ego strength increased, cerebellar volume increased. When considering gender differences, as male phobic anxiety and ambition increased, cerebellar volume decreased. As female hostility, tenseness, and the state of anxiety increased, cerebellar volume decreased.

Discussion & Conclusion

This study also indicated that cerebellar volume or changes in cerebellar volume could be one of parameters which can diagnose the possibility of psychological diseases.
PREDICTION OF POSTOPERATIVE DELIRIUM BY BLOOD METABOLOME
Authors: Arai *Naohiro , Sugiura Yuki , Nakajima Shinichiro , Wada Masataka , Moriyama Sotaro , Mimura Yu , Takayama Kousuke , Niinomi Kanta , Boku Shuken , Mimura Masaru , Takebayashi Minoru , Uchida Hiroyuki , Noda Yoshihiro
Published: February 2025

Background

Delirium is a notable risk factor for cognitive dysfunction and poor prognosis. Despite its importance, there is currently no established blood marker that can predict postoperative delirium in the preoperative period.

Aims & Objectives

We aimed to examine that water-soluble metabolites, lipids, and cytokines in peripheral blood could uniquely classify postoperative delirium. In addition, we investigated whether changes in neuroinflammation-related and water-soluble metabolites in the indoleamine 2,3-dioxygenase (IDO) pathway could predict postoperative delirium.

Method

We designed a prospective cohort study of postoperative delirium and received approval from the Keio University School of Medicine Ethics Committee in December 2017. We used a comprehensive metabolomics and cytokine panel analysis involving 18 subjects in the delirium group and 24 subjects in the non-delirium group to determine whether preoperative blood metabolites, lipids, and cytokines could predict postoperative delirium. We also performed non-targeted metabolomics to investigate unanticipated small molecular weight metabolites in addition to IDO pathway metabolites and their correlations with cytokines indicative of an activated immune state. In addition, we conducted an in vitro experiment to test secretion with T-cell receptor stimulation on T cells.

Results & Discussion

We found that preoperative levels of amino acid catabolites, especially tryptophan catabolites produced via the IDO pathway, were higher in the delirium group than in the non-delirium group. These catabolites were validated as reliable predictors of postoperative delirium. Interestingly, the delirium group had elevated levels of tryptophan catabolites even before surgery, but only a limited increase in these levels was observed postoperatively. This suggests that the tryptophan catabolic pathway may be activated preoperatively in patients at high risk for developing delirium. In addition, our non-targeted metabolomic analysis identified a set of preoperatively elevated gamma-glutamyl dipeptides as significant discriminators of postoperative delirium. In vitro experiments showed that T- cell receptor stimulation resulted in increased tryptophan metabolism and specific gamma-glutamyl dipeptide secretion, which may explain increased metabolic byproducts in postoperative delirium.

Conclusion

Our study highlights the potential of blood concentrations of amino acid catabolites and dipeptides, including those secreted extracellularly upon T-cell activation, as reliable predictors of postoperative delirium.
GENDER DIFFERENCE ON THE MEDIATION EFFECTS OF FILIAL PIETY ON THE ASSOCIATION BETWEEN CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND DEPRESSIVE SYMPTOMS IN OLDER ADULTS
Authors: Chang *Cheng-Chen , Chen Chun-Min , Wu I-Chien , Hsiung Agnes C , Chang Hsing-Yi
Published: February 2025

Background

Filial piety is viewed as a strong family support for Chinese people and is strongly associated with depressive symptoms. It is unknown if gender and filial piety could mediate the relationship between chronic obstructive pulmonary disease (COPD) and depression. There is a strong association between COPD and depressive symptoms; however, the mediating effect of filial piety, a form of social support, on this association is unknown. Since deterioration of lung function can be an indicator of COPD and there is a gender difference in the effects of social support, we hypothesized that pulmonary function is inversely related to depression, and the relationship is mediated by filial piety differently by gender.

Aims & Objectives

We aim to investigate whether filial piety mediates the association between lung function and depression in community-dwelling older people by using the Data from The Healthy Aging Longitudinal Study in Taiwan (HALST).

Method

Data for this study were from the HALST, which is a longitudinal study recruiting people aged 55 and above from seven selected communities in Taiwan. A total of 5664 participants were enrolled in the first wave of the study since October 2008. We analyzed data from the second wave which started in 2013. Pulmonary function was taken between 2016 and 2019; only Community dwelling adults aged 65 and above were analyzed in this study. Pulmonary function, depressive symptoms, and filial piety expectation (FPE) and receipt of filial piety (RFP) were collected. The interaction and mediation of filial piety between lung function and depression was analyzed.

Results

In older men, forced expiratory volume in the first second (FEV1) was inversely correlated with depression (β = -0.1452, p = 0.001) with no mediation effect of FPE. In older women, FEV1 was negatively associated with FPE, but FPE did not increase the risk of depression (β = 0.0713, p = 0.07). In both older men and women, FEV1 was negatively associated with RFP, while RFP reduced the risk of depression (p< 0.001). In older women, the correlation between FEV1 and depression was not statistically significant with complete mediation of RFP.

Discussion & Conclusion

This is the largest study to assess gender difference of mediation effect of filial piety on the relationship between lung function and depressive symptoms in a community-dwelling elderly population. Our results suggested that PRFP independently modified the association of FEV1 and depression in both sexes. After controlling for possible covariates, PRFP was negatively correlated with depression symptoms. In older men, PRFP had a partial mediation effect on the relationship between FEV1 and depression, whereas PRFP had a complete mediation effect on older women. Feelings of insufficient filial piety may increase the likelihood of depression, especially in older women with worse lung function.