Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献_第4页

Serum lipid and plasma fatty acid profiles in PTSD patients and healthy individuals: Associations with symptoms, cognitive function, and inflammatory markers

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-02-21 DOI: 10.1016/j.pnpbp.2025.111298

Shintaro Ogawa , Hiroaki Hori , Madoka Niwa , Mariko Itoh , Mingming Lin , Fuyuko Yoshida , Keiko Ino , Hitomi Kawanishi , Megumi Narita , Wakako Nakano , Risa Imai , Mie Matsui , Toshiko Kamo , Hiroshi Kunugi , Kotaro Hattori , Yoshiharu Kim

Increasing evidence suggests that posttraumatic stress disorder (PTSD), a serious mental health condition, is associated with physical health problems. Lipid-related molecules are crucial for central nervous system functions associated with PTSD symptoms; however, case-control studies exploring the relationship between PTSD and lipid-related molecules are scarce. We examined 68 civilian PTSD patients and 97 healthy controls, evaluating PTSD symptoms, childhood maltreatment history, suicidality, and cognitive functions. Cholesterol, triglycerides, and inflammation-related marker levels were analyzed in serum, while fatty acid levels were measured in plasma. Compared to controls, patients exhibited significantly lower high-density lipoprotein cholesterol and n-6 linoleic acid levels, alongside higher saturated palmitic acid levels and the triene-to-tetraene (T/T) ratio. PTSD symptoms, particularly hyperarousal, were significantly positively correlated with n-6 γ-linolenic, n-6 dihomo-γ-linolenic, and n-9 mead acid levels, and the T/T ratio. Cognitive functions were significantly positively correlated with n-3 docosahexaenoic acid and total n-3 fatty acid levels, and negatively correlated with saturated lauric, palmitic, and total saturated fatty acid levels. Suicidality was significantly positively correlated with dihomo-γ-linolenic acid, mead acid levels, and the T/T ratio, and negatively correlated with polyunsaturated fatty acid (PUFA) levels. Inflammation-related marker levels were significantly correlated with higher palmitic, n-9 oleic, and total n-9 fatty acid levels, and lower linoleic acid and PUFA levels. Latent profile analysis (LPA) revealed distinct subgroups associated with unique fatty acid profiles. These lipid-related alterations may improve the understanding of PTSD pathophysiology. Distinct fatty acid profiles identified by LPA may help subtype PTSD patients and guide nutrition-based personalized treatment strategies.

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引用次数: 0

Integrative gray matter volume and molecular analyses of altered intrinsic neural timescale in internet gaming disorder

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-02-21 DOI: 10.1016/j.pnpbp.2025.111296

Longyao Ma , Bohui Mei , Mengzhe Zhang , Qiuying Tao , Jieping Sun , Jinghan Dang , Yan Lang , Weijian Wang , Yarui Wei , Shaoqiang Han , Jingliang Cheng , Yong Zhang

Background

Internet gaming disorder (IGD) frequently features abnormalities in emotional and cognitive processing, for which the specific neurobiological mechanisms are not known. The intrinsic neural timescale (INT) gradient reflects how long neural information is stored in a specialized brain region and represents its function. Therefore, we investigated whether IGD exhibited altered INT and accompanying gray matter volume (GMV) and underlying molecular architectural abnormalities.

Methods

Resting-state functional magnetic resonance data from 57 patients with IGD (IGDs) and 50 demographically matched healthy controls (HCs) were collected, and INT was calculated by assessing the autocorrelation of intrinsic neural signals. Voxel-based morphometric analysis was conducted to calculate whole-brain GMV. Then, comparing INT between groups and correlation analysis with clinical characteristics was performed. Furthermore, correlations between INT and PET- and SPECT-driven maps were used to examine specific neurotransmitter system alternations.

Result

Compared to HCs, IGDs exhibited shorter timescales in the bilateral insula, bilateral parahippocampal gyrus, left amygdala, and left superior temporal pole. The decreased INT in the right insula was positively correlated with the severity of internet addiction. Interestingly, the shorter timescales are spatially associated with the serotonergic system.

Conclusion

This study suggests atypical emotional and cognitive processing deficits in localized brain regions of IGDs. And these findings establish a link between abnormal local neurodynamics and structures and neurotransmitters, which facilitates synthesized comprehension of IGDs and provides new perspectives for treatment.

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引用次数: 0

White matter integrity and verbal memory following a first episode of psychosis: A longitudinal study

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-02-20 DOI: 10.1016/j.pnpbp.2025.111294

Joseph Ghanem , Jana F. Totzek , Charlie Henri-Bellemare , Delphine Raucher-Chéné , Gregory Kiar , Raihaan Patel , M. Mallar Chakravarty , Jai L. Shah , Ridha Joober , Ashok Malla , Martin Lepage , Katie M. Lavigne

Psychotic disorders are heterogeneous disorders for which there is evidence of structural and functional brain abnormalities. The role of white matter integrity, often measured via Fractional Anisotropy (FA), has played a controversial role in individuals with a first episode of psychosis (FEP). Similarly, some FEP studies have observed that higher FA is associated with better verbal memory, but others failed to find such an association. Studying the early stages of psychosis represents a promising avenue to overcome previous confounding factors and characterize the disease in its early clinical stages.

Eighty individuals with a FEP were recruited from a specialized early intervention program for psychosis alongside 55 non-clinical controls from the community matched for age and sex. Both groups were followed and scanned 4 times: at baseline (within 3 months after program entry), 6 months, 12 months, and 18 months. Tract-Based Spatial Statistics (TBSS) were used on 3.0 Tesla diffusion-weighted images to extract fractional anisotropy values for white matter regions of interest in accordance with the John Hopkins University white-matter tractography atlas. The analysis revealed no significant main effect of group or time, and no significant associations between FA and verbal memory. Overall, differences in FA are small early in the course of illness and longer follow-up periods may be required to identify possible changes during a critical intervention window.

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引用次数: 0

A naturalistic retrospective evaluation of the utility of pharmacogenetic testing based on CYP2D6 e CYP2C19 profiling in antidepressants treatment in a cohort of patients with major depressive disorder

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-02-17 DOI: 10.1016/j.pnpbp.2025.111292

Alessio Squassina , Pasquale Paribello , Marco Pinna , Martina Contu , Claudia Pisanu , Donatella Congiu , Giovanni Severino , Anna Meloni , Andrea Carta , Claudio Conversano , Francesco Mola , Maria Del Zompo , Federico Bernoni d'Aversa , Alessandra Minelli , Massimo Gennarelli , Federica Pinna , Bernardo Carpiniello , Mirko Manchia

Response to antidepressants (ADs) is highly variable and partly genetically driven, but the utility of pharmacogenetic testing in guiding ADs treatment is still controversial. We conducted a retrospective, naturalistic study to explore the utility of CYP2C6 and CYP2C19 genotyping in ADs treatment in a sample of 156 patients diagnosed with major depressive disorder from south Sardinia (Italy). Clinical data, including history of medication regimens, adverse reactions, and response to ADs were collected over the last five years preceding recruitment. Patients received pharmacogenetic testing at recruitment and were classified depending on whether their history of treatment regimen followed the recommendations of the Clinical Pharmacogenetics Implementation Consortium (CPIC)).

Non-responders to ADs had a larger number of therapeutic regimens and of medication changes due to lack of response compared to responders. Patients with at least one incongruent regimen had a larger number of total therapeutic changes and fewer congruent regimens. Metabolizing phenotypes of CYP2D6 were not associated with response to ADs or changes in regimen of any kind. However, the group of ultra-rapid metabolizers for CYP2C19 showed significantly smaller improvement in symptoms while the poor-metabolizers showed a larger number of medication changes for side effects compared to normal, intermediate and rapid metabolizers. Our findings suggest that the implementation of pharmacogenetic testing based on CYP2C19 could be clinically useful in guiding AD treatment, but further studies are warranted to investigate the clinical implications of implementing PGx testing in depression.

{"title":"A naturalistic retrospective evaluation of the utility of pharmacogenetic testing based on CYP2D6 e CYP2C19 profiling in antidepressants treatment in a cohort of patients with major depressive disorder","authors":"Alessio Squassina , Pasquale Paribello , Marco Pinna , Martina Contu , Claudia Pisanu , Donatella Congiu , Giovanni Severino , Anna Meloni , Andrea Carta , Claudio Conversano , Francesco Mola , Maria Del Zompo , Federico Bernoni d'Aversa , Alessandra Minelli , Massimo Gennarelli , Federica Pinna , Bernardo Carpiniello , Mirko Manchia","doi":"10.1016/j.pnpbp.2025.111292","DOIUrl":"10.1016/j.pnpbp.2025.111292","url":null,"abstract":"<div><div>Response to antidepressants (ADs) is highly variable and partly genetically driven, but the utility of pharmacogenetic testing in guiding ADs treatment is still controversial. We conducted a retrospective, naturalistic study to explore the utility of CYP2C6 and CYP2C19 genotyping in ADs treatment in a sample of 156 patients diagnosed with major depressive disorder from south Sardinia (Italy). Clinical data, including history of medication regimens, adverse reactions, and response to ADs were collected over the last five years preceding recruitment. Patients received pharmacogenetic testing at recruitment and were classified depending on whether their history of treatment regimen followed the recommendations of the Clinical Pharmacogenetics Implementation Consortium (CPIC)).</div><div>Non-responders to ADs had a larger number of therapeutic regimens and of medication changes due to lack of response compared to responders. Patients with at least one incongruent regimen had a larger number of total therapeutic changes and fewer congruent regimens. Metabolizing phenotypes of CYP2D6 were not associated with response to ADs or changes in regimen of any kind. However, the group of ultra-rapid metabolizers for CYP2C19 showed significantly smaller improvement in symptoms while the poor-metabolizers showed a larger number of medication changes for side effects compared to normal, intermediate and rapid metabolizers. Our findings suggest that the implementation of pharmacogenetic testing based on CYP2C19 could be clinically useful in guiding AD treatment, but further studies are warranted to investigate the clinical implications of implementing PGx testing in depression.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111292"},"PeriodicalIF":5.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Addicted brains on brief abstinence: Similarities and differences in functional connectivity patterns between internet gaming disorder and tobacco use disorder

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-02-17 DOI: 10.1016/j.pnpbp.2025.111286

Xuefeng Xu, Bo Yang, Yanbin Zheng, Haosen Ni, Guang-Heng Dong

Background

Many studies have attempted to understand the neural basis of internet gaming disorder (IGD) to explore if IGD could be diagnosed as an addictive behavior. However, those findings were often inconsistent due to the participants having varying craving levels. Individual brain activities in the abstinence state are different from that in the neutral state. Therefore, exploring the responses of the brain during abstinence in IGD and comparing them with substance addiction is crucial in understanding this complex, craving-prone disorder.

Methods

Three groups of male participants were recruited: IGD (61), tobacco use disorder (TUD) (61), and health controls (80). Resting-state functional Magnetic Resonance Imaging data were collected after brief abstinence (not gaming/smoking for about 1.5 h). First, we identified abnormal brain regions with altered amplitude of low-frequency fluctuations (ALFF) in IGD and TUD. Then, using these regions as the regions of interest, we conducted a functional connectivity (FC) analysis to explore the similarities and differences between IGD and TUD. Finally, we used a neural network analysis to build a classification model based on ALFF results.

Results

The abnormal brain regions with altered ALFF were observed in both IGD and TUD, including the superior frontal gyrus, orbitofrontal cortex, precentral gyrus, caudate, and thalamus. FC analysis showed similarities in the orbitofrontal regions, specifically between caudate-nucleus accumbens and thalamus-precentral gyrus, and differences in the executive control and reward regions. Neural network analysis demonstrated that abnormal ALFF brain regions can effectively classify addicted individuals from health controls.

Conclusions

This study showed that brain regions in IGD and TUD had similar ALFF changes during brief abstinence. However, FC analyses revealed contrasting results. FC in IGD increased, while it decreased in TUD. These differences may be due to IGD's internal craving, unlike nicotine for TUD. These findings deepen our understanding of the neural mechanisms of IGD.

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引用次数: 0

Microglia-derived sEV: Friend or foe in the pathogenesis of cognitive impairment

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-02-13 DOI: 10.1016/j.pnpbp.2025.111287

Lilin Chen , Wei Wang

As immune cells, microglia serve a dual role in cognition. Microglia-derived sEV actively contribute to the development of cognitive impairment by selectively targeting specific cells through various substances such as proteins, RNA, DNA, lipids, and metabolic waste. In recent years, there has been an increasing focus on understanding the pathogenesis and therapeutic potential of sEV. This comprehensive review summarizes the detrimental effects of M1 microglial sEV on pathogenic protein transport, neuroinflammation, disruption of the blood-brain barrier (BBB), neuronal death and synaptic dysfunction in relation to cognitive damage. Additionally, it highlights the beneficial effects of M2 microglia on alleviating cognitive impairment based on evidence from cellular experiments and animal studies. Furthermore, since microglial-secreted sEV can be found in cerebrospinal fluid or cross the BBB into plasma circulation, they play a crucial role in diagnosing cognitive impairment. However, using sEV as biomarkers is still at an experimental stage and requires further clinical validation. Future research should aim to explore the mechanisms underlying microglial involvement in various nervous system disorders to identify novel targets for clinical interventions.

{"title":"Microglia-derived sEV: Friend or foe in the pathogenesis of cognitive impairment","authors":"Lilin Chen , Wei Wang","doi":"10.1016/j.pnpbp.2025.111287","DOIUrl":"10.1016/j.pnpbp.2025.111287","url":null,"abstract":"<div><div>As immune cells, microglia serve a dual role in cognition. Microglia-derived sEV actively contribute to the development of cognitive impairment by selectively targeting specific cells through various substances such as proteins, RNA, DNA, lipids, and metabolic waste. In recent years, there has been an increasing focus on understanding the pathogenesis and therapeutic potential of sEV. This comprehensive review summarizes the detrimental effects of M1 microglial sEV on pathogenic protein transport, neuroinflammation, disruption of the blood-brain barrier (BBB), neuronal death and synaptic dysfunction in relation to cognitive damage. Additionally, it highlights the beneficial effects of M2 microglia on alleviating cognitive impairment based on evidence from cellular experiments and animal studies. Furthermore, since microglial-secreted sEV can be found in cerebrospinal fluid or cross the BBB into plasma circulation, they play a crucial role in diagnosing cognitive impairment. However, using sEV as biomarkers is still at an experimental stage and requires further clinical validation. Future research should aim to explore the mechanisms underlying microglial involvement in various nervous system disorders to identify novel targets for clinical interventions.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111287"},"PeriodicalIF":5.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Two pores instead of one: Gating pore current and the electrical leak in autism and epilepsy

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-02-11 DOI: 10.1016/j.pnpbp.2025.111291

Ahmed Eltokhi , Tamer M. Gamal El-Din

Imagine the brain as a dynamic city, where countless vehicles traverse major arterial roads and branching side streets. The smooth traffic flow depends on a balance between excitatory neurons, which act as main roads encouraging vehicles to move forward, and inhibitory neurons, represented by branching side streets that regulate and control the traffic flow back onto the main route. Both systems work in tandem to maintain efficient operations, preventing gridlock or chaos. Zooming in further, the voltage-gated ion channels within neurons resemble traffic lights on arterial roads or side streets. Green means go, red means stop, and yellow signals caution. These channels regulate the flow of bioelectric signals, coordinating transitions between green, yellow, and red—analogous to an action potential. In excitatory neurons (major roads), voltage-gated sodium channels act as green lights, allowing sodium ions to flow in during depolarization. In contrast, voltage-gated potassium channels serve as yellow lights, eventually signaling red to terminate the action potential. In inhibitory neurons (side streets), sodium influx produces action potentials that ultimately control and limit traffic on the major roads. This analogy can be extended to describe neuropsychiatric and neurological disorders, such as autism spectrum disorder (ASD) and epilepsy, which arise from mutations in voltage-gated ion channels. These mutations alter the channels' ability to open and close properly, disrupting the timing and duration of red, yellow and green signals and impairing traffic flow. Now, picture yourself on a major arterial road with green and red flickering simultaneously. Such a disastrous scenario could lead to even more dangerous outcomes, with cars moving when they should stop or stopping when they should move. This specific analogy illustrates a key feature of certain mutations in voltage-gated ion channels that result in the gating pore current (I_gp), a secondary pore that leaks electrical current. This mini-review focuses on I_gp caused by mutations in the gating charge residues of voltage-gated ion channels. We will discuss how I_gp contributes to the pathophysiology of ASD and epilepsy and explore therapeutic strategies targeting this mechanism.

{"title":"Two pores instead of one: Gating pore current and the electrical leak in autism and epilepsy","authors":"Ahmed Eltokhi , Tamer M. Gamal El-Din","doi":"10.1016/j.pnpbp.2025.111291","DOIUrl":"10.1016/j.pnpbp.2025.111291","url":null,"abstract":"<div><div>Imagine the brain as a dynamic city, where countless vehicles traverse major arterial roads and branching side streets. The smooth traffic flow depends on a balance between excitatory neurons, which act as main roads encouraging vehicles to move forward, and inhibitory neurons, represented by branching side streets that regulate and control the traffic flow back onto the main route. Both systems work in tandem to maintain efficient operations, preventing gridlock or chaos. Zooming in further, the voltage-gated ion channels within neurons resemble traffic lights on arterial roads or side streets. Green means go, red means stop, and yellow signals caution. These channels regulate the flow of bioelectric signals, coordinating transitions between green, yellow, and red—analogous to an action potential. In excitatory neurons (major roads), voltage-gated sodium channels act as green lights, allowing sodium ions to flow in during depolarization. In contrast, voltage-gated potassium channels serve as yellow lights, eventually signaling red to terminate the action potential. In inhibitory neurons (side streets), sodium influx produces action potentials that ultimately control and limit traffic on the major roads. This analogy can be extended to describe neuropsychiatric and neurological disorders, such as autism spectrum disorder (ASD) and epilepsy, which arise from mutations in voltage-gated ion channels. These mutations alter the channels' ability to open and close properly, disrupting the timing and duration of red, yellow and green signals and impairing traffic flow. Now, picture yourself on a major arterial road with green and red flickering simultaneously. Such a disastrous scenario could lead to even more dangerous outcomes, with cars moving when they should stop or stopping when they should move. This specific analogy illustrates a key feature of certain mutations in voltage-gated ion channels that result in the gating pore current (I<sub>gp</sub>), a secondary pore that leaks electrical current. This mini-review focuses on I<sub>gp</sub> caused by mutations in the gating charge residues of voltage-gated ion channels. We will discuss how I<sub>gp</sub> contributes to the pathophysiology of ASD and epilepsy and explore therapeutic strategies targeting this mechanism.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111291"},"PeriodicalIF":5.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Peripheral transcutaneous electrical stimulation to improve cognition: a review of the main effects in healthy humans and in mildly cognitively impaired patient populations

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-02-10 DOI: 10.1016/j.pnpbp.2025.111290

Giulia Fiorentini , Eva Massé , Stefania C. Ficarella , Giulia Torromino

Peripheral nerve stimulation (PNS) is an ancient technique, up to now mainly used for pain management. The least invasive approach for PNS is transcutaneous electrical stimulation (TENS), which is performed by delivering mild electric currents through the skin and, depending on the stimulation pattern, activates the somatosensory Aβ-, Aδ- and C-fibers. In addition to its use for pain relief, accumulating data indicates that TENS can have broad-spectrum cognitive effects through the activation of neuromodulatory brain pathways. This review aims to summarize the current evidence on the cognitive effects of TENS, from healthy participants and mildly cognitively affected patients. Most studies on this topic have investigated the effects of TENS on memory, while fewer studies have explored attention, executive functions, and verbal fluency. Overall, promising evidence suggests that TENS may exert positive effects on specific cognitive functions. Further research is needed to build consensus on the most effective stimulation protocols, for both neurorehabilitation and enhancement, and to better understand the neurobiological mechanisms underlying the cognitive effects of TENS.

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引用次数: 0

Genetic insights of lipid metabolism and lipid-lowering drugs with Lewy body dementia risk: Evidence from Mendelian randomization

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-02-08 DOI: 10.1016/j.pnpbp.2025.111282

Hanyu Zhang , Zengyuan Zhou , Jie Gu , Yingnan Lin , Yunyun Yan , Xiaonan Chen , Meixiang Fan , Yanyan Huang

Background

Lewy body dementia (LBD) is the second common dementia, with unclear mechanisms and limited treatment options. Dyslipidemia has been implicated in LBD, but the role of lipid-lowering drugs remains underexplored. This study aims to investigate the association between lipid traits, drug targets, and LBD risk using Mendelian Randomization (MR) analysis.

Methods

We performed univariable and multivariable MR analyses to evaluate the causal effects of lipid traits on the risk of LBD. Then, drug-target MR analysis and subtype analysis were conducted to evaluate the effects of lipid-lowering therapies on LBD.

Results

In univariable MR, genetically predicted low-density lipoprotein cholesterol (LDL-C) and remnant cholesterol (RC) levels were associated with an increased risk of LBD. Mediation analysis suggested a potential interaction between LDL-C and RC in influencing LBD risk. Drug-target MR analysis identified significant associations between genetically proxied inhibition of ANGPTL3, CETP, and HMGCR and LBD risk.

Conclusion

This MR analysis provided evidence that elevated LDL-C and RC may increase the risk of LBD. Additionally, targeting ANGPTL3, CETP, and HMGCR may represent potential therapeutic strategies for the prevention or treatment of LBD.

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引用次数: 0

The acute effects of methoxphenidine on behaviour and pharmacokinetics profile in animal model

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-02-08 DOI: 10.1016/j.pnpbp.2025.111285

Kristýna Štefková-Mazochová , Hynek Danda , Vladimír Mazoch , Lucie Olejníková-Ladislavová , Klára Šíchová , Natálie Paškanová , Magdaléna Vágnerová , Bronislav Jurásek , Pavel Ryšánek , Martin Šíma , Adam Šafanda , Quang Hiep Bui , Martin Kuchař , Tomáš Páleníček

Methoxphenidine (MXP) is classified as a new psychoactive substance that has recently emerged on the illicit drug market. Understanding the pharmacological and behavioural profiles of newly emerging drugs is essential for a better understanding of their psychotropic effects and potential toxicity. Therefore, in this study, we investigated a broad range of effects of acute MXP administration: pharmacokinetics in the brain and serum; behaviour (open field and prepulse inhibition), systemic toxicity (lethal dose; LD 50), and histopathology changes in parenchymal organs of Wistar rats.

MXP rapidly crossed the blood-brain barrier, reaching peak median concentrations in both serum and brain 30 min post-administration, followed by an elimination phase with a half-life of 2.15 h. Locomotor activity in the open field test displayed a dose-response effect at low to moderate doses (10–20 mg/kg MXP). At higher doses (40 mg/kg), locomotor activity decreased. All doses of MXP significantly disrupted prepulse inhibition and the effect was present during the onset of its action as well as 60 min after treatment. Additionally, MXP demonstrated moderate acute toxicity, with an estimated LD50 of 500 mg/kg when administered subcutaneously.

In summary, MXP exhibited a profile similar to typical dissociative anesthetics, producing stimulant and anxiogenic effects at lower doses, sedative effects at higher doses, and disrupting sensorimotor gating. The accumulation of MXP in brain tissue is likely to contribute to acute intoxication in humans, potentially leading to negative experiences. Our findings highlight the potentially dangerous effects of recreational MXP use and underscore the risks of inducing serious adverse health outcomes.

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引用次数: 0