Pub Date : 2025-02-13DOI: 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":"https://doi.org/10.1016/j.pnpbp.2025.111287","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"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}
Pub Date : 2025-02-11DOI: 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 (Igp), a secondary pore that leaks electrical current. This mini-review focuses on Igp caused by mutations in the gating charge residues of voltage-gated ion channels. We will discuss how Igp 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}
Pub Date : 2025-02-10DOI: 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.
{"title":"Peripheral transcutaneous electrical stimulation to improve cognition: a review of the main effects in healthy humans and in mildly cognitively impaired patient populations","authors":"Giulia Fiorentini , Eva Massé , Stefania C. Ficarella , Giulia Torromino","doi":"10.1016/j.pnpbp.2025.111290","DOIUrl":"10.1016/j.pnpbp.2025.111290","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111290"},"PeriodicalIF":5.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411470","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}
Pub Date : 2025-02-08DOI: 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.
{"title":"Genetic insights of lipid metabolism and lipid-lowering drugs with Lewy body dementia risk: Evidence from Mendelian randomization","authors":"Hanyu Zhang , Zengyuan Zhou , Jie Gu , Yingnan Lin , Yunyun Yan , Xiaonan Chen , Meixiang Fan , Yanyan Huang","doi":"10.1016/j.pnpbp.2025.111282","DOIUrl":"10.1016/j.pnpbp.2025.111282","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 <em>ANGPTL3</em>, <em>CETP</em>, and <em>HMGCR</em> and LBD risk.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111282"},"PeriodicalIF":5.3,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143378014","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}
Pub Date : 2025-02-08DOI: 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.
{"title":"The acute effects of methoxphenidine on behaviour and pharmacokinetics profile in animal model","authors":"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","doi":"10.1016/j.pnpbp.2025.111285","DOIUrl":"10.1016/j.pnpbp.2025.111285","url":null,"abstract":"<div><div>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.</div><div>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.</div><div>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.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111285"},"PeriodicalIF":5.3,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143378609","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}
Sulcal pits, defined as the deepest points of the cortical surface and identified as stable landmarks, exhibit a consistent emergence sequence that aligns with established gyrification patterns, underscoring their potential as markers for early neurodevelopmental trajectories. Here, we investigate the potential of sulcal pits in characterizing the etiological roots of neurodevelopmental traits and disorders.
This systematic review (PROSPERO register: CRD42022347303) was conducted according to PRISMA guidelines. Searches were performed in PubMed, Web of Science (WOS), and Scopus, initially identifying 102 articles, from which 53 were screened and 19 finally included. The articles were categorized into two main groups: those exploring the ontogenetic processes of sulcal pits and those investigating their relationship with neurodevelopmental phenotypes in health and disease.
The review findings indicate that individuals with congenital conditions or neurodevelopmental disorders exhibit distinct patterns of sulcal pits that correlate with cognitive traits. Additionally, graph analyses consistently show lower mean similarity within individuals from affected groups, suggesting that variations in sulcal pit patterns reflect the impact of neurodevelopmental disturbances.
These results highlight the potential of sulcal pits to capture instabilities in early brain development. However, they also point to a lack of comprehensive biological interpretation in the current literature. Further research is needed to enhance our understanding of the significance of sulcal pits in neurodevelopmental outcomes and to advance their use as diagnostic tools.
{"title":"The sulcal pits as neurodevelopmental markers: A systematic review about their potential use in clinical practice","authors":"Noemí Hostalet , Pilar Salgado-Pineda , Neus Martínez-Abadías , Mar Fatjó-Vilas","doi":"10.1016/j.pnpbp.2025.111289","DOIUrl":"10.1016/j.pnpbp.2025.111289","url":null,"abstract":"<div><div>Sulcal pits, defined as the deepest points of the cortical surface and identified as stable landmarks, exhibit a consistent emergence sequence that aligns with established gyrification patterns, underscoring their potential as markers for early neurodevelopmental trajectories. Here, we investigate the potential of sulcal pits in characterizing the etiological roots of neurodevelopmental traits and disorders.</div><div>This systematic review (PROSPERO register: CRD42022347303) was conducted according to PRISMA guidelines. Searches were performed in PubMed, Web of Science (WOS), and Scopus, initially identifying 102 articles, from which 53 were screened and 19 finally included. The articles were categorized into two main groups: those exploring the ontogenetic processes of sulcal pits and those investigating their relationship with neurodevelopmental phenotypes in health and disease.</div><div>The review findings indicate that individuals with congenital conditions or neurodevelopmental disorders exhibit distinct patterns of sulcal pits that correlate with cognitive traits. Additionally, graph analyses consistently show lower mean similarity within individuals from affected groups, suggesting that variations in sulcal pit patterns reflect the impact of neurodevelopmental disturbances.</div><div>These results highlight the potential of sulcal pits to capture instabilities in early brain development. However, they also point to a lack of comprehensive biological interpretation in the current literature. Further research is needed to enhance our understanding of the significance of sulcal pits in neurodevelopmental outcomes and to advance their use as diagnostic tools.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111289"},"PeriodicalIF":5.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384004","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}
Pub Date : 2025-02-07DOI: 10.1016/j.pnpbp.2025.111288
Mauro Scala , María del Rocío González Soltero , Alberto Bellido Esteban , José Miguel Biscaia Fernández , Verónica Romero-Ferreiro , Alessandro Serretti , Giuseppe Fanelli , Roberto Rodriguez-Jimenez
Backgrounds
Oropharyngeal microbiota may be implicated in the onset and progression of psychotic disorders. This scoping review aims to map the existing evidence concerning the composition, diversity, and metabolic pathways of the oropharyngeal microbiota in patients aged 18 to 65 with a main diagnosis of a psychotic disorder, including individuals at clinical high-risk for psychosis (CHRP) or experiencing first episode psychosis (FEP).
Methods
The scoping review was performed according to the PRISMA-ScR checklist. The systematic literature search was conducted using PubMed, Web of Science, and CINAHL until February 2024.
Results
Seven cross-sectional studies were included, comprising 43 individuals at CHRP, 13 with FEP, 85 with first-episode of schizophrenia (FES), 171 with schizophrenia, and 8 with another schizophrenia spectrum disorder. The oropharyngeal microbiota showed an increase in Lactobacillus gasseri abundance in schizophrenia, and in Firmicutes/Proteobacteria phylum ratio in patients experiencing CHR-P and FES. In schizophrenia, an altered β-diversity was observed alongside increased metabolic pathways related to metabolite transporters. In FES, higher α-diversity and disruptions in amino acid, carbohydrate, and xenobiotic metabolism pathways were found. Hydrogen sulfide (H2S)-producing bacteria were generally enriched in all the stages of disease. Correlations were observed between oropharyngeal microbiota and psychotic symptom domains.
Conclusions
Potential microbial signatures, such as Lactobacillus gasseri and H2S-producing bacteria, were identified in the oropharyngeal microbiota. Alterations in the oropharyngeal microbiota composition and function may be associated with different stages of psychotic disorders, with some overlap between CHR-P and FES.
{"title":"Oropharyngeal microbiota in patients with psychotic disorders: A scoping review on compositional and functional alterations","authors":"Mauro Scala , María del Rocío González Soltero , Alberto Bellido Esteban , José Miguel Biscaia Fernández , Verónica Romero-Ferreiro , Alessandro Serretti , Giuseppe Fanelli , Roberto Rodriguez-Jimenez","doi":"10.1016/j.pnpbp.2025.111288","DOIUrl":"10.1016/j.pnpbp.2025.111288","url":null,"abstract":"<div><h3>Backgrounds</h3><div>Oropharyngeal microbiota may be implicated in the onset and progression of psychotic disorders. This scoping review aims to map the existing evidence concerning the composition, diversity, and metabolic pathways of the oropharyngeal microbiota in patients aged 18 to 65 with a main diagnosis of a psychotic disorder, including individuals at clinical high-risk for psychosis (CHR<img>P) or experiencing first episode psychosis (FEP).</div></div><div><h3>Methods</h3><div>The scoping review was performed according to the PRISMA-ScR checklist. The systematic literature search was conducted using PubMed, Web of Science, and CINAHL until February 2024.</div></div><div><h3>Results</h3><div>Seven cross-sectional studies were included, comprising 43 individuals at CHR<img>P, 13 with FEP, 85 with first-episode of schizophrenia (FES), 171 with schizophrenia, and 8 with another schizophrenia spectrum disorder. The oropharyngeal microbiota showed an increase in <em>Lactobacillus gasseri</em> abundance in schizophrenia, and in <em>Firmicutes/Proteobacteria</em> phylum ratio in patients experiencing CHR-P and FES. In schizophrenia, an altered β-diversity was observed alongside increased metabolic pathways related to metabolite transporters. In FES, higher α-diversity and disruptions in amino acid, carbohydrate, and xenobiotic metabolism pathways were found. Hydrogen sulfide (H<sub>2</sub>S)-producing bacteria were generally enriched in all the stages of disease. Correlations were observed between oropharyngeal microbiota and psychotic symptom domains.</div></div><div><h3>Conclusions</h3><div>Potential microbial signatures, such as <em>Lactobacillus gasseri</em> and H<sub>2</sub>S-producing bacteria, were identified in the oropharyngeal microbiota. Alterations in the oropharyngeal microbiota composition and function may be associated with different stages of psychotic disorders, with some overlap between CHR-P and FES.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111288"},"PeriodicalIF":5.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383980","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}
Major depressive disorder (MDD) and bipolar disorder (BD) share various clinical behaviors and have confounded clinical diagnoses. Converging studies have suggested MDD and BD as disorders with abnormal communication among functional brain networks involved in mental activity and redirection. However, whether MDD and BD show disease-specific alterations in network information interaction remains unclear. This study collected resting-state functional MRI data of 98 patients with MDD, 55 patients with BD, and sex-, age-, and education-matched 95 healthy controls. Spectral dynamic causal model (spDCM) was used to investigate effective connectivities among three large-scale intrinsic functional networks including the default mode network (DMN), salience network (SN), and dorsal attention network (DAN). Effective connectivities showing disease-specific changes were then used as input features of support vector models to predict clinical symptoms and classify individuals with MDD and BD. Compared with healthy controls, both the MDD and BD groups showed increased DAN → SN connectivity. However, within-network connectivities of DMN and DAN showed opposite effects on the diseases. Notably, MDD and BD also showed different alterations on a connectivity loop of SN → DAN → DMN → SN, which could be used to predict the clinical symptom severity of either MDD or BD. Individuals with MDD and BD could be further classified by using connectivities showing opposite disease effects. Our findings reveal common and unique alterations of network interactions in MDD and BD, and further suggest disease-specific neuroimaging markers for clinical diagnosis.
{"title":"Disease-specific alterations of effective connectivity across anti-correlated networks in major depressive disorder and bipolar disorder","authors":"Yun-Shuang Fan , Saike Zhang , Wei Sheng , Jing Guo , Hezong Ling , Qian Cui , Wei Huang , Huafu Chen","doi":"10.1016/j.pnpbp.2025.111283","DOIUrl":"10.1016/j.pnpbp.2025.111283","url":null,"abstract":"<div><div>Major depressive disorder (MDD) and bipolar disorder (BD) share various clinical behaviors and have confounded clinical diagnoses. Converging studies have suggested MDD and BD as disorders with abnormal communication among functional brain networks involved in mental activity and redirection. However, whether MDD and BD show disease-specific alterations in network information interaction remains unclear. This study collected resting-state functional MRI data of 98 patients with MDD, 55 patients with BD, and sex-, age-, and education-matched 95 healthy controls. Spectral dynamic causal model (spDCM) was used to investigate effective connectivities among three large-scale intrinsic functional networks including the default mode network (DMN), salience network (SN), and dorsal attention network (DAN). Effective connectivities showing disease-specific changes were then used as input features of support vector models to predict clinical symptoms and classify individuals with MDD and BD. Compared with healthy controls, both the MDD and BD groups showed increased DAN → SN connectivity. However, within-network connectivities of DMN and DAN showed opposite effects on the diseases. Notably, MDD and BD also showed different alterations on a connectivity loop of SN → DAN → DMN → SN, which could be used to predict the clinical symptom severity of either MDD or BD. Individuals with MDD and BD could be further classified by using connectivities showing opposite disease effects. Our findings reveal common and unique alterations of network interactions in MDD and BD, and further suggest disease-specific neuroimaging markers for clinical diagnosis.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111283"},"PeriodicalIF":5.3,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374650","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}
Pub Date : 2025-02-05DOI: 10.1016/j.pnpbp.2025.111284
Pin Wang , Heya Luan , Shaoqi Li , Xiaodong Han , Wenxian Sun , Jin Gong , Chang Xu , Runqi Chen , Cuibai Wei
Background
Extensive perivascular spaces (PVS) burden has been reported to be associated with neurodegenerative diseases and brain structure; however, the causal effects has not been determined yet. Therefore, this study aimed to investigate the causal effect of extensive PVS burden on neurodegenerative diseases and brain structure through Mendelian randomization (MR) analysis.
Methods
Two-sample bidirectional MR was conducted based on publicly available genome-wide association studies (GWAS) summary statistics. Causal estimates of extensive PVS burden on neurodegenerative diseases and brain structure were primarily assessed using the inverse-variance weighted (IVW) method, supplemented by additional methods, including MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses were performed to assess heterogeneity and pleiotropy. In addition, we explored whether brain structure act as a mediating factor in the pathway from extensive PVS burden to neurodegenerative diseases.
Results
Our MR study found that extensive PVS burden in white matter (WM-PVS) burden was associated with lower Alzheimer's disease (AD) risk (IVW OR (95 % CI) = 0.963(0.929 to 0.999), P = 0.0428), with no heterogeneity and pleiotropy detected. In addition, following FDR correction, we found bidirectional causal relationships between extensive PVS burden and brain structure. Moreover, our results of the mediated analysis showed that the surface area of parahippocampal, as a mediating variable, plays an important role in the causal relationship between WM-PVS and AD. The mediation effect is 18 %.
Conclusions
Our study provides evidence for the causal associations of different extensive PVS burden phenotypes with neurodegenerative diseases and brain structures, improving our understanding of the complex relationships between different brain injuries.
{"title":"Extensive perivascular spaces burden causally affects neurodegenerative diseases and brain structure: A two-sample bidirectional Mendelian randomization study","authors":"Pin Wang , Heya Luan , Shaoqi Li , Xiaodong Han , Wenxian Sun , Jin Gong , Chang Xu , Runqi Chen , Cuibai Wei","doi":"10.1016/j.pnpbp.2025.111284","DOIUrl":"10.1016/j.pnpbp.2025.111284","url":null,"abstract":"<div><h3>Background</h3><div>Extensive perivascular spaces (PVS) burden has been reported to be associated with neurodegenerative diseases and brain structure; however, the causal effects has not been determined yet. Therefore, this study aimed to investigate the causal effect of extensive PVS burden on neurodegenerative diseases and brain structure through Mendelian randomization (MR) analysis.</div></div><div><h3>Methods</h3><div>Two-sample bidirectional MR was conducted based on publicly available genome-wide association studies (GWAS) summary statistics. Causal estimates of extensive PVS burden on neurodegenerative diseases and brain structure were primarily assessed using the inverse-variance weighted (IVW) method, supplemented by additional methods, including MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses were performed to assess heterogeneity and pleiotropy. In addition, we explored whether brain structure act as a mediating factor in the pathway from extensive PVS burden to neurodegenerative diseases.</div></div><div><h3>Results</h3><div>Our MR study found that extensive PVS burden in white matter (WM-PVS) burden was associated with lower Alzheimer's disease (AD) risk (IVW OR (95 % CI) = 0.963(0.929 to 0.999), <em>P</em> = 0.0428), with no heterogeneity and pleiotropy detected. In addition, following FDR correction, we found bidirectional causal relationships between extensive PVS burden and brain structure. Moreover, our results of the mediated analysis showed that the surface area of parahippocampal, as a mediating variable, plays an important role in the causal relationship between WM-PVS and AD. The mediation effect is 18 %.</div></div><div><h3>Conclusions</h3><div>Our study provides evidence for the causal associations of different extensive PVS burden phenotypes with neurodegenerative diseases and brain structures, improving our understanding of the complex relationships between different brain injuries.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111284"},"PeriodicalIF":5.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143348783","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}
Pub Date : 2025-02-03DOI: 10.1016/j.pnpbp.2025.111279
Zhen Xuen Brandon Low, Shin Jie Yong, Hayam A Alrasheed, Maha F Al-Subaie, Nawal A Al Kaabi, Mubarak Alfaresi, Hawra Albayat, Jawaher Alotaibi, Ali Al Bshabshe, Ameen S S Alwashmi, Amal A Sabour, Maha A Alshiekheid, Zainab H Almansour, Huda Alharthi, Hani A Al Ali, Adel A Almoumen, Nabil A Alqasimi, Hajir AlSaihati, Alfonso J Rodriguez-Morales, Ali A Rabaan
Rationale: In our ongoing battle against the coronavirus 2019 (COVID-19) pandemic, a major challenge is the enduring symptoms that continue after acute infection. Also known as Long COVID, post-COVID-19 syndrome (PCS) often comes with debilitating symptoms like fatigue, disordered sleep, olfactory dysfunction, and cognitive issues ("brain fog"). Currently, there are no approved treatments for PCS. Recent research has uncovered that the severity of PCS is inversely linked to circulating serotonin levels, highlighting the potential of serotonin-modulating therapeutics for PCS. Therefore, we propose that serotonergic psychedelics, acting mainly via the 5-HT2A serotonin receptor, hold promise for treating PCS.
Objectives: Our review aims to elucidate potential mechanisms by which serotonergic psychedelics may alleviate the symptoms of PCS.
Results: Potential mechanisms through which serotonergic psychedelics may alleviate PCS symptoms are discussed, with emphasis on their effects on inflammation, neuroplasticity, and gastrointestinal function. Additionally, this review explores the potential of serotonergic psychedelics in mitigating endothelial dysfunction, a pivotal aspect of PCS pathophysiology implicated in organ dysfunction. This review also examines the potential role of serotonergic psychedelics in alleviating specific PCS symptoms, which include olfactory dysfunction, cognitive impairment, sleep disturbances, and mental health challenges.
Conclusions: Emerging evidence suggests that serotonergic psychedelics may alleviate PCS symptoms. However, further high-quality research is needed to thoroughly assess their safety and efficacy in treating patients with PCS.
{"title":"Serotonergic psychedelics as potential therapeutics for post-COVID-19 syndrome (or Long COVID): A comprehensive review.","authors":"Zhen Xuen Brandon Low, Shin Jie Yong, Hayam A Alrasheed, Maha F Al-Subaie, Nawal A Al Kaabi, Mubarak Alfaresi, Hawra Albayat, Jawaher Alotaibi, Ali Al Bshabshe, Ameen S S Alwashmi, Amal A Sabour, Maha A Alshiekheid, Zainab H Almansour, Huda Alharthi, Hani A Al Ali, Adel A Almoumen, Nabil A Alqasimi, Hajir AlSaihati, Alfonso J Rodriguez-Morales, Ali A Rabaan","doi":"10.1016/j.pnpbp.2025.111279","DOIUrl":"10.1016/j.pnpbp.2025.111279","url":null,"abstract":"<p><strong>Rationale: </strong>In our ongoing battle against the coronavirus 2019 (COVID-19) pandemic, a major challenge is the enduring symptoms that continue after acute infection. Also known as Long COVID, post-COVID-19 syndrome (PCS) often comes with debilitating symptoms like fatigue, disordered sleep, olfactory dysfunction, and cognitive issues (\"brain fog\"). Currently, there are no approved treatments for PCS. Recent research has uncovered that the severity of PCS is inversely linked to circulating serotonin levels, highlighting the potential of serotonin-modulating therapeutics for PCS. Therefore, we propose that serotonergic psychedelics, acting mainly via the 5-HT2A serotonin receptor, hold promise for treating PCS.</p><p><strong>Objectives: </strong>Our review aims to elucidate potential mechanisms by which serotonergic psychedelics may alleviate the symptoms of PCS.</p><p><strong>Results: </strong>Potential mechanisms through which serotonergic psychedelics may alleviate PCS symptoms are discussed, with emphasis on their effects on inflammation, neuroplasticity, and gastrointestinal function. Additionally, this review explores the potential of serotonergic psychedelics in mitigating endothelial dysfunction, a pivotal aspect of PCS pathophysiology implicated in organ dysfunction. This review also examines the potential role of serotonergic psychedelics in alleviating specific PCS symptoms, which include olfactory dysfunction, cognitive impairment, sleep disturbances, and mental health challenges.</p><p><strong>Conclusions: </strong>Emerging evidence suggests that serotonergic psychedelics may alleviate PCS symptoms. However, further high-quality research is needed to thoroughly assess their safety and efficacy in treating patients with PCS.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111279"},"PeriodicalIF":5.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257404","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号