Pub Date : 2025-01-19DOI: 10.1016/j.pnpbp.2025.111255
Arshman S. Sahid , Melissa J. Bebbington , Abigail Marcus , Sarah J. Baracz , Kelsey S. Zimmermann , JuLee Oei , Meredith C. Ward , Kelly J. Clemens
The opioid crisis continues to escalate, disproportionately affecting women of reproductive age. Traditionally the first line of treatment for pregnant women with opioid use disorder is the mu-opioid receptor agonist methadone. However, in recent years, the use of buprenorphine as a replacement therapy has increased as it has fewer side-effects and longer duration of action. Either drug significantly improves outcomes for the mother, but their impact on the developing infant is less certain. To this end, we directly compared the effects of perinatal methadone (MET; 9 mg/kg/day starting dose) versus buprenorphine (BUP; 1 mg/kg/day starting dose) delivered via mini osmotic pump on the long-term behavior of offspring and associated molecular changes in the brain. Opioid exposure across pregnancy resulted in reduced weight gain and smaller litters compared to sham controls, and female pups in particular gained weight at a slower rate across development. Opioid treatment delayed neuromuscular reflex development, with subtle differences observed between MET and BUP. As juveniles, pups with prenatal MET exposure showed poor object recognition, although both MET and BUP have led to deficits in place recognition task. Immunofluorescence studies found corresponding decreases in astrocytes and myelin-positive cells in the hippocampus in both MET and BUP pups. Overall, both MET and BUP were associated with significant developmental and cognitive delays and changes in markers of neuronal development and inflammation, particularly in the hippocampus. The majority of changes were similar between MET and BUP-treated pups, suggesting that gestational exposure to either drug has a similar long-term negative impact on offspring.
{"title":"Perinatal exposure to methadone or buprenorphine impairs hippocampal-dependent cognition and brain development in juvenile rats","authors":"Arshman S. Sahid , Melissa J. Bebbington , Abigail Marcus , Sarah J. Baracz , Kelsey S. Zimmermann , JuLee Oei , Meredith C. Ward , Kelly J. Clemens","doi":"10.1016/j.pnpbp.2025.111255","DOIUrl":"10.1016/j.pnpbp.2025.111255","url":null,"abstract":"<div><div>The opioid crisis continues to escalate, disproportionately affecting women of reproductive age. Traditionally the first line of treatment for pregnant women with opioid use disorder is the mu-opioid receptor agonist methadone. However, in recent years, the use of buprenorphine as a replacement therapy has increased as it has fewer side-effects and longer duration of action. Either drug significantly improves outcomes for the mother, but their impact on the developing infant is less certain. To this end, we directly compared the effects of perinatal methadone (MET; 9 mg/kg/day starting dose) versus buprenorphine (BUP; 1 mg/kg/day starting dose) delivered via mini osmotic pump on the long-term behavior of offspring and associated molecular changes in the brain. Opioid exposure across pregnancy resulted in reduced weight gain and smaller litters compared to sham controls, and female pups in particular gained weight at a slower rate across development. Opioid treatment delayed neuromuscular reflex development, with subtle differences observed between MET and BUP. As juveniles, pups with prenatal MET exposure showed poor object recognition, although both MET and BUP have led to deficits in place recognition task. Immunofluorescence studies found corresponding decreases in astrocytes and myelin-positive cells in the hippocampus in both MET and BUP pups. Overall, both MET and BUP were associated with significant developmental and cognitive delays and changes in markers of neuronal development and inflammation, particularly in the hippocampus. The majority of changes were similar between MET and BUP-treated pups, suggesting that gestational exposure to either drug has a similar long-term negative impact on offspring.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111255"},"PeriodicalIF":5.3,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016528","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 : 2025-01-19DOI: 10.1016/j.pnpbp.2025.111259
Steven A. Barker
Renewed interest in the clinical use of psychedelic drugs acknowledges their therapeutic effectiveness. It has also provided a changing frame of reference for older psychedelic drug study data, especially regarding concentrations of N, N-dimethyltryptamine (DMT) reported in rodent brains and recent discoveries in DMT receptor interactions in rat brain neurons and select brain areas. The mode of action of DMT in its newly defined role as a neuroplastogen, its effectiveness in treating neuropsychiatric disorders, and its binding to intracellular sigma-1 and 5HT2a receptors may define these possible roles.
Recent data also show psychedelics promote neuroplasticity via activation of sigma-1 receptors associated with the endoplasmic reticulum and binding to 5-HT2a receptors predominantly related to the intracellular membrane of the Golgi apparatus in cortical neurons and the failure of DMT to occupy cell surface 5-HT2a receptors. While DMT has been proposed as the endogenous ligand for sigma-1, there is no identified ligand for intracellular 5-HT2a receptors, which serotonin cannot acquire. DMT is proposed to be the missing endogenous ligand.
These data further suggest that DMT may be involved in brain development in rat pups. Brain levels of DMT have also been shown to be elevated by stress in the rat and appear to be under an inducible, adaptive, physiological regulatory system control. With DMT acting as the natural ligand for intracellular 5HT2a receptors in the Golgi, it may also explain the subjective effects observed from the administration of psychedelics in general and define some of the natural roles for DMT in particular.
{"title":"N, N-dimethyltryptamine (DMT) in rodent brain: Concentrations, distribution, and recent pharmacological data","authors":"Steven A. Barker","doi":"10.1016/j.pnpbp.2025.111259","DOIUrl":"10.1016/j.pnpbp.2025.111259","url":null,"abstract":"<div><div>Renewed interest in the clinical use of psychedelic drugs acknowledges their therapeutic effectiveness. It has also provided a changing frame of reference for older psychedelic drug study data, especially regarding concentrations of <em>N</em>, <em>N</em>-dimethyltryptamine (DMT) reported in rodent brains and recent discoveries in DMT receptor interactions in rat brain neurons and select brain areas. The mode of action of DMT in its newly defined role as a neuroplastogen, its effectiveness in treating neuropsychiatric disorders, and its binding to intracellular sigma-1 and 5HT2a receptors may define these possible roles.</div><div>Recent data also show psychedelics promote neuroplasticity via activation of sigma-1 receptors associated with the endoplasmic reticulum and binding to 5-HT2a receptors predominantly related to the intracellular membrane of the Golgi apparatus in cortical neurons and the failure of DMT to occupy cell surface 5-HT2a receptors. While DMT has been proposed as the endogenous ligand for sigma-1, there is no identified ligand for intracellular 5-HT2a receptors, which serotonin cannot acquire. DMT is proposed to be the missing endogenous ligand.</div><div>These data further suggest that DMT may be involved in brain development in rat pups. Brain levels of DMT have also been shown to be elevated by stress in the rat and appear to be under an inducible, adaptive, physiological regulatory system control. With DMT acting as the natural ligand for intracellular 5HT2a receptors in the Golgi, it may also explain the subjective effects observed from the administration of psychedelics in general and define some of the natural roles for DMT in particular.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111259"},"PeriodicalIF":5.3,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016535","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 : 2025-01-19DOI: 10.1016/j.pnpbp.2025.111261
Hannelore Findeis, Maria Strauß
Introduction
Attention-deficit/hyperactivity disorder is a chronic disorder that begins in childhood and often persists into adulthood. There are clinical observations of a cycle-dependent efficacy of psychostimulants in the treatment of ADHD. This relationship appears to be poorly researched.
Methods
A narrative literature review is used to provide an overview of the current state of research and to draw implications for necessary future research.
Results
Two studies examined the influence of psychostimulants on female sex hormones in women with ADHD. Another four studies suggested that ADHD symptoms worsen during the luteal phase of the menstrual cycle. Two studies provided a specific intervention tailored to the menstrual cycle.
Discussion
Women with ADHD remain understudied and are likely to be mistreated. Investigation of the efficacy of psychostimulants in menstruating women with ADHD seems necessary and long overdue.
Conclusion
This highlights the gender health gap in our society and the need for further research to develop an understanding of behavioural and neuroscientific processes in order to adapt treatment strategies for women with ADHD.
{"title":"The effects of psychostimulants in menstruating women with ADHD – A gender health gap in ADHD treatment?","authors":"Hannelore Findeis, Maria Strauß","doi":"10.1016/j.pnpbp.2025.111261","DOIUrl":"10.1016/j.pnpbp.2025.111261","url":null,"abstract":"<div><h3>Introduction</h3><div>Attention-deficit/hyperactivity disorder is a chronic disorder that begins in childhood and often persists into adulthood. There are clinical observations of a cycle-dependent efficacy of psychostimulants in the treatment of ADHD. This relationship appears to be poorly researched.</div></div><div><h3>Methods</h3><div>A narrative literature review is used to provide an overview of the current state of research and to draw implications for necessary future research.</div></div><div><h3>Results</h3><div>Two studies examined the influence of psychostimulants on female sex hormones in women with ADHD. Another four studies suggested that ADHD symptoms worsen during the luteal phase of the menstrual cycle. Two studies provided a specific intervention tailored to the menstrual cycle.</div></div><div><h3>Discussion</h3><div>Women with ADHD remain understudied and are likely to be mistreated. Investigation of the efficacy of psychostimulants in menstruating women with ADHD seems necessary and long overdue.</div></div><div><h3>Conclusion</h3><div>This highlights the gender health gap in our society and the need for further research to develop an understanding of behavioural and neuroscientific processes in order to adapt treatment strategies for women with ADHD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111261"},"PeriodicalIF":5.3,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016532","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 : 2025-01-17DOI: 10.1016/j.pnpbp.2025.111254
Vicente Molina , Inés Fernández-Linsenbarth , Rosa Beño-Ruiz- de- la- Sierra , Emma Osorio-Iriarte , Alejandro Roig , Antonio Arjona , Víctor Rodríguez , Pablo Núñez , Jesús Poza , Alvaro Díez-Revuelta , Claudia Rodríguez-Valbuena , Gema Mijancos-Martínez , Alejandro Bachiller , Miguel Angel Mañanas
Background
Informational integration and differentiation of the cortex can be tested by methods such as the perturbational complexity index (PCI) combined with TMS-induced activity perturbation. The PCI is obtained by stimulating the cortex with TMS and measuring the resulting spatiotemporal cortical responses with high-density EEG.
Methods
We have compared PCI between 26 patients with schizophrenia (15 males), 15 of them First Episode (FE) (7 males), and 22 healthy controls (12 males).
Results
Values of PCI were significantly lower in patients with schizophrenia, as well as in FE considered alone. There was no significant relation between anomalous self-experiences or symptoms and PCI values in the patients: PCI values were unrelated to treatment doses or illness duration.
Conclusions
Our data suggest that spatiotemporal cortical responses to TMS pulses are reduced in patients regarding variability or spatial extension, which could imply a lower capacity for sustaining informational complexity.
{"title":"Lower perturbational complexity index after transcranial magnetic stimulation in schizophrenia patients","authors":"Vicente Molina , Inés Fernández-Linsenbarth , Rosa Beño-Ruiz- de- la- Sierra , Emma Osorio-Iriarte , Alejandro Roig , Antonio Arjona , Víctor Rodríguez , Pablo Núñez , Jesús Poza , Alvaro Díez-Revuelta , Claudia Rodríguez-Valbuena , Gema Mijancos-Martínez , Alejandro Bachiller , Miguel Angel Mañanas","doi":"10.1016/j.pnpbp.2025.111254","DOIUrl":"10.1016/j.pnpbp.2025.111254","url":null,"abstract":"<div><h3>Background</h3><div>Informational integration and differentiation of the cortex can be tested by methods such as the perturbational complexity index (PCI) combined with TMS-induced activity perturbation. The PCI is obtained by stimulating the cortex with TMS and measuring the resulting spatiotemporal cortical responses with high-density EEG.</div></div><div><h3>Methods</h3><div>We have compared PCI between 26 patients with schizophrenia (15 males), 15 of them First Episode (FE) (7 males), and 22 healthy controls (12 males).</div></div><div><h3>Results</h3><div>Values of PCI were significantly lower in patients with schizophrenia, as well as in FE considered alone. There was no significant relation between anomalous self-experiences or symptoms and PCI values in the patients: PCI values were unrelated to treatment doses or illness duration.</div></div><div><h3>Conclusions</h3><div>Our data suggest that spatiotemporal cortical responses to TMS pulses are reduced in patients regarding variability or spatial extension, which could imply a lower capacity for sustaining informational complexity.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111254"},"PeriodicalIF":5.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016527","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 : 2025-01-17DOI: 10.1016/j.pnpbp.2025.111256
Huiqin Liu , Shuhua Chen , Hong Xiang , Jie Xiao , Shaoli Zhao , Xiao Zhang , Zhihao Shu , Jing Zhang , Jie Ouyang , Quanjun Liu , Qisheng Quan , Jianing Fan , Peng Gao , Xinru Zheng , Alex F. Chen , Hongwei Lu
The study investigates how Sphingosine-1-phosphate receptor 3 (S1PR3) and the Chronic Unpredictable Mild Stress (CUMS) affects depression-like behaviors. The S1P/S1PR3 signaling pathway is known to play a role in mood regulation, but it is not yet fully understood how it is connected to depression. This study looks to further explore this topic. To investigate the effect of CUMS on S1PR3 expression in hippocampus neurons and the synaptic plasticity, we observed animals' behavior with Sucrose Preference Test (SPT), Forced Swim Test (FST) and Open Field Test (OFT). Combining molecular and histological analysis, we investigated the S1PR3 expression, the change in synapse density, and synaptic structure change in the hippocampus. The CUMS caused a significant decrease in the S1PR3 expression, the density of the synaptic spine and synaptic ultrastructure change in mice. On the other hand, over-expression of S1PR3 by adeno-associated virus (AAV) in hippocampal neurons alleviated the depressive-like behaviors and synaptic deficits observed in stress-susceptible animals. Furthermore, the depressive-like phenotype and synaptic impairments were normalized by the expression of RhoA, implicating the RhoA/ROCK1 pathway in S1PR3 actions. Collectively, our findings provide strong evidence that S1PR3 plays a key role in hippocampal synaptic plasticity and depression and that modulation of S1PR3/RhoA/ROCK1 signaling may offer a novel therapeutic strategy for MDD. This study not only underscores the therapeutic potential of S1PR3 but also provides novel insights into the molecular mechanisms underlying depression.
{"title":"S1PR3 in hippocampal neurons improves synaptic plasticity and decreases depressive behavior via downregulation of RhoA/ROCK1","authors":"Huiqin Liu , Shuhua Chen , Hong Xiang , Jie Xiao , Shaoli Zhao , Xiao Zhang , Zhihao Shu , Jing Zhang , Jie Ouyang , Quanjun Liu , Qisheng Quan , Jianing Fan , Peng Gao , Xinru Zheng , Alex F. Chen , Hongwei Lu","doi":"10.1016/j.pnpbp.2025.111256","DOIUrl":"10.1016/j.pnpbp.2025.111256","url":null,"abstract":"<div><div>The study investigates how Sphingosine-1-phosphate receptor 3 (S1PR3) and the Chronic Unpredictable Mild Stress (CUMS) affects depression-like behaviors. The S1P/S1PR3 signaling pathway is known to play a role in mood regulation, but it is not yet fully understood how it is connected to depression. This study looks to further explore this topic. To investigate the effect of CUMS on S1PR3 expression in hippocampus neurons and the synaptic plasticity, we observed animals' behavior with Sucrose Preference Test (SPT), Forced Swim Test (FST) and Open Field Test (OFT). Combining molecular and histological analysis, we investigated the S1PR3 expression, the change in synapse density, and synaptic structure change in the hippocampus. The CUMS caused a significant decrease in the S1PR3 expression, the density of the synaptic spine and synaptic ultrastructure change in mice. On the other hand, over-expression of S1PR3 by adeno-associated virus (AAV) in hippocampal neurons alleviated the depressive-like behaviors and synaptic deficits observed in stress-susceptible animals. Furthermore, the depressive-like phenotype and synaptic impairments were normalized by the expression of RhoA, implicating the RhoA/ROCK1 pathway in S1PR3 actions. Collectively, our findings provide strong evidence that S1PR3 plays a key role in hippocampal synaptic plasticity and depression and that modulation of S1PR3/RhoA/ROCK1 signaling may offer a novel therapeutic strategy for MDD. This study not only underscores the therapeutic potential of S1PR3 but also provides novel insights into the molecular mechanisms underlying depression.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111256"},"PeriodicalIF":5.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016529","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 : 2025-01-16DOI: 10.1016/j.pnpbp.2025.111257
Ping Tu , Xirongguli Halili , Siyi Zhang , Jing Yang , Yongbei Xiao
Background
Hyperbaric oxygen therapy (HBOT) is considered a potential treatment for autism spectrum disorders, aiming to improve the underlying pathophysiological mechanisms. It has been studied in several clinical trials, but the effectiveness is still controversial.
Purpose
This systematic review aimed to systematically evaluate the effectiveness of hyperbaric oxygen therapy in the treatment of autism in children and adolescents.
Methods
We systematically searched seven databases (PubMed, Embase, Cochrane Libraries, Web of Science, CNKI, Wanfang, and SinoMed) up to March 20, 2024, as well as references lists. The included studies evaluated the effect of HBOT on improving the core symptoms of autism and other specific symptoms (e.g., communication, sociability, cognitive awareness, behavior), including RCTs and quasiexperimental studies. The Cochrane Collaboration's Risk of Bias Assessment Tool for Randomized Trials (RoB2.0) and the JBI Risk of Bias Tool for Quasi-Experimental Studies were used as quality assessment tools. A random effects model was used to conduct a meta-analysis of the core and specific symptoms of autism. Sensitivity analyses and meta-regression were performed to identify sources of heterogeneity and assess result robustness. A Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence certainty analysis was performed for outcomes. This systematic review is registered with PROSPERO (CRD42024527220).
Results
A total of 17 studies with 890 patients were ultimately included in the metaanalysis. The meta-analysis revealed moderately large, significant effects of hyperbaric oxygen therapy, reducing core symptoms of autism [SMD = −0.66, 95 % CI (−1.04, −0.28), P = 0.0006], and improving three aspects of daily performances (communication [SMD = −0.88, 95 % CI (−1.71,-0.04), P = 0.04], cognitive awareness [SMD = −0.93, 95 % CI (−1.51, −0.35), P = 0.002], and behavior [SMD = −0.80, 95 % CI (− 1.46, −0.13), P = 0.02] in children and adolescents with autism. This systematic review and meta-analysis have limitations such as poor quality and high heterogeneity of the included study.
Conclusion
These findings underscore the potential benefits of hyperbaric oxygen therapy in managing autism-related symptoms and improving daily functioning in affected children and adolescents. Future rigorously designed, high-quality studies are required to confirm the efficacy of hyperbaric oxygen therapy and establish standard treatment protocols.
背景：高压氧治疗（HBOT）被认为是一种潜在的治疗自闭症谱系障碍的方法，旨在改善其潜在的病理生理机制。它已经在几个临床试验中进行了研究，但其有效性仍然存在争议。目的：本系统综述旨在系统评价高压氧治疗儿童和青少年自闭症的有效性。方法：系统检索截止到2024年3月20日的PubMed、Embase、Cochrane Libraries、Web of Science、CNKI、万方、SinoMed等7个数据库及文献列表。纳入的研究评估了HBOT对改善自闭症核心症状和其他特定症状（如沟通、社交、认知意识、行为）的效果，包括随机对照试验和准实验研究。采用Cochrane协作组织的随机试验偏倚风险评估工具（RoB2.0）和JBI准实验研究偏倚风险评估工具作为质量评估工具。采用随机效应模型对自闭症的核心症状和特殊症状进行meta分析。进行敏感性分析和meta回归以确定异质性来源并评估结果的稳健性。对结果进行建议评估、发展和评价分级（GRADE）证据确定性分析。本系统评价已在普洛斯彼罗注册（CRD42024527220）。结果：共有17项研究，890名患者最终被纳入荟萃分析。荟萃分析显示中等大,高压氧治疗的重要影响,减少核心孤独症的症状(SMD = -0.66,95 % CI (-1.04, -0.28), P = 0.0006],和改善日常表现的三个方面(通信(SMD = -0.88,95 % CI (-1.71, -0.04), P = 0.04],认知意识(SMD = -0.93,95 % CI (-1.51, -0.35), P = 0.002],和行为(SMD = -0.80,95 % CI (- 1.46, -0.13), P = 0.02]在自闭症儿童和青少年。本系统综述和荟萃分析存在纳入研究的质量差、异质性高等局限性。结论：这些发现强调了高压氧治疗在控制自闭症相关症状和改善受影响儿童和青少年日常功能方面的潜在益处。未来需要严格设计、高质量的研究来证实高压氧治疗的疗效，并建立标准的治疗方案。
{"title":"The effectiveness of hyperbaric oxygen therapy in children and adolescents and with autism spectrum disorders: A systematic review and meta-analysis","authors":"Ping Tu , Xirongguli Halili , Siyi Zhang , Jing Yang , Yongbei Xiao","doi":"10.1016/j.pnpbp.2025.111257","DOIUrl":"10.1016/j.pnpbp.2025.111257","url":null,"abstract":"<div><h3>Background</h3><div>Hyperbaric oxygen therapy (HBOT) is considered a potential treatment for autism spectrum disorders, aiming to improve the underlying pathophysiological mechanisms. It has been studied in several clinical trials, but the effectiveness is still controversial.</div></div><div><h3>Purpose</h3><div>This systematic review aimed to systematically evaluate the effectiveness of hyperbaric oxygen therapy in the treatment of autism in children and adolescents.</div></div><div><h3>Methods</h3><div>We systematically searched seven databases (PubMed, Embase, Cochrane Libraries, Web of Science, CNKI, Wanfang, and SinoMed) up to March 20, 2024, as well as references lists. The included studies evaluated the effect of HBOT on improving the core symptoms of autism and other specific symptoms (e.g., communication, sociability, cognitive awareness, behavior), including RCTs and quasiexperimental studies. The Cochrane Collaboration's Risk of Bias Assessment Tool for Randomized Trials (RoB2.0) and the JBI Risk of Bias Tool for Quasi-Experimental Studies were used as quality assessment tools. A random effects model was used to conduct a meta-analysis of the core and specific symptoms of autism. Sensitivity analyses and meta-regression were performed to identify sources of heterogeneity and assess result robustness. A Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence certainty analysis was performed for outcomes. This systematic review is registered with PROSPERO (CRD42024527220).</div></div><div><h3>Results</h3><div>A total of 17 studies with 890 patients were ultimately included in the metaanalysis. The meta-analysis revealed moderately large, significant effects of hyperbaric oxygen therapy, reducing core symptoms of autism [SMD = −0.66, 95 % CI (−1.04, −0.28), <em>P</em> = 0.0006], and improving three aspects of daily performances (communication [SMD = −0.88, 95 % CI (−1.71,-0.04), <em>P</em> = 0.04], cognitive awareness [SMD = −0.93, 95 % CI (−1.51, −0.35), <em>P</em> = 0.002], and behavior [SMD = −0.80, 95 % CI (− 1.46, −0.13), <em>P</em> = 0.02] in children and adolescents with autism. This systematic review and meta-analysis have limitations such as poor quality and high heterogeneity of the included study.</div></div><div><h3>Conclusion</h3><div>These findings underscore the potential benefits of hyperbaric oxygen therapy in managing autism-related symptoms and improving daily functioning in affected children and adolescents. Future rigorously designed, high-quality studies are required to confirm the efficacy of hyperbaric oxygen therapy and establish standard treatment protocols.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111257"},"PeriodicalIF":5.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016531","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 : 2025-01-10Epub Date: 2025-01-07DOI: 10.1016/j.pnpbp.2025.111251
Juliana Lima Constantino, Jens H van Dalfsen, Sara Massetti, Jeanine Kamphuis, Robert A Schoevers
Psilocybin represents a novel therapeutic approach for individuals with major depressive disorder (MDD) who do not respond to conventional antidepressant treatment. Investigating the influence of psilocybin on the pathophysiological processes involved in MDD could enhance our neurobiological understanding of the presumed antidepressant action mechanism. This systematic review aims to summarize the results of human studies investigating changes in blood-based biomarkers of MDD to guide future research on potentially relevant analytes that could be monitored in clinical trials. A systematic search was performed in MEDLINE, Embase, and Web of Science to retrieve studies investigating changes in serum and plasma levels of neurotrophic, immunologic, neuroendocrine, and metabolic markers. Nine studies were included, describing findings on 15 biomarkers, exclusively in healthy participants. Studies consistently reported a decrease in interleukin-6, C-reactive protein, and eosinophils, and an increase in cortisol, prolactin, oxytocin, thyroid-stimulating hormone, adrenocorticotropic hormone, brain-derived neurotrophic factor, and free fatty acids following psilocybin administration. Less consistent effects were observed on interleukin-1β, interleukin-8, tumour necrosis factor-alpha, soluble urokinase plasminogen activator receptor, and growth hormone. The results are in line with preclinical studies and provide initial support from human studies that psilocybin potentially leads to beneficial effects on biomarkers of MDD. However, given the limited number of studies, findings should be approached with caution prior to replication. Further research should include larger samples, clinical populations, longer-term assessment, rigorous experimental designs, and account for the potential confounding of psychological stress related to the psychedelic experience.
裸盖菇素为传统抗抑郁药物治疗无效的重度抑郁症（MDD）患者提供了一种新的治疗方法。研究裸盖菇素对重度抑郁症病理生理过程的影响可以增强我们对假定的抗抑郁作用机制的神经生物学理解。本系统综述旨在总结研究MDD血液生物标志物变化的人类研究结果，以指导未来可能在临床试验中监测的相关分析物的研究。在MEDLINE、Embase和Web of Science中进行了系统的检索，以检索有关血清和血浆中神经营养、免疫、神经内分泌和代谢标志物水平变化的研究。纳入了9项研究，描述了15种生物标志物的发现，仅针对健康参与者。研究一致报告说，服用裸盖菇素后，白细胞介素-6、c反应蛋白和嗜酸性粒细胞减少，皮质醇、催乳素、催产素、促甲状腺激素、促肾上腺皮质激素、脑源性神经营养因子和游离脂肪酸增加。对白细胞介素-1β、白细胞介素-8、肿瘤坏死因子- α、可溶性尿激酶纤溶酶原激活物受体和生长激素的影响不一致。该结果与临床前研究一致，并提供了人类研究的初步支持，即裸盖菇素可能对重度抑郁症的生物标志物产生有益影响。然而，鉴于研究数量有限，在重复之前应谨慎对待研究结果。进一步的研究应该包括更大的样本、临床人群、更长期的评估、严格的实验设计，并考虑与迷幻体验相关的心理压力的潜在混淆。
{"title":"Neurobiological mechanisms of antidepressant properties of psilocybin: A systematic review of blood biomarkers.","authors":"Juliana Lima Constantino, Jens H van Dalfsen, Sara Massetti, Jeanine Kamphuis, Robert A Schoevers","doi":"10.1016/j.pnpbp.2025.111251","DOIUrl":"10.1016/j.pnpbp.2025.111251","url":null,"abstract":"<p><p>Psilocybin represents a novel therapeutic approach for individuals with major depressive disorder (MDD) who do not respond to conventional antidepressant treatment. Investigating the influence of psilocybin on the pathophysiological processes involved in MDD could enhance our neurobiological understanding of the presumed antidepressant action mechanism. This systematic review aims to summarize the results of human studies investigating changes in blood-based biomarkers of MDD to guide future research on potentially relevant analytes that could be monitored in clinical trials. A systematic search was performed in MEDLINE, Embase, and Web of Science to retrieve studies investigating changes in serum and plasma levels of neurotrophic, immunologic, neuroendocrine, and metabolic markers. Nine studies were included, describing findings on 15 biomarkers, exclusively in healthy participants. Studies consistently reported a decrease in interleukin-6, C-reactive protein, and eosinophils, and an increase in cortisol, prolactin, oxytocin, thyroid-stimulating hormone, adrenocorticotropic hormone, brain-derived neurotrophic factor, and free fatty acids following psilocybin administration. Less consistent effects were observed on interleukin-1β, interleukin-8, tumour necrosis factor-alpha, soluble urokinase plasminogen activator receptor, and growth hormone. The results are in line with preclinical studies and provide initial support from human studies that psilocybin potentially leads to beneficial effects on biomarkers of MDD. However, given the limited number of studies, findings should be approached with caution prior to replication. Further research should include larger samples, clinical populations, longer-term assessment, rigorous experimental designs, and account for the potential confounding of psychological stress related to the psychedelic experience.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111251"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958996","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 : 2025-01-10DOI: 10.1016/j.pnpbp.2024.111201
Dylan Chou , Hsien-Yu Peng , Tzer-Bin Lin , Ming-Chun Hsieh , Cheng-Yuan Lai , Chau-Shoun Lee
Methylone (3,4-methylenedioxy-N-methylcathinone) is a rapid-acting entactogen that has demonstrated significant benefits for patients with post-traumatic stress disorder (PTSD) and exhibits good tolerability in phase 1 clinical trials. Despite these promising results, its preclinical effects on fear memory regulation and the underlying mechanisms remain largely unexplored. This study aims to investigate the impact of methylone on auditory fear extinction and its influence on neuronal and synaptic activity in the basolateral amygdala (BLA). Using C57BL/6 mice, we employed an auditory fear conditioning paradigm along with immunofluorescent staining, extracellular electrophysiological recording, and chemogenetic techniques. The results revealed that administering methylone at a dosage of 10 mg/kg, in conjunction with extinction trials, significantly decreased the retrieval of both recent and remote fear memories. Additionally, methylone effectively inhibited the renewal of remote fear memories and blocked spontaneous recovery. It also reduced fear generalization to both context and tone. At the cellular level, methylone increased c-fos expression in the BLA and induced sustained elevations in long-term potentiation and long-term depression at the synaptic level. Furthermore, intra-BLA microinfusion of methylone directly enhanced the extinction memory. Chemogenetic activation of the BLA mimicked the effects of methylone, whereas chemogenetic inhibition blocked them. These findings suggest that methylone modulates fear memories through its action on the BLA. This preclinical study offers a knowledge base and critical insights into the potential future application of methylone for PTSD treatment.
美托酮（3,4-亚甲二氧基-N-甲基卡西酮）是一种速效诱导剂，对创伤后应激障碍（PTSD）患者有显著疗效，在一期临床试验中表现出良好的耐受性。尽管取得了这些令人鼓舞的成果，但它对恐惧记忆调节的临床前效应及其内在机制在很大程度上仍未得到探索。本研究旨在探讨甲酮对听觉恐惧消退的影响及其对杏仁基底外侧（BLA）神经元和突触活动的影响。我们以 C57BL/6 小鼠为研究对象，采用了听觉恐惧条件反射范式、免疫荧光染色、细胞外电生理记录和化学遗传学技术。结果表明，在进行消减试验的同时给小鼠注射 10 毫克/千克剂量的甲酮，可显著减少小鼠对近期和远期恐惧记忆的检索。此外，甲酮还能有效抑制远期恐惧记忆的更新并阻止自发恢复。它还减少了对环境和音调的恐惧泛化。在细胞水平上，甲酮增加了 BLA 中 c-fos 的表达，并在突触水平上诱导长期电位和长期抑制的持续升高。此外，在BLA内微量注入甲酮可直接增强消退记忆。BLA的化学基因激活模拟了甲酮的作用，而化学基因抑制则阻断了这种作用。这些研究结果表明，甲酮通过其对BLA的作用来调节恐惧记忆。这项临床前研究为未来可能应用甲酮治疗创伤后应激障碍提供了知识基础和重要见解。
{"title":"Methylone regulates fear memory and amygdala activity: A potential treatment for posttraumatic stress disorder?","authors":"Dylan Chou , Hsien-Yu Peng , Tzer-Bin Lin , Ming-Chun Hsieh , Cheng-Yuan Lai , Chau-Shoun Lee","doi":"10.1016/j.pnpbp.2024.111201","DOIUrl":"10.1016/j.pnpbp.2024.111201","url":null,"abstract":"<div><div>Methylone (3,4-methylenedioxy-<em>N</em>-methylcathinone) is a rapid-acting entactogen that has demonstrated significant benefits for patients with post-traumatic stress disorder (PTSD) and exhibits good tolerability in phase 1 clinical trials. Despite these promising results, its preclinical effects on fear memory regulation and the underlying mechanisms remain largely unexplored. This study aims to investigate the impact of methylone on auditory fear extinction and its influence on neuronal and synaptic activity in the basolateral amygdala (BLA). Using C57BL/6 mice, we employed an auditory fear conditioning paradigm along with immunofluorescent staining, extracellular electrophysiological recording, and chemogenetic techniques. The results revealed that administering methylone at a dosage of 10 mg/kg, in conjunction with extinction trials, significantly decreased the retrieval of both recent and remote fear memories. Additionally, methylone effectively inhibited the renewal of remote fear memories and blocked spontaneous recovery. It also reduced fear generalization to both context and tone. At the cellular level, methylone increased c-fos expression in the BLA and induced sustained elevations in long-term potentiation and long-term depression at the synaptic level. Furthermore, intra-BLA microinfusion of methylone directly enhanced the extinction memory. Chemogenetic activation of the BLA mimicked the effects of methylone, whereas chemogenetic inhibition blocked them. These findings suggest that methylone modulates fear memories through its action on the BLA. This preclinical study offers a knowledge base and critical insights into the potential future application of methylone for PTSD treatment.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111201"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711829","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 : 2025-01-10DOI: 10.1016/j.pnpbp.2024.111226
Yang-An Li , Juan Yao , Xuan Li , Ke-Hui Hu
The parabrachial nucleus (PBN) is responsible for integrating both internal and external sensory information and controlling/regulating a wide range of physiological processes, such as feeding, thermogenesis, nociceptive and pruritic sensations, and respiration. Recently, the PBN has been found to be involved in mediating wakefulness maintenance, sleep-wake transition, exogenous neuromodulation of awakening, and arousal-promoting process triggered by drastic changes in the internal environments, such as hypercapnia, hypoxia, and hypertension. Multiple neural pathways and subpopulations of neurons are responsible for arousal-promoting effects of the PBN. The medial PBN seems to be more important for the maintenance of physiological arousal, while the lateral PBN are more crucial in mediating interoception-driven arousal. Glutamatergic projection from the PBN to the basal forebrain (BF) and GABAergic projection from the BF to the cerebral cortex GABAergic neurons are the most pivotal neural pathways for awareness-promotion. Here, we review the relevant literature in this field in recent years and emphasize the potential prospects of PBN stimulation in translational medicine for the rehabilitation of disorders of consciousness.
{"title":"Arousal-promoting effect of the parabrachial nucleus and the underlying mechanisms: Recent advances","authors":"Yang-An Li , Juan Yao , Xuan Li , Ke-Hui Hu","doi":"10.1016/j.pnpbp.2024.111226","DOIUrl":"10.1016/j.pnpbp.2024.111226","url":null,"abstract":"<div><div>The parabrachial nucleus (PBN) is responsible for integrating both internal and external sensory information and controlling/regulating a wide range of physiological processes, such as feeding, thermogenesis, nociceptive and pruritic sensations, and respiration. Recently, the PBN has been found to be involved in mediating wakefulness maintenance, sleep-wake transition, exogenous neuromodulation of awakening, and arousal-promoting process triggered by drastic changes in the internal environments, such as hypercapnia, hypoxia, and hypertension. Multiple neural pathways and subpopulations of neurons are responsible for arousal-promoting effects of the PBN. The medial PBN seems to be more important for the maintenance of physiological arousal, while the lateral PBN are more crucial in mediating interoception-driven arousal. Glutamatergic projection from the PBN to the basal forebrain (BF) and GABAergic projection from the BF to the cerebral cortex GABAergic neurons are the most pivotal neural pathways for awareness-promotion. Here, we review the relevant literature in this field in recent years and emphasize the potential prospects of PBN stimulation in translational medicine for the rehabilitation of disorders of consciousness.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111226"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878503","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 : 2025-01-10DOI: 10.1016/j.pnpbp.2024.111232
Shin-Chang Kuo , Chun-Long Lin , Yi-Wei Yeh , Chun-Yen Chen , Yu-Chieh Huang , Ting-Yu Chang , You-Ping Yang , Jhih-Syuan Huang , Bao-Zhu Yang , San-Yuan Huang
Objective
Alcohol use disorder (AUD) is a complex neuropsychiatric condition influenced by genetic and environmental factors. Nerve growth factor (NGF) plays a crucial role in neuronal neuroplasticity and chronic alcohol consumption may alter NGF levels in specific brain regions. The study investigates the associations between NGF gene polymorphisms, susceptibility to AUD, and specific stress and personality characteristics.
Methods
Our study involved 1133 participants from a homogeneous Han Chinese population, 587 of whom had AUD and 546 were controls. To minimize potential confounding factors, the AUD group was stratified by sex and age at baseline. A total of 414 participants completed the Life Event Questionnaires (LEQ), while 559 participants completed the Tridimensional Personality Questionnaire (TPQ).
Results
The NGF's rs7523654 and rs11102929 loci were significantly associated with AUD, especially in female subgroups. Additional haplotype research confirmed similar findings. AUD patients showed more vital propensities for novelty seeking (NS) and harm avoidance (HA) compared to controls. Additionally, they recorded higher negative LEQ results. Notably, HA and negative LEQ scores among AUD people were significantly affected by the SNP rs11102929 in the NGF gene. The age at which AUD first manifested and NS scores showed a reverse link, suggesting that a higher NS characteristic may predispose people to develop AUD earlier in life.
Conclusion
The findings suggest that the NGF gene may influence AUD susceptibility and its links to personality traits and life stress. However, the small sample of women with AUD limits the reliability of these associations, highlighting the need for further study.
{"title":"The role of personality traits and life stress in alcohol use disorder: Insights from NGF gene polymorphisms of Han Chinese population in Taiwan","authors":"Shin-Chang Kuo , Chun-Long Lin , Yi-Wei Yeh , Chun-Yen Chen , Yu-Chieh Huang , Ting-Yu Chang , You-Ping Yang , Jhih-Syuan Huang , Bao-Zhu Yang , San-Yuan Huang","doi":"10.1016/j.pnpbp.2024.111232","DOIUrl":"10.1016/j.pnpbp.2024.111232","url":null,"abstract":"<div><h3>Objective</h3><div>Alcohol use disorder (AUD) is a complex neuropsychiatric condition influenced by genetic and environmental factors. Nerve growth factor (NGF) plays a crucial role in neuronal neuroplasticity and chronic alcohol consumption may alter NGF levels in specific brain regions. The study investigates the associations between <em>NGF</em> gene polymorphisms, susceptibility to AUD, and specific stress and personality characteristics.</div></div><div><h3>Methods</h3><div>Our study involved 1133 participants from a homogeneous Han Chinese population, 587 of whom had AUD and 546 were controls. To minimize potential confounding factors, the AUD group was stratified by sex and age at baseline. A total of 414 participants completed the Life Event Questionnaires (LEQ), while 559 participants completed the Tridimensional Personality Questionnaire (TPQ).</div></div><div><h3>Results</h3><div>The <em>NGF</em>'s rs7523654 and rs11102929 loci were significantly associated with AUD, especially in female subgroups. Additional haplotype research confirmed similar findings. AUD patients showed more vital propensities for novelty seeking (NS) and harm avoidance (HA) compared to controls. Additionally, they recorded higher negative LEQ results. Notably, HA and negative LEQ scores among AUD people were significantly affected by the SNP rs11102929 in the <em>NGF</em> gene. The age at which AUD first manifested and NS scores showed a reverse link, suggesting that a higher NS characteristic may predispose people to develop AUD earlier in life.</div></div><div><h3>Conclusion</h3><div>The findings suggest that the <em>NGF</em> gene may influence AUD susceptibility and its links to personality traits and life stress. However, the small sample of women with AUD limits the reliability of these associations, highlighting the need for further study.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111232"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886476","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}
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