Pub Date : 2025-01-10DOI: 10.1016/j.pnpbp.2024.111215
MeShell Green , Charles A. Veltri , Walter C. Prozialeck , Oliver Grundmann
Kratom (Mitragyna speciosa, Korth.) is a tropical tree that is indigenous to Southeast Asia. When ingested, kratom leaves or decoctions from the leaves have been reported to produce complex stimulant and opioid-like effects. For generations native populations in Southeast Asia have used kratom products to stave off fatigue, improve mood, alleviate pain and manage symptoms of opioid withdrawal. Over the past 15–20 years, kratom use has spread to Western nations including the United States, where many individuals are using kratom products for the self-management of pain, opioid use disorder, anxiety and depression. The increased use of kratom has triggered a surge in research into the biochemistry, pharmacology and behavioral effects of kratom and its active constituents, especially mitragynine and 7-hydroxymitragynine. In this review, we highlight some of the recent animal studies showing that kratom and its constituent compounds have potential beneficial effects in animal models of pain, anxiety, depression and opioid dependence. We also highlight studies showing that kratom can modulate the functioning of opioid, noradrenergic, serotonergic and dopaminergic systems. The highlighted studies strongly suggest that kratom and its constituents may form the basis for the development of novel therapeutic agents.
Kratom （Mitragyna speciosa, north .）是一种原产于东南亚的热带树木。据报道，当摄入时，苦参叶或苦参叶的煎剂会产生复杂的兴奋剂和阿片样物质。几代人以来，东南亚的土著居民一直使用kratom产品来缓解疲劳、改善情绪、缓解疼痛和控制阿片类药物戒断症状。在过去的15-20 年里，kratom的使用已经蔓延到包括美国在内的西方国家，在那里，许多人使用kratom产品来自我管理疼痛、阿片类药物使用障碍、焦虑和抑郁。kratom使用量的增加引发了对kratom及其活性成分的生物化学、药理学和行为影响的研究激增，特别是米特拉金和7-羟基米特拉金。在这篇综述中，我们重点介绍了最近的一些动物研究，这些研究表明克拉通及其成分化合物对疼痛、焦虑、抑郁和阿片类药物依赖的动物模型有潜在的有益作用。我们还强调研究表明，克拉通可以调节阿片，去甲肾上腺素能，血清素能和多巴胺能系统的功能。突出的研究强烈表明，克拉托姆及其成分可能成为开发新型治疗剂的基础。
{"title":"The neuropharmacology of kratom, a novel psychoactive natural product","authors":"MeShell Green , Charles A. Veltri , Walter C. Prozialeck , Oliver Grundmann","doi":"10.1016/j.pnpbp.2024.111215","DOIUrl":"10.1016/j.pnpbp.2024.111215","url":null,"abstract":"<div><div>Kratom (<em>Mitragyna speciosa,</em> Korth.) is a tropical tree that is indigenous to Southeast Asia. When ingested, kratom leaves or decoctions from the leaves have been reported to produce complex stimulant and opioid-like effects. For generations native populations in Southeast Asia have used kratom products to stave off fatigue, improve mood, alleviate pain and manage symptoms of opioid withdrawal. Over the past 15–20 years, kratom use has spread to Western nations including the United States, where many individuals are using kratom products for the self-management of pain, opioid use disorder, anxiety and depression. The increased use of kratom has triggered a surge in research into the biochemistry, pharmacology and behavioral effects of kratom and its active constituents, especially mitragynine and 7-hydroxymitragynine. In this review, we highlight some of the recent animal studies showing that kratom and its constituent compounds have potential beneficial effects in animal models of pain, anxiety, depression and opioid dependence. We also highlight studies showing that kratom can modulate the functioning of opioid, noradrenergic, serotonergic and dopaminergic systems. The highlighted studies strongly suggest that kratom and its constituents may form the basis for the development of novel therapeutic agents.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111215"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815052","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.2024.111220
Yuting Yang , Qi Lan , Wenting Liang , Mingzhu Zhou , Wenping Zhao , Pingyuan Gong
Backgrounds
The influence of serotonin function on social phobia has been well-documented, yet the polygenic risk score of serotonergic polymorphisms for social phobia remains unclear.
Methods
We assessed two aspects of social phobia (i.e., social interaction anxiety and social phobia scrutiny fear) and created a polygenic risk score of seven serotonergic polymorphisms in two independent samples.
Results
The results from both samples indicated that a greater polygenic risk score, denoting a higher risk of anxiety, was associated with higher levels of social interaction anxiety and social phobia scrutinizing fear. Interestingly, the association between polygenic risk score and social interaction anxiety was mediated by interpersonal adaptability.
Conclusion
These findings demonstrate the importance of serotonergic polymorphisms in social phobia and unveil a psychological pathway whereby interpersonal adaptability mediates the effect of serotonergic polymorphisms on social phobia.
{"title":"A two-sample study on the relationship between polygenic risk score of serotonergic polymorphisms and social phobia: Interpersonal adaptability as a mediator","authors":"Yuting Yang , Qi Lan , Wenting Liang , Mingzhu Zhou , Wenping Zhao , Pingyuan Gong","doi":"10.1016/j.pnpbp.2024.111220","DOIUrl":"10.1016/j.pnpbp.2024.111220","url":null,"abstract":"<div><h3>Backgrounds</h3><div>The influence of serotonin function on social phobia has been well-documented, yet the polygenic risk score of serotonergic polymorphisms for social phobia remains unclear.</div></div><div><h3>Methods</h3><div>We assessed two aspects of social phobia (i.e., social interaction anxiety and social phobia scrutiny fear) and created a polygenic risk score of seven serotonergic polymorphisms in two independent samples.</div></div><div><h3>Results</h3><div>The results from both samples indicated that a greater polygenic risk score, denoting a higher risk of anxiety, was associated with higher levels of social interaction anxiety and social phobia scrutinizing fear. Interestingly, the association between polygenic risk score and social interaction anxiety was mediated by interpersonal adaptability.</div></div><div><h3>Conclusion</h3><div>These findings demonstrate the importance of serotonergic polymorphisms in social phobia and unveil a psychological pathway whereby interpersonal adaptability mediates the effect of serotonergic polymorphisms on social phobia.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111220"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840104","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.2024.111222
Olivia O.F. Williams , Madeleine Coppolino , Cecilia B. Micelli , Ryan T. McCallum , Paula T. Henry-Duru , Joshua D. Manduca , Jasmin Lalonde , Melissa L. Perreault
There are substantial differences in the characteristics of males and females with an autism spectrum disorder (ASD), yet there is little knowledge surrounding the mechanistic underpinnings of these differences. The valproic acid (VPA) rodent model is based upon the human fetal valproate spectrum disorder, which is associated with increased risk of developing ASD. This model, which displays significant social, learning, and memory alterations, has therefore been widely used to further our understanding of specific biological features of ASD. However, to date, almost all of the studies employing this model have used male rodents. To fill this knowledge gap, we evaluated sex differences for neuronal activity, morphology, and glycogen synthase kinase-3 (GSK-3) signaling in primary cortical (CTX) and hippocampal (HIP) neurons prepared from rats exposed to VPA in utero. In vivo, sex-specific VPA-induced alterations in the frontal CTX transcriptome at birth were also determined. Overall, VPA induced more robust changes in neuronal function and structure in the CTX than in the HIP. Male- and female-derived primary CTX neurons from rats exposed to prenatal VPA had elevated activity and showed more disorganized firing. In the HIP, only the female VPA neurons showed elevated firing, while the male VPA neurons exhibited disorganized activity. Dendritic arborization of CTX neurons from VPA rats was less complex in both sexes, though this was more pronounced in the females. Conversely, both female and male HIP neurons from VPA rats showed elevated complexity distal to the soma. Female VPA CTX neurons also had an elevated number of dendritic spines. The relative activity of the α and β isoforms of GSK-3 were suppressed in both female and male VPA CTX neurons, with no changes in the HIP neurons. On postnatal day 0, alterations in CTX genes associated with neuropeptides (e.g., penk, pdyn) and receptors (e.g., drd1, adora2a) were seen in both sexes, though they were downregulated in females and upregulated in males. Together these findings suggest that substantial sex differences in neuronal structure and function in the VPA model may have relevance to the reported sex differences in idiopathic ASD.
{"title":"Prenatal exposure to valproic acid induces sex-specific alterations in rat cortical and hippocampal neuronal structure and function in vitro","authors":"Olivia O.F. Williams , Madeleine Coppolino , Cecilia B. Micelli , Ryan T. McCallum , Paula T. Henry-Duru , Joshua D. Manduca , Jasmin Lalonde , Melissa L. Perreault","doi":"10.1016/j.pnpbp.2024.111222","DOIUrl":"10.1016/j.pnpbp.2024.111222","url":null,"abstract":"<div><div>There are substantial differences in the characteristics of males and females with an autism spectrum disorder (ASD), yet there is little knowledge surrounding the mechanistic underpinnings of these differences. The valproic acid (VPA) rodent model is based upon the human fetal valproate spectrum disorder, which is associated with increased risk of developing ASD. This model, which displays significant social, learning, and memory alterations, has therefore been widely used to further our understanding of specific biological features of ASD. However, to date, almost all of the studies employing this model have used male rodents. To fill this knowledge gap, we evaluated sex differences for neuronal activity, morphology, and glycogen synthase kinase-3 (GSK-3) signaling in primary cortical (CTX) and hippocampal (HIP) neurons prepared from rats exposed to VPA <em>in utero</em>. <em>In vivo</em>, sex-specific VPA-induced alterations in the frontal CTX transcriptome at birth were also determined. Overall, VPA induced more robust changes in neuronal function and structure in the CTX than in the HIP. Male- and female-derived primary CTX neurons from rats exposed to prenatal VPA had elevated activity and showed more disorganized firing. In the HIP, only the female VPA neurons showed elevated firing, while the male VPA neurons exhibited disorganized activity. Dendritic arborization of CTX neurons from VPA rats was less complex in both sexes, though this was more pronounced in the females. Conversely, both female and male HIP neurons from VPA rats showed elevated complexity distal to the soma. Female VPA CTX neurons also had an elevated number of dendritic spines. The relative activity of the α and β isoforms of GSK-3 were suppressed in both female and male VPA CTX neurons, with no changes in the HIP neurons. On postnatal day 0, alterations in CTX genes associated with neuropeptides (<em>e.g.</em>, <em>penk</em>, <em>pdyn</em>) and receptors (<em>e.g.</em>, <em>drd1</em>, <em>adora2a</em>) were seen in both sexes, though they were downregulated in females and upregulated in males<em>.</em> Together these findings suggest that substantial sex differences in neuronal structure and function in the VPA model may have relevance to the reported sex differences in idiopathic ASD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111222"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866380","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 : 2025-01-10DOI: 10.1016/j.pnpbp.2024.111239
Hong Yu , Zuoxi Li , Xiao Gao , Xuehuan Liu , Weiwei Cui , Ningjun Li , Xinying Lian , Can Li , Jun Liu
Background
The mechanisms underlying the complex relationship between autoimmune hypothyroidism and neurological disorders remain unclear. We conducted a comprehensive analysis of associations between alternative splicing, transcriptomics, and proteomics data and autoimmune hypothyroidism.
Methods
Splicing-wide association studies (SWAS), proteome-wide association studies (PWAS), and transcriptome-wide association studies (TWAS) were used to identify genes and proteins that regulate autoimmune hypothyroidism within the brain axis. We performed TWAS on GTEx V8 thyroid tissue data to identify autoimmune hypothyroidism-associated thyroid axis genes. A FUSION analysis of overlapping genes in the brain and thyroid axes and brain splicing weights was conducted to determine the influence of alternative splicing in the brain on thyroid tissue gene expression.
Results
SWAS identified 223 alternative splicing events, TWAS identified 270 genes, and PWAS revealed five genes (FDPS, PPIL3, PEX6, MMAB, and ALDH2) encoding proteins associated with autoimmune hypothyroidism. Neuroimaging analyses revealed distinct brain-imaging phenotypes associated with these five genes. TWAS of thyroid tissue identified four genes (FDPS, PPIL3, MMAB, and ALDH2) associated with the brain axis related to thyroid tissue. A FUSION analysis indicated that alternative splicing changes in ALDH2 in brain tissue influenced its expression in thyroid tissue.
Conclusion
Integrating brain splicing, proteomic, and transcriptomic data supports the association between specific genes and proteins in the brain and autoimmune hypothyroidism. Additionally, ALDH2 alternative splicing in brain tissue influences its thyroid tissue expression. These findings provide new insights into the molecular basis of autoimmune hypothyroidism, facilitating future pathogenesis research.
{"title":"Multi-omics data integration reveals novel genes related to autoimmune hypothyroidism in the brain: A molecular basis for the brain–thyroid axis","authors":"Hong Yu , Zuoxi Li , Xiao Gao , Xuehuan Liu , Weiwei Cui , Ningjun Li , Xinying Lian , Can Li , Jun Liu","doi":"10.1016/j.pnpbp.2024.111239","DOIUrl":"10.1016/j.pnpbp.2024.111239","url":null,"abstract":"<div><h3>Background</h3><div>The mechanisms underlying the complex relationship between autoimmune hypothyroidism and neurological disorders remain unclear. We conducted a comprehensive analysis of associations between alternative splicing, transcriptomics, and proteomics data and autoimmune hypothyroidism.</div></div><div><h3>Methods</h3><div>Splicing-wide association studies (SWAS), proteome-wide association studies (PWAS), and transcriptome-wide association studies (TWAS) were used to identify genes and proteins that regulate autoimmune hypothyroidism within the brain axis. We performed TWAS on GTEx V8 thyroid tissue data to identify autoimmune hypothyroidism-associated thyroid axis genes. A FUSION analysis of overlapping genes in the brain and thyroid axes and brain splicing weights was conducted to determine the influence of alternative splicing in the brain on thyroid tissue gene expression.</div></div><div><h3>Results</h3><div>SWAS identified 223 alternative splicing events, TWAS identified 270 genes, and PWAS revealed five genes (<em>FDPS</em>, <em>PPIL3</em>, <em>PEX6</em>, <em>MMAB</em>, and <em>ALDH2</em>) encoding proteins associated with autoimmune hypothyroidism. Neuroimaging analyses revealed distinct brain-imaging phenotypes associated with these five genes. TWAS of thyroid tissue identified four genes (<em>FDPS</em>, <em>PPIL3</em>, <em>MMAB</em>, and <em>ALDH2</em>) associated with the brain axis related to thyroid tissue. A FUSION analysis indicated that alternative splicing changes in <em>ALDH2</em> in brain tissue influenced its expression in thyroid tissue.</div></div><div><h3>Conclusion</h3><div>Integrating brain splicing, proteomic, and transcriptomic data supports the association between specific genes and proteins in the brain and autoimmune hypothyroidism. Additionally, <em>ALDH2</em> alternative splicing in brain tissue influences its thyroid tissue expression. These findings provide new insights into the molecular basis of autoimmune hypothyroidism, facilitating future pathogenesis research.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111239"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907924","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.2025.111248
Marie-Louis Wronski , Franziska Gronow , John Schlömer , Fabio Bernardoni , Daniel Geisler , Arne Doose , Dominic Arold , Nadine Schwanke , Franziska Ludwicki , Veit Roessner , Joseph A. King , Stefan Ehrlich
Background
The thalamus is a complex subcortical brain structure that plays a role in various cognitive functions. Few studies have focused on thalamic nuclei-specific alterations and potential neurohormonal involvement in eating disorders including anorexia nervosa (AN).
Methods
We employed a FreeSurfer segmentation tool to compare thalamic nuclei volumes cross-sectionally between females with AN (n = 131, 12–29 years) and age-matched healthy females (HC, n = 131). Potential associations with BMI, leptin, and psychiatric symptoms were analyzed via robust linear regression.
Results
Most thalamic nuclei volumes were reduced in both hemispheres in AN versus HC. The spread of alterations ranged between −39.7 % and +3.8 % (average −9.8 %, ηp2 = 0.16). Left laterodorsal and pulvinar inferior nuclei showed positive associations with leptin in AN. Leptin mediated the effect of BMI on both thalamic nuclei volumes.
Conclusions
In AN, thalamic nuclei are altered to different degrees with laterodorsal nuclei emerging as substantially reduced. Leptin seems to be mechanistically involved in the reduction of some thalamic nuclei, further supporting the investigation of experimental leptin treatment for AN. Effect sizes observed for thalamic nuclei reductions in AN exceed other brain structures as well as other psychiatric disorders, which demonstrates the importance of the thalamus as a target structure in research on AN.
{"title":"Structural alterations of thalamic nuclei and their associations with leptin levels in patients with anorexia nervosa","authors":"Marie-Louis Wronski , Franziska Gronow , John Schlömer , Fabio Bernardoni , Daniel Geisler , Arne Doose , Dominic Arold , Nadine Schwanke , Franziska Ludwicki , Veit Roessner , Joseph A. King , Stefan Ehrlich","doi":"10.1016/j.pnpbp.2025.111248","DOIUrl":"10.1016/j.pnpbp.2025.111248","url":null,"abstract":"<div><h3>Background</h3><div>The thalamus is a complex subcortical brain structure that plays a role in various cognitive functions. Few studies have focused on thalamic nuclei-specific alterations and potential neurohormonal involvement in eating disorders including anorexia nervosa (AN).</div></div><div><h3>Methods</h3><div>We employed a FreeSurfer segmentation tool to compare thalamic nuclei volumes cross-sectionally between females with AN (<em>n</em> = 131, 12–29 years) and age-matched healthy females (HC, n = 131). Potential associations with BMI, leptin, and psychiatric symptoms were analyzed via robust linear regression.</div></div><div><h3>Results</h3><div>Most thalamic nuclei volumes were reduced in both hemispheres in AN versus HC. The spread of alterations ranged between −39.7 % and +3.8 % (average −9.8 %, η<sub>p</sub><sup>2</sup> = 0.16). Left laterodorsal and pulvinar inferior nuclei showed positive associations with leptin in AN. Leptin mediated the effect of BMI on both thalamic nuclei volumes.</div></div><div><h3>Conclusions</h3><div>In AN, thalamic nuclei are altered to different degrees with laterodorsal nuclei emerging as substantially reduced. Leptin seems to be mechanistically involved in the reduction of some thalamic nuclei, further supporting the investigation of experimental leptin treatment for AN. Effect sizes observed for thalamic nuclei reductions in AN exceed other brain structures as well as other psychiatric disorders, which demonstrates the importance of the thalamus as a target structure in research on AN.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111248"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973360","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 : 2025-01-10DOI: 10.1016/j.pnpbp.2024.111246
Agnieszka Mechlińska, Adam Włodarczyk
{"title":"Measuring the effects of ketogenic diet on neuropsychiatric disorder: A scoping review – Letter to the Editor","authors":"Agnieszka Mechlińska, Adam Włodarczyk","doi":"10.1016/j.pnpbp.2024.111246","DOIUrl":"10.1016/j.pnpbp.2024.111246","url":null,"abstract":"","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111246"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923880","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.2025.111250
Mingxuan Lu , Jiayao Zhang , Qi Zhang , Jiyu Sun , Danni Zou , Jinyin Huang , Weicai Liu
Eating behavior stands as a fundamental determinant of animal survival and growth, intricately regulated by an amalgamation of internal and external stimuli. Coordinated movements of facial muscles and the mandible orchestrate prey capture and food processing, propelled by the allure of taste and rewarding food properties. Conversely, satiation, pain, aversion, negative emotion or perceived threats can precipitate the cessation or avoidance of eating activities. In recent years, the parasubthalamic nucleus (PSTN), located in the lateral hypothalamic area, has emerged as a focal point in feeding research. PSTN neurons assume pivotal roles within multiple feeding circuits, bridging central feeding centers with peripheral organs. They intricately modulate regulation of oral sensorimotor functions, hedonic feeding, appetite motivation and the processing of satiation and aversive signals, thereby orchestrating the initiation or termination of feeding behaviors. This review delves into the distinctive neuronal subpopulations within the PSTN and their associated neural networks, aiming to refine our comprehension of the neural underpinnings of feeding while also seeking to unearth more efficacious therapeutic avenues for feeding and eating disorders.
{"title":"The parasubthalamic nucleus: A novel eating center in the brain","authors":"Mingxuan Lu , Jiayao Zhang , Qi Zhang , Jiyu Sun , Danni Zou , Jinyin Huang , Weicai Liu","doi":"10.1016/j.pnpbp.2025.111250","DOIUrl":"10.1016/j.pnpbp.2025.111250","url":null,"abstract":"<div><div>Eating behavior stands as a fundamental determinant of animal survival and growth, intricately regulated by an amalgamation of internal and external stimuli. Coordinated movements of facial muscles and the mandible orchestrate prey capture and food processing, propelled by the allure of taste and rewarding food properties. Conversely, satiation, pain, aversion, negative emotion or perceived threats can precipitate the cessation or avoidance of eating activities. In recent years, the parasubthalamic nucleus (PSTN), located in the lateral hypothalamic area, has emerged as a focal point in feeding research. PSTN neurons assume pivotal roles within multiple feeding circuits, bridging central feeding centers with peripheral organs. They intricately modulate regulation of oral sensorimotor functions, hedonic feeding, appetite motivation and the processing of satiation and aversive signals, thereby orchestrating the initiation or termination of feeding behaviors. This review delves into the distinctive neuronal subpopulations within the PSTN and their associated neural networks, aiming to refine our comprehension of the neural underpinnings of feeding while also seeking to unearth more efficacious therapeutic avenues for feeding and eating disorders.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111250"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959066","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.2024.111240
F.L. Mikulic , M. Sagud , M. Nikolac Perkovic , S. Kudlek Mikulic , L. Ganoci , M. Bajs Janovic , S. Janovic , I. Filipcic Simunovic , A. Mihaljevic Peles , M. Bozicevic , Z. Bradas , N. Pivac
Brain-derived neurotrophic factor (BDNF) is implicated in the etiology of schizophrenia, and peripheral BDNF levels are affected by the short-term antipsychotic treatment. However, the data on their long-term effects on BDNF levels are scarce, and there is no information whether BDNF levels change during sustained remission in relation to values in healthy individuals. The aim of the present study was to compare serum BDNF levels in patients in long-term remission and healthy controls.
This study is an extension of our previous research on the effects of olanzapine and risperidone on serum BDNF in acute-episode patients with schizophrenia. Patients who remained in remission for at least 3 years on the same antipsychotic regimen (40 % of the initial cohort) were included. Symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). Serum BDNF levels were measured by ELISA in patients in remission (N = 20), evaluated at baseline, after 6 weeks of treatment and after 3 years of treatment, and in healthy individuals (N = 40).
At baseline (p = 0.046) and after 6 weeks of treatment (p = 0.028), patients had significantly lower BDNF levels than controls. However, after 3 years of continuous antipsychotic maintenance treatment, serum BDNF levels were increased compared to baseline and values after 6 weeks of treatment in remitted patients, and were also significantly higher in patients than in healthy controls (p = 0.002).
Antipsychotic medications appear to have distinct effects on serum BDNF levels in short-and long-term treatment. It remains to be determined if such finding may be related to potential neuroprotective effects of antipsychotic maintenance treatment.
{"title":"Long-term effects of antipsychotics on serum BDNF levels in patients with schizophrenia","authors":"F.L. Mikulic , M. Sagud , M. Nikolac Perkovic , S. Kudlek Mikulic , L. Ganoci , M. Bajs Janovic , S. Janovic , I. Filipcic Simunovic , A. Mihaljevic Peles , M. Bozicevic , Z. Bradas , N. Pivac","doi":"10.1016/j.pnpbp.2024.111240","DOIUrl":"10.1016/j.pnpbp.2024.111240","url":null,"abstract":"<div><div>Brain-derived neurotrophic factor (BDNF) is implicated in the etiology of schizophrenia, and peripheral BDNF levels are affected by the short-term antipsychotic treatment. However, the data on their long-term effects on BDNF levels are scarce, and there is no information whether BDNF levels change during sustained remission in relation to values in healthy individuals. The aim of the present study was to compare serum BDNF levels in patients in long-term remission and healthy controls.</div><div>This study is an extension of our previous research on the effects of olanzapine and risperidone on serum BDNF in acute-episode patients with schizophrenia. Patients who remained in remission for at least 3 years on the same antipsychotic regimen (40 % of the initial cohort) were included. Symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). Serum BDNF levels were measured by ELISA in patients in remission (<em>N</em> = 20), evaluated at baseline, after 6 weeks of treatment and after 3 years of treatment, and in healthy individuals (<em>N</em> = 40).</div><div>At baseline (<em>p</em> = 0.046) and after 6 weeks of treatment (<em>p</em> = 0.028), patients had significantly lower BDNF levels than controls. However, after 3 years of continuous antipsychotic maintenance treatment, serum BDNF levels were increased compared to baseline and values after 6 weeks of treatment in remitted patients, and were also significantly higher in patients than in healthy controls (<em>p</em> = 0.002).</div><div>Antipsychotic medications appear to have distinct effects on serum BDNF levels in short-and long-term treatment. It remains to be determined if such finding may be related to potential neuroprotective effects of antipsychotic maintenance treatment.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111240"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916086","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.2024.111228
Ting-Ting Zhu , Ming-Ming Zhao , Dan Xu , Yi Cai , Guilin Liu , Rumi Murayama , Yong Yue , Jian-Jun Yang , Kenji Hashimoto
Postoperative cognitive dysfunction (POCD) is characterized by a decline in cognitive functions, including memory, attention, and executive abilities, following surgery, with no effective therapeutic drugs currently available. Arketamine, the (R)-enantiomer of ketamine, has shown promise in mitigating cognitive deficits in animal models. In this study, we investigated whether arketamine could ameliorate cognitive deficits in a mouse model of POCD, with a focus on the role of transforming growth factor (TGF)-β1 in its effects. POCD mice displayed cognitive impairments and demyelination in the corpus callosum. A single arketamine injection (10 mg/kg) significantly improved both cognitive function and demyelination in the corpus callosum of POCD mice. Notably, pretreatment with RepSox (10 mg/kg), a TGF-β receptor 1 inhibitor, significantly blocked the beneficial effects of arketamine on cognitive deficits and demyelination. Moreover, intranasal administration of TGF-β1 (3.0 μg/kg) markedly alleviated cognitive impairments and demyelination in POCD mice. These findings suggest that arketamine exerts its effects through a TGF-β1-dependent mechanism, positioning it as a potential therapeutic option for POCD.
{"title":"Arketamine alleviates cognitive impairments and demyelination in mice with postoperative cognitive dysfunction via TGF-β1 activation","authors":"Ting-Ting Zhu , Ming-Ming Zhao , Dan Xu , Yi Cai , Guilin Liu , Rumi Murayama , Yong Yue , Jian-Jun Yang , Kenji Hashimoto","doi":"10.1016/j.pnpbp.2024.111228","DOIUrl":"10.1016/j.pnpbp.2024.111228","url":null,"abstract":"<div><div>Postoperative cognitive dysfunction (POCD) is characterized by a decline in cognitive functions, including memory, attention, and executive abilities, following surgery, with no effective therapeutic drugs currently available. Arketamine, the (<em>R</em>)-enantiomer of ketamine, has shown promise in mitigating cognitive deficits in animal models. In this study, we investigated whether arketamine could ameliorate cognitive deficits in a mouse model of POCD, with a focus on the role of transforming growth factor (TGF)-β1 in its effects. POCD mice displayed cognitive impairments and demyelination in the corpus callosum. A single arketamine injection (10 mg/kg) significantly improved both cognitive function and demyelination in the corpus callosum of POCD mice. Notably, pretreatment with RepSox (10 mg/kg), a TGF-β receptor 1 inhibitor, significantly blocked the beneficial effects of arketamine on cognitive deficits and demyelination. Moreover, intranasal administration of TGF-β1 (3.0 μg/kg) markedly alleviated cognitive impairments and demyelination in POCD mice. These findings suggest that arketamine exerts its effects through a TGF-β1-dependent mechanism, positioning it as a potential therapeutic option for POCD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111228"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886475","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}
3,4-Methylenedioxymethamphetamine (MDMA; Ecstasy) is a widely abused recreational drug that has also gained interest for potential clinical applications in mental health. With the growing recognition of gut microbiota's role in mental health, this study examined whether repeated oral MDMA administration could affect gut microbiota in the small intestine, cecum, and colon of male rats. Repeated oral MDMA administration (10 mg/kg/day for 14 days) caused significant changes in the gut microbiota across these regions, with distinct effects observed in each. PICRUSt2 analysis revealed significant alterations in several metabolic pathways in these regions, indicating potential shifts in microbial functional capabilities associated with MDMA treatment. Untargeted metabolomics analysis revealed that MDMA significantly altered levels of two metabolites-ferulic acid and methylmalonic acid-in the colon, without changes in the blood, small intestine, or cecum. Notably, methylmalonic acid levels in the colon positively correlated with Lawsonibacter and Oscillibacter. These findings suggest that repeated oral MDMA treatment can alter gut microbiota composition across intestinal regions, potentially contributing to its pharmacological effects.
{"title":"Effects of 3,4-methylenedioxymethamphetamine on the gut microbiota and metabolites in the small intestine, cecum, and colon of male rats.","authors":"Dan Xu, Akifumi Eguchi, Rumi Murayama, Guilin Liu, Mingming Zhao, Tingting Zhu, Yi Cai, Yong Yue, Xiayun Wan, Yuko Fujita, Chisato Mori, Kenji Hashimoto","doi":"10.1016/j.pnpbp.2024.111223","DOIUrl":"10.1016/j.pnpbp.2024.111223","url":null,"abstract":"<p><p>3,4-Methylenedioxymethamphetamine (MDMA; Ecstasy) is a widely abused recreational drug that has also gained interest for potential clinical applications in mental health. With the growing recognition of gut microbiota's role in mental health, this study examined whether repeated oral MDMA administration could affect gut microbiota in the small intestine, cecum, and colon of male rats. Repeated oral MDMA administration (10 mg/kg/day for 14 days) caused significant changes in the gut microbiota across these regions, with distinct effects observed in each. PICRUSt2 analysis revealed significant alterations in several metabolic pathways in these regions, indicating potential shifts in microbial functional capabilities associated with MDMA treatment. Untargeted metabolomics analysis revealed that MDMA significantly altered levels of two metabolites-ferulic acid and methylmalonic acid-in the colon, without changes in the blood, small intestine, or cecum. Notably, methylmalonic acid levels in the colon positively correlated with Lawsonibacter and Oscillibacter. These findings suggest that repeated oral MDMA treatment can alter gut microbiota composition across intestinal regions, potentially contributing to its pharmacological effects.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111223"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866370","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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