Individual neurobiological heterogeneity among patients with tobacco use disorder (TUD) hampers the identification of neuroimaging phenotypes.
Methods
The current study recruited 122 TUD individuals and 57 healthy controls, and obtained their 3D-T1 images. Heterogeneity through discriminative analysis (HYDRA) was applied to uncover the potential subtype of TUD where regional gray matter volume (GMV) was treated as the feature. Then we examined the clinical, neuroimaging and molecular characteristics of subtypes.
Results
Two distinct neuroanatomical subtypes were found. In subtype 1, TUD individuals showed decreased GMV in right orbitofrontal cortex (OFC), while subtype 2 exhibited distributed pattern of widely GMV increase. Moreover, subtype 1 showed older initial smoking age, longer duration of smoking than Subtype 2. Persistent smoking behavior in subtype 1 is more likely caused by substance dependence/addiction rather than psychosocial factors. GMV correlated negatively with cumulative tobacco exposure in Subtype 1 but not in Subtype 2. Besides, neuroanatomical aberrance in subtype 1 was mainly associated with dopamine system, while neuroanatomical abnormalities in subtype 2 were primarily associated with GABAa.
Conclusions
Overall, our results revealed two opposite neuroanatomical subtypes of TUD, which largely overlapped with their clinical and molecular features respectively. TUD subtypes taxonomy based on objective anatomy could help to facilitate the development of individualized treatment for TUD.
{"title":"Neuroanatomical subtypes of tobacco use disorder and relationship with clinical and molecular features","authors":"Mengzhe Zhang, Xiaoyu Niu, Jinghan Dang, Jieping Sun, Qiuying Tao, Weijian Wang, Shaoqiang Han, Jingliang Cheng, Yong Zhang","doi":"10.1016/j.pnpbp.2024.111235","DOIUrl":"10.1016/j.pnpbp.2024.111235","url":null,"abstract":"<div><h3>Background</h3><div>Individual neurobiological heterogeneity among patients with tobacco use disorder (TUD) hampers the identification of neuroimaging phenotypes.</div></div><div><h3>Methods</h3><div>The current study recruited 122 TUD individuals and 57 healthy controls, and obtained their 3D-T1 images. Heterogeneity through discriminative analysis (HYDRA) was applied to uncover the potential subtype of TUD where regional gray matter volume (GMV) was treated as the feature. Then we examined the clinical, neuroimaging and molecular characteristics of subtypes.</div></div><div><h3>Results</h3><div>Two distinct neuroanatomical subtypes were found. In subtype 1, TUD individuals showed decreased GMV in right orbitofrontal cortex (OFC), while subtype 2 exhibited distributed pattern of widely GMV increase. Moreover, subtype 1 showed older initial smoking age, longer duration of smoking than Subtype 2. Persistent smoking behavior in subtype 1 is more likely caused by substance dependence/addiction rather than psychosocial factors. GMV correlated negatively with cumulative tobacco exposure in Subtype 1 but not in Subtype 2. Besides, neuroanatomical aberrance in subtype 1 was mainly associated with dopamine system, while neuroanatomical abnormalities in subtype 2 were primarily associated with GABAa.</div></div><div><h3>Conclusions</h3><div>Overall, our results revealed two opposite neuroanatomical subtypes of TUD, which largely overlapped with their clinical and molecular features respectively. TUD subtypes taxonomy based on objective anatomy could help to facilitate the development of individualized treatment for TUD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111235"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900462","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.2025.111252
Zeqiang LinLi , Kang Hu , Qingdong Guo , Shuixia Guo
Aging of the human brain involves intricate biological processes, resulting in complex changes in structure and function. While the effects of aging on gray matter (GM) connectivity are extensively studied, white matter (WM) functional changes have received comparatively less attention. This study examines age-related WM functional dynamics using resting-state fMRI across the adult lifespan. We identified GM and WM functional networks (FNs) using k-means clustering. Static and dynamic analyses of WM functional network connectivity (FNC) were performed to explore age effects on WM-FNs and recurrent patterns of dynamic FNC. We identified 9 WM and 12 GM FNs. Age-related effects on WM FNC strength and WM-GM FNC dynamics included linear positive and U-shaped age trajectories in static FNC strength, and linear negative and inverted U-shaped trajectories in FNC temporal variability. Three distinct brain states with significant age-related differences were identified and validated. These findings were largely replicated in the validation analysis. High integration and low temporal variability in WM-GM FNC may indicate reduced adaptability of the network system in older adults, offering insights into brain aging processes.
{"title":"Static and dynamic connectivity structure of white-matter functional networks across the adult lifespan","authors":"Zeqiang LinLi , Kang Hu , Qingdong Guo , Shuixia Guo","doi":"10.1016/j.pnpbp.2025.111252","DOIUrl":"10.1016/j.pnpbp.2025.111252","url":null,"abstract":"<div><div>Aging of the human brain involves intricate biological processes, resulting in complex changes in structure and function. While the effects of aging on gray matter (GM) connectivity are extensively studied, white matter (WM) functional changes have received comparatively less attention. This study examines age-related WM functional dynamics using resting-state fMRI across the adult lifespan. We identified GM and WM functional networks (FNs) using k-means clustering. Static and dynamic analyses of WM functional network connectivity (FNC) were performed to explore age effects on WM-FNs and recurrent patterns of dynamic FNC. We identified 9 WM and 12 GM FNs. Age-related effects on WM FNC strength and WM-GM FNC dynamics included linear positive and U-shaped age trajectories in static FNC strength, and linear negative and inverted U-shaped trajectories in FNC temporal variability. Three distinct brain states with significant age-related differences were identified and validated. These findings were largely replicated in the validation analysis. High integration and low temporal variability in WM-GM FNC may indicate reduced adaptability of the network system in older adults, offering insights into brain aging processes.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111252"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985356","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: 2024-11-29DOI: 10.1016/j.pnpbp.2024.111199
Chao Chen, Shilin Sun, Ruoyi Chen, Zixuan Guo, Xinyue Tang, Guanmao Chen, Pan Chen, Guixian Tang, Li Huang, Ying Wang
Background: Numerous neuroimaging studies utilizing resting-state functional imaging and voxel-based morphometry (VBM) have identified variations in distinct brain regions among individuals with attention-deficit/hyperactivity disorder (ADHD). However, the results have been inconsistent.
Methods: A comprehensive voxel-wise meta-analysis was performed on studies employing resting-state functional imaging and gray matter volume (GMV), examining discrepancies between individuals with ADHD and neurotypical controls (NCs). The analysis utilized the Seed-based d Mapping software.
Results: A systematic review of the literature identified 21 functional imaging studies (595 ADHD and 564 controls) and 50 GMV studies (1907 ADHD and 1611 controls). In general, individuals with ADHD exhibited increased resting-state functional activity in the right parahippocampal gyrus and bilateral orbitofrontal cortex (OFC), as well as decreased resting-state functional activity in the bilateral cingulate cortex (including the posterior cingulate cortex [PCC], median cingulate cortex [MCC], and anterior cingulate cortex [ACC]). The VBM meta-analysis revealed decreased GMV in the bilateral OFC, right putamen (extending to right superior temporal gyrus [STG]), left inferior frontal gyrus (IFG), right superior frontal gyrus (SFG), ACC, and precentral gyrus among individuals with ADHD.
Conclusions: The multimodal meta-analyses indicated that individuals with ADHD exhibit abnormalities in both function and structure in the bilateral OFC. In addition, a few regions exhibited only functional or only structural abnormalities in ADHD, such as in the limbic, prefrontal, primary sensorimotor regions.
{"title":"A multimodal neuroimaging meta-analysis of functional and structural brain abnormalities in attention-deficit/hyperactivity disorder.","authors":"Chao Chen, Shilin Sun, Ruoyi Chen, Zixuan Guo, Xinyue Tang, Guanmao Chen, Pan Chen, Guixian Tang, Li Huang, Ying Wang","doi":"10.1016/j.pnpbp.2024.111199","DOIUrl":"10.1016/j.pnpbp.2024.111199","url":null,"abstract":"<p><strong>Background: </strong>Numerous neuroimaging studies utilizing resting-state functional imaging and voxel-based morphometry (VBM) have identified variations in distinct brain regions among individuals with attention-deficit/hyperactivity disorder (ADHD). However, the results have been inconsistent.</p><p><strong>Methods: </strong>A comprehensive voxel-wise meta-analysis was performed on studies employing resting-state functional imaging and gray matter volume (GMV), examining discrepancies between individuals with ADHD and neurotypical controls (NCs). The analysis utilized the Seed-based d Mapping software.</p><p><strong>Results: </strong>A systematic review of the literature identified 21 functional imaging studies (595 ADHD and 564 controls) and 50 GMV studies (1907 ADHD and 1611 controls). In general, individuals with ADHD exhibited increased resting-state functional activity in the right parahippocampal gyrus and bilateral orbitofrontal cortex (OFC), as well as decreased resting-state functional activity in the bilateral cingulate cortex (including the posterior cingulate cortex [PCC], median cingulate cortex [MCC], and anterior cingulate cortex [ACC]). The VBM meta-analysis revealed decreased GMV in the bilateral OFC, right putamen (extending to right superior temporal gyrus [STG]), left inferior frontal gyrus (IFG), right superior frontal gyrus (SFG), ACC, and precentral gyrus among individuals with ADHD.</p><p><strong>Conclusions: </strong>The multimodal meta-analyses indicated that individuals with ADHD exhibit abnormalities in both function and structure in the bilateral OFC. In addition, a few regions exhibited only functional or only structural abnormalities in ADHD, such as in the limbic, prefrontal, primary sensorimotor regions.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111199"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774736","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.2024.111211
Qian Zhang , Aoxiang Zhang , Ziyuan Zhao , Qian Li , Yongbo Hu , Xiaoqi Huang , Graham J. Kemp , Weihong Kuang , Youjin Zhao , Qiyong Gong
Introduction
Major depressive disorder (MDD) is a debilitating and heterogeneous disease. Many MDD patients experience concurrent anxiety symptoms, often referred to as anxious depression (MDD-ANX). The relationships between network alterations in structural connectivity (SC) and functional connectivity (FC) in MDD and its anxiety-related subtype remain areas that require further investigation.
Methods
We investigated SC-FC coupling at the system and regional levels in 80 never-treated first-episode MDD patients and 80 healthy control (HC) subjects. For brain systems and regions showing significant between-group coupling differences, we further conducted subgroup comparisons between MDD-ANX, non-anxious depression (MDD-NANX) and HC. We also investigated topological features at the corresponding levels, and assessed the correlation patterns between significant coupling alterations and the topological and clinical characteristics.
Results
Relative to HC, MDD patients showed increased SC-FC coupling in the temporal system (right hippocampus and left superior temporal gyrus [STG]) but decreased coupling in the parietal system (right postcentral gyrus and left angular gyrus). These systems and regions were further characterized by disturbed inter-module connections and impaired structural network efficiency in MDD. Notably, SC-FC coupling of the right hippocampus was significantly increased in MDD-ANX compared to MDD-NANX, which further showed distinct correlation patterns with structural network efficiency.
Conclusions
Alterations in both SC-FC coupling and topological properties in the temporal and parietal regions provide insights into the interplay between the structural and functional network abnormalities in MDD. SC-FC coupling alterations in the right hippocampus, associated with structural nodal efficiency, may be implicated in the neuropathology of anxious depression.
{"title":"Temporoparietal structural-functional coupling abnormalities in drug-naïve first-episode major depressive disorder","authors":"Qian Zhang , Aoxiang Zhang , Ziyuan Zhao , Qian Li , Yongbo Hu , Xiaoqi Huang , Graham J. Kemp , Weihong Kuang , Youjin Zhao , Qiyong Gong","doi":"10.1016/j.pnpbp.2024.111211","DOIUrl":"10.1016/j.pnpbp.2024.111211","url":null,"abstract":"<div><h3>Introduction</h3><div>Major depressive disorder (MDD) is a debilitating and heterogeneous disease. Many MDD patients experience concurrent anxiety symptoms, often referred to as anxious depression (MDD-ANX). The relationships between network alterations in structural connectivity (SC) and functional connectivity (FC) in MDD and its anxiety-related subtype remain areas that require further investigation.</div></div><div><h3>Methods</h3><div>We investigated SC-FC coupling at the system and regional levels in 80 never-treated first-episode MDD patients and 80 healthy control (HC) subjects. For brain systems and regions showing significant between-group coupling differences, we further conducted subgroup comparisons between MDD-ANX, non-anxious depression (MDD-NANX) and HC. We also investigated topological features at the corresponding levels, and assessed the correlation patterns between significant coupling alterations and the topological and clinical characteristics.</div></div><div><h3>Results</h3><div>Relative to HC, MDD patients showed increased SC-FC coupling in the temporal system (right hippocampus and left superior temporal gyrus [STG]) but decreased coupling in the parietal system (right postcentral gyrus and left angular gyrus). These systems and regions were further characterized by disturbed inter-module connections and impaired structural network efficiency in MDD. Notably, SC-FC coupling of the right hippocampus was significantly increased in MDD-ANX compared to MDD-NANX, which further showed distinct correlation patterns with structural network efficiency.</div></div><div><h3>Conclusions</h3><div>Alterations in both SC-FC coupling and topological properties in the temporal and parietal regions provide insights into the interplay between the structural and functional network abnormalities in MDD. SC-FC coupling alterations in the right hippocampus, associated with structural nodal efficiency, may be implicated in the neuropathology of anxious depression.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111211"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792858","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.2024.111213
S. Chiappini , A. Guirguis , N. Schifano , J.M. Corkery , F. Semeraro , A. Mosca , G. D’Andrea , G. Duccio Papanti , D. Arillotta , G. Floresta , G. Martinotti , F. Schifano
Intranasal esketamine, approved with oral antidepressants for adults with treatment-resistant depression (TRD), is the S-enantiomer of ketamine and has higher potency and affinity for N-Methyl-d-Aspartate receptors. Administered intranasally, it offers rapid absorption and onset, essential for severe depressive symptoms or suicidal impulses. Comparative studies on esketamine and ketamine's urological safety profiles show esketamine has lower or comparable risks of renal and urinary disorders. Ketamine, however, has documented cases of nephrotoxicity and severe urological issues in recreational users.
The study aims to further evaluate and compare these profiles against other antidepressants and antipsychotics using the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) data. ADR cases were reported to the FDA up to May 12, 2024, being drugs listed including esketamine, ketamine, quetiapine, aripiprazole, olanzapine, risperidone, citalopram, escitalopram, paroxetine, fluoxetine, sertraline, duloxetine, venlafaxine, amitriptyline, and clomipramine.
Risperidone showed the highest ADRs (107,418) and serious cases (71,515), with significant renal and urinary disorders reported, including acute kidney injury and urinary incontinence. Olanzapine, quetiapine, and aripiprazole also had high serious ADRs. Venlafaxine and fluoxetine were notable among antidepressants for acute kidney injury. Esketamine and ketamine were associated with lower urinary tract symptoms and nephrolithiasis. Disproportionality analysis revealed ketamine had higher odds of renal and urinary disorders compared to other drug classes, while esketamine had lower or comparable odds.
The data suggest a relatively favorable tolerability profile for these drugs, especially esketamine. However, the results highlight the necessity for more extensive studies to evaluate long-term safety and optimize treatment protocols.
{"title":"Comparative safety of prescribed Esketamine and ketamine in relation to renal and urinary disorders: A pharmacovigilance perspective","authors":"S. Chiappini , A. Guirguis , N. Schifano , J.M. Corkery , F. Semeraro , A. Mosca , G. D’Andrea , G. Duccio Papanti , D. Arillotta , G. Floresta , G. Martinotti , F. Schifano","doi":"10.1016/j.pnpbp.2024.111213","DOIUrl":"10.1016/j.pnpbp.2024.111213","url":null,"abstract":"<div><div>Intranasal esketamine, approved with oral antidepressants for adults with treatment-resistant depression (TRD), is the S-enantiomer of ketamine and has higher potency and affinity for N-Methyl-<span>d</span>-Aspartate receptors. Administered intranasally, it offers rapid absorption and onset, essential for severe depressive symptoms or suicidal impulses. Comparative studies on esketamine and ketamine's urological safety profiles show esketamine has lower or comparable risks of renal and urinary disorders. Ketamine, however, has documented cases of nephrotoxicity and severe urological issues in recreational users.</div><div>The study aims to further evaluate and compare these profiles against other antidepressants and antipsychotics using the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) data. ADR cases were reported to the FDA up to May 12, 2024, being drugs listed including esketamine, ketamine, quetiapine, aripiprazole, olanzapine, risperidone, citalopram, escitalopram, paroxetine, fluoxetine, sertraline, duloxetine, venlafaxine, amitriptyline, and clomipramine.</div><div>Risperidone showed the highest ADRs (107,418) and serious cases (71,515), with significant renal and urinary disorders reported, including acute kidney injury and urinary incontinence. Olanzapine, quetiapine, and aripiprazole also had high serious ADRs. Venlafaxine and fluoxetine were notable among antidepressants for acute kidney injury. Esketamine and ketamine were associated with lower urinary tract symptoms and nephrolithiasis. Disproportionality analysis revealed ketamine had higher odds of renal and urinary disorders compared to other drug classes, while esketamine had lower or comparable odds.</div><div>The data suggest a relatively favorable tolerability profile for these drugs, especially esketamine. However, the results highlight the necessity for more extensive studies to evaluate long-term safety and optimize treatment protocols.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111213"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796442","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.2024.111215
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}
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