Brain disorders (Amsterdam, Netherlands)最新文献

Lidocaine mitigates cognitive decline in elderly patients after video-assisted thoracoscopic surgery: A double-blind randomized controlled clinical trial 利多卡因减轻电视胸腔镜手术后老年患者的认知能力下降：一项双盲随机对照临床试验

Brain disorders (Amsterdam, Netherlands)

Pub Date : 2026-01-27 DOI: 10.1016/j.dscb.2026.100308

Wang Yong , Xu Xiaoqiang , Jing Yibing , Huang Jian , Yu Lizhong

Background

: Postoperative cognitive decline (POCD) can occur in elderly patients after surgery and is associated with poor outcomes. Lidocaine is an antiarrhythmic and anesthetic agent, with analgesic and anti-inflammatory properties. We aimed to explore the influence of lidocaine on POCD in elderly patients undergoing video-assisted thoracoscopic lobectomy.

Methods

: This was a prospective double-blind randomized controlled clinical trial performed between January 2022 and August 2024. Eligible patients ≥ 65 years old scheduled for video-assisted pulmonary lobectomy under general anesthesia with one-lung ventilation were randomized into lidocaine (1.5 mg/kg lidocaine at anesthesia induction followed by continuous intravenous infusion at 1.5mg/kg/hr) or control (same dose of normal saline) group. Mini-Mental State Examination (MMSE), serum IL-6 and S100β levels, and cerebral oxygen extraction rate (CREO₂) were measured before and after surgery.

Results

: A total of 80 patients, with 40 patients in each group, completed the trial. Compared with pre-operation, MMSE scores in control group were significantly decreased on postoperative days 1 and 3 (P < 0.05), which was mitigated in lidocaine group. Serum IL-6 and S100β levels were significantly increased in control group on postoperative days 1 and 3 (P < 0.05), which was also mitigated in lidocaine group. In addition, CERO₂ was significantly increased in 30 and 60 min after initiation of one-lung ventilation in control group (P < 0.05), which was also mitigated in lidocaine group.

Conclusion

: Lidocaine could mitigate cognitive decline after video-assisted thoracoscopy with one-lung ventilation. Its effect might be related to anti-neuroinflammation and reduced cerebral oxygen metabolic rate.

背景：老年患者术后认知能力下降（POCD）可发生，并与不良预后相关。利多卡因是一种抗心律失常和麻醉剂，具有镇痛和抗炎特性。我们的目的是探讨利多卡因对接受胸腔镜肺叶切除术的老年患者POCD的影响。方法：这是一项前瞻性双盲随机对照临床试验，于2022年1月至2024年8月进行。年龄≥65岁，拟行电视辅助肺叶切除术，全麻单肺通气，随机分为利多卡因组（麻醉诱导时1.5mg/kg利多卡因，随后以1.5mg/kg/hr持续静脉输注）和对照组（等量生理盐水）。测量患者术前、术后精神状态检查（MMSE）、血清IL-6、S100β水平及脑氧提取率（CREO2）。结果：共80例患者完成试验，每组40例。与术前比较，对照组术后第1天、第3天MMSE评分均显著降低（P < 0.05），利多卡因组较术前有所缓解。对照组患者术后第1、3天血清IL-6、S100β水平显著升高（P < 0.05），利多卡因组患者血清IL-6、S100β水平有所缓解。另外，对照组在单肺通气开始后30、60 min CERO2明显升高（P < 0.05），利多卡因组也有所缓解。结论：利多卡因可减轻电视胸腔镜单肺通气术后认知能力下降。其作用可能与抗神经炎症和降低脑氧代谢率有关。

{"title":"Lidocaine mitigates cognitive decline in elderly patients after video-assisted thoracoscopic surgery: A double-blind randomized controlled clinical trial","authors":"Wang Yong , Xu Xiaoqiang , Jing Yibing , Huang Jian , Yu Lizhong","doi":"10.1016/j.dscb.2026.100308","DOIUrl":"10.1016/j.dscb.2026.100308","url":null,"abstract":"<div><h3>Background</h3><div><strong>:</strong> Postoperative cognitive decline (POCD) can occur in elderly patients after surgery and is associated with poor outcomes. Lidocaine is an antiarrhythmic and anesthetic agent, with analgesic and anti-inflammatory properties. We aimed to explore the influence of lidocaine on POCD in elderly patients undergoing video-assisted thoracoscopic lobectomy.</div></div><div><h3>Methods</h3><div><strong>:</strong> This was a prospective double-blind randomized controlled clinical trial performed between January 2022 and August 2024. Eligible patients ≥ 65 years old scheduled for video-assisted pulmonary lobectomy under general anesthesia with one-lung ventilation were randomized into lidocaine (1.5 mg/kg lidocaine at anesthesia induction followed by continuous intravenous infusion at 1.5mg/kg/hr) or control (same dose of normal saline) group. Mini-Mental State Examination (MMSE), serum IL-6 and S100β levels, and cerebral oxygen extraction rate (CREO<sub>2</sub>) were measured before and after surgery.</div></div><div><h3>Results</h3><div><strong>:</strong> A total of 80 patients, with 40 patients in each group, completed the trial. Compared with pre-operation, MMSE scores in control group were significantly decreased on postoperative days 1 and 3 (<em>P</em> < 0.05), which was mitigated in lidocaine group. Serum IL-6 and S100β levels were significantly increased in control group on postoperative days 1 and 3 (<em>P</em> < 0.05), which was also mitigated in lidocaine group. In addition, CERO<sub>2</sub> was significantly increased in 30 and 60 min after initiation of one-lung ventilation in control group (<em>P</em> < 0.05), which was also mitigated in lidocaine group.</div></div><div><h3>Conclusion</h3><div><strong>:</strong> Lidocaine could mitigate cognitive decline after video-assisted thoracoscopy with one-lung ventilation. Its effect might be related to anti-neuroinflammation and reduced cerebral oxygen metabolic rate.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"21 ","pages":"Article 100308"},"PeriodicalIF":0.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Guillain–Barré syndrome following dengue infection in an adult patient: a case report 成人登革热感染后吉兰-巴罗综合征1例报告

Brain disorders (Amsterdam, Netherlands)

Pub Date : 2026-01-13 DOI: 10.1016/j.dscb.2026.100306

Nikhat Shahla Afsar , Sumaiya Farah Marisa , Nishat Ali , Md. Imrul Hasan , Mohammad Mahfuzur Rahman , Sayat Quayum Mohona , Rayhan Uddin Ahmed , Mehadi Hasan , Anika Shahidullah , Chowdhury Adnan Sami

Background

Dengue fever is a viral disease that presents with a wide range of neurological features. Although less frequent, Guillain–Barré Syndrome (GBS) is a life-threatening, postinfectious neurological sequela.

Case summary

A 44-year-old Bangladeshi male presented with flaccid quadriplegia during the recovery phase of serologically confirmed dengue fever. Cerebrospinal fluid (CSF) analysis showed albuminocytologic dissociation. The patient was treated with intravenous immunoglobulin therapy and supportive measures, including mechanical ventilation. His condition improved after 14 days of critical care.

Conclusion

This case underscores the importance of maintaining a high index of suspicion for GBS in patients with dengue fever in endemic regions. Early diagnosis and multidisciplinary management are essential for better outcomes.

登革热是一种病毒性疾病，具有广泛的神经系统特征。吉兰-巴罗综合征（GBS）虽不常见，但却是一种危及生命的感染后神经系统后遗症。一名44岁孟加拉国男性在经血清学证实的登革热恢复阶段表现为弛缓性四肢瘫痪。脑脊液（CSF）分析显示白蛋白细胞分离。患者接受静脉免疫球蛋白治疗和支持措施，包括机械通气。经过14天的重症监护，他的病情有所好转。结论本病例强调了在登革热流行地区对登革热患者保持高怀疑指数的重要性。早期诊断和多学科管理对于改善预后至关重要。

引用次数: 0

Heterozygous FBXO7 as potential genetic modifiers in early-onset Parkinson’s disease with levodopa responsive non-motor features 杂合子FBXO7作为具有左旋多巴反应性非运动特征的早发性帕金森病的潜在遗传修饰因子

Brain disorders (Amsterdam, Netherlands)

Pub Date : 2025-12-24 DOI: 10.1016/j.dscb.2025.100305

Lorenzo Malfer , Andrea Giorgi , Tina Liu , Capucine Piat , Ali Zare Dehnavi , Owen A. Ross , Zhiyv Niu , Eduardo E. Benarroch , James H. Bower , Rodolfo Savica

Objective

To report a retrospective clinical series of four patients diagnosed with early-onset Parkinson’s disease (EOPD) carrying heterozygous variants of uncertain significance (VUSs) in the FBXO7 gene.

Background

FBXO7 encodes an F-box-domain-containing protein involved in the mitophagy process, and mutations in this gene have been associated with PARK15, an atypical form of Parkinson’s disease (PD) with an autosomal recessive inheritance pattern.

Methods

Patients were identified using the Mayo Clinic Data Explorer. All the cases with a heterozygous FBXO7 variant and a clinical diagnosis of EOPD evaluated at Mayo Clinic between 2017 and 2024 were included. Clinical features, genetic testing, imaging, and treatment data were obtained retrospectively from medical records review. Motor symptoms were assessed using the UPDRS part-III score, and non-motor symptoms were assessed using the NMSS score.

Results

Four patients met the inclusion criteria. All exhibited a non-motor predominant phenotype, with significant autonomic features either as an early presentation or as a preeminent component. These features manifested with a broad spectrum of symptoms including sialorrhea, constipation, urinary urgency, orthostatic intolerance and altered heat sensitivity. DaTscan imaging, available in three of the four cases, was consistent with a PD diagnosis. All patients responded well to levodopa treatment, showing substantial improvement in both motor and non-motor symptoms (NMSS).

Conclusion

FBXO7 may play a role as a phenotypic gene modifier and contribute to the development of EOPD characterized by levodopa-responsive, non-motor-predominant features in heterozygous variant carriers. Specifically, these features appear to be associated with central autonomic dysfunction, particularly affecting the parasympathetic vagal nuclei.

目的回顾性分析4例早发性帕金森病（EOPD）患者的FBXO7基因杂合不确定意义变异（VUSs）。fbxo7编码一种参与有丝分裂过程的含f -box结构域蛋白，该基因的突变与PARK15有关，PARK15是一种非典型帕金森病（PD），具有常染色体隐性遗传模式。方法使用Mayo Clinic Data Explorer对患者进行识别。纳入2017年至2024年间在梅奥诊所评估的所有杂合FBXO7变异并临床诊断为EOPD的病例。临床特征、基因检测、影像学和治疗资料回顾性地从医疗记录中获得。运动症状采用UPDRS part-III评分进行评估，非运动症状采用NMSS评分进行评估。结果4例患者符合纳入标准。所有表现出非运动显性表型，具有显著的自主神经特征，无论是作为早期表现还是作为突出组成部分。这些特征表现为广泛的症状，包括唾液、便秘、尿急、体位不耐受和热敏性改变。4例中有3例的DaTscan成像与PD诊断一致。所有患者对左旋多巴治疗反应良好，运动和非运动症状（NMSS）均有显著改善。结论fbxo7可能是一种表型基因修饰因子，参与了杂合变异携带者发生以左旋多巴反应、非运动显性为特征的EOPD。具体来说，这些特征似乎与中枢自主神经功能障碍有关，特别是影响副交感迷走神经核。

{"title":"Heterozygous FBXO7 as potential genetic modifiers in early-onset Parkinson’s disease with levodopa responsive non-motor features","authors":"Lorenzo Malfer , Andrea Giorgi , Tina Liu , Capucine Piat , Ali Zare Dehnavi , Owen A. Ross , Zhiyv Niu , Eduardo E. Benarroch , James H. Bower , Rodolfo Savica","doi":"10.1016/j.dscb.2025.100305","DOIUrl":"10.1016/j.dscb.2025.100305","url":null,"abstract":"<div><h3>Objective</h3><div>To report a retrospective clinical series of four patients diagnosed with early-onset Parkinson’s disease (EOPD) carrying heterozygous variants of uncertain significance (VUSs) in the <em>FBXO</em>7 gene.</div></div><div><h3>Background</h3><div><em>FBXO</em>7 encodes an F-box-domain-containing protein involved in the mitophagy process, and mutations in this gene have been associated with PARK15, an atypical form of Parkinson’s disease (PD) with an autosomal recessive inheritance pattern.</div></div><div><h3>Methods</h3><div>Patients were identified using the <em>Mayo Clinic Data Explorer</em>. All the cases with a heterozygous <em>FBXO</em>7 variant and a clinical diagnosis of EOPD evaluated at Mayo Clinic between 2017 and 2024 were included. Clinical features, genetic testing, imaging, and treatment data were obtained retrospectively from medical records review. Motor symptoms were assessed using the UPDRS part-III score, and non-motor symptoms were assessed using the NMSS score.</div></div><div><h3>Results</h3><div>Four patients met the inclusion criteria. All exhibited a non-motor predominant phenotype, with significant autonomic features either as an early presentation or as a preeminent component. These features manifested with a broad spectrum of symptoms including sialorrhea, constipation, urinary urgency, orthostatic intolerance and altered heat sensitivity. DaTscan imaging, available in three of the four cases, was consistent with a PD diagnosis. All patients responded well to levodopa treatment, showing substantial improvement in both motor and non-motor symptoms (NMSS).</div></div><div><h3>Conclusion</h3><div><em>FBXO</em>7 may play a role as a phenotypic gene modifier and contribute to the development of EOPD characterized by levodopa-responsive, non-motor-predominant features in heterozygous variant carriers. Specifically, these features appear to be associated with central autonomic dysfunction, particularly affecting the parasympathetic vagal nuclei.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"21 ","pages":"Article 100305"},"PeriodicalIF":0.0,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spinal cord compression secondary to spinal extradural myeloid sarcoma in acute myeloid leukaemia: A case report and literature review 急性髓性白血病中脊髓硬膜外髓系肉瘤继发的脊髓压迫：1例报告并文献复习

Brain disorders (Amsterdam, Netherlands)

Pub Date : 2025-12-01 DOI: 10.1016/j.dscb.2025.100303

Prakash Palave , Nitin Naikwade , Ashvini Mahamuni , Egemen Gok , Kivanc Yangi , Ismail Bozkurt , Bipin Chaurasia

Introduction

Myeloid sarcoma (MS) is a rare pathology that includes immature myeloid progenitor cells and is an infrequent form of acute myeloid leukemia (AML). It may occur de novo or be associated with other myeloproliferative disorders. Spinal involvement is rare but has the potential to result in catastrophic neurological consequences if not diagnosed promptly. Here, we present a young patient initially diagnosed with myelofibrosis whose disease evolved to AML and then thoracic extradural MS and acute spinal cord compression.

Case presentation

A 27-year-old woman came with paraparesis and worsening upper back pain. MRI demonstrated an extradural mass in the thoracic spine, causing compression of the spinal cord. Urgent decompressive laminectomy and subtotal resection were performed. Histopathology was positive for myeloid precursor cell sheets with myeloperoxidase, CD68, and CD43, which diagnosed MS. Postoperative course was uneventful, and adjuvant chemotherapy was initiated in her.

Conclusion

Thoracic spinal MS represents a diagnostic and therapeutic emergency that may arise during leukemic transformation of chronic myeloproliferative neoplasms such as myelofibrosis. Early radiologic evaluation, tissue diagnosis, and immediate surgical decompression are crucial for achieving optimal neurological outcomes. This case highlights maintaining a high suspicion of spinal MS in patients with evolving myeloid diseases since early multimodal treatment can avoid permanent neurological damage and may improve survival.

髓系肉瘤（MS）是一种罕见的病理，包括未成熟的髓系祖细胞，是急性髓系白血病（AML）的一种罕见形式。它可能从头发生或与其他骨髓增生性疾病有关。脊髓受累是罕见的，但有可能导致灾难性的神经后果，如果不及时诊断。在这里，我们报告了一位最初诊断为骨髓纤维化的年轻患者，其疾病发展为急性髓性白血病，然后发展为胸椎硬膜外MS和急性脊髓压迫。病例介绍：一名27岁女性患者出现麻痹和上背部疼痛加重。MRI显示胸椎硬膜外肿块，导致脊髓受压。行紧急椎板减压切除术和次全切除术。组织病理学检查髓系前细胞片伴髓过氧化物酶、CD68和CD43阳性，诊断为多发性硬化症。术后过程顺利，患者开始辅助化疗。结论胸椎多发性硬化是慢性骨髓增生性肿瘤（如骨髓纤维化）白血病转化过程中可能出现的诊断和治疗急症。早期放射学评估、组织诊断和立即手术减压对于获得最佳神经预后至关重要。该病例强调了对进展中的髓系疾病患者保持高度怀疑，因为早期多模式治疗可以避免永久性神经损伤，并可能提高生存率。

{"title":"Spinal cord compression secondary to spinal extradural myeloid sarcoma in acute myeloid leukaemia: A case report and literature review","authors":"Prakash Palave , Nitin Naikwade , Ashvini Mahamuni , Egemen Gok , Kivanc Yangi , Ismail Bozkurt , Bipin Chaurasia","doi":"10.1016/j.dscb.2025.100303","DOIUrl":"10.1016/j.dscb.2025.100303","url":null,"abstract":"<div><h3>Introduction</h3><div>Myeloid sarcoma (MS) is a rare pathology that includes immature myeloid progenitor cells and is an infrequent form of acute myeloid leukemia (AML). It may occur de novo or be associated with other myeloproliferative disorders. Spinal involvement is rare but has the potential to result in catastrophic neurological consequences if not diagnosed promptly. Here, we present a young patient initially diagnosed with myelofibrosis whose disease evolved to AML and then thoracic extradural MS and acute spinal cord compression.</div></div><div><h3>Case presentation</h3><div>A 27-year-old woman came with paraparesis and worsening upper back pain. MRI demonstrated an extradural mass in the thoracic spine, causing compression of the spinal cord. Urgent decompressive laminectomy and subtotal resection were performed. Histopathology was positive for myeloid precursor cell sheets with myeloperoxidase, CD68, and CD43, which diagnosed MS. Postoperative course was uneventful, and adjuvant chemotherapy was initiated in her.</div></div><div><h3>Conclusion</h3><div>Thoracic spinal MS represents a diagnostic and therapeutic emergency that may arise during leukemic transformation of chronic myeloproliferative neoplasms such as myelofibrosis. Early radiologic evaluation, tissue diagnosis, and immediate surgical decompression are crucial for achieving optimal neurological outcomes. This case highlights maintaining a high suspicion of spinal MS in patients with evolving myeloid diseases since early multimodal treatment can avoid permanent neurological damage and may improve survival.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"21 ","pages":"Article 100303"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145685136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CRISPR-Cas9 gene editing in neuropsychiatric disorders: Challenges and promising avenues CRISPR-Cas9基因编辑在神经精神疾病中的应用：挑战和有希望的途径

Brain disorders (Amsterdam, Netherlands)

Pub Date : 2025-12-01 DOI: 10.1016/j.dscb.2025.100304

Nicholas Aderinto , Gbolahan Olatunji , Emmanuel Kokori , Ismaila Ajayi Yusuf , Moradeyo Abdulrahmon , Emmanuel Egbunu , Temiloluwa Oluwakorede Adefusi , Opabode Mountain Obasanjo , John Aboje , Ikponmwosa Jude Ogieuhi , Oluwatobiloba Oluwatomisin Apampa

This review explores the transformative potential of CRISPR-Cas9 gene editing technology in neuropsychiatric disorders. Neuropsychiatric conditions, marked by genetic and environmental factors, pose significant global health challenges. Traditional treatments often address symptoms, leaving underlying genetic anomalies untouched. CRISPR-Cas9, renowned for its unparalleled precision, presents an opportunity to unravel the complex genetic architecture contributing to disorders like schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). The review explores specific applications of CRISPR technology, showcasing studies targeting genes associated with these disorders and exploring alternative splicing mechanisms, microexon involvement, and the role of master regulators. Despite the revolutionary promise of CRISPR, challenges and limitations must be addressed. Technical challenges, such as achieving allele-specific modifications and minimising off-target effects, require ongoing research. Safety concerns, ethical considerations regarding germline editing, and potential unintended consequences emphasise the need for cautious implementation. Ongoing research aims to refine CRISPR techniques, enhance precision, and overcome current challenges. Collaboration between scientists, ethicists, clinicians, and patient advocacy groups is pivotal for responsible implementation. Identifying specific genes or pathways for therapeutic targeting holds promise for personalised and precise interventions. This review envisions a future where the responsible integration of CRISPR technology transforms the understanding and treatment of neuropsychiatric disorders, providing a multidimensional approach that balances scientific innovation with ethical considerations.

这篇综述探讨了CRISPR-Cas9基因编辑技术在神经精神疾病中的变革潜力。以遗传和环境因素为特征的神经精神疾病构成了重大的全球健康挑战。传统的治疗方法通常只解决症状，而不触及潜在的基因异常。CRISPR-Cas9以其无与伦比的精确度而闻名，它提供了一个机会来揭示导致精神分裂症、双相情感障碍、重度抑郁症、自闭症谱系障碍（ASD）和注意力缺陷/多动障碍（ADHD）等疾病的复杂遗传结构。这篇综述探讨了CRISPR技术的具体应用，展示了针对与这些疾病相关的基因的研究，并探索了其他剪接机制、微外显子参与和主调控因子的作用。尽管CRISPR具有革命性的前景，但挑战和局限性必须得到解决。技术挑战，如实现等位基因特异性修饰和最小化脱靶效应，需要持续研究。安全问题、有关生殖细胞编辑的伦理考虑以及潜在的意外后果都强调了谨慎实施的必要性。正在进行的研究旨在改进CRISPR技术，提高精度，并克服当前的挑战。科学家、伦理学家、临床医生和患者倡导团体之间的合作对于负责任的实施至关重要。确定治疗靶向的特定基因或途径有望实现个性化和精确的干预。这篇综述展望了一个未来，CRISPR技术的负责任整合改变了对神经精神疾病的理解和治疗，提供了一种平衡科学创新与伦理考虑的多维方法。

{"title":"CRISPR-Cas9 gene editing in neuropsychiatric disorders: Challenges and promising avenues","authors":"Nicholas Aderinto , Gbolahan Olatunji , Emmanuel Kokori , Ismaila Ajayi Yusuf , Moradeyo Abdulrahmon , Emmanuel Egbunu , Temiloluwa Oluwakorede Adefusi , Opabode Mountain Obasanjo , John Aboje , Ikponmwosa Jude Ogieuhi , Oluwatobiloba Oluwatomisin Apampa","doi":"10.1016/j.dscb.2025.100304","DOIUrl":"10.1016/j.dscb.2025.100304","url":null,"abstract":"<div><div>This review explores the transformative potential of CRISPR-Cas9 gene editing technology in neuropsychiatric disorders. Neuropsychiatric conditions, marked by genetic and environmental factors, pose significant global health challenges. Traditional treatments often address symptoms, leaving underlying genetic anomalies untouched. CRISPR-Cas9, renowned for its unparalleled precision, presents an opportunity to unravel the complex genetic architecture contributing to disorders like schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). The review explores specific applications of CRISPR technology, showcasing studies targeting genes associated with these disorders and exploring alternative splicing mechanisms, microexon involvement, and the role of master regulators. Despite the revolutionary promise of CRISPR, challenges and limitations must be addressed. Technical challenges, such as achieving allele-specific modifications and minimising off-target effects, require ongoing research. Safety concerns, ethical considerations regarding germline editing, and potential unintended consequences emphasise the need for cautious implementation. Ongoing research aims to refine CRISPR techniques, enhance precision, and overcome current challenges. Collaboration between scientists, ethicists, clinicians, and patient advocacy groups is pivotal for responsible implementation. Identifying specific genes or pathways for therapeutic targeting holds promise for personalised and precise interventions. This review envisions a future where the responsible integration of CRISPR technology transforms the understanding and treatment of neuropsychiatric disorders, providing a multidimensional approach that balances scientific innovation with ethical considerations.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"21 ","pages":"Article 100304"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145737014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic characterisation of ATXN2 in Australian amyotrophic lateral sclerosis 澳大利亚肌萎缩性侧索硬化症患者ATXN2基因的遗传特征

Brain disorders (Amsterdam, Netherlands)

Pub Date : 2025-11-21 DOI: 10.1016/j.dscb.2025.100301

Sharlynn S.L. Wu , Emily P. McCann , Sandrine Chan Moi Fat , Natalie Grima , Lyndal Henden , Liam G. Fearnley , Patrick Chiu , Kelly L. Williams , Dominic B. Rowe , Garth A. Nicholson , Matthew C. Kiernan , Ian P. Blair , Shu Yang , Jennifer A. Fifita

Large expansions of a trinucleotide repeat encoding a polyglutamine tract in ATXN2 are a known cause of spinocerebellar ataxia 2, and intermediate length expansions in this gene have been reported as a risk factor and phenotypic modifier for amyotrophic lateral sclerosis (ALS). Here we present a comprehensive analysis of the genetic contribution of ATXN2 to ALS within an Australian cohort of 821 ALS cases. We performed association for both disease status and ALS clinical phenotypes, with careful consideration of repeat size and composition, and the presence of additional genetic variants within ATXN2. The largest expansion detected among cases was 33 repeat units, and 32 in controls, while the most common repeat size was 22. Intermediate expansions of 30–33 repeats were significantly more common in ALS cases (1.95 %) than controls (0.42 %, p = 0.02543), and we found this association to be primarily driven by familial rather than sporadic ALS cases (frequency of 4.30 % vs 1.65 % and p = 0.00790 vs 0.05799). All intermediate expansions in ALS cases harboured at least one CAA synonymous interruption. No association was found between intermediate expansions and site or age of disease onset, or disease duration. However, larger intermediate repeat sizes of 32–33 repeats were associated with a shorter disease duration (median=27.35 months) when compared with cases who harboured an ATXN2 repeat size in the normal range (median=35.47 months, p = 1.89 × 10^–6). These findings indicate that intermediately expanded ATXN2 repeats may play an important gene modifier role in Australian ALS cohorts.

编码ATXN2中聚谷氨酰胺束的三核苷酸重复序列的大量扩增是脊髓小脑性共济失调2的已知原因，该基因的中等长度扩增已被报道为肌萎缩性侧索硬化症（ALS）的危险因素和表型修饰因子。在此，我们对澳大利亚821例ALS病例队列中ATXN2基因对ALS的遗传贡献进行了全面分析。我们对疾病状态和ALS临床表型进行了关联，仔细考虑了重复序列的大小和组成，以及ATXN2中存在的其他遗传变异。病例中检测到的最大扩增数为33个重复单位，对照组中为32个重复单位，而最常见的重复单位为22个。30-33重复的中间扩增在ALS病例中（1.95%）比对照组（0.42%,p = 0.02543）更为常见，我们发现这种关联主要是由家族性而不是散发性ALS病例驱动的（频率为4.30% vs 1.65%, p = 0.00790 vs 0.05799）。ALS病例的所有中间扩张都至少有一次CAA同义中断。没有发现中间扩张与发病部位、发病年龄或病程相关。然而，与ATXN2重复序列在正常范围内的病例（中位数=35.47个月，p = 1.89 × 10-6）相比，32-33重复序列较大的中间重复序列与较短的疾病持续时间（中位数=27.35个月）相关。这些发现表明，中等扩展的ATXN2重复序列可能在澳大利亚ALS队列中发挥重要的基因修饰作用。

{"title":"Genetic characterisation of ATXN2 in Australian amyotrophic lateral sclerosis","authors":"Sharlynn S.L. Wu , Emily P. McCann , Sandrine Chan Moi Fat , Natalie Grima , Lyndal Henden , Liam G. Fearnley , Patrick Chiu , Kelly L. Williams , Dominic B. Rowe , Garth A. Nicholson , Matthew C. Kiernan , Ian P. Blair , Shu Yang , Jennifer A. Fifita","doi":"10.1016/j.dscb.2025.100301","DOIUrl":"10.1016/j.dscb.2025.100301","url":null,"abstract":"<div><div>Large expansions of a trinucleotide repeat encoding a polyglutamine tract in <em>ATXN2</em> are a known cause of spinocerebellar ataxia 2, and intermediate length expansions in this gene have been reported as a risk factor and phenotypic modifier for amyotrophic lateral sclerosis (ALS). Here we present a comprehensive analysis of the genetic contribution of <em>ATXN2</em> to ALS within an Australian cohort of 821 ALS cases. We performed association for both disease status and ALS clinical phenotypes, with careful consideration of repeat size and composition, and the presence of additional genetic variants within <em>ATXN2</em>. The largest expansion detected among cases was 33 repeat units, and 32 in controls, while the most common repeat size was 22. Intermediate expansions of 30–33 repeats were significantly more common in ALS cases (1.95 %) than controls (0.42 %, <em>p</em> = 0.02543), and we found this association to be primarily driven by familial rather than sporadic ALS cases (frequency of 4.30 % vs 1.65 % and <em>p</em> = 0.00790 vs 0.05799). All intermediate expansions in ALS cases harboured at least one CAA synonymous interruption. No association was found between intermediate expansions and site or age of disease onset, or disease duration. However, larger intermediate repeat sizes of 32–33 repeats were associated with a shorter disease duration (median=27.35 months) when compared with cases who harboured an <em>ATXN2</em> repeat size in the normal range (median=35.47 months, <em>p</em> = 1.89 × 10<sup>–6</sup>). These findings indicate that intermediately expanded <em>ATXN2</em> repeats may play an important gene modifier role in Australian ALS cohorts.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"21 ","pages":"Article 100301"},"PeriodicalIF":0.0,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pattern of central nervous system related diseases and deaths: a 10-year study in a Ghanaian tertiary care facility 中枢神经系统相关疾病和死亡模式：加纳三级保健机构的10年研究

Brain disorders (Amsterdam, Netherlands)

Pub Date : 2025-11-20 DOI: 10.1016/j.dscb.2025.100300

Ansumana Bockarie , Richael Odarkor Mills , Kofi Ulzen-Appiah , Albert Akpalu , Cecelia Smith-Togobo , Bernice Akua Frimpong , Ishmael Obeng-Ofosu , George Nkrumah Osei , Josephine Anterkyi Bentil , Patrick Adu , David Larbi Simpong

Background

Neurological disorders can have a significant impact on mortality rates. Despite the prevalence of central nervous system related diseases (CNSDs) in Ghana, limited information exists regarding their contribution to death. This study sought to characterize death patterns of patients with CNSDs in a Ghanaian tertiary hospital.

Methods

A cross-sectional study was conducted utilizing archival mortality data from 2010 to 2019, retrieved from the mortuary logbook of the Cape Coast Teaching Hospital. Variables such as age, sex, and cause of death were expressed as proportions. Line graphs were used to visualize temporal trends in death cases, while bar graphs were used to illustrate the distribution of various conditions constituting CNSDs. Binary logistic regression was applied to identify associations between demographic factors and cerebrovascular accident (CVA) associated deaths.

Results

A total of 9356 deaths were recorded between 2010 and 2019 of which CNSDs contributed 454 (4.9 %). The majority of deaths resulting from CNSDs were contributed by cerebrovascular accidents (CVAs) 93 % (424/454). Within the study area, more females (51.4 %) died from CVAs than males (49.6 %). Logistic regression analysis further revealed that individuals aged above 60 years had the highest odds of dying from CVAs (OR 48.2, CI 10.9–212.7, p < 0.001) followed by persons aged 40–60 years (OR = 40.4, CI 8.1–200.7, p < 0.001) compared to those below 40 years old.

Conclusion

Cerebrovascular accident was the leading cause of death resulting from CNSDs in this study, particularly among individuals aged 40 and above. To address this burden, regular screenings and public education is recommended.

背景：神经系统疾病对死亡率有重大影响。尽管中枢神经系统相关疾病（cnsd）在加纳流行，但关于其导致死亡的信息有限。本研究旨在描述加纳一家三级医院cnsd患者的死亡模式。方法利用2010年至2019年海岸角教学医院太平间日志中的死亡率档案数据进行横断面研究。年龄、性别和死因等变量以比例表示。线形图用于可视化死亡病例的时间趋势，而柱状图用于说明构成cnsd的各种条件的分布。采用二元logistic回归来确定人口统计学因素与脑血管事故（CVA）相关死亡之间的关联。结果2010 - 2019年共记录死亡病例9356例，其中CNSDs占454例（4.9%）。cnsd导致的大多数死亡是脑血管意外（cva）造成的，占93%（424/454）。在研究区域内，女性（51.4%）比男性（49.6%）死于CVAs。Logistic回归分析进一步显示，60岁以上人群死于心血管疾病的几率最高（OR为48.2，CI为10.9-212.7,p < 0.001），其次是40 - 60岁人群（OR = 40.4， CI为8.1-200.7,p < 0.001）。结论脑血管意外是本研究中cnsd死亡的主要原因，尤其是40岁及以上人群。为解决这一负担，建议进行定期筛查和公众教育。

{"title":"Pattern of central nervous system related diseases and deaths: a 10-year study in a Ghanaian tertiary care facility","authors":"Ansumana Bockarie , Richael Odarkor Mills , Kofi Ulzen-Appiah , Albert Akpalu , Cecelia Smith-Togobo , Bernice Akua Frimpong , Ishmael Obeng-Ofosu , George Nkrumah Osei , Josephine Anterkyi Bentil , Patrick Adu , David Larbi Simpong","doi":"10.1016/j.dscb.2025.100300","DOIUrl":"10.1016/j.dscb.2025.100300","url":null,"abstract":"<div><h3>Background</h3><div>Neurological disorders can have a significant impact on mortality rates. Despite the prevalence of central nervous system related diseases (CNSDs) in Ghana, limited information exists regarding their contribution to death. This study sought to characterize death patterns of patients with CNSDs in a Ghanaian tertiary hospital.</div></div><div><h3>Methods</h3><div>A cross-sectional study was conducted utilizing archival mortality data from 2010 to 2019, retrieved from the mortuary logbook of the Cape Coast Teaching Hospital. Variables such as age, sex, and cause of death were expressed as proportions. Line graphs were used to visualize temporal trends in death cases, while bar graphs were used to illustrate the distribution of various conditions constituting CNSDs. Binary logistic regression was applied to identify associations between demographic factors and cerebrovascular accident (CVA) associated deaths.</div></div><div><h3>Results</h3><div>A total of 9356 deaths were recorded between 2010 and 2019 of which CNSDs contributed 454 (4.9 %). The majority of deaths resulting from CNSDs were contributed by cerebrovascular accidents (CVAs) 93 % (424/454). Within the study area, more females (51.4 %) died from CVAs than males (49.6 %). Logistic regression analysis further revealed that individuals aged above 60 years had the highest odds of dying from CVAs (OR 48.2, CI 10.9–212.7, <em>p</em> < 0.001) followed by persons aged 40–60 years (OR = 40.4, CI 8.1–200.7, <em>p</em> < 0.001) compared to those below 40 years old.</div></div><div><h3>Conclusion</h3><div>Cerebrovascular accident was the leading cause of death resulting from CNSDs in this study, particularly among individuals aged 40 and above. To address this burden, regular screenings and public education is recommended.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"21 ","pages":"Article 100300"},"PeriodicalIF":0.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association between tuberculosis and Guillain–Barré syndrome: a systematic review 结核病与格林-巴- <s:1>综合征之间的关系：一项系统综述

Brain disorders (Amsterdam, Netherlands)

Pub Date : 2025-11-19 DOI: 10.1016/j.dscb.2025.100299

Chowdhury Adnan Sami , Refaya Tasnim , Husna Rafsana , Joydip Chowdhury , Samiha Jabin Susmita , Anika Tabassum , Mohammad Ferdous Ur Rahaman , Shohael Mahmud Arafat

Background

Tuberculosis (TB) is highly prevalent in low- and middle-income countries and may present with diverse neurological complications. Its possible association with Guillain–Barré Syndrome (GBS) is rarely reported, but recognition is important because it poses diagnostic challenges and has impotant implications for management in endemic settings.

Methods

We systematically reviewed literature from PubMed, Scopus, Google Scholar, Web of Science, and Semantic Scholar (to December 2024) following PRISMA guidelines.

Results

We identified 29 cases of TB-associated GBS, with the highest number reported from India (44.8 %). Pulmonary TB was the predominant form (62.1 %), with acute inflammatory demyelinating polyneuropathy (AIDP, 20.7 %) most common. A majority (60.7 %) developed GBS within two weeks of TB symptom onset. Clinical outcomes included complete recovery in 58.6 % and mortality in 17.2 %.

Conclusion

Current evidence is limited to case reports and small series, suggesting TB may potentially act as a trigger for GBS, but causality remains unproven. Further controlled studies are needed to clarify mechanisms and outcomes.

结核病（TB）在低收入和中等收入国家高度流行，并可能伴有多种神经系统并发症。它可能与格林-巴- 综合征（GBS）有关的报道很少，但认识到这一点很重要，因为它带来了诊断挑战，并对流行环境中的管理具有重要意义。方法我们按照PRISMA指南系统地回顾了PubMed、Scopus、b谷歌Scholar、Web of Science和Semantic Scholar（截至2024年12月）的文献。结果共发现29例结核相关GBS病例，其中印度报告的病例最多（44.8%）。肺结核是主要形式（62.1%），急性炎症性脱髓鞘性多神经病变（AIDP, 20.7%）最常见。大多数（60.7%）在结核症状出现的两周内发展为GBS。临床结果包括58.6%的患者完全康复，17.2%的患者死亡。结论：目前的证据仅限于病例报告和小系列，表明结核病可能是GBS的潜在触发因素，但因果关系尚未得到证实。需要进一步的对照研究来阐明其机制和结果。

{"title":"Association between tuberculosis and Guillain–Barré syndrome: a systematic review","authors":"Chowdhury Adnan Sami , Refaya Tasnim , Husna Rafsana , Joydip Chowdhury , Samiha Jabin Susmita , Anika Tabassum , Mohammad Ferdous Ur Rahaman , Shohael Mahmud Arafat","doi":"10.1016/j.dscb.2025.100299","DOIUrl":"10.1016/j.dscb.2025.100299","url":null,"abstract":"<div><h3>Background</h3><div>Tuberculosis (TB) is highly prevalent in low- and middle-income countries and may present with diverse neurological complications. Its possible association with Guillain–Barré Syndrome (GBS) is rarely reported, but recognition is important because it poses diagnostic challenges and has impotant implications for management in endemic settings.</div></div><div><h3>Methods</h3><div>We systematically reviewed literature from PubMed, Scopus, Google Scholar, Web of Science, and Semantic Scholar (to December 2024) following PRISMA guidelines.</div></div><div><h3>Results</h3><div>We identified 29 cases of TB-associated GBS, with the highest number reported from India (44.8 %). Pulmonary TB was the predominant form (62.1 %), with acute inflammatory demyelinating polyneuropathy (AIDP, 20.7 %) most common. A majority (60.7 %) developed GBS within two weeks of TB symptom onset. Clinical outcomes included complete recovery in 58.6 % and mortality in 17.2 %.</div></div><div><h3>Conclusion</h3><div>Current evidence is limited to case reports and small series, suggesting TB may potentially act as a trigger for GBS, but causality remains unproven. Further controlled studies are needed to clarify mechanisms and outcomes.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"21 ","pages":"Article 100299"},"PeriodicalIF":0.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Early diagnosis of Parkinson's disease pathogenesis using biofluidic biomarkers with a focus on α-synuclein 以α-突触核蛋白为重点的生物流体标志物早期诊断帕金森病发病机制

Brain disorders (Amsterdam, Netherlands)

Pub Date : 2025-11-15 DOI: 10.1016/j.dscb.2025.100297

N. Aghakhani , A. Arzoo , B. Dorflinger , S.Z. Athari , G. Mohaddes

Parkinson's disease (PD) is the second most frequent neurodegenerative disease of the nervous system. The pathogenesis of PD is not yet fully understood; however, some investigations suggest that neuroinflammation, genetic mutations, and mitochondrial dysfunction may underlie the disease mechanism. Though the manifestations of dopaminergic neuronal degeneration and Lewy body presentation are rigorously documented, the interaction of these factors that presumably lead to such manifestations is far less understood. This article aims to delineate specific diagnostic correlates or biomarkers that have previously shown promise as potential avenues for physician consideration or impetuses for fruitful future research. Potentially, integrating diagnostic biofluid biomarkers, clinical history, and imaging techniques can significantly enhance the accuracy of PD diagnosis. Progress has been made in identifying biomarkers in biofluids for PD. Oxidative stress, inflammatory markers, and alpha-synuclein (α-syn) have been briefly discussed in the existing literature and warrant further investigation. The evaluation of combined biomarkers, along with α-syn, may improve diagnostic accuracy in diagnosing PD, which could be achieved by focusing on large-scale clinical assessments of biofluids.

Significance Statement

Early diagnosis of Parkinson's Disease using biofluidic biomarkers is crucial for improving patient outcomes by enabling earlier detection and intervention, reducing misdiagnosis.

帕金森病（PD）是第二常见的神经系统退行性疾病。PD的发病机制尚不完全清楚；然而，一些研究表明，神经炎症、基因突变和线粒体功能障碍可能是疾病机制的基础。虽然多巴胺能神经元变性和路易体表现的表现被严格记录，但这些因素之间的相互作用可能导致这些表现的理解还远远不够。这篇文章的目的是描述特定的诊断相关物或生物标记物，这些生物标记物之前已经显示出作为医生考虑的潜在途径或推动未来富有成效的研究的希望。潜在地，整合诊断生物流体生物标志物、临床病史和成像技术可以显著提高PD诊断的准确性。在生物液体中识别PD的生物标志物方面取得了进展。氧化应激、炎症标志物和α-突触核蛋白（α-syn）已在现有文献中进行了简要讨论，值得进一步研究。联合评价生物标志物，以及α-syn，可能会提高PD诊断的准确性，这可以通过专注于大规模的生物流体临床评估来实现。使用生物流体生物标志物进行帕金森病的早期诊断对于改善患者预后至关重要，因为它可以实现早期发现和干预，减少误诊。

{"title":"Early diagnosis of Parkinson's disease pathogenesis using biofluidic biomarkers with a focus on α-synuclein","authors":"N. Aghakhani , A. Arzoo , B. Dorflinger , S.Z. Athari , G. Mohaddes","doi":"10.1016/j.dscb.2025.100297","DOIUrl":"10.1016/j.dscb.2025.100297","url":null,"abstract":"<div><div>Parkinson's disease (PD) is the second most frequent neurodegenerative disease of the nervous system. The pathogenesis of PD is not yet fully understood; however, some investigations suggest that neuroinflammation, genetic mutations, and mitochondrial dysfunction may underlie the disease mechanism. Though the manifestations of dopaminergic neuronal degeneration and Lewy body presentation are rigorously documented, the interaction of these factors that presumably lead to such manifestations is far less understood. This article aims to delineate specific diagnostic correlates or biomarkers that have previously shown promise as potential avenues for physician consideration or impetuses for fruitful future research. Potentially, integrating diagnostic biofluid biomarkers, clinical history, and imaging techniques can significantly enhance the accuracy of PD diagnosis. Progress has been made in identifying biomarkers in biofluids for PD. Oxidative stress, inflammatory markers, and alpha-synuclein (α-syn) have been briefly discussed in the existing literature and warrant further investigation. The evaluation of combined biomarkers, along with α-syn, may improve diagnostic accuracy in diagnosing PD, which could be achieved by focusing on large-scale clinical assessments of biofluids.</div></div><div><h3>Significance Statement</h3><div>Early diagnosis of Parkinson's Disease using biofluidic biomarkers is crucial for improving patient outcomes by enabling earlier detection and intervention, reducing misdiagnosis.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"20 ","pages":"Article 100297"},"PeriodicalIF":0.0,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145579290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The neurobiological and behavioral impacts of adulterants in drugs of abuse 药物滥用中掺杂物对神经生物学和行为的影响

Brain disorders (Amsterdam, Netherlands)

Pub Date : 2025-11-05 DOI: 10.1016/j.dscb.2025.100296

Mason Hochstetler , Anastasia Dodge , Swarup Mitra

This review examines how the presence of adulterants in drugs of abuse can disrupt the neurobiological, behavioral, and physiological processes associated with substance use disorder (SUD). Adulteration, the practice of adding foreign substances to illicit drugs to increase potency or profits, has dangerous and often life-threatening consequences for users. These pharmacologically active ingredients interact with neurobiological pathways in both brain and body, altering the addictive properties of the primary substance and complicating treatment efforts. This includes changes in neurotransmitter activity and alterations in brain circuitry, which increase the likelihood of continued substance use and relapse. In turn, behavioral outcomes are significantly affected, with individuals often experiencing cravings, impaired decision-making, precipitated overdose, and stronger compulsive drug-seeking behaviors. This review primarily highlights the non-abused adulterants and how pairing them with drugs of abuse can alter wide-ranging brain mechanisms. The analysis focuses primarily on preclinical studies while drawing connections to relevant clinical data when available to offer a comprehensive understanding of the impact of SUD on behavioral and physiological outcomes.

本文综述了滥用药物中掺杂物的存在如何破坏与物质使用障碍（SUD）相关的神经生物学、行为和生理过程。掺假，即在非法药物中加入外来物质以提高效力或利润的做法，对使用者具有危险，往往危及生命的后果。这些药物活性成分与大脑和身体的神经生物学途径相互作用，改变主要物质的成瘾特性，使治疗工作复杂化。这包括神经递质活动的变化和脑回路的改变，这增加了继续使用药物和复发的可能性。反过来，行为结果受到显著影响，个体经常经历渴望，决策受损，沉淀过量，以及更强的强迫性药物寻求行为。这篇综述主要强调了未滥用的掺假物以及如何将它们与滥用药物配对可以改变广泛的大脑机制。该分析主要侧重于临床前研究，同时在可用的情况下与相关临床数据联系起来，以全面了解SUD对行为和生理结果的影响。

{"title":"The neurobiological and behavioral impacts of adulterants in drugs of abuse","authors":"Mason Hochstetler , Anastasia Dodge , Swarup Mitra","doi":"10.1016/j.dscb.2025.100296","DOIUrl":"10.1016/j.dscb.2025.100296","url":null,"abstract":"<div><div>This review examines how the presence of adulterants in drugs of abuse can disrupt the neurobiological, behavioral, and physiological processes associated with substance use disorder (SUD). Adulteration, the practice of adding foreign substances to illicit drugs to increase potency or profits, has dangerous and often life-threatening consequences for users. These pharmacologically active ingredients interact with neurobiological pathways in both brain and body, altering the addictive properties of the primary substance and complicating treatment efforts. This includes changes in neurotransmitter activity and alterations in brain circuitry, which increase the likelihood of continued substance use and relapse. In turn, behavioral outcomes are significantly affected, with individuals often experiencing cravings, impaired decision-making, precipitated overdose, and stronger compulsive drug-seeking behaviors. This review primarily highlights the non-abused adulterants and how pairing them with drugs of abuse can alter wide-ranging brain mechanisms. The analysis focuses primarily on preclinical studies while drawing connections to relevant clinical data when available to offer a comprehensive understanding of the impact of SUD on behavioral and physiological outcomes.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"20 ","pages":"Article 100296"},"PeriodicalIF":0.0,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145528025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0