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Functional connectivity changes in males with nicotine addiction: A triple network model study. 尼古丁成瘾男性的功能连接变化:三重网络模型研究
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-02 DOI: 10.1016/j.pnpbp.2024.111187
Jieping Sun, Huiyu Huang, Jinghan Dang, Mengzhe Zhang, Xiaoyu Niu, Qiuying Tao, Yimeng Kang, Longyao Ma, Bohui Mei, Weijian Wang, Shaoqiang Han, Jingliang Cheng, Yong Zhang

Background: Nicotine addiction (NA) is recognized as a significant neurobehavioral disorder that affects both individuals and society. It is suggested that alterations in functional network connectivity (FNC) within specific brain networks underlie its neurobiological basis.

Methods: The default mode network (DMN), executive control network (ECN), and salience network (SN) are identified using data from the Human Connectome Project. The study includes 47 individuals with NA and 35 normal controls (NC), all of whom undergo resting-state fMRI alongside smoking-related clinical assessments. A sliding window analysis is employed to assess connectivity metrics, including static functional network connectivity (FNC), standard deviation (SD), and coefficient of variation (CV), to compare information integration between the groups. Participants with NA are classified based on longitudinal changes in Fagerström Test for Nicotine Dependence (FTND) scores over six years into three categories: addiction tendency (AT), withdrawal tendency (WT), and stable tendency (ST). Correlation analyses are conducted to explore relationships between FNC abnormalities and clinical assessments.

Results: Individuals with NA exhibit reduced static FNC (p_FDR = 0.029) between the dorsal DMN and the right ECN, accompanied by increased SD (p_FDR = 0.029) and CV (p_FDR = 0.029). A significant increase in SD (p_FDR = 0.049) is also observed in the dorsal DMN and left ECN. Correlations indicate that the SD of the dorsal DMN and right ECN relates to the pharmacological dimension of the Russell Smoking Reasons Questionnaire (RRSQ) scale (r = 0.416, p_FDR = 0.044), while CV correlates with changes in the FTND over six years (r = -0.391, p_FDR = 0.044) and the pharmacological dimension of the RRSQ scale (r = 0.402, p_FDR = 0.044). Post-hoc subgroup analyses reveal that these FNC intensity changes are present among WT patients (p_FDR < 0.05).

Conclusions: Alterations in brain network function within the DMN and ECN are suggested to precede behavioral changes in NA. These findings are interpreted as potential neurobiological markers of nicotine addiction.

背景:尼古丁成瘾(NA)被认为是一种影响个人和社会的重要神经行为障碍。有人认为,特定大脑网络内功能网络连接(FNC)的改变是其神经生物学基础:方法:利用 "人类连接组计划"(Human Connectome Project)的数据,确定默认模式网络(DMN)、执行控制网络(ECN)和显著性网络(SN)。研究对象包括47名NA患者和35名正常对照者(NC),他们都接受了静息态fMRI检查和与吸烟相关的临床评估。研究采用滑动窗口分析法评估连通性指标,包括静态功能网络连通性(FNC)、标准偏差(SD)和变异系数(CV),以比较两组之间的信息整合情况。根据六年来法格斯特伦尼古丁依赖测试(FTND)得分的纵向变化,将NA患者分为三类:成瘾倾向(AT)、戒断倾向(WT)和稳定倾向(ST)。进行相关性分析以探讨 FNC 异常与临床评估之间的关系:结果:NA患者的背侧DMN和右侧ECN之间的静态FNC减少(p_FDR = 0.029),同时SD(p_FDR = 0.029)和CV(p_FDR = 0.029)增加。在背侧 DMN 和左侧 ECN 中也观察到 SD(p_FDR = 0.049)的明显增加。相关性表明,背侧DMN和右侧ECN的SD与罗素吸烟原因问卷(RRSQ)量表的药理学维度相关(r = 0.416,p_FDR = 0.044),而CV与六年来FTND的变化相关(r = -0.391,p_FDR = 0.044),与RRSQ量表的药理学维度相关(r = 0.402,p_FDR = 0.044)。事后亚组分析显示,WT 患者中也存在这些 FNC 强度变化(p_FDR 结论):DMN和ECN内大脑网络功能的改变被认为先于NA的行为改变。这些发现被解释为尼古丁成瘾的潜在神经生物学标记。
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引用次数: 0
Structural and functional alterations in different types of delusions across schizophrenia spectrum: A systematic review 精神分裂症谱系中不同类型妄想的结构和功能改变:系统综述。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-30 DOI: 10.1016/j.pnpbp.2024.111185
<div><h3>Background</h3><div>Despite the high clinical role of delusions as a transnosological psychopathological phenomenon, the number of experimental studies on the different types of delusions across schizophrenia spectrum is still relatively small, and their results are somehow inconsistent. We aimed to understand the current state of knowledge regarding the structural and functional brain alterations in delusions to determine whether particular types of delusions are associated with specific brain changes and to identify common alterations underlying the formation and persistence of delusions regardless of their content.</div></div><div><h3>Methods</h3><div>For this systematic review, we followed PRISMA guidelines to search in PubMed for English papers published between 1953 and September 30, 2023. The initial inclusion criteria for screening purposes were articles that investigated delusions or subclinical delusional beliefs in schizophrenia spectrum disorders, high clinical or genetic risk for schizophrenia using fMRI, sMRI or/and dwMRI methods. Exclusion criteria during the screening phase were articles that investigated lesion-induced or substance-induced delusions, delusions in Alzheimer's disease and other neurocognitive disorders, single case studies and non-human studies. The publication metadata were uploaded to the web-tool for working on systematic reviews, Rayyan. For each of the studies, a table was filled out with detailed information.</div></div><div><h3>Results</h3><div>We found 1752 records, of which 95 full-text documents were reviewed and included in the current paper. Both nonspecific and particular types of delusions were associated with widespread structural and functional alterations. The most prominent areas affected across all types of delusions were the superior temporal cortex (predominantly left language processing areas), anterior cingulate/medial prefrontal cortex and insula. The most reproducible findings in paranoia may be alterations in the functioning of the amygdala and its interactions with other regions. Somatic delusions and delusional infestation were mostly characterized by alterations in the insula and thalamus.</div></div><div><h3>Discussion</h3><div>The data are ambiguous; however, in general the predictive processing framework seems to be the most widely accepted approach to explaining different types of delusions. Aberrant prediction errors signaling during processing of social, self-generated and sensory information may lead to inaccuracies in assessing the intentions of others, self-relevancy of ambiguous stimuli, misattribution of self-generated actions and unusual sensations, which could provoke delusional ideation with persecutory, reference, control and somatic content correspondingly. However, currently available data are still insufficient to draw conclusions about the specific biological mechanisms of predictive coding account of delusions. Thus, further studies exploring more homogeneou
背景:尽管妄想作为一种跨病理的精神病理现象在临床上发挥着重要作用,但针对精神分裂症谱系中不同类型妄想的实验研究数量仍然相对较少,其结果也不尽一致。我们旨在了解目前有关妄想中大脑结构和功能改变的知识状况,以确定特定类型的妄想是否与特定的大脑改变有关,并找出妄想形成和持续的共同改变,无论其内容如何:在本系统性综述中,我们遵循PRISMA指南,在PubMed上搜索1953年至2023年9月30日期间发表的英文论文。筛选的初始纳入标准是使用 fMRI、sMRI 或/和 dwMRI 方法研究精神分裂症谱系障碍中的妄想或亚临床妄想信念、精神分裂症高临床风险或遗传风险的文章。筛选阶段的排除标准是研究病变诱发或药物诱发妄想、阿尔茨海默病和其他神经认知障碍的妄想、单个病例研究和非人类研究的文章。出版物元数据已上传至系统综述工作网络工具 Rayyan。每项研究的详细信息都填写在表格中:结果:我们找到了 1752 条记录,其中 95 份全文文献经过审阅后被纳入本文。非特异性妄想和特殊类型妄想都与广泛的结构和功能改变有关。在所有妄想类型中,受影响最明显的区域是颞上皮层(主要是左侧语言处理区)、前扣带回/内侧前额叶皮层和岛叶。妄想症中最易重复的发现可能是杏仁核功能的改变及其与其他区域的相互作用。躯体妄想症和妄想侵袭症的主要特征是脑岛和丘脑的改变:数据模棱两可,但总的来说,预测处理框架似乎是解释不同类型妄想的最广为接受的方法。在处理社会信息、自我产生的信息和感觉信息时,异常的预测错误可能导致对他人意图的评估不准确、模糊刺激的自我相关性、对自我产生的行为和异常感觉的错误归因,从而引发相应的具有迫害性、参照性、控制性和躯体性内容的妄想。然而,现有的数据还不足以对妄想症预测编码的具体生物机制得出结论。因此,还需要进一步的研究来探索更多的同质群体以及妄想类型与诊断之间的相互作用。本综述还存在一些局限性。研究病变、药物滥用或神经变性诱发妄想的研究,以及使用 fMRI、sMRI 或 dwMRI 以外模式的研究均未纳入综述。由于文献数量相对较少,我们根据妄想的特定类型对其进行了系统化处理,而结果也可能受到患者诊断、是否接受治疗、治疗类型、病程长短等因素的影响。
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引用次数: 0
Shared polygenic susceptibility to treatment response in severe affective and psychotic disorders: Evidence from GWAS data sets 严重情感障碍和精神病治疗反应的共同多基因易感性:来自 GWAS 数据集的证据
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-28 DOI: 10.1016/j.pnpbp.2024.111183
While schizophrenia (SCZ), bipolar disorder (BD) and major depressive disorder (MDD) genetically correlate, the pleiotropy underlying response/resistance to drugs used in these disorders has not been investigated. The aim of this study is to analyze the genetic relationship between treatment-resistant schizophrenia (TRS), response to lithium in BD (respLi) and response to antidepressants in MDD (respAD) using the conditional/conjunctional false discovery rate (cond/conjFDR) methodology, based on the hypothesis that shared mechanisms related to a common psychopathology factor underlie these phenotypes. A cross-trait polygenic enrichment for TRS conditioned on associations with respLi was observed. The conjFDR analysis identified rs11631065 (chr15:66654304) as a shared locus between them. One of the genes at this locus is MAP2K1, previously reported as associated with TRS after conditioning on body mass index genome-wide association study (GWAS). The set of genes at TRS-respLi conjFDR < 0.95 showed enrichment in response to psychotropic drugs in severe mental disorders from GWAS Catalog as well as in neurodevelopment and synaptic pathways. In conclusion, our study constitutes the first evidence of a transdiagnostic genetic signal associated with response to different pharmacological treatments in psychotic and affective disorders. It is necessary to confirm these results when larger GWAS of these phenotypes are available.
虽然精神分裂症(SCZ)、双相情感障碍(BD)和重度抑郁障碍(MDD)在遗传学上存在相关性,但这些疾病对药物的反应/耐药性背后的多向性尚未得到研究。本研究的目的是利用条件/联合假发现率(cond/conjFDR)方法分析耐药精神分裂症(TRS)、BD 患者对锂盐的反应(respLi)和 MDD 患者对抗抑郁药的反应(respAD)之间的遗传关系,其假设是这些表型是由与共同精神病理学因素相关的共享机制造成的。在与 respLi 相关的条件下,观察到 TRS 的跨性状多基因富集。conjFDR分析确定了rs11631065(chr15:66654304)是它们之间的共享位点。该基因位点上的一个基因是 MAP2K1,以前曾有报道称该基因与体重指数全基因组关联研究(GWAS)相关。在 TRS-respLi conjFDR < 0.95 处的基因集显示,GWAS 目录中的严重精神障碍患者对精神药物的反应以及神经发育和突触通路都有富集。总之,我们的研究首次证明了跨诊断遗传信号与精神病和情感障碍患者对不同药物治疗的反应有关。有必要在对这些表型进行更大规模的 GWAS 研究时证实这些结果。
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引用次数: 0
Duration of aversive memory in zebrafish after a single shock 斑马鱼单次电击后的厌恶记忆持续时间。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-28 DOI: 10.1016/j.pnpbp.2024.111182
Studies on memory consolidation and reconsolidation, memory loss, and the associated biochemical mechanisms have garnered interest in the past decades due to knowledge of memory performance-affecting factors such as stress, emotions, sleep, age, several neurological diseases, drugs, and chemical pollutants. Memory research has been using animal models, with increased interest in the zebrafish model. This freshwater fish species shows a wide range of behaviors relevant to memory research such as social behavior, aggression, and predator avoidance; however, few studies have investigated the duration of long-term memory. Hence, we designed an experiment to test memory duration by exposing zebrafish to avoidance conditioning using electroshock as the aversive stimulus. Zebrafish were trained to avoid the black side of a black-and-white tank and subsequently tested for aversive memory at 24 h, 48 h, 72 h, 96 h, 168 h, and 240 h. At the 72 h-interval, another zebrafish group was trained and exposed to MK-801(NMDAr antagonist) and then tested. The fish retained memories of the task and avoided the black side of the tank for up to 7 days. At 10 days post-training, the animals could no longer retrieve the aversive memory. Zebrafish treated with MK-801 did not retrieve memory. Knowledge of memory and of long-term memory duration is crucial for optimizing the zebrafish model for use in research investigating cognitive impairments such as memory loss and its ramifications. Additionally, identifying a long-term aversive memory lasting up to 7 days in zebrafish enables further research into the neuronal changes underlying this persistence. Such in-depth investigation could bring valuable insights into memory mechanisms and facilitate targeted interventions for memory-related conditions.
过去几十年来,由于人们了解了影响记忆表现的因素,如压力、情绪、睡眠、年龄、多种神经系统疾病、药物和化学污染物,有关记忆巩固和再巩固、记忆丧失以及相关生化机制的研究引起了人们的兴趣。记忆研究一直在使用动物模型,对斑马鱼模型的兴趣与日俱增。这种淡水鱼表现出与记忆研究相关的多种行为,如社交行为、攻击行为和躲避捕食者的行为;然而,很少有研究对长期记忆的持续时间进行调查。因此,我们设计了一个实验,让斑马鱼接受以电击为厌恶刺激的回避条件反射来测试记忆的持续时间。训练斑马鱼避开黑白水槽的黑色一侧,然后在24小时、48小时、72小时、96小时、168小时和240小时后测试其厌恶记忆。在 72 小时的间隔期,另一组斑马鱼接受训练并接触 MK-801(NMDAr 拮抗剂),然后进行测试。这些斑马鱼保留了对任务的记忆,并在长达 7 天的时间里避开水箱的黑色一侧。在训练后的 10 天内,斑马鱼不再能找回厌恶记忆。用 MK-801 处理过的斑马鱼无法恢复记忆。了解记忆和长期记忆的持续时间对于优化斑马鱼模型以用于研究认知障碍(如记忆丧失及其影响)至关重要。此外,确定斑马鱼的长期厌恶记忆可持续长达 7 天,有助于进一步研究这种持续性背后的神经元变化。这种深入研究可为记忆机制带来宝贵的见解,并有助于对记忆相关疾病进行有针对性的干预。
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引用次数: 0
The pediatric psychopharmacology of autism spectrum disorder: A systematic review - Part II: The future 自闭症谱系障碍的儿科精神药理学:系统综述第二部分:未来。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-28 DOI: 10.1016/j.pnpbp.2024.111176
Part I of this systematic review summarized the state-of-the-art of pediatric psychopharmacology for Autism Spectrum Disorder (ASD), a severe and lifelong neurodevelopmental disorder. The purpose of this Part II follow-up article is to provide a systematic overview of the experimental psychopharmacology of ASD. To this aim, we have first identified in the Clinicaltrials.gov website all the 157 pharmacological and nutraceutical compounds which have been experimentally tested in children and adolescents with ASD using the randomized placebo-controlled trial (RCT) design. After excluding 24 drugs already presented in Part I, a systematic review spanning each of the remaining 133 compounds was registered on Prospero (ID: CRD42023476555), performed on PubMed (August 8, 2024), and completed with EBSCO, PsycINFO (psychology and psychiatry literature) and the Cochrane Database of Systematic reviews, yielding a total of 115 published RCTs, including 57 trials for 23 pharmacological compounds and 48 trials for 17 nutraceuticals/supplements. Melatonin and oxytocin were not included, because recent systematic reviews have been already published for both these compounds. RCTs of drugs with the strongest foundation in preclinical research, namely arbaclofen, balovaptan and bumetanide have all failed to reach their primary end-points, although efforts to target specific patient subgroups do warrant further investigation. For the vast majority of compounds, including cannabidiol, vasopressin, and probiotics, insufficient evidence of efficacy and safety is available. However, a small subset of compounds, including N-acetylcysteine, folinic acid, l-carnitine, coenzyme Q10, sulforaphane, and metformin may already be considered, with due caution, for clinical use, because there is promising evidence of efficacy and a high safety profile. For several other compounds, such as secretin, efficacy can be confidently excluded, and/or the data discourage undertaking new RCTs. Part I and Part II summarize “drug-based” information, which will be ultimately merged to provide clinicians with a “symptom-based” consensus statement in a conclusive Part III, with the overarching aim to foster evidence-based clinical practices and to organize new strategies for future clinical trials.
自闭症谱系障碍(ASD)是一种严重的终身性神经发育障碍,本系统综述的第一部分总结了自闭症谱系障碍儿科精神药理学的最新进展。本文第二部分的目的是系统地概述 ASD 的实验精神药理学。为此,我们首先在 Clinicaltrials.gov 网站上确定了所有 157 种药物和营养保健品,这些药物和保健品采用随机安慰剂对照试验 (RCT) 设计,在患有 ASD 的儿童和青少年身上进行了实验测试。在剔除第一部分已介绍的 24 种药物后,我们在 Prospero(ID:CRD42023476555)上对剩余的 133 种化合物逐一进行了系统综述(ID:CRD42023476555),在 PubMed(2024 年 8 月 8 日)上进行了综述,并在 EBSCO、PsycINFO(心理学和精神病学文献)和 Cochrane 系统综述数据库中完成了综述,共获得 115 项已发表的 RCT,其中包括 23 种药理化合物的 57 项试验和 17 种营养品/补充剂的 48 项试验。褪黑素和催产素未包括在内,因为这两种化合物最近都已发表了系统综述。阿巴洛芬、巴洛伐坦和布美他尼等临床前研究基础最为雄厚的药物的临床试验均未能达到主要终点,但针对特定患者亚群的研究确实值得进一步研究。包括大麻二酚、血管加压素和益生菌在内的绝大多数化合物的疗效和安全性证据不足。然而,一小部分化合物,包括 N-乙酰半胱氨酸、亚叶酸、左旋肉碱、辅酶 Q10、舒乐安定和二甲双胍,已经可以在谨慎的情况下考虑用于临床,因为已经有了很好的疗效证据和较高的安全性。至于其他几种化合物,如胰泌素,其疗效可以肯定地排除,并且/或者数据不鼓励进行新的 RCT 研究。第一部分和第二部分总结了 "以药物为基础 "的信息,这些信息最终将合并到第三部分,为临床医生提供一份 "以症状为基础 "的共识声明,其总体目标是促进循证临床实践,并为未来的临床试验制定新的策略。
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引用次数: 0
Abnormal intrinsic brain functional network dynamics in stroke and correlation with neuropsychiatric symptoms revealed based on lesion and cerebral blood flow 基于病变和脑血流揭示脑卒中固有脑功能网络动态异常及与神经精神症状的相关性
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-28 DOI: 10.1016/j.pnpbp.2024.111181
There has been a lack of clarity about the mechanisms of widespread network dysfunctions after stroke. This study aimed to reveal dynamic functional network alternations following stroke based on lesion and brain perfusion. We prospectively enrolled 125 acute ischaemic stroke patients (25 were transient ischemic attack (TIA) patients) and 49 healthy controls with assessed the severity of their depression, anxiety, fatigue, and apathy. We performed dynamic functional network connectivity (DFNC) analysis using the sliding window method. The common static FC biomarkers of stroke were used to define functional states and calculated stroke-specific changes in dynamic indicators. Next, ridge regression (RR) analyses were performed on the dynamic indicators using voxel-wise lesion maps, cerebral blood flow (CBF) difference maps (removal of voxels overlapping lesions) and a combination of both. Mediation analyses were used to characterize the effect of dynamic networks changes on the relationship between lesion, CBF, and neuropsychological scores. Our results showed that DFNC identified three functional states with three dynamic metrics extracted for subsequent analyses. RR analyses show that both CBF and lesions partially explain post-stroke dysfunction (CBF: dynamic indicator1: R2 = 0.110, p = 0.163; dynamic indicator2: R2 = 0.277, p = 0.006; dynamic indicator3: R2 = 0.125, p = 0.121; lesion: dynamic indicator1: R2 = 0.132, p = 0.109; dynamic indicator2: R2 = 0.238, p = 0.015; dynamic indicator3: R2 = 0.131, p = 0.110). In addition, combining the two can improve the efficacy of explanations. Finally, exploratory mediation analyses identified that dynamic functional network changes can mediate between CBF, lesion and neuropsychiatric disorders. Our results suggest that CBF and lesion can be combined to improve the interpretation of dynamic network dysfunction after stroke.
脑卒中后广泛的网络功能障碍的机制尚不清楚。本研究旨在揭示中风后基于病变和脑灌注的动态功能网络交替。我们前瞻性地招募了 125 名急性缺血性脑卒中患者(其中 25 人为短暂性脑缺血发作(TIA)患者)和 49 名健康对照者,并评估了他们抑郁、焦虑、疲劳和冷漠的严重程度。我们采用滑动窗口法进行了动态功能网络连通性(DFNC)分析。我们使用中风常见的静态 FC 生物标记物来定义功能状态,并计算中风特异性动态指标的变化。接着,我们使用体素病灶图、脑血流(CBF)差图(去除重叠病灶的体素)以及两者的组合对动态指标进行了脊回归(RR)分析。我们使用中介分析来描述动态网络变化对病变、CBF 和神经心理评分之间关系的影响。我们的结果表明,DFNC 确定了三种功能状态,并提取了三种动态指标用于后续分析。RR分析表明,CBF和病变都能部分解释卒中后的功能障碍(CBF:动态指标1:R2=0.110,p=0.163;动态指标2:R2=0.277,p=0.006;动态指标3:R2=0.125,p=0.121;病变:动态指标1:R2=0.132,p=0.109;动态指标2:R2=0.238,p=0.015;动态指标3:R2=0.131,p=0.110)。此外,将两者结合起来可以提高解释的有效性。最后,探索性中介分析发现,动态功能网络变化可以在 CBF、病变和神经精神障碍之间起到中介作用。我们的研究结果表明,将 CBF 和病变结合起来可以改善对卒中后动态网络功能障碍的解释。
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引用次数: 0
White matter integrity upon progesterone antagonism in individuals with premenstrual dysphoric disorder: A randomized placebo-controlled diffusion tensor imaging study 黄体酮拮抗剂对经前性欲障碍患者白质完整性的影响:随机安慰剂对照弥散张量成像研究。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-23 DOI: 10.1016/j.pnpbp.2024.111179

Background

Premenstrual dysphoric disorder (PMDD) is a depressive disorder triggered by fluctuations of progesterone and estradiol during the luteal phase of the menstrual cycle. Selective progesterone receptor modulation (SPRM), while exerting an antagonistic effect on progesterone and maintaining estradiol on moderate levels, has shown beneficial effects on the mental symptoms of PMDD. Progesterone is also known for its neuroprotective effects, while synthetic progestins have been suggested to promote myelination. However, the impact of SPRM treatment on white matter microstructure is unexplored.

Methods

Diffusion tensor imaging was employed to collect data on white matter integrity in patients with PMDD, before and after treatment with ulipristal acetate (an SPRM) or placebo, as part of a double-blind randomized controlled-trial. Tract based spatial statistics were performed to investigate SPRM treatment vs. placebo longitudinal effects on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), on the whole white matter skeleton.

Results

Voxel-wise analyses indicated no change over time in any white matter microstructure metrics in individuals treated with SPRM versus placebo. Improvement in PMDD symptoms did not correlate with changes in white matter microstructure. In secondary, exploratory, cross-sectional comparisons during treatment, the SPRM group displayed lower FA and higher MD, RD, and AD than the placebo group in several tracts.

Conclusion

The main findings suggest that SPRM treatment did not impact white matter microstructure compared with placebo. However, secondary exploratory analyses yielded between-group differences after treatment, which call for further investigation on the tracts potentially impacted by progesterone antagonism.

Clinical trial registration

EUDRA-CT 2016–001719-19; “Selective progesterone receptor modulators for treatment of premenstrual dysphoric disorder. A randomized, double-blind, placebo-controlled study.”; https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001719-19/SE
背景:经前期情感障碍(PMDD)是一种由月经周期黄体期的孕酮和雌二醇波动引发的抑郁障碍。选择性黄体酮受体调节(SPRM)可对黄体酮产生拮抗作用,并将雌二醇维持在适度水平,从而对 PMDD 的精神症状产生有益影响。孕酮还具有神经保护作用,而合成孕激素被认为可促进髓鞘形成。然而,SPRM 治疗对白质微观结构的影响尚未得到研究:方法:在一项双盲随机对照试验中,采用弥散张量成像技术收集了PMDD患者在接受醋酸乌利司他(一种SPRM)或安慰剂治疗前后白质完整性的数据。对整个白质骨架上的分数各向异性(FA)、平均弥散度(MD)、径向弥散度(RD)和轴向弥散度(AD)进行了基于簇的空间统计,以研究 SPRM 治疗与安慰剂的纵向影响:结果:体素分析表明,接受SPRM治疗的患者与接受安慰剂治疗的患者相比,其白质微观结构指标随时间的推移均无变化。PMDD 症状的改善与白质微结构的变化无关。在治疗期间进行的次要、探索性横断面比较中,SPRM组在几个束中显示出较低的FA和较高的MD、RD和AD:主要研究结果表明,与安慰剂相比,SPRM 治疗不会影响白质微观结构。然而,次要探索性分析得出了治疗后的组间差异,这要求进一步研究可能受孕酮拮抗作用影响的束:临床试验注册:EUDRA-CT 2016-001719-19;"选择性孕酮受体调节剂治疗经前期情感障碍。随机、双盲、安慰剂对照研究";https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001719-19/SE。
{"title":"White matter integrity upon progesterone antagonism in individuals with premenstrual dysphoric disorder: A randomized placebo-controlled diffusion tensor imaging study","authors":"","doi":"10.1016/j.pnpbp.2024.111179","DOIUrl":"10.1016/j.pnpbp.2024.111179","url":null,"abstract":"<div><h3>Background</h3><div>Premenstrual dysphoric disorder (PMDD) is a depressive disorder triggered by fluctuations of progesterone and estradiol during the luteal phase of the menstrual cycle. Selective progesterone receptor modulation (SPRM), while exerting an antagonistic effect on progesterone and maintaining estradiol on moderate levels, has shown beneficial effects on the mental symptoms of PMDD. Progesterone is also known for its neuroprotective effects, while synthetic progestins have been suggested to promote myelination. However, the impact of SPRM treatment on white matter microstructure is unexplored.</div></div><div><h3>Methods</h3><div>Diffusion tensor imaging was employed to collect data on white matter integrity in patients with PMDD, before and after treatment with ulipristal acetate (an SPRM) or placebo, as part of a double-blind randomized controlled-trial. Tract based spatial statistics were performed to investigate SPRM treatment vs. placebo longitudinal effects on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), on the whole white matter skeleton.</div></div><div><h3>Results</h3><div>Voxel-wise analyses indicated no change over time in any white matter microstructure metrics in individuals treated with SPRM versus placebo. Improvement in PMDD symptoms did not correlate with changes in white matter microstructure. In secondary, exploratory, cross-sectional comparisons during treatment, the SPRM group displayed lower FA and higher MD, RD, and AD than the placebo group in several tracts.</div></div><div><h3>Conclusion</h3><div>The main findings suggest that SPRM treatment did not impact white matter microstructure compared with placebo. However, secondary exploratory analyses yielded between-group differences after treatment, which call for further investigation on the tracts potentially impacted by progesterone antagonism.</div></div><div><h3>Clinical trial registration</h3><div>EUDRA-CT 2016–001719-19; “Selective progesterone receptor modulators for treatment of premenstrual dysphoric disorder. A randomized, double-blind, placebo-controlled study.”; <span><span>https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001719-19/SE</span><svg><path></path></svg></span></div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513099","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}
引用次数: 0
Exploring the impact of biological sex on intrinsic connectivity networks in PTSD: A data-driven approach. 探索生理性别对创伤后应激障碍内在连接网络的影响:数据驱动法
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-22 DOI: 10.1016/j.pnpbp.2024.111180
Andrew A Nicholson, Jonathan M Lieberman, Niki Hosseini-Kamkar, Kristen Eckstrand, Daniela Rabellino, Breanne Kearney, David Steyrl, Sandhya Narikuzhy, Maria Densmore, Jean Théberge, Fardous Hosseiny, Ruth A Lanius

Introduction: Sex as a biological variable (SABV) may help to account for the differential development and expression of post-traumatic stress disorder (PTSD) symptoms among trauma-exposed males and females. Here, we investigate the impact of SABV on PTSD-related neural alterations in resting-state functional connectivity (rsFC) within three core intrinsic connectivity networks (ICNs): the salience network (SN), central executive network (CEN), and default mode network (DMN).

Methods: Using an independent component analysis (ICA), we compared rsFC of the SN, CEN, and DMN between males and females, with and without PTSD (n = 47 females with PTSD, n = 34 males with PTSD, n = 36 healthy control females, n = 20 healthy control males) via full factorial ANCOVAs. Additionally, linear regression analyses were conducted with clinical variables (i.e., PTSD and depression symptoms, childhood trauma scores) in order to determine intrinsic network connectivity characteristics specific to SABV. Furthermore, we utilized machine learning classification models to predict the biological sex and PTSD diagnosis of individual participants based on intrinsic network activity patterns.

Results: Our findings revealed differential network connectivity patterns based on SABV and PTSD diagnosis. Males with PTSD exhibited increased intra-SN (i.e., SN-anterior insula) rsFC and increased DMN-right superior parietal lobule/precuneus/superior occipital gyrus rsFC as compared to females with PTSD. There were also differential network connectivity patterns for comparisons between the PTSD and healthy control groups for males and females, separately. We did not observe significant correlations between clinical measures of interest and brain region clusters which displayed significant between group differences as a function of biological sex, thus further reinforcing that SABV analyses are likely not confounded by these variables. Furthermore, machine learning classification models accurately predicted biological sex and PTSD diagnosis among novel/unseen participants based on ICN activation patterns.

Conclusion: This study reveals groundbreaking insights surrounding the impact of SABV on PTSD-related ICN alterations using data-driven methods. Our discoveries contribute to further defining neurobiological markers of PTSD among females and males and may offer guidance for differential sex-related treatment needs.

导言:性别作为生物变量(SABV)可能有助于解释创伤后应激障碍(PTSD)症状在遭受创伤的男性和女性中的不同发展和表现。在此,我们研究了 SABV 对创伤后应激障碍相关神经静息态功能连接(rsFC)改变的影响,这些改变发生在三个核心内在连接网络(ICN)中:显著性网络(SN)、中央执行网络(CEN)和默认模式网络(DMN):利用独立成分分析(ICA),我们通过全因子方差分析比较了患有和未患有创伤后应激障碍的男性和女性(n = 47 名患有创伤后应激障碍的女性,n = 34 名患有创伤后应激障碍的男性,n = 36 名健康对照组女性,n = 20 名健康对照组男性)的显著性网络(SN)、中央执行网络(CEN)和默认模式网络(DMN)的rsFC。此外,我们还对临床变量(即创伤后应激障碍和抑郁症状、童年创伤评分)进行了线性回归分析,以确定 SABV 所特有的内在网络连接特征。此外,我们还利用机器学习分类模型,根据内在网络活动模式预测参与者的生理性别和创伤后应激障碍诊断:结果:我们的研究结果显示了基于 SABV 和创伤后应激障碍诊断的不同网络连接模式。与女性创伤后应激障碍患者相比,男性创伤后应激障碍患者的SN内(即SN-岛叶前部)rsFC增加,DMN-顶叶右上/楔回/枕上回rsFC增加。在创伤后应激障碍组和健康对照组的比较中,男性和女性的网络连接模式也存在差异。我们没有观察到相关临床指标与脑区集群之间存在明显的相关性,而这些脑区集群在生理性别的作用下显示出明显的组间差异,从而进一步证实了 SABV 分析可能不会受到这些变量的干扰。此外,机器学习分类模型根据 ICN 激活模式准确预测了新的/未见过的参与者的生理性别和创伤后应激障碍诊断:本研究利用数据驱动方法揭示了 SABV 对创伤后应激障碍相关 ICN 改变的影响,具有开创性意义。我们的发现有助于进一步确定女性和男性创伤后应激障碍的神经生物学标志物,并为与性别相关的不同治疗需求提供指导。
{"title":"Exploring the impact of biological sex on intrinsic connectivity networks in PTSD: A data-driven approach.","authors":"Andrew A Nicholson, Jonathan M Lieberman, Niki Hosseini-Kamkar, Kristen Eckstrand, Daniela Rabellino, Breanne Kearney, David Steyrl, Sandhya Narikuzhy, Maria Densmore, Jean Théberge, Fardous Hosseiny, Ruth A Lanius","doi":"10.1016/j.pnpbp.2024.111180","DOIUrl":"https://doi.org/10.1016/j.pnpbp.2024.111180","url":null,"abstract":"<p><strong>Introduction: </strong>Sex as a biological variable (SABV) may help to account for the differential development and expression of post-traumatic stress disorder (PTSD) symptoms among trauma-exposed males and females. Here, we investigate the impact of SABV on PTSD-related neural alterations in resting-state functional connectivity (rsFC) within three core intrinsic connectivity networks (ICNs): the salience network (SN), central executive network (CEN), and default mode network (DMN).</p><p><strong>Methods: </strong>Using an independent component analysis (ICA), we compared rsFC of the SN, CEN, and DMN between males and females, with and without PTSD (n = 47 females with PTSD, n = 34 males with PTSD, n = 36 healthy control females, n = 20 healthy control males) via full factorial ANCOVAs. Additionally, linear regression analyses were conducted with clinical variables (i.e., PTSD and depression symptoms, childhood trauma scores) in order to determine intrinsic network connectivity characteristics specific to SABV. Furthermore, we utilized machine learning classification models to predict the biological sex and PTSD diagnosis of individual participants based on intrinsic network activity patterns.</p><p><strong>Results: </strong>Our findings revealed differential network connectivity patterns based on SABV and PTSD diagnosis. Males with PTSD exhibited increased intra-SN (i.e., SN-anterior insula) rsFC and increased DMN-right superior parietal lobule/precuneus/superior occipital gyrus rsFC as compared to females with PTSD. There were also differential network connectivity patterns for comparisons between the PTSD and healthy control groups for males and females, separately. We did not observe significant correlations between clinical measures of interest and brain region clusters which displayed significant between group differences as a function of biological sex, thus further reinforcing that SABV analyses are likely not confounded by these variables. Furthermore, machine learning classification models accurately predicted biological sex and PTSD diagnosis among novel/unseen participants based on ICN activation patterns.</p><p><strong>Conclusion: </strong>This study reveals groundbreaking insights surrounding the impact of SABV on PTSD-related ICN alterations using data-driven methods. Our discoveries contribute to further defining neurobiological markers of PTSD among females and males and may offer guidance for differential sex-related treatment needs.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513098","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}
引用次数: 0
Prenatal ethanol exposure impairs hippocampal plasticity and cognition in adolescent mice 产前接触乙醇会损害青春期小鼠的海马可塑性和认知能力
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-22 DOI: 10.1016/j.pnpbp.2024.111174

Background

Prenatal alcohol exposure (PAE) induces a wide range of neurodevelopmental disabilities that are grouped under the term ‘fetal alcohol spectrum disorders’ (FASD). The effects of PAE on brain development are dependent on complex neurochemical events, including modification of AMPA receptors (AMPARs). We have recently found that chronic ethanol (EtOH) exposure decreases AMPA-mediated neurotransmission and expression through the overexpression of the specific microRNA (miR)137 and 501-3p, which target GluA1 AMPA subunit, in the developing hippocampus in vitro. Here, we explored how PAE mice may alter AMPAergic synapses in the hippocampus, and its effects on behavior.

Methods

To model PAE, we exposed C57Bl/6 pregnant mice to 10 % EtOH during during the first 10 days of gestation (GD 0–10; equivalent to the first trimester of pregnancy in humans). AMPA subunits postsynaptic expression in the hippocampus, electrical properties of CA1 neurons, memory recognition, and locomotor functions were then analyzed in adolescent PAE-exposed offspring.

Results

PAE adolescent mice showed dysregulation of AMPAergic neurotransmission, and increased miR 501-3p expression, associated with a significant reduction of spontaneous AMPA currents and intrinsic somatic excitability. In addition, PAE reduced the phosphorylation of AMPAR-containing GluA1 subunit, despite an increase in its total levels. Of note, the total levels of GluA2 and GluA3 AMPA receptors were enhanced as well. Consistently, at behavioral level, PAE reduced object recognition without altering locomotor activity.

Conclusions

Our study shows that PAE leads to dysfunctional formation of AMPAergic synapses that could be responsible for neurobehavioral impairments, contributing to the understanding of the pathogenesis of FASD.
背景:产前酒精暴露(PAE)会诱发多种神经发育障碍,这些障碍被归类为 "胎儿酒精谱系障碍"(FASD)。PAE 对大脑发育的影响取决于复杂的神经化学事件,包括 AMPA 受体(AMPARs)的改变。我们最近发现,慢性乙醇(EtOH)暴露会通过在体外发育的海马中过表达靶向 GluA1 AMPA 亚基的特异性 microRNA(miR)137 和 501-3p,从而降低 AMPA 介导的神经传递和表达。在此,我们探讨了 PAE 小鼠如何改变海马中的 AMPA 能突触及其对行为的影响:为了建立 PAE 模型,我们在 C57Bl/6 怀孕小鼠妊娠期的前 10 天(GD 0-10;相当于人类妊娠期的前三个月)将其暴露于 10% 的 EtOH 中。然后分析了暴露于 PAE 的青春期后代海马中 AMPA 亚基突触后表达、CA1 神经元的电特性、记忆识别和运动功能:结果:PAE 暴露的青少年小鼠表现出 AMPA 能神经传递失调,miR 501-3p 表达增加,与自发 AMPA 电流和内在体细胞兴奋性显著降低有关。此外,PAE 还减少了含 AMPAR 的 GluA1 亚基的磷酸化,尽管其总水平有所增加。值得注意的是,GluA2 和 GluA3 AMPA 受体的总水平也有所提高。同样,在行为水平上,PAE会降低物体识别能力,但不会改变运动活动:我们的研究表明,PAE 导致 AMPA 能突触形成障碍,这可能是神经行为障碍的原因,有助于了解 FASD 的发病机制。
{"title":"Prenatal ethanol exposure impairs hippocampal plasticity and cognition in adolescent mice","authors":"","doi":"10.1016/j.pnpbp.2024.111174","DOIUrl":"10.1016/j.pnpbp.2024.111174","url":null,"abstract":"<div><h3>Background</h3><div>Prenatal alcohol exposure (PAE) induces a wide range of neurodevelopmental disabilities that are grouped under the term ‘fetal alcohol spectrum disorders’ (FASD). The effects of PAE on brain development are dependent on complex neurochemical events, including modification of AMPA receptors (AMPARs). We have recently found that chronic ethanol (EtOH) exposure decreases AMPA-mediated neurotransmission and expression through the overexpression of the specific microRNA (miR)137 and 501-3p, which target GluA1 AMPA subunit, in the developing hippocampus in vitro. Here, we explored how PAE mice may alter AMPAergic synapses in the hippocampus, and its effects on behavior.</div></div><div><h3>Methods</h3><div>To model PAE, we exposed C57Bl/6 pregnant mice to 10 % EtOH during during the first 10 days of gestation (GD 0–10; equivalent to the first trimester of pregnancy in humans). AMPA subunits postsynaptic expression in the hippocampus, electrical properties of CA1 neurons, memory recognition, and locomotor functions were then analyzed in adolescent PAE-exposed offspring.</div></div><div><h3>Results</h3><div>PAE adolescent mice showed dysregulation of AMPAergic neurotransmission, and increased miR 501-3p expression, associated with a significant reduction of spontaneous AMPA currents and intrinsic somatic excitability. In addition, PAE reduced the phosphorylation of AMPAR-containing GluA1 subunit, despite an increase in its total levels. Of note, the total levels of GluA2 and GluA3 AMPA receptors were enhanced as well. Consistently, at behavioral level, PAE reduced object recognition without altering locomotor activity.</div></div><div><h3>Conclusions</h3><div>Our study shows that PAE leads to dysfunctional formation of AMPAergic synapses that could be responsible for neurobehavioral impairments, contributing to the understanding of the pathogenesis of FASD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513101","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}
引用次数: 0
Psychedelic-related deaths in England, Wales and Northern Ireland (1997–2022) 英格兰、威尔士和北爱尔兰与迷幻药有关的死亡人数(1997-2022 年)。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-20 DOI: 10.1016/j.pnpbp.2024.111177

Background

Psychedelic drugs are increasingly visible in society once more, but their risks and adverse effects have received less attention than perhaps they should. While fatalities associated with psychedelics appear rare, a systematic approach to characterising their aetiology is required to inform harm minimisation efforts.

Aims

This study aimed to analyse prevalence and characteristics of psychedelic-related deaths in England, Wales, and Northern Ireland, between 1997 and 2022.

Methods

We analysed coroner reports submitted to the National Programme on Substance Use Mortality where psychedelic serotonergic agonist drugs were involved in the death, and conducted a thematic framework analysis to explore potential factors associated with their occurrence.

Results

We identified 28 cases where psychedelics were implicated (75 %, N = 21) or potentially implicated (25 %, N = 7) in the death; 19 of these involving psychedelic tryptamines (LSD 39 %, N = 11; Psilocybin 21 %, N = 6; DMT 7 %, N = 2), and 9 psychedelic phenethylamines (incl. NBOMes 18 %, N = 5). Most deaths were deemed accidental by the coroner (86 %, N = 24), including both traumatic injuries and drug toxicities; most cases involved multiple implicated drugs (68 %, N = 19); and most of the deceased were under 30 years of age (82 %, N = 23). Thematic framework analysis identified nine themes in the deaths across three categories. ‘Polysubstance use’ was the most common theme (82 % of cases, N = 23/28), followed by a suboptimal ‘physical environment’ (70 % of cases where this information was available, N = 14/20).

Conclusions

The profound and often unpredictable effects of psychedelics pose a unique profile of risks and adverse reactions. Nevertheless, psychedelic-related deaths remain very rare in comparison to other recreational drugs, and frequently involve polydrug use. Implications for harm reduction and policy are discussed.
背景:迷幻药在社会上的曝光率越来越高,但其风险和不良影响却没有得到应有的关注。虽然与迷幻药有关的死亡事件似乎很少见,但仍需要一种系统的方法来描述其病因,以便为尽量减少伤害的努力提供信息。目的:本研究旨在分析1997年至2022年期间英格兰、威尔士和北爱尔兰与迷幻药有关的死亡事件的发生率和特征:我们分析了提交给 "国家药物使用死亡率计划"(National Programme on Substance Use Mortality)的验尸官报告中涉及迷幻药血清素能激动剂类药物的死亡案例,并进行了主题框架分析,以探索与这些案例发生相关的潜在因素:我们发现28例死亡与迷幻药有关(75%,N = 21)或可能与迷幻药有关(25%,N = 7);其中19例涉及迷幻色胺类药物(迷幻剂39%,N = 11;迷幻药21%,N = 6;DMT 7%,N = 2),9例涉及迷幻苯乙胺类药物(包括NBOMes 18%,N = 5)。大多数死亡被验尸官认定为意外死亡(86%,N = 24),包括外伤和药物中毒;大多数病例涉及多种涉案药物(68%,N = 19);大多数死者年龄在 30 岁以下(82%,N = 23)。主题框架分析确定了三类死亡案例中的九个主题。使用多种药物 "是最常见的主题(82%的病例,N = 23/28),其次是 "物理环境 "不理想(70%的病例有此信息,N = 14/20):结论:迷幻药的影响深远且往往难以预测,因此具有独特的风险和不良反应。尽管如此,与其他娱乐性药物相比,与迷幻药相关的死亡仍然非常罕见,而且经常涉及多种药物的使用。本文讨论了减少伤害和制定政策的意义。
{"title":"Psychedelic-related deaths in England, Wales and Northern Ireland (1997–2022)","authors":"","doi":"10.1016/j.pnpbp.2024.111177","DOIUrl":"10.1016/j.pnpbp.2024.111177","url":null,"abstract":"<div><h3>Background</h3><div>Psychedelic drugs are increasingly visible in society once more, but their risks and adverse effects have received less attention than perhaps they should. While fatalities associated with psychedelics appear rare, a systematic approach to characterising their aetiology is required to inform harm minimisation efforts.</div></div><div><h3>Aims</h3><div>This study aimed to analyse prevalence and characteristics of psychedelic-related deaths in England, Wales, and Northern Ireland, between 1997 and 2022.</div></div><div><h3>Methods</h3><div>We analysed coroner reports submitted to the National Programme on Substance Use Mortality where psychedelic serotonergic agonist drugs were involved in the death, and conducted a thematic framework analysis to explore potential factors associated with their occurrence.</div></div><div><h3>Results</h3><div>We identified 28 cases where psychedelics were implicated (75 %, <em>N</em> = 21) or potentially implicated (25 %, <em>N</em> = 7) in the death; 19 of these involving psychedelic tryptamines (LSD 39 %, <em>N</em> = 11; Psilocybin 21 %, <em>N</em> = 6; DMT 7 %, <em>N</em> = 2), and 9 psychedelic phenethylamines (incl. NBOMes 18 %, <em>N</em> = 5). Most deaths were deemed accidental by the coroner (86 %, <em>N</em> = 24), including both traumatic injuries and drug toxicities; most cases involved multiple implicated drugs (68 %, <em>N</em> = 19); and most of the deceased were under 30 years of age (82 %, <em>N</em> = 23). Thematic framework analysis identified nine themes in the deaths across three categories. ‘Polysubstance use’ was the most common theme (82 % of cases, <em>N</em> = 23/28), followed by a suboptimal ‘physical environment’ (70 % of cases where this information was available, <em>N</em> = 14/20).</div></div><div><h3>Conclusions</h3><div>The profound and often unpredictable effects of psychedelics pose a unique profile of risks and adverse reactions. Nevertheless, psychedelic-related deaths remain very rare in comparison to other recreational drugs, and frequently involve polydrug use. Implications for harm reduction and policy are discussed.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513102","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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Progress in Neuro-Psychopharmacology & Biological Psychiatry
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