Biomarkers in Neuropsychiatry最新文献

英文中文

Hippocampal glutamate and verbal episodic memory in the psychosis spectrum: A preliminary report 精神病谱系中的海马体谷氨酸和言语情景记忆：初步报告

Q2 Medicine

Biomarkers in Neuropsychiatry

Pub Date : 2025-12-01 DOI: 10.1016/j.bionps.2025.100135

Nicolas R. Bolo , Victor Zeng , David Parker , Elena Ivleva , Jennifer McDowell , Sarah Keedy , Carol A. Tamminga , Godfrey Pearlson , Elliot S. Gershon , Scott Hill , Brett Clementz , Matcheri Keshavan

The Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium categorized individuals with psychosis into 3 biologically distinct Biotypes (B1, B2, B3) based on cognitive and EEG measures. Deficient verbal episodic memory (VEM, a contributor to Biotype determination), is strongly associated with poor clinical outcome. Hippocampal glutamatergic circuits support VEM. Furthermore, glutamatergic mechanisms, implicated in cognitive and psychotic symptoms, are proposed as novel treatment targets. We used MRS to measure hippocampus glutamate and N-acetyl-aspartate (NAA) concentrations (non-contributors to Biotype) in psychosis vs. healthy-controls (HC). We examined VEM vs. glutamate relationships across DSM-IV diagnoses and Biotypes. We compared fits of linear and quadratic regression models. Glutamate was non-significantly lower in B1, higher in B2, and similar in B3 vs. HC. NAA did not differ. Quadratic models with Biotype-based groups provided best fits using the adjusted R² and AIC criteria. In B1, reduced glutamate tended to associate with deficient VEM, suggesting reduced excitatory glutamatergic signaling, which could be compensated by glutamate enhancing treatments, increasing production of synaptic glutamate or NMDAR mediated currents. In B2, higher glutamate and the accentuated inverted-U shaped VEM vs. glutamate relationship suggest high levels of dysregulated glutamatergic activity possibly related to deficient inhibitory GABAergic control. In B3, the independence of VEM and glutamate suggests that, in contrast to B1 and B2, B3 may be more sensitive to non-glutamatergic or GABAergic neurotransmitter system-targeted compounds to maintain healthy memory function. Because of the limited sample size, the interpretation of results is of a tentative nature. Results help explain the role of hippocampal glutamatergic neurotransmission in VEM deficits in psychotic disorders and motivate distinct treatment strategies for individuals with psychosis stratified by Biotype.

双相精神分裂症中间表型网络（B-SNIP）联盟基于认知和脑电图测量将精神病患者分为3种生物学上不同的生物型（B1, B2, B3）。缺乏言语情景记忆（VEM，一个生物型决定因素）与不良临床结果密切相关。海马谷氨酸回路支持VEM。此外，与认知和精神病症状有关的谷氨酸能机制被认为是新的治疗靶点。我们使用MRS测量精神病患者与健康对照组（HC）的海马谷氨酸和n-乙酰-天冬氨酸（NAA）浓度（非生物型贡献者）。我们在DSM-IV诊断和生物型中检查了VEM与谷氨酸的关系。我们比较了线性和二次回归模型的拟合。谷氨酸在B1组无显著降低，在B2组升高，在B3组与HC组相似。NAA没有异议。使用调整后的R2和AIC标准，以生物型为基础的二次模型提供了最佳拟合。在B1中，谷氨酸减少倾向于与VEM缺陷相关，表明兴奋性谷氨酸能信号减少，这可以通过谷氨酸增强治疗，增加突触谷氨酸或NMDAR介导电流的产生来补偿。在B2中，较高的谷氨酸和强化的倒u型VEM与谷氨酸的关系表明，高水平的谷氨酸能活性失调可能与抑制性gaba能控制不足有关。在B3中，VEM和谷氨酸的独立性表明，与B1和B2相比，B3可能对非谷氨酸能或gaba能神经递质系统靶向化合物更敏感，以维持健康的记忆功能。由于样本量有限，对结果的解释是尝试性的。结果有助于解释海马谷氨酸能神经传递在精神障碍VEM缺陷中的作用，并为按生物型分层的精神病患者提供不同的治疗策略。

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引用次数: 0

Erratum to “Can neurocognitive assessment be a lower-cost substitute for biomarkers in predicting progression from mild cognitive impairment (MCI) to Alzheimer’s disease (AD)? A narrative review” Biomarkers in Neuropsychiatry, Volume 9 (2023), 100069 在预测轻度认知障碍（MCI）到阿尔茨海默病（AD）的进展方面，神经认知评估能否成为生物标志物的低成本替代品？“神经精神病学中的生物标志物，卷9(2023),100069。

Q2 Medicine

Biomarkers in Neuropsychiatry

Pub Date : 2025-12-01 DOI: 10.1016/j.bionps.2025.100131

Lea Daou , Alaeddine El Alayli , Fadi Constantinos , Georgette Dib , Marc Barakat

引用次数: 0

Associations of social and genetic background variables to neuro-cognitive biomarkers of psychosis 社会和遗传背景变量与精神病神经认知生物标志物的关联

Q2 Medicine

Biomarkers in Neuropsychiatry

Pub Date : 2025-09-27 DOI: 10.1016/j.bionps.2025.100134

Parker V. Jarrett , Kiernan L. O’Mara , Audrey L. Berardi , Kelsey E. Roberts , John T. Greco , Rebekah L. Trotti , David A. Parker , Sarah K. Keedy , Godfrey D. Pearlson , Matcheri S. Keshavan , S. Kristian Hill , Elena I. Ivleva , Carol A. Tamminga , Jennifer E. McDowell , Ezra Susser , Brett A. Clementz

Socioeconomic (SES) and ethno-racial factors may tilt psychosis diagnoses for persons from different backgrounds. Clinical diagnoses depend on patient and informant reports and are suspected of being susceptible to unintended bias. Diagnoses using laboratory tests are thought to be objective. Social disadvantages, however, alter brain functions related to psychosis. Race and class bias in laboratory medical diagnostics is an area of concern. To probe these issues for psychosis diagnoses, we describe relationships of SES, race/ethnicity, and ancestral genetic background to 11 integrated laboratory bio-factors that are associated with DSM categories and distinguish B-SNIP Biotypes. A series of analyses evaluated relationships of social factors and ancestry-related genetic background to those bio-factors: (i) canonical correlation revealed that SES and race (a social construct) are strongly associated (r²=.305) with cognitive performance and measures of brain physiology (prominently ERP magnitudes); genetic background neither significantly added to nor altered the structure of those associations; (ii) regression models illustrated that cognitive performance, intrinsic brain activity, and ERP magnitudes are substantially to modestly predicted by SES/race/genetic background, with SES/race accounting for the most variance on cognitive performance (approximately 25 %); (iii) regardless of including SES/race in differential diagnosis models, group differences between psychosis Biotypes were largely (85 %) preserved on bio-factor scores. For DSM diagnoses, less than 11 % of psychosis group differences were preserved. These outcomes illustrate that social factors are associated with psychosis-related laboratory tests. Nevertheless, SES/race did not substantially modify differential diagnosis of psychosis Biotypes. Using laboratory tests for psychosis differential diagnosis may facilitate the usefulness of stratification approaches, aid investigations of psychosis neurobiology and environmental risk, and improve treatment selections and approaches for all persons suffering with idiopathic psychosis.

社会经济（SES）和民族-种族因素可能倾向于不同背景的人的精神病诊断。临床诊断依赖于患者和信息提供者的报告，并被怀疑容易受到意外偏差的影响。使用实验室检查的诊断被认为是客观的。然而，社会不利因素会改变与精神病相关的大脑功能。实验室医学诊断中的种族和阶级偏见是一个值得关注的领域。为了探讨精神病诊断中的这些问题，我们描述了SES、种族/民族和祖先遗传背景与11个与DSM分类相关的综合实验室生物因子的关系，并区分了B-SNIP生物型。一系列的分析评估了社会因素和与祖先相关的遗传背景与这些生物因素的关系：(i)典型相关表明，社会地位和种族（一种社会结构）与认知表现和脑生理测量（显著的ERP值）密切相关（r2=.305）；遗传背景既没有显著增加也没有改变这些关联的结构；（ii）回归模型表明，认知表现、内在大脑活动和ERP大小基本上或适度地由SES/种族/遗传背景预测，其中SES/种族对认知表现的方差最大（约为25% %）；（iii）无论在鉴别诊断模型中是否包括SES/种族，在生物因子评分上，精神病生物型之间的组间差异在很大程度上（85 %）得以保留。对于DSM诊断，精神病组的差异保留了不到11% %。这些结果表明，社会因素与精神病相关的实验室测试有关。然而，社会经济地位/种族并没有实质性地改变精神病生物型的鉴别诊断。使用实验室测试进行精神病鉴别诊断，可以促进分层方法的有效性，有助于精神病神经生物学和环境风险的调查，并改善所有特发性精神病患者的治疗选择和方法。

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引用次数: 0

Fatty acids as potential biomarkers of stearoyl-CoA desaturase inhibition: Variation in healthy subjects and Parkinson's disease patients 脂肪酸作为硬脂酰辅酶a去饱和酶抑制的潜在生物标志物：健康受试者和帕金森病患者的差异

Q2 Medicine

Biomarkers in Neuropsychiatry

Pub Date : 2025-06-14 DOI: 10.1016/j.bionps.2025.100132

Pepijn P.N.M. Eijsvogel , Andriy A. Gorbenko , Dan F. Tardiff , Michelle Skupien , Ken Rhodes , Robert H. Scannevin , Yalcin Yavuz , Emilie M.J. van Brummelen , Brigitte Robertson , Philip H.C. Kremer , Geert Jan Groeneveld

This study aimed to assess the naturally occurring variation in plasma fatty acids in healthy subjects and Parkinson’s disease (PD) patients. Alpha-synuclein (aSyn) plays a major role in Parkinson’s disease. Inhibition of stearoyl-CoA desaturase (SCD) reduces levels of mono-unsaturated C16 and C18 fatty acids, which are involved in aSyn toxicity in vitro and in vivo. The ratio of mono-unsaturated to saturated fatty acids (fatty acid desaturase index (FA-DI)) in plasma after SCD-inhibition correlates with effects on brain FA-DI. However, the FA-DI normal values and the inter- and intra-day variation in PD-patients and healthy subjects is unknown. Ten PD-patients (54 –73 years) and ten age-matched healthy subjects were included. On three consecutive days, fatty acids fractions and concentrations were measured throughout the day. Outcomes are expressed as estimated mean, and the coefficient of variation (CV%) in percentage. For C16 FA-DI, the inter-subject CV% was 20.7 % in healthy subjects, and 37.7 % in PD-patients. The intra-subject CV% over days was 14.0 % in healthy subjects, and 14.2 % in PD-patients, and within days 5.1 % in healthy subjects, and 5.9 % in PD-patients. For C18 FA-DI, the inter-subject CV% was 14.8 % in healthy subjects, and 16.0 % in PD-patients. The intra-subject CV% over days was 11.0 % in healthy subjects, and 8.6 % in PD-patients, and within days 8.4 % in healthy subjects, and 6.7 % in PD-patients. The observed extent of variability in healthy subjects and PD-patients support C16 and C18 FA-DI as suitable biomarkers to demonstrate target engagement in plasma, of for example SCD-inhibitors, in both healthy subjects and PD-patients.

本研究旨在评估健康受试者和帕金森病患者血浆脂肪酸的自然变化。α -突触核蛋白（aSyn）在帕金森病中起主要作用。抑制硬脂酰辅酶a去饱和酶（SCD）可降低单不饱和C16和C18脂肪酸的水平，这与体外和体内的aSyn毒性有关。scd抑制后血浆单不饱和脂肪酸与饱和脂肪酸的比值（脂肪酸去饱和酶指数（FA-DI））与脑FA-DI的影响相关。然而，pd患者和健康受试者的FA-DI正常值以及日间和日间变化尚不清楚。纳入10例pd患者（54 -73岁）和10例年龄匹配的健康受试者。连续三天，全天测量脂肪酸的含量和浓度。结果以估计平均值表示，变异系数（CV%）以百分比表示。对于C16 FA-DI，健康受试者的受试者间CV%为20.7 %，pd患者的受试者间CV%为37.7 %。健康受试者的受试者内CV%在几天内为14.0 %，pd患者为14.2 %，健康受试者在几天内为5.1 %，pd患者为5.9 %。对于C18 FA-DI，健康受试者的受试者间CV%为14.8 %，pd患者的受试者间CV%为16.0 %。健康人体内CV%在几天内为11.0 %，pd患者为8.6 %；健康人体内CV%在几天内为8.4 %，pd患者为6.7 %。在健康受试者和pd患者中观察到的变异性程度支持C16和C18 FA-DI作为证明健康受试者和pd患者血浆中靶标参与的合适生物标志物，例如scd抑制剂。

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引用次数: 0

Corrigendum to “Football-related concussions and head impacts are associated with changes in retinal structure and signaling” [Biomark. Neuropsychiatry 10 (2024) 100091] “与足球有关的脑震荡和头部撞击与视网膜结构和信号的变化有关”[生物标记]的勘误表。神经精神病学10 (2024)100091]

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Biomarkers in Neuropsychiatry

Pub Date : 2025-06-01 DOI: 10.1016/j.bionps.2024.100118

Steven M. Silverstein , Jason Atlas , Mia Young , Lyvia Bertolace , Iwona Juskiewicz , Kian Merchant-Borna , Sarah Dermady , Yonatan Abrham , Kyle Green , Jeff Bazarian , Rajeev S. Ramchandran , Brian P. Keane

引用次数: 0

Erratum regarding missing disclosure statements of previously published articles 关于先前发表的文章缺少披露声明的勘误

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Biomarkers in Neuropsychiatry

Pub Date : 2025-06-01 DOI: 10.1016/j.bionps.2025.100127

引用次数: 0

GABA dysfunction in schizophrenia: The GABAA receptor as a potential therapeutic target 精神分裂症的GABA功能障碍：GABAA受体作为潜在的治疗靶点

Q2 Medicine

Biomarkers in Neuropsychiatry

Pub Date : 2025-05-23 DOI: 10.1016/j.bionps.2025.100130

Brandon L.M. Crotchett, Seth D. Reighard, Henry A. Nasrallah

Schizophrenia is a complex psychiatric disorder characterized by debilitating positive, negative, and cognitive symptoms, whose etiology is traditionally attributed to dopamine dysregulation. While dopamine receptor antagonists effectively alleviate positive symptoms, they fail to address the persistent cognitive and negative symptom domains of disease. Growing evidence supports a broader neurobiological framework in which cortical excitation-inhibition (E/I) imbalance acts as an upstream contributor to dopaminergic dysregulation in schizophrenia, with the neurotransmitters gamma-aminobutyric acid (GABA) and glutamate playing a critical role in this homeostasis. Herein, we summarize such evidence, including preclinical findings from animal models of schizophrenia that support the role of GABAergic dysfunction in disease pathophysiology and validate the GABA_A receptor as a promising therapeutic target. We review the potential of subtype-selective GABA_A receptor modulators to restore E/I balance and improve symptoms currently resistant to antidopaminergic agents. Key challenges and considerations for the future development of these therapeutics are also discussed, emphasizing the importance of targeting E/I imbalance to better understand and treat the network-level dysfunction underlying schizophrenia.

精神分裂症是一种复杂的精神障碍，其特征是衰弱的阳性、阴性和认知症状，其病因传统上归因于多巴胺失调。虽然多巴胺受体拮抗剂有效缓解阳性症状，但它们无法解决疾病的持续认知和阴性症状领域。越来越多的证据支持一个更广泛的神经生物学框架，其中皮层兴奋抑制（E/I）失衡是精神分裂症中多巴胺能失调的上游因素，神经递质γ -氨基丁酸（GABA）和谷氨酸在这种内稳态中起着关键作用。在此，我们总结了这些证据，包括精神分裂症动物模型的临床前发现，这些发现支持GABAA能功能障碍在疾病病理生理中的作用，并验证了GABAA受体是一个有希望的治疗靶点。我们回顾了亚型选择性GABAA受体调节剂恢复E/I平衡和改善目前对抗多巴胺能药物耐药症状的潜力。本文还讨论了这些治疗方法未来发展的关键挑战和考虑因素，强调了针对E/I失衡的重要性，以更好地理解和治疗精神分裂症潜在的网络水平功能障碍。

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引用次数: 0

Multidimensional perspectives on (bio)markers: Linking clinical and biological insights across psychiatric disorders, supporting a transdiagnostic model （生物）标记物的多维视角：将精神疾病的临床和生物学见解联系起来，支持跨诊断模型

Q2 Medicine

Biomarkers in Neuropsychiatry

Pub Date : 2025-05-20 DOI: 10.1016/j.bionps.2025.100129

Dusan Hirjak

This editorial serves as an introduction to the Special Issue "Biomarkers of Trans-Nosological Functional Domains", offering an overview of its central themes and contributions.

这篇社论作为特刊“跨疾病功能域的生物标志物”的介绍，提供了其中心主题和贡献的概述。

引用次数: 0

Dimensions of psychosis in delirious and catatonic trauma critically Ill patients 精神错乱和紧张性创伤危重病人的精神病维度

Q2 Medicine

Biomarkers in Neuropsychiatry

Pub Date : 2025-05-08 DOI: 10.1016/j.bionps.2025.100128

Ming-Ray Xu , Trey W. McGonigle , Jinyuan Liu , Robert S. Dittus , Stephan Heckers , Pratik P. Pandharipande , Shawniqua Williams Roberson , Mayur B. Patel , E. Wesley Ely , Jo Ellen Wilson

Objective

We examined the effect of delirium and catatonia on psychosis symptom presentation in trauma intensive care unit (TICU) patients without previous history of serious psychiatric illness.

Design

Prospective observational cohort study at a single academic medical center TICU, enrolling adult patients with critical illness secondary to traumatic injury excluding patients with significant psychiatric history. ICU patients received once-daily DSM-5 delirium and catatonia evaluations, and Clinician-Related Dimensions of Psychosis Severity Scale (CRDPSS) assessment. Patients were grouped by delirium and/or catatonia diagnosis with Kruskal-Wallis and Pearson’s Chi-square testing of differences between groups in CRDPSS scores.

Main Results

74 patients were sorted into delirium and/or catatonia groups for the dimensions of psychosis analysis. Catatonia was common in this critically ill trauma population with 26 % prevalence. Patients with delirium and/or catatonia diagnoses had differing severities of psychosis symptoms from those with neither condition. CRDPSS total scores were significantly different between the groups (p = 0.011).

Conclusions

Further investigation is needed to explore commonalities in the mechanisms underpinning ICU psychosis and to identify specific psychotic symptom manifestations suggestive of delirium versus catatonia.

目的探讨谵妄和紧张症对创伤重症监护病房（TICU）无严重精神疾病史患者精神病症状表现的影响。设计在单一学术医疗中心TICU进行前瞻性观察队列研究，纳入创伤性损伤继发危重疾病的成年患者，排除有明显精神病史的患者。ICU患者接受每日一次的DSM-5谵妄和紧张症评估，以及精神病严重程度临床相关维度量表（CRDPSS）评估。根据谵妄和/或紧张症的诊断对患者进行分组，使用Kruskal-Wallis和Pearson卡方检验各组之间CRDPSS评分的差异。主要结果74例患者按精神病维度分为谵妄组和（或）紧张症组。紧张症在重症创伤人群中很常见，患病率为26% %。诊断为谵妄和/或紧张症的患者与未诊断为谵妄和/或紧张症的患者具有不同程度的精神病症状。CRDPSS总分组间比较差异有统计学意义（p = 0.011）。结论需要进一步研究ICU精神病发病机制的共性，并确定谵妄与紧张症的具体精神病症状表现。

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引用次数: 0

Genetic predictors of attempted suicide among South Indian adolescents and young adults: A case-control study 南印度青少年和年轻人自杀未遂的遗传预测因素：一项病例对照研究

Q2 Medicine

Biomarkers in Neuropsychiatry

Pub Date : 2025-03-26 DOI: 10.1016/j.bionps.2025.100126

Anju Mathew , Ann Mary Alex , Chathathayil Mohammedali Shafeeque , Saboora Beegum Muthubeevi , Vijayakumar Krishnapillai , Moinak Banerjee

Background

Suicide among adolescents and young adults is an alarming public health issue globally. Though studies suggest the link between genetic factors and suicidal behavior, there is a paucity of studies of specific genetic variants in adolescents and young adults. Hence this study explored the genetic predictors for attempted suicide among adolescents and young adults, by studying the genetic basis of serotonin and dopamine synthesis, transport, and degradation machinery.

Methods

A Case-control association study was conducted comprising individuals with attempted suicide (cases n = 80), 13–29 years of age, belonging to Malayalam speaking Dravidian population, and attending a tertiary care center in South India. Age, sex, and ethnicity matched controls (n = 267) with no history of attempted suicide were also considered from the same ethnic population. Genotyping was performed for functionally critical SNP in serotonin receptor, Tryptophan hydroxylase, Tyrosine hydroxylase, and Catechol-o-methyl transferase. Statistical significance for allelic and genotypic comparisons and their odds ratios were computed.

Results

The Tyrosine Hydroxylase THrs2070762 and Tryptophan Hydroxylase TPH1rs211105 genetic variants showed a statistically significant association with attempted suicide phenotype.

Conclusion

The study suggests that the genetic variants in Tyrosine Hydroxylase and Tryptophan Hydroxylase are predictive of attempted suicide among adolescents and young adults. Understanding the genetic variations will help in identifying and managing high-risk individuals.

青少年和青壮年自杀是一个令人担忧的全球公共卫生问题。尽管研究表明遗传因素与自杀行为之间存在联系，但对青少年和年轻人中特定基因变异的研究却很少。因此，本研究通过研究血清素和多巴胺合成、转运和降解机制的遗传基础，探讨了青少年和年轻人自杀未遂的遗传预测因素。方法采用病例-对照关联研究，纳入13-29岁，属于马拉雅拉姆语德拉威人，在印度南部三级保健中心就诊的自杀未遂个体（病例n = 80）。年龄、性别和种族匹配的对照组（n = 267）也被认为来自同一种族的人群，没有自杀未遂史。对5 -羟色胺受体、色氨酸羟化酶、酪氨酸羟化酶和儿茶酚-o-甲基转移酶的功能关键SNP进行基因分型。计算等位基因和基因型比较的统计学显著性及其优势比。结果酪氨酸羟化酶THrs2070762和色氨酸羟化酶TPH1rs211105基因变异与自杀未遂表型有统计学意义。结论酪氨酸羟化酶和色氨酸羟化酶基因变异可预测青少年和青壮年自杀未遂。了解遗传变异将有助于识别和管理高风险个体。

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