Biological psychiatry global open science最新文献_第7页

Association Between Maternal Genome-Wide Polygenic Scores for Psychiatric and Neurodevelopmental Disorders and Adverse Perinatal Events: A Danish Population-Based Study 精神和神经发育障碍的母亲全基因组多基因评分与不良围产期事件之间的关联：一项基于丹麦人群的研究

IF 3.7 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2025-09-17 DOI: 10.1016/j.bpsgos.2025.100613

Fenfen Ge , Yue Wang , Xiaoqin Liu , Trine Munk-Olsen , Kathrine Bang Madsen , Emil Michael Pedersen , Clara Albiñana , Esben Agerbo , Cynthia M. Bulik , Liselotte Vogdrup Petersen , Unnur A. Valdimarsdottir , Bjarni Jóhann Vilhjálmsson

Background

Phenotypic links between psychiatric disorders and adverse perinatal events are increasingly being reported, but the mechanisms remain unclear. In this study, we aimed to assess how polygenic scores (PGSs) for 8 psychiatric conditions influence perinatal risk.

Methods

The main analysis included 13,085 mothers and their corresponding birth information. PGSs for psychiatric conditions were estimated using genome-wide association study data (excluding the iPSYCH cohort) via LDpred2 and used as exposures. Ten adverse perinatal events from Danish national registers served as outcomes. Associations were analyzed using logistic or multinomial regression, with false discovery rate correction applied.

Results

We found that PGSs for psychiatric conditions were associated with heavy smoking (attention-deficit/hyperactivity disorder [ADHD], anxiety, and depression), lower likelihood of being overweight/obese (schizophrenia, anorexia nervosa, and obsessive-compulsive disorder [OCD]), very young maternal age (<20 years) at childbirth (ADHD, depression, and anxiety), and non-cohabitation (ADHD, schizophrenia, anxiety, and depression). Little evidence of an association between maternal PGSs for psychiatric conditions and birth weight, gestational age, and labor presentation was identified. We identified a novel dose-response relationship in which higher PGSs for ADHD, anxiety, and depression were associated with a greater cumulative burden of adverse perinatal events, whereas higher PGSs for anorexia nervosa and OCD were linked to a lower burden.

Conclusions

High genetic liability for psychiatric conditions may partially explain the observed phenotypic associations between maternal mental illness and adverse perinatal events, with higher genetic liability generally associated with either an increase or decrease in the cumulative burden of adverse perinatal events in a dose-response–like manner.

背景精神疾病和不良围产期事件之间的表型联系越来越多地被报道，但其机制尚不清楚。在这项研究中，我们旨在评估8种精神疾病的多基因评分（pgs）如何影响围产期风险。方法对13085名产妇及其分娩信息进行主要分析。通过LDpred2使用全基因组关联研究数据（不包括iPSYCH队列）估计精神疾病的pgs，并将其作为暴露。丹麦国家登记的10个不良围产期事件作为结局。使用逻辑回归或多项回归分析关联，并应用错误发现率校正。结果我们发现，精神疾病的pgs与重度吸烟（注意力缺陷/多动障碍[ADHD]、焦虑和抑郁）、较低的超重/肥胖可能性（精神分裂症、神经性厌食症和强迫症[OCD]）、分娩时母亲年龄过小（20岁）（注意力缺陷多动症、抑郁和焦虑）和非同居（注意力缺陷多动症、精神分裂症、焦虑和抑郁）有关。很少有证据表明母亲精神疾病的pgs与出生体重、胎龄和分娩表现之间存在关联。我们发现了一种新的剂量-反应关系，ADHD、焦虑和抑郁的高pgs与更大的不良围产期事件累积负担相关，而神经性厌食症和强迫症的高pgs与较低的负担相关。结论较高的精神疾病遗传倾向可能部分解释了观察到的孕产妇精神疾病与围产期不良事件之间的表型关联，较高的遗传倾向通常与围产期不良事件累积负担的增加或减少呈剂量-反应样关系。

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引用次数: 0

Clinical Criteria to Guide Antineuronal Antibody Testing for People With Early and Persistent Psychosis Attending Mental Health Services 指导参加精神卫生服务的早期和持续性精神病患者抗神经元抗体检测的临床标准

IF 3.7 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2025-09-17 DOI: 10.1016/j.bpsgos.2025.100612

Gemma McKeon , Andrea Baker , Stefan Blum , David Gillis , Kerri Prain , Judith M. Greer , George Bruxner , Michael E. Benros , Sean Hatherill , Shuichi Suetani , Dan Siskind , Kate Murphy , Hitesh Joshi , Jackie Curtis , Brian O’Donoghue , Iain Macmillan , Eva Malacova , Anita Pelecanos , Patrick Waters , Belinda Lennox , James G. Scott

Background

Early detection of autoimmune psychosis (AP) mediated by antineuronal antibodies (Abs) is critical for achieving optimal clinical outcomes. However, evidence remains limited regarding who should be tested and how Ab-positive cases should be managed. In this large-scale study, we evaluated proposed clinical criteria for targeted Ab testing in psychiatric services and described the clinical course of seropositive patients.

Methods

Individuals with early psychosis (EP) or persistent psychosis (PP) were prospectively assessed with clinical criteria to determine high- or low-risk status for AP. Blood samples were collected for Ab testing using a fixed cell-based assay. Seropositive individuals were invited for detailed review, including clinical, functional, and cognitive assessments at baseline and a 12-month follow-up. Blood samples were collected from 754 individuals (EP: n = 352, PP: n = 402).

Results

Abs were present in 2.3% (17/754), including 3.4% (12/352) of patients with EP and 1.2% (5/402) of patients with PP. AP was confirmed in 2 cerebrospinal fluid (CSF)–positive high-risk individuals (total: 2/754, 0.3%; EP: 1/352, 0.3%; PP: 1/402, 0.2%). Both improved with immunotherapy. Although some low-risk patients were seropositive, none were diagnosed clinically with AP.

Conclusions

AP prevalence was low in this cohort. Targeted testing informed by clinical high-risk criteria successfully identified 2 immunotherapy-responsive AP cases. This approach appears feasible but requires further validation. People with psychosis and high-risk AP features should be considered for Ab testing in sera and CSF where indicated. Further research is required to embed targeted Ab testing into mental health services.

背景：抗神经元抗体（Abs）介导的自身免疫性精神病（AP）的检测对于获得最佳临床结果至关重要。然而，关于谁应该接受检测以及如何处理ab阳性病例的证据仍然有限。在这项大规模研究中，我们评估了精神科服务中靶向Ab检测的拟议临床标准，并描述了血清阳性患者的临床病程。方法采用临床标准对早期精神病（EP）或持续性精神病（PP）患者进行前瞻性评估，以确定AP的高风险或低风险状态。采用固定细胞法采集血样进行Ab检测。血清阳性个体被邀请进行详细的审查，包括临床、功能和认知评估基线和12个月的随访。共采集754例（EP: n = 352, PP: n = 402）血液样本。结果抗体阳性率为2.3%(17/754)，其中EP患者阳性率为3.4% (12/352)，PP患者阳性率为1.2%（5/402）。2例脑脊液（CSF）阳性高危人群中证实有AP（总数：2/754,0.3%;EP: 1/352, 0.3%; PP: 1/402, 0.2%）。两种情况在免疫治疗后都有所改善。尽管部分低危患者血清检测呈阳性，但临床均未诊断出ap。结论该队列中ap患病率较低。根据临床高危标准进行的靶向检测成功鉴定出2例免疫治疗反应性AP病例。这种方法似乎可行，但需要进一步验证。有精神病和高危AP特征的患者应考虑在血清和脑脊液中进行Ab检测。将有针对性的Ab型抗体检测纳入心理健康服务需要进一步的研究。

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引用次数: 0

Autism Heterogeneity Related to Preterm Birth: Multi-Ancestry Results From the Simons Foundation Powering Autism Research for Knowledge Sample 与早产相关的自闭症异质性：来自西蒙斯基金会为自闭症研究提供知识样本的多祖先结果

IF 3.7 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2025-09-17 DOI: 10.1016/j.bpsgos.2025.100614

Charikleia Chatzigeorgiou , Zeynep Asgel , Marina Natividad Avila , Behrang Mahjani , Vahe Khachadourian , Tade Souaiaia , Niamh Mullins , Magdalena Janecka

Background

Autism spectrum disorder (ASD) shows significant clinical variability, likely due to a combination of genetic and environmental factors. Preterm birth is a known risk factor for ASD, occurring in approximately 13% of diagnosed individuals. While genetic factors contribute to preterm birth in the general population, the relationship between genetic variation, preterm birth, and ASD heterogeneity remains unclear.

Methods

We investigated the genetic factors associated with preterm birth in 31,947 autistic individuals using data from the SPARK (Simons Foundation Powering Autism Research for Knowledge) sample. We conducted 3 ancestry-specific genome-wide association studies for African/African American, admixed American, and non-Finnish European ancestries, followed by a meta-analysis of 3308 preterm cases and 28,639 controls using METAL. Functional mapping and gene-based analyses were performed using FUMA, and genetic correlations were estimated using LDSC and Popcorn. Polygenic risk scores (PRSs) were computed with BridgePRS, using PRS of preterm birth in the general population.

Results

Our study identified ancestry-specific genetic loci associated with preterm birth in ASD cases. Although the meta-analysis results were not statistically significant, the estimated single nucleotide polymorphism heritability was 14%, indicating a meaningful contribution of common genetic variants. Across ancestry groups, preterm birth status was not significantly associated with PRSs for any psychiatric or medical conditions analyzed. However, polygenic liability to preterm birth in the general population was linked to several congenital anomalies after multiple testing adjustments.

Conclusions

These findings highlight the importance of diverse ancestries and early-life exposures in understanding ASD heterogeneity. Future research should replicate these findings in larger samples and explore rare variants associated with preterm birth to better understand the relationship between gestational duration and clinical and genetic differences in ASD.

自闭症谱系障碍（ASD）表现出显著的临床变异性，可能是遗传和环境因素共同作用的结果。早产是自闭症谱系障碍的一个已知危险因素，约13%的确诊个体发生早产。虽然遗传因素在一般人群中会导致早产，但遗传变异、早产和ASD异质性之间的关系尚不清楚。方法我们使用SPARK （Simons Foundation powered Autism Research for Knowledge）样本的数据，对31947名自闭症患者的早产相关遗传因素进行了调查。我们对非裔/非裔美国人、混血儿美国人和非芬兰血统的欧洲人进行了3项谱系特异性全基因组关联研究，随后使用METAL对3308例早产病例和28639例对照进行了荟萃分析。使用fua进行功能定位和基于基因的分析，并使用LDSC和Popcorn估计遗传相关性。使用BridgePRS计算多基因风险评分（PRSs），使用一般人群早产的PRSs。结果我们的研究确定了谱系特异性基因位点与ASD患者早产相关。虽然meta分析结果没有统计学意义，但估计的单核苷酸多态性遗传率为14%，表明常见遗传变异的贡献有意义。在整个祖先群体中，早产状况与任何精神或医学状况的PRSs分析没有显着关联。然而，在多次测试调整后，一般人群的多基因早产倾向与几种先天性异常有关。这些发现强调了不同的祖先和早期生活暴露对理解ASD异质性的重要性。未来的研究应该在更大的样本中复制这些发现，并探索与早产相关的罕见变异，以更好地了解妊娠期与ASD临床和遗传差异之间的关系。

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引用次数: 0

Social Determinants of Health Influence Brain and Cognitive Function in Youth 影响青少年大脑和认知功能的社会因素

IF 3.7 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2025-09-12 DOI: 10.1016/j.bpsgos.2025.100590

Lucina Q. Uddin

引用次数: 0

Therapeutic Shifts and Scientific Influence in Treatment-Resistant Depression Research: A Data-Driven Perspective 难治性抑郁症研究中的治疗转变和科学影响：数据驱动的视角

IF 3.7 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2025-09-09 DOI: 10.1016/j.bpsgos.2025.100610

Yunsheng Liu , Zengwei Kou

Background

Treatment-resistant depression (TRD) remains a major psychiatric challenge, with therapeutic paradigms evolving over the last 50 years. However, research on TRD is fragmented across molecular mechanisms, clinical interventions, and epidemiological trends, highlighting the need for a comprehensive synthesis to guide future studies and enhance clinical outcomes.

Methods

We conducted a large-scale bibliometric analysis of 16,198 TRD-related publications from PubMed, Web of Science, and Scopus (1974–2025). Using CiteSpace, VOSviewer, and Bibliometrix, we quantified publication trends, collaborative networks, and thematic shifts. Special attention was paid to influential researchers and institutions, as well as examining the shifting research focus from traditional invasive therapies, including deep brain stimulation, to emerging pharmacological advancements such as ketamine-based treatments.

Results

We identified leading countries, institutions, and key contributors on TRD research. Thematic clusters revealed sustained focus on neurobiological mechanisms (glutamate dysfunction, inflammation) and clinical efficacy. A pivotal shift from invasive techniques (dominant before 2000) to ketamine-based therapies was observed, with ketamine-related publications surging after 2010. High-impact journals such as Biological Psychiatry and American Journal of Psychiatry anchored 3 intellectual clusters: molecular neuropharmacology, pathophysiology, and clinical psychiatry. Despite progress, gaps persist in understanding ketamine’s systemic effects and noncanonical NMDA receptor roles.

Conclusions

This bibliometric study traces TRD research evolution from the 1970s onward, revealing key shifts from invasive interventions to novel pharmacotherapies such as ketamine, a transformative advance highlighting a mechanism-driven approach. By analyzing influential contributors, collaborations, and emerging trends, our work synthesizes decades of fragmented knowledge, providing clinicians and researchers with a cohesive road map for future TRD investigations.

背景：难治性抑郁症（TRD）仍然是一个重大的精神病学挑战，在过去的50年里，治疗范式不断发展。然而，关于TRD的研究在分子机制、临床干预和流行病学趋势方面是碎片化的，这突出表明需要全面综合以指导未来的研究并提高临床结果。方法对1974-2025年PubMed、Web of Science和Scopus中与trd相关的16,198篇论文进行了大规模的文献计量学分析。利用CiteSpace、VOSviewer和Bibliometrix，我们量化了出版趋势、合作网络和主题变化。会议对有影响力的研究人员和机构给予了特别关注，并审查了研究重点从传统侵入性治疗（包括深部脑刺激）转向新兴药理学进展（如氯胺酮治疗）的情况。结果：我们确定了TRD研究的主要国家、机构和主要贡献者。专题集群显示持续关注神经生物学机制（谷氨酸功能障碍，炎症）和临床疗效。从侵入性技术（2000年之前占主导地位）到基于氯胺酮的治疗方法发生了关键转变，与氯胺酮相关的出版物在2010年之后激增。诸如《生物精神病学》和《美国精神病学杂志》这样的高影响力期刊锚定了3个知识集群：分子神经药理学、病理生理学和临床精神病学。尽管取得了进展，但在理解氯胺酮的全身效应和非规范NMDA受体的作用方面仍然存在差距。这项文献计量学研究追溯了自20世纪70年代以来TRD研究的演变，揭示了从侵入性干预到新型药物治疗（如氯胺酮）的关键转变，这是一个突出机制驱动方法的变革性进步。通过分析有影响力的贡献者、合作和新兴趋势，我们的工作综合了几十年来零散的知识，为临床医生和研究人员提供了未来TRD调查的连贯路线图。

{"title":"Therapeutic Shifts and Scientific Influence in Treatment-Resistant Depression Research: A Data-Driven Perspective","authors":"Yunsheng Liu , Zengwei Kou","doi":"10.1016/j.bpsgos.2025.100610","DOIUrl":"10.1016/j.bpsgos.2025.100610","url":null,"abstract":"<div><h3>Background</h3><div>Treatment-resistant depression (TRD) remains a major psychiatric challenge, with therapeutic paradigms evolving over the last 50 years. However, research on TRD is fragmented across molecular mechanisms, clinical interventions, and epidemiological trends, highlighting the need for a comprehensive synthesis to guide future studies and enhance clinical outcomes.</div></div><div><h3>Methods</h3><div>We conducted a large-scale bibliometric analysis of 16,198 TRD-related publications from PubMed, Web of Science, and Scopus (1974–2025). Using CiteSpace, VOSviewer, and Bibliometrix, we quantified publication trends, collaborative networks, and thematic shifts. Special attention was paid to influential researchers and institutions, as well as examining the shifting research focus from traditional invasive therapies, including deep brain stimulation, to emerging pharmacological advancements such as ketamine-based treatments.</div></div><div><h3>Results</h3><div>We identified leading countries, institutions, and key contributors on TRD research. Thematic clusters revealed sustained focus on neurobiological mechanisms (glutamate dysfunction, inflammation) and clinical efficacy. A pivotal shift from invasive techniques (dominant before 2000) to ketamine-based therapies was observed, with ketamine-related publications surging after 2010. High-impact journals such as <em>Biological Psychiatry</em> and <em>American Journal of Psychiatry</em> anchored 3 intellectual clusters: molecular neuropharmacology, pathophysiology, and clinical psychiatry. Despite progress, gaps persist in understanding ketamine’s systemic effects and noncanonical NMDA receptor roles.</div></div><div><h3>Conclusions</h3><div>This bibliometric study traces TRD research evolution from the 1970s onward, revealing key shifts from invasive interventions to novel pharmacotherapies such as ketamine, a transformative advance highlighting a mechanism-driven approach. By analyzing influential contributors, collaborations, and emerging trends, our work synthesizes decades of fragmented knowledge, providing clinicians and researchers with a cohesive road map for future TRD investigations.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100610"},"PeriodicalIF":3.7,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145324657","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

Electrophysiological Biomarkers Reflect Target Engagement and Response Using Deep Brain Stimulation for Obsessive-Compulsive Disorder 电生理生物标志物反映目标参与和反应使用深部脑刺激强迫症

IF 3.7 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2025-09-09 DOI: 10.1016/j.bpsgos.2025.100609

Tine Van Bogaert , Martijn Figee , Brian H. Kopell , Andrew Smith , Jungho Cha , Ha Neul Song , Davide Momi , Zarghona Imtiaz , Sanjana Murthy , Sonia Olson , Elisa Xu , Helen Mayberg , Myles Mc Laughlin , Ki Sueng Choi , Allison C. Waters

Background

Deep brain stimulation (DBS) of the anterior limb of the internal capsule (ALIC) is an effective treatment for severe, treatment-resistant obsessive-compulsive disorder (OCD). However, optimizing lead placement and stimulation parameters remains a challenge. DBS evoked potentials (EPs) recorded with electroencephalography (EEG) during surgical lead placement could serve as intraoperative biomarkers for target engagement and clinical efficacy.

Methods

We obtained intraoperative EEG recordings on the forehead from 10 patients (2 nonresponders) undergoing ALIC DBS surgery for OCD. Monopolar stimulation at 2 Hz was delivered through all electrode contacts, and EEG EPs were analyzed in relation to stimulation contact, white matter connectivity to the prefrontal cortical regions of interest (assessed via probabilistic tractography), and reduction in symptom severity (assessed with the Yale-Brown Obsessive Compulsive Scale).

Results

We observed consistent DBS EPs with 3 oscillatory peaks (∼35, ∼75, and ∼120 ms) across all patients. EP amplitude varied across contacts, with the largest responses occurring when the location of stimulation overlapped with the preoperatively defined tractographic target. Higher EP amplitudes recorded on the forehead correlated with greater white matter connectivity to the ventromedial prefrontal cortex/orbitofrontal cortex and ventrolateral prefrontal cortex. Treatment nonresponders exhibited less consistent EP waveforms across lead contacts.

Conclusions

These findings suggest that intraoperative EPs provide valuable insights into ALIC DBS target engagement. EP characteristics may serve as biomarkers to refine DBS targeting and predict clinical response, offering a potential tool for optimizing DBS therapy for OCD.

脑深部电刺激（DBS）的前肢内囊（ALIC）是一种有效的治疗严重的，治疗难治性强迫症（OCD）。然而，优化导联剂的放置和增产参数仍然是一个挑战。脑电图（EEG）记录的脑起搏器诱发电位（EPs）可作为术中靶接触和临床疗效的生物标志物。方法对10例接受ALIC DBS手术治疗强迫症的患者（2例无反应）进行术中脑电图记录。通过所有电极接触传递2hz的单极刺激，并分析脑电图EPs与刺激接触、白质与感兴趣的前额皮质区域的连通性（通过概率神经束造影评估）以及症状严重程度的降低（用耶鲁-布朗强迫症量表评估）的关系。我们在所有患者中观察到一致的DBS EPs有3个振荡峰（~ 35、~ 75和~ 120 ms）。EP振幅在接触过程中变化，当刺激位置与术前确定的牵道图目标重叠时，发生最大的反应。前额记录的高电位振幅与腹内侧前额叶皮层/眼窝前额叶皮层和腹外侧前额叶皮层之间的白质连接性增强相关。治疗无应答者在铅触点处表现出不太一致的电位波形。结论术中EPs为ALIC DBS靶标结合提供了有价值的见解。EP特征可以作为生物标志物来完善DBS靶向和预测临床反应，为优化DBS治疗强迫症提供了一个潜在的工具。

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引用次数: 0

Cortical GABAergic Neuron Dysregulation in Schizophrenia Is Age Dependent 精神分裂症患者皮质gaba能神经元失调与年龄相关

IF 3.7 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2025-09-08 DOI: 10.1016/j.bpsgos.2025.100606

Daniel Kiss , Xiaolin Zhou , Nicole Endresz , Keon Arbabi , Alex Gonzalez Segura , Daniel Felsky , Andreea O. Diaconescu , Etienne Sibille , Shreejoy J. Tripathy

Background

Cortical GABAergic (gamma-aminobutyric acidergic) neuron dysregulation is implicated in schizophrenia (SCZ), but it remains unclear whether these changes are due to altered cell proportions or per-cell changes in messenger RNA (mRNA) expression.

Methods

We analyzed 14 bulk and cell type–specific RNA sequencing (RNA-seq) datasets from 1408 individuals (672 SCZ cases, 736 controls) across 3 neocortical regions. We deconvolved GABAergic cell-subtype proportions from bulk RNA-seq and benchmarked them against single-nucleus RNA-seq and stereological densities from matched donors. We assessed SCZ- and age-associated changes in cell proportions and per-cell gene expression.

Results

SCZ was associated with altered proportions of neocortical parvalbumin (PVALB) and somatostatin (SST) cells, depending on the subject’s age at death. Younger SCZ cases (age < 70 years) showed reduced PVALB and SST cell proportions, while older cases showed unchanged or increased proportions compared with controls. Earlier-onset SCZ, associated with more severe clinical symptoms, was linked to greater reductions in these cell types. Additionally, there was robust evidence for reduced per-cell SST and vasoactive intestinal peptide mRNA among younger cases with SCZ.

Conclusions

These findings suggest that SCZ is associated with complex, age-dependent alterations in GABAergic neurons, particularly affecting PVALB and SST cells. Our study underscores the importance of age-stratified analyses in SCZ, suggesting that distinct pathological processes underlie GABAergic neuron dysregulation across different age and symptom-severity groups and warranting tailored therapeutic approaches.

皮质GABAergic （γ -氨基丁酸能）神经元失调与精神分裂症（SCZ）有关，但尚不清楚这些变化是由于细胞比例的改变还是细胞内信使RNA （mRNA）表达的改变。方法我们分析了1408个个体（672例SCZ病例，736例对照组）在3个新皮质区域的14个大容量和细胞类型特异性RNA测序（RNA-seq）数据集。我们从大量RNA-seq中解卷积GABAergic细胞亚型比例，并将其与匹配供体的单核RNA-seq和体视学密度进行比较。我们评估了SCZ和年龄相关的细胞比例和每个细胞基因表达的变化。结果scz与新皮质小白蛋白（PVALB）和生长抑素（SST）细胞比例的改变有关，这取决于受试者死亡时的年龄。较年轻的SCZ病例（年龄70岁）显示PVALB和SST细胞比例降低，而较年长的病例与对照组相比，PVALB和SST细胞比例不变或增加。早发性SCZ与更严重的临床症状相关，与这些细胞类型的更大减少有关。此外，有强有力的证据表明，年轻SCZ患者的每细胞SST和血管活性肠肽mRNA降低。这些发现表明SCZ与gaba能神经元复杂的年龄依赖性改变有关，特别是影响PVALB和SST细胞。我们的研究强调了SCZ中年龄分层分析的重要性，表明不同的病理过程是不同年龄和症状严重程度组gaba能神经元失调的基础，需要量身定制的治疗方法。

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引用次数: 0

Using Multi-Omic Signatures in the Understanding of Inflammation and Psychosis: Can Methylation-Derived White Blood Cell Proportions Guide Early Intervention? 使用多组学特征来理解炎症和精神病：甲基化衍生的白细胞比例能否指导早期干预？

IF 3.7 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2025-09-08 DOI: 10.1016/j.bpsgos.2025.100580

Scott Richard Clark , Victoria Kiriaki Arnet , Magdalene C. Jawahar , Catherine Toben , K. Oliver Schubert , Azmeraw T. Amare

引用次数: 0

Bipolar Disorder VII: Family History and Its Relationship With Suicide Attempts, Severity, and the Prophylactic Effect of Lithium Treatment in a Long-Term Follow-Up Study of Bipolar Disorder 双相情感障碍VII：家族史及其与自杀企图、严重程度的关系，以及锂治疗在双相情感障碍长期随访研究中的预防作用

IF 3.7 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2025-09-06 DOI: 10.1016/j.bpsgos.2025.100608

Per-Olof Nylander , Erik Lexne , Christer Lehman , Lars Brudin , Finn Bengtsson

Background

Family history (FH) of affective disorders (ADs) is important for the course of bipolar disorder (BD).

Methods

In a long-term study (mean 25 years), 192 patients with BD diagnosed by DSM-IV criteria were recruited from lithium dispensaries. Differences between patients with and without an FH of ADs were studied.

Results

Patients with an FH of AD had poorer lithium response (p = .027), earlier age of onset (AOO) (p < .001), were younger (p = .009), made suicide attempts (SAs) earlier after onset (p = .012), and had more episodes/year (p = .017) and depressive episodes/year (p = .010) before SA. SAs were more common (p = .028) in patients with an FH of AD. SAs were more common (p = .001) before lithium treatment, and SAs (p < .001) were only present in patients with an FH of AD within the first 5 years after AOO. Patients with an FH of AD had more episodes (p = .009), episodes/year (p = .002), depressive episodes (p < .001), and depressive episodes/year (p < .001) during their lifetime. Before lithium, episodes (p = .009), depressive episodes (p = .006), and depressive episodes/year (p = .010) were more common in patients with an FH of AD. Manic episodes (p = .020) were more common in patients with no FH of AD. On lithium, episodes (p = .010), episodes/year (p = .001), depressive episodes (p < .001), and depressive episodes/year (p < .001) were more common in patients with an FH of AD. FH of suicide was present only among patients with an FH of AD (p < .001).

Conclusions

BD patients with an FH of AD have a more severe form of BD with a special effect on SAs, AOO, episodes, and lithium response in BD.

情感性障碍家族史（FH）对双相情感障碍（BD）的病程具有重要意义。方法在一项长期研究中（平均25年），从锂药房招募192例符合DSM-IV标准的BD患者。研究了有和没有ad FH的患者之间的差异。结果AD FH患者锂离子反应较差（p = 0.027），发病年龄较早（p < 0.001），年龄较小（p = 0.009），发病后自杀未遂（p = 0.012）早（p = 0.012）， SA前每年发作次数较多（p = 0.017），抑郁发作次数较多（p = 0.010）。sa在AD的FH患者中更为常见（p = 0.028）。锂治疗前SAs更为常见（p = 0.001），而SAs仅存在于AOO后前5年内的AD FH患者中（p < 0.001）。AD的FH患者在其一生中有更多的发作（p = 0.009）、发作/年（p = 0.002）、抑郁发作（p < 0.001）和抑郁发作/年（p < 0.001）。在使用锂离子治疗前，发作（p = 0.009）、抑郁发作（p = 0.006）和抑郁发作/年（p = 0.010）在AD的FH患者中更为常见。躁狂症发作（p = 0.020）在无FH或AD患者中更为常见。在锂治疗中，发作（p = 0.010）、发作/年（p = 0.001）、抑郁发作（p < 0.001）和抑郁发作/年（p < 0.001）在FH / AD患者中更为常见。自杀念头仅存在于阿尔茨海默病患者中（p < .001）。结论伴有AD的FH的BD患者具有更严重的BD形式，对BD的sa、AOO、发作和锂反应有特殊影响。

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引用次数: 0

Prediction of Episodic Memory With Multiomics Scores 用多组学评分预测情景记忆

IF 3.7 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2025-09-06 DOI: 10.1016/j.bpsgos.2025.100607

Anni L.K. Malmberg , Matti Pirinen , Johannes Kettunen , Katri Räikkönen , Johan G. Eriksson , Jari Lahti

Background

Episodic memory (EM) refers to the ability to encode and recall events—a vital cognitive function for healthy cognitive aging and an endophenotype for dementia.

Methods

Using genome- and metabolome-wide least absolute shrinkage and selection operator (LASSO) analysis, we developed polygenic (LASSO-PRS) and metabolic risk scores (MRS) in ∼68.5-year-old individuals (n = 897). We also applied the Bayesian regression method PRS-CS to an external genome-wide meta-analysis (GWAMA, N = 29,785, age > 18 years) to derive another PRS (GWAMA-PRS). We assessed incremental variances (R²) in EM explained by the PRSs and MRS separately and in combination beyond the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score in 104 independent ∼68.5-year-old individuals. Finally, we validated the PRSs in 2 independent pediatric cohorts (N = 309, age = ∼11.9 years; N = 443, age = ∼8.6 years).

Results

In the independent sample of ∼68.5-year-old individuals, compared with CAIDE score alone, accounting additionally for either MRS, LASSO-PRS, or GWAMA-PRS increased R² by 1.6, 5.6, and 4.5 percentage points (pp), respectively, while accounting additionally for MRS + LASSO-PRS or MRS + GWAMA-PRS increased R² by 7.8 and 6.4 pp, respectively. Both LASSO-PRS (all false discovery rate [FDR]–adjusted p values = .01–.03) and GWAMA-PRS (all FDR-adjusted p values = .03) were significantly associated with EM in all models, while the CAIDE score and MRS were not (all FDR-adjusted p values > .05). PRSs were not associated with EM in the pediatric cohorts (all FDR-adjusted p values > .05).

Conclusions

Genomics added predictive value to EM beyond epidemiological risk factors in adults, but the same was not observed with metabolomics. Adult-derived PRSs did not predict EM in children.

异速记忆（EM）是指编码和回忆事件的能力，是健康认知衰老的重要认知功能，也是痴呆症的一种内表型。方法利用基因组和代谢组最小绝对收缩和选择算子（LASSO）分析，我们在~ 68.5岁的个体（n = 897）中建立了多基因（LASSO- prs）和代谢风险评分（MRS）。我们还将贝叶斯回归方法PRS- cs应用于外部全基因组荟萃分析（GWAMA, N = 29,785，年龄>； 18岁），以获得另一个PRS （GWAMA-PRS）。我们评估了104名独立~ 68.5岁个体的心血管危险因素、衰老和痴呆发生率（CAIDE）评分之外，PRSs和MRS单独或联合解释的EM的增量方差（R2）。最后，我们在2个独立的儿科队列（N = 309，年龄= ~ 11.9岁；N = 443，年龄= ~ 8.6岁）中验证了PRSs。结果在68.5岁个体的独立样本中，与单独CAIDE评分相比，额外考虑MRS、LASSO-PRS或GWAMA-PRS分别使R2增加1.6、5.6和4.5个百分点（pp），而额外考虑MRS + LASSO-PRS或MRS + GWAMA-PRS分别使R2增加7.8和6.4个百分点（pp）。LASSO-PRS(所有错误发现率[FDR]调整后的p值= 0.01 -。在所有模型中，GWAMA-PRS（均经fdr校正p值= .03）与EM显著相关，而CAIDE评分和MRS无显著相关（均经fdr校正p值>； 0.05）。在儿科队列中，PRSs与EM无关（所有经fdr校正的p值>； 0.05）。结论基因组学对成人EM的预测价值超过流行病学危险因素，但代谢组学没有观察到同样的预测价值。成人衍生的PRSs不能预测儿童的EM。

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