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The possibility of patients with adult-onset Niemann-Pick disease type C in cases diagnosed with schizophrenia: Analysis of NPC novel biomarkers 在诊断为精神分裂症的病例中,成人发病的尼曼-皮克病C型患者的可能性:NPC新生物标志物的分析
IF 3.2 2区 医学 Q1 PSYCHIATRY Pub Date : 2026-03-01 Epub Date: 2026-01-05 DOI: 10.1016/j.jpsychires.2026.01.009
Kumiko Fujii , Masamitsu Maekawa , Aya Narita , Yoshikatsu Eto , Masataka Shinozaki , Yosefu Arime , Hiroaki Okayasu , Kazutaka Shimoda , Yuji Ozeki

Background

When patients with schizophrenia on antipsychotic medication present neurological symptoms, it is often considered to be side effects of antipsychotics. In contrast, Niemann-Pick disease type C (NPC) has a wide variety of symptoms, and the diagnosis of adult-onset NPC is difficult. In this study, we measured novel biomarkers of NPC and examined the possibility of NPC in patients diagnosed with schizophrenia.

Methods

Five patients with schizophrenia and neurological symptoms were evaluated using the NPC Suspicion Index, and urinary bile acid and blood oxysterol levels were measured by LC-MS/MS and Q-TOF LC/MS. Lysosphingomyelin (SPC) and Lyso-SM-509(PPCS), reported as novel biomarkers for NPC, were measured in the plasma of 163 patients with schizophrenia and 111 healthy controls using LC-MS/MS. NPC1 and NPC2 gene analyses were performed on 124 patients using the next-generation sequencer. In one patient, Filipin staining was performed using skin fibroblasts.

Results

Among the five patients, one patient had an abnormal urinary bile acid level. Levels of SPC were significantly higher in patients than in healthy controls. Genetic analysis revealed no genetic mutations associated with the etiology. The patient who underwent Filipin staining had cholesterol-stained pale and was determined to be a variant type. However, it would be more accurate to state that no patients were identified as NPC based on these biomarkers.

Conclusion

Among the patients with schizophrenia, there were no cases that were definitively diagnosed as NPC, but some patients had features of NPC. It is important to evaluate mental and neurological symptoms in light of this possibility.
背景:当精神分裂症患者服用抗精神病药物时出现神经系统症状,通常被认为是抗精神病药物的副作用。相比之下,尼曼-皮克病C型(NPC)的症状多种多样,成人发病的NPC诊断困难。在这项研究中,我们测量了鼻咽癌的新生物标志物,并检查了诊断为精神分裂症的患者中鼻咽癌的可能性。方法:采用NPC怀疑指数评价5例精神分裂症患者的神经系统症状,采用LC-MS/MS和Q-TOF LC/MS测定尿胆汁酸和血氧甾醇水平。采用LC-MS/MS对163例精神分裂症患者和111例健康对照者的血浆中溶血鞘磷脂(SPC)和溶血鞘磷脂-509(PPCS)进行了检测。使用新一代测序仪对124例患者进行NPC1和NPC2基因分析。在一名患者中,使用皮肤成纤维细胞进行Filipin染色。结果:5例患者中,1例患者尿胆汁酸异常。患者的SPC水平明显高于健康对照组。遗传分析显示没有与病因相关的基因突变。接受菲利平染色的患者有胆固醇染色的苍白,被确定为变异型。然而,更准确的说法是,没有患者根据这些生物标志物被确定为鼻咽癌。结论:在精神分裂症患者中,没有明确诊断为鼻咽癌的病例,但部分患者具有鼻咽癌的特征。鉴于这种可能性,评估精神和神经症状是很重要的。
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引用次数: 0
Can exercise reduce the risk of suicidal ideation and behaviors in youth at school? A 12-month cluster randomized control trial 运动能降低青少年在校期间自杀意念和行为的风险吗?一项为期12个月的随机对照试验。
IF 3.2 2区 医学 Q1 PSYCHIATRY Pub Date : 2026-03-01 Epub Date: 2025-12-11 DOI: 10.1016/j.jpsychires.2025.12.025
André O. Werneck , Xinhe Tian , Weicong Lu , Danping Li , Tao Liu , Shiyun Wu , Xiaoyue Li , Runhua Wang , Yanling Gao , Xian Li , Jinyong Chen , Davy Vancampfort , Marco Solmi , Nicholas Fabiano , Felipe Schuch , Paul L. Plener , Roger S. McIntyre , Kwok-Fai So , Brendon Stubbs , Kangguang Lin
Our aim was to investigate the effect of an aerobic exercise intervention on risk of suicidal ideation, behaviors and nonsuicidal self-injury among adolescents. This analysis included secondary outcomes of a randomized controlled trial investigating a 12-month aerobic exercise intervention. The intervention consisted of six months of supervised exercise delivered in a school setting, followed by six months of unsupervised exercise. There were three-four sessions of supervised moderate-intensity activities (60–80 % maximum heart rate) lasting 30 min each, with an additional of 10 min of warm-up and cool-down over the initial period. Different clusters of students were randomized into either exercise or a psychoeducation control group. Risk of suicidal ideation and nonsuicidal self-injury were assessed using the Inventory of Statements About Self-Injury, and suicidal behavior was assessed using the Columbia-Suicide Severity Rating Scale. The outcomes were analyzed using intention to treat analyses. Trial registration (ClinicalTrials.gov register, NCT04816617). The final sample was composed of 628 adolescents (13.0 ± 0.4 years, 43.3 % girls). In the adjusted models, there was no intervention effect on nonsuicidal self-injury for the whole sample or according to baseline subclinical levels of depressive symptoms. The exercise group presented a 49 % lower incidence of nonsuicidal self-injury incidence in participants with low baseline levels of physical activity (IRR: 0.49; 95 %CI: 0.25–0.97). There was no effect of the intervention on risk of suicidal ideation and suicidal behavior. A 12-month aerobic exercise intervention was associated with lower incidence of nonsuicidal self-injury in participants with low baseline levels of physical activity. The exercise intervention had no effect on the risk suicidal ideation and suicidal behavior.
我们的目的是调查有氧运动干预对青少年自杀意念、行为和非自杀自伤风险的影响。该分析包括一项调查12个月有氧运动干预的随机对照试验的次要结果。干预包括在学校环境中进行为期六个月的有监督的锻炼,随后是为期六个月的无监督锻炼。有3 - 4次有监督的中等强度活动(60- 80%最大心率),每次持续30分钟,在初始阶段额外进行10分钟的热身和冷却。不同组的学生被随机分为锻炼组和心理教育对照组。自杀意念和非自杀自伤风险采用自伤陈述量表进行评估,自杀行为采用哥伦比亚自杀严重程度评定量表进行评估。使用意向治疗分析对结果进行分析。试验注册(ClinicalTrials.gov注册,NCT04816617)。最终样本由628名青少年组成(13.0±0.4岁,43.3%为女孩)。在调整后的模型中,对于整个样本或根据基线亚临床抑郁症状水平,对非自杀性自伤没有干预作用。在低基线体力活动水平的参与者中,运动组的非自杀性自伤发生率降低了49% (IRR: 0.49; 95% CI: 0.25-0.97)。干预对自杀意念和自杀行为的风险没有影响。在基线体力活动水平较低的参与者中,12个月的有氧运动干预与较低的非自杀性自伤发生率相关。运动干预对自杀意念和自杀行为风险无影响。
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引用次数: 0
Stimulant and non-stimulant ADHD medication prescriptions for homeless veteran service users with mental illness 为患有精神疾病的无家可归的退伍军人提供兴奋剂和非兴奋剂的ADHD药物处方
IF 3.2 2区 医学 Q1 PSYCHIATRY Pub Date : 2026-03-01 Epub Date: 2026-01-09 DOI: 10.1016/j.jpsychires.2026.01.017
Katherine A. Koh , Dorota Szymkowiak , Jack Tsai

Objective

Prescribing of ADHD medications has not been examined in the US homeless population. This study examined frequency of prescriptions for stimulant and non-stimulant ADHD medications, as well as risky and potentially inappropriate prescribing (RPIP) of stimulants, in three groups of veterans with mental illness.

Methods

Using 2021–2022 national VA administrative data, we compared frequency of stimulant and non-stimulant ADHD medication prescriptions using logistic regression between homeless veterans (n = 105,062), veterans in the Department of Housing and Urban Development-VA Supportive Housing (HUD-VASH; n = 33,884), and independently housed (IH) veterans (n = 1,875,083). We also compared indicators of RPIP of stimulants using chi-square tests between the three groups.

Results

Adjusted for sociodemographic, clinical, and health care utilization characteristics, homeless veterans were less likely to be prescribed stimulants (adjusted odds ratio (aOR) = 0.80, 99 % CI = 0.76–0.85) relative to IH veterans and more likely to be prescribed non-stimulants (aOR = 1.12, CI = 1.06–1.18). However, among veterans prescribed stimulants, homeless veterans had more indicators of RPIP, including being prescribed stimulants in the presence of a psychotic disorder (7.9 % vs. 6.4 % for HUD-VASH vs. 2.2 % for IH, p < .001).

Conclusion

Homeless veterans with mental illness were less likely to be prescribed stimulants and more likely to be prescribed non-stimulant ADHD medications relative to IH veterans with mental illness. However, RPIP of stimulant prescriptions was more common for homeless and HUD-VASH veterans relative to IH veterans.
目的:在美国无家可归的人群中,尚未对ADHD药物的处方进行研究。这项研究调查了三组患有精神疾病的退伍军人中兴奋剂和非兴奋剂药物的处方频率,以及有风险和潜在不适当的兴奋剂处方(RPIP)。方法使用2021-2022年国家退伍军人管理局的数据,我们使用logistic回归比较了无家可归的退伍军人(n = 105,062)、住房和城市发展部-退伍军人保障性住房(HUD-VASH; n = 33,884)和独立居住(IH)退伍军人(n = 1,875,083)之间兴奋剂和非兴奋剂ADHD药物处方的频率。我们还使用卡方检验比较了三组之间兴奋剂的RPIP指标。结果:经社会人口学、临床和卫生保健利用特征调整后,无家可归退伍军人相对于IH退伍军人更不可能开兴奋剂处方(调整优势比(aOR) = 0.80, 99% CI = 0.76-0.85),而更可能开非兴奋剂处方(aOR = 1.12, CI = 1.06-1.18)。然而,在服用兴奋剂的退伍军人中,无家可归的退伍军人有更多的RPIP指标,包括在存在精神障碍的情况下服用兴奋剂(HUD-VASH为7.9%,IH为6.4%,IH为2.2%,p < 0.001)。结论与患有精神疾病的无家可归退伍军人相比,患有精神疾病的无家可归退伍军人服用兴奋剂的可能性更小,而服用非兴奋剂类药物的可能性更大。然而,相对于IH退伍军人,兴奋剂处方的RPIP在无家可归者和HUD-VASH退伍军人中更为常见。
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引用次数: 0
Autonomic dysfunctions in psychotic disorders, interaction with antipsychotic intervention and treatment resistance: a comprehensive systematic review and meta-analysis 精神障碍中的自主神经功能障碍,与抗精神病药物干预和治疗抵抗的相互作用:一项全面的系统回顾和荟萃分析。
IF 3.2 2区 医学 Q1 PSYCHIATRY Pub Date : 2026-03-01 Epub Date: 2025-12-18 DOI: 10.1016/j.jpsychires.2025.12.041
Federica Iannotta , Felice Iasevoli , Claudio Caiazza , Michele Fornaro , Maria Nolano , Andrea de Bartolomeis

Background

Autonomic nervous system (ANS) dysfunctions have been increasingly implicated as a feature of psychoses’ pathophysiology. The specificity of these alterations and the role of antipsychotic medication remain controversial.

Methods

We conducted a systematic review and meta-analysis, following a predetermined protocol (PROSPERO/CRD42024510812) to assess heart-rate variability (HRV), electrodermal activity (EDA), and peripheral biomarkers in psychotic disorders. We searched PubMed and EMBASE from inception until July 2024. We conducted random-effects meta-analyses and assessed heterogeneity, publication bias, and risk of bias.

Results

Patients with psychosis showed a significant reduction in HRV compared to healthy controls, especially in indices reflecting parasympathetic activity. This result was evident in both treated and untreated patients and was also observed in the comparison between patients with psychosis and affective disorders. Among all antipsychotics, clozapine was associated with the greatest reduction in HRV. EDA and peripheral markers, i.e., alpha amylase and catecholamines, did not show significant differences between patients with psychosis and healthy controls. However, the skin conductance level (SCL) showed a trend to decrease after the introduction of antipsychotics.

Conclusions

These results suggest that ANS dysregulations may be a core feature of psychosis, only partially dependent on pharmacological treatment, suggesting a potential primary dysregulation within the Central Autonomic Network. Disruptions in neurotransmitter systems, particularly acetylcholine, may contribute. Autonomic profiling could refine psychiatric diagnosis, helping with tailored interventions. Longitudinal studies are needed to explore their potential in predicting treatment response.
背景:自主神经系统(ANS)功能障碍越来越多地被认为是精神病病理生理的一个特征。这些改变的特异性和抗精神病药物的作用仍然存在争议。方法:我们根据预先确定的方案(PROSPERO/CRD42024510812)进行了系统回顾和荟萃分析,以评估精神障碍患者的心率变异性(HRV)、皮电活动(EDA)和外周生物标志物。我们检索了PubMed和EMBASE从成立到2024年7月。我们进行了随机效应荟萃分析,并评估了异质性、发表偏倚和偏倚风险。结果:与健康对照相比,精神病患者的HRV显著降低,尤其是反映副交感神经活动的指标。这一结果在治疗和未治疗的患者中都很明显,在精神病和情感性障碍患者的比较中也可以观察到。在所有抗精神病药物中,氯氮平与HRV的最大降低相关。EDA和外周标志物,即α淀粉酶和儿茶酚胺,在精神病患者和健康对照组之间没有显着差异。然而,皮肤电导水平(SCL)在引入抗精神病药物后呈下降趋势。结论:这些结果表明,ANS失调可能是精神病的核心特征,仅部分依赖于药物治疗,这表明中枢自主神经网络可能存在原发性失调。神经递质系统的紊乱,尤其是乙酰胆碱,可能是原因之一。自主神经分析可以改进精神病诊断,帮助进行量身定制的干预。需要进行纵向研究以探索其在预测治疗反应方面的潜力。
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引用次数: 0
Astrocyte-mediated hippocampal damage in the pathogenesis of dysexecutive syndrome following COVID-19: A narrative review 星形胶质细胞介导的海马损伤在COVID-19后执行障碍综合征发病机制中的作用:一项叙述性综述。
IF 3.2 2区 医学 Q1 PSYCHIATRY Pub Date : 2026-03-01 Epub Date: 2026-01-03 DOI: 10.1016/j.jpsychires.2026.01.007
Antonino Messina , Fabrizio Bella , Giuliana Maccarone , Gabriele Avincola , Maria Salvina Signorelli
SARS-CoV-2 infection has been implicated in hippocampal damage, contributing to the pathogenesis of dysexecutive syndrome observed in post-COVID-19 patients. Given the growing prevalence of long-COVID worldwide, understanding how SARS-CoV-2 affects hippocampal structure and function has become an urgent scientific and clinical priority. The hippocampus—crucial for memory, emotional regulation, and executive functioning—is especially susceptible to viral-driven neuroinflammatory cascades. SARS-CoV-2 triggers astrocyte and microglia activation, disrupts blood–brain barrier integrity, and induces cytokine-mediated neurotoxicity, ultimately impairing neuroplasticity and neurogenesis. These mechanisms converge to produce cognitive and affective disturbances—most notably fatigue, apathy, low mood, and executive dysfunction—that typify dysexecutive syndrome in long-COVID.
This review synthesizes current evidence from clinical and experimental studies, integrating findings on viral neurotropism, hippocampal hypometabolism, and astrocyte-mediated neurodegeneration. Distinctions between depressive symptoms driven by neuroinflammation and classical depressive disorders are clarified to improve diagnostic accuracy and guide personalized treatment. Emerging data on the neuroprotective role of COVID-19 vaccination—particularly its capacity to modulate microglial activation and support hippocampal neurogenesis—are also examined. Overall, the findings underscore the need for targeted therapeutic strategies aimed at modulating neuroinflammation and supporting hippocampal plasticity, including cognitive rehabilitation approaches.
Longitudinal studies are essential to elucidate the enduring impact of SARS-CoV-2 on hippocampal function and to inform effective clinical interventions.
SARS-CoV-2感染与海马损伤有关,有助于在covid -19后患者中观察到的执行障碍综合征的发病机制。鉴于全球范围内长冠状病毒的流行率越来越高,了解SARS-CoV-2如何影响海马结构和功能已成为迫切的科学和临床重点。海马体对记忆、情绪调节和执行功能至关重要,它特别容易受到病毒驱动的神经炎症级联反应的影响。SARS-CoV-2触发星形胶质细胞和小胶质细胞激活,破坏血脑屏障完整性,诱导细胞因子介导的神经毒性,最终损害神经可塑性和神经发生。这些机制汇聚在一起,产生认知和情感障碍——最明显的是疲劳、冷漠、情绪低落和执行功能障碍——这是长期covid中典型的执行障碍综合征。这篇综述综合了目前临床和实验研究的证据,整合了病毒嗜神经性、海马低代谢和星形胶质细胞介导的神经变性的发现。阐明由神经炎症引起的抑郁症状与典型抑郁障碍之间的区别,以提高诊断准确性并指导个性化治疗。还研究了关于COVID-19疫苗的神经保护作用的新数据,特别是其调节小胶质细胞激活和支持海马神经发生的能力。总的来说,研究结果强调需要有针对性的治疗策略,旨在调节神经炎症和支持海马可塑性,包括认知康复方法。纵向研究对于阐明SARS-CoV-2对海马功能的持久影响以及为有效的临床干预提供信息至关重要。
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引用次数: 0
Effect of adding cognitive behavioral therapy to quetiapine on suicide risk, depressive symptoms, and coping style in adult patients with mood disorders 认知行为疗法加喹硫平对成年情绪障碍患者自杀风险、抑郁症状和应对方式的影响
IF 3.2 2区 医学 Q1 PSYCHIATRY Pub Date : 2026-03-01 Epub Date: 2026-01-03 DOI: 10.1016/j.jpsychires.2026.01.005
Ke Wang, Shan Cai, Xin-Rong Duanmu, Chen-Yu Ma, Rui Yan, Yan-Rui Cui, Lin Zhou, Liu-Liu Xu

Objective

Quetiapine is an atypical antipsychotic with a broad spectrum of use including anti-anxiety and mood stabilizing properties and has proved effective in mood disorders, such as major depressive disorder and bipolar depression. An integration of cognitive behavioral therapy (CBT) with pharmacological treatment has shown to outperform drugs alone in reducing suicide risk for patients with mood disorders. In this study, we investigated the effect of adding cognitive behavioral therapy (CBT) to quetiapine on suicide risk, depressive symptoms, and coping style in adult patients with mood disorders.

Methods

One hundred and thirty-seven patients were randomized to QUE group (n = 70) and QUE + CBT group (n = 67). The primary outcome was suicide risk assessed by the Nurses’ Global Assessment of Suicide Risk (NGASR) scale. The secondary outcomes were depressive symptoms assessed by the 24-item Hamilton Depression Rating Scale (HDRS-24) and coping style assessed by the Simplified Coping Style Questionnaire (SCSQ).

Results

The QUE + CBT group showed a significantly lower percentage with high suicide risk in the modified intention-to-treat population than the QUE group after 12-week intervention (χ2 = 5.50; p = 0.02). The analysis of covariance (ANCOVA) controlling for baseline scores indicated a significantly main effect of treatment in scores of NGASR [F(1, 135) = 25.30, p < 0.01, partial η2 = 0.16], HDRS-24 [F(1, 135) = 27.00, p < 0.01, partial η2 = 0.17], positive coping [F(1, 135) = 10.00, p < 0.01, partial η2 = 0.07] and negative coping of SCSQ [F(1, 135) = 26.70, p < 0.01, partial η2 = 0.17], suggesting that lower scores of NGASR and HDRS-24, a higher positive coping score, and a lower negative coping score in the QUE + CBT group than in the QUE group after 12-week intervention.

Conclusion

These results suggest that adding CBT to quetiapine could decrease suicide risk, improve depressive symptoms, and enhance coping style for adult patients with mood disorders.
目的:喹硫平是一种非典型抗精神病药物,具有广泛的抗焦虑和情绪稳定特性,已被证明对情绪障碍(如重度抑郁症和双相抑郁症)有效。认知行为疗法(CBT)与药物治疗相结合,在降低情绪障碍患者自杀风险方面的效果优于单独使用药物。在本研究中,我们研究了认知行为疗法(CBT)与喹硫平联合治疗对成年情绪障碍患者自杀风险、抑郁症状和应对方式的影响。方法:137例患者随机分为QUE组(n = 70)和QUE + CBT组(n = 67)。主要结果是自杀风险评估护士全球自杀风险评估(NGASR)量表。次要结局采用24项汉密尔顿抑郁评定量表(HDRS-24)评估抑郁症状,采用简化应对方式问卷(SCSQ)评估应对方式。结果:干预12周后,QUE + CBT组在修改意向治疗人群中的高自杀风险百分比明显低于QUE组(χ2 = 5.50; p = 0.02)。控制基线得分的协方差分析(ANCOVA)显示,治疗对NGASR得分[F(1,135) = 25.30, p 2 = 0.16]、HDRS-24得分[F(1,135) = 27.00, p 2 = 0.17]、积极应对[F(1,135) = 10.00, p 2 = 0.07]、SCSQ消极应对[F(1,135) = 26.70, p 2 = 0.17]有显著的主效应,提示NGASR和HDRS-24得分越低,积极应对得分越高。干预12周后,QUE + CBT组的消极应对得分低于QUE组。结论:在喹硫平基础上加用CBT可降低成年心境障碍患者自杀风险,改善抑郁症状,改善应对方式。
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引用次数: 0
Implicit social animations lead to distinct changes of dopaminergic, corticostriatal and thalamocortical functional connectivity in schizophrenia and bipolar disorder 内隐社会动画导致精神分裂症和双相情感障碍患者多巴胺能、皮质纹状体和丘脑皮质功能连通性发生明显变化
IF 3.2 2区 医学 Q1 PSYCHIATRY Pub Date : 2026-03-01 Epub Date: 2026-01-08 DOI: 10.1016/j.jpsychires.2026.01.016
Ricardo Martins , João Valente Duarte , Nuno Madeira , António Macedo , Miguel Castelo-Branco

Objective

Theory of mind (ToM) is a central pillar of social cognition and crucial for effective social interactions. Impairment in ToM is a major predictor of global functioning in schizophrenia (SCZ) and bipolar disorder (BPD). Based on the hypothesis that subcortical and reward circuit functional connectivity is distinct in SCZ and BPD and can be better revealed using ToM task-based approaches, we tested whether functional connectivity patterns of cortico-subcortical networks are a discriminative feature of these disorders.

Methods

We conducted a cross-sectional study (n = 60) to investigate the modulation of task-induced functional connectivity in SCZ (n = 20), BPD (n = 20), and healthy controls (n = 20) during implicit ToM processing with a visual paradigm leading to the interpretation of social meaning based on simple geometric figures with implied social content. Functional connectivity was estimated using generalized psychophysiological analysis of functional magnetic resonance imaging data.

Results

We found unique connectivity patterns in SCZ and BPD within subcortical loops. The SCZ group exhibited specifically disrupted connectivity in corticostriatal and thalamocortical pathways involving ToM and the mesolimbic pathways. A single common pattern of aberrant connectivity in BPD and SCZ occurred between the VTA and dorsal striatum, suggesting increased midbrain-striatal (actor-critic) connectivity in both disorders.

Conclusions

The unique patterns of altered connectivity in SCZ (imbalance between striatothalamic and thalamocortical connectivity), and BPD, while sharing a common pattern of increase between VTA and dorsal striatum, may represent candidate biomarkers of pathophysiological significance, or as biological targets for validating differential therapeutic neuromodulation.
目的心理理论是社会认知的核心支柱,对有效的社会互动至关重要。ToM损伤是精神分裂症(SCZ)和双相情感障碍(BPD)患者整体功能的主要预测因子。假设SCZ和BPD中皮层下和奖励回路的功能连接是不同的,并且可以通过基于ToM任务的方法更好地揭示,基于这一假设,我们测试了皮质-皮层下网络的功能连接模式是否是这些疾病的判别特征。方法采用横断面研究(n = 60),研究了SCZ (n = 20)、BPD (n = 20)和健康对照(n = 20)在内隐ToM加工过程中任务诱发功能连通性的调节,该加工采用视觉范式导致基于简单几何图形隐含社会内容的社会意义解释。使用功能磁共振成像数据的广义心理生理分析来估计功能连通性。结果我们在皮层下环路中发现了SCZ和BPD独特的连接模式。SCZ组在皮质纹状体和丘脑皮质通路中表现出特别的连接中断,包括ToM和中边缘通路。BPD和SCZ中一个共同的异常连通性模式发生在VTA和背侧纹状体之间,表明这两种疾病中中脑纹状体(行为者批评)的连通性增加。结论SCZ(纹状体和丘脑皮质连通性失衡)和BPD的独特连通性改变模式,以及VTA和背侧纹状体之间共同的增加模式,可能是具有病理生理意义的候选生物标志物,或作为验证差异治疗性神经调节的生物学靶点。
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引用次数: 0
A translational neuroscience & computational evaluation of a D1R partial agonist for schizophrenia (TRANSCENDS): Rationale and study design of a brain-based clinical trial 精神分裂症D1R部分激动剂的转化神经科学和计算评估(TRANSCENDS):基于大脑的临床试验的基本原理和研究设计
IF 3.2 2区 医学 Q1 PSYCHIATRY Pub Date : 2026-03-01 Epub Date: 2025-12-16 DOI: 10.1016/j.jpsychires.2025.12.020
Clara Fonteneau , Zailyn Tamayo , Ally Price , Lining Pan , Yvette Afriyie-Agyemang , Shriya Agrawal , Audrey Butler , Courtney Cail , Monica Calkins , Ananthsrinivas Rao Chakilam , Kimberlee Forselius-Bielen , Geena Fram , Allea Frazier , Roberto Gil , Preetika Govil , David L. Gray , Jack Grinband , Ruben C. Gur , Natalka K. Haubold , Zachary Heffernan , John H. Krystal
Despite decades of research, cognitive impairment remains a critical untreated symptom for many patients with schizophrenia. One way to accelerate the development of pro-cognitive therapies for schizophrenia is to evaluate compounds using biomarker approaches tailored to relevant neural mechanisms. While D1/D5 receptor (D1R/D5R) agonism has been extensively studied in neuroscience, its therapeutic potential for cognitive impairment in schizophrenia remains untapped. The Translational Neuroscience & Computational Evaluation of a D1R Partial Agonist for Schizophrenia (TRANSCENDS) clinical trial tests this mechanism using a ‘target engagement’ approach. Multiple, double-blind doses of a D1/D5R partial agonist were administered in advance of a functional neuroimaging (fMRI) session that deployed a cognitive paradigm explicitly designed to capture a translational micro-circuit mechanism underlying spatial working memory in patients with schizophrenia. Specifically, this study will assess whether the D1R/D5R partial agonist CVL-562 induces a dose-dependent engagement of spatial working memory circuits in schizophrenia using fMRI. This design, and the use of spatial working memory neural circuits as a dependent measure, was selected on the basis of a translational and computational understanding of prefrontal micro-circuitry and a mechanistic understanding of the role of D1R/D5Rs in schizophrenia. To enhance data integration and scalability, TRANSCENDS employs an automated informatics framework for seamless neuroimaging data sharing and electronic clinical data capture. This ensures high-standards for regulatory compliance, data quality, and data sharing across sites, improving aspects of current clinical trial data management. We share the study design and approach with the goal of advancing future pro-cognitive drug development and strategies for developing mechanistically-driven biomarkers in psychiatry.
尽管经过了几十年的研究,认知障碍仍然是许多精神分裂症患者未得到治疗的一个关键症状。加速发展精神分裂症的认知疗法的一种方法是使用针对相关神经机制量身定制的生物标志物方法来评估化合物。虽然D1/D5受体(D1R/D5R)激动作用在神经科学中已被广泛研究,但其治疗精神分裂症认知障碍的潜力尚未开发。精神分裂症D1R部分激动剂的转化神经科学计算评估(TRANSCENDS)临床试验使用“靶标参与”方法测试了这一机制。在功能神经成像(fMRI)检查之前,研究人员给药D1/D5R部分激动剂多次双盲剂量,该检查部署了一个明确设计的认知范式,以捕捉精神分裂症患者空间工作记忆背后的翻译微电路机制。具体来说,本研究将使用fMRI评估D1R/D5R部分激动剂CVL-562是否诱导精神分裂症患者空间工作记忆回路的剂量依赖性参与。基于对前额叶微电路的翻译和计算理解,以及对D1R/D5Rs在精神分裂症中的作用的机制理解,选择了这种设计,并使用空间工作记忆神经回路作为依赖测量。为了增强数据集成和可扩展性,TRANSCENDS采用自动化信息学框架进行无缝神经成像数据共享和电子临床数据捕获。这确保了高标准的法规遵从性、数据质量和跨站点的数据共享,改进了当前临床试验数据管理的各个方面。我们分享研究设计和方法的目标是推进未来的亲认知药物开发和开发精神病学中机械驱动的生物标志物的策略。
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引用次数: 0
Imaging transcriptomics identifies gene signatures associated with cortical thinning in schizophrenia 成像转录组学鉴定与精神分裂症患者皮质变薄相关的基因特征。
IF 3.2 2区 医学 Q1 PSYCHIATRY Pub Date : 2026-03-01 Epub Date: 2026-01-03 DOI: 10.1016/j.jpsychires.2026.01.008
Ye Tu , Shenrui Li , Shaodi Guan , Yueyang Xin , Hong Tao , Zhiqiang Zhou , Shaofang Wang , Hongwei Jiang , Hui Xu

Background

Schizophrenia, a debilitating neuropsychiatric disorder with profound socioeconomic consequences, manifests characteristic cortical thinning patterns observable through neuroimaging. While structural magnetic resonance imaging (MRI) studies consistently demonstrate these anatomical disturbances, their molecular signatures remain poorly understood.

Methods

We employed an integrative neuroimaging-transcriptomic approach, combining structural MRI data from 50 schizophrenia patients and 125 healthy controls with postmortem gene expression profiles from the Allen Human Brain Atlas. Spatial relationships between transcriptional patterns and cortical thickness variations were quantified using partial least squares regression. Subsequent analyses included gene ontology enrichment, cell-type deconvolution, and protein-protein interaction network.

Results

Schizophrenia patients demonstrated significant cortical thinning in limbic and paralimbic regions critical for emotional processing, including anterior cingulate and insular cortices. Imaging transcriptomic analyses revealed strong associations between cortical alterations and schizophrenia-risk genes STON2, ANK3, and KCNN3. Enriched biological pathways included stress-responsive signaling, calcium homeostasis, and synaptic plasticity. Cell-type analyses implicated excitatory and inhibitory neurons, together with microglia, while network analysis identified KCNB1, PTGS2, and TPT1 as central molecular hubs.

Conclusions

This study reveals specific molecular correlates of cortical thinning in schizophrenia, highlighting biological mechanisms that may contribute to structural abnormalities. The identified genes and pathways offer potential therapeutic targets for addressing both neuroanatomical changes and affective disturbances in schizophrenia.
背景:精神分裂症是一种衰弱的神经精神疾病,具有深刻的社会经济后果,通过神经影像学可以观察到其特征性的皮层变薄模式。虽然结构磁共振成像(MRI)研究一致地证明了这些解剖紊乱,但它们的分子特征仍然知之甚少。方法:我们采用了一种综合神经成像-转录组学方法,将来自50名精神分裂症患者和125名健康对照者的结构MRI数据与来自Allen人类大脑图谱的死后基因表达谱相结合。利用偏最小二乘回归量化了转录模式与皮质厚度变化之间的空间关系。随后的分析包括基因本体富集、细胞型反褶积和蛋白-蛋白相互作用网络。结果:精神分裂症患者在包括前扣带和岛状皮质在内的对情绪处理至关重要的边缘和副边缘区域表现出明显的皮质变薄。成像转录组学分析显示,皮质改变与精神分裂症风险基因STON2、ANK3和KCNN3之间存在强烈关联。富集的生物通路包括应激反应信号、钙稳态和突触可塑性。细胞类型分析涉及兴奋性和抑制性神经元,以及小胶质细胞,而网络分析确定KCNB1, PTGS2和TPT1是中心分子枢纽。结论:这项研究揭示了精神分裂症患者皮层变薄的特定分子相关,强调了可能导致结构异常的生物学机制。已确定的基因和途径为解决精神分裂症的神经解剖变化和情感障碍提供了潜在的治疗靶点。
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引用次数: 0
Mapping dopamine's role in obsessive-compulsive disorder: A scoping review of neural circuits, brain regions, and behavioral implications 绘制多巴胺在强迫症中的作用:神经回路、大脑区域和行为影响的范围审查
IF 3.2 2区 医学 Q1 PSYCHIATRY Pub Date : 2026-03-01 Epub Date: 2025-12-12 DOI: 10.1016/j.jpsychires.2025.12.007
Pedro Mota , Maria Picó-Pérez , Pedro Morgado
Dopamine plays a central role in various brain functions and has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). This scoping review examines the role of dopamine in OCD, focusing on its impact on neural circuits, brain regions, and behavioral manifestations. Evidence from 19 studies reveals consistent dopaminergic dysfunction across key brain structures, particularly in the cortico-striato-thalamo-cortical (CSTC) circuits. Altered dopamine receptor availability was observed in the dorsal striatum, ventral striatum, and anterior cingulate cortex, contributing to cognitive rigidity, emotional dysregulation, and compulsive behaviors. Pharmacological findings highlight the complexity of dopamine's role, with both hyperdopaminergic and hypodopaminergic states influencing symptoms. Dopamine antagonists and partial agonists have demonstrated efficacy in targeting overactivation of striatum and restoring cortical balance. These findings underscore the importance of dopamine as a therapeutic target and highlight the need for circuit-specific interventions and tailored treatment strategies.
多巴胺在各种脑功能中起着核心作用,并与强迫症(OCD)的病理生理学有关。这篇综述探讨了多巴胺在强迫症中的作用,重点是它对神经回路、大脑区域和行为表现的影响。来自19项研究的证据表明,在关键的大脑结构中,特别是在皮质-纹状体-丘脑-皮层(CSTC)回路中,多巴胺能功能障碍是一致的。在背纹状体、腹侧纹状体和前扣带皮层中观察到多巴胺受体可用性的改变,导致认知僵硬、情绪失调和强迫行为。药理学研究结果强调了多巴胺作用的复杂性,高多巴胺能和低多巴胺能状态都会影响症状。多巴胺拮抗剂和部分激动剂在纹状体过度激活和恢复皮层平衡方面已被证明有效。这些发现强调了多巴胺作为治疗靶点的重要性,并强调了对特定回路的干预和量身定制的治疗策略的必要性。
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引用次数: 0
期刊
Journal of psychiatric research
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