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Aging disrupts the coordination between mRNA and protein expression in mouse and human midbrain
IF 11 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-29 DOI: 10.1038/s41380-025-02909-1
Silas A. Buck, Samuel J. Mabry, Jill R. Glausier, Tabitha Banks-Tibbs, Caroline Ward, Jenesis Kozel, Chen Fu, Kenneth N. Fish, David A. Lewis, Ryan W. Logan, Zachary Freyberg

Age-related dopamine (DA) neuron loss is a primary feature of Parkinson’s disease. However, whether similar biological processes occur during healthy aging, but to a lesser degree, remains unclear. We therefore determined whether midbrain DA neurons degenerate during aging in mice and humans. In mice, we identified no difference in midbrain neuron numbers throughout aging. Despite this, we found age-related decreases in midbrain mRNA expression of tyrosine hydroxylase (Th), the rate limiting enzyme of DA synthesis. Among midbrain glutamatergic cells, we similarly identified age-related declines in vesicular glutamate transporter 2 (Vglut2) mRNA expression. In co-transmitting Th+/Vglut2+ neurons, Th and Vglut2 transcripts decreased with aging. However, Th and Vglut2 protein levels in striatal synaptic release sites (e.g., terminals and axonal projections) did not differ throughout aging. Similar to the mouse, an initial study of human brain showed no effect of aging on midbrain neuron number with a concomitant decrease in TH and VGLUT2 mRNA expression. Unlike in mice, the density of striatal TH+ dopaminergic terminals was lower in aged human subjects. However, TH and VGLUT2 protein levels were unaffected in the remaining striatal boutons. Finally, in contrast to Th and Vglut2 mRNA, expression of most ribosomal genes in Th+ neurons was either maintained or even upregulated during aging. This suggests a homeostatic mechanism where age-related declines in transcriptional efficiency are overcome by ongoing ribosomal translation. Overall, we demonstrate species-conserved transcriptional effects of aging in midbrain dopaminergic and glutamatergic neurons that are not accompanied by marked cell death or lower striatal protein expression. This opens the door to novel therapeutic approaches to maintain neurotransmission and bolster neuronal resilience.

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引用次数: 0
Correction: Assessment and ascertainment in psychiatric molecular genetics: challenges and opportunities for cross-disorder research.
IF 9.6 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-28 DOI: 10.1038/s41380-025-02914-4
Na Cai, Brad Verhulst, Ole A Andreassen, Jan Buitelaar, Howard J Edenberg, John M Hettema, Michael Gandal, Andrew Grotzinger, Katherine Jonas, Phil Lee, Travis T Mallard, Manuel Mattheisen, Michael C Neale, John I Nurnberger, Wouter J Peyrot, Elliot M Tucker-Drob, Jordan W Smoller, Kenneth S Kendler
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引用次数: 0
D1 dopamine receptor antagonists as a new therapeutic strategy to treat autistic-like behaviours in lysosomal storage disorders 将 D1 多巴胺受体拮抗剂作为治疗溶酶体储积症中自闭症样行为的新疗法
IF 11 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-26 DOI: 10.1038/s41380-025-02904-6
Maria De Risi, Lorenzo Cusimano, Xabier Bujanda Cundin, Mariateresa Pizzo, Ylenia Gigante, Mariagrazia Monaco, Chiara Di Eugenio, Elvira De Leonibus

Lysosomal storage disorders characterized by defective heparan sulfate (HS) degradation, such as Mucopolysaccharidosis type IIIA-D (MPS-IIIA-D), result in neurodegeneration and dementia in children. However, dementia is preceded by severe autistic-like behaviours (ALBs), presenting as hyperactivity, stereotypies, social interaction deficits, and sleep disturbances. The absence of experimental studies on ALBs’ mechanisms in MPS-III has led clinicians to adopt symptomatic treatments, such as antipsychotics, which are used for non-genetic neuropsychiatric disorders. However, they have limited efficacy in MPS-III and lead to higher extrapyramidal effects, leaving ALBs in MPS-IIIA as an unmet medical need with a significant burden on patients and their families. Using mouse and cellular models of MPS-IIIA, we have previously shown that ALBs result from increased proliferation of mesencephalic dopamine neurons during embryogenesis. In adulthood, MPS-IIIA mice exhibit an imbalance of dopaminergic receptor subtypes, resulting in striatal overstimulation of the D1 dopamine receptor (D1R)-direct pathway, contrasting with a downregulation of the D2 dopamine receptor (D2R)-indirect pathway. In this study, we aimed to provide an evidence-based pharmacological approach for managing ALBs in MPS-IIIA. We hypothesized that rebalancing dopaminergic receptor signalling with a D1R antagonist, rather than a D2 antagonist, would lead to safe and effective treatment. Neither risperidone nor methylphenidate improves ALBs in the MPS-IIIA mouse model, with the former showing increased cataleptic (extrapyramidal-like) side effects compared to littermate wild-type animals. Methylphenidate, however, showed some beneficial effects on neuroinflammation and later manifesting dementia-like behaviours. In contrast, ecopipam, a D1 antagonist already used in the clinic for other neuropsychiatric disorders, rescues ALBs, cognition, D1 hyperactivity, and does not worsen neurodegenerative signs. These results align with recent evidence highlighting the clinical relevance of D1 antagonists for neuropsychiatric disorders and pave the way for their use in managing psychotic symptoms in neurodegenerative disorders such as dementia with Lewy bodies.

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引用次数: 0
Longitudinal evolution of the transdiagnostic prodrome to severe mental disorders: a dynamic temporal network analysis informed by natural language processing and electronic health records 严重精神障碍的跨诊断前驱症状的纵向演变:由自然语言处理和电子健康记录提供信息的动态时间网络分析
IF 11 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-22 DOI: 10.1038/s41380-025-02896-3
Maite Arribas, Joseph M. Barnby, Rashmi Patel, Robert A. McCutcheon, Daisy Kornblum, Hitesh Shetty, Kamil Krakowski, Daniel Stahl, Nikolaos Koutsouleris, Philip McGuire, Paolo Fusar-Poli, Dominic Oliver

Modelling the prodrome to severe mental disorders (SMD), including unipolar mood disorders (UMD), bipolar mood disorders (BMD) and psychotic disorders (PSY), should consider both the evolution and interactions of symptoms and substance use (prodromal features) over time. Temporal network analysis can detect causal dependence between and within prodromal features by representing prodromal features as nodes, with their connections (edges) indicating the likelihood of one feature preceding the other. In SMD, node centrality could reveal insights into important prodromal features and potential intervention targets. Community analysis can identify commonly occurring feature groups to define SMD at-risk states. This retrospective (2-year) cohort study aimed to develop a global transdiagnostic SMD network of the temporal relationships between prodromal features and to examine within-group differences with sub-networks specific to UMD, BMD and PSY. Electronic health records (EHRs) from South London and Maudsley (SLaM) NHS Foundation Trust were included from 6462 individuals with SMD diagnoses (UMD:2066; BMD:740; PSY:3656). Validated natural language processing algorithms extracted the occurrence of 61 prodromal features every three months from two years to six months before SMD onset. Temporal networks of prodromal features were constructed using generalised vector autoregression panel analysis, adjusting for covariates. Edge weights (partial directed correlation coefficients, z) were reported in autocorrelative, unidirectional and bidirectional relationships. Centrality was calculated as the sum of (non-autoregressive) connections leaving (out-centrality, cout) or entering (in-centrality, cin) a node. The three sub-networks (UMD, BMD, PSY) were compared using permutation analysis, and community analysis was performed using Spinglass. The SMD network revealed strong autocorrelations (0.04 ≤ z ≤ 0.10), predominantly positive connections, and identified aggression (cout = 0.103) and tearfulness (cin = 0.134) as the most central features. Sub-networks for UMD, BMD, and PSY showed minimal differences, with 3.5% of edges differing between UMD and PSY, 0.8% between UMD and BMD, and 0.4% between BMD and PSY. Community analysis identified one positive psychotic community (delusional thinking-hallucinations-paranoia) and two behavioural communities (aggression-cannabis use-cocaine use-hostility, aggression-agitation-hostility) as the most common. This study represents the most extensive temporal network analysis conducted on the longitudinal interplay of SMD prodromal features. The findings provide further evidence to support transdiagnostic early detection services across SMD, refine assessments to detect individuals at risk and identify central features as potential intervention targets.

对包括单极情绪障碍(UMD)、双相情绪障碍(BMD)和精神障碍(PSY)在内的严重精神障碍(SMD)的前驱期进行建模,应考虑症状和物质使用(前驱期特征)随时间的演变和相互作用。时间网络分析可以通过将前驱特征表示为节点来检测前驱特征之间和内部的因果依赖性,它们的连接(边)表明一个特征先于另一个特征的可能性。在SMD中,节点中心性可以揭示重要的前驱特征和潜在的干预目标。社区分析可以识别常见的特征组,以定义SMD处于危险状态。这项回顾性(2年)队列研究旨在建立一个全球跨诊断的SMD网络,了解前驱特征之间的时间关系,并研究UMD、BMD和PSY特异性子网络的组内差异。来自南伦敦和莫兹利NHS基金会信托基金的电子健康记录(EHRs)来自6462名SMD诊断患者(UMD:2066;弹道导弹防御:740;小组:3656)。经过验证的自然语言处理算法在SMD发病前2 - 6个月每3个月提取61个前驱特征。前驱特征的时间网络使用广义向量自回归面板分析构建,调整协变量。边权(偏有向相关系数,z)具有自相关、单向和双向关系。中心性被计算为离开(外中心性,cout)或进入(中心性,cin)节点的(非自回归)连接的总和。采用排列分析比较3个子网络(UMD、BMD、PSY),并采用Spinglass进行群落分析。SMD网络表现出较强的自相关性(0.04≤z≤0.10),以正向连接为主,攻击性(cout = 0.103)和泪流满面(cin = 0.134)是最主要的特征。UMD、BMD和PSY的子网络差异很小,UMD和PSY之间的边缘差异为3.5%,UMD和BMD之间的边缘差异为0.8%,BMD和PSY之间的边缘差异为0.4%。社区分析确定了一个积极的精神病社区(妄想思维-幻觉-偏执)和两个行为社区(攻击-大麻使用-可卡因使用-敌意,攻击-激动-敌意)是最常见的。这项研究代表了对SMD前驱特征的纵向相互作用进行的最广泛的时间网络分析。研究结果为支持跨SMD的跨诊断早期检测服务提供了进一步的证据,改进了检测高危个体的评估,并确定了作为潜在干预目标的核心特征。
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引用次数: 0
Risk of suicide and all-cause death in patients with mental disorders: a nationwide cohort study 精神障碍患者的自杀和全因死亡风险:一项全国性队列研究
IF 11 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-22 DOI: 10.1038/s41380-025-02887-4
Hyewon Kim, Jin Hyung Jung, Kyungdo Han, Hong Jin Jeon

Mental disorders are associated with an increased risk of premature death, including suicide. This study aimed to examine the risk of suicide and all-cause death in patients with mental disorders after considering demographic, clinical, and lifestyle factors. Data from the National Health Insurance Sharing Service database and linked data from Statistics Korea were used. In total, 3,951,398 people aged ≥20 years were eligible for this study. Among the participants, 14 types of mental disorders were identified, and the subsequent incidences of suicide and all-cause death were monitored. The mean age of those with mental disorders and those without mental disorders was 56.5 (SD, 13.6) years and 46.6 (SD, 13.6) years, respectively. During an average follow-up period of 11.1 years (SD, 1.5), 249,830 participants died, of whom 12,290 died by suicide. Overall, the risk of suicide and all-cause death was higher in people with mental disorders than in controls. The risk of suicide was the highest among those with personality disorders, followed by those with bipolar disorder and schizophrenia spectrum disorder. The risk of all-cause death was the highest among those with intellectual disability, followed by those with schizophrenia spectrum disorder and alcohol use disorder. In conclusion, the risk of suicide and all-cause death increased among those with mental disorders, but there was substantial variation between the types of mental disorders for both suicide and all-cause death.

精神障碍与包括自杀在内的过早死亡风险增加有关。本研究的目的是在考虑人口统计学、临床和生活方式因素后,检查精神障碍患者自杀和全因死亡的风险。数据来自国家健康保险共享服务数据库和韩国统计局的相关数据。总共有3,951,398名年龄≥20岁的人符合本研究的条件。在参与者中,确定了14种类型的精神障碍,并监测了随后的自杀和全因死亡发生率。精神障碍组和无精神障碍组的平均年龄分别为56.5 (SD, 13.6)岁和46.6 (SD, 13.6)岁。在平均11.1年的随访期间(标准差1.5),249,830名参与者死亡,其中12,290人死于自杀。总体而言,精神障碍患者的自杀和全因死亡风险高于对照组。人格障碍患者的自杀风险最高,其次是双相情感障碍患者和精神分裂症谱系障碍患者。智力障碍患者的全因死亡风险最高,其次是精神分裂症谱系障碍患者和酒精使用障碍患者。综上所述,精神障碍患者自杀和全因死亡的风险增加,但自杀和全因死亡的精神障碍类型之间存在实质性差异。
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引用次数: 0
Differential impacts of germline and adult aggrecan knockout in PV+ neurons on perineuronal nets and PV+ neuronal function 种系和成体PV+神经元聚集蛋白敲除对神经元周围网络和PV+神经元功能的差异影响
IF 11 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-22 DOI: 10.1038/s41380-025-02894-5
Sverre Grødem, Elise Holter Thompson, Malin Benum Røe, Guro Helen Vatne, Ingeborg Nymoen Nystuen, Alessio Buccino, Tarjei Otterstad, Torkel Hafting, Marianne Fyhn, Kristian Kinden Lensjø

Perineuronal nets (PNNs) are a condensed form of extracellular matrix primarily found around parvalbumin-expressing (PV+) interneurons. The postnatal maturation of PV+ neurons is accompanied with the formation of PNNs and reduced plasticity. Alterations in PNN and PV+ neuron function have been described for mental disorders such as schizophrenia and autism. The formation of PNNs is highly dependent on aggrecan, a proteoglycan encoded by the ACAN gene, but it remains unknown if it is produced by the PV+ neurons themselves. Thus, we established a knockout (KO) mouse model (ACANflx/PVcre) and an adeno-associated virus to specifically eliminate aggrecan production from PV+ neurons, in the germline or adult animals, respectively. The germline KO (ACANflx/PVcre) eliminated the expression of PNNs labeled by Wisteria floribunda agglutinin (WFA), the most commonly used PNN marker. Surprisingly, electrophysiological properties of PV+ interneurons and ocular dominance plasticity of adult ACANflx/PVcre mice were similar to controls. In contrast, AAV-mediated ACAN knockout in adult mice increased ocular dominance plasticity. Moreover, in vivo Chondroitinase ABC treatment of KO mice resulted in reduced firing rate of PV+ cells and increased frequency of spontaneous excitatory postsynaptic currents (sEPSC), a phenotype associated with chABC treatment of WT animals. These findings suggest that compensatory mechanisms may be activated during development in response to the germline loss of aggrecan. Indeed, qPCR of bulk tissue indicates that other PNN components, including neurocan and tenascin-R, are expressed at higher levels in the KO animals. Finally, behavioral testing revealed that ACANflx/PVcre mice had similar long-term memory as controls in the Morris water maze. However, they employed bolder search strategies during spatial learning and showed lower level of anxiety-related behavior in an open field and zero maze.

神经周围网(PNNs)是细胞外基质的浓缩形式,主要存在于表达小蛋白(PV+)的中间神经元周围。出生后PV+神经元的成熟伴随着pnn的形成和可塑性的降低。PNN和PV+神经元功能的改变已被描述为精神障碍,如精神分裂症和自闭症。pnn的形成高度依赖于聚合蛋白,这是一种由ACAN基因编码的蛋白多糖,但它是否由PV+神经元自身产生尚不清楚。因此,我们建立了敲除(KO)小鼠模型(ACANflx/PVcre)和腺相关病毒,分别在种系动物和成年动物中特异性地消除PV+神经元的聚集蛋白产生。种系KO (ACANflx/PVcre)消除了Wisteria floribunda凝集素(WFA)标记的PNN的表达,WFA是最常用的PNN标志物。令人惊讶的是,成年ACANflx/PVcre小鼠PV+中间神经元的电生理特性和眼优势可塑性与对照组相似。相比之下,aav介导的ACAN敲除在成年小鼠中增加了眼优势可塑性。此外,KO小鼠体内软骨素酶ABC处理导致PV+细胞放电率降低,自发兴奋性突触后电流(sEPSC)频率增加,这是一种与WT动物chABC处理相关的表型。这些发现表明,补偿机制可能在发育过程中被激活,以响应种系聚集蛋白的丢失。事实上,大块组织的qPCR表明,其他PNN成分,包括neurocan和tenascin-R,在KO动物中表达水平较高。最后,行为测试显示,在Morris水迷宫中,ACANflx/PVcre小鼠具有与对照组相似的长期记忆。然而,在空间学习过程中,他们采用了更大胆的搜索策略,在开阔场地和零迷宫中表现出较低的焦虑相关行为。
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引用次数: 0
Reply to “Concerns regarding the interpretation of Shank3 protein isoforms expressed in Shank3B−/− mice: potential off-target effects by a neomycin resistance cassette” 回复“对Shank3B - / -小鼠中表达的Shank3蛋白亚型的解释的担忧:新霉素耐药盒的潜在脱靶效应”
IF 11 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-22 DOI: 10.1038/s41380-025-02903-7
Yi-Zhi Wang, Jeffrey N. Savas

We would like to express our sincere gratitude to Dr. Ruiying Ma and Dr. Kihoon Han for their thoughtful comments on our recent publication, “Neuron type-specific proteomics reveals distinct Shank3 proteoforms in iSPNs and dSPNs lead to striatal synaptopathy in Shank3B–/– mice“ [1, 2]. We are delighted by their strong interest in our work and found their two publications on Shank3NT both insightful and potentially relevant [3, 4]. Their research highlights the presence of Shank3NT in the Shank3B–/– brain and proposes a potential hypothesis that this may be due to potential off-target effects related to the neomycin resistance cassette in the Shank3 gene of the Shank3B–/– mouse model.

Drs. Ma and Han raised concerns about our decision not to discuss the potential “off-target effects related to the neomycin resistance cassette in the Shank3 gene” in this widely used mouse model of autism spectrum disorder (ASD). They also expressed unease over the wording in our paper’s title, specifically “distinct Shank3 proteoforms in iSPNs and dSPNs in Shank3B−/− mice.”

我们衷心感谢马瑞英博士和Kihoon Han博士对我们最近发表的论文《神经元类型特异性蛋白质组学揭示了Shank3B - / -小鼠中ispn和dSPNs中不同的Shank3蛋白形式导致纹状体突触病变》[1,2]的周到评论。我们很高兴他们对我们的工作有浓厚的兴趣,并发现他们在Shank3NT上发表的两篇文章既富有洞察力,又具有潜在的相关性[3,4]。他们的研究强调了Shank3B - / -大脑中Shank3NT的存在,并提出了一种潜在的假设,即这可能是由于Shank3B - / -小鼠模型中Shank3基因中新霉素耐药盒的潜在脱靶效应。Ma和Han对我们决定不讨论在这种广泛使用的自闭症谱系障碍(ASD)小鼠模型中潜在的“与Shank3基因中新霉素耐药盒相关的脱靶效应”表示担忧。他们还对我们论文标题中的措辞表示不安,特别是“Shank3B - / -小鼠的ispn和dspn中不同的Shank3蛋白形态”。
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引用次数: 0
Frequency-specific and state-dependent neural responses to brain stimulation 对大脑刺激的频率特异性和状态依赖性神经反应
IF 11 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-20 DOI: 10.1038/s41380-025-02892-7
Huichun Luo, Xiaolai Ye, Hui-Ting Cai, Mo Wang, Yue Wang, Qiangqiang Liu, Ying Xu, Ziyu Mao, Yanqing Cai, Jing Hong, Chencheng Zhang, Pengfei Wei, Yong Lu, Quanying Liu, Jiwen Xu, Ti-Fei Yuan

Non-invasive brain stimulation is promising for treating many neuropsychiatric and neurological conditions. It could be optimized by understanding its intracranial responses in different brain regions. We implanted multi-site intracranial electrodes and systematically assessed the acute responses in these regions to transcranial alternating current stimulation (tACS) at different frequencies. We observed robust neural oscillation changes in the hippocampus and amygdala in response to non-invasive tACS procedures, and these effects were frequency-specific and state-dependent. Notably, the hippocampus responded most strongly and stably to 10 Hz stimulation, with pronounced changes across a wide frequency range, suggesting the potential of 10 Hz oscillatory stimulation to modulate a broad range of neural activity related to cognitive functions. Future work with increased sample sizes is required to determine the clinical implications of these findings for therapeutic efficiency.

非侵入性脑刺激有望治疗许多神经精神和神经系统疾病。通过了解其在不同脑区的颅内反应,可以对其进行优化。我们植入多位点颅内电极,系统评估这些区域对不同频率经颅交流电刺激(tACS)的急性反应。我们观察到,在非侵入性tACS治疗过程中,海马和杏仁核出现了强劲的神经振荡变化,这些影响是频率特异性和状态依赖性的。值得注意的是,海马体对10hz的刺激反应最为强烈和稳定,在很宽的频率范围内都有明显的变化,这表明10hz振荡刺激可能调节与认知功能相关的广泛的神经活动。未来需要增加样本量的工作来确定这些发现对治疗效率的临床意义。
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引用次数: 0
Treatment-resistant depression: role of genetic factors in the perspective of clinical stratification and treatment personalisation 难治性抑郁症:遗传因素在临床分层和治疗个性化中的作用
IF 11 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-18 DOI: 10.1038/s41380-025-02899-0
Chiara Fabbri

Treatment-resistant depression (TRD) is associated with chronic depression, suicidal behaviours, and reduced quality of life. TRD has a demonstrated genetic component, estimated around 8% based on common genetic variation in unrelated individuals. However, only six genome-wide association studies of TRD were published, and no replicated signals at locus or gene level have been identified; furthermore, apparently opposite results were reported in terms of genetic overlap between TRD and other traits. Other than limited power, an important issue of previous studies was the scarce consideration of TRD heterogeneity, as TRD likely comprises different groups and talking about TRDs could be more appropriate. This review points out important issues in the definition of TRD and differences across samples included in previous studies, which can be partly responsible for the inconsistency across results. Different definitions of TRD should not be expected to have similar genetic profiles, and the whole TRD group can partitioned into subgroups, based on clinical and biological features, to increase reproducibility, as exemplified by recent findings. This can be a key factor to develop/repurpose targeted treatments, or simply to aid a more personalised prescription of available medications compared to current clinical practice, that is largely concentrated on the prescription of a limited number of antidepressants compared to those available.

难治性抑郁症(TRD)与慢性抑郁症、自杀行为和生活质量下降有关。TRD具有已证实的遗传成分,根据不相关个体的常见遗传变异估计约为8%。然而,仅发表了6项TRD全基因组关联研究,未发现位点或基因水平上的复制信号;此外,在TRD与其他性状的遗传重叠方面,报道了明显相反的结果。除了有限的研究能力外,以往研究的一个重要问题是很少考虑TRD的异质性,因为TRD可能由不同的群体组成,谈论TRD可能更合适。这篇综述指出了TRD定义中的重要问题,以及以往研究中样本之间的差异,这可能是导致结果不一致的部分原因。不应期望不同的TRD定义具有相似的遗传谱,最近的研究结果表明,整个TRD组可以根据临床和生物学特征划分为亚组,以增加可重复性。这可能是开发/重新定位靶向治疗的关键因素,或者仅仅是与目前的临床实践相比,帮助更个性化的现有药物处方,目前的临床实践主要集中在处方数量有限的抗抑郁药。
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引用次数: 0
Effects of oxytocin administration on non-social executive functions in humans: a preregistered systematic review and meta-analysis 催产素对人类非社会执行功能的影响:一项预注册的系统回顾和荟萃分析
IF 11 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-18 DOI: 10.1038/s41380-024-02871-4
Heemin Kang, Bernt D. Glaser, Alina I. Sartorius, Kristin Audunsdottir, Emilie Smith-Meyer Kildal, Terje Nærland, Ole A. Andreassen, Lars T. Westlye, Daniel S. Quintana

Background

Oxytocin has received considerable research attention for its role in affiliative behaviors, particularly regarding its pro-social effects. More recent evidence has pointed to a broader role of oxytocin signaling, which includes non-social cognitive processes. However, meta-analytic data on oxytocin’s effects on non-social cognition is currently limited.

Methods

We registered plans for a systematic review and meta-analysis on the effects of oxytocin administration on non-social executive functions prior to data collection via a time-stamped protocol. We performed searches in PubMed, Europe PubMed Central, and the Bielefeld Academic Search Engine. We conducted a meta-analysis of 20 effect estimates from 13 eligible studies. Subgroup meta-analyses and a test for publication bias were also performed.

Results

We found no overall significant effect of oxytocin administration on non-social executive functions (p = 0.30; Hedges’ g = 0.07). However, effect sizes across sub-categories of executive function varied, where the effect of oxytocin administration was the largest for cognitive flexibility (p = 0.02; Hedges’ g = 0.2). Publication bias was assessed using Robust Bayesian Meta-Analysis, which yielded moderate support for the absence of publication bias (BFPB = 0.32).

Conclusion

Our analysis suggests that oxytocin’s effects may extend beyond social cognitive processing as data synthesis provided evidence supporting a role in non-social cognitive flexibility. The data and analysis output from this meta-analysis can be viewed in a point-and-click web application.

催产素因其在附属行为中的作用,特别是其亲社会效应而受到了相当多的研究关注。最近的证据指出了催产素信号的更广泛作用,其中包括非社会认知过程。然而,关于催产素对非社会认知影响的meta分析数据目前有限。方法在数据收集之前,我们注册了一项系统评价和荟萃分析,研究催产素对非社会执行功能的影响。我们在PubMed, Europe PubMed Central和Bielefeld学术搜索引擎中进行了搜索。我们对13项符合条件的研究的20项效应估计进行了荟萃分析。还进行了亚组荟萃分析和发表偏倚检验。结果我们发现催产素对非社会执行功能的总体影响不显著(p = 0.30;对冲基金的g = 0.07)。然而,执行功能子类别的效应大小各不相同,其中催产素对认知灵活性的影响最大(p = 0.02;对冲的g = 0.2)。发表偏倚采用稳健贝叶斯荟萃分析进行评估,结果中等支持无发表偏倚(BFPB = 0.32)。我们的分析表明,催产素的作用可能超出了社会认知加工,因为数据综合提供了证据支持催产素在非社会认知灵活性中的作用。该元分析的数据和分析输出可以在点击式web应用程序中查看。
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引用次数: 0
期刊
Molecular Psychiatry
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