MOLECULAR PSYCHIATRY分子精神病学
MOLECULAR PSYCHIATRY(英文缩写 MOL PSYCHIATR),ISSN 1359-4184,eISSN 1476-5578,中文译名:分子精神病学 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-11-01 至 2026-10-31，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 13.437 | Q1 |
| 2022 | 11.000 | Q1 |
| 2023 | 9.600 | Q1 |
| 2024 | 10.100 | Q1 |
| 2025 | 10.400 | Q1 |
MOLECULAR PSYCHIATRY 最新收录文献
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1. Psychedelics and disorders of consciousness: a new frontier in neurotherapeutics.
PMID:日期:2026-10-03Disorders of consciousness (DoC), including coma, unresponsive wakefulness syndrome (also known as vegetative state), and minimally conscious state, represent profound disruptions in awareness and responsiveness due to severe brain injury, with limited therapeutic options available. Recent advancements in neuroimaging have improved our ability to detect residual brain activity in DoC patients, but effective interventions remain elusive. Psychedelics like psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT), which modulate brain network dynamics and enhance neural plasticity, have emerged as candidate pharmacological probes and potential therapeutic strategies for DoC. These substances primarily exert their effects through serotonin 2 A (5-HT) receptor agonism, inducing widespread changes in cortical activity and connectivity, in contrast to the reduced connectivity typically seen in DoC. The entropic brain hypothesis suggests that psychedelics increase neural entropy, potentially fostering more flexible brain states that could facilitate recovery in DoC patients by restoring communication between isolated brain regions. While direct human feasibility evidence has recently emerged from initial pilot and case studies, controlled clinical evidence demonstrating sustained restoration of consciousness remains absent. Consequently, key challenges such as determining optimal dosing, safety, and ethical considerations must be addressed before clinical application. This perspective reviews the neurobiological mechanisms of psychedelics, their potential for treating DoC, and the clinical and methodological hurdles to overcome, emphasizing the need for interdisciplinary research to translate these ideas into effective therapies. Moreover, this exploration contributes to a deeper understanding of consciousness and its modulation through pharmacological means.
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3. Network adaptability governs resilience and susceptibility to social defeat.
3. 网络适应性决定韧性和对社会逆境的易感性PMID:日期:2026-09-29Stress resilience-the ability to maintain mental health after adversity-manifests in humans and rodents as efficient threat-safety discrimination and fear extinction. Although behavioral differences between resilient and susceptible individuals are well documented, the brain-wide structural signatures that distinguish resilience, susceptibility, and impaired threat learning remain poorly defined. Using a translational mouse model of chronic social defeat stress in male C57BL/6 J mice (n = 55), combined with preregistered multimodal magnetic resonance imaging with graph-theoretical analyses, we identify structural and network-level correlates of three behavioral phenotypes. Resilient animals exhibited greater microstructural complexity in prefrontal regions, and showed signatures consistent with enhanced inhibitory gating within amygdalar circuits. In contrast, susceptible animals-defined behaviorally by fear generalization and resistance to extinction-exhibited dentate gyrus alterations across all measures, suggesting diminished microstructural adaptability. A third phenotype, impaired threat learning-mice that failed to avoid individuals from a threatening strain-was associated with altered CA1/CA2 microstructure and reduced structural connectivity in pons, pointing to disrupted hippocampal-brainstem interactions during memory consolidation. These findings demonstrate that resilience, susceptibility, and impaired threat learning arise from dissociable patterns of brain organization, with resilience reflecting adaptive circuit-level organization and susceptibility and impaired threat learning exhibiting distinct forms of microstructural and network reorganization.
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4. Double-blind, randomized clinical trial targeting theta oscillations with transcranial alternating current stimulation (tACS) for cognitive control in male methamphetamine patients.
PMID:日期:2026-09-29Methamphetamine use disorder is associated with significant cognitive control deficits, and effective treatments remain limited. Frontal midline theta (FM-theta) oscillations are implicated in cognitive control, but whether theta-frequency transcranial alternating current stimulation (theta-tACS) can improve proactive and reactive control in this population remains unclear. This study initially enrolled 68 male participants diagnosed with methamphetamine use disorder according to DSM-5 criteria. Among them, 56 individuals completed all study procedures and were included in the final analysis. Cognitive control was assessed using a conditional stop-signal task with concurrent EEG recording. The stimulation protocol comprised 15 consecutive daily sessions, during which participants received either active theta-tACS or sham stimulation (2 mA, FCz - Pz montage) in a double-blind design. Following the 15-day theta-tACS stimulation, patients exhibited a significant improvement in preparation cost (p = 0.001) and an increased inhibition rate (p = 0.003). EEG analyses showed that tACS selectively enhanced late-stage proactive control-related theta power (p = 0.026), without significantly modulating theta activity associated with reactive control (p > 0.05). Importantly, the tACS stimulation restored the functional coupling between FM-theta activity and proactive control performance (p = 0.04), and baseline late-stage theta power at T0 positively predicted improvement in preparation cost (ΔT1 - T0) during proactive control (p = 0.01). Finally, a mediation analysis revealed that the tACS-induced improvement in inhibition rate was mediated by the enhanced preparation cost. These findings suggested theta-tACS enhances proactive control by restoring the functional coupling between FM-theta activity and proactive control, which in turn triggers a cascading improvement in reactive control.
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5. Lithium chloride in vitro treatment shows potential to rescue the neuronal phenotype caused by WDFY3 haploinsufficiency.
PMID:日期:2026-09-27We provide a comprehensive phenotypic characterization of loss-of-function (LoF) variants in WDFY3 based on the largest cohort reported to date (n = 32). Our findings define a monogenic disorder marked by neuropsychiatric features (including autism and ADHD), mild to moderate neurodevelopmental delay, and variable brain growth - most commonly macrocephaly and in one case reduced head circumference. To investigate the effect of WDFY3 LoF we performed knockdown (KD) in the human neuroblastoma cell line SH-SY5Y and used a Wdfy3-haploinsufficient mouse model. WDFY3 KD impaired clearance of protein aggregates and decreased protein levels of the ubiquitin-binding protein p62. Transcriptomic analyses identified dysregulation in gene networks that are primarily involved in nervous system development, neuron projection, MAPK/ERK1/2, and WNT/β-catenin signaling. This was confirmed at protein level. Neuronal cell proliferation was increased, as evidenced by elevated cell counts and proliferation markers Ki-67 and PCNA. Conversely, neuronal cell differentiation was impaired, as indicated by reduced neurite outgrowth. We show that β-catenin is downregulated, while GSK3B is upregulated. LiCl activates WNT/β-catenin signaling by inhibiting GSK3B. We thus tested LiCl treatment, which significantly increased WDFY3 expression. Moreover, in vitro treatment improved the neurite branching capacity of Wdfy3-haploinsufficient neurons above the level of the wild type, although this specific effect appeared independent of WNT/β-catenin signaling. In sum, we expand on the phenotype related to WDFY3 LoF and provide insights into the pathophysiology using in vitro human and murine neuronal models. Our findings suggest that LiCl may serve as a potential therapeutic strategy for patients with WDFY3 LoF variants.
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6. Diagnosing autoimmune encephalitis in psychiatry: clinical recommendations and unresolved challenges from the GENERATE network.
6. 精神科自身免疫性脑炎的诊断：GENERATE网络的临床建议与未解决的挑战PMID:日期:2026-09-25[中文摘要] 精神科综合征可由潜在自身免疫性脑炎（AE）引起。这在精神病学与神经病学的交界处构成了诊断挑战。尽管AE多表现为合并的、复杂的神经精神综合征，但部分AE患者（初期）可能以 predominant 或孤立的精神症状就诊。这些病例难以分类，且不同临床环境下的诊断方法差异很大。本文来自德国自身免疫性脑炎研究网络（GENERATE），为精神科诊疗环境中疑似AE导致精神科综合征患者的诊断评估提供了来自精神病学和神经病学的跨学科专家建议。它将当前科学证据与不同医疗环境中常规临床实践的实际经验考量相结合。所提出的检测AE精神表现的诊断方法强调合理的、逐步的评估，包括临床评估、磁共振成像、脑电图、血液检测、脑脊液（CSF）分析以及血清和CSF中的神经元/胶质抗体检测。对于诊断不明确的个体，[¹⁸F]氟脱氧葡萄糖正电子发射断层扫描和先进抗体检测（例如，基于活细胞的检测）或神经影像技术（例如，体积分析）可提供额外的支持性信息。文中讨论了诊断模式的典型发现和局限性，以促进恰当解读并避免识别不足或过度诊断。重要的是，这些建议并非旨在定义新的疾病实体或诊断标准，而是为了支持对疑似由潜在AE引起的精神科综合征患者采取协调且务实的诊断方法。最后，概述了免疫精神病学这一不断发展领域中的关键未解决问题，并描述了有前景的研究策略。
[英文摘要] Psychiatric syndromes can be caused by underlying autoimmune encephalitis (AE). This represents a diagnostic challenge at the interface of psychiatry and neurology. While AE mostly manifests with a combined, complex neuropsychiatric syndrome, some patients with AE may (initially) present with predominant or isolated psychiatric symptoms. These cases can be difficult to classify, and diagnostic approaches vary considerably across clinical settings. This paper from the GErman NEtwork for Research on AuToimmune Encephalitis (GENERATE) provides interdisciplinary expert recommendations from psychiatry and neurology for the diagnostic evaluation of patients with suspected AE as the cause of psychiatric syndromes for psychiatric care settings. It integrates current scientific evidence with practical, empirical considerations from routine clinical care in different healthcare settings. The proposed diagnostic approach to detect psychiatric manifestations of AE emphasizes a rational, stepwise evaluation incorporating clinical assessment, magnetic resonance imaging, electroencephalography, blood testing, cerebrospinal fluid (CSF) analysis, and neuronal/glial antibody testing in serum and CSF. In diagnostically ambiguous individuals, [¹⁸F]fluorodeoxyglucose positron-emission-tomography and advanced antibody testing (e.g., live-cell-based assays) or neuroimaging techniques (e.g., volumetric analysis) may provide additional supportive information. Typical findings and limitations of diagnostic modalities are discussed to facilitate appropriate interpretation and to avoid under-recognition or overdiagnosis. Importantly, these recommendations do not aim to define new disease entities or diagnostic criteria, but rather to support a harmonized and pragmatic diagnostic approach to patients presenting with psychiatric syndromes suspected to be caused by underlying AE. Finally, key unresolved issues in this evolving field of immunopsychiatry are outlined, and promising research strategies are described.
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7. Multi-omics characterization of chronic social defeat stress recall-activated nuclei in Arc-GFP mice.
7. Arc-GFP小鼠中慢性社会挫败应激回忆激活核团的多组学表征PMID:日期:2026-09-24Susceptibility to chronic social stressors often results in the development of mental health disorders including major depressive and anxiety disorders. In contrast, some individuals remain resilient even after repeated stress exposure. Understanding the molecular drivers underlying these divergent phenotypic outcomes is crucial. However, previous studies using the chronic social defeat (CSD) stress model have been limited by the use of bulk tissues investigating single omics domains. To overcome these limitations, here, we applied the CSD mouse model to Arc-GFP mice for investigating the mechanistic divergence between susceptibility and resilience, specifically in stress recall-activated nuclei. By conducting an in-depth analysis of the less-known differential methylome landscape in the ventral hippocampus, we noted unique phenotype-specific alterations in multiple biological processes with an overrepresentation of GTPase-related mechanisms. Interestingly, the differentially methylated regions were enriched in ETS transcription factor binding sites (TFBSs), important targets of the Ras-ETS signaling pathway. This differential methylation in the ETS TFBSs could form the basis of persisting stress effects long after stressor exposure. Furthermore, by integrating the methylome modifications with transcriptomic alterations, we delineated the GTPase-related mechanisms differentially activated in the resilient and susceptible phenotypes with alterations in endocytosis overrepresented in the susceptible phenotype. Overall, our findings reveal novel insights underlying the resilience-susceptibility divergence.
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8. Disrupted PQBP1-HNRNPU-LINE-1 axis underlies aberrant neurodevelopment in renpenning syndrome.
8. 破坏的PQBP1-HNRNPU-LINE-1轴是Renpenning综合征神经发育异常的基础PMID:日期:2026-09-24Mutations in RNA splicing factor PQBP1 cause Renpenning syndrome (RS), yet whether LINE-1 (L1) contributes to RS pathogenesis remains unclear. Here, we generated human forebrain organoids model carrying a novel patient-derived PQBP1 variant (c.28 C > G; p.R10G), and observed impaired neurogenesis in RS organoids. Bulk and single-cell RNA-sequencing revealed that PQBP1 R10G mutation upregulated evolutionarily ancient L1 expression and induced aberrant L1 splicing, resulting in the redundant production of non-canonical L1-containing transcripts. Mechanistically, disrupted PQBP1-HNRNPU interaction by PQBP1 R10G mutation impaired U1/U2 small nuclear ribonucleoprotein (snRNP) recruitment to splicing sites, leading to increased L1-containing intron retention of neurodevelopmental genes, including WDR11. L1 retention reduced canonical WDR11 transcripts and consequently protein expression. Canonical WDR11, not L1-containing isoform, ameliorated the neurodevelopmental deficits of RS organoids. Together, our findings establish the dysregulated PQBP1-HNRNPU-L1 axis as a pathogenic driver of RS and nominate WDR11 as a potential therapeutic target for RS.
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9. Resilience beyond diagnosis: prospective neural correlates of better-than-expected outcomes in depression.
9. 超越诊断的韧性：抑郁症中优于预期结果的预期神经关联PMID:日期:2026-09-23Resilience, the ability to adapt positively in the face of adversity, is shaped by combined influences of risk and protective factors. Previous neuroimaging studies on resilience have predominantly focused on single factors, often operationalizing resilience dichotomously as the absence of psychiatric disorders despite adversity. In this prospective magnetic resonance imaging study, we defined resilience as "better-than-expected" depressive symptom severity (Hamilton Depression Rating Scale) relative to cumulative risk across 22 risk and protective variables. Using ridge-regularized regression in N = 1804 participants (955 healthy, 849 depressed) from the Marburg-Münster Affective Disorders Cohort Study, we predicted symptom severity and derived residuals as measures of resilience. Residuals were then used to predict gray matter volume (GMV) and cortical thickness at baseline (T1) and two-year follow-up (T2; N = 808). This approach was complemented by extreme-group comparisons of resilient (better-than-expected outcome) and vulnerable (worse-than-expected outcome) individuals. Cumulative risk explained 49.6% of variance in depressive symptoms at T1 and 40.1% at T2. Residual scores showed moderate temporal stability (r = 0.32, p < 0.001). Region-of-interest and whole-brain analyses revealed no morphometric associations with resilience at T1. In contrast, higher resilience at T1 predicted lower GMV in the left inferior orbitofrontal gyrus (IOFG) and temporal pole at T2 (ROI, p<0.001, r = 0.18), with no changes in cortical thickness. Taken together, resilience to cumulative risk, defined as better-than-expected depressive symptom severity, was not associated with immediate brain structural differences. However, prospective analyses revealed smaller GMV in the IOFG and temporal pole over time, potentially reflecting greater neural efficiency or delayed biological costs.
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10. Hippocampal AdipoR1 regulates the microglial response and delays disease progression in a mouse model of Alzheimer's disease.
10. 海马AdipoR1调控小胶质细胞反应并延缓阿尔茨海默病小鼠模型的疾病进展PMID:日期:2026-09-23Adiponectin, a key regulator of peripheral lipid metabolism, exhibits a positive correlation between its reduced peripheral and central levels and cognitive function in Alzheimer's disease (AD). Previous studies suggest that adiponectin primarily crosses the blood-brain barrier to exert its neuroprotective and anti-inflammatory effects within the brain. However, the detailed mechanisms through which adiponectin improves cognitive function in AD remain unclear. This study found that APP/PS1 mice exhibited cognitive impairment accompanied by decreased peripheral adiponectin levels and reduced adiponectin receptor 1 (AdipoR1) expression in the hippocampus (with no change in AdipoR2 expression). Knockdown of AdipoR1 in the hippocampus induced cognitive impairment and neuroinflammation in C57BL/6 J mice. Overexpression of AdipoR1 improved cognitive function, suppressed microglial activation and expression of inflammatory factors, promoted β-amyloid (Aβ) clearance, and inhibited excessive synaptic phagocytosis by microglia in AD model mice. In vitro and in vivo experiments revealed that AdipoR1 may regulate the activation and function of hippocampal microglia in AD by modulating their autophagy to reduce abnormal lipid droplet (LD) accumulation. This study demonstrates that AdipoR1 is a highly promising therapeutic target for restoring lipid homeostasis in AD microglia, coordinating the regulation of their phagocytic function, and delaying disease progression.