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Has Deep Brain Stimulation Shown Its Full Potential in Treatment-Resistant Depression? A Scoping Review 脑深部电刺激在治疗难治性抑郁症中发挥了全部潜力吗?范围检讨
IF 3.7 Q2 NEUROSCIENCES Pub Date : 2026-05-01 Epub Date: 2025-12-23 DOI: 10.1016/j.bpsgos.2025.100682
Liene Puke , Joelle Rosselet Amoussou , Armin von Gunten , Julien Elowe
Major depressive disorder is increasingly conceptualized as a networkopathy involving dysfunction across brain networks rather than isolated regions. This perspective has supported the use of deep brain stimulation (DBS) in treatment-resistant depression (TRD), where conventional therapies have failed. In this scoping review, we examined peer-reviewed studies on bilateral DBS for TRD, with a focus on the relationship between stimulation targets, conceptual frameworks of depression, and clinical outcome measures. A comprehensive literature search was conducted in September 2024 across 6 bibliographic databases, supplemented by citation tracking strategies to identify additional relevant studies. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we screened and selected studies based on predefined eligibility criteria. The review identified significant variability in how TRD is defined, which brain targets are selected, and how these are associated with specific symptom dimensions. Anatomical targets varied widely, reflecting differing neurobiological rationales. While most studies assessed symptom severity using standardized scales such as the Montgomery–Åsberg Depression Rating Scale or Hamilton Depression Rating Scale, a minority of studies (8 of 48 [16.7%]) did not specify which symptom dimensions were expected to respond to DBS. Despite methodological heterogeneity, DBS appears promising for symptom alleviation in TRD. However, its clinical benefits remain to be fully established. The review highlights the need for greater standardization, including consistent definitions of TRD, clear symptom mapping, and improved integration of patient-reported and functional outcomes. Although most existing studies focus on bilateral stimulation, future work should also explore unilateral and multitarget approaches to advance toward more personalized neuromodulation strategies.
重度抑郁症越来越被认为是一种涉及整个大脑网络功能障碍的网络病,而不是孤立的区域。这一观点支持了在传统疗法失败的难治性抑郁症(TRD)中使用深部脑刺激(DBS)。在这篇范围综述中,我们检查了同行评议的双侧DBS治疗TRD的研究,重点关注刺激目标、抑郁症概念框架和临床结果测量之间的关系。本文于2024年9月对6个书目数据库进行了全面的文献检索,并辅以引文跟踪策略来识别其他相关研究。根据系统评价和荟萃分析(PRISMA) 2020指南的首选报告项目,我们根据预定义的资格标准筛选和选择研究。该综述发现,在如何定义TRD、选择哪些脑靶点以及这些靶点如何与特定症状维度相关联方面存在显著差异。解剖靶点差异很大,反映了不同的神经生物学原理。虽然大多数研究使用标准化量表(如Montgomery -Åsberg抑郁评定量表或Hamilton抑郁评定量表)来评估症状严重程度,但少数研究(48项研究中的8项[16.7%])并未指定哪些症状维度预计对DBS有反应。尽管方法上存在异质性,但DBS似乎有望缓解TRD的症状。然而,其临床益处仍有待充分确定。该综述强调需要加强标准化,包括一致的TRD定义、明确的症状定位以及改进患者报告和功能结果的整合。虽然大多数现有的研究集中在双侧刺激,但未来的工作还应探索单侧和多靶点的方法,以推进更个性化的神经调节策略。
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引用次数: 0
Causal Effects of Enhanced Parenting on Resting-State Graph Properties of Adolescents at Risk for Maltreatment 强化教养对有虐待风险青少年静息状态图特性的因果影响
IF 3.7 Q2 NEUROSCIENCES Pub Date : 2026-03-01 Epub Date: 2025-10-29 DOI: 10.1016/j.bpsgos.2025.100646
Marta Korom , Mary Dozier , Hung-Wei Bernie Chen , Elisa Macera , Nim Tottenham , Jeffrey M. Spielberg

Background

In this study, we investigated the sustained causal effects of enhanced early caregiving quality on adolescent brain network properties approximately 11 years after families received an attachment-based parenting intervention.

Methods

Participants included 60 adolescents whose parents were referred by Child Protective Services (CPS) because of risk for child maltreatment and 35 adolescents from families without a CPS history (total N = 95). CPS-involved families were randomly assigned to either the target intervention (Attachment and Biobehavioral Catch-up [ABC]) (n = 31) or a control intervention (Developmental Education for Families [DEF]) (n = 29) before the infants turned 2. During adolescence (meanage = 13.4 years, SD = 0.37), participants underwent a 6-minute resting-state functional magnetic resonance imaging scan.

Results

Graph-theoretical analyses were completed with intervention status as the group-level predictor of interest. Adolescents who received the ABC intervention exhibited distinct global and local network properties compared with the DEF group. The ABC group demonstrated lower current-flow global efficiency and more hierarchical structure, indicating intervention-driven modulation of connectome-wide neurodevelopmental outcomes. Node-specific analyses also indicated intervention effects on clustering coefficients and communicability distances in frontal, limbic, and parietal cortices, suggesting nuanced effects of early interventions on local network properties. Exploratory moderation analyses revealed associations between brain network metrics and externalizing symptoms in the DEF group—indicative of neurobiological risk—that were absent in the ABC and low-risk groups.

Conclusions

The results suggest that the ABC intervention causally shapes the development of the resting-state connectome and associated regulatory health, offering insights into the neural pathways through which early enhanced care may get under the skin of at-risk adolescents.
在本研究中,我们调查了在家庭接受基于依恋的父母干预大约11年后,早期照顾质量的提高对青少年大脑网络特性的持续因果影响。方法研究对象包括父母因虐待儿童风险而被儿童保护服务(CPS)转介的60名青少年和来自无CPS史家庭的35名青少年(总N = 95)。参与cps的家庭在婴儿2岁之前被随机分配到目标干预(依恋和生物行为追赶[ABC]) (n = 31)或对照干预(家庭发展教育[DEF]) (n = 29)。在青少年时期(平均13.4岁,SD = 0.37),参与者接受了6分钟的静息状态功能磁共振成像扫描。结果以干预状态作为组水平感兴趣的预测因子,完成了图-理论分析。与DEF组相比,接受ABC干预的青少年表现出明显的全局和局部网络特性。ABC组表现出较低的电流整体效率和更分层的结构,表明干预驱动的连接体全神经发育结果的调节。节点特异性分析还表明,干预对额叶、边缘和顶叶皮层的聚类系数和交流距离有影响,表明早期干预对局部网络特性有细微影响。探索性调节分析揭示了DEF组中脑网络指标与外化症状之间的关联——这表明了神经生物学风险,而这在ABC组和低风险组中是不存在的。结论:ABC干预与静息状态连接体的发育和相关的调节健康有因果关系,为早期加强护理可能在高危青少年皮肤下的神经通路提供了见解。
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引用次数: 0
Lower Gyrification of the Ventromedial Prefrontal Cortex in Posttraumatic Stress Disorder: An ENIGMA-PTSD Study 创伤后应激障碍的腹内侧前额叶皮层下回化:一项ENIGMA-PTSD研究。
IF 3.7 Q2 NEUROSCIENCES Pub Date : 2026-03-01 Epub Date: 2025-12-18 DOI: 10.1016/j.bpsgos.2025.100679
Ahmed Hussain , C. Lexi Baird , Ashley A. Huggins , Courtney C. Russell , Delin Sun , Leonel Rangel-Jimenez , Chadi G. Abdallah , Michael Angstadt , Geoffrey May , Hannah Berg , Jennifer U. Blackford , Josh Cisler , Judith K. Daniels , Nicholas D. Davenport , Richard J. Davidson , Maria Densmore , Seth G. Disner , Wissam El-Hage , Amit Etkin , Negar Fani , Rajendra A. Morey

Background

Cortical gyrification involves the formation of folds in the cerebral cortex, coinciding with key neurodevelopmental processes. Its strong correlation with increased cortical surface area and decreased cortical thickness may improve cortical signaling efficiency by decreasing cortico-cortical distance. Differences in brain structure have been found in posttraumatic stress disorder (PTSD), yet few small studies have examined cortical gyrification.

Methods

Gyrification was quantified using FreeSurfer’s Local Gyrification Index (lGI), derived from 3-dimensional T1-weighted volumetric brain magnetic resonance imaging in 1876 participants (PTSD n = 789, control n = 1087) across 24 sites from the ENIGMA-PGC (Enhancing Neuro Imaging Genetics through Meta-Analysis and Psychiatric Genomics Consortium) PTSD working group. Using a region of interest–based approach, we fitted a linear mixed-effects model with age (mean = 35.6, SD = 9.23, range = 8–95), sex (female = 967 [52%], male = 909 [48%]), pial surface area, PTSD, and random site effects to test associations between PTSD diagnosis/severity and regional lGI. We examined moderating effects of depression, childhood trauma, age, and sex.

Results

PTSD diagnosis and severity were both associated with lower lGI for the right medial orbitofrontal and right rostral anterior cingulate cortices. The interaction of PTSD and age was associated with lower lGI for the rostral middle frontal cortex bilaterally. Contrasting comorbid PTSD and major depressive disorder with the PTSD-only group showed that comorbidity was associated with lower lGI in the left inferior and medial temporal cortices.

Conclusions

Lower lGI, which is associated with impaired signaling efficiency, was observed in the PTSD group compared with the control group for the ventromedial prefrontal cortex, a region that has been strongly implicated in associative fear learning and extinction. It is possible that PTSD accelerates the typical age-associated decline in lGI of the rostral middle frontal cortices.
背景:皮层回转涉及大脑皮层褶皱的形成,与关键的神经发育过程相一致。它与皮质表面积增加和皮质厚度减少密切相关,可能通过减少皮质-皮质距离来提高皮质信号传导效率。在创伤后应激障碍(PTSD)中已经发现了大脑结构的差异,但很少有小型研究检查皮质回旋。方法:使用FreeSurfer的局部旋转指数(lGI)对旋转进行量化,该指数来源于来自ENIGMA-PGC(通过meta分析增强神经成像遗传学和精神基因组学联盟)PTSD工作组的24个站点的1876名参与者(PTSD n = 789,对照组n = 1087)的三维t1加权体积脑磁共振成像。采用基于区域兴趣的方法,我们拟合了一个线性混合效应模型,包括年龄(平均值= 35.6,SD = 9.23,范围= 8-95)、性别(女性= 967[52%],男性= 909[48%])、脑平顶表面积、PTSD和随机部位效应,以检验PTSD诊断/严重程度与区域lGI之间的关系。我们研究了抑郁、童年创伤、年龄和性别的调节作用。结果:创伤后应激障碍的诊断和严重程度均与右侧眶额内侧和右侧吻侧前扣带皮层的低lGI有关。创伤后应激障碍和年龄的相互作用与双侧额叶中吻侧的低lGI有关。将合并PTSD和重度抑郁症的患者与仅合并PTSD的患者进行对比,发现合并PTSD与左下颞叶和内侧颞叶的lGI降低有关。结论:与对照组相比,PTSD组的腹内侧前额叶皮层(一个与联想恐惧学习和消退密切相关的区域)的lGI水平较低,与信号传导效率受损有关。创伤后应激障碍可能加速了典型的与年龄相关的吻侧中额叶皮层lGI下降。
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引用次数: 0
Motivational Significance of Control Failures as a Window on Risk for Problematic Alcohol Involvement 控制失败作为问题酒精介入风险窗口的动机意义
IF 3.7 Q2 NEUROSCIENCES Pub Date : 2026-03-01 Epub Date: 2025-12-17 DOI: 10.1016/j.bpsgos.2025.100658
Bruce D. Bartholow
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引用次数: 0
Brain State Dynamics in Ketamine-Induced Dissociation Resemble Those in Posttraumatic Stress Disorder 氯胺酮诱导解离的脑状态动力学与创伤后应激障碍相似
IF 3.7 Q2 NEUROSCIENCES Pub Date : 2026-03-01 Epub Date: 2025-11-13 DOI: 10.1016/j.bpsgos.2025.100655
Noam Goldway , Taly Markovits , Naomi Fine , Tom Fruchtman-Steinbok , Guy Gurevitch , Gustavo Deco , Haggai Sharon , Talma Hendler

Background

Dissociation, an altered state of consciousness in which individuals feel detached from their body, environment, and sense of self, is a common feature of posttraumatic stress disorder (PTSD). Despite its significance, the neurocognitive processes underlying dissociation remain poorly understood, potentially limiting diagnostic precision and treatment efficacy in PTSD.

Methods

To address this gap, we applied network control theory to resting-state functional magnetic resonance imaging to examine neural dynamics during dissociative states in 2 contexts: healthy volunteers (n = 30) undergoing intravenous administration of ketamine, an anesthetic known to induce dissociative states, and patients with PTSD receiving an intervention aimed at alleviating dissociative symptoms (a secondary analysis of data from 78 patients who participated in previously conducted clinical trials).

Results

Ketamine administration led to resting-state brain dynamics resembling those observed in patients with PTSD before treatment, characterized by an increased dominance of a default mode network (DMN) meta-state and a decreased dominance of a somatomotor network (SOM) meta-state. Posttreatment reduction in the dominance of the DMN meta-state correlated with a decrease in dissociative symptoms in patients with PTSD. Computational modeling analysis revealed that after treatment, patients with PTSD exhibited a more organized and less entropic brain state. However, contrary to our hypothesis, ketamine administration did not lead to significant changes in these entropy-related indices.

Conclusions

Dissociative states, whether induced by pharmacological manipulation or clinical condition, are accompanied by increased dominance of the DMN meta-state and reduced dominance of the SOM meta-state.
分离是一种意识状态的改变,在这种状态下,个体感觉与他们的身体、环境和自我意识分离,这是创伤后应激障碍(PTSD)的一个常见特征。尽管它具有重要意义,但人们对解离背后的神经认知过程知之甚少,这可能会限制PTSD的诊断准确性和治疗效果。为了解决这一问题,我们将网络控制理论应用于静息状态功能磁共振成像,研究两种情况下分离状态下的神经动力学:健康志愿者(n = 30)接受氯胺酮静脉注射,氯胺酮是一种已知可诱导解离状态的麻醉剂,PTSD患者接受旨在减轻解离症状的干预(对78名参与先前进行的临床试验的患者的数据进行二次分析)。结果氯胺酮导致静息状态脑动力学与治疗前PTSD患者相似,其特征是默认模式网络(DMN)元状态的优势增加,体运动网络(SOM)元状态的优势降低。治疗后DMN元状态主导地位的降低与PTSD患者分离症状的减少相关。计算模型分析显示,治疗后,PTSD患者表现出更有组织和更少熵的大脑状态。然而,与我们的假设相反,氯胺酮的施用并没有导致这些熵相关指数的显著变化。结论游离状态,无论是由药物操作还是临床条件引起的,都伴随着DMN元状态优势的增加和SOM元状态优势的减少。
{"title":"Brain State Dynamics in Ketamine-Induced Dissociation Resemble Those in Posttraumatic Stress Disorder","authors":"Noam Goldway ,&nbsp;Taly Markovits ,&nbsp;Naomi Fine ,&nbsp;Tom Fruchtman-Steinbok ,&nbsp;Guy Gurevitch ,&nbsp;Gustavo Deco ,&nbsp;Haggai Sharon ,&nbsp;Talma Hendler","doi":"10.1016/j.bpsgos.2025.100655","DOIUrl":"10.1016/j.bpsgos.2025.100655","url":null,"abstract":"<div><h3>Background</h3><div>Dissociation, an altered state of consciousness in which individuals feel detached from their body, environment, and sense of self, is a common feature of posttraumatic stress disorder (PTSD). Despite its significance, the neurocognitive processes underlying dissociation remain poorly understood, potentially limiting diagnostic precision and treatment efficacy in PTSD.</div></div><div><h3>Methods</h3><div>To address this gap, we applied network control theory to resting-state functional magnetic resonance imaging to examine neural dynamics during dissociative states in 2 contexts: healthy volunteers (<em>n</em> = 30) undergoing intravenous administration of ketamine, an anesthetic known to induce dissociative states, and patients with PTSD receiving an intervention aimed at alleviating dissociative symptoms (a secondary analysis of data from 78 patients who participated in previously conducted clinical trials).</div></div><div><h3>Results</h3><div>Ketamine administration led to resting-state brain dynamics resembling those observed in patients with PTSD before treatment, characterized by an increased dominance of a default mode network (DMN) meta-state and a decreased dominance of a somatomotor network (SOM) meta-state. Posttreatment reduction in the dominance of the DMN meta-state correlated with a decrease in dissociative symptoms in patients with PTSD. Computational modeling analysis revealed that after treatment, patients with PTSD exhibited a more organized and less entropic brain state. However, contrary to our hypothesis, ketamine administration did not lead to significant changes in these entropy-related indices.</div></div><div><h3>Conclusions</h3><div>Dissociative states, whether induced by pharmacological manipulation or clinical condition, are accompanied by increased dominance of the DMN meta-state and reduced dominance of the SOM meta-state.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100655"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885158","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
Stress History Modulates Corticotropin-Releasing Factor Neurons to Establish Resilience 应激史调节促肾上腺皮质激素释放因子神经元建立弹性
IF 3.7 Q2 NEUROSCIENCES Pub Date : 2026-03-01 Epub Date: 2025-11-19 DOI: 10.1016/j.bpsgos.2025.100656
Sherod E. Haynes , Anthony Lacagnina , Hyun Seong Seo , Fang Li , Xiao Yang , Muhammad Furqan Afzal , Carole Morel , Aurelie Menigoz , Kanaka Rajan , Roger L. Clem , Barbara Juarez , Helen S. Mayberg , Donald G. Rainnie , Larry J. Young , Ming-Hu Han

Background

Cumulative stress is a major risk factor for developing major depressive disorder (MDD), but not everyone experiencing chronic stress develops MDD. In those who do not, it is unclear at what point or by what mechanism a trajectory of stable resiliency emerges.

Methods

Utilizing a 10-day repeated social defeat stress (RSDS) model for MDD, we observed that a critical period between 7 and 10 daily defeats marks the phenotypical divergence of resilient from susceptible male mice. Cell-type selective electrophysiology, chemogenetics, optogenetics, and RNA quantification were used to investigate the nature of stress effects on neuroadaptation in the oval nucleus of the bed nucleus of the stria terminalis (BNSTov) required to determine resilience.

Results

In response to ongoing stress, corticotropin-releasing factor (CRF+, but not CRF) neurons of the BNSTov displayed a sustained increased firing rate in resilient but not susceptible mice. This neurophysiological adaptation was self-sustaining, but only after 7 critical stress exposures, indicating that the process of developing resilience is dependent on stress history.

Conclusions

Our study reveals a novel process by which individuals may persist in the face of adversity by way of stress-provoked activation, not inhibition of a key CRF limbic region that establishes a pathway to resilience.
背景累积压力是发展为重度抑郁症(MDD)的主要风险因素,但并不是每个经历慢性压力的人都会发展为重度抑郁症。对于那些不这样做的国家,目前尚不清楚在什么时候或通过什么机制出现了稳定的弹性轨迹。方法利用MDD的10天重复社会失败应激(RSDS)模型,我们观察到7 - 10天失败的关键时期标志着抗性和易感雄性小鼠的表型差异。采用细胞型选择性电生理学、化学遗传学、光遗传学和RNA定量研究了应激对终纹床核(BNSTov)卵形核神经适应的影响。结果在应激小鼠中,促肾上腺皮质激素释放因子(CRF+,而非CRF -)神经元对持续应激的反应显示出持续增加的放电率。这种神经生理适应是自我维持的,但仅在7次临界应激暴露之后,表明恢复力的发展过程依赖于应激史。结论我们的研究揭示了一个新的过程,即个体可能通过应激激活的方式在逆境中坚持下来,而不是通过抑制一个关键的CRF边缘区域来建立恢复力的途径。
{"title":"Stress History Modulates Corticotropin-Releasing Factor Neurons to Establish Resilience","authors":"Sherod E. Haynes ,&nbsp;Anthony Lacagnina ,&nbsp;Hyun Seong Seo ,&nbsp;Fang Li ,&nbsp;Xiao Yang ,&nbsp;Muhammad Furqan Afzal ,&nbsp;Carole Morel ,&nbsp;Aurelie Menigoz ,&nbsp;Kanaka Rajan ,&nbsp;Roger L. Clem ,&nbsp;Barbara Juarez ,&nbsp;Helen S. Mayberg ,&nbsp;Donald G. Rainnie ,&nbsp;Larry J. Young ,&nbsp;Ming-Hu Han","doi":"10.1016/j.bpsgos.2025.100656","DOIUrl":"10.1016/j.bpsgos.2025.100656","url":null,"abstract":"<div><h3>Background</h3><div>Cumulative stress is a major risk factor for developing major depressive disorder (MDD), but not everyone experiencing chronic stress develops MDD. In those who do not, it is unclear at what point or by what mechanism a trajectory of stable resiliency emerges.</div></div><div><h3>Methods</h3><div>Utilizing a 10-day repeated social defeat stress (RSDS) model for MDD, we observed that a critical period between 7 and 10 daily defeats marks the phenotypical divergence of resilient from susceptible male mice. Cell-type selective electrophysiology, chemogenetics, optogenetics, and RNA quantification were used to investigate the nature of stress effects on neuroadaptation in the oval nucleus of the bed nucleus of the stria terminalis (BNSTov) required to determine resilience.</div></div><div><h3>Results</h3><div>In response to ongoing stress, corticotropin-releasing factor (CRF<sup>+</sup>, but not CRF<sup>−</sup>) neurons of the BNSTov displayed a sustained increased firing rate in resilient but not susceptible mice. This neurophysiological adaptation was self-sustaining, but only after 7 critical stress exposures, indicating that the process of developing resilience is dependent on stress history.</div></div><div><h3>Conclusions</h3><div>Our study reveals a novel process by which individuals may persist in the face of adversity by way of stress-provoked activation, not inhibition of a key CRF limbic region that establishes a pathway to resilience.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100656"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038037","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
Moving Beyond Self-Report in Characterizing Drug Addiction: Using Drug-Biased Behavior to Predict Treatment Completion and Dropout in Heroin-Primary, Medication-Maintained Opioid Use Disorder 超越自我报告表征药物成瘾:使用药物偏见行为来预测海洛因原发性药物维持阿片类药物使用障碍的治疗完成和退出
IF 3.7 Q2 NEUROSCIENCES Pub Date : 2026-03-01 Epub Date: 2025-12-09 DOI: 10.1016/j.bpsgos.2025.100667
Natalie McClain , Ahmet O. Ceceli , Kathryn Drury , Greg Kronberg , Eric L. Garland , Nelly Alia-Klein , Rita Z. Goldstein

Background

Drug addiction is accompanied by enhanced salience attributed to drug over nondrug cues. This bias can be objectively measured and is reliable but underutilized in informing clinical end points, where self-report measures are most commonly used, with limited success.

Methods

We investigated whether behavioral picture choice (laboratory-simulated measure of drug seeking) and verbal fluency (drug and nondrug words generated) revealed drug-biased processing in 59 individuals with opioid use disorder (iOUDs) compared with 29 healthy control (HC) individuals; assessed twice, we also inspected the test-retest reliability of these tools. All iOUDs were heroin primary, abstinent (160.58 ± 188.18 days), and stabilized on medication for OUD at an inpatient treatment facility at baseline. Then, we tested whether, compared with self-report measures, these drug-biased behavioral measures could better predict prospective outcome measures in the iOUDs, i.e., study treatment completion as further validated using dropout from inpatient treatment.

Results

Results revealed that the iOUDs exhibited higher drug choice (ps < .036) and drug fluency (p = .008) compared with the HC individuals; task performance demonstrated the strong test-retest reliability of these measures. Controlling for cognitive demographics, the self-report drug-use severity and craving measures did not show significant associations with study treatment completion (|β| < 0.47, ps > .290), but drug-biased choice did (β = −0.75, p = .036; model comparison: ΔR2 = 0.10, p = .027). Importantly, these results were validated using inpatient treatment dropout as the outcome (drug-biased choice: β = 0.81, p = .049; model comparison: ΔR2 = 0.11, p = .035).

Conclusions

This study is the first to demonstrate reliable drug-biased choice and fluency in iOUDs. Compared with traditional self-reported drug-use and craving measures, the objective drug-biased cognitive behavioral measure was a significant predictor of treatment-related outcomes.
药物成瘾伴随着药物对非药物线索的显著性增强。这种偏倚是可以客观测量的,并且是可靠的,但在告知临床终点方面没有得到充分利用,其中自我报告测量最常用,成功率有限。方法研究了59名阿片类药物使用障碍(iOUDs)患者与29名健康对照(HC)患者的行为图片选择(实验室模拟药物寻找测量)和语言流畅性(生成药物和非药物单词)是否揭示了药物偏向加工;经过两次评估,我们还检查了这些工具的重测可靠性。所有宫内节育者均为海洛因原发者,戒断期(160.58±188.18天),基线时在住院治疗机构服药后病情稳定。然后,我们测试了与自我报告测量相比,这些药物偏倚行为测量是否能更好地预测宫内节育器的前瞻性结果测量,即通过住院治疗退出进一步验证的研究治疗完成情况。结果:与HC组相比,ioud组在药物选择(ps < .036)和药物流畅性(p = .008)方面表现出更高的水平;任务表现证明了这些测量的强重测信度。控制认知人口统计学,自我报告的药物使用严重程度和渴望措施与研究治疗完成没有显着关联(|β| < 0.47, ps > .290),但药物偏倚选择有显着关联(β = - 0.75, p = 0.036;模型比较:ΔR2 = 0.10, p = 0.027)。重要的是,这些结果以住院治疗退出作为结果(药物偏倚选择:β = 0.81, p = 0.049;模型比较:ΔR2 = 0.11, p = 0.035)。结论本研究首次证实了宫内节育器的药物偏向选择和流畅性。与传统的自我报告药物使用和渴望测量相比,客观药物偏见认知行为测量是治疗相关结果的显著预测因子。
{"title":"Moving Beyond Self-Report in Characterizing Drug Addiction: Using Drug-Biased Behavior to Predict Treatment Completion and Dropout in Heroin-Primary, Medication-Maintained Opioid Use Disorder","authors":"Natalie McClain ,&nbsp;Ahmet O. Ceceli ,&nbsp;Kathryn Drury ,&nbsp;Greg Kronberg ,&nbsp;Eric L. Garland ,&nbsp;Nelly Alia-Klein ,&nbsp;Rita Z. Goldstein","doi":"10.1016/j.bpsgos.2025.100667","DOIUrl":"10.1016/j.bpsgos.2025.100667","url":null,"abstract":"<div><h3>Background</h3><div>Drug addiction is accompanied by enhanced salience attributed to drug over nondrug cues. This bias can be objectively measured and is reliable but underutilized in informing clinical end points, where self-report measures are most commonly used, with limited success.</div></div><div><h3>Methods</h3><div>We investigated whether behavioral picture choice (laboratory-simulated measure of drug seeking) and verbal fluency (drug and nondrug words generated) revealed drug-biased processing in 59 individuals with opioid use disorder (iOUDs) compared with 29 healthy control (HC) individuals; assessed twice, we also inspected the test-retest reliability of these tools. All iOUDs were heroin primary, abstinent (160.58 ± 188.18 days), and stabilized on medication for OUD at an inpatient treatment facility at baseline. Then, we tested whether, compared with self-report measures, these drug-biased behavioral measures could better predict prospective outcome measures in the iOUDs, i.e., study treatment completion as further validated using dropout from inpatient treatment.</div></div><div><h3>Results</h3><div>Results revealed that the iOUDs exhibited higher drug choice (<em>p</em>s &lt; .036) and drug fluency (<em>p</em> = .008) compared with the HC individuals; task performance demonstrated the strong test-retest reliability of these measures. Controlling for cognitive demographics, the self-report drug-use severity and craving measures did not show significant associations with study treatment completion (|β| &lt; 0.47, <em>p</em>s &gt; .290), but drug-biased choice did (β = −0.75, <em>p</em> = .036; model comparison: Δ<em>R</em><sup>2</sup> = 0.10, <em>p</em> = .027). Importantly, these results were validated using inpatient treatment dropout as the outcome (drug-biased choice: β = 0.81, <em>p</em> = .049; model comparison: Δ<em>R</em><sup>2</sup> = 0.11, <em>p</em> = .035).</div></div><div><h3>Conclusions</h3><div>This study is the first to demonstrate reliable drug-biased choice and fluency in iOUDs. Compared with traditional self-reported drug-use and craving measures, the objective drug-biased cognitive behavioral measure was a significant predictor of treatment-related outcomes.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100667"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038039","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
Rare Variants in Antisense Long Noncoding RNA–Protein-Coding Gene Overlap Regions Contribute to Obsessive-Compulsive Disorder 反义长非编码rna -蛋白编码基因重叠区域的罕见变异与强迫症有关。
IF 3.7 Q2 NEUROSCIENCES Pub Date : 2026-03-01 Epub Date: 2025-12-23 DOI: 10.1016/j.bpsgos.2025.100683
Seulgi Jung , Madison Caballero , Shelby Smout , Behrang Mahjani

Background

Obsessive-compulsive disorder (OCD) is a prevalent neuropsychiatric disorder with an incompletely understood genetic basis, limiting targeted therapeutic options. Although previous rare-variant studies have primarily focused on protein-coding genes, the contribution of rare regulatory noncoding variants remains largely unexplored.

Methods

We analyzed whole-genome sequencing data from 2561 OCD cases and 12,974 controls from the All of Us Research Program to investigate rare conserved variants within 992 genomic regions where antisense long noncoding RNAs (lncRNAs) overlap protein-coding genes, using both Fisher’s exact test and the Optimal Sequence Kernel Association Test for association testing.

Results

We identified significant enrichment of rare conserved variants in the KNCN/MKNK1-AS1 overlap region in OCD cases (odds ratio = 5.1, false discovery rate < .05). This enrichment was significant in overlapping regions of genes with low evolutionary constraint. Expression analysis revealed strong coexpression of KNCN and MKNK1-AS1 specifically in striatal brain regions (nucleus accumbens: r = 0.83, putamen: r = 0.81, caudate: r = 0.79)—key components of circuits disrupted in OCD. Genes coexpressed with this regulatory pair were enriched for synaptic vesicle dynamics, calcium signaling, and established OCD risk genes from genome-wide association studies (false discovery rate < .05).

Conclusions

These results highlight the importance of rare noncoding regulatory variation in OCD genetics. The association of KNCN/MKNK1-AS1 variants with OCD suggests that antisense lncRNA–protein-coding overlap regions may contribute to disease susceptibility and represent potential therapeutic targets.
背景:强迫症(OCD)是一种普遍存在的神经精神疾病,其遗传基础尚不完全清楚,这限制了有针对性的治疗选择。虽然以前的罕见变异研究主要集中在蛋白质编码基因上,但罕见的调节非编码变异的贡献仍然很大程度上未被探索。方法:我们分析了来自All of Us研究计划的2561例强迫症患者和12974例对照组的全基因组测序数据,研究了992个基因组区域中反义长非编码rna (lncRNAs)重叠蛋白编码基因的罕见保守变异,使用Fisher精确检验和最优序列核关联检验进行关联检验。结果:我们在强迫症患者中发现了KNCN/MKNK1-AS1重叠区域的罕见保守变异显著富集(优势比= 5.1,错误发现率< 0.05)。这种富集在低进化约束的基因重叠区域中是显著的。表达分析显示,KNCN和MKNK1-AS1在纹状体脑区(伏隔核:r = 0.83,壳核:r = 0.81,尾状核:r = 0.79)特异性强共表达,这是强迫症回路中断的关键成分。与该调控对共表达的基因在突触囊泡动力学、钙信号传导和全基因组关联研究中建立的强迫症风险基因中富集(错误发现率< 0.05)。结论:这些结果强调了强迫症遗传中罕见的非编码调控变异的重要性。KNCN/MKNK1-AS1变异与强迫症的关联表明,反义lncrna蛋白编码重叠区可能与疾病易感性有关,并代表着潜在的治疗靶点。
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引用次数: 0
Phenome-Wide Associations of Polygenic Scores for Schizophrenia and Major Depression in 100,000 Chinese Adults 10万名中国成年人精神分裂症和重度抑郁症多基因评分的全表型关联
IF 3.7 Q2 NEUROSCIENCES Pub Date : 2026-03-01 Epub Date: 2025-12-22 DOI: 10.1016/j.bpsgos.2025.100681
Baihan Wang , Sam Morris , Hannah Fry , Andri Iona , Jonathan Clarke , Kuang Lin , Igor Pupko , Christiana Kartsonaki , Derrick A. Bennett , Yiping Chen , Huaidong Du , Ling Yang , Daniel Avery , Dan Schmidt-Valle , Shixian Feng , Dianjianyi Sun , Canqing Yu , Jun Lv , Pei Pei , Junshi Chen , Iona Y. Millwood

Background

China faces significant mental health challenges, with unique associations between mental disorders and other traits observed in its population.

Methods

Based on summary statistics of existing genome-wide association studies in East Asian ancestry (EAS) and European ancestry (EUR) populations, we tested the associations of polygenic scores (PGSs) for schizophrenia (SCZ) and major depression (MD) with 254 phenotypes in 100,640 Chinese adults. We also conducted genetic correlation and Mendelian randomization analyses to assess the consistency of these associations across ancestries and infer causality.

Results

The PGSs predicted SCZ (R2 = 2.63%–3.07%) and MD (R2 = 0.21%–0.71%) and were associated with various sociodemographic, lifestyle, and physical factors. Interestingly, based on summary statistics in the EAS population, the schizophrenia PGS was inversely associated with smoking initiation, and the MD PGS was inversely associated with body mass index. Across populations, opposing genetic correlations were observed between smoking initiation and SCZ (inverse in the EAS population, positive in the EUR population) and between body mass index and MD (inverse in the EAS population, positive in the EUR population). Univariable Mendelian randomization supported the causality of these relationships in the EUR population, but multivariable analyses suggested that pleiotropic effects on other related traits (e.g., cannabis use, unhealthy lifestyle) might have influenced the associations.

Conclusions

Our study suggests the context specificity of relationships between mental disorders and other traits, highlighting a potential role of sociocultural factors.
背景:中国面临着重大的精神卫生挑战,在其人群中观察到精神障碍与其他特征之间存在独特的关联。方法:基于东亚血统(EAS)和欧洲血统(EUR)人群现有全基因组关联研究的汇总统计,我们测试了100,640名中国成年人中精神分裂症(SCZ)和重度抑郁症(MD)的多基因评分(PGSs)与254种表型的相关性。我们还进行了遗传相关性和孟德尔随机化分析,以评估这些关联在不同祖先之间的一致性,并推断因果关系。结果:pgs预测SCZ (r2 = 2.63% ~ 3.07%)和MD (r2 = 0.21% ~ 0.71%),并与各种社会人口、生活方式和身体因素相关。有趣的是,根据EAS人群的汇总统计,精神分裂症PGS与开始吸烟呈负相关,MD PGS与体重指数呈负相关。在人群中,观察到吸烟开始与SCZ(在EAS人群中为负相关,在EUR人群中为正相关)以及体重指数与MD(在EAS人群中为负相关,在EUR人群中为正相关)之间存在相反的遗传相关性。单变量孟德尔随机化在欧洲人群中支持这些关系的因果关系,但多变量分析表明,对其他相关特征(例如,大麻使用,不健康的生活方式)的多效性效应可能影响了这些关联。结论:我们的研究表明,精神障碍与其他特征之间的关系具有情境特异性,强调了社会文化因素的潜在作用。
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引用次数: 0
The Old and the New: Promising Interventions for Bipolar Disorder Combining Mood-Stabilizing Medication With Nutritional Ketosis 新旧:有希望的干预双相情感障碍结合情绪稳定药物与营养性酮症
IF 3.7 Q2 NEUROSCIENCES Pub Date : 2026-03-01 Epub Date: 2026-01-13 DOI: 10.1016/j.bpsgos.2025.100677
Mary L. Phillips
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引用次数: 0
期刊
Biological psychiatry global open science
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