Pub Date : 2026-06-01Epub Date: 2026-01-30DOI: 10.1016/j.jad.2026.121310
Hana Ballum , Christine Dri , Sonya Liao , Minyi Yu , Gia Han Le , Sabrina Wong , Kayla M. Teopiz , Angela T.H. Kwan , Roger Ho , Hayun Choi , Joshua D. Rosenblat , Maj Vinberg , Heidi K.Y.Lo , Roger S. McIntyre
Background
Results from extant studies indicate that type 2 diabetes mellitus (T2DM) is associated with decreased cognitive function and increased risk for dementia, notably Alzheimer's Disease (AD). Herein, we aimed to evaluate the effect of glucacon-like peptide-1 receptor agonists (GLP-1 RAs) on cognitive measures in persons with cognitive impairment and T2DM from available systematic reviews and meta-analyses.
Methods
A literature search was conducted using Web of Science and MEDLINE from inception to July 15, 2025. Article screening and data extraction were conducted by three reviewers (H.B., C.D., S.L.). Primary research studies examining race, sex, children, animals and neurodegenerative diseases other than AD were excluded.
Results
Nine systematic reviews and meta-analyses examining the effect of GLP-1 RAs on cognitive function in adults with T2DM were included. Evidence suggests that GLP-1 RAs are associated with a reduction in overall cognitive decline in adults with T2DM and dementia/AD. Replicated findings from meta-analyses indicated that GLP-1 RAs improved performance on cognitive assessments (total learning; p = 0.039; p < 0.00001). Some meta-analyses observed a change in cognitive measures but lacked sufficient statistical significance (p > 0.05).
Conclusions
GLP-1 RAs positively affect cognitive function in AD patients with T2DM. However, their efficacy on disparate cognitive domains requires further replication in larger scale controlled clinical trials.
{"title":"The effect of glucagon-like peptide 1 (GLP-1) receptor agonists on cognition: A systematic review of systematic reviews and meta-analyses","authors":"Hana Ballum , Christine Dri , Sonya Liao , Minyi Yu , Gia Han Le , Sabrina Wong , Kayla M. Teopiz , Angela T.H. Kwan , Roger Ho , Hayun Choi , Joshua D. Rosenblat , Maj Vinberg , Heidi K.Y.Lo , Roger S. McIntyre","doi":"10.1016/j.jad.2026.121310","DOIUrl":"10.1016/j.jad.2026.121310","url":null,"abstract":"<div><h3>Background</h3><div>Results from extant studies indicate that type 2 diabetes mellitus (T2DM) is associated with decreased cognitive function and increased risk for dementia, notably Alzheimer's Disease (AD). Herein, we aimed to evaluate the effect of glucacon-like peptide-1 receptor agonists (GLP-1 RAs) on cognitive measures in persons with cognitive impairment and T2DM from available systematic reviews and meta-analyses.</div></div><div><h3>Methods</h3><div>A literature search was conducted using Web of Science and MEDLINE from inception to July 15, 2025. Article screening and data extraction were conducted by three reviewers (H.B., C.D., S.L.). Primary research studies examining race, sex, children, animals and neurodegenerative diseases other than AD were excluded.</div></div><div><h3>Results</h3><div>Nine systematic reviews and meta-analyses examining the effect of GLP-1 RAs on cognitive function in adults with T2DM were included. Evidence suggests that GLP-1 RAs are associated with a reduction in overall cognitive decline in adults with T2DM and dementia/AD. Replicated findings from meta-analyses indicated that GLP-1 RAs improved performance on cognitive assessments (total learning; <em>p</em> = 0.039; <em>p</em> < 0.00001). Some meta-analyses observed a change in cognitive measures but lacked sufficient statistical significance (<em>p</em> > 0.05).</div></div><div><h3>Conclusions</h3><div>GLP-1 RAs positively affect cognitive function in AD patients with T2DM. However, their efficacy on disparate cognitive domains requires further replication in larger scale controlled clinical trials.</div></div>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"402 ","pages":"Article 121310"},"PeriodicalIF":4.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-06-01Epub Date: 2026-02-05DOI: 10.1016/j.jad.2026.121353
Jun Zhou , Aijun Liao , Xiaoqian Ma , Zihao Yang , Chunwang Li , Ying He , Xiaogang Chen
Background
Cognitive dysfunction is a prevalent symptom in patients with bipolar II disorder (BD-II) depression, yet its underlying neural mechanisms remain insufficiently understood. This study aimed to investigate the relationship between local spontaneous neural activity and cognitive dysfunction in BD-II depression using the Regional Homogeneity (ReHo) method.
Methods
A total of 77 first-episode drug-naïve patients with BD-II depression and 69 healthy controls (HC) underwent magnetic resonance imaging (MRI) scans. Cognitive function was assessed using the Hopkins Verbal Learning Test-Revised (HVLT-R), Stroop Color and Word Test (SCWT), Verbal Fluency Test (VFT), and Wisconsin Card Sorting Test (WCST).
Results
Patients with BD-II depression exhibited widespread cognitive impairments across multiple domains, including verbal learning and memory, reaction time, executive function, working memory, semantic retrieval, and cognitive flexibility. Moreover, significant alterations in ReHo values were observed in several key brain regions, such as the precentral and postcentral gyri, precuneus, medial frontal gyrus (MFG), triangular part of inferior frontal gyrus, and Rolandic operculum. Notably, after Bonferroni correction, ReHo values in the right MFG were significantly correlated with both immediate and delayed recall scores on the HVLT-R (all P < 0.0002), suggesting a crucial role of this region in cognitive processes.
Conclusion
These findings indicate that abnormal neural activity in specific brain regions may serve as potential neurobiological markers of cognitive dysfunction in BD-II depression. Identifying these neural correlates could contribute to a better understanding of the pathophysiology of BD-II and inform the development of targeted therapeutic strategies.
{"title":"Relationship between regional homogeneity changes and cognitive dysfunction in patients with first-episode drug-naïve bipolar II disorder in the depressive phase","authors":"Jun Zhou , Aijun Liao , Xiaoqian Ma , Zihao Yang , Chunwang Li , Ying He , Xiaogang Chen","doi":"10.1016/j.jad.2026.121353","DOIUrl":"10.1016/j.jad.2026.121353","url":null,"abstract":"<div><h3>Background</h3><div>Cognitive dysfunction is a prevalent symptom in patients with bipolar II disorder (BD-II) depression, yet its underlying neural mechanisms remain insufficiently understood. This study aimed to investigate the relationship between local spontaneous neural activity and cognitive dysfunction in BD-II depression using the Regional Homogeneity (ReHo) method.</div></div><div><h3>Methods</h3><div>A total of 77 first-episode drug-naïve patients with BD-II depression and 69 healthy controls (HC) underwent magnetic resonance imaging (MRI) scans. Cognitive function was assessed using the Hopkins Verbal Learning Test-Revised (HVLT-R), Stroop Color and Word Test (SCWT), Verbal Fluency Test (VFT), and Wisconsin Card Sorting Test (WCST).</div></div><div><h3>Results</h3><div>Patients with BD-II depression exhibited widespread cognitive impairments across multiple domains, including verbal learning and memory, reaction time, executive function, working memory, semantic retrieval, and cognitive flexibility. Moreover, significant alterations in ReHo values were observed in several key brain regions, such as the precentral and postcentral gyri, precuneus, medial frontal gyrus (MFG), triangular part of inferior frontal gyrus, and Rolandic operculum. Notably, after Bonferroni correction, ReHo values in the right MFG were significantly correlated with both immediate and delayed recall scores on the HVLT-R (all <em>P</em> < 0.0002), suggesting a crucial role of this region in cognitive processes.</div></div><div><h3>Conclusion</h3><div>These findings indicate that abnormal neural activity in specific brain regions may serve as potential neurobiological markers of cognitive dysfunction in BD-II depression. Identifying these neural correlates could contribute to a better understanding of the pathophysiology of BD-II and inform the development of targeted therapeutic strategies.</div></div>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"402 ","pages":"Article 121353"},"PeriodicalIF":4.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-06-01Epub Date: 2026-02-02DOI: 10.1016/j.jad.2026.121328
Nicolas L. Camacho , Michael S. Gaffrey
The emergence of depression during the preschool years is well established. However, the neural correlates of depressive symptoms during this developmental period remain relatively understudied. Prior work has suggested a concurrent association between left amygdala salience reactivity (i.e., reward and loss versus neutral) and depressive symptoms in early childhood. Replication and extension into the predictive utility of the amygdala and other relevant neurobiological correlates are now needed. The current longitudinal study conducted a conceptual replication and extension of prior work using task-based functional Magnetic Resonance Imaging in a sample of 4–8-year-old children. We investigated whether reward-related reactivity in a priori regions of interest were associated with parent-reported early childhood depressive symptoms concurrently (N = 114; 54% female) and approximately one year later (N = 75; 53% female). Left amygdala salience reactivity and right caudate and medial prefrontal cortex reward reactivity (i.e., reward versus neutral) negatively associated with concurrent childhood depressive symptom severity. Only right caudate reward reactivity negatively associated with childhood depressive symptom severity one year later. Results replicate prior research suggesting an association between amygdala response to salient outcomes during reward processing and concurrent depressive symptom elevations in young children. They also provide novel information supporting the potential role of right caudate reactivity during reward processing as a biomarker of future elevations in depressive symptoms. These findings provide neurobiological insights into our developmental understanding of early emerging depressive symptoms and underscore early childhood as an important developmental period for understanding depression.
{"title":"Early childhood neural reward-related reactivity concurrently and prospectively associates with depressive symptom severity","authors":"Nicolas L. Camacho , Michael S. Gaffrey","doi":"10.1016/j.jad.2026.121328","DOIUrl":"10.1016/j.jad.2026.121328","url":null,"abstract":"<div><div>The emergence of depression during the preschool years is well established. However, the neural correlates of depressive symptoms during this developmental period remain relatively understudied. Prior work has suggested a concurrent association between left amygdala salience reactivity (i.e., reward and loss versus neutral) and depressive symptoms in early childhood. Replication and extension into the predictive utility of the amygdala and other relevant neurobiological correlates are now needed. The current longitudinal study conducted a conceptual replication and extension of prior work using task-based functional Magnetic Resonance Imaging in a sample of 4–8-year-old children. We investigated whether reward-related reactivity in a priori regions of interest were associated with parent-reported early childhood depressive symptoms concurrently (<em>N</em> = 114; 54% female) and approximately one year later (<em>N</em> = 75; 53% female). Left amygdala salience reactivity and right caudate and medial prefrontal cortex reward reactivity (i.e., reward versus neutral) negatively associated with concurrent childhood depressive symptom severity. Only right caudate reward reactivity negatively associated with childhood depressive symptom severity one year later. Results replicate prior research suggesting an association between amygdala response to salient outcomes during reward processing and concurrent depressive symptom elevations in young children. They also provide novel information supporting the potential role of right caudate reactivity during reward processing as a biomarker of future elevations in depressive symptoms. These findings provide neurobiological insights into our developmental understanding of early emerging depressive symptoms and underscore early childhood as an important developmental period for understanding depression.</div></div>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"402 ","pages":"Article 121328"},"PeriodicalIF":4.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-06-01Epub Date: 2026-01-26DOI: 10.1016/j.jad.2026.121273
Ying Shao , Zheyi Zhou , Junyu Mao , Pengfei Xu , Yuejia Luo , Fengqiong Yu , Suiping Wang
Background
Major depressive disorder (MDD) is conceptualized as a disorder of brain circuit function, particularly involving the default mode network (DMN). Repetitive transcranial magnetic stimulation (rTMS) emerged as an effective treatment for major depressive disorder (MDD), while its mechanisms and predictors of response remain poorly understood.
Methods
We retrospectively analyzed 70 patients with MDD received either active (n = 41) or sham (n = 29) rTMS. The resting-state fMRI was performed before and after treatment to assess dynamic functional connectivity. The left dorsal lateral prefrontal cortex (lDLPFC) was selected as the target site for rTMS, based on individualized functional connectivity with the right nucleus accumbens (NAcc) as the seed region. We tested the hypothesis that rTMS remediates depression by increasing modular flexibility, a measure of a brain region's dynamic functional integration and that baseline flexibility would predict clinical outcomes.
Results
Active rTMS produced a significantly greater reduction in Hamilton Depression Rating Scale (HAMD) scores, when compared to sham group (t = −2.70, p = .009). This clinical improvement was paralleled by a significant increase in the modular flexibility of the bilateral medial prefrontal cortex (MPFC), a key DMN hub. The magnitude of this flexibility increase was directly correlated with the degree of symptom reduction in the active group (r = 0.323, p = .045). Importantly, a support vector regression model demonstrated that pre-treatment modular flexibility in DMN nodes significantly predicted post-treatment HAMD scores (r = 0.391, p = .011).
Conclusions
These findings provide compelling evidence that rTMS exerts its therapeutic effects by remodeling the dynamic architecture of the DMN, enhancing its flexibility. Baseline modular flexibility constitutes a promising, mechanistically inspired biomarker for personalizing rTMS therapy. This work advances a dynamic network model of neuromodulation, shifting the focus from static dysfunction to the restoration of neural adaptability.
重度抑郁障碍（MDD）被定义为一种脑回路功能障碍，特别是涉及默认模式网络（DMN）。重复经颅磁刺激（rTMS）作为一种治疗重度抑郁症（MDD）的有效方法出现，但其机制和反应预测因素仍知之甚少。方法回顾性分析70例重度抑郁症患者，分别接受了主动（n = 41）和假性（n = 29） rTMS治疗。在治疗前后分别进行静息状态fMRI以评估动态功能连接。基于与右侧伏隔核（NAcc）作为种子区的个体化功能连接，选择左侧背外侧前额叶皮层（lDLPFC）作为rTMS的靶区。我们测试了rTMS通过增加模块化灵活性来治疗抑郁症的假设，模块化灵活性是衡量大脑区域动态功能整合的一种方法，并且基线灵活性可以预测临床结果。结果与假手术组相比，主动rTMS治疗组汉密尔顿抑郁评定量表（HAMD）得分显著降低（t = - 2.70, p = 0.009）。这种临床改善与双侧内侧前额叶皮质（MPFC）的模块化灵活性显著增加是并行的，MPFC是DMN的关键枢纽。这种灵活性增加的幅度与活跃组症状减轻的程度直接相关（r = 0.323, p = 0.045）。重要的是，支持向量回归模型表明，预处理前DMN节点的模块化灵活性显著预测处理后HAMD评分（r = 0.391, p = 0.011）。结论rTMS通过重塑DMN的动态结构，增强其灵活性来发挥其治疗作用。基线模块化灵活性是一种很有前途的、受机械启发的生物标志物，可用于个性化rTMS治疗。本研究提出了一个神经调节的动态网络模型，将焦点从静态功能障碍转移到神经适应性的恢复。
{"title":"Predicting rTMS treatment efficacy in depression based on modular flexibility of functional connectivity","authors":"Ying Shao , Zheyi Zhou , Junyu Mao , Pengfei Xu , Yuejia Luo , Fengqiong Yu , Suiping Wang","doi":"10.1016/j.jad.2026.121273","DOIUrl":"10.1016/j.jad.2026.121273","url":null,"abstract":"<div><h3>Background</h3><div>Major depressive disorder (MDD) is conceptualized as a disorder of brain circuit function, particularly involving the default mode network (DMN). Repetitive transcranial magnetic stimulation (rTMS) emerged as an effective treatment for major depressive disorder (MDD), while its mechanisms and predictors of response remain poorly understood.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 70 patients with MDD received either active (<em>n</em> = 41) or sham (<em>n</em> = 29) rTMS. The resting-state fMRI was performed before and after treatment to assess dynamic functional connectivity. The left dorsal lateral prefrontal cortex (lDLPFC) was selected as the target site for rTMS, based on individualized functional connectivity with the right nucleus accumbens (NAcc) as the seed region. We tested the hypothesis that rTMS remediates depression by increasing modular flexibility, a measure of a brain region's dynamic functional integration and that baseline flexibility would predict clinical outcomes.</div></div><div><h3>Results</h3><div>Active rTMS produced a significantly greater reduction in Hamilton Depression Rating Scale (HAMD) scores, when compared to sham group (<em>t</em> = −2.70, <em>p</em> = .009). This clinical improvement was paralleled by a significant increase in the modular flexibility of the bilateral medial prefrontal cortex (MPFC), a key DMN hub. The magnitude of this flexibility increase was directly correlated with the degree of symptom reduction in the active group (<em>r</em> = 0.323, <em>p</em> = .045). Importantly, a support vector regression model demonstrated that pre-treatment modular flexibility in DMN nodes significantly predicted post-treatment HAMD scores (<em>r</em> = 0.391, <em>p</em> = .011).</div></div><div><h3>Conclusions</h3><div>These findings provide compelling evidence that rTMS exerts its therapeutic effects by remodeling the dynamic architecture of the DMN, enhancing its flexibility. Baseline modular flexibility constitutes a promising, mechanistically inspired biomarker for personalizing rTMS therapy. This work advances a dynamic network model of neuromodulation, shifting the focus from static dysfunction to the restoration of neural adaptability.</div></div>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"402 ","pages":"Article 121273"},"PeriodicalIF":4.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-06-01Epub Date: 2026-02-04DOI: 10.1016/j.jad.2026.121340
Íñigo Alberdi-Páramo , Helena Morales-Ríos , Marta Navas-Tejedor , Jesús Enrique Ibáñez-Vizoso , José Luis Carrasco-Perera , Marina Díaz-Marsá
Background
Suicide is a major global public health concern. Although data on suicide mortality are well documented, large-scale studies examining the clinical and behavioral profiles of suicide attempts (SAs) presenting to Psychiatric Emergency Departments (PEDs) remain scarce, particularly in Spain. This study aimed to describe epidemiological patterns, clinical correlates, and care pathway discontinuities associated with suicidal behavior in a major urban PED.
Methods
A retrospective observational study was conducted using prospectively collected data from 40,306 consecutive presentations for suicidal ideation and/or SAs at the PED of Hospital Clínico San Carlos (Madrid, Spain) between 2006 and 2018. Variables included age, sex, ICD-10 psychiatric diagnosis, method of attempt, recurrence (repeat emergency presentations), and disposition following triage (psychiatric filiation).
Results
Suicidal behavior was more frequent among women (54.9%). Two age peaks emerged: one in young adults (18–24 years) and a second in middle-aged adults (34–46 years). Drug overdose was the most common method, predominantly among women (68% of intoxications), whereas higher-lethality methods (e.g., hanging, jumping) were more frequent in men. Psychiatric history was present in 86.6% of presentations. The most prevalent diagnoses were specific personality disorders in women and schizophrenia or alcohol use disorder in men. Only 70.9% of presentations were immediately routed to specialized psychiatric care after triage.
Conclusions
The gender paradox in suicidal behavior is reflected in diagnostic patterns and method choice. High recurrence of emergency presentations underscores the central role of PEDs as points of clinical contact, while the 29.1% gap in immediate psychiatric filiation represents an observed discontinuity in care pathways. These findings may help inform efforts to optimize triage processes and strengthen continuity of care following emergency presentations for suicidal behavior.
背景：自杀是一个主要的全球公共卫生问题。尽管关于自杀死亡率的数据有很好的记录，但对精神科急诊科（PEDs）的自杀企图（SAs）的临床和行为特征进行大规模研究仍然很少，特别是在西班牙。本研究旨在描述一个主要城市PED中与自杀行为相关的流行病学模式、临床相关性和护理路径不连续性。方法：对2006年至2018年期间在西班牙马德里Clínico圣卡洛斯医院（Hospital San Carlos, Madrid, Spain） PED连续就诊的40,306例自杀意念和/或sa患者的前瞻性数据进行回顾性观察性研究。变量包括年龄、性别、ICD-10精神病诊断、尝试方法、复发（重复急诊表现）和分诊后的处置（精神病倾向）。结果：自杀行为在女性中更为常见（54.9%）。出现了两个年龄高峰：一个在年轻人（18-24 岁），第二个在中年人（34-46 岁）。药物过量是最常见的方法，主要在女性中（68%的中毒），而高致死率的方法（如上吊、跳楼）在男性中更为常见。86.6%的患者有精神病史。最普遍的诊断是女性的特定人格障碍和男性的精神分裂症或酒精使用障碍。在分诊后，只有70.9%的患者被立即送往专门的精神科治疗。结论：自杀行为中的性别矛盾体现在诊断方式和方法选择上。急诊的高复发率强调了儿科医生作为临床联络点的核心作用，而29.1%的即时精神科就诊差距代表了观察到的护理途径的不连续性。这些发现可能有助于优化分诊过程，并加强自杀行为紧急就诊后护理的连续性。
{"title":"Clinical and epidemiological profiles of suicidal behavior in psychiatric emergency users: A 13-year retrospective study of 40,306 cases in Madrid, Spain","authors":"Íñigo Alberdi-Páramo , Helena Morales-Ríos , Marta Navas-Tejedor , Jesús Enrique Ibáñez-Vizoso , José Luis Carrasco-Perera , Marina Díaz-Marsá","doi":"10.1016/j.jad.2026.121340","DOIUrl":"10.1016/j.jad.2026.121340","url":null,"abstract":"<div><h3>Background</h3><div>Suicide is a major global public health concern. Although data on suicide mortality are well documented, large-scale studies examining the clinical and behavioral profiles of suicide attempts (SAs) presenting to Psychiatric Emergency Departments (PEDs) remain scarce, particularly in Spain. This study aimed to describe epidemiological patterns, clinical correlates, and care pathway discontinuities associated with suicidal behavior in a major urban PED.</div></div><div><h3>Methods</h3><div>A retrospective observational study was conducted using prospectively collected data from 40,306 consecutive presentations for suicidal ideation and/or SAs at the PED of Hospital Clínico San Carlos (Madrid, Spain) between 2006 and 2018. Variables included age, sex, ICD-10 psychiatric diagnosis, method of attempt, recurrence (repeat emergency presentations), and disposition following triage (psychiatric filiation).</div></div><div><h3>Results</h3><div>Suicidal behavior was more frequent among women (54.9%). Two age peaks emerged: one in young adults (18–24 years) and a second in middle-aged adults (34–46 years). Drug overdose was the most common method, predominantly among women (68% of intoxications), whereas higher-lethality methods (e.g., hanging, jumping) were more frequent in men. Psychiatric history was present in 86.6% of presentations. The most prevalent diagnoses were specific personality disorders in women and schizophrenia or alcohol use disorder in men. Only 70.9% of presentations were immediately routed to specialized psychiatric care after triage.</div></div><div><h3>Conclusions</h3><div>The gender paradox in suicidal behavior is reflected in diagnostic patterns and method choice. High recurrence of emergency presentations underscores the central role of PEDs as points of clinical contact, while the 29.1% gap in immediate psychiatric filiation represents an observed discontinuity in care pathways. These findings may help inform efforts to optimize triage processes and strengthen continuity of care following emergency presentations for suicidal behavior.</div></div>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"402 ","pages":"Article 121340"},"PeriodicalIF":4.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-06-01Epub Date: 2026-02-04DOI: 10.1016/j.jad.2026.121350
Raquel Kosted , Alli Waddell , Ken Adolph , Gregory A. Fonzo
Ketamine is known to be a rapid-acting antidepressant, but there is limited evidence regarding which types of patients are best-suited to this treatment and whether adjunctive psychotherapy improves outcomes. In a sample of 224 patients who received five ketamine infusions at a private clinic, this study uses Bayesian mixed modeling to examine the effects of early life stress (measured with the Adverse Childhood Experiences [ACE] survey) and treatment modality (ketamine-assisted therapy [KAT] vs. infusions only) on antidepressant response, and whether these effects interact. Depression symptoms were assessed prior to each infusion using the Patient Health Questionnaire-9 survey. Depression symptoms improved over time (time: β = −4.4, 95% Credible Interval [−6.8, −1.9]), with decelerating rates of improvement (quadratic time: β = 2.6, [0.4, 4.8]). Symptom trajectories did not differ between treatment modalities (time*treatment condition: β = 0.8, [−1.6, 3.1]). Higher ACE scores were associated with greater symptom reduction (time*ACE: β = −0.6, [−0.9, −0.3]), independent of treatment modality (time*ACE*treatment condition: β = −0.5, [−1.1, 0.2]). Exploratory analyses revealed that younger adults show greater treatment response to ketamine infusions alone compared to KAT, while the opposite is observed in older adults (time*treatment condition*age: β = −0.1, [−0.3, −0.03]). Furthermore, the relationship between higher ACE scores and greater symptom reduction may be particularly strong within younger adults, with this association reversing at older ages (time*ACE*age: β = 0.02, [0.002, 0.04]). In summary, enhanced magnitude of symptom reduction for those with greater early life stress exposure, especially in younger adults, suggests a potentially unique and targeted benefit of ketamine over conventional antidepressants for this population.
{"title":"Age-related moderation of adjunctive psychotherapy and early life stress effects on depression symptom reductions following ketamine treatment: Initial insights from a large, naturalistic sample","authors":"Raquel Kosted , Alli Waddell , Ken Adolph , Gregory A. Fonzo","doi":"10.1016/j.jad.2026.121350","DOIUrl":"10.1016/j.jad.2026.121350","url":null,"abstract":"<div><div>Ketamine is known to be a rapid-acting antidepressant, but there is limited evidence regarding which types of patients are best-suited to this treatment and whether adjunctive psychotherapy improves outcomes. In a sample of 224 patients who received five ketamine infusions at a private clinic, this study uses Bayesian mixed modeling to examine the effects of early life stress (measured with the Adverse Childhood Experiences [ACE] survey) and treatment modality (ketamine-assisted therapy [KAT] vs. infusions only) on antidepressant response, and whether these effects interact. Depression symptoms were assessed prior to each infusion using the Patient Health Questionnaire-9 survey. Depression symptoms improved over time (time: β = −4.4, 95% Credible Interval [−6.8, −1.9]), with decelerating rates of improvement (quadratic time: β = 2.6, [0.4, 4.8]). Symptom trajectories did not differ between treatment modalities (time*treatment condition: β = 0.8, [−1.6, 3.1]). Higher ACE scores were associated with greater symptom reduction (time*ACE: β = −0.6, [−0.9, −0.3]), independent of treatment modality (time*ACE*treatment condition: β = −0.5, [−1.1, 0.2]). Exploratory analyses revealed that younger adults show greater treatment response to ketamine infusions alone compared to KAT, while the opposite is observed in older adults (time*treatment condition*age: β = −0.1, [−0.3, −0.03]). Furthermore, the relationship between higher ACE scores and greater symptom reduction may be particularly strong within younger adults, with this association reversing at older ages (time*ACE*age: β = 0.02, [0.002, 0.04]). In summary, enhanced magnitude of symptom reduction for those with greater early life stress exposure, especially in younger adults, suggests a potentially unique and targeted benefit of ketamine over conventional antidepressants for this population.</div></div>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"402 ","pages":"Article 121350"},"PeriodicalIF":4.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-06-01Epub Date: 2026-02-05DOI: 10.1016/j.jad.2026.121349
Robert L. Seilheimer , Liming Qiu , Giovanna Rocchio , Young-Hoon Nho , Gustavo Campos , Andreas Horn , Camarin E. Rolle , Vivek P. Buch , T. Mindy Ganguly , Mario Cristancho , Desmond J. Oathes , Lily Brown , Bijan Pesaran , Andrew D. Krystal , Eddie F. Chang , Moses A. Lee , Kai J. Miller , Daniel A.N. Barbosa , Nolan R. Williams , Casey H. Halpern , Katherine W. Scangos
Introduction
Treatment-refractory obsessive-compulsive disorder (trOCD) is a complex network disorder that may require personalized treatment strategies due to disease heterogeneity. A multi-site, multi-stage, double-blinded, randomized crossover clinical trial is underway, using stereo-electroencephalography (sEEG) to guide selection of multi-nodal targets for deep brain stimulation (DBS) for trOCD.
Objectives
To describe the clinical trial design, emphasizing personalized surgical targeting strategies that ensure the feasibility and precision of sEEG electrode placement, and enable adequate sampling of relevant targets in trOCD for network evaluation and modulation.
Methods
Adults with severe trOCD (Yale-Brown Obsessive Compulsive Scale ≥28) who meet eligibility criteria are enrolled in this three-stage clinical trial (NCT05623306). Stage 1 involves sEEG electrode implantation in trOCD implicated regions and inpatient evaluation. Individualized probabilistic tractography-guided target refinement is performed for surgical planning. Multimodal recordings are taken while participants stay in the psychiatric monitoring unit for 12 days. In stage 2, up to four permanent DBS electrodes are implanted followed by stimulation optimization. Stage 3 is the randomized, double-blinded crossover phase.
Expected outcomes
Safety, feasibility and preliminary efficacy will be assessed in this ongoing study. We anticipate that the use of sEEG to guide selection of multi-nodal targets for DBS will be safe, feasible and result in clinically meaningful improvements in symptom severity and functional impairment in trOCD.
Discussion
We present the clinical protocol of sEEG-guided investigation of brain networks involved in trOCD and describe our tractography-guided surgical targeting strategy designed to optimize individualized network engagement and neuromodulation.
{"title":"Stereo-encephalography-guided multi-lead deep brain stimulation for treatment-refractory obsessive compulsive disorder – Study design and individualized surgical targeting approach","authors":"Robert L. Seilheimer , Liming Qiu , Giovanna Rocchio , Young-Hoon Nho , Gustavo Campos , Andreas Horn , Camarin E. Rolle , Vivek P. Buch , T. Mindy Ganguly , Mario Cristancho , Desmond J. Oathes , Lily Brown , Bijan Pesaran , Andrew D. Krystal , Eddie F. Chang , Moses A. Lee , Kai J. Miller , Daniel A.N. Barbosa , Nolan R. Williams , Casey H. Halpern , Katherine W. Scangos","doi":"10.1016/j.jad.2026.121349","DOIUrl":"10.1016/j.jad.2026.121349","url":null,"abstract":"<div><h3>Introduction</h3><div>Treatment-refractory obsessive-compulsive disorder (trOCD) is a complex network disorder that may require personalized treatment strategies due to disease heterogeneity. A multi-site, multi-stage, double-blinded, randomized crossover clinical trial is underway, using stereo-electroencephalography (sEEG) to guide selection of multi-nodal targets for deep brain stimulation (DBS) for trOCD.</div></div><div><h3>Objectives</h3><div>To describe the clinical trial design, emphasizing personalized surgical targeting strategies that ensure the feasibility and precision of sEEG electrode placement, and enable adequate sampling of relevant targets in trOCD for network evaluation and modulation.</div></div><div><h3>Methods</h3><div>Adults with severe trOCD (Yale-Brown Obsessive Compulsive Scale ≥28) who meet eligibility criteria are enrolled in this three-stage clinical trial (<span><span>NCT05623306</span><svg><path></path></svg></span>). Stage 1 involves sEEG electrode implantation in trOCD implicated regions and inpatient evaluation. Individualized probabilistic tractography-guided target refinement is performed for surgical planning. Multimodal recordings are taken while participants stay in the psychiatric monitoring unit for 12 days. In stage 2, up to four permanent DBS electrodes are implanted followed by stimulation optimization. Stage 3 is the randomized, double-blinded crossover phase.</div></div><div><h3>Expected outcomes</h3><div>Safety, feasibility and preliminary efficacy will be assessed in this ongoing study. We anticipate that the use of sEEG to guide selection of multi-nodal targets for DBS will be safe, feasible and result in clinically meaningful improvements in symptom severity and functional impairment in trOCD.</div></div><div><h3>Discussion</h3><div>We present the clinical protocol of sEEG-guided investigation of brain networks involved in trOCD and describe our tractography-guided surgical targeting strategy designed to optimize individualized network engagement and neuromodulation.</div></div>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"402 ","pages":"Article 121349"},"PeriodicalIF":4.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-06-01Epub Date: 2026-02-06DOI: 10.1016/j.jad.2026.121342
Bomgyeol Kim , JaeWon Hyun , Hun Kang , Seongmi Choi , Jin-kyung Lee , JiYeon Choi
Background
We investigated associations between the Social Network Index (SNI) and cognitive impairment and depressive symptoms among healthy older adults in South Korea, focusing on distinctions among age subgroups within the older population.
Methods
Data were derived from the 2023 National Survey of Older Koreans. From an initial sample of 10,078 adults aged ≥65 years, we excluded proxy respondents, individuals officially registered with disability, classified as frail, and diagnosed with depression, dementia, Parkinson's disease, or two or more other chronic conditions by physician. The final analytic sample comprised 3379 healthy older adults. Multiple logistic regression analyses were conducted to examine associations between SNI and cognitive impairment and depressive symptoms in the full sample, as well as in the subgroups of young-old and middle-old and oldest-old groups.
Results
Participants with low SNI had significantly higher odds of cognitive impairment (adjusted odds ratio [aOR] = 1.72; 95% confidence interval [CI]: 1.35–2.18) and depressive symptoms (aOR = 2.35; 95% CI: 1.54–3.59) compared to those with high SNI. These associations remained significant in both young-old (65–74 years; cognitive impairment aOR = 1.79, 95% CI: 1.34–2.37; depressive symptoms aOR = 2.07, 95% CI: 1.24–3.47) and middle-old and oldest-old groups (≥75 years; cognitive impairment aOR = 1.70, 95% CI: 1.07–2.70; depressive symptoms aOR = 2.85, 95% CI: 1.27–6.42).
Conclusions
Our findings underscore the significant associations between social connectedness and cognitive and mental health in later life and suggest that targeted interventions promoting social engagement may be particularly beneficial for older age groups with limited social networks.
{"title":"Social network index and its association with cognitive impairment and depressive symptoms in healthy older adults: Age-stratified analysis","authors":"Bomgyeol Kim , JaeWon Hyun , Hun Kang , Seongmi Choi , Jin-kyung Lee , JiYeon Choi","doi":"10.1016/j.jad.2026.121342","DOIUrl":"10.1016/j.jad.2026.121342","url":null,"abstract":"<div><h3>Background</h3><div>We investigated associations between the Social Network Index (SNI) and cognitive impairment and depressive symptoms among healthy older adults in South Korea, focusing on distinctions among age subgroups within the older population.</div></div><div><h3>Methods</h3><div>Data were derived from the 2023 National Survey of Older Koreans. From an initial sample of 10,078 adults aged ≥65 years, we excluded proxy respondents, individuals officially registered with disability, classified as frail, and diagnosed with depression, dementia, Parkinson's disease, or two or more other chronic conditions by physician. The final analytic sample comprised 3379 healthy older adults. Multiple logistic regression analyses were conducted to examine associations between SNI and cognitive impairment and depressive symptoms in the full sample, as well as in the subgroups of young-old and middle-old and oldest-old groups.</div></div><div><h3>Results</h3><div>Participants with low SNI had significantly higher odds of cognitive impairment (adjusted odds ratio [aOR] = 1.72; 95% confidence interval [CI]: 1.35–2.18) and depressive symptoms (aOR = 2.35; 95% CI: 1.54–3.59) compared to those with high SNI. These associations remained significant in both young-old (65–74 years; cognitive impairment aOR = 1.79, 95% CI: 1.34–2.37; depressive symptoms aOR = 2.07, 95% CI: 1.24–3.47) and middle-old and oldest-old groups (≥75 years; cognitive impairment aOR = 1.70, 95% CI: 1.07–2.70; depressive symptoms aOR = 2.85, 95% CI: 1.27–6.42).</div></div><div><h3>Conclusions</h3><div>Our findings underscore the significant associations between social connectedness and cognitive and mental health in later life and suggest that targeted interventions promoting social engagement may be particularly beneficial for older age groups with limited social networks.</div></div>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"402 ","pages":"Article 121342"},"PeriodicalIF":4.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-15Epub Date: 2025-12-22DOI: 10.1016/j.jad.2025.120978
Mireia Orgilés, Víctor Amorós-Reche, Jose P. Espada
Background
Suicidal ideation and behavior represent a serious public health concern, particularly during adolescence, and are closely linked to symptoms of depression and anxiety. Although previous studies have examined the network structure of suicidality and emotional symptoms, gaps remain regarding how different stages of suicidal ideation and behavior relate to internalizing symptoms. This study aimed to estimate the lifetime prevalence of suicidal ideation and behavior, examine the associations between depressive and anxiety symptoms and distinct forms of suicidal behavior, and compare symptom networks between adolescents who had or had not reported such experiences.
Methods
A total of 4160 Spanish adolescents participated in this nationwide study, completing the Paykel Suicide Scale and the Assessment System of Children and Adolescents.
Results
12.7 % of participants reported suicidal ideation and 3.6 % had attempted suicide, with higher rates among girls and older adolescents. Network analyses revealed that worthlessness, anhedonia, sadness, crying, panic attacks and intrusive thoughts were consistently associated with both passive and active suicidal ideation and attempts. Moreover, adolescents who had experienced suicidal ideation or attempts displayed stronger interconnections among depressive symptoms and between depressive and anxiety symptoms.
Limitations
The sample was partially based on convenience sampling, and the large amount of network comparisons limited power.
Conclusion
These findings provide a comprehensive view of the psychopathological structure underlying suicidality in adolescence and contribute to the identification of key emotional symptoms that may be targets for early intervention and prevention strategies.
{"title":"A network analysis of symptom-level associations between suicidality, depression and anxiety in Spanish adolescents","authors":"Mireia Orgilés, Víctor Amorós-Reche, Jose P. Espada","doi":"10.1016/j.jad.2025.120978","DOIUrl":"10.1016/j.jad.2025.120978","url":null,"abstract":"<div><h3>Background</h3><div>Suicidal ideation and behavior represent a serious public health concern, particularly during adolescence, and are closely linked to symptoms of depression and anxiety. Although previous studies have examined the network structure of suicidality and emotional symptoms, gaps remain regarding how different stages of suicidal ideation and behavior relate to internalizing symptoms. This study aimed to estimate the lifetime prevalence of suicidal ideation and behavior, examine the associations between depressive and anxiety symptoms and distinct forms of suicidal behavior, and compare symptom networks between adolescents who had or had not reported such experiences.</div></div><div><h3>Methods</h3><div>A total of 4160 Spanish adolescents participated in this nationwide study, completing the Paykel Suicide Scale and the Assessment System of Children and Adolescents.</div></div><div><h3>Results</h3><div>12.7 % of participants reported suicidal ideation and 3.6 % had attempted suicide, with higher rates among girls and older adolescents. Network analyses revealed that worthlessness, anhedonia, sadness, crying, panic attacks and intrusive thoughts were consistently associated with both passive and active suicidal ideation and attempts. Moreover, adolescents who had experienced suicidal ideation or attempts displayed stronger interconnections among depressive symptoms and between depressive and anxiety symptoms.</div></div><div><h3>Limitations</h3><div>The sample was partially based on convenience sampling, and the large amount of network comparisons limited power.</div></div><div><h3>Conclusion</h3><div>These findings provide a comprehensive view of the psychopathological structure underlying suicidality in adolescence and contribute to the identification of key emotional symptoms that may be targets for early intervention and prevention strategies.</div></div>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"401 ","pages":"Article 120978"},"PeriodicalIF":4.9,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-15Epub Date: 2026-01-26DOI: 10.1016/j.jad.2026.121281
Jacques D. Marleau , Mélissa Généreux
Objective
To evaluate the factor structure of the 4-item Patient Health Questionnaire (PHQ-4), which aims to screen for two dimensions: anxiety and depression.
Method
Data from three surveys conducted in Quebec in 2021 among adult respondents were used to test whether a two-factor structure fits better than a one-factor model. Confirmatory factor analyses will be used to determine the best-fitting model.
Results
Confirmatory factor analyses revealed that the two-factor structure is more appropriate than the one-factor model. Measurement invariance of the two-factor model was observed across several indicators (gender, language, place of birth, housing status, etc.), except for age. Convergent and divergent validity were also established. These findings were consistent across all three surveys.
Conclusion
Given the strong psychometric properties of the two-factor model, its use is recommended among the adult population in Quebec. The consistency of the results further supports its validity and applicability.
{"title":"Validation of the PHQ-4 in the general population of Quebec, Canada","authors":"Jacques D. Marleau , Mélissa Généreux","doi":"10.1016/j.jad.2026.121281","DOIUrl":"10.1016/j.jad.2026.121281","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the factor structure of the 4-item Patient Health Questionnaire (PHQ-4), which aims to screen for two dimensions: anxiety and depression.</div></div><div><h3>Method</h3><div>Data from three surveys conducted in Quebec in 2021 among adult respondents were used to test whether a two-factor structure fits better than a one-factor model. Confirmatory factor analyses will be used to determine the best-fitting model.</div></div><div><h3>Results</h3><div>Confirmatory factor analyses revealed that the two-factor structure is more appropriate than the one-factor model. Measurement invariance of the two-factor model was observed across several indicators (gender, language, place of birth, housing status, etc.), except for age. Convergent and divergent validity were also established. These findings were consistent across all three surveys.</div></div><div><h3>Conclusion</h3><div>Given the strong psychometric properties of the two-factor model, its use is recommended among the adult population in Quebec. The consistency of the results further supports its validity and applicability.</div></div>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"401 ","pages":"Article 121281"},"PeriodicalIF":4.9,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146076433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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