Pub Date : 2026-01-01Epub Date: 2025-09-08DOI: 10.1016/j.bpsgos.2025.100606
Daniel Kiss , Xiaolin Zhou , Nicole Endresz , Keon Arbabi , Alex Gonzalez Segura , Daniel Felsky , Andreea O. Diaconescu , Etienne Sibille , Shreejoy J. Tripathy
Background
Cortical GABAergic (gamma-aminobutyric acidergic) neuron dysregulation is implicated in schizophrenia (SCZ), but it remains unclear whether these changes are due to altered cell proportions or per-cell changes in messenger RNA (mRNA) expression.
Methods
We analyzed 14 bulk and cell type–specific RNA sequencing (RNA-seq) datasets from 1408 individuals (672 SCZ cases, 736 controls) across 3 neocortical regions. We deconvolved GABAergic cell-subtype proportions from bulk RNA-seq and benchmarked them against single-nucleus RNA-seq and stereological densities from matched donors. We assessed SCZ- and age-associated changes in cell proportions and per-cell gene expression.
Results
SCZ was associated with altered proportions of neocortical parvalbumin (PVALB) and somatostatin (SST) cells, depending on the subject’s age at death. Younger SCZ cases (age < 70 years) showed reduced PVALB and SST cell proportions, while older cases showed unchanged or increased proportions compared with controls. Earlier-onset SCZ, associated with more severe clinical symptoms, was linked to greater reductions in these cell types. Additionally, there was robust evidence for reduced per-cell SST and vasoactive intestinal peptide mRNA among younger cases with SCZ.
Conclusions
These findings suggest that SCZ is associated with complex, age-dependent alterations in GABAergic neurons, particularly affecting PVALB and SST cells. Our study underscores the importance of age-stratified analyses in SCZ, suggesting that distinct pathological processes underlie GABAergic neuron dysregulation across different age and symptom-severity groups and warranting tailored therapeutic approaches.
{"title":"Cortical GABAergic Neuron Dysregulation in Schizophrenia Is Age Dependent","authors":"Daniel Kiss , Xiaolin Zhou , Nicole Endresz , Keon Arbabi , Alex Gonzalez Segura , Daniel Felsky , Andreea O. Diaconescu , Etienne Sibille , Shreejoy J. Tripathy","doi":"10.1016/j.bpsgos.2025.100606","DOIUrl":"10.1016/j.bpsgos.2025.100606","url":null,"abstract":"<div><h3>Background</h3><div>Cortical GABAergic (gamma-aminobutyric acidergic) neuron dysregulation is implicated in schizophrenia (SCZ), but it remains unclear whether these changes are due to altered cell proportions or per-cell changes in messenger RNA (mRNA) expression.</div></div><div><h3>Methods</h3><div>We analyzed 14 bulk and cell type–specific RNA sequencing (RNA-seq) datasets from 1408 individuals (672 SCZ cases, 736 controls) across 3 neocortical regions. We deconvolved GABAergic cell-subtype proportions from bulk RNA-seq and benchmarked them against single-nucleus RNA-seq and stereological densities from matched donors. We assessed SCZ- and age-associated changes in cell proportions and per-cell gene expression.</div></div><div><h3>Results</h3><div>SCZ was associated with altered proportions of neocortical parvalbumin (PVALB) and somatostatin (SST) cells, depending on the subject’s age at death. Younger SCZ cases (age < 70 years) showed reduced PVALB and SST cell proportions, while older cases showed unchanged or increased proportions compared with controls. Earlier-onset SCZ, associated with more severe clinical symptoms, was linked to greater reductions in these cell types. Additionally, there was robust evidence for reduced per-cell SST and vasoactive intestinal peptide mRNA among younger cases with SCZ.</div></div><div><h3>Conclusions</h3><div>These findings suggest that SCZ is associated with complex, age-dependent alterations in GABAergic neurons, particularly affecting PVALB and SST cells. Our study underscores the importance of age-stratified analyses in SCZ, suggesting that distinct pathological processes underlie GABAergic neuron dysregulation across different age and symptom-severity groups and warranting tailored therapeutic approaches.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100606"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145324652","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}
Pub Date : 2026-01-01Epub Date: 2025-09-17DOI: 10.1016/j.bpsgos.2025.100613
Fenfen Ge , Yue Wang , Xiaoqin Liu , Trine Munk-Olsen , Kathrine Bang Madsen , Emil Michael Pedersen , Clara Albiñana , Esben Agerbo , Cynthia M. Bulik , Liselotte Vogdrup Petersen , Unnur A. Valdimarsdottir , Bjarni Jóhann Vilhjálmsson
Background
Phenotypic links between psychiatric disorders and adverse perinatal events are increasingly being reported, but the mechanisms remain unclear. In this study, we aimed to assess how polygenic scores (PGSs) for 8 psychiatric conditions influence perinatal risk.
Methods
The main analysis included 13,085 mothers and their corresponding birth information. PGSs for psychiatric conditions were estimated using genome-wide association study data (excluding the iPSYCH cohort) via LDpred2 and used as exposures. Ten adverse perinatal events from Danish national registers served as outcomes. Associations were analyzed using logistic or multinomial regression, with false discovery rate correction applied.
Results
We found that PGSs for psychiatric conditions were associated with heavy smoking (attention-deficit/hyperactivity disorder [ADHD], anxiety, and depression), lower likelihood of being overweight/obese (schizophrenia, anorexia nervosa, and obsessive-compulsive disorder [OCD]), very young maternal age (<20 years) at childbirth (ADHD, depression, and anxiety), and non-cohabitation (ADHD, schizophrenia, anxiety, and depression). Little evidence of an association between maternal PGSs for psychiatric conditions and birth weight, gestational age, and labor presentation was identified. We identified a novel dose-response relationship in which higher PGSs for ADHD, anxiety, and depression were associated with a greater cumulative burden of adverse perinatal events, whereas higher PGSs for anorexia nervosa and OCD were linked to a lower burden.
Conclusions
High genetic liability for psychiatric conditions may partially explain the observed phenotypic associations between maternal mental illness and adverse perinatal events, with higher genetic liability generally associated with either an increase or decrease in the cumulative burden of adverse perinatal events in a dose-response–like manner.
{"title":"Association Between Maternal Genome-Wide Polygenic Scores for Psychiatric and Neurodevelopmental Disorders and Adverse Perinatal Events: A Danish Population-Based Study","authors":"Fenfen Ge , Yue Wang , Xiaoqin Liu , Trine Munk-Olsen , Kathrine Bang Madsen , Emil Michael Pedersen , Clara Albiñana , Esben Agerbo , Cynthia M. Bulik , Liselotte Vogdrup Petersen , Unnur A. Valdimarsdottir , Bjarni Jóhann Vilhjálmsson","doi":"10.1016/j.bpsgos.2025.100613","DOIUrl":"10.1016/j.bpsgos.2025.100613","url":null,"abstract":"<div><h3>Background</h3><div>Phenotypic links between psychiatric disorders and adverse perinatal events are increasingly being reported, but the mechanisms remain unclear. In this study, we aimed to assess how polygenic scores (PGSs) for 8 psychiatric conditions influence perinatal risk.</div></div><div><h3>Methods</h3><div>The main analysis included 13,085 mothers and their corresponding birth information. PGSs for psychiatric conditions were estimated using genome-wide association study data (excluding the iPSYCH cohort) via LDpred2 and used as exposures. Ten adverse perinatal events from Danish national registers served as outcomes. Associations were analyzed using logistic or multinomial regression, with false discovery rate correction applied.</div></div><div><h3>Results</h3><div>We found that PGSs for psychiatric conditions were associated with heavy smoking (attention-deficit/hyperactivity disorder [ADHD], anxiety, and depression), lower likelihood of being overweight/obese (schizophrenia, anorexia nervosa, and obsessive-compulsive disorder [OCD]), very young maternal age (<20 years) at childbirth (ADHD, depression, and anxiety), and non-cohabitation (ADHD, schizophrenia, anxiety, and depression). Little evidence of an association between maternal PGSs for psychiatric conditions and birth weight, gestational age, and labor presentation was identified. We identified a novel dose-response relationship in which higher PGSs for ADHD, anxiety, and depression were associated with a greater cumulative burden of adverse perinatal events, whereas higher PGSs for anorexia nervosa and OCD were linked to a lower burden.</div></div><div><h3>Conclusions</h3><div>High genetic liability for psychiatric conditions may partially explain the observed phenotypic associations between maternal mental illness and adverse perinatal events, with higher genetic liability generally associated with either an increase or decrease in the cumulative burden of adverse perinatal events in a dose-response–like manner.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100613"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520766","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}
Pub Date : 2026-01-01Epub Date: 2025-10-23DOI: 10.1016/j.bpsgos.2025.100611
Florian Freudenberg
{"title":"NO Time to Die: Nitric Oxide’s Ongoing Relevance in Mental Disorders","authors":"Florian Freudenberg","doi":"10.1016/j.bpsgos.2025.100611","DOIUrl":"10.1016/j.bpsgos.2025.100611","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100611"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145365068","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}
Pub Date : 2026-01-01Epub Date: 2025-09-30DOI: 10.1016/j.bpsgos.2025.100622
Jody Tanabe , Jordan Hickman , Andy Tekriwal , Joseph Sakai , Aviva Abosch , Steven Ojemann , Joseph P. Schacht , John A. Thompson
A major goal for substance use disorder (SUD) treatment is the reduction of drug craving, which contributes to continued drug use and relapse. Pathological craving is thought to reflect dysfunction in neural networks, sparking a growing interest in modulating the mesocorticolimbic reward and related networks to decrease craving and improve outcomes. Although initial studies of neuromodulation in SUDs have produced promising results, biomarkers for craving remain elusive. Advances in deep brain stimulation (DBS) now allow recording of local field potentials (LFPs) in the nucleus accumbens (NAc), the central hub of the reward circuit, thus paving the way for a novel LFP biomarker for craving. Insights into mechanistic models of craving that relate localized electrophysiology to distributed circuit activity are in the earliest stages. At the same time, performing invasive DBS surgery on individuals with SUD is a formidable challenge and underscores the need to refine our understanding of noninvasive functional magnetic resonance imaging (fMRI)–defined network biomarkers of craving. Here, we review the literature on LFPs and single-unit neural activity during craving and reward, highlighting recent findings of craving-related NAc LFPs in humans. Next, we review fMRI studies of cue craving in the context of potential neuromodulation targets based on a triple network model. Third, we briefly review relationships between electrophysiology and fMRI in general. Lastly, we suggest future research directions that integrate neuromodulation, electrophysiological recording, and neuroimaging to improve our understanding of craving in SUD.
{"title":"Electrophysiology and Functional Magnetic Resonance Imaging of Cue Craving: Potential Biomarkers for Therapeutic Neuromodulation in Addiction","authors":"Jody Tanabe , Jordan Hickman , Andy Tekriwal , Joseph Sakai , Aviva Abosch , Steven Ojemann , Joseph P. Schacht , John A. Thompson","doi":"10.1016/j.bpsgos.2025.100622","DOIUrl":"10.1016/j.bpsgos.2025.100622","url":null,"abstract":"<div><div>A major goal for substance use disorder (SUD) treatment is the reduction of drug craving, which contributes to continued drug use and relapse. Pathological craving is thought to reflect dysfunction in neural networks, sparking a growing interest in modulating the mesocorticolimbic reward and related networks to decrease craving and improve outcomes. Although initial studies of neuromodulation in SUDs have produced promising results, biomarkers for craving remain elusive. Advances in deep brain stimulation (DBS) now allow recording of local field potentials (LFPs) in the nucleus accumbens (NAc), the central hub of the reward circuit, thus paving the way for a novel LFP biomarker for craving. Insights into mechanistic models of craving that relate localized electrophysiology to distributed circuit activity are in the earliest stages. At the same time, performing invasive DBS surgery on individuals with SUD is a formidable challenge and underscores the need to refine our understanding of noninvasive functional magnetic resonance imaging (fMRI)–defined network biomarkers of craving. Here, we review the literature on LFPs and single-unit neural activity during craving and reward, highlighting recent findings of craving-related NAc LFPs in humans. Next, we review fMRI studies of cue craving in the context of potential neuromodulation targets based on a triple network model. Third, we briefly review relationships between electrophysiology and fMRI in general. Lastly, we suggest future research directions that integrate neuromodulation, electrophysiological recording, and neuroimaging to improve our understanding of craving in SUD.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100622"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520845","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}
Pub Date : 2026-01-01Epub Date: 2025-09-06DOI: 10.1016/j.bpsgos.2025.100607
Anni L.K. Malmberg , Matti Pirinen , Johannes Kettunen , Katri Räikkönen , Johan G. Eriksson , Jari Lahti
Background
Episodic memory (EM) refers to the ability to encode and recall events—a vital cognitive function for healthy cognitive aging and an endophenotype for dementia.
Methods
Using genome- and metabolome-wide least absolute shrinkage and selection operator (LASSO) analysis, we developed polygenic (LASSO-PRS) and metabolic risk scores (MRS) in ∼68.5-year-old individuals (n = 897). We also applied the Bayesian regression method PRS-CS to an external genome-wide meta-analysis (GWAMA, N = 29,785, age > 18 years) to derive another PRS (GWAMA-PRS). We assessed incremental variances (R2) in EM explained by the PRSs and MRS separately and in combination beyond the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score in 104 independent ∼68.5-year-old individuals. Finally, we validated the PRSs in 2 independent pediatric cohorts (N = 309, age = ∼11.9 years; N = 443, age = ∼8.6 years).
Results
In the independent sample of ∼68.5-year-old individuals, compared with CAIDE score alone, accounting additionally for either MRS, LASSO-PRS, or GWAMA-PRS increased R2 by 1.6, 5.6, and 4.5 percentage points (pp), respectively, while accounting additionally for MRS + LASSO-PRS or MRS + GWAMA-PRS increased R2 by 7.8 and 6.4 pp, respectively. Both LASSO-PRS (all false discovery rate [FDR]–adjusted p values = .01–.03) and GWAMA-PRS (all FDR-adjusted p values = .03) were significantly associated with EM in all models, while the CAIDE score and MRS were not (all FDR-adjusted p values > .05). PRSs were not associated with EM in the pediatric cohorts (all FDR-adjusted p values > .05).
Conclusions
Genomics added predictive value to EM beyond epidemiological risk factors in adults, but the same was not observed with metabolomics. Adult-derived PRSs did not predict EM in children.
{"title":"Prediction of Episodic Memory With Multiomics Scores","authors":"Anni L.K. Malmberg , Matti Pirinen , Johannes Kettunen , Katri Räikkönen , Johan G. Eriksson , Jari Lahti","doi":"10.1016/j.bpsgos.2025.100607","DOIUrl":"10.1016/j.bpsgos.2025.100607","url":null,"abstract":"<div><h3>Background</h3><div>Episodic memory (EM) refers to the ability to encode and recall events—a vital cognitive function for healthy cognitive aging and an endophenotype for dementia.</div></div><div><h3>Methods</h3><div>Using genome- and metabolome-wide least absolute shrinkage and selection operator (LASSO) analysis, we developed polygenic (LASSO-PRS) and metabolic risk scores (MRS) in ∼68.5-year-old individuals (<em>n</em> = 897). We also applied the Bayesian regression method PRS-CS to an external genome-wide meta-analysis (GWAMA, <em>N</em> = 29,785, age > 18 years) to derive another PRS (GWAMA-PRS). We assessed incremental variances (<em>R</em><sup>2</sup>) in EM explained by the PRSs and MRS separately and in combination beyond the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score in 104 independent ∼68.5-year-old individuals. Finally, we validated the PRSs in 2 independent pediatric cohorts (<em>N</em> = 309, age = ∼11.9 years; <em>N</em> = 443, age = ∼8.6 years).</div></div><div><h3>Results</h3><div>In the independent sample of ∼68.5-year-old individuals, compared with CAIDE score alone, accounting additionally for either MRS, LASSO-PRS, or GWAMA-PRS increased <em>R</em><sup>2</sup> by 1.6, 5.6, and 4.5 percentage points (pp), respectively, while accounting additionally for MRS + LASSO-PRS or MRS + GWAMA-PRS increased <em>R</em><sup>2</sup> by 7.8 and 6.4 pp, respectively. Both LASSO-PRS (all false discovery rate [FDR]–adjusted <em>p</em> values = .01–.03) and GWAMA-PRS (all FDR-adjusted <em>p</em> values = .03) were significantly associated with EM in all models, while the CAIDE score and MRS were not (all FDR-adjusted <em>p</em> values > .05). PRSs were not associated with EM in the pediatric cohorts (all FDR-adjusted <em>p</em> values > .05).</div></div><div><h3>Conclusions</h3><div>Genomics added predictive value to EM beyond epidemiological risk factors in adults, but the same was not observed with metabolomics. Adult-derived PRSs did not predict EM in children.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100607"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145324650","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}
Pub Date : 2026-01-01Epub Date: 2025-09-09DOI: 10.1016/j.bpsgos.2025.100610
Yunsheng Liu , Zengwei Kou
Background
Treatment-resistant depression (TRD) remains a major psychiatric challenge, with therapeutic paradigms evolving over the last 50 years. However, research on TRD is fragmented across molecular mechanisms, clinical interventions, and epidemiological trends, highlighting the need for a comprehensive synthesis to guide future studies and enhance clinical outcomes.
Methods
We conducted a large-scale bibliometric analysis of 16,198 TRD-related publications from PubMed, Web of Science, and Scopus (1974–2025). Using CiteSpace, VOSviewer, and Bibliometrix, we quantified publication trends, collaborative networks, and thematic shifts. Special attention was paid to influential researchers and institutions, as well as examining the shifting research focus from traditional invasive therapies, including deep brain stimulation, to emerging pharmacological advancements such as ketamine-based treatments.
Results
We identified leading countries, institutions, and key contributors on TRD research. Thematic clusters revealed sustained focus on neurobiological mechanisms (glutamate dysfunction, inflammation) and clinical efficacy. A pivotal shift from invasive techniques (dominant before 2000) to ketamine-based therapies was observed, with ketamine-related publications surging after 2010. High-impact journals such as Biological Psychiatry and American Journal of Psychiatry anchored 3 intellectual clusters: molecular neuropharmacology, pathophysiology, and clinical psychiatry. Despite progress, gaps persist in understanding ketamine’s systemic effects and noncanonical NMDA receptor roles.
Conclusions
This bibliometric study traces TRD research evolution from the 1970s onward, revealing key shifts from invasive interventions to novel pharmacotherapies such as ketamine, a transformative advance highlighting a mechanism-driven approach. By analyzing influential contributors, collaborations, and emerging trends, our work synthesizes decades of fragmented knowledge, providing clinicians and researchers with a cohesive road map for future TRD investigations.
背景：难治性抑郁症（TRD）仍然是一个重大的精神病学挑战，在过去的50年里，治疗范式不断发展。然而，关于TRD的研究在分子机制、临床干预和流行病学趋势方面是碎片化的，这突出表明需要全面综合以指导未来的研究并提高临床结果。方法对1974-2025年PubMed、Web of Science和Scopus中与trd相关的16,198篇论文进行了大规模的文献计量学分析。利用CiteSpace、VOSviewer和Bibliometrix，我们量化了出版趋势、合作网络和主题变化。会议对有影响力的研究人员和机构给予了特别关注，并审查了研究重点从传统侵入性治疗（包括深部脑刺激）转向新兴药理学进展（如氯胺酮治疗）的情况。结果：我们确定了TRD研究的主要国家、机构和主要贡献者。专题集群显示持续关注神经生物学机制（谷氨酸功能障碍，炎症）和临床疗效。从侵入性技术（2000年之前占主导地位）到基于氯胺酮的治疗方法发生了关键转变，与氯胺酮相关的出版物在2010年之后激增。诸如《生物精神病学》和《美国精神病学杂志》这样的高影响力期刊锚定了3个知识集群：分子神经药理学、病理生理学和临床精神病学。尽管取得了进展，但在理解氯胺酮的全身效应和非规范NMDA受体的作用方面仍然存在差距。这项文献计量学研究追溯了自20世纪70年代以来TRD研究的演变，揭示了从侵入性干预到新型药物治疗（如氯胺酮）的关键转变，这是一个突出机制驱动方法的变革性进步。通过分析有影响力的贡献者、合作和新兴趋势，我们的工作综合了几十年来零散的知识，为临床医生和研究人员提供了未来TRD调查的连贯路线图。
{"title":"Therapeutic Shifts and Scientific Influence in Treatment-Resistant Depression Research: A Data-Driven Perspective","authors":"Yunsheng Liu , Zengwei Kou","doi":"10.1016/j.bpsgos.2025.100610","DOIUrl":"10.1016/j.bpsgos.2025.100610","url":null,"abstract":"<div><h3>Background</h3><div>Treatment-resistant depression (TRD) remains a major psychiatric challenge, with therapeutic paradigms evolving over the last 50 years. However, research on TRD is fragmented across molecular mechanisms, clinical interventions, and epidemiological trends, highlighting the need for a comprehensive synthesis to guide future studies and enhance clinical outcomes.</div></div><div><h3>Methods</h3><div>We conducted a large-scale bibliometric analysis of 16,198 TRD-related publications from PubMed, Web of Science, and Scopus (1974–2025). Using CiteSpace, VOSviewer, and Bibliometrix, we quantified publication trends, collaborative networks, and thematic shifts. Special attention was paid to influential researchers and institutions, as well as examining the shifting research focus from traditional invasive therapies, including deep brain stimulation, to emerging pharmacological advancements such as ketamine-based treatments.</div></div><div><h3>Results</h3><div>We identified leading countries, institutions, and key contributors on TRD research. Thematic clusters revealed sustained focus on neurobiological mechanisms (glutamate dysfunction, inflammation) and clinical efficacy. A pivotal shift from invasive techniques (dominant before 2000) to ketamine-based therapies was observed, with ketamine-related publications surging after 2010. High-impact journals such as <em>Biological Psychiatry</em> and <em>American Journal of Psychiatry</em> anchored 3 intellectual clusters: molecular neuropharmacology, pathophysiology, and clinical psychiatry. Despite progress, gaps persist in understanding ketamine’s systemic effects and noncanonical NMDA receptor roles.</div></div><div><h3>Conclusions</h3><div>This bibliometric study traces TRD research evolution from the 1970s onward, revealing key shifts from invasive interventions to novel pharmacotherapies such as ketamine, a transformative advance highlighting a mechanism-driven approach. By analyzing influential contributors, collaborations, and emerging trends, our work synthesizes decades of fragmented knowledge, providing clinicians and researchers with a cohesive road map for future TRD investigations.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100610"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145324657","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}
A common feature of cannabis use disorder (CUD) is an intense reactivity to cannabis cues, which are becoming increasingly visible due to the growth in its decriminalization, accessibility, and marketing of cannabis products. The brain’s automatic reactivity to cannabis cues can trigger craving and subsequent use. In this study, we aimed to test neural activity during cannabis cue reactivity in non–treatment-seeking individuals with moderate-to-severe CUD and past attempts to cut down/quit.
Methods
The study examined 65 individuals with moderate-to-severe CUD and 43 control participants, with a functional magnetic resonance imaging cannabis cue-reactivity task and assessment of mental health and substance use as well as cognitive testing. Group differences in neural responses to cannabis cue reactivity were examined, adjusting for age and sex; correlations with cannabis use characteristics and mental health variables were assessed, accounting for recent substance use.
Results
Compared with control participants, individuals with CUD showed greater brain activity during cannabis cue reactivity in the superior/middle occipital, medial/lateral orbitofrontal cortex, anterior/posterior cingulate, cerebellar, hippocampus, and middle temporal and lateral parietal cortices (p < .05; cluster k > 10, familywise error corrected). Greater occipital/cerebellar activity correlated with greater subjective arousal toward cannabis images and cannabis withdrawal scores, while anterior cingulate/inferior parietal activity negatively correlated with urinary level of 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol:creatinine (ps < .05).
Conclusions
Exposure to cannabis cues can elicit greater activity within salience evaluation/attention, motivation, and disinhibition pathways of addiction neurocircuitry in people with moderate-to-severe CUD, consistent with prominent neuroscientific theories of addiction and findings with other substances. Interventions that can suppress brain activity in salience and attention circuits during cannabis cue reactivity may help reduce craving and subsequent use.
大麻使用障碍（CUD）的一个共同特征是对大麻的强烈反应，由于大麻产品的非犯罪化、可及性和营销的增长，这种反应越来越明显。大脑对大麻的自动反应会引发对大麻的渴望和随后的使用。在这项研究中，我们旨在测试中度至重度CUD患者在大麻线索反应期间的神经活动，这些患者没有寻求治疗，过去曾尝试减少/戒烟。方法对65例中重度CUD患者和43例对照患者进行功能性磁共振成像大麻线索反应任务、心理健康和物质使用评估以及认知测试。研究了大麻线索反应的神经反应组差异，并根据年龄和性别进行了调整；评估了大麻使用特征和心理健康变量之间的相关性，考虑到最近的物质使用情况。结果与对照组相比，CUD患者在大麻线索反应过程中，在枕上/枕中、眶额内侧/外侧皮层、扣带前部/后部、小脑、海马、颞叶中部和顶叶外侧皮层表现出更大的大脑活动（p < 0.05；聚类k >； 10，家庭误差校正）。枕叶/小脑活动越活跃，对大麻图像和大麻戒断评分的主观唤醒程度越高，而前扣带/下顶叶活动与尿中11- no -9-羧基-Δ9-tetrahydrocannabinol：肌酐水平呈负相关（ps < 0.05）。结论暴露于大麻线索可引起中重度CUD患者成瘾神经回路的显着性评价/注意、动机和去抑制通路的更大活动，这与著名的成瘾神经科学理论和其他物质的研究结果一致。在大麻线索反应期间，可以抑制大脑突出和注意回路活动的干预措施可能有助于减少渴望和随后的使用。
{"title":"The Neurocircuitry of Cannabis Cue Reactivity in Cannabis Use Disorder: A Functional Neuroimaging Study","authors":"Valentina Lorenzetti , Hannah Sehl , Arush Honnedevasthana Arun , Eugene McTavish , Adam Clemente , Hannah Thomson , Marianna Quinones-Valera , Alexandra Gaillard , Emillie Beyer , Diny Thomson , Janna Cousijn , Izelle Labuschagne , Peter Rendell , Gill Terrett , Chao Suo , Lisa-Marie Greenwood , Victoria Manning , Govinda Poudel","doi":"10.1016/j.bpsgos.2025.100638","DOIUrl":"10.1016/j.bpsgos.2025.100638","url":null,"abstract":"<div><h3>Background</h3><div>A common feature of cannabis use disorder (CUD) is an intense reactivity to cannabis cues, which are becoming increasingly visible due to the growth in its decriminalization, accessibility, and marketing of cannabis products. The brain’s automatic reactivity to cannabis cues can trigger craving and subsequent use. In this study, we aimed to test neural activity during cannabis cue reactivity in non–treatment-seeking individuals with moderate-to-severe CUD and past attempts to cut down/quit.</div></div><div><h3>Methods</h3><div>The study examined 65 individuals with moderate-to-severe CUD and 43 control participants, with a functional magnetic resonance imaging cannabis cue-reactivity task and assessment of mental health and substance use as well as cognitive testing. Group differences in neural responses to cannabis cue reactivity were examined, adjusting for age and sex; correlations with cannabis use characteristics and mental health variables were assessed, accounting for recent substance use.</div></div><div><h3>Results</h3><div>Compared with control participants, individuals with CUD showed greater brain activity during cannabis cue reactivity in the superior/middle occipital, medial/lateral orbitofrontal cortex, anterior/posterior cingulate, cerebellar, hippocampus, and middle temporal and lateral parietal cortices (<em>p</em> < .05; cluster <em>k</em> > 10, familywise error corrected). Greater occipital/cerebellar activity correlated with greater subjective arousal toward cannabis images and cannabis withdrawal scores, while anterior cingulate/inferior parietal activity negatively correlated with urinary level of 11-Nor-9-carboxy-Δ<sup>9</sup>-tetrahydrocannabinol:creatinine (<em>p</em>s < .05).</div></div><div><h3>Conclusions</h3><div>Exposure to cannabis cues can elicit greater activity within salience evaluation/attention, motivation, and disinhibition pathways of addiction neurocircuitry in people with moderate-to-severe CUD, consistent with prominent neuroscientific theories of addiction and findings with other substances. Interventions that can suppress brain activity in salience and attention circuits during cannabis cue reactivity may help reduce craving and subsequent use.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100638"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684514","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}
Pub Date : 2026-01-01Epub Date: 2025-10-28DOI: 10.1016/j.bpsgos.2025.100642
Kateryna Golovina , Mai Gutvilig , Ripsa Niemi , Christian Hakulinen
Background
Previous research has shown assortative mating across various psychiatric disorders; however, their definitions of partnership have often been limited, and the timing of relationship formation has been imprecise. In this study, we aimed to comprehensively examine assortative mating across the full spectrum of mental disorders using population-wide register data from Finland that include information on the formation of both marriages and cohabiting unions.
Methods
We used nationwide data on all cohabitations and marriages between 2000 and 2020 from the Finnish Population Register (n = 1,271,242 partnerships). Broad and specific categories of mental disorder diagnoses were retrieved from both primary and secondary health care registers in Finland. We calculated tetrachoric correlations between partners’ mental disorder diagnoses, considering only diagnoses received before the start of cohabitation or marriage.
Results
Assortative mating was observed across the full spectrum of mental disorders, with the strongest within-disorder correlations for schizophrenia, psychotic disorders, organic mental disorders, and intellectual disabilities (r > 0.50). Moderate correlations were found for mood and anxiety disorders. Adjusting for birth decade and excluding comorbidities slightly attenuated the associations but did not change the overall patterns.
Conclusions
This study suggests that assortative mating is prevalent in mental disorders. Assortative mating may contribute to the transmission and clustering of mental disorders within families, highlighting the importance of considering partner selection in mental health research and policy making.
{"title":"Assortative Mating Across the Full Spectrum of Mental Disorders: A Nationwide Finnish Register Study","authors":"Kateryna Golovina , Mai Gutvilig , Ripsa Niemi , Christian Hakulinen","doi":"10.1016/j.bpsgos.2025.100642","DOIUrl":"10.1016/j.bpsgos.2025.100642","url":null,"abstract":"<div><h3>Background</h3><div>Previous research has shown assortative mating across various psychiatric disorders; however, their definitions of partnership have often been limited, and the timing of relationship formation has been imprecise. In this study, we aimed to comprehensively examine assortative mating across the full spectrum of mental disorders using population-wide register data from Finland that include information on the formation of both marriages and cohabiting unions.</div></div><div><h3>Methods</h3><div>We used nationwide data on all cohabitations and marriages between 2000 and 2020 from the Finnish Population Register (<em>n</em> = 1,271,242 partnerships). Broad and specific categories of mental disorder diagnoses were retrieved from both primary and secondary health care registers in Finland. We calculated tetrachoric correlations between partners’ mental disorder diagnoses, considering only diagnoses received before the start of cohabitation or marriage.</div></div><div><h3>Results</h3><div>Assortative mating was observed across the full spectrum of mental disorders, with the strongest within-disorder correlations for schizophrenia, psychotic disorders, organic mental disorders, and intellectual disabilities (<em>r</em> > 0.50). Moderate correlations were found for mood and anxiety disorders. Adjusting for birth decade and excluding comorbidities slightly attenuated the associations but did not change the overall patterns.</div></div><div><h3>Conclusions</h3><div>This study suggests that assortative mating is prevalent in mental disorders. Assortative mating may contribute to the transmission and clustering of mental disorders within families, highlighting the importance of considering partner selection in mental health research and policy making.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100642"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684592","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}
Pub Date : 2026-01-01Epub Date: 2025-09-26DOI: 10.1016/j.bpsgos.2025.100618
Fabiana Ventura , Pedro Frias , Daniel Rodrigues da Silva , Alexander McGirr , Gonçalo Cotovio , Albino J. Oliveira-Maia
Background
Repetitive transcranial magnetic stimulation (rTMS) is cleared by the Food and Drug Administration for major depression, and recently received breakthrough status for bipolar depression (BDep). However, evidence on its efficacy and safety and optimal protocols for BDep remains limited. We conducted a systematic review to synthesize available data on rTMS for BDep.
Methods
We systematically searched 4 literature databases for studies published between 1995 and 2025 treating participants with acute BDep (1097 articles). The primary outcome for the meta-analysis was change in mean depression severity scores from baseline. Determinants of treatment response were assessed using meta-regression and subgroup meta-analyses.
Results
Fifty-six articles were included, representing a total of 1709 patients with BDep. Active TMS had superior antidepressant efficacy relative to sham in randomized controlled trials (RCTs) (Cohen’s d = 0.40). Rates of treatment-emergent mania or hypomania were low and equivalent to those found for sham (odds ratio = 1.3; 95% CI, 0.7–2.4). A large effect size for antidepressant effectiveness was found when pooling active arms of RCTs with data from uncontrolled studies (Cohen’s d = 1.4), with rates of response (46.81%) and remission (28.25%) similar to those described for MDD and preserved in subanalyses for high-frequency protocols, including intermittent theta burst stimulation (iTBS) delivered to the left dorsolateral prefrontal cortex (DLPFC) and low-frequency protocols delivered to the right DLPFC. Higher baseline illness severity and more treatment sessions were predictors of greater antidepressant effect.
Conclusions
TMS is efficacious and safe in BDep, with response and remission rates on par with rates for unipolar depression. High- and low-frequency protocols on the left and right DLPFC, respectively, are robustly associated with positive outcomes, with left DLPFC iTBS showing noninferiority to more widely used high-frequency rTMS protocols.
重复经颅磁刺激（rTMS）已被美国食品和药物管理局批准用于治疗重度抑郁症，最近在治疗双相抑郁症（BDep）方面取得了突破性进展。然而，关于其有效性和安全性以及BDep的最佳方案的证据仍然有限。我们进行了一项系统综述，以综合rTMS治疗BDep的现有数据。方法系统检索4个文献数据库，检索1995 - 2025年间发表的治疗急性BDep的研究（1097篇）。荟萃分析的主要结果是平均抑郁严重程度评分从基线的变化。采用荟萃回归和亚组荟萃分析评估治疗反应的决定因素。结果纳入56篇文献，共1709例BDep患者。在随机对照试验（RCTs）中，活性经颅磁刺激相对于假经颅磁刺激具有更好的抗抑郁疗效（Cohen’s d = 0.40）。治疗后出现的躁狂症或轻躁症发生率较低，与假手术组相当（优势比= 1.3;95% CI, 0.7-2.4）。当将随机对照试验的有效组与非对照研究的数据（Cohen’s d = 1.4）合并时，发现抗抑郁药物有效性的大效应量，反应率（46.81%）和缓解率（28.25%）与MDD相似，并保留在高频方案的亚分析中，包括间歇性θ波爆发刺激（iTBS）传递到左背外侧前额叶皮层（DLPFC）和低频方案传递到右DLPFC。更高的基线疾病严重程度和更多的治疗时间是更大的抗抑郁效果的预测因子。结论stms治疗BDep有效且安全，其缓解率与单极抑郁症相当。左侧和右侧DLPFC的高频和低频方案分别与阳性结果显著相关，左侧DLPFC iTBS与更广泛使用的高频rTMS方案表现出非劣效性。
{"title":"Efficacy, Effectiveness, and Safety of Transcranial Magnetic Stimulation for Bipolar Depression: A Systematic Review and Meta-Analysis","authors":"Fabiana Ventura , Pedro Frias , Daniel Rodrigues da Silva , Alexander McGirr , Gonçalo Cotovio , Albino J. Oliveira-Maia","doi":"10.1016/j.bpsgos.2025.100618","DOIUrl":"10.1016/j.bpsgos.2025.100618","url":null,"abstract":"<div><h3>Background</h3><div>Repetitive transcranial magnetic stimulation (rTMS) is cleared by the Food and Drug Administration for major depression, and recently received breakthrough status for bipolar depression (BDep). However, evidence on its efficacy and safety and optimal protocols for BDep remains limited. We conducted a systematic review to synthesize available data on rTMS for BDep.</div></div><div><h3>Methods</h3><div>We systematically searched 4 literature databases for studies published between 1995 and 2025 treating participants with acute BDep (1097 articles). The primary outcome for the meta-analysis was change in mean depression severity scores from baseline. Determinants of treatment response were assessed using meta-regression and subgroup meta-analyses.</div></div><div><h3>Results</h3><div>Fifty-six articles were included, representing a total of 1709 patients with BDep. Active TMS had superior antidepressant efficacy relative to sham in randomized controlled trials (RCTs) (Cohen’s <em>d</em> = 0.40). Rates of treatment-emergent mania or hypomania were low and equivalent to those found for sham (odds ratio = 1.3; 95% CI, 0.7–2.4). A large effect size for antidepressant effectiveness was found when pooling active arms of RCTs with data from uncontrolled studies (Cohen’s <em>d</em> = 1.4), with rates of response (46.81%) and remission (28.25%) similar to those described for MDD and preserved in subanalyses for high-frequency protocols, including intermittent theta burst stimulation (iTBS) delivered to the left dorsolateral prefrontal cortex (DLPFC) and low-frequency protocols delivered to the right DLPFC. Higher baseline illness severity and more treatment sessions were predictors of greater antidepressant effect.</div></div><div><h3>Conclusions</h3><div>TMS is efficacious and safe in BDep, with response and remission rates on par with rates for unipolar depression. High- and low-frequency protocols on the left and right DLPFC, respectively, are robustly associated with positive outcomes, with left DLPFC iTBS showing noninferiority to more widely used high-frequency rTMS protocols.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100618"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571564","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}
Pub Date : 2026-01-01Epub Date: 2025-11-17DOI: 10.1016/j.bpsgos.2025.100641
Deepak K. Sarpal
{"title":"Artificial Intelligence Meets Ultra-High-Field Neuroimaging to Examine Psychosis","authors":"Deepak K. Sarpal","doi":"10.1016/j.bpsgos.2025.100641","DOIUrl":"10.1016/j.bpsgos.2025.100641","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100641"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571562","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}
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