Biological psychiatry. Cognitive neuroscience and neuroimaging最新文献

{"title":"Resting-state Neural Signatures of Moral Injury: Associations with Rumination.","authors":"Travis M Fulton, Alfonsina Guelfo, Aziz Elbasheir, Timothy J McDermott, Jiwon Lee, Vishwadeep Ahluwalia, Timothy D Ely, Emma Lathan-Powell, Negar Fani","doi":"10.1016/j.bpsc.2025.08.001","DOIUrl":"10.1016/j.bpsc.2025.08.001","url":null,"abstract":"<p><strong>Background: </strong>Moral injury (MI) is a condition that may emerge following a violation of an individual's moral code. MI leads to significant functional impairment in many trauma-exposed civilians with rumination proposed as a mechanism of action. Little is known about the neuropathophysiology of different MI dimensions, including MI related to transgressions caused by the self or others. We examined links between facets of MI, resting-state amplitude of low frequency fluctuations (ALFF) and rumination in trauma-exposed civilians.</p><p><strong>Methods: </strong>Sixty adults (18-65 years, 51 female) completed measures of moral injury (Moral Injury Exposure and Symptom Scale for Civilians, MIESS-C), rumination (Response Styles Questionnaire, RSQ), and resting-state fMRI. Voxel-wise linear regression on ALFF was performed with rumination and MIESS-C-derived self, other, and betrayal-related MI as regressors.</p><p><strong>Results: </strong>Betrayal-related MI associated with higher ALFF in the bilateral precuneus and left medial prefrontal cortex. Other-related MI associated with lower ALFF in the left dorsolateral prefrontal cortex and insula (voxel-wise p<.001, cluster false discovery rate-corrected p<.05). Rumination severity was positively associated with betrayal-related ALFF clusters in the bilateral precuneus r =0.32, p =0.012, and left medial prefrontal cortex, r =0.31, p =0.017.</p><p><strong>Conclusions: </strong>Results reveal distinct neural signatures of MI, with betrayal-related MI associated with greater ALFF in default mode network regions, and this activation related to rumination severity. Other-related MI linked with diminished activation in cognitive control and interoceptive network regions, which may reflect physiological withdrawal. These signatures are attractive candidate neuromodulatory targets.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12415846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144877240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebellar-Prefrontal Connectivity Predicts Negative Symptom Severity Across the Psychosis Spectrum.","authors":"Sean A Yarrell, Sophia H Blyth, Alexandra B Moussa-Tooks, Baxter P Rogers, Anna Huang, Neil D Woodward, Stephan Heckers, Roscoe O Brady, Heather Burrell Ward","doi":"10.1016/j.bpsc.2025.07.013","DOIUrl":"10.1016/j.bpsc.2025.07.013","url":null,"abstract":"<p><strong>Background: </strong>Negative symptom severity predicts functional outcome and quality of life in people with psychosis. However, negative symptoms are poorly responsive to medication, and existing literature has not converged on their neurobiological basis. Previous work in small schizophrenia samples has observed that lower cerebellar-dorsolateral prefrontal cortex (DLPFC) connectivity is associated with higher negative symptom severity and that increasing cerebellar-DLPFC connectivity with neuromodulation reduces negative symptoms. We extended this finding by testing associations between cerebellar-DLPFC connectivity, negative symptoms, and cognitive performance in a large sample of individuals with psychosis.</p><p><strong>Methods: </strong>Individuals with psychosis spectrum disorders (n=260) underwent resting-state fMRI and clinical characterization using the Positive and Negative Symptoms Scale and the Screen for Cognitive Impairment in Psychiatry. Using a previously identified cerebellar region as a seed, we measured connectivity to the DLPFC and regressed connectivity against negative symptom severity, covarying for age, sex, and scanner. We then tested if cognitive performance indirectly affected the relationship between connectivity and negative symptom severity.</p><p><strong>Results: </strong>Across the psychosis spectrum, higher cerebellar-DLPFC connectivity was associated with lower negative symptom severity (r=-0.17, p=.007). This connectivity-negative symptoms relationship was not affected by psychosis subtype or duration of illness. Better delayed verbal learning was associated with higher cerebellar-DLPFC connectivity (r=.13, p=.034) and had a significant indirect effect on the relationship between connectivity and negative symptoms.</p><p><strong>Conclusions: </strong>Our results extend relationships between cerebellar-DLPFC connectivity, negative symptom severity, and cognitive performance across the psychosis spectrum. Larger neuromodulation studies should test if increasing cerebellar-DLPFC connectivity reduces negative symptoms in psychotic disorders.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859984","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}

{"title":"Brain Myelin in Children with ADHD: A Longitudinal T1w/T2w-ratio Study.","authors":"M Dipnall Lillian, Ian Fuelscher, Y M Yang Joseph, Jian Chen, M Craig Jeffrey, Vicki Anderson, Daryl Efron, J Silk Timothy","doi":"10.1016/j.bpsc.2025.07.012","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.07.012","url":null,"abstract":"<p><strong>Background: </strong>Research has demonstrated a broad network of dysfunction across the brain in Attention Deficit/Hyperactivity Disorder (ADHD), suggesting the potential role of white matter (WM) organization. This study sought to estimate the developmental trajectories of brain WM myelination in children with ADHD.</p><p><strong>Methods: </strong>Neuroimaging and clinical data were collected as part of a longitudinal community-based pediatric cohort (N_scans=400; 195 with ADHD; age range, 9-14 years). Brain WM myelin was examined for 71 WM tracts across 3 time points using the T1w/T2w-ratio. Tracts were defined via a deep-learning based automated tractography method, performed on participant diffusion-weighted imaging. Linear and non-linear regression was conducted to examine group differences in T1w/T2w-ratio values. In addition to this, voxel-wise analysis was undertaken at each time point.</p><p><strong>Results: </strong>Brain-wide, children with ADHD were found to exhibit the same developmental profile as those without ADHD for WM myelin. No group effects were seen at a cross-sectional or longitudinal level. In agreement with previous work, modelling suggests non-linear developmental increases with age across most tract. This non-linear relationship was characterized by a positive parabolic, or U-shaped developmental trajectory.</p><p><strong>Conclusions: </strong>These findings indicate that there may not be distinct difference in the development of brain white matter myelination between children with and without ADHD. However, this suggests that previously reported differences in ADHD brain WM development may be attributable to properties other than myelin, such as fiber architecture and axon diameter. This further informs the understanding of brain development and highlights the need for further multi-modal longitudinal work.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144823416","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}

{"title":"Disrupted Large-Scale Brain Network Connectivity in Prolonged Grief Disorder: Relationship with Grief-Related Avoidance, Yearning, and Intrusive Thoughts.","authors":"Nutta-On P Blair, Gyujoon Hwang, B Douglas Ward, Stacy A Claesges, Abigail R Webber, Keri R Hainsworth, Yang Wang, Charles F Reynolds, Elliot A Stein, Joseph S Goveas","doi":"10.1016/j.bpsc.2025.07.011","DOIUrl":"10.1016/j.bpsc.2025.07.011","url":null,"abstract":"<p><strong>Background: </strong>Large-scale brain network dysfunctions have been implicated in multiple neuropsychiatric disorders. Disrupted interactions between these networks may similarly underlie key symptoms in prolonged grief disorder (PGD).</p><p><strong>Methods: </strong>In a cross-sectional, functional magnetic resonance imaging study, resting-state functional connectivity (rsFC) between large-scale networks were compared in demographic- and time since loss-equated older adults with probable PGD (n=42) and those with integrated grief (n=45). Group independent component analysis revealed multiple networks, eight of which (salience, default mode, left and right executive control, ventral attention, dorsal attention, sensorimotor, and visual) were selected for further analyses, with rsFC strength between all network pairs computed. Networks with significant group differences were further assessed using fractional amplitude of low-frequency fluctuations (fALFF) to determine within-network differences. The relationships between connectivity measures and clinical symptoms were explored independently in the PGD and integrated grief groups.</p><p><strong>Results: </strong>Higher rsFC between the salience (SN) and default mode (DMN) networks was observed in PGD compared with integrated grief (p_corrected = 0.014), which positively correlated with grief severity (p_corrected = 0.04) and grief-related avoidance (p_corrected = 0.04). In PGD, higher fALFF was observed in the DMN (p_uncorrected = 0.04), but not the SN. Principal component analysis revealed four symptom dimensions, with connectivity between multiple brain networks extending beyond SN and DMN associated with an intrusive thoughts/yearning/avoidance component.</p><p><strong>Conclusions: </strong>Aberrant connectivity between the SN and DMN appears to be a neurobiological correlate of grief severity and avoidance in PGD. Broader between-network connectivity disruptions correlate with intrusive thoughts, yearning, and avoidance, warranting further investigations into the mechanistic role of brain network dysfunction in PGD.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12346161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deriving Mendelian Randomization-based Causal Networks of Brain Imaging Phenotypes and Bipolar Disorder.","authors":"Shane O'Connell, Brielin C Brown, Dara M Cannon, Pilib Ó Broin, Nadine Parker, Dag Alnæs, Lars T Westlye, Saikat Banerjee, Leila Nabulsi, Emma Corley, Ole A Andreassen, David A Knowles, Niamh Mullins","doi":"10.1016/j.bpsc.2025.07.010","DOIUrl":"10.1016/j.bpsc.2025.07.010","url":null,"abstract":"<p><strong>Background: </strong>Neuroanatomical variation in individuals with bipolar disorder (BD) has been previously described in observational studies. However, the causal dynamics of these relationships remain unexplored.</p><p><strong>Methods: </strong>We performed Mendelian Randomization of 297 structural and functional neuroimaging phenotypes from the UK Biobank and BD using GWAS summary statistics. We carried out a suite of sensitivity analyses and examined phenotypic categories with the greatest effect on BD. We applied a novel inverse sparse regression model which accounts for covariance between sets of correlated effects to estimate 'direct causal effects' (DCE), representing the effect of one phenotype conditional on all other effects. We used DCE weights to create causal scores for BD using neuroimaging data from three clinical cohorts.</p><p><strong>Results: </strong>We found 28 significant causal relationship pairs after multiple testing corrections containing BD as a term, 27 of which described neuroimaging phenotype effects on BD. White matter tract phenotypes have larger absolute effects on BD than vice versa in MR tests and estimated direct causal effect solutions. We found that white matter phenotypes had significantly larger out-degrees than non-white matter tract phenotypes across network solutions. A causal score constructed using neuroimaging causal estimates was a significant predictor of BD in an adolescent cohort (O.R.=0.79).</p><p><strong>Conclusion: </strong>Mendelian randomization analyses suggest that neuroanatomical variation, specifically in white matter tracts such as the longitudinal fasciculi, is likely a cause rather than a consequence of BD. Verification of estimated causal relationships requires replication and triangulation of evidence approaches using other study designs.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777194","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}

{"title":"Larger Neural Responses to Reward in Gambling Disorder: Relationships with Depression and Gambling Severity.","authors":"Maria Kryza-Lacombe, Samantha V Abram, Marc N Potenza, R Scott Mackin, Ken J Lau, Spero C Nicholas, Judith M Ford, Steven L Batki, Daniel H Mathalon, Susanna L Fryer","doi":"10.1016/j.bpsc.2025.07.008","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.07.008","url":null,"abstract":"<p><strong>Background: </strong>For most people, gambling is a type of entertainment that engages pleasure, risk, and reward drives. However, some individuals develop gambling disorder (GD), a behavioral addiction involving continued gambling despite negative consequences. Disturbances in reward neurocircuitry have been implicated in GD, but are not well-characterized, including how neural alterations relate to clinical symptomatology of GD and commonly co-occurring presentations such as depression.</p><p><strong>Methods: </strong>EEG was recorded while participants with GD (n=26) and comparison subjects (HCs=54) completed a slot machine task. Event-related potential components (ERPs) reflecting reward anticipation (stimulus preceding negativity: SPN) and reward outcome evaluation (reward positivity: RewP; late positive potential: LPP) were assessed. Within GD, we examined associations between reward ERPs and a clinical summary score that reflected greater problem-gambling and depressive symptoms, and lower global functioning.</p><p><strong>Results: </strong>Compared to HCs, GD participants had larger (more negative) SPN amplitudes to possible wins vs. total-miss losses (t=2.45, p=.017), equivalent RewP amplitudes, and higher LPP amplitudes (F=9.08, p=.003) to both wins (t=2.90, p=.004) and near-miss losses (t=2.69, p=.004). More severe clinical symptomatology covaried with more negative SPN amplitudes (Spearman's rho=-.523, p=.021, FDR-corrected), but not with RewP or LPP.</p><p><strong>Conclusions: </strong>Individuals with GD show larger neural responses during reward anticipation (SPN) and late-stage processing of reward outcomes (LPP). Exaggerated neural responses during reward anticipation are most pronounced among individuals with more severe clinical symptomatology. These findings suggest that excessive reward anticipation as well as heightened salience to outcomes, regardless of valence, are potential mechanisms underlying GD.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765887","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}

{"title":"Encoding-Retrieval Similarity Reveals Distinct Neural Reinstatement of Safety Memories Following Counterconditioning in Posttraumatic Stress Disorder.","authors":"Elizabeth A Bauer, Samuel E Cooper, Nicole E Keller, Josh M Cisler, Joseph E Dunsmoor","doi":"10.1016/j.bpsc.2025.07.007","DOIUrl":"10.1016/j.bpsc.2025.07.007","url":null,"abstract":"<p><strong>Background: </strong>Posttraumatic stress disorder (PTSD) is characterized by deficits in the ability to retrieve extinction memories, which likely contribute to symptom relapse over time. Adapting a hybrid Pavlovian conditioning and episodic memory paradigm, we examined whether counterconditioning produces a more stable and persistent long-term neural memory trace of safety compared with standard extinction in the ventromedial prefrontal cortex (vmPFC)-a region associated with the learning and retrieval of safety.</p><p><strong>Methods: </strong>Participants consisted of 32 individuals (27 female) who met diagnostic criteria for PTSD and 21 healthy (13 female) comparison participants. Participants completed a multiday Pavlovian conditioning and episodic memory paradigm with standard extinction/counterconditioning.</p><p><strong>Results: </strong>In healthy adults, we identified overlapping multivariate patterns of functional magnetic resonance imaging activity in the vmPFC associated with the formation and 24-hour retrieval of stimuli that underwent counterconditioning, but neural reinstatement diminished after ∼1 month. This pattern was reversed in PTSD, such that neural reinstatement of counterconditioning was not observed the day after safety learning but did emerge a month later. Interestingly, participants with PTSD showed reinstatement of standard extinction memories in the dorsal anterior cingulate cortex-a region associated with learning and retrieval of threat-both 24 hours and 1 month after safety learning.</p><p><strong>Conclusions: </strong>These results provide the first evidence that counterconditioning may stabilize a long-term safety memory trace in PTSD. These effects seem to emerge over longer time scales, suggesting that counterconditioning could be an effective strategy for sustained treatment gains.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762670","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}

{"title":"Altered striatal functional gradients in obsessive-compulsive disorder.","authors":"Lachlan Webb, Luke Hearne, Ye E Tian, Andrew Zalesky, Conor Robinson, Caitlin V Hall, Saurabh Sonkusare, Bjorn Burgher, Michael Breakspear, Garance M Meyer, Andreas Horn, Sebastien Naze, Philip Mosley, Luca Cocchi","doi":"10.1016/j.bpsc.2025.07.006","DOIUrl":"10.1016/j.bpsc.2025.07.006","url":null,"abstract":"<p><strong>Background: </strong>Obsessive-compulsive disorder (OCD) is associated with functional alterations in how the striatum interacts with the rest of the brain. However, the characterization of these changes in OCD is incomplete. Mapping functional striatal gradients provides a new opportunity to fill this knowledge gap. These gradients provide a spatial representation of continuous changes in whole-brain connectivity within striatal regions. Thus, OCD-related differences in striatal gradients imply changes in the functional organisation of striatal connections.</p><p><strong>Methods: </strong>We calculated spatial striatal gradients linked to whole brain activity in 52 people with OCD and 45 controls. Gradients were computed with individuals at rest and when they underwent a threat-safety reversal task. Using a longitudinal dataset of 47 people with OCD, we investigated possible associations between changes in striatal gradient topology and fluctuations in symptom severity.</p><p><strong>Results: </strong>Results showed group differences in the main gradient topology at rest, specifically in striatal regions overlapping with the putamen and caudate. Individuals showing a reduction in symptoms over time tended to change their gradient topology in favour of the control participants' average topology. Finally, gradients linked to the appraisal of safety-reversal, but not threat-reversal, showed a group difference in a region separating the right nucleus accumbens and the putamen.</p><p><strong>Conclusions: </strong>This study advances knowledge of striatal connectivity profiles in OCD, supporting a core role of distinct changes in striatal topology in the expression of symptoms. Collectively, these results encourage studies assessing neural mechanisms driving the dynamic reorganisation of striatal topology and the development of therapies leveraging striato-cortical plasticity.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736005","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}

{"title":"Structural covariance of early visual cortex is negatively associated with PTSD symptoms: A Mega-Analysis from the ENIGMA PTSD workgroup.","authors":"Nathaniel G Harnett, Soumyaa Joshi, Poornima Kumar, Courtney Russell, Daniel G Dillon, Justin T Baker, Diego A Pizzagalli, Milissa L Kaufman, Lisa N Nickerson, Neda Jahanshad, Lauren E Salminen, Sophia I Thomopoulos, Jessie L Frijling, Dick J Veltman, Saskia B J Koch, Laura Nawijn, Mirjam van Zuiden, Ye Zhu, Gen Li, Jonathan Ipser, Xi Zhu, Orren Ravid, Sigal Zilcha-Mano, Amit Lazarov, Benjamin Suarez-Jimenez, Delin Sun, Ahmed Hussain, Ashley A Huggins, Tanja Jovanovic, Sanne J H van Rooij, Negar Fani, Anna R Hudson, Anika Sierk, Antje Manthey, Henrik Walter, Nic J A van der Wee, Steven J A van der Werff, Robert R J M Vermeiren, Pavel Říha, Lauren A M Lebois, Isabelle M Rosso, Elizabeth A Olson, Israel Liberzon, Mike Angstadt, Seth G Disner, Scott R Sponheim, Sheri-Michelle Koopowitz, David Hofmann, Rongfeng Qi, Adi Maron-Katz, Austin Kunch, Hong Xie, Wissam El-Hage, Hannah Berg, Steven E Bruce, Katie A McLaughlin, Matthew Peverill, Kelly Sambrook, Marisa Ross, Ryan J Herringa, Jack B Nitschke, Richard J Davidson, Terri A deRoon-Cassini, Carissa W Tomas, Jacklynn M Fitzgerald, Jennifer Urbano Blackford, Bunmi O Olatunji, Steven M Nelson, Evan M Gordon, Maria Densmore, Jean Théberge, Richard W J Neufeld, Miranda Olff, Li Wang, Dan J Stein, Yuval Neria, Jennifer S Stevens, Sven C Mueller, Judith K Daniels, Ivan Rektor, Anthony King, Nicholas D Davenport, Thomas Straube, Guangming Lu, Amit Etkin, Xin Wang, Yann Quidé, Shmuel Lissek, Josh Cisler, Daniel W Grupe, Christine Larson, Brandee Feola, Geoffrey May, Chadi G Abdallah, Ruth Lanius, Paul M Thompson, Rajendra A Morey, Kerry Ressler","doi":"10.1016/j.bpsc.2025.07.005","DOIUrl":"10.1016/j.bpsc.2025.07.005","url":null,"abstract":"<p><strong>Background: </strong>Identifying robust neural signatures of posttraumatic stress disorder (PTSD) symptoms is important to facilitate precision psychiatry and help in understanding and treatment of the disorder. Emergent research suggests structural covariance of early visual regions is associated with later PTSD development. However, large-scale analyses are needed - in heterogeneous samples of trauma-exposed and trauma naive individuals - to determine if such a neural signature is a robust marker of vulnerability.</p><p><strong>Methods: </strong>We analyzed data from the ENIGMA-PTSD dataset (n = 2,814) and the Human Connectome Project - Young Adult (HCP-YA) dataset (n = 890) to investigate whether structural covariance of early visual cortex is associated with either PTSD symptoms or perceived stress. Structural covariance was derived from a multimodal pattern previously identified in recent trauma survivors, and participant loadings on the profile were included in linear mixed effects models to evaluate associations with stress.</p><p><strong>Results: </strong>Early visual cortex covariance loadings were negatively associated with PTSD symptoms in the ENIGMA-PTSD dataset. The relationship persisted when accounting for prior childhood maltreatment; supporting PTSD symptom specificity, no relationship was observed with depressive symptoms and no association was observed between loadings and perceived stress measures in the HCP-YA dataset.</p><p><strong>Conclusion: </strong>Structural covariance of early visual cortex was robustly associated with PTSD symptoms across an international, heterogeneous sample of trauma survivors. Future studies should aim to identify specific mechanisms that underlie structural alterations in the visual cortex to better understand posttrauma psychopathology.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutamatergic modulation of brain function in psychosis: A systematic review of neuroimaging studies.","authors":"Ioana Varvari, Lara Bolte, Chiara Colli, Valentina Mancini, Matthew M Nour, Philip McGuire, Robert A McCutcheon","doi":"10.1016/j.bpsc.2025.07.004","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.07.004","url":null,"abstract":"<p><strong>Background: </strong>Aberrant dopamine and glutamate signalling are implicated in the pathophysiology of schizophrenia. Existing treatments primarily target dopamine pathways underlying positive symptoms but have relatively little effect on cognitive and negative symptoms. Glutamatergic modulators may treat the latter symptom domains, and neuroimaging studies have the potential to identify therapeutic mechanisms. We conducted a systematic review to examine functional neuroimaging studies of glutamatergic modulators in psychosis, and determine whether these agents alter brain activity, chemistry, or functional connectivity, and if such changes map onto clinical outcomes.</p><p><strong>Methods: </strong>Following PRISMA guidelines (PROSPERO: CRD42024549120), Medline, Embase, and PsycINFO were searched from inception to June 2024 for studies administering pharmacologic glutamate modulators to individuals with psychosis, employing functional neuroimaging (1H-MRS, fMRI, ASL, PET, EEG, or MEG). Twenty-seven articles met inclusion criteria, encompassing 841 participants.</p><p><strong>Results: </strong>Evidence from ¹H-MRS suggests that sarcosine, N-Acetylcysteine, and Riluzole reduce glutamate concentrations in frontal and hippocampal regions, but no clinical outcomes investigated. Resting-state and task-based fMRI studies suggest that NMDAR modulators may normalise measures of functional dysconnectivity, though effects were often short-lived and did not always correspond to sustained symptom improvements. Similarly, EEG studies consistently identified normalisation of mismatch negativity and gamma oscillations, but correlations with symptom or cognitive outcomes were inconsistent.</p><p><strong>Conclusions: </strong>While glutamatergic modulators show measurable effects on brain chemistry and electrophysiology, the relationship to robust, durable clinical benefits remains elusive. Future work should employ larger, longer duration, and multimodal imaging studies to clarify the precise mechanisms, optimal dosing, and patient subgroups most likely to benefit from glutamatergic interventions in psychosis.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700648","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}