Neurobiology of Stress最新文献

{"title":"The Legacy of Seymour Levine","authors":"Michael J. Meaney","doi":"10.1016/j.ynstr.2026.100834","DOIUrl":"10.1016/j.ynstr.2026.100834","url":null,"abstract":"<div><div>This essay assumes an historical perspective intended to highlight the major contributions of Seymour “Gig” Levine to the conceptual scaffold that guides so much of the current research in development and psychopathology. I suggest that perhaps Levine's most important contribution was to establish an experimental framework that served to transition the clinical observations of Freud and the attachment theories of Bowlby into modern Psychology/Psychiatry.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"43 ","pages":"Article 100834"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activity of VMS-projecting mPFC neurons encodes individual vulnerability to chronic restraint stress in male mice","authors":"Yaqiu Tang,&nbsp;Xin Gong,&nbsp;Mengyu Dai,&nbsp;Zhen Wang,&nbsp;Dongdong Shi","doi":"10.1016/j.ynstr.2026.100833","DOIUrl":"10.1016/j.ynstr.2026.100833","url":null,"abstract":"<div><div>The medial prefrontal cortex (mPFC) is critically involved in stress-related behaviors, specifically via the subpopulation of neurons that project to the ventromedial striatum (VMS). However, whether VMS-projecting mPFC neurons contribute to individual differences in behavioral responses to chronic stress remains unclear. Here, using a chronic restraint stress (CRS) model, we observed heterogeneous CRS-induced behavioral responses and stratified mice into relatively susceptible (SUS) and resilient (RES) subgroups based on a composite stress-related behavioral profile. To investigate the underlying neural basis, we performed <em>in vivo</em> fiber photometry to monitor calcium dynamics of VMS-projecting mPFC excitatory neurons before (baseline), during, and after CRS. We found that SUS mice exhibited significantly higher peak ΔF/F signals compared to RES mice even prior to stress exposure, and displayed persistently elevated activity during and after CRS. To further assess cellular mechanisms, we performed ex vivo whole-cell recordings from projection-defined neurons and found that VMS-projecting mPFC neurons in SUS mice exhibit increased intrinsic excitability, characterized by enhanced firing responses to depolarizing current injection. Chemogenetic activation of these neurons increased stress-related behaviors, whereas their inhibition attenuated CRS-associated behavioral abnormalities in susceptible mice. What's more, future studies are needed to determine whether these mPFC–VMS circuit features generalize to females. Together, these findings support the VMS-projecting mPFC neurons as a candidate neural substrate associated with individual differences in stress-related behavioral vulnerability.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"43 ","pages":"Article 100833"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13351384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpersonal stress, epigenetic indices of inflammation, and depressive symptoms: Longitudinal associations from adolescence to young adulthood","authors":"Stefanos Mastrotheodoros ,&nbsp;Winni Schalkwijk ,&nbsp;Michelle de Groot ,&nbsp;Sinan Gülöksüz ,&nbsp;Stefanie A. Nelemans ,&nbsp;Jim van Os ,&nbsp;Bart P.F. Rutten ,&nbsp;Wim Meeus ,&nbsp;Marco P. Boks ,&nbsp;Susan Branje","doi":"10.1016/j.ynstr.2026.100832","DOIUrl":"10.1016/j.ynstr.2026.100832","url":null,"abstract":"<div><h3>Background</h3><div>Adolescent interpersonal stress increases depression risk, and chronic low-grade inflammation may act as a potential underlying biological mechanism.</div></div><div><h3>Methods</h3><div>We explored longitudinal associations between interpersonal stress, inflammation, and depressive symptoms from adolescence to young adulthood, using DNA methylation (DNAm) indices of C-reactive protein (CRP) from saliva. Data were collected from <em>N</em> = 434 adolescents (RADAR-Y study, 56.4% male) and analyzed in preregistered structural equation models. Interpersonal stress was estimated from repeated measures of parent-adolescent conflict, parental psychological control, parental criticism, and peer victimization.</div></div><div><h3>Results</h3><div>Interpersonal stress was not associated with DNAm indices of CRP at age 17 or age 25, nor with depressive symptoms at age 27. In exploratory analyses examining parent versus peer-related stress separately, higher negative parenting–but not peer victimization–was nominally associated with one out of three DNAm indices of CRP at age 17 (Hillary index, <em>β</em> = .15, <em>p</em> = .035), with no association at age 25.</div></div><div><h3>Conclusion</h3><div>This study did not show an association of either interpersonal stress or inflammation with later depressive symptoms and thereby could not identify inflammation as a potential mediator. Our findings tentatively suggest timing-dependent differential effects of family versus peer-related stress on epigenetic indices of inflammation, which may be further explored in future studies.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"43 ","pages":"Article 100832"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148342835","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}

{"title":"NMDA receptor–dependent structural plasticity links early life stress to persistent aggression","authors":"Jessica T. Jacobs,&nbsp;Jacob C. Nordman","doi":"10.1016/j.ynstr.2026.100831","DOIUrl":"10.1016/j.ynstr.2026.100831","url":null,"abstract":"<div><div>Early life stress (ELS) is a major risk factor for reactive and pathological aggression that can persist long after the original stress exposure. Across species, ELS produces enduring alterations in the neural circuits that regulate social behavior and aggression, yet the molecular, structural, and circuit mechanisms that stabilize these changes remain poorly defined. Emerging evidence implicates N-methyl-D-aspartate receptor (NMDAR)-dependent structural plasticity in aggression circuits as a mechanism linking early adversity to persistent aggressive behavior.</div><div>In this review, we present a hypothesis-driven narrative that synthesizes clinical, postmortem, imaging, and preclinical evidence to define a testable framework for future research. We focus on how ELS may recruit NMDAR signaling to reshape excitatory connectivity within aggression circuits, with particular emphasis on the posterior ventral medial amygdala to ventrolateral ventromedial hypothalamus pathway. Within this pathway, preclinical studies suggest that ELS increases dendritic spine density, promotes excitatory shaft synaptogenesis, and biases synaptic input toward proximal dendritic locations predicted to exert stronger effects on neuronal firing. We propose that this location-specific remodeling may increase circuit excitability, thereby lowering the threshold for aggressive responding.</div><div>We further examine the translational potential of targeting NMDAR-dependent plasticity, focusing on the clinically available antagonists ketamine and memantine. By integrating molecular, structural, circuit-level, and clinical perspectives, we propose that NMDAR-dependent control of synapse formation and location represents a plausible mechanism through which ELS persistently biases neural circuits that regulate aggression. Targeting these processes may provide new strategies for reducing pathological aggression following ELS.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"43 ","pages":"Article 100831"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13312528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148352751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydroxytyrosol confers resilience against the depressive, anxiogenic and cognition-disruptive effects of chronic stress","authors":"Ariyawan Tantipongpiradet ,&nbsp;Reeta Davis ,&nbsp;Enrico A. Altieri ,&nbsp;Kevin E. O'Connor ,&nbsp;Keith J. Murphy","doi":"10.1016/j.ynstr.2026.100824","DOIUrl":"10.1016/j.ynstr.2026.100824","url":null,"abstract":"<div><div>Our understanding of the causal mechanisms of disorders such as anxiety and depression remains rudimentary. There is a pressing need to develop disease-modifying and preventative therapies that can be administered early and reduce symptom emergence. Here, we used a novel chronic unpredictable restraint stress (CURS) model in female and male rats to investigate the protective potential of biotechnologically-produced hydroxytyrosol. The CURS model produced indicators of anxiety, depression, cognitive deficits and social dysfunction in the elevated plus maze, sucrose preference test, novel object recognition and social interaction, respectively. Oral dosing with hydroxytyrosol (50 mg/kg/day, oral jelly formulation) prior to and during the period of restraint stress successfully protected against the anxiety, mood, social and cognitive symptoms mediated by chronic stress. The effect of hydroxytyrosol on behaviour was accompanied by the prevention of stress-induced declines in dopamine and serotonin and increased serum levels of corticosterone. Using single-cell RNA sequencing (scRNA-seq) of the hippocampus, we identified transcriptional signatures associated with chronic stress and their normalisation by hydroxytyrosol. Chronic unpredictable restraint stress caused widespread transcriptional dysregulation across neurons, astrocytes, and microglia. Gene Ontology and KEGG analyses revealed stress-related dysregulation of glutamatergic, GABAergic, dopaminergic, and cholinergic transmission. Neurodegenerative disease-associated transcriptional modules were enriched in the genes dysregulated by chronic stress and pathways related to synaptic vesicle cycling, neurotransmitter release, oxidative phosphorylation, and protein translation were prominently disrupted. Hydroxytyrosol treatment markedly attenuated these transcriptional changes, preserving the expression of genes involved in synaptic signalling, mitochondrial integrity, and protein homeostasis, thereby protecting cognitive and mood/stress regulation functions. These findings demonstrate that hydroxytyrosol exerts broad neuroprotective and stress-resilience effects by preserving neuronal transcriptional homeostasis, identifying hydroxytyrosol as a potent dietary bioactive that can buffer the molecular and behavioural sequelae of chronic stress.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"42 ","pages":"Article 100824"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148167305","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}

{"title":"Differential associations between early life adversity subtypes and adolescent stress reactivity across neuroendocrine, autonomic, immune, and metabolic systems","authors":"Kate R. Kuhlman ,&nbsp;Alexander J. Pugh ,&nbsp;Emma L. Rodgers","doi":"10.1016/j.ynstr.2026.100827","DOIUrl":"10.1016/j.ynstr.2026.100827","url":null,"abstract":"<div><div>Early life adversity (ELA) is a heterogeneous construct that can include the consequences of poverty, maltreatment, or serious accidents. This study characterized associations between subtypes of ELA and the physiological responses of multiple systems to acute psychosocial stress. Studies to date have focused on HPA axis reactivity, often neglecting the stress-reactive SNS, HPG axis, metabolic, and innate immune systems. We hypothesized that emotional, physical, and non-intentional ELA would differentially affect stress reactivity in each of these systems. Nine salivary samples, collected serially across the administration of a Trier Social Stress Test for Children (TSST-C), were collected from 92 adolescents [mean age 13.9 (SD = 1.57)] and assayed for cortisol, testosterone, DHEA, uric acid, salivary ɑ-amylase, and interleukin-6 (IL-6). Emotional ELA was associated with a steeper cortisol response to the stressor [<em>b(SE)</em> = 0.007 (0.003), <em>p</em> = .013]. Physical ELA was associated with IL-6 having steeper activation [<em>b(SE)</em> = 0.002 (0.001), <em>p</em> = .047] and recovery slopes [<em>b(SE)</em> = 0.00002 (0.00001), <em>p</em> = .03]. After accounting for age, sex, and body mass index, associations between physical ELA and IL-6 were attenuated. Findings are aligned with the theory of biological salience, which states physiological systems are differentially sensitive to experiences of adversity throughout childhood. Indeed, that different types of ELA are differentially associated with stress reactivity suggests a need for specificity and nuance in studies exploring associations between childhood environment and later biological functioning. Different forms of ELA are likely differentially salient to physiological systems that have distinct and evolutionarily conserved functions which may shape how the individual responds to psychosocial stress later in life. If confirmed with further evidence, biological salience may help to explain previously equivocal associations between ELA and adverse lifespan health outcomes.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"42 ","pages":"Article 100827"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148167306","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}

{"title":"Corrigendum to “The insular cortex-nucleus tractus solitarius glutamatergic pathway involved in acute stress-induced gastric mucosal damage in rats” [Neurobiol. Stress (2025) 100723]","authors":"Zepeng Wang ,&nbsp;Xinyu Li ,&nbsp;Yuanyuan Li ,&nbsp;Xuehan Sun ,&nbsp;Yuxue Wang ,&nbsp;Tong Lu ,&nbsp;Dongqin Zhao ,&nbsp;Xiaoli Ma ,&nbsp;Haiji Sun","doi":"10.1016/j.ynstr.2026.100811","DOIUrl":"10.1016/j.ynstr.2026.100811","url":null,"abstract":"","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"42 ","pages":"Article 100811"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148231436","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}

{"title":"Infant-mother attachment security and cortisol reactivity during the strange situation procedure: Longitudinal associations with maternal depressive symptoms and infant temperament","authors":"Lauren R. Bader ,&nbsp;Brenda L. Volling ,&nbsp;Paige Safyer ,&nbsp;Elizabeth Tengelitsch ,&nbsp;Alissa Huth- Bocks ,&nbsp;Catherine Hiltz ,&nbsp;Richard Gonzalez ,&nbsp;Lin Tan ,&nbsp;Juan F. Lopez ,&nbsp;Delia M. Vazquez","doi":"10.1016/j.ynstr.2026.100826","DOIUrl":"10.1016/j.ynstr.2026.100826","url":null,"abstract":"<div><div>This study examined the influence of infant-mother attachment security on the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and cortisol stress responses in 14-month-old infants. Eighty-two mother-infant dyads participated in the Strange Situation Procedure (SSP), with salivary cortisol sampled across four time points. Infant attachment security, maternal depressive symptoms, and infant temperament were assessed longitudinally over the first postnatal year. Infant cortisol trajectories differed by attachment security: insecurely attached infants had significantly higher baseline cortisol, which declined following the SSP, whereas securely attached infants had lower baseline cortisol and a trend toward increased cortisol post-stressor. Maternal cortisol declined over time for all groups, with no differences between mothers of secure and insecure infants. Mothers of securely attached infants experienced sub-clinical depressive symptoms at 32 weeks pre-partum, with a decline of symptoms to a normal range during the first year postpartum. Negative infant temperament increased over the first year but was not associated with attachment security or cortisol response. These findings demonstrate that infant-mother attachment quality shapes infant HPA axis regulation independent of maternal depressive symptoms or negative infant temperament, suggesting the importance of early identification and intervention for attachment difficulties to promote adaptive stress physiology in infants.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"42 ","pages":"Article 100826"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148167307","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}

{"title":"Future Leaders in Stress: the next generation of stress neurobiology","authors":"Jessica L. Bolton ,&nbsp;Natalie Matosin","doi":"10.1016/j.ynstr.2026.100822","DOIUrl":"10.1016/j.ynstr.2026.100822","url":null,"abstract":"","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"42 ","pages":"Article 100822"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148231438","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}

{"title":"Corrigendum to “Transcriptomic analysis of chronic social instability stress during adolescence reveals major shifts in the extracellular matrix” [Neurobiol. Stress (2026) 100799]","authors":"Ming Yin Chu ,&nbsp;Luca A. Hategan ,&nbsp;Amanda M. Leonetti ,&nbsp;Fiona O. Ramnaraign ,&nbsp;Samuel Holm ,&nbsp;Savithru Kannuri ,&nbsp;Timothy A.B. McLean ,&nbsp;Laura Neira-Diaz ,&nbsp;Meghana C. Malagi ,&nbsp;Cheryl M. McCormick ,&nbsp;Brandon J. Walters","doi":"10.1016/j.ynstr.2026.100818","DOIUrl":"10.1016/j.ynstr.2026.100818","url":null,"abstract":"","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"42 ","pages":"Article 100818"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148231439","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}