Brain, Behavior, and Immunity最新文献

{"title":"Increases in inflammation are associated with decreased trust of racial out-group members","authors":"Natalie M. Antenucci ,&nbsp;Mallory J. Feldman ,&nbsp;Tatum A. Jolink ,&nbsp;Taylor N. West ,&nbsp;Megan N. Cardenas ,&nbsp;Gabriella M. Alvarez ,&nbsp;Keely A. Muscatell","doi":"10.1016/j.bbi.2025.106242","DOIUrl":"10.1016/j.bbi.2025.106242","url":null,"abstract":"<div><div>While social group divisions occur naturally, inauspicious contexts like pathogen threat may exacerbate divides, driving in-group favoritism and out-group derogation. Minimal work has examined biological underpinnings of intergroup dynamics, particularly immune changes likely to accompany pathogen threat. To address this, we administered the influenza vaccine to 44 young adult participants. Before and after receiving the vaccine, participants completed a modified affect misattribution procedure, wherein they rated the trustworthiness of racial in-group and out-group faces. Participants also provided pre- and post-vaccine blood samples which were assayed for the inflammatory cytokine interleukin-6 (IL-6). Results showed a negative association between inflammatory reactivity and ratings of out-group faces: those who experienced greater increases in IL-6 rated racial out-group faces as less trustworthy than those with less IL-6 reactivity. This work begins exploring the role of inflammation in intergroup processes and findings, while preliminary, suggest a novel biological process that is associated with intergroup perception.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106242"},"PeriodicalIF":7.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145826965","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":"Dissecting the genetic relationship between severe mental disorders and autoimmune diseases","authors":"Erik D. Wiström ,&nbsp;Julian Fuhrer ,&nbsp;Alexey Shadrin ,&nbsp;Vera Fominykh ,&nbsp;Kevin S. O’Connell ,&nbsp;Piotr Jaholkowski ,&nbsp;Nils Eiel Steen ,&nbsp;Sara E. Stinson ,&nbsp;Pravesh Parekh ,&nbsp;Oleksandr Frei ,&nbsp;Linn Rødevand ,&nbsp;Nadine Parker ,&nbsp;Jan Haavik ,&nbsp;Srdjan Djurovic ,&nbsp;Anders M. Dale ,&nbsp;Ole A. Andreassen ,&nbsp;Olav B. Smeland","doi":"10.1016/j.bbi.2025.106249","DOIUrl":"10.1016/j.bbi.2025.106249","url":null,"abstract":"<div><div>Severe mental disorders have been linked to immune system dysfunction. While a genetic association between mental disorders and autoimmune diseases has been suggested, their genetic relationship remains incompletely understood. Utilizing a complementary set of statistical analyses, we conducted a comprehensive investigation of the genetic architecture between severe mental disorders (major depression (MD), bipolar disorder (BD), and schizophrenia (SCZ)) and seven autoimmune diseases (autoimmune thyroiditis, celiac disease, inflammatory bowel disease (IBD), multiple sclerosis, psoriasis, rheumatoid arthritis, and type 1 diabetes), involving a total of 667,518 cases from 10 genome-wide association studies. While MD was positively genetically correlated with five autoimmune diseases, BD and SCZ were only positively correlated with IBD, suggesting differences in the genetic signal shared with autoimmunity across these mental disorders. A considerable fraction of genetic variants influencing autoimmune diseases (range 17.1–88.4 %) was estimated to overlap with mental disorders; however, this constitutes only a minor part of genetic variants influencing the more polygenic mental disorders. Finally, we identified 172 genetic loci jointly affecting mental disorders and autoimmune diseases, implicating both lipid metabolism and TNF signaling. In conclusion, MD, BD, and SCZ have a small but distinct genetic overlap with autoimmune diseases, which may inform new possible immune targets for treatment in mental illness.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106249"},"PeriodicalIF":7.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145862177","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":"Acute peripheral versus central inhibition of insulin receptors differentially alters cytokine and blood–brain barrier responses to an inflammatory stimulus","authors":"Tanmai Bandarupalli ,&nbsp;Cassidy Noonan ,&nbsp;Kim Hansen ,&nbsp;Riley Weaver ,&nbsp;Kristen Baumann ,&nbsp;William A. Banks ,&nbsp;Michelle A. Erickson ,&nbsp;Elizabeth M. Rhea","doi":"10.1016/j.bbi.2025.106251","DOIUrl":"10.1016/j.bbi.2025.106251","url":null,"abstract":"<div><div>The blood–brain barrier (BBB)’s role in protecting the brain from exposure to harmful circulating factors has led to its disruption being implicated in neurodegenerative diseases such as vascular dementia and Alzheimer’s disease. Insulin resistance, defined by an impaired response to insulin, is a common feature of metabolic disorders and neurodegenerative diseases. Importantly, individuals can possess peripheral insulin resistance independent of central insulin resistance and vice versa. States of insulin resistance, like diabetes mellitus for peripheral insulin resistance and Alzheimer’s disease for central insulin resistance, are associated with inflammation and BBB disruption. However, the contributions of acute impairment of insulin receptor signaling solely in the periphery versus the brain to inflammation and BBB disruption are not clear. As central vs peripheral insulin resistance could have different effects on inflammation, we characterized the effects of acute central versus peripheral insulin receptor inhibition with or without an inflammatory insult, using lipopolysaccharide (LPS) as a prototypic immune stimulus. Male CD-1 mice were treated with an insulin receptor antagonist (S961), peripherally (intraperitoneal) or centrally (intranasal). This treatment was then followed by an intraperitoneal administration of either saline or LPS 30 min later, at a single 3 mg/kg dose known to cause inflammation and BBB disruption. Assays of BBB disruption and brain and serum collection were done 28 h after the injections. Metabolic hormones, cytokines, and the acute phase protein serum amyloid a (SAA) were then measured in serum and brain homogenates. In the absence of LPS, central S961 reduced serum hormones including ghrelin, gastric inhibitory peptide (GIP), and glucagon. Peripheral S961 significantly increased many cytokines in both brain and blood, whereas central S961 decreased serum SAA and increased a few cytokines. BBB integrity was not affected by S961 alone, but central S961 decreased LPS-induced BBB disruption and also lowered serum levels of SAA. These findings highlight the differential effects of peripheral versus central insulin receptor inhibition on cytokine responses and BBB integrity in the presence and absence of acute inflammation, elucidating differences in the molecular mechanisms for insulin receptor signaling depending on the location of signaling dysfunction. The results suggest a potential neuroprotective role of acute central insulin inhibition during acute inflammation.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106251"},"PeriodicalIF":7.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883114","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":"Altered gut microbiome function in ADHD: More Prevotella, less vitamin B12 biosynthesis, and beneficial modulation by synbiotic treatment","authors":"Miranda Stiernborg ,&nbsp;Liu L. Yang ,&nbsp;Elin Skott ,&nbsp;MaiBritt Giacobini ,&nbsp;Philippe A. Melas ,&nbsp;Justine W Debelius ,&nbsp;Catharina Lavebratt","doi":"10.1016/j.bbi.2026.106259","DOIUrl":"10.1016/j.bbi.2026.106259","url":null,"abstract":"<div><div>The effect of psychostimulant medication in ADHD on the gut microbiome remains unknown. Oral Synbiotic 2000, comprising multiple lactic acid bacteria and dietary fibers, reduces psychiatric symptoms and plasma immune markers in ADHD, but its impact on the gut microbiome is unexplored. This study aimed to (i) study the fecal bacterial microbiome, focusing on species and bacterial gene modules, in ADHD patients and neurotypical controls, and (ii) examine microbiome changes attributable to Synbiotic 2000. Fecal samples were collected from 147 participants at baseline, and 106 completers at follow-up from a randomized placebo-controlled trial of Synbiotic 2000 conducted in children and adults with ADHD. At baseline, adult samples were compared to those of 52 adult controls, and patients on psychostimulants were compared to those not on psychostimulants in adults and children separately. The fecal microbiome was sequenced using shallow shotgun sequencing and analyzed for diversity and differential abundance using machine learning. Plasma short-chain fatty acids (SCFAs) and serum vitamin B12 levels were measured. At baseline, adult ADHD patients had significantly different abundances of four species compared to controls. In children, those on psychostimulants exhibited a higher abundance of species from the genus <em>Prevotella</em>, alongside a lower abundance of the vitamin B12-synthesis module, M00122, than those not on such medication. The lower M00122 abundance was associated with a looser stool consistency, implicating a shorter colonic transit time. Synbiotic 2000 did not affect taxonomic or functional α-diversity in adults or children. However, looser baseline stool consistency was linked to greater increases in evenness in the Synbiotic group over time. There was a significant Synbiotic-specific effect on taxonomic and functional β-diversity, not only the increased abundance of the Synbiotic 2000 species<em>.</em> Plasma levels of formic acid and propionic acid increased towards control levels in the Synbiotic group. In conclusion, distinct species were differently abundant in adults with ADHD compared to controls. The implications of the lower abundance of the vitamin B12-synthesis module, in children on psychostimulant medication, for the gut ecosystem and host intestine remain to be elucidated. Synbiotic 2000 influenced the taxonomy and functionality of the fecal microbiome and increased plasma SCFA levels towards normal. Further research is warranted to explore the clinical implications of microbiome modulation in the treatment of ADHD.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106259"},"PeriodicalIF":7.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916990","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":"Using social risk factors to predict allostatic biotypes of depression: A latent profile and multinomial regression analysis","authors":"Jay O’Shields ,&nbsp;Helisha Soni ,&nbsp;Orion Mowbray","doi":"10.1016/j.bbi.2025.106243","DOIUrl":"10.1016/j.bbi.2025.106243","url":null,"abstract":"<div><h3>Objective</h3><div>Major depression is often difficult to treat, particularly among individuals exposed to psychosocial risks like childhood maltreatment, loneliness, and recent stress. These experiences may lead to biological dysregulation consistent with allostatic load theory. This study explored whether distinct biological profiles among adults with depression are associated with specific psychosocial and health-related factors.</div></div><div><h3>Method</h3><div>Data were drawn from the Midlife in the United States study (MIDUS), including 367 participants with clinically significant depressive symptoms (CES-D ≥ 16). Latent profile analysis identified biological profiles based on 23 biomarkers across seven systems: inflammation, glucose, sympathetic and parasympathetic nervous systems, HPA-axis, cardiovascular, and lipids. Multinomial regression models examined associations between profile membership and psychosocial (childhood maltreatment, loneliness, recent stress), health (alcohol use, smoking, exercise), and demographic variables (sex, race/ethnicity, age, education).</div></div><div><h3>Results</h3><div>A five-profile solution best fit the data: High Inflammation &amp; Glucose (<em>n</em> = 74), Low PNS (<em>n</em> = 83), High PNS (<em>n</em> = 73), Healthy Depression (<em>n</em> = 67), and High HPA-Axis (<em>n</em> = 70). Childhood maltreatment significantly predicted membership in the High Inflammation &amp; Glucose and Low PNS profiles compared to the Healthy Depression group, even after controlling for health behaviors and demographics. Loneliness and recent stress were not significant predictors.</div></div><div><h3>Conclusion</h3><div>Childhood maltreatment is a predictor of biological dysregulation in depression, differentially predicting profiles characterized by inflammatory and metabolic vs parasympathetic functioning. These may represent different vulnerability pathways from social experiences to depressive illness. Incorporating measurement strategies specific to these pathways may aide in selecting treatment options for people who have depression and a history of childhood maltreatment.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106243"},"PeriodicalIF":7.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145826944","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 “Acute effects of interferon-alpha on cellular anabolic and catabolic processes are associated with the development of fatigue during Interferon-alpha-based therapy for Hepatitis-C: A preliminary study” [Brain Behav. Immun. 123 (2025) 717–724]","authors":"Eva Periche-Tomas ,&nbsp;Annamaria Cattaneo ,&nbsp;Nadia Cattane ,&nbsp;Claudia Bone ,&nbsp;Jeremy Tibble ,&nbsp;Edward T. Bullmore ,&nbsp;Carmine Pariante ,&nbsp;Neil A. Harrison","doi":"10.1016/j.bbi.2026.106287","DOIUrl":"10.1016/j.bbi.2026.106287","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106287"},"PeriodicalIF":7.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028432","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":"Acute ischaemic stroke alters the composition and function of circulating B cells","authors":"Mehwish Younas ,&nbsp;Harry R. Deijnen ,&nbsp;Ruth Stephens ,&nbsp;Alison Harris ,&nbsp;Thomas O. Williams ,&nbsp;Sabrina Tamburrano ,&nbsp;Ian E. Prise ,&nbsp;Craig J. Smith ,&nbsp;Stuart M. Allan ,&nbsp;Laura McCulloch ,&nbsp;John R. Grainger ,&nbsp;Barry W. McColl","doi":"10.1016/j.bbi.2025.106244","DOIUrl":"10.1016/j.bbi.2025.106244","url":null,"abstract":"<div><div>Distinct B cell populations are found in circulation, including those with innate-like properties, that have varied functions in pathogen protection, vaccination and immunoregulation. The effects of tissue injury on circulating B cell populations are poorly explored. Here we show that, following acute ischaemic stroke (AIS), a common cause of neurological disability associated with systemic immune dysfunction, the circulating B cell compartment has altered functionality, alongside marked reductions in marginal zone (MZ)-like B cells, an innate-like B cell subset. Of note, release of Immunoglobulin (Ig) M, a key innate-like B cell-derived factor important in anti-bacterial responses, and regulatory cytokines including IL-6 and IL-10, was impaired upon stimulation of sorted B cells from AIS patients. B cells express adrenergic receptors (ARs), in both control and AIS patients, and release of the β2-AR agonist noradrenaline (NA) is elevated acutely following stroke. <em>In vitro</em> exposure of B cells from healthy individuals to NA recapitulated some of the functional modulation observed in AIS patients. Moreover, increased cell death of MZ-like B cells was observed in response to NA. Secondary infection is a common post-stroke complication that could be responsible for altered B cell characteristics. However, in line with the impact of NA on B cell populations, alterations were largely driven by stroke rather than secondary infection. Taken together, these findings demonstrate that neuroimmune factors are an important signal that could rapidly modify defined B cell populations early after tissue injury and highlight altered innate-like B cell function as a previously unappreciated characteristic of the systemic immunological response to acute stroke.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106244"},"PeriodicalIF":7.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843673","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":"Subacute loss of olfactory neurons following SARS-CoV-2 infection in hamsters","authors":"Clara Bourgon ,&nbsp;Laetitia Merle-Nguyen ,&nbsp;Juliette Jacquelin ,&nbsp;Isis Leguay ,&nbsp;Luc Jouneau ,&nbsp;Bernard Klonjkowski ,&nbsp;Sophie Le Poder ,&nbsp;Nicolas Meunier","doi":"10.1016/j.bbi.2026.106274","DOIUrl":"10.1016/j.bbi.2026.106274","url":null,"abstract":"<div><div>The loss of smell has been a hallmark of the COVID-19 pandemic. Odorant detection relies on neurons present in the olfactory epithelium supported by sustentacular cells. The latter are massively infected by SARS-CoV-2 along with infiltration of innate immune cells and desquamation of the olfactory epithelium. This destruction leads to release of olfactory epithelium cells into the lumen of the nasal cavity, but the extent of the loss of mature olfactory neurons remains to be clarified. In this study, we compared the spatiotemporal evolution of the olfactory epithelium during SARS-CoV-2 infection with associated smell impairment in hamsters. The olfactory performance of infected hamsters decreases as early as 2 days post-infection (dpi), then gradually recovers through 17 dpi. While the infection is mostly resolved after 4 dpi in the nasal cavity, we observed a subacute decrease of the mature olfactory neuron population which almost completely disappear at 11 dpi. Furthermore, regeneration of the olfactory epithelium does not start until 8 dpi and leads to a high fraction of immature olfactory neurons. The delayed regeneration and persistent alteration of the olfactory neuron population was correlated with a prolonged expression of inflammatory cytokines and a rapid decrease of the levels of anti-inflammatory markers linked to regeneration. Overall, our results suggest that the regeneration process is altered in some areas of the olfactory epithelium leading to delayed recovery of the epithelium. The later may explain the prolonged smell alteration linked to SARS-CoV-2 infection.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106274"},"PeriodicalIF":7.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965370","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":"Daily affect and behavior in relation to inflammatory and metabolic health: An ambulatory assessment study","authors":"Noa van Zwieten ,&nbsp;George Aalbers ,&nbsp;Femke Lamers ,&nbsp;Erik J. Giltay ,&nbsp;Manon H.J. Hillegers ,&nbsp;Brenda W.J.H. Penninx","doi":"10.1016/j.bbi.2026.106282","DOIUrl":"10.1016/j.bbi.2026.106282","url":null,"abstract":"<div><h3>Background</h3><div>Daily life stress is associated with biological dysregulations including elevated inflammatory markers and poorer metabolic (immunometabolic) health, but it remains unclear how they are connected to daily life affect and behaviors. We examined whether daily life affect and behaviors were associated with immunometabolic health, and whether associations were moderated by the presence of a current depression/anxiety diagnosis.</div></div><div><h3>Methods</h3><div>In the Netherlands Study of Depression and Anxiety, participants (n = 357) with and without depression/anxiety self-reported positive affect (PA) and negative affect (NA) 5x/day while continuously wearing a research-grade actigraphy device for 14 days. We quantified four affect variables (i.e., M and SD of PA and NA) and three behavioral variables (i.e., minutes spent in moderate-to-vigorous physical activity [MVPA], sleep duration, and relative amplitude [RA; measure of circadian rhythmicity]), averaged across 14 days. We used linear regression analyses to explore their associations with three immunometabolic health outcomes: (1) inflammation index (based on C-Reactive Protein and Interleukin-6 levels), (2) metabolic index (based on five metabolic syndrome components), and (3) BMI (Body Mass Index), and examined if these associations were moderated by the presence of a current depression/anxiety diagnosis.</div></div><div><h3>Results</h3><div>Analyses showed that higher MVPA and RA were consistently associated with lower inflammation index (B = −0.19; B = −0.12), metabolic index (B = −0.14, B = −0.15), and BMI (B = −1.23; B = −1.30) (all <em>p</em>’s &lt; 0.011). Longer sleep duration was associated with lower BMI (B = −0.80, <em>p</em> = 0.027). Affect variables were not associated with immunometabolic health outcomes (<em>p</em>’s &gt; 0.05). Associations were independent of mental health status (<em>p</em>’s &gt; 0.05).</div></div><div><h3>Conclusions</h3><div>Our findings suggest that more minutes spent in MVPA and a more pronounced circadian rhythm, assessed with actigraphy, are important correlates of better immunometabolic health, and highlight the potential of ambulatory assessment in understanding immunometabolic health.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106282"},"PeriodicalIF":7.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973932","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":"Effects of Dopaminergic Therapy with Levodopa (L-DOPA) on Fear and Anxiety-Related Circuits and Symptoms in Patients with Depression and Higher Inflammation","authors":"Genevieve E. Craig ,&nbsp;Neeti D. Mehta ,&nbsp;Mandakh Bekhbat ,&nbsp;Kate P. Revill ,&nbsp;Michael J. Lucido ,&nbsp;Changdo Hong ,&nbsp;Evanthia C. Wommack ,&nbsp;Wendy M. Baer ,&nbsp;Ebrahim Haroon ,&nbsp;Andrew H. Miller ,&nbsp;Zhihao Li ,&nbsp;Jennifer C. Felger","doi":"10.1016/j.bbi.2025.106252","DOIUrl":"10.1016/j.bbi.2025.106252","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Inflammatory biomarkers such as cytokines and C-reactive protein (CRP) are reliably elevated in patients with major depressive disorder (MDD) as well as fear and anxiety-related disorders. Moreover, inflammatory biomarkers have been associated with lower functional connectivity (FC) in reward and threat-related circuits that contribute to symptom severity. Prior work has linked low FC in reward circuitry and symptoms of anhedonia to inflammation effects on striatal dopamine (DA), including our studies involving administration of the DA precursor, levodopa (L-DOPA). Nevertheless, the mechanisms of inflammation associations with fear and anxiety-related circuits and symptoms are not fully understood. Given recent interest in DA in the amygdala in anxiety and the effects of inflammation, we examined a potential role for DA in relationships between inflammation, lower right amygdala-ventromedial prefrontal cortex (vmPFC) FC, and symptoms of anxiety and post-traumatic stress disorder (PTSD). Leveraging data from our studies in medically-stable, unmedicated adults with a primary MDD diagnosis, we tested the hypothesis that acute (250 mg; Study 1, n = 30) and sub-chronic (150–450 mg/day/week; Study 2, n = 18) L-DOPA (administered with carbidopa) versus placebo would increase right amygdala-vmPFC resting state (rs)FC (using a targeted, &lt;em&gt;a priori&lt;/em&gt; approach) in patients with higher (but not lower) inflammation, in relation to comorbid anxiety and PTSD symptoms. In patients enrolled to have a range of CRP concentrations and rsFC before and after acute, within-subject challenge with both L-DOPA and placebo (double-blind, randomized order ∼ 1-week apart; Study 1), a CRP by treatment interaction (F[1,28] = 1.33, p &lt; 0.05) revealed that right amygdala-vmPFC rsFC was increased by L-DOPA versus placebo only in patients with CRP &gt; versus ≤ 2 mg/L (p &lt; 0.05). In MDD patients recruited to have CRP &gt; 2 mg/L in Study 2, L-DOPA increased right amygdala-vmPFC rsFC versus placebo (F[1,12] = 9.24, p &lt; 0.05), with two of three L-DOPA doses (150 and 450 mg/day) increasing rsFC versus placebo at a predetermined threshold of ≥ 20 %. Repeated L-DOPA versus placebo further decreased self-reported anxiety symptoms and state anxiety (F[2,16] = 11.87, p &lt; 0.01), with all three L-DOPA doses significantly decreasing state anxiety (p &lt; 0.05). Right amygdala-vmPFC rsFC responses to L-DOPA also associated with greater reductions in state anxiety (r = -0.72, p &lt; 0.05). Similarly, L-DOPA decreased PTSD symptom severity versus placebo across all four PTSD symptom clusters (B-E) in patients with significant PTSD symptoms at baseline (n = 11; all p &lt; 0.05), with right amygdala-vmPFC rsFC responses to L-DOPA versus placebo negatively correlating with improved Intrusion symptoms (r = -0.81, p &lt; 0.05). These findings suggest a role for DA in the effects of inflammation on fear and anxiety-related circuits and symptoms, while supporting the use of ","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106252"},"PeriodicalIF":7.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888626","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}