Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"The striatal heterogeneous nuclear ribonucleoprotein H1 mRNA targetome associated with methamphetamine administration and behavior","authors":"Qiu T. Ruan ,&nbsp;William B. Lynch ,&nbsp;Rebecca H. Cole ,&nbsp;Michael A. Rieger ,&nbsp;Britahny M. Baskin ,&nbsp;Sophia A. Miracle ,&nbsp;Jacob A. Beierle ,&nbsp;Emily J. Yao ,&nbsp;Jiayi W. Cox ,&nbsp;Amarpreet Kandola ,&nbsp;Kayla T. Richardson ,&nbsp;Melanie M. Chen ,&nbsp;Julia C. Billups ,&nbsp;R. Keith Babbs ,&nbsp;Peter E.A. Ash ,&nbsp;Benjamin Wolozin ,&nbsp;Karen K. Szumlinski ,&nbsp;W. Evan Johnson ,&nbsp;Joseph D. Dougherty ,&nbsp;Camron D. Bryant","doi":"10.1016/j.pnpbp.2025.111598","DOIUrl":"10.1016/j.pnpbp.2025.111598","url":null,"abstract":"<div><div>Methamphetamine addiction remains a major public health concern in the United States that has paralleled the opioid epidemic. Psychostimulant use disorders have a heritable genetic component that remains unexplained. Methamphetamine targets membrane and vesicular transporters to increase synaptic dopamine, norepinephrine, and serotonin. We previously identified <em>Hnrnph1</em> (heterogeneous nuclear ribonucleoprotein H1) as a quantitative trait gene underlying methamphetamine behavioral sensitivity. <em>Hnrnph1</em> encodes the RNA-binding protein hnRNP H1 that is ubiquitously expressed in neurons throughout the adult brain. Gene-edited mice with a heterozygous frameshift deletion in <em>Hnrnph1's</em> first coding exon showed reduced methamphetamine-induced dopamine release and behaviors. To potentially inform the mechanism linking hnRNP H with methamphetamine behavior, we surveyed the mRNA targetome of hnRNP H via cross-linking immunoprecipitation coupled with RNA-sequencing in striatum at baseline and at 30 min post-methamphetamine in wild-type female and male C57BL/6 J mice. Methamphetamine induced changes in RNA-binding targets of hnRNP H in mice, including 3’UTRs of enriched mRNAs involved in synaptic plasticity. Targetome, transcriptome, and spliceome analyses triangulated on <em>Cacna2d2</em> which showed methamphetamine-induced changes in hnRNP H binding, gene expression and splicing. Pre-treatment with pregabalin, an inhibitor of CACNA2D2 and CACNA2D1 voltage-gated calcium channel subunits, attenuated methamphetamine-induced locomotor activity, suggesting CACNA2D2 could contribute to methamphetamine locomotor stimulant sensitivity. Our study identifies a dynamic hnRNP H RNA targetome that can respond rapidly to methamphetamine and could potentially contribute to synaptic plasticity and behavior. Given our discovery-based findings, future studies will require directly validating the link between methamphetamine-induced changes in hnRNP H binding, gene regulation, synaptic plasticity, and behavior.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111598"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844236","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":"The neural pathways and genetic substrates of non-suicidal self-injury as a “sensation of pain” addiction in drug-naïve depressed adolescents","authors":"Xianliang Chen ,&nbsp;Hui Chen ,&nbsp;Sihong Li ,&nbsp;Huajia Tang ,&nbsp;Jiawei Zhou ,&nbsp;Bohao Cheng ,&nbsp;Zhengqian Jiang ,&nbsp;Yanyue Ye ,&nbsp;Jiali Liu ,&nbsp;Peiqu Liu ,&nbsp;Fengmei Lu ,&nbsp;Jiansong Zhou","doi":"10.1016/j.pnpbp.2025.111597","DOIUrl":"10.1016/j.pnpbp.2025.111597","url":null,"abstract":"<div><h3>Background</h3><div>Emerging evidence posits repetitive non-suicidal self-injury (NSSI) shares behavioral and neurobiological parallels with addiction. However, the neural mechanisms underlying NSSI, particularly within the framework of “sensation of pain” addiction, remain poorly understood. This study combines the effective connectivity (EC) and transcriptomic profiling to explore addiction-related neural circuit and their potential genetic substrates of NSSI.</div></div><div><h3>Method</h3><div>A total of 76 medication-free adolescents with depression were included in the study, comprising 36 with NSSI (NSSI group) and 40 without NSSI (non-NSSI group). The addictive subscale of the Ottawa Self-Injury Inventory (OSI) was used to assess the addictive features of NSSI in the NSSI group. Resting-state functional magnetic resonance imaging were analyzed using Spectral dynamic causal modeling to explore the directed neural interactions within predefined circuits of “sensation of pain” addiction. Correlation analyses were performed between the EC and clinical data. Spatial transcriptomic mapping integrated with Allen Human Brain Atlas further detect alterations in connectivity-associated gene expression signatures.</div></div><div><h3>Results</h3><div>Compared with the non-NSSI group, the NSSI group exhibited four distinct EC alterations from the ventral tegmental area (VTA) to left amygdala (AMYG), from the right medial prefrontal cortex (mPFC) to right AMYG, from the left ventral striatum (VS) to right insula (INS) and from the right VS to left AMYG. Crucially, EC values from the VTA to left AMYG and from the right VS to left AMYG are associated with the addictive characteristics and the NSSI frequency, respectively. Genes associated with altered connectivity patterns primarily focus on the brain development, axon, dendrite, oligodendrocytes, D1+ spiny neurons, D2+ spiny neurons, and cholinergic neurons of habenula.</div></div><div><h3>Conclusion</h3><div>Our findings yield empirical support for reconceptualizing the NSSI within behavioral addiction frameworks, revealing underlying neurobiological pathways and genetic basis driving repeated NSSI. Notably, EC from the VTA to the left AMYG was positively associated with the addictive features of NSSI, highlighting a potentially important neural pathway underlying its addictive nature. The identified EC dysfunction and associated genetic markers could offer novel potential targets for therapeutic interventions.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111597"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835231","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":"Neuropharmacological targets for schizophrenia treatment: An update","authors":"Caroline Araujo Costa Lima ,&nbsp;Marta Eduarda Oliveira Barbosa ,&nbsp;Fábio José Coelho Souza-Junior ,&nbsp;Sarah Viana Farias ,&nbsp;Eneas Andrade Fontes-Junior ,&nbsp;Cristiane Socorro Ferraz Maia","doi":"10.1016/j.pnpbp.2025.111580","DOIUrl":"10.1016/j.pnpbp.2025.111580","url":null,"abstract":"<div><div>Schizophrenia is a severe chronic psychiatric disorder that affects around 24 million people worldwide. It is characterized by a combination of positive (such as hallucinations and delusions), negative (including asociality, alogia, and avolition), and cognitive symptoms (implicating attention, memory, and executive functions). These symptoms contribute to significant personal, social and occupational impairments, substantially affecting the patients' quality of life. The etiology of schizophrenia is multifactorial, involving both genetics and environmental factors, with strong evidence supporting a neurodevelopmental origin. Additionally, schizophrenia pathophysiology has been associated with dysregulations in several systems, including the dopaminergic, glutamatergic and purinergic systems, and a chronic neuroinflammatory process. These findings reinforce that this condition is most likely the result of a complex relationship between biological, environmental, and neurochemical factors. Current pharmacological treatment remains focused on dopaminergic activity, particularly through the use of antipsychotics. However, both the glutamatergic and purinergic systems have been explored as possible therapeutic targets and have presented themselves as promising alternatives. In addition, the interaction between all these neurochemical systems in the context of schizophrenia has been poorly reported. Here, we provide a perspective of the dopaminergic, glutamatergic, and purinergic pathways integration, contributing to schizophrenia pathophysiology, suggesting potential targets for pharmacological approaches.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111580"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752342","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":"Uncovering novel endocannabinoidome-gut microbiome-brain axis-based therapeutic targets in a Fragile X Syndrome mouse model","authors":"Antonella Campanale ,&nbsp;Hayatte-Dounia Mir ,&nbsp;Elizabeth Dumais ,&nbsp;Antonio Inserra ,&nbsp;Nicolas Flamand ,&nbsp;Mallar Chakravarty ,&nbsp;Ilse Gantois ,&nbsp;Nadeem Siddiqui ,&nbsp;Nahum Sonenberg ,&nbsp;Gabriella Gobbi ,&nbsp;Cristoforo Silvestri ,&nbsp;Vincenzo Di Marzo","doi":"10.1016/j.pnpbp.2025.111575","DOIUrl":"10.1016/j.pnpbp.2025.111575","url":null,"abstract":"<div><h3>Background</h3><div>Autism Spectrum Disorder (ASD) is a neurodevelopmental condition associated with increased risk of psychiatric, gastrointestinal, and metabolic comorbidities. Recent studies highlight the bidirectional role of the gut microbiome (GM) and endocannabinoidome (eCBome)-axis in the gut-brain axis, suggesting its therapeutic potential for ASD and comorbidities.</div></div><div><h3>Methods</h3><div>We investigated the eCBome-GM-brain axis in the Fragile X Messenger Ribonucleoprotein 1 (<em>Fmr1</em>^{<em>−/y</em>}) mouse model, known as a genetic model of ASD, to identify therapeutic targets. Fecal GM composition was analysed by 16S rDNA sequencing, brain eCBome profile by HPLC-MS/MS and qRT-PCR, and fecal short chain fatty acids by GC-FID.</div></div><div><h3>Results</h3><div>Significant eCBome-GM-brain axis dysregulation was observed in <em>Fmr1</em>^{<em>−/y</em>} compared to wild-type mice. GM analyses revealed potential gut dysbiosis, increased permeability, and inflammation. Specifically, elevated <em>Akkermansia</em> and <em>Eubacterium siraeum</em>—linked to gut barrier dysfunction—and <em>Ruminococcus</em> and <em>Clostridium</em>, associated with ASD severity, were identified. Concurrently, decreased levels of the gut health biomarker <em>Roseburia</em> and the taxa <em>Helicobacte</em>r and <em>Anaeroplasma</em> were observed.</div><div>Brain region-specific eCBome alterations underscored neuroinflammation. In the HPC, reduced anti-inflammatory dihomogamma-linolenic acid (DGLA) was accompanied by elevated pro-inflammatory 12-hydroxy-heptadecatrienoic acid, a mediator of microglial activation. In the PFC, decreased DGLA, 1/2-linoleoylglycerol, and N-linoleoyl-ethanolamine suggested neuroinflammation; elevated prostaglandin D2, a marker of autophagy impairment, underscores further mechanisms of dysfunction. Upregulation of cannabinoid type 2 and PPAR-γ receptor genes in the PFC suggested a compensatory response to neuroinflammation. Correlations between eCBome and GM alterations highlighted potential links between gut dysbiosis, systemic inflammation, and neurodevelopmental atypicalities.</div></div><div><h3>Conclusions</h3><div>The <em>Fmr1</em>^{<em>−/y</em>} ASD mouse model harbors significant eCBome-GM-brain axis alterations. This study highlights specific GM taxa and eCBome components as potential therapeutic targets for clinical validation in Fragile X Syndrome and ASD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111575"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745513","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":"Alterations in edge-centric functional connectivity in patients with major depressive disorder and their genetic mechanisms: A transcriptome-neuroimaging correlation study","authors":"Fanghui Dong ,&nbsp;Kaili Che ,&nbsp;Yinghong Shi ,&nbsp;Heng Ma ,&nbsp;Feng Zhao ,&nbsp;Haizhu Xie ,&nbsp;Ning Mao ,&nbsp;Tongpeng Chu ,&nbsp;Xin Zhao","doi":"10.1016/j.pnpbp.2025.111603","DOIUrl":"10.1016/j.pnpbp.2025.111603","url":null,"abstract":"<div><h3>Background</h3><div>Previous studies on brain functional networks in Major Depressive Disorder (MDD) have mainly focused on node changes, but the dynamics of edge-to-edge connectivity remain unclear. This study combines edge-centric functional connectivity (eFC) and whole-brain transcriptomics to reveal higher-order network interactions in MDD.</div></div><div><h3>Methods</h3><div>We enrolled 163 MDD patients and 135 healthy controls (HCs). First, time series were extracted to construct the functional connectivity (FC) matrix. Then, edges were extracted from this matrix, and their Pearson correlation coefficients were calculated to construct the eFC matrix. Between-group differences in eFC were compared. Subsequently, support vector machines (SVM), random forest (RF) and extreme gradient boosting (XGBoost) models were built to evaluate the classification performance of eFC in diagnosing MDD. Finally, by integrating transcriptomic data, we identified genes whose spatial expression profiles were associated with eFC alterations and performed functional enrichment analysis.</div></div><div><h3>Results</h3><div>We observed that compared to HCs, there are extensive changes in eFC. Specifically, individuals with MDD exhibited increased eFC in the left Superior frontal gyrus, right Middle frontal gyrus and bilateral Inferior temporal gyrus, while displaying decreased eFC in the bilateral Caudate nucleus. The classification results demonstrated that models based on eFC features outperformed those based on traditional FC in key metrics, and this advantage remained stable across different algorithms. Partial least squares (PLS) analysis revealed that alterations in eFC in MDD patients are associated with specific gene expression profiles. These genes were significantly enriched in pathways related to ion channels and synaptic transmission. These findings were replicated in validation cohort and HarvardOxford brain atlas.</div></div><div><h3>Conclusion</h3><div>Our study revealed alterations in the eFC network in MDD patients and their associations with gene expression profiles, providing a novel perspective to advance the understanding of MDD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111603"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879421","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":"Unveiling the vestibular system's role in anxiety and the promise of electrical vestibular stimulation (VeNS) therapy","authors":"Wiktoria Ratajczak","doi":"10.1016/j.pnpbp.2025.111601","DOIUrl":"10.1016/j.pnpbp.2025.111601","url":null,"abstract":"<div><h3>Purpose of the review</h3><div>Generalized Anxiety Disorder (GAD) is a chronic and prevalent psychiatric condition affecting approximately 4.05 % of the global population, with a higher incidence in women and early onset in childhood. GAD is associated with significant mental, emotional, and physical impairments, including insomnia, metabolic syndrome, and other psychiatric comorbidities such as depression. Current treatment options include pharmacotherapy and cognitive behavioural therapy (CBT), face challenges such as side effects, long treatment durations, and accessibility issues. This review explores the role of the vestibular system in anxiety pathophysiology and examines the potential of electrical vestibular stimulation (VeNS) as a novel, safe, and effective treatment option.</div></div><div><h3>Recent findings</h3><div>While the exact pathophysiology of anxiety remains unclear, recent studies suggest that GAD involves complex neurobiological mechanisms, including dysregulated inhibitory neurotransmission, hyperactivity of the amygdala, and impaired connectivity in anxiety-related neural circuits. The vestibular system has been identified as a critical modulator of emotional and stress responses, with vestibular dysfunction being linked to heightened anxiety levels. VeNS, a non-invasive neuromodulation technique, has demonstrated effectiveness in reducing anxiety symptoms by influencing key brain structures, including the amygdala, prefrontal cortex, hippocampus, and locus coeruleus. Clinical trials have shown significant reductions in GAD-7 scores and improvements in sleep and overall quality of life following VeNS treatment.</div></div><div><h3>Summary: electrical</h3><div>Vestibular stimulation (VeNS) has emerged as a promising, non-invasive therapeutic approach for managing GAD. By targeting the vestibular system's extensive neural connections, VeNS modulates anxiety-related brain regions, regulates stress responses, and enhances emotional well-being. Clinical evidence supports its efficacy in significantly reducing anxiety symptoms and improving sleep quality. Given its favorable safety profile and ease of use, VeNS presents a viable alternative or complementary option to conventional pharmacological and psychotherapeutic treatments for anxiety disorders.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111601"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879490","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":"Sex heterogeneity of functional brain network dynamics in autism spectrum disorder based on the high-amplitude co-fluctuation analysis","authors":"Le Gao ,&nbsp;Yue Hou ,&nbsp;Xiaojiao Dong ,&nbsp;Chenchen Wang ,&nbsp;Dong Cui ,&nbsp;Xiaonan Guo","doi":"10.1016/j.pnpbp.2025.111604","DOIUrl":"10.1016/j.pnpbp.2025.111604","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a neurodevelopmental condition exhibiting marked sex heterogeneity in functional connectivity. Given that high-amplitude co-fluctuation patterns dominate whole-brain functional connectivity, this study investigated sex heterogeneity in these patterns in ASD from the perspective of temporal variability. Resting-state functional magnetic resonance imaging data were obtained from the Autism Brain Imaging Data Exchange database, comprising 284 males/65 females with ASD and 340 male/119 female typical controls. High-amplitude co-fluctuation patterns were obtained using an edge time series analysis, and temporal variability of intra-network and inter-network functional architecture was calculated to characterize functional brain network dynamics. A two-way analysis of variance was further conducted to explore sex heterogeneity of functional brain network dynamics in ASD. At the intra-network level, significant diagnosis-by-sex interactions were observed in the default-mode network (DMN), salience network (SAN), cingulo-opercular network (CO), motor and somatosensory network (SMN), subcortical network (SUB), and visual network (VN). In ASD, sex differences in temporal variability were reduced in the DMN, SMN, and VN, increased in the CO and SUB, and an additional sex difference emerged in the SAN relative to controls. In contrast, at the inter-network level, all brain networks showed varying degrees of diagnosis-by-sex interaction effects. Moreover, network-level functional connectivity dynamics predicted the severity of social interaction impairments in females with ASD and social communication impairments in males with ASD, respectively. These findings reveal the sex heterogeneity of functional brain network dynamics in ASD, and highlight the potential role of altered high-amplitude co-fluctuations in the sex-specific neural mechanism underlying ASD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111604"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879466","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":"Corticosterone regulates the balance between freezing and rearing in defensive responses to predator threat","authors":"J.L. Baumbach ,&nbsp;C.Y.Y. Mui ,&nbsp;A.M. Leonetti ,&nbsp;L.J. Martin","doi":"10.1016/j.pnpbp.2025.111579","DOIUrl":"10.1016/j.pnpbp.2025.111579","url":null,"abstract":"<div><div>The hormonal stress response critically shapes how animals respond to threats. We examined how corticosterone (CORT) synthesis modulates defensive behaviors in mice exposed to the synthetic predator odor 2,4,5-trimethylthiazoline (TMT). Pharmacological inhibition of CORT synthesis using metyrapone reduced freezing and increased rearing during TMT exposure, without impairing threat recognition—evidenced by robust conditioned place aversion and context-specific freezing. We also found that freezing increased upon repeated TMT exposure, but this effect was blunted when CORT synthesis was blocked during the initial encounter. Furthermore, stress priming via restraint or footshock replicated the effects of prior TMT exposure, enhancing freezing and suppressing rearing. These findings suggest that while recognition of TMT's aversiveness remains intact without CORT, this hormone is essential for determining the qualitative and temporal dynamics of defensive responses. Our results reveal a key role for CORT in shaping behavioral flexibility during threat perception.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111579"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145726764","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":"Circulating levels of gut hormones in anorexia nervosa before and after short-term weight restoration","authors":"Theresa Kolb ,&nbsp;Louisa Licht ,&nbsp;Friederike I. Tam ,&nbsp;Evelina M. Stender ,&nbsp;Michaela Ohme ,&nbsp;Alessandra Borsini ,&nbsp;Stefan Ehrlich ,&nbsp;Nikolaos Perakakis","doi":"10.1016/j.pnpbp.2025.111576","DOIUrl":"10.1016/j.pnpbp.2025.111576","url":null,"abstract":"<div><div>Gastrointestinal hormones such as glucagon-like peptide-1 (GLP-1), gastric inhibitory peptide (GIP), glucagon, and glicentin are important regulators of appetite and glucose homeostasis. While agonists of GLP-1 and GIP receptors are approved treatments for type 2 diabetes and obesity, their role in anorexia nervosa (AN) remains largely unknown.</div><div>In this study, we measured fasting serum levels of GLP-1, GIP, glucagon, and glicentin in 80 female patients with AN before (acAN-T1) and after short-term weight restoration (acAN-T2) compared to 80 age-matched female healthy controls (HC).</div><div>GIP levels were higher (42.9%) in acAN-T1 than in HC, while GLP-1, glicentin, and glucagon showed no group differences. Additionally, acAN-T1 patients exhibited lower fasting glucose (<em>-</em>8.4%) and insulin (<em>-</em>42.6%) levels than HC. In acAN-T2, GIP, GLP-1, and glicentin levels decreased (<em>-</em>30.4%, <em>-</em>9.7%, −15.7 %, respectively), with only GIP normalizing. Glucose and insulin levels increased (4.5% and 41.4%, respectively), although they remained lower than in HC.</div><div>Importantly, changes in GIP levels after short-term weight restoration negatively correlated (<em>r</em> = <em>-</em>0.279) with changes in glucose levels. Furthermore, GIP levels in acAN-T1 were positively associated with disordered eating and depressive symptoms, independent of BMI-SDS.</div><div>These results reveal that GIP shows a distinct pattern of dysregulation and normalization in AN and link GIP levels to both glucose metabolism and symptom severity in AN. Thus, our findings support the rationale for investigating GIP receptor-targeted therapies in AN.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111576"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696344","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":"Lactobacillus-rich microbiota promotes adaptive behavioral responses to multifactorial stress and preserves gut function, while antibiotic-induced dysbiosis suppresses these effects in mice","authors":"Luiza S. Marques,&nbsp;Juliano T.K. Jung,&nbsp;Maiza Carlin,&nbsp;Maria C.B.F. de Albuquerque,&nbsp;Cristina W. Nogueira","doi":"10.1016/j.pnpbp.2025.111590","DOIUrl":"10.1016/j.pnpbp.2025.111590","url":null,"abstract":"<div><div>The microbiota–gut–brain axis regulates gastrointestinal and neurobehavioral processes, including stress responses. Although stress and dysbiosis independently impact host physiology, their combined effects remain poorly understood. This study evaluated antibiotic-induced dysbiosis and multifactorial stress (MFS) effects on stress-coping and intestinal functionality by exploring the microbiota-gut-brain interaction. Male Swiss mice were divided into Control, Dysbiosis, MFS, and Dysbiosis+MFS groups. Dysbiosis was induced by administration of 10 mL/kg/day of an antibiotic cocktail containing Vancomycin 0.5 g/L, Metronidazole 1 g/L, Neomycin Sulfate 1 g/L, and Ampicillin 1 g/L. In MFS groups, mice underwent a 7-day multifactorial model (tail pressure, predator odor, water deprivation, 45° tilted cage, food deprivation, immobilization, and predator sound). Mice performed elevated plus maze, forced swimming, and tail suspension tests. Intestinal transit rate (%), fecal moisture content, and relative weights of the cecum and adrenal glands were assessed. Protein contents of occludin, claudin-1, and 5-HT4R in the colon, and glucocorticoid receptor in the hippocampus were determined. The microbiota profile of colorectal feces was analyzed by 16S rRNA sequencing. Dysbiosis and MFS interaction impacted the total sequences and alpha diversity of gut microbiota. Dysbiosis modified the composition of gut microbiota at the phylum, genus, and species levels, while MFS maintained Lactobacillus abundance. Dysbiosis induced intestinal dysfunction, while MFS attenuated intestinal barrier disruption without affecting other dysbiosis-induced effects. Dysbiosis and MFS individually decreased the weight gain of mice. Dysbiosis mitigated adaptive stress-coping behavior induced by MFS. Lactobacillus-rich microbiota promoted adaptive stress-coping behaviors and preserved gut function, while antibiotic-induced dysbiosis impaired both.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111590"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776703","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}