Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Astrocytic extracellular matrix proteins in ADHD: The role of thrombospondin - 1, Sparc, and Sparcl-1.","authors":"Nilüfer Yildiz Kismet, Selen Sezen Gökçearslan, Serenay Elgün Ülkar, Sadettin Burak Açikel","doi":"10.1016/j.pnpbp.2026.111731","DOIUrl":"https://doi.org/10.1016/j.pnpbp.2026.111731","url":null,"abstract":"<p><p>Astrocyte-derived extracellular matrix (ECM) proteins are critical for synaptic development and glutamatergic signaling, yet their role in attention deficit hyperactivity disorder (ADHD) remains poorly understood. This study examined serum levels of Thrombospondin-1 (Tsp-1), Sparc, and Sparcl-1 in children with ADHD and explored their associations with behavioral symptoms, executive dysfunction, and social impairments. Eighty-six children aged 6-12 years participated: 46 medication-naive with ADHD and 40 age- and sex-matched neurotypical controls. Clinical measures included the Conners' Parent Rating Scale-Revised: Long Form (CPRS-R:L), Social Responsiveness Scale (SRS), and Behavior Rating Inventory of Executive Function (BRIEF). Serum levels of Tsp-1, Sparc, and Sparcl-1 were quantified via ELISA. Children with ADHD exhibited significantly lower serum levels of Tsp-1 (p < 0.001), Sparc (p = 0.020), and Sparcl-1 (p = 0.049) than controls. Lower Sparc levels were associated with poorer executive functioning and reduced social responsiveness, while lower Tsp-1 levels were positively associated with higher ADHD symptom severity. This study provides the first evidence of reduced serum astrocyte-derived ECM proteins in children with ADHD, implicating glia-mediated synaptic dysregulation in the disorder's pathophysiology. These findings suggest a novel glia-centered mechanism and support the potential of ECM proteins as biomarkers for ADHD subtypes and as targets for future therapeutic interventions.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111731"},"PeriodicalIF":3.9,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846086","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":"Structural brain network alterations in schizophrenia and ultra-high risk populations: Linking olfactory dysfunction to clinical symptoms.","authors":"Huiqing Peng, Ying He, Xiaogang Chen, Shuting Chen, Zongchang Li, Chunwang Li, Ke Jin, Liu Yuan, Xiaoqian Ma","doi":"10.1016/j.pnpbp.2026.111729","DOIUrl":"https://doi.org/10.1016/j.pnpbp.2026.111729","url":null,"abstract":"<p><strong>Background: </strong>Olfactory dysfunction is an early feature of schizophrenia, but its structural brain network basis remains unclear, especially in ultra-high risk (UHR) individuals.</p><p><strong>Methods: </strong>We recruited 99 drug-naive first-episode schizophrenia patients (FES), 72 UHR individuals (followed for 2 years), and 69 healthy controls individuals (HC). Olfactory function was assessed by using the Odor Stick Identification Test for the Japanese (OSIT-J). Structural MRI data were processed to measure cortical volume and thickness across 8 brain networks. General linear models and partial correlation analyses were conducted. Mediation analysis assessed whether brain network alterations mediated the relationship between olfactory function and symptoms. Logistic regression assessed psychosis conversion in UHR.</p><p><strong>Results: </strong>Both FES and UHR groups exhibited reduced OSIT-J scores and decreased brain network volumes compared to that of the HC group (p_-FDR < 0.05), with the default mode network (DMN) and frontoparietal network (FPN) showing the strongest associations with olfactory performance. Mediation analysis revealed that DMN and FPN volumes mediated the relationship between olfactory impairment and clinical symptoms in both FES and UHR. Poorer OSIT-J scores predicted psychosis conversion in UHR (OR = 0.35, p = 0.009), with the combined OSIT-J and intracranial volume model achieving high predictive accuracy (AUC = 0.86).</p><p><strong>Conclusion: </strong>Olfactory impairment is closely linked to structural alterations in DMN and FPN, which mediate its impact on symptoms. When combined with structural brain measures, the OSIT-J may contribute to risk assessment of UHR transition to schizophrenia.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111729"},"PeriodicalIF":3.9,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846125","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":"Deep brain stimulation: A narrative review of its applicability for major depressive disorder.","authors":"Sandra S Meirelles, Lucas C Pedro, Karla F Zocatelli, Gabriel S Mondo, Flávia K Rigo, Gislaine Z Réus","doi":"10.1016/j.pnpbp.2026.111721","DOIUrl":"https://doi.org/10.1016/j.pnpbp.2026.111721","url":null,"abstract":"<p><strong>Objectives: </strong>This article reviews the existing literature on DBS in the context of MDD, with particular attention to treatment-resistant depression (TRD), and provides a comprehensive, up-to-date overview of its mechanisms, efficacy, and potential challenges.</p><p><strong>Background: </strong>Deep brain stimulation (DBS) has established itself as an effective intervention for movement disorders, such as Parkinson's disease, in which stimulation of structures including the subthalamic nucleus and the internal globus pallidus provides significant symptom relief. In recent years, its application has been increasingly explored in psychiatric disorders, particularly major depressive disorder (MDD). However, a substantial proportion of patients do not respond adequately to conventional treatments and are classified as having treatment-resistant depression (TRD). DBS has recently been approved by the Food and Drug Administration (FDA) for treatment-resistant obsessive-compulsive disorder (OCD), while its potential role in MDD-especially in TRD-remains under investigation.</p><p><strong>Methods: </strong>Through a qualitative, exploratory analysis based on bibliographic searches, this study aims to inform and update academics and healthcare professionals on recent discoveries and applications of DBS in the treatment of MDD and TRD, thereby advancing science and improving public health and social well-being.</p><p><strong>Results: </strong>Existing studies have investigated several neural targets involved in mood regulation, including the subgenual cingulate cortex, subthalamic nucleus, globus pallidus, and, in exploratory models, the amygdala. Available evidence suggests that modulation of these circuits may contribute to improvements in depressive symptoms in treatment-resistant cases, although variability in study design, patient selection, and stimulation parameters remains significant.</p><p><strong>Conclusions: </strong>DBS represents a promising but still evolving therapeutic strategy for treatment-resistant depression. Further research is needed to refine targeting strategies, optimize stimulation protocols, and better establish long-term efficacy and safety.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111721"},"PeriodicalIF":3.9,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846084","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":"Serotonergic psychedelics for Autism spectrum disorder: Neurobiological mechanisms and translational prospects.","authors":"Zhen Xuen Brandon Low","doi":"10.1016/j.pnpbp.2026.111717","DOIUrl":"https://doi.org/10.1016/j.pnpbp.2026.111717","url":null,"abstract":"<p><p>Autism Spectrum Disorder (ASD) is characterized by persistent social-communication deficits, cognitive rigidity, and atypical sensory processing. Current pharmacological treatments, including risperidone and aripiprazole, provide only limited symptomatic relief and do not address the underlying neurobiological mechanisms. Converging evidence implicates dysregulated serotonergic signaling, impaired neuroplasticity, and chronic neuroimmune activation as central features of ASD pathophysiology. Serotonergic psychedelics, such as psilocybin and LSD, act as high-affinity 5-HT_2A receptor agonists and have re-emerged as candidates for modulating these core pathways. In this Review, we synthesize molecular, cellular, and systems-level findings suggesting that psychedelics may transiently relax overly rigid cortical priors, reopen critical periods for social learning, and recalibrate dysfunctional neural circuits in ASD. These compounds enhance synaptic plasticity via BDNF and mTOR signaling, modulate cortical oscillations, and suppress neuroinflammation by shifting microglial phenotypes and suppressing pro-inflammatory cytokines. Systems-level frameworks, including the REBUS and anarchic brain hypotheses, contextualize how psychedelics induce globally integrated, less constrained brain states that may counteract the hyper-segregated connectivity commonly observed in ASD. While preclinical and early human studies report improvements in sociability, sensory responsiveness, and behavioural flexibility, rigorous clinical trials are urgently needed to establish safety, efficacy, and optimal developmental windows for intervention. We conclude by outlining a translational roadmap to guide future research, emphasizing the need for structured integration with behavioural therapies, attention to ASD heterogeneity, ethical considerations, and the potential to shift ASD treatment beyond symptomatic management toward disease-modifying intervention.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111717"},"PeriodicalIF":3.9,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147789503","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 neural pathways and genetic substrates of non-suicidal self-injury as a 'sensation of pain' addiction in drug-naïve depressed adolescents\" [Prog Neuropsychopharmacol Biol Psychiatry. 2026 Jan 2;144: 111597].","authors":"Xianliang Chen, Hui Chen, Sihong Li, Huajia Tang, Jiawei Zhou, Bohao Cheng, Zhengqian Jiang, Yanyue Ye, Jiali Liu, Peiqu Liu, Fengmei Lu, Jiansong Zhou","doi":"10.1016/j.pnpbp.2026.111694","DOIUrl":"https://doi.org/10.1016/j.pnpbp.2026.111694","url":null,"abstract":"","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111694"},"PeriodicalIF":3.9,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147700769","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":"Prenatal polysubstance exposure alters behaviour in zebrafish larvae","authors":"Lise Hermant ,&nbsp;Gabriel D. Bossé","doi":"10.1016/j.pnpbp.2026.111686","DOIUrl":"10.1016/j.pnpbp.2026.111686","url":null,"abstract":"<div><div>Substance use during pregnancy has been linked to various adverse outcomes in infants, including congenital disabilities, neurodevelopmental delays, and long-term effects such as learning difficulties. An additional concern is that newborns are often exposed to multiple substances in utero. The biological consequences of such exposure remain largely unknown. Zebrafish offer an exciting alternative to fill this gap and deepen our understanding of the biological impact of prenatal multidrug exposure. We utilized zebrafish's scalability to expose embryos to some of the most commonly used substances: nicotine, alcohol, opioids, and all their possible combinations. After embryonic drug exposure, we conducted a detailed behavioural analysis across three developmental stages. Our results revealed drug-specific outcomes, including both synergistic and antagonistic effects. Furthermore, we identified distinctive effects across development, highlighting potential developmental shifts and individual differences in resilience. Overall, these findings demonstrate that prenatal polydrug exposure results in complex, stage-dependent effects, sometimes antagonistic, which cannot be predicted from single-drug outcomes. Our study emphasizes the value of zebrafish as a model for investigating polydrug interactions and provides a framework for exploring biomarkers of vulnerability and resilience in offspring.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"146 ","pages":"Article 111686"},"PeriodicalIF":3.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576484","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":"Serum IGF-1 and anxiety trajectories in Parkinson's disease","authors":"Shuai Chen ,&nbsp;Yu-Xin Niu ,&nbsp;Chen-Hong Li ,&nbsp;Xue-Feng Xiang ,&nbsp;Jing-Yu Shao ,&nbsp;Hong-Qi Yang ,&nbsp;Kai Ma ,&nbsp;Jie-Wen Zhang","doi":"10.1016/j.pnpbp.2026.111683","DOIUrl":"10.1016/j.pnpbp.2026.111683","url":null,"abstract":"<div><h3>Objective</h3><div>Insulin-like growth factor-1 (IGF-1), a neuroprotective polypeptide, has been implicated in the pathophysiology of Parkinson's disease (PD). Although cross-sectional studies have reported an inverse relationship between serum IGF-1 levels and anxiety in PD patients, the longitudinal effects of IGF-1 on anxiety symptoms remain unclear.</div></div><div><h3>Methods</h3><div>A total of 405 early-stage, drug-naive PD patients and 191 matched healthy controls from the Parkinson's Progression Markers Initiative (PPMI) database were included in this study. In the PD cohort, linear mixed-effects (LME) models were used to examine the association between baseline IGF-1 levels (analyzed as both continuous and categorical variables) and longitudinal changes in State-Trait Anxiety Inventory (STAI) scores over 10 years.</div></div><div><h3>Results</h3><div>Among the 405 drug-naive, early-stage PD patients, 64.9% were male. At baseline, the mean age was 61.68 ± 9.74 years, mean disease duration was 0.55 ± 0.55 years, and mean STAI score was 65.36 ± 18.38. Median baseline IGF-1 levels were 126.5 ng/mL in PD patients (<em>n</em> = 405) and 118.8 ng/mL in healthy controls (<em>n</em> = 191), with no significant difference (<em>p</em> = 0.457). After adjusting for covariates, the LME model treating IGF-1 as a continuous variable showed no significant association with baseline STAI scores. However, the IGF-1 × time interaction was significant (β = −0.003, <em>p</em> = 0.038), suggesting that higher IGF-1 levels were associated with a slower progression of anxiety symptoms over time. Similarly, in the tertile model, the middle and high IGF-1 groups showed significantly slower progression of anxiety over 10 years (Group × Time interaction: β = −0.79 and − 0.70; <em>p</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>This study provided longitudinal evidence of a negative association between serum IGF-1 levels and the progression of anxiety symptoms in PD patients, which may serve as a potential biomarker for the progression of anxiety symptoms in PD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"146 ","pages":"Article 111683"},"PeriodicalIF":3.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576649","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":"Low-dose antipsychotics ameliorate maternal separation-induced ultrasound vocalization deficits in the vasopressin-deficient Brattleboro rat pups","authors":"Bibiána Török ,&nbsp;Anna Fodor ,&nbsp;Barbara Klausz ,&nbsp;János Varga ,&nbsp;Dóra Zelena","doi":"10.1016/j.pnpbp.2026.111682","DOIUrl":"10.1016/j.pnpbp.2026.111682","url":null,"abstract":"<div><div>Beyond its classical function in salt-water homeostasis, vasopressin plays an important role in higher-order brain functions, including social behaviour. Deficits in social communication are core feature of many neurological and psychiatric disorders, including autism spectrum disorder (ASD), and can be modelled in rodents through maternal separation-induced ultrasonic vocalizations (MS-USV, 30–50 kHz). Consistent with its role in social interaction, vasopressin-deficient Brattleboro rat pups emit fewer MS-USVs. We hypothesized that antipsychotics, approved for irritability and related behavioural manifestations in ASD, could normalize this deficit.</div><div>We studied 7- to 8-day-old vasopressin-deficient Brattleboro pups and compared them with their heterozygous littermates. Each pup was placed in a 2 L glass beaker for 10 min while MS-USV was recorded using a bat detector. We administered haloperidol, clozapine, olanzapine, risperidone, aripiprazole or vehicle and the genotype was determined retrospectively.</div><div>Vasopressin-deficient pups vocalized significantly less than their counterparts. Low, non-sedative doses of various antipsychotics (except haloperidol) increased MS-USV in vasopressin-deficient pups to levels comparable to controls. However, higher doses, which induced sedation (measured by increased righting reflex latency or negative geotaxis latency) or stress (indicated by elevated adrenocorticotropin and corticosterone levels), reduced MS-USV in control pups as well.</div><div>These findings indicate that reduced MS-USV in vasopressin-deficient Brattleboro pups provides a useful model for studying impairments in early-life social communication, which may also be highly relevant in the context of ASD. The responsiveness to low-dose pharmacological intervention further supports the model's relevance for investigating mechanisms and potential therapeutic strategies targeting social behavioural alterations.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"146 ","pages":"Article 111682"},"PeriodicalIF":3.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147596116","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":"Metabolomics analysis of serum biomarkers and metabolic pathways in addictive disorders: Focus on internet gaming disorder and alcohol use disorder","authors":"Joon Hwan Jang ,&nbsp;Soo Hyun Lee ,&nbsp;Hyun-Mee Park ,&nbsp;Mi Jung Ji ,&nbsp;Bogyoung Choi ,&nbsp;So Young Yoo ,&nbsp;Jung-Seok Choi ,&nbsp;Ji Eun Lee","doi":"10.1016/j.pnpbp.2026.111705","DOIUrl":"10.1016/j.pnpbp.2026.111705","url":null,"abstract":"<div><h3>Introduction</h3><div>Metabolomics technologies provide a means to uncover metabolic disturbances and the associated signaling pathways in addictive disorders such as alcohol use disorder (AUD) and internet gaming disorder (IGD). While it is anticipated that common or distinctive metabolic pathways may be implicated in AUD and IGD groups, there have been few studies of comparative metabolomic analysis for these two addictive disorders.</div></div><div><h3>Methods</h3><div>In the current study, we investigated the metabolomic profiles of serum samples obtained from ninety-nine young adults aged 18–35 years, comprising individuals with AUD (<em>n</em> = 30), IGD (<em>n</em> = 34), and healthy controls (HCs, <em>n</em> = 35) using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q TOF-MS).</div></div><div><h3>Results</h3><div>From the untargeted metabolomic analysis of the serum samples, 26 metabolites exhibited statistically significant changes (FDR-adjusted <em>p</em>-value &lt;0.05 and fold change &gt;1.5) between individuals with AUD or IGD and HCs. Among these metabolites, six, including <em>N</em>-acetyltryptophan, L-formylkynurenine, and 3,4-dihydroxymandelic acid, exhibited increased or decreased levels in both the AUD and IGD groups compared to HCs. Metabolic pathway analysis revealed that the tyrosine metabolism pathway was specific to both the AUD and IGD groups, whereas sphingolipid metabolism and steroid hormone biosynthesis were activated in the AUD group compared to individuals with IGD and HCs.</div></div><div><h3>Conclusion</h3><div>While the current study is the first attempt to conduct comparative metabolomic analyses of the substance and non-substance-related addictions, the findings will broaden the understanding of the molecular mechanisms underlying addictive behaviors and offer important biomarkers for diagnosing and devising therapeutic strategies for these addictive disorders.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"146 ","pages":"Article 111705"},"PeriodicalIF":3.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147724931","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":"Aberrant inter-subject functional heterogeneity in frontoparietal and attention networks marks tobacco use disorder","authors":"Xuefeng Xu,&nbsp;Guang-Heng Dong","doi":"10.1016/j.pnpbp.2026.111695","DOIUrl":"10.1016/j.pnpbp.2026.111695","url":null,"abstract":"<div><h3>Background</h3><div>Tobacco use disorder (TUD) represents a significant global health challenge. Inter-subject variability in functional connectivity (IVFC) serves as a key neural indicator for explaining cognitive differences; however, its characteristics and genetic underpinnings in the TUD individuals remain unclear.</div></div><div><h3>Methods</h3><div>This study included 200 male TUD patients and 185 male healthy controls (HCs) who underwent magnetic resonance imaging scanning. IVFC was constructed at both the regional (ROI) and network levels. Five machine learning methods, including the support vector machines (SVM) were employed to evaluate the predictive and classificatory performance of IVFC. Neurochemical and genetic analyses were further conducted to explore potential genetic mechanisms.</div></div><div><h3>Results</h3><div>The TUD group exhibited significantly higher IVFC at both the ROI and network levels compared to HCs. SVM and other models effectively distinguished TUD patients from HCs, identifying the frontoparietal network (FPN), ventral attention network (VAN), and dorsal attention network (DAN) as the most discriminative features. ROI-level IVFC was significantly associated with the spatial distribution of key neurotransmitter systems, including dopamine, and correlated with the expression of 4427 genes. These genes were enriched in pathways related to synaptic function and the phosphorylation regulation.</div></div><div><h3>Conclusion</h3><div>Compared to HCs, individuals with TUD exhibited significant IVFC abnormalities, with disruptions in the FPN, VAN, and DAN as core neural features. Within the TUD group, ROI-level IVFCs were associated with neurotransmitter systems and gene expression, offering preliminary insights into clinical heterogeneity. These findings suggest that IVFC alterations—particularly in the FPN, VAN, and DAN—may serve as candidate neuroimaging biomarkers for TUD, pending validation in future longitudinal studies.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"146 ","pages":"Article 111695"},"PeriodicalIF":3.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147647245","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}