Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Orbitofrontal rTMS modulates inferior parietal lobule functional reorganization to alleviate negative symptoms in first-episode, drug-naïve patients with schizophrenia","authors":"Kexu Zhang ,&nbsp;Xiong Jiao ,&nbsp;Yanli Zhang ,&nbsp;Ningning Zeng ,&nbsp;Min Wang ,&nbsp;Kun Li ,&nbsp;Ziliang Wang ,&nbsp;Junfeng Sun ,&nbsp;Jijun Wang ,&nbsp;Qiang Hu","doi":"10.1016/j.pnpbp.2025.111602","DOIUrl":"10.1016/j.pnpbp.2025.111602","url":null,"abstract":"<div><h3>Background</h3><div>Recent studies have identified the orbitofrontal cortex (OFC) as a potential target for alleviating negative symptoms in schizophrenia. However, the neurobiological mechanisms underlying repetitive transcranial magnetic stimulation (rTMS) delivered to the OFC remain unclear.</div></div><div><h3>Methods</h3><div>In this randomized controlled trial, seventy first-episode, drug-naïve patients with schizophrenia were assigned to receive either 20 sessions of active 1 Hz rTMS over the right lateral OFC (<em>N</em> = 36) or sham stimulation (<em>N</em> = 34). Clinical outcomes were measured using the Positive and Negative Syndrome Scale (PANSS). Resting-state functional MRI data were collected before and after treatment to assess changes in regional brain activity and functional connectivity, using fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and seed-based connectivity analyses.</div></div><div><h3>Results</h3><div>Compared to sham stimulation, active OFC-rTMS led to significantly greater reductions in PANSS scores (total: 22.7 vs. 14.3, <em>p</em> = 0.003, Cohen's d = 0.733; negative: 6.2 vs. 4.0, <em>p</em> = 0.037, Cohen's d = 0.510). Neuroimaging analyses revealed increased spontaneous activity (fALFF and ReHo) in the right OFC and bilateral inferior parietal lobule (IPL), along with enhanced functional connectivity between the OFC and IPL in the active rTMS group. Importantly, IPL-related functional reorganization was significantly associated with symptom improvement, particularly in negative and general domains.</div></div><div><h3>Conclusions</h3><div>These findings suggest that rTMS targeting the OFC exerts therapeutic effects in schizophrenia by modulating IPL function and OFC–IPL connectivity. The IPL may serve as a critical downstream node mediating the clinical benefits of OFC-rTMS, offering novel insights into network-based neuromodulation strategies for negative symptoms.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111602"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879434","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":"Distinguishing resilience from susceptibility: Brain network alterations during fear learning in response to childhood unpredictability","authors":"Xinyu Cao ,&nbsp;Shanshan Wang ,&nbsp;Junhui Zhang ,&nbsp;Yanqing Zhang ,&nbsp;Jingjing Luo ,&nbsp;Yuanyuan Chen ,&nbsp;Jiaxin Xiang ,&nbsp;Jianjun Zhu","doi":"10.1016/j.pnpbp.2025.111587","DOIUrl":"10.1016/j.pnpbp.2025.111587","url":null,"abstract":"<div><div>Not all individuals exposed to childhood unpredictability develop psychopathology. This study breaks new ground by identifying the neural network signatures that distinguish resilience from susceptibility following such adversity. Using fear learning paradigms, we acquired fMRI data from 213 participants and constructed whole-brain functional connectivity networks. Innovatively, we employed dual resilience metrics—psychological (depressive symptoms) and biological (inflammatory TNF-alpha levels)—to classify participants into resilient and susceptible groups. Graph theory analysis found that the resilient group exhibited a sparser global network structure compared to the susceptible group. At the nodal level, the susceptible group showed increased nodal degree centrality in eight brain regions across multiple functional networks, compared to both the resilient and control groups. Furthermore, network-based statistic revealed that the resilient group demonstrated stronger connectivity between the default mode network (DMN) and both the frontoparietal and attention networks during fear learning. In contrast, susceptibility was associated with stronger connectivity between the visual network (VN), dorsal attention network (DAN), DMN, and frontoparietal network (FPN), alongside weaker connectivity within and between the DMN, DAN, and FPN. Importantly, network connectivity-based models predicted an individual's classification into the resilient or susceptible group with 89 % accuracy. Our findings uncover abnormal connectome organization within the DMN, DAN, FPN, and VN, shedding light on the neural mechanisms underlying vulnerability and resilience in the context of childhood unpredictability. By identifying these neurobiological markers of resilience, our work opens new avenues for early identification of vulnerability and development of targeted interventions to promote adaptive brain functioning in at-risk populations.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111587"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776722","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":"Topologic but not volumetric differences diversify sex effects on thalamic nuclei in drug-naive patients with major depressive disorder","authors":"Yidan Wang ,&nbsp;Xinyue Hu ,&nbsp;Lianqing Zhang ,&nbsp;Hailong Li ,&nbsp;Yingxue Gao ,&nbsp;Mengyue Tang ,&nbsp;Zilin Zhou ,&nbsp;Shuangwei Chai ,&nbsp;Liqiong Liu ,&nbsp;Weihong Kuang ,&nbsp;Qiyong Gong ,&nbsp;Xiaoqi Huang","doi":"10.1016/j.pnpbp.2025.111594","DOIUrl":"10.1016/j.pnpbp.2025.111594","url":null,"abstract":"<div><h3>Background</h3><div>The thalamus is a crucial subcortical structure in etiological models of major depressive disorder (MDD). Given the well-documented sex differences in MDD prevalence and clinical manifestations, it remains unclear whether these differences are linked to structural characteristics of thalamus. This study aimed to investigate the divergent sex effects on thalamus nuclei in drug-naive patients with MDD.</div></div><div><h3>Methods</h3><div>High-resolution 3D T1-weighted and diffusion tensor imaging images were obtained for 174 drug-naive patients with MDD and 118 age-, sex-, education years- and handedness-matched healthy controls (HCs). The thalamus was segmented into 22 nuclei using FreeSurfer. A general linear model (GLM) was used to test sex-by-diagnosis interactions for volumes of whole thalamus and individual nuclei between groups. We also performed a graph theory analysis of the structural covariance network (SCN) of thalamic nuclei in females and males with MDD, compared to their sex-matched HCs, respectively.</div></div><div><h3>Results</h3><div>There were no significant sex-by-diagnosis interactions in whole thalamus or nuclei volumes. The disruptions of SCN were observed in females with MDD, including lower nodal degree in left lateral posterior (LP) nucleus, lower betweenness centrality across several nuclei in the left intralaminar and bilateral antero-lateral nuclei group, and higher betweenness and closeness centrality in right pulvinar lateral nucleus, compared to female HCs. Males with MDD displayed lower nodal degree in left ventral anterior magnocellular and right medial ventral reuniens nuclei and higher betweenness centrality in left mediodorsal lateral parvocellular nucleus relative to male HCs. Moreover, male HCs exhibited higher closeness centrality in the right LP nucleus than female HCs.</div></div><div><h3>Conclusion</h3><div>These findings represent the first evidence of sex-specific alterations in the topological properties rather than the volumes of thalamic nuclei in early untreated patients with MDD, indicating the structural reorganization of SCN of thalamic nuclei may represent a potential neuro-mechanism underlying sex differences in MDD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111594"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844240","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":"Presence of an unfamiliar peer reverses escalated cocaine intake in male rats: Involvement of the subthalamic nucleus","authors":"Cassandre Vielle,&nbsp;Lucie Vignal,&nbsp;Alix Tiran-Cappello,&nbsp;Julie Meffre,&nbsp;Nicolas Maurice,&nbsp;Mickael Degoulet,&nbsp;Cécile Brocard,&nbsp;Florence Pelletier,&nbsp;Yann Pelloux ,&nbsp;Christelle Baunez","doi":"10.1016/j.pnpbp.2025.111588","DOIUrl":"10.1016/j.pnpbp.2025.111588","url":null,"abstract":"<div><div>The immediate social context critically modulates drug consumption. The presence of an unfamiliar conspecific, naive to the drug, at the time of consumption reduces cocaine self-administration in male rats during short-access sessions, as well as drug intake in human cocaine users. The subthalamic nucleus (STN), a brain structure involved in cocaine addiction and limbic processes, has been proposed to mediate such social influence on this limited level of drug intake. Whether this influence extends to escalated drug consumption remains an open question. In this study, we compared the effect of the presence of an unfamiliar peer, naive to cocaine, on cocaine self-administration in rats having been exposed to either short (2 h) or long-access sessions (6 h). We showed that the presence of the peer markedly reduced both limited and escalated cocaine intake in male rats. Preliminary tests in females revealed no effect of the peer's presence during short-access sessions; therefore, subsequent experiments were conducted in males only. Assessing the effect of STN photo-inhibition or high frequency (HF) stimulation in male rats, we demonstrated that it had no effect in the absence of the conspecific in short-access sessions, but STN photo-manipulation suppressed the influence of the peer's presence. Moreover, STN photo-inhibition and HF stimulation decreased drug consumption in long-access sessions, but no additive effect was observed when associated with the peer's presence, confirming an overriding effect of STN manipulation. Taken together, these results highlight the potential influence of socially oriented manipulations on cocaine intake and further position the STN as a critical mediator of the effect of social presence on addictive-like behaviors.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111588"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145792050","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":"On the possibility to modulate psychopathic traits via non-invasive brain stimulation: A systematic review and meta-analysis","authors":"Célia F. Camara ,&nbsp;Carmen S. Sergiou ,&nbsp;Andrés Molero Chamizo ,&nbsp;Alejandra Sel ,&nbsp;Nathzidy G. Rivera Urbina ,&nbsp;Michael A. Nitsche ,&nbsp;Paul H.P. Hanel","doi":"10.1016/j.pnpbp.2025.111582","DOIUrl":"10.1016/j.pnpbp.2025.111582","url":null,"abstract":"<div><div>The affective and interpersonal features of psychopathy describe impairments in socio-affective processes such as affective empathy, prosocial motivation and guilt. Research in neuroscience shows that these processes are associated with distinct neural circuits and cortical excitability patterns that appear to be dysregulated in individuals with psychopathy, with emerging research suggesting the potential of non-invasive brain stimulation (NIBS) to address such disruptions. To investigate this possibility, we conducted a meta-analysis of 64 sham- or active-controlled studies (122 effects) across three modalities: repeated transcranial magnetic stimulation (rTMS), theta-burst stimulation (TBS), and transcranial direct current stimulation (tDCS). Protocols were classified as excitatory (high-frequency rTMS, anodal tDCS) or inhibitory (low-frequency rTMS, continuous TBS, cathodal tDCS) depending on the expected polarity and directionality of their effects. Excitatory protocols yielded small-to-moderate improvements in socio-affective outcomes (Hedges' g ≈ 0.33–0.33), whereas only cathodal tDCS produced modest reductions among inhibitory protocols (g = −0.43). However, over 90 % of the included studies were conducted in healthy adult samples, limiting direct generalizability to psychopathy. In fact, the only available study in psychopathic individuals reported null effects. Together, these findings provide preliminary proof-of-concept for the potential of NIBS to modulate socio-affective processes relevant to psychopathy but also point to substantial methodological variability and the absence of direct evidence for psychopathy treatment in current research. Addressing these gaps is essential to evaluate the feasibility of implementing NIBS methods as a viable intervention for psychopathy.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111582"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745414","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":"Hypersensitization of peripheral immune cells from major depressive disorder patients is mildly attenuated by fluoxetine in vitro","authors":"Yingqian Zhang ,&nbsp;Qi Lai ,&nbsp;Tangcong Chen ,&nbsp;Yueyang Luo ,&nbsp;Mengdie Li ,&nbsp;Mengqi Niu ,&nbsp;Jing Li ,&nbsp;Michael Maes","doi":"10.1016/j.pnpbp.2026.111608","DOIUrl":"10.1016/j.pnpbp.2026.111608","url":null,"abstract":"<div><div>Major depressive disorder (MDD) is accompanied by activation of the immune-inflammatory response system (IRS) and the compensatory immunoregulatory system (CIRS). Fluoxetine, the most commonly used selective serotonin reuptake inhibitor (SSRI), shows anti-inflammatory effects in both MDD patients and depressive-like behaviors in rodents. The present study examines the effects of fluoxetine on immune profiles, such as M1 and M2 macrophages, T helper (Th)1, Th2, Th17, IRS, and CIRS in MDD and healthy controls (HC). Culture supernatant of immunogen-stimulated whole blood of 18 MDD and 18 HC was measured for 48 cytokines using a multiplex assay. The effects of three fluoxetine concentrations (0.1 mM, 0.01 mM, and 0.001 mM) were examined. MDD was characterized by significantly increased M1, M2, Th1, Th2, Th17, IRS, and CIRS profiles under the stimulation of phytohemagglutinin (PHA) and lipopolysaccharide (LPS). Fluoxetine exhibited different effects on immune functions when comparing culture supernatant from MDD to HC. In HC samples, the administration of fluoxetine did not impact the immune system. In MDD samples, fluoxetine administration significantly reduces the stimulated production of Th1, Th17, M2, IRS, Th2, as well as IL-1 and TNF signaling pathways. Fluoxetine significantly attenuated the production of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, IL-12, interferon-γ, chemokines (CCL27, CXCL10), growth factors, and colony-stimulating factors. However, this suppressant effect is merely partial, insufficient to normalize the immune sensitization in the culture supernatant from MDD patients. In summary, fluoxetine has highly significant immunoregulatory effects in patients with MDD and not in controls. Unfortunately, these effects only partly attenuate the immune sensitization in MDD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111608"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967952","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":"Lower plasma DHEAS and BDNF levels as indicators of cognitive decline","authors":"Marcela Konjevod ,&nbsp;Nikola Balic ,&nbsp;Lucija Tudor ,&nbsp;Suzana Uzun ,&nbsp;Matea Nikolac Perkovic ,&nbsp;Barbara Vuic ,&nbsp;Tina Milos ,&nbsp;Gordana Nedic Erjavec ,&nbsp;Ninoslav Mimica ,&nbsp;Nela Pivac ,&nbsp;Dubravka Svob Strac","doi":"10.1016/j.pnpbp.2026.111605","DOIUrl":"10.1016/j.pnpbp.2026.111605","url":null,"abstract":"<div><div>Gradual loss of cognitive abilities is common during ageing but might also result in mild cognitive impairment and dementia. Research suggests that neurotrophins, such as brain derived neurotrophic factor (BDNF), and neurosteroids, such as dehydroepiandrosterone (DHEA) and its sulphate (DHEAS), play crucial role in cognitive functions and are often dysregulated in neurocognitive disorders. This study aimed to investigate variations in the genes for BDNF and sulfotransferase 2A1 (SULT2A1), the enzyme converting DHEA into DHEAS, as well as plasma BDNF and DHEAS levels, in individuals with normal cognition, and mild, moderate, and severe cognitive impairment. Cognitive functions of 453 participants were evaluated using Mini-Mental State Examination (MMSE) and Clock Drawing test (CDT). Genotyping of <em>BDNF</em> (rs6265) and <em>SULT2A1</em> (rs2637125) polymorphisms was conducted, and plasma BDNF and DHEAS concentrations were determined by enzyme-linked immunosorbent assays (ELISA). Obtained results demonstrated that participants with moderate to severe cognitive impairment had significantly lower plasma BDNF and DHEAS levels, compared to individuals with normal cognition. In contrast to DHEAS, BDNF changes were more pronounced in men than in women. However, no significant associations of <em>BDNF</em> rs6265 and <em>SULT2A1</em> rs2637125 polymorphisms with cognitive decline, or with plasma BDNF and DHEAS levels, respectively, were observed. Compared to CDT, MMSE was superior in distinguishing plasma BDNF and DHEAS variations, especially between individuals with mild and moderate to severe cognitive impairment. Further studies should investigate the potential of BDNF and DHEAS as peripheral biomarkers of cognitive decline and possible benefits of their replacement therapy in neurocognitive disorders.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111605"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907236","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":"Population pharmacokinetic analysis for simultaneous fit of clozapine and norclozapine concentrations in adult psychiatric patients","authors":"Bojana Panić ,&nbsp;Vera Lukić ,&nbsp;Katarina Vučićević ,&nbsp;Branislava Miljković ,&nbsp;Srđan Milovanović ,&nbsp;Marija Jovanović","doi":"10.1016/j.pnpbp.2025.111583","DOIUrl":"10.1016/j.pnpbp.2025.111583","url":null,"abstract":"<div><h3>Background</h3><div>Clozapine (CLZ) exhibits a high potential for pharmacokinetic interactions due to its extensive and complex metabolism. Additionally, several patient-related factors contribute to the pharmacokinetic variability, making treatment optimization even more challenging. The goal of this study was to develop a parent-metabolite population pharmacokinetic model for CLZ and its primary metabolite norclozapine (NCLZ) and to evaluate sources of variability in a real-world clinical setting.</div></div><div><h3>Methods</h3><div>Data from routine therapeutic drug monitoring (TDM) of 126 adult in- and out-patients with psychiatric disorders were used for the analysis. A nonlinear mixed-effects modeling approach was applied for data analysis to simultaneously fit CLZ and NCLZ concentrations.</div></div><div><h3>Results</h3><div>A one-compartment model for the drug with an additional compartment for NCLZ was used to fit the concentration-time data. The population pharmacokinetic value of oral clearance for CLZ (CL/F) for a typical patient (female, non-smoker) was 26.4 L/h. Male sex and positive smoking status were associated with an increase in CL/F of 25.9 % and 29.2 %, respectively. The estimated value of metabolite clearance (CL_m/F) for a typical patient was 29.6 L/h, while male sex and valproic acid (VPA) use were associated with its increases for 45.1 % and 95.5 %, respectively.</div></div><div><h3>Conclusion</h3><div>The developed population pharmacokinetic model describes the simultaneous disposition of CLZ and NCLZ in adult psychiatric patients, accounting for impact of patient and co-therapy factors. In addition to the well-established effects of sex and smoking status on CLZ pharmacokinetics, the model characterizes the significant impact of VPA co-therapy, primarily on NCLZ disposition.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111583"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145738864","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":"Optimizing multi-site schizophrenia differentiation: MRI harmonization with 20 controls per scanner in a study of 3560 subjects across 15 MRI scanners","authors":"Naoki Hashimoto ,&nbsp;Kiyotaka Nemoto ,&nbsp;Masaki Fukunaga ,&nbsp;Junya Matsumoto ,&nbsp;Naohiro Okada ,&nbsp;Kentaro Morita ,&nbsp;Hidenaga Yamamori ,&nbsp;Michiko Fujimoto ,&nbsp;Yuka Yasuda ,&nbsp;Michihiko Koeda ,&nbsp;Takahiko Kawashima ,&nbsp;Morio Aki ,&nbsp;Daiki Sasabayashi ,&nbsp;Daisuke Fujikane ,&nbsp;Kenichiro Harada ,&nbsp;Maeri Yamamoto ,&nbsp;Shuhei Ishikawa ,&nbsp;Naomi Hasegawa ,&nbsp;Satsuki Ito ,&nbsp;Kazutaka Ohi ,&nbsp;Ryota Hashimoto","doi":"10.1016/j.pnpbp.2026.111607","DOIUrl":"10.1016/j.pnpbp.2026.111607","url":null,"abstract":"<div><div>Although structural abnormalities has been reported in schizophrenia, generalizability across MRI scanners and protocols remains a major limitation for clinical application.</div><div>Our previous study demonstrated that general linear model (GLM)-based harmonization can effectively distinguish patients with schizophrenia from healthy controls (HC) across MRI scanners. In this method, regions of interest (ROIs) showing volume reduction in schizophrenia were pre-defined, and age, sex, and total intracranial volume were included as dependent variables in the scanner and protocol specific GLM (spsGLM). The residuals (ε) of the spsGLM, the difference between estimated and measured ROI volume, were used as an indicator of schizophrenia.</div><div>In the present study, we assessed required number of HC to apply this method, and adapted it to a larger dataset. We analyzed data from 1179 schizophrenia patients and 2381 HC across 15 MRI scanners. The minimum number of HC required was estimated to be 20. To avoid sampling bias, 20 HC were randomly selected 1000 times, and spsGLM model fitting was implemented for each set. The coefficients of spsGLM were calculated by averaging the results of 1000 trials, and ε was computed. Receiver operating characteristic (ROC) analyses were performed to evaluate ε.</div><div>Results indicated that the area under the curve (AUC) from ROC analysis ranged from 0.66 to 0.83. ROC analysis using full sample showed an AUC of 0.74. These results were comparable to those obtained using ComBat harmonization or a Random Forrest classifier.</div><div>In conclusion, scanning 20 HC enables our GLM-based harmonization method to generalize across scanners.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111607"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907259","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":"Distinct cortical inhibitory profiles in schizophrenia and bipolar disorder: A TMS-EEG study of GABAb function","authors":"Gema Mijancos-Martínez ,&nbsp;Inés Fernández-Linsenbarth ,&nbsp;Alejandro Bachiller ,&nbsp;Rosa Beño-Ruiz de la Sierra ,&nbsp;Emma Osorio-Iriarte ,&nbsp;Alejandro Roig ,&nbsp;Claudia Rodríguez-Valbuena ,&nbsp;Juan Carlos Fiorini-Talavera ,&nbsp;Saúl J. Ruiz-Gómez ,&nbsp;Ricardo D. Mancha ,&nbsp;Vicente Molina ,&nbsp;Miguel Angel Mañanas","doi":"10.1016/j.pnpbp.2025.111593","DOIUrl":"10.1016/j.pnpbp.2025.111593","url":null,"abstract":"<div><h3>Background</h3><div>EEG recordings associated with transcranial magnetic stimulation (TMS) with paired pulse paradigms allow the in vivo assessment of cortical inhibitory function. The long-interval cortical inhibition (LICI) paradigm can be used to estimate this function related to GABAb receptors.</div></div><div><h3>Methods</h3><div>We compared LICI values between 25 patients with schizophrenia, 16 patients with bipolar disorder (BD), and 23 healthy controls (HC). We also assessed the relationship between LICI values and cognitive performance, as well as the treatment with antipsychotics, benzodiazepines, and anticonvulsants.</div></div><div><h3>Results</h3><div>LICI was significantly lower in patients with schizophrenia than in controls, but not in BD patients. In the former group, LICI was negatively associated with cognitive performance and positive symptoms. However, benzodiazepines increased LICI values, which does not explain its decrease in schizophrenia patients.</div></div><div><h3>Conclusions</h3><div>Our data support the existence of a functional inhibitory deficit mediated by GABAb receptors in schizophrenia, that is associated with cognitive performance and symptoms. In the context of existing literature, this deficit may characterize a subgroup of patients with this diagnosis.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111593"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145841435","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}