Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Beyond surgery: Repurposing anesthetics for treatment of central nervous system disorders","authors":"Joana Mielko ,&nbsp;Julia Pakulska ,&nbsp;Amelia Oszczyk ,&nbsp;Klaudia Lustyk ,&nbsp;Karolina Pytka ,&nbsp;Kinga Sałaciak","doi":"10.1016/j.pnpbp.2025.111386","DOIUrl":"10.1016/j.pnpbp.2025.111386","url":null,"abstract":"<div><div>The development of new drugs is a complex, expensive, and time-consuming process, often fraught with a high likelihood of failure. Amid these obstacles, drug repurposing, which identifies new therapeutic applications for already existing medications, offers a more economical and time-saving approach, particularly in the challenging field of neurological and psychiatric disorders. This narrative review explores both preclinical and clinical studies to examine the potential of anesthetics such as ketamine, nitrous oxide, isoflurane, sevoflurane, propofol, dexmedetomidine, and sodium oxybate in treating central nervous system disorders. Various research highlights the potential of anesthetics to provide rapid antidepressant effects, enhance learning and memory, improve synaptic plasticity, and offer neuroprotective benefits, demonstrating promise for treating depression, post-traumatic stress disorder, cognitive decline, traumatic brain injury, and neurodegenerative disorders. Anesthetics appear to alleviate symptoms in neurological conditions, likely by modulating GABAergic and glutamatergic pathways. However, challenges such as dose-dependent neurotoxicity, variability in preclinical and clinical outcomes, as well as environmental concerns remain significant issues. Future research is essential to optimize dosing strategies, ensure long-term safety, and gain a deeper understanding of the precise mechanisms of action. The concept of anesthetics' repurposing presents a unique solution to tackle the challenges in neurological and psychiatric therapy by providing a platform for the development of new and improved therapies.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111386"},"PeriodicalIF":5.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921928","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-dependent upregulation in oxylipins involved in inflammation resolution in the cerebellum of Niemann-Pick disease C1 mice","authors":"Sandra M. Camunas-Alberca ,&nbsp;Maria Moran-Garrido ,&nbsp;Ángel Gaudioso ,&nbsp;Felipe da Costa Souza ,&nbsp;Ana Gradillas ,&nbsp;Maria Dolores Ledesma ,&nbsp;Coral Barbas ,&nbsp;Ameer Y. Taha","doi":"10.1016/j.pnpbp.2025.111387","DOIUrl":"10.1016/j.pnpbp.2025.111387","url":null,"abstract":"<div><div>Unresolved inflammation in the cerebellum is implicated in motor and cognitive decline in Niemann-Pick disease type C (NPC), a neurodegenerative lysosomal storage disorder caused by pathogenic mutations in the <em>Npc1</em> gene encoding a cholesterol transporter protein. It is unclear whether unresolved inflammation in NPC stems from impairments in lipid-mediated resolution. For this reason, free lipid mediators (i.e., oxylipins) involved in inflammation resolution, as well as esterified lipid mediators known to regulate the bioavailability of free oxylipins were quantified using Reverse-Phase Ultra- Performance Liquid Chromatography coupled to negative Electrospray Ionization and Triple Quadrupole Tandem Mass Spectrometry (RP-UPLC-ESI(−)-QqQ-MS/MS) in <em>Npc1</em> knock-in (NPC1ki) and Wildtype (WT) mice. Total cholesterol and fatty acids including polyunsaturated fatty acid (PUFA) precursors to oxylipins, were quantified using Gas Chromatography coupled to Flame Ionization Detection (GC-FID). Compared to WT mice, female NPC1ki mice, but not males, exhibited significantly elevated levels of free pro-resolving fatty acid epoxides (EpETrE and EpDPE) from the cytochrome P450 (CYP) pathway. Esterified mono- and dihydroxy lipid mediators derived from the lipoxygenase (LOX) and soluble epoxide hydrolase (sEH) pathways were mainly increased in NPC1ki females, suggesting enhanced sequestration of pro-inflammatory LOX and sEH metabolites. While PUFAs and cholesterol concentrations were not significantly different between groups, myristic (C14:0) and palmitoleic acid (C16:1n-7) were significantly elevated in female NPC1ki mice compared to WT controls. These findings suggest sex-specific adaptations in inflammation resolution pathways in NPC, with females exhibiting distinct inflammatory responses that may drive sex-related differences in disease pathogenesis. Our findings underscore the need for sex-specific therapeutic approaches to improve NPC treatment outcomes.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111387"},"PeriodicalIF":5.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948429","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":"Amygdala-insula response to neutral stimuli and the prospective prediction of anxiety sensitivity","authors":"Shannon E. MacDonald ,&nbsp;Claudia R. Becker ,&nbsp;Annmarie MacNamara","doi":"10.1016/j.pnpbp.2025.111384","DOIUrl":"10.1016/j.pnpbp.2025.111384","url":null,"abstract":"<div><h3>Background</h3><div>Anxiety sensitivity (AS) – the tendency to perceive benign physiological stimuli as harmful – is a risk factor for anxiety disorders. Cross-sectionally, AS has been linked to increased negative &gt; neutral neural activity in key nodes implicated in threat detection and interoceptive – i.e., the amygdala (AMYG) and insula (INS). Examining the unique contributions of AMYG-INS blood‑oxygen-level-dependent (BOLD) response to neutral and negative stimuli to the prospective prediction of AS could increase understanding of the factors predisposing individuals to worsening AS over time.</div></div><div><h3>Methods</h3><div>Forty-six participants, including 33 patients with mixed internalizing disorders, underwent fMRI scans to assess insula and amygdala activation in response to neutral and negative pictures. AS was measured via self-report at baseline (Time 1) and approximately 1.5 years later (Time 2). We assessed whether BOLD to negative and/or neutral pictures at baseline predicted changes in AS over time.</div></div><div><h3>Results</h3><div>Greater insula and amygdala activation in response to neutral pictures at baseline predicted higher AS 1.5 years later, controlling for initial levels of AS and BOLD response to negative pictures. Cross-sectionally, greater insula and amygdala activation in response to negative pictures relative to neutral pictures was associated with higher Time 1 AS.</div></div><div><h3>Conclusions</h3><div>Heightened AMYG-INS BOLD to benign stimuli precedes and may place individuals at risk for increased AS. Once established, heightened AS appears to be characterized by a neural pattern that is more often-observed in the internalizing disorders – i.e., exaggerated response to negative (&gt; neutral) stimuli.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111384"},"PeriodicalIF":5.3,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894410","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":"Infralimbic deep brain stimulation: The impact of frequency and timing on extinction and reinstatement of morphine-seeking behaviors in male rats","authors":"Masoud Seddighfar ,&nbsp;Zahra Bahmani ,&nbsp;Abbas Haghparast","doi":"10.1016/j.pnpbp.2025.111383","DOIUrl":"10.1016/j.pnpbp.2025.111383","url":null,"abstract":"<div><div>Opioid use disorder poses a substantial public health burden. While existing treatments have limitations in achieving long-term abstinence, deep brain stimulation (DBS) emerges as a promising alternative for patients with treatment-refractory addiction. The infralimbic (IL) region has been increasingly recognized by recent studies as a critical brain area involved in addiction, making it a potential target for novel treatments. This study investigates the efficacy of high- and low-frequency DBS within the IL in modulating extinction and reinstatement of morphine-induced conditioned place preference (CPP). After the morphine CPP was established (5 mg/kg; sc), 30-min HFS or LFS session (130 or 10 Hz, 200 μA, 60 μs, respectively) was applied in the IL during two experimental paradigms: daily sessions during the extinction period or a single session prior to the reinstatement test. Following extinction, drug-seeking behavior was reinstated by a morphine priming dose (1 mg/kg; sc). The results indicated that both HFS and LFS during extinction days significantly shortened the extinction duration and prevented the reinstatement of drug-seeking behavior. Furthermore, a single session of DBS prior to priming-dose administration showed that HFS significantly inhibited the reoccurrence of morphine-seeking behavior, while LFS failed to prevent the morphine-primed reinstatement. The results also demonstrated that receiving HFS during the extinction period is more effective in reducing the reinstatement of morphine-seeking behavior compared to that when used in a single session. In conclusion, this research indicates that DBS of the IL can influence addiction-related behaviors across a spectrum of frequencies. Additionally, the therapeutic effectiveness of DBS may vary depending on the timing of its application.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111383"},"PeriodicalIF":5.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890823","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":"Neuroadaptation in neurodegenerative diseases: compensatory mechanisms and therapeutic approaches","authors":"Spandana Rajendra Kopalli ,&nbsp;Tapan Behl ,&nbsp;Lalji Baldaniya ,&nbsp;Suhas Ballal ,&nbsp;Kamal Kant Joshi ,&nbsp;Renu Arya ,&nbsp;Bhumi Chaturvedi ,&nbsp;Ashish Singh Chauhan ,&nbsp;Rakesh Verma ,&nbsp;Minesh Patel ,&nbsp;Sanmati Kumar Jain ,&nbsp;Ankita Wal ,&nbsp;Monica Gulati ,&nbsp;Sushruta Koppula","doi":"10.1016/j.pnpbp.2025.111375","DOIUrl":"10.1016/j.pnpbp.2025.111375","url":null,"abstract":"<div><div>Progressive neuronal loss is a hallmark of neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's, and Amyotrophic Lateral Sclerosis (ALS), which cause cognitive and motor impairment. Delaying the onset and course of symptoms is largely dependent on neuroadaptation, the brain's ability to restructure in response to damage. The molecular, cellular, and systemic processes that underlie neuroadaptation are examined in this study. These mechanisms include gliosis, neurogenesis, synaptic plasticity, and changes in neurotrophic factors. Axonal sprouting, dendritic remodelling, and compensatory alterations in neurotransmitter systems are important adaptations observed in NDDs; nevertheless, these processes may shift to maladaptive plasticity, which would aid in the advancement of the illness. Amyloid and tau pathology-induced synaptic alterations in Alzheimer's disease emphasize compensatory network reconfiguration. Dopamine depletion causes a major remodelling of the basal ganglia in Parkinson's disease, and non-dopaminergic systems compensate. Both ALS and Huntington's disease rely on motor circuit rearrangement and transcriptional dysregulation to slow down functional deterioration. Neuroadaptation is, however, constrained by oxidative stress, compromised autophagy, and neuroinflammation, particularly in elderly populations. The goal of emerging therapy strategies is to improve neuroadaptation by pharmacologically modifying neurotrophic factors, neuroinflammation, and synaptic plasticity. Neurostimulation, cognitive training, and physical rehabilitation are instances of non-pharmacological therapies that support neuroplasticity. Restoring compensating systems may be possible with the use of stem cell techniques and new gene treatments. The goal of future research is to combine biomarkers and individualized medicines to maximize neuroadaptive responses and decrease the course of illness. In order to reduce neurodegeneration and enhance patient outcomes, this review highlights the dual function of neuroadaptation in NDDs and its potential as a therapeutic target.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111375"},"PeriodicalIF":5.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882941","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 the ultrasonic vocalization sequences in pups of an autism spectrum disorder mouse model: A longitudinal study over age and sex","authors":"Swapna Agarwalla ,&nbsp;M.S. Yuvarani ,&nbsp;Sharba Bandyopadhyay","doi":"10.1016/j.pnpbp.2025.111372","DOIUrl":"10.1016/j.pnpbp.2025.111372","url":null,"abstract":"<div><div>Social communication deficit is a hallmark of autism spectrum disorders (ASDs). Mouse ultrasonic-vocalizations (USVs), with communicative significance, are extensively used to probe vocalization-based social communication impairment. Despite the predictable nature of mouse USVs, very few studies have taken advantage of the same. The current work explores USV pup-isolation-call (PIC) features and alterations in structural content of predictive PIC sequences of the well-established in-utero valproic-acid (VPA) exposure-based ASDs model. Our study shows that along with call features, even higher-order USV structures undergo alterations in the ASDs model at all developmental ages and sexes. Confirming prior observations, we found reduced call rates and durations, as well as heightened peak frequencies in ASD model pups. Our data also highlights trends in call features, syllable composition, and transitions across sexes and age. The ASD female mice exhibited higher within group heterogeneity in syllable composition and transition over age compared to ASD males or typically developing males and females. Analysis of sequences of USVs emitted by pups using mutual information between syllables at different positions revealed that dependencies between syllables were higher in typically developing mice of both sexes compared to ASD model pups. In brief, we found that PICs call features were altered in VPA mouse models both for male and female pups and their vocalizations lack the complex syllable sequence order emitted by typically developing ones. Our studies will help establish and further investigate ASD mouse models to get a clearer picture of abnormalities related to social communication deficits over sexes and age.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111372"},"PeriodicalIF":5.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863917","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":"Dietary inflammatory index during pregnancy and its relationship with gyrification and IQ in young adult offspring","authors":"Klara Mareckova ,&nbsp;Lada Holland ,&nbsp;Radek Marecek ,&nbsp;Lenka Andryskova ,&nbsp;Milan Brazdil ,&nbsp;Samantha Dawson ,&nbsp;Yuliya S. Nikolova","doi":"10.1016/j.pnpbp.2025.111373","DOIUrl":"10.1016/j.pnpbp.2025.111373","url":null,"abstract":"<div><div>Maternal diet during pregnancy has been associated with brain development and cognitive function in offspring, but the mechanisms mediating these relationships remain poorly understood. We conducted a longitudinal neuroimaging follow-up of a prenatal birth cohort and used Food Frequency Questionnaires completed by the mother in mid-pregnancy to calculate prenatal Dietary Inflammatory Index (DII) and tested its relationship with brain gyrification, an index of early brain development, and IQ in young adults (<em>n</em> = 179, age 28–30). The longitudinal gyrification data were available for a subset of these individuals (<em>n</em> = 77, age 23–24). A higher maternal pro-inflammatory diet during pregnancy, as represented by higher DII, was associated with worse verbal IQ but not performance IQ in young adulthood. These findings were independent of sex and remained significant after adjusting for maternal education, maternal stressful life events during pregnancy, maternal smoking during pregnancy, prenatal supplements (e.g. folic acid, iron, zinc, calcium, vitamins), and maternal age at birth. Moreover, higher DII was associated with altered cortical gyrification in the early as well as the late 20, particularly in men. Gyrification of the anterior middle and inferior frontal gyrus mediated the relationship between prenatal DII and verbal IQ in young adulthood. These findings support the use of cortical gyrification as a proxy marker of early brain development and suggest it may underlie the relationship between maternal diet during pregnancy and its long-term impact on cognitive skills in offspring. They also have important implications for pregnant women who might be able to optimize the brain development and verbal IQ of their children through an anti-inflammatory diet.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111373"},"PeriodicalIF":5.3,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859895","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":"Disrupted interhemispheric functional and structural connectivity in patients with major depressive disorder","authors":"Qianqian Li ,&nbsp;Li Qi ,&nbsp;Gu Zhang ,&nbsp;Jiajia Hao ,&nbsp;Qiufang Ren ,&nbsp;Jian Guan ,&nbsp;Yuqian Zhan ,&nbsp;Yue Yu ,&nbsp;Jinying Yang ,&nbsp;Kai Wang ,&nbsp;Tongjian Bai","doi":"10.1016/j.pnpbp.2025.111374","DOIUrl":"10.1016/j.pnpbp.2025.111374","url":null,"abstract":"<div><h3>Background</h3><div>Major depressive disorder (MDD) is associated with disrupted interhemispheric cooperation. However, the relationship between structural and functional alterations in interhemispheric cooperation in patients with MDD remains unclear. We investigated the associations between voxel-mirrored homotopic connectivity (VMHC) and radial diffusivity (RD) within the corpus callosum (CC) and their links to depressive symptoms in patients with MDD.</div></div><div><h3>Methods</h3><div>Sixty patients with MDD and 38 healthy controls (HCs) were assessed using resting-state functional MRI (rs-fMRI) and diffusion MRI (dMRI) to evaluate interhemispheric functional connectivity (VMHC) and structural integrity (RD) in the CC subregions. Group comparisons, correlation analyses, and mediation analyses were conducted to identify the significant differences, relationships, and indirect effects.</div></div><div><h3>Results</h3><div>Patients with MDD showed significantly reduced VMHC in the bilateral postcentral gyrus and lingual gyrus and increased RD in the CC subregions CC3, CC4, and CC5, indicating impaired functional and structural connectivity. Lower VMHC in the lingual gyrus was negatively correlated with depressive severity, whereas increased RD in the CC4 and CC5 was positively correlated with depressive symptoms. Mediation analysis revealed that the VMHC in the lingual gyrus fully mediated the relationship between RD in CC5 and depressive symptoms, suggesting a pathway through which structural impairments may affect mood through abnormal functional connectivity.</div></div><div><h3>Limitations</h3><div>The cross-sectional design limits the assessment of changes over time, and focusing solely on interhemispheric connectivity may overlook other networks involved in MDD.</div></div><div><h3>Conclusion</h3><div>These findings provide preliminary evidence for disrupted interhemispheric coordination in MDD, with both functional and structural connectivity impairments linked to depressive symptoms. The mediating effect of the VMHC in the lingual gyrus highlights the potential role of interhemispheric connectivity in the pathophysiology of MDD. Our results provide an integrative perspective on the functional and microstructural organization of the brain in patients with MDD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111374"},"PeriodicalIF":5.3,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878595","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":"Tactile stimulation ameliorates haloperidol-induced movement disturbances in rats by promoting neuromodulation on dopaminergic and glutamatergic systems in nigrostriatal brain area","authors":"J.L.O. Rosa ,&nbsp;P. Brivio ,&nbsp;D.R. Rossato ,&nbsp;M.B. Fontoura ,&nbsp;L.E.M. Souza ,&nbsp;F. Fumagalli ,&nbsp;F. Calabrese ,&nbsp;M.E. Burger","doi":"10.1016/j.pnpbp.2025.111376","DOIUrl":"10.1016/j.pnpbp.2025.111376","url":null,"abstract":"<div><div>The antipsychotic haloperidol (HAL) primarily antagonizes dopaminergic type-2 receptors. It is known that antipsychotic treatment are commonly related with extrapyramidal syndrome (EPS), which involves movement disorders such as parkinsonism, akathisia and tardive dyskinesia. Tactile stimulation (TS) has been helpful in animal models of drug abuse and depression, raising our interest in evaluating its possible benefits on extrapyramidal HAL-induced side-effects in male adult rats. Subsequently to a sub-chronic model of EPS, TS reversed orofacial dyskinesia and movement impairments induced by HAL and promoted beneficial modulations on dopaminergic and glutamatergic systems in nigrostriatal brain area. Given these outcomes, it is important to consider that: i) TS can help to control and/or reduce movement disorders consequent to antipsychotic treatment; ii) TS can help to better clarify the imbalanced of dopaminergic system haloperidol promotes. Based on our current and previous studies about the benefits of TS, we hypothesize that the TS may represent an important therapeutic target to treat neuromotor disorders originating in the nigrostriatal system.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111376"},"PeriodicalIF":5.3,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868518","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 volume of thalamic nuclei and genetic expression in first-episode psychotic patients, and their association with childhood adversity","authors":"Uriel K.A. Elvira ,&nbsp;Olga Rivero ,&nbsp;Alba Postiguillo ,&nbsp;Gracian García-Marti ,&nbsp;Maria Jose Escarti ,&nbsp;Eduardo J. Aguilar ,&nbsp;Javier David-Lluesma ,&nbsp;Maria Dolores Molto ,&nbsp;Marta Perez-Rando ,&nbsp;Juan Nacher","doi":"10.1016/j.pnpbp.2025.111371","DOIUrl":"10.1016/j.pnpbp.2025.111371","url":null,"abstract":"<div><div>Childhood maltreatment is a significant risk factor for schizophrenia, and there are correlations between these adversities and thalamic gray matter density. The thalamus, a subcortical structure with various nuclei with specific connections, relays sensory information and participates in higher cognitive processes. Thalamic alterations are evident in psychotic disorders, and early-life adversities may affect its development, potentially contributing to psychosis. However, no evidence exists of volumetric alterations in thalamic nuclei in first-episode psychosis (FEP) patients related to early traumatic events. This study recruited 70 FEP patients and 68 age-matched healthy controls, who underwent 3 T structural MRI and clinical scales, including the Childhood Trauma Questionnaire (CTQ). The thalamus was analyzed for shape and segmented into nuclei to assess volume. Additionally, peripheral blood was analyzed for the expression of <em>VCAN, CSGALNACT1, ST8SIA4, NRGN, SP4,</em> and <em>TOX</em> genes, which are related to neuronal plasticity in the thalamus and psychosis. Results showed volumetric reductions in the whole thalamus and specific nuclei (lateral posterior, lateral geniculate, medial geniculate, ventrolateral, centromedian, anteroventral, mediodorsal, and pulvinar). The thalamus did not show shape alterations. A significant association was observed between physical neglect during childhood and the volume of the left thalamus and its anteroventral nucleus. Reduced expression of <em>ST8SIA4</em> and <em>SP4</em> genes was detected in FEP patients compared to healthy controls, with correlations between thalamic nuclei volumes and gene expression differing between groups. In conclusion, this study links thalamic nuclei volume with childhood adversities in FEP and highlights changes in <em>ST8SIA4</em> and <em>SP4</em> expression, correlating with thalamic nuclei volumes.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111371"},"PeriodicalIF":5.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859819","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}