Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Common neural correlates of chronic pain – A systematic review and meta-analysis of resting-state fMRI studies","authors":"Juliana Fiúza-Fernandes ,&nbsp;Joana Pereira-Mendes ,&nbsp;Madalena Esteves ,&nbsp;Joaquim Radua ,&nbsp;Maria Picó-Pérez ,&nbsp;Hugo Leite-Almeida","doi":"10.1016/j.pnpbp.2025.111326","DOIUrl":"10.1016/j.pnpbp.2025.111326","url":null,"abstract":"<div><div>Maladaptive brain plasticity has been reported in chronic pain (CP) conditions, though it remains unclear if there are common alterations across pathologies. Therefore, we systematically synthesized literature comparing resting-state functional magnetic resonance imaging (rs-fMRI) in CP patients and healthy controls (HC), and meta-analyzed data whenever applicable. Separate meta-analyses were performed for each method – (fractional) amplitude of low-frequency fluctuations (fALFF, ALFF), regional homogeneity (ReHo), seed-based connectivity (according to the seed) and independent component analysis (according to the network). In qualitative synthesis, sensory-discriminative pain processing – thalamus, insula, temporal and sensory cortices – and cognitive and emotional processing – cingulate, prefrontal and parietal cortices and precuneus – regions concentrated CP/HC differences. Meta-analyses revealed decreased ALFF and increased ReHo in the precuneus, increased fALFF in the left posterior insula and disrupted within- and cross-network connectivity of default mode network (DMN) nodes, as well as altered connectivity in top-down pain modulation pathways. Specifically, it showed decreased anterior and increased posterior components' representation within DMN, enhanced connectivity between the medial prefrontal cortex (mPFC, part of the DMN) and anterior insula (part of the salience network), and decreased mPFC connectivity with the periaqueductal gray matter (PAG). Collectively, results suggest that CP disrupts the natural functional organization of the brain, particularly impacting DMN nodes (mPFC and precuneus), insula and top-town pain modulation circuits.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111326"},"PeriodicalIF":5.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyroptosis; igniting neuropsychiatric disorders from mild depression to aging-related neurodegeneration","authors":"Kiavash Hushmandi ,&nbsp;Russel J. Reiter ,&nbsp;Najma Farahani ,&nbsp;William C. Cho ,&nbsp;Mina Alimohammadi ,&nbsp;Seyedeh Mahdieh Khoshnazar","doi":"10.1016/j.pnpbp.2025.111325","DOIUrl":"10.1016/j.pnpbp.2025.111325","url":null,"abstract":"<div><div>Neuropsychiatric disorders significantly impact global health and socioeconomic well-being, highlighting the urgent need for effective treatments. Chronic inflammation, often driven by the innate immune system, is a key feature of many neuropsychiatric conditions. NOD-like receptors (NLRs), which are intracellular sensors, detect danger signals and trigger inflammation. Among these, NLR protein (NLRP) inflammasomes play a crucial role by releasing pro-inflammatory cytokines and inducing a particular cell death process known as pyroptosis. Pyroptosis is defined as a proinflammatory form of programmed cell death executed by cysteine-aspartic proteases, also known as caspases. Currently, the role of pyroptotic flux has emerged as a critical factor in innate immunity and the pathogenesis of multiple diseases. Emerging evidence suggests that the induction of pyroptosis, primarily due to NLRP inflammasome activation, is involved in the pathophysiology of various neuropsychiatric disorders, including depression, stress-related issues, schizophrenia, autism spectrum disorders, and neurodegenerative diseases. Within this framework, the current review explores the complex relationship between pyroptosis and neuropsychiatric diseases, aiming to identify potential therapeutic targets for these challenging conditions.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111325"},"PeriodicalIF":5.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620291","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":"Exploring the causal relationship between delirium and sarcopenia using bidirectional two-sample Mendelian randomization study","authors":"Rui Zhou ,&nbsp;Yumeng Fu ,&nbsp;Peiling Wan,&nbsp;Baoli Cheng","doi":"10.1016/j.pnpbp.2025.111327","DOIUrl":"10.1016/j.pnpbp.2025.111327","url":null,"abstract":"<div><h3>Background</h3><div>Population-based studies have validated the significant associations between delirium and sarcopenia. Nonetheless, the causality remains ambiguous. This study aims to elucidate the causal associations between delirium and sarcopenia, as well as the causal effects of medication use on both conditions.</div></div><div><h3>Methods</h3><div>A bidirectional two-sample Mendelian randomization (MR) analysis was performed based on public genome-wide association studies (GWAS) data. Causal effects were evaluated through the inverse-variance weighted (IVW) method as the principal analysis, supplemented by the weighted median, weighted mode. Cochran's Q test, MR-Egger regression, MR-PRESSO test and leave-one-out were applied for sensitivity analyses.</div></div><div><h3>Results</h3><div>The IVW method indicated a causal relationship between genetically predicted low hand-grip strength and delirium (OR = 1.31, 95 % CI: 1.02–1.67, <em>P</em> = 0.032). Additionally, diuretics (OR = 1.05, 95 % CI: 1.03–1.07, <em>P</em> &lt; 0.001) and glucocorticoids (OR = 1.06, 95 % CI: 1.01–1.12, <em>P</em> = 0.012) were causally associated with appendicular lean mass, and diabetes medications (OR = 1.04, 95 % CI: 1.02–1.06, <em>P</em> = 0.001) and immunosuppressants (OR = 1.05, 95 % CI: 1.02–1.09, <em>P</em> = 0.005) causally associated with low hand-grip strength. Alternative analytic methods yielded consistent results. Heterogeneity and horizontal pleiotropy were evident in associations between medication use and both delirium and sarcopenia, but the results remained consistent after excluding outliers.</div></div><div><h3>Conclusion</h3><div>This study provided evidence of a causal relationship between genetically predicted low hand-grip strength and delirium. However, the analysis revealed that medication use did not appear to act as a mediating factor between these two conditions. Larger population-based studies are needed to validate these findings.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111327"},"PeriodicalIF":5.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620290","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":"Age-related abnormalities in brain functional and molecular neuroimaging signatures in first-episode depression","authors":"Yu Jiang ,&nbsp;Yuan Chen ,&nbsp;Ruiping Zheng ,&nbsp;Bingqian Zhou ,&nbsp;Ying Wei ,&nbsp;Shuying Li ,&nbsp;Shaoqiang Han ,&nbsp;Yong Zhang ,&nbsp;Jingliang Cheng","doi":"10.1016/j.pnpbp.2025.111330","DOIUrl":"10.1016/j.pnpbp.2025.111330","url":null,"abstract":"<div><div>Abnormalities in resting-state brain activity have been demonstrated in depression patients with different ages, yet the age-related changes in dynamics of brain activity in depression are still limited. Here, we investigated the impacts of age on dynamics of brain activity and the molecular architecture. Resting-state functional magnetic resonance images were obtained from 138 first-episode depression patients and 120 healthy volunteers. All the participants were classified into two age cohorts, including adolescents and adults. Two-way analysis of variance was performed to examine the effect of age on dynamic amplitude of low-frequency fluctuations (ALFF) in depression. Then, cross-modal correlation analyses between dynamic ALFF and neurotransmitter maps were established. Significant diagnosis-by-age interaction of dynamic ALFF was located in medial frontal gyrus, supplementary motor area, postcentral gyrus, paracentral lobule and rolandic operculum. Dynamic ALFF alterations in the diagnosis-by-age interaction effect were associated with serotonergic, dopaminergic, noradrenergic, and GABAergic systems. These findings highlight the interaction between depression and age in brain functional and molecular neuroimaging signatures, which may be useful for future treatment strategies of different ages of depression.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111330"},"PeriodicalIF":5.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620289","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":"Integrated genetic analysis and single cell-RNA sequencing for brain image-derived phenotypes and Parkinson's disease","authors":"Lin Pan ,&nbsp;Laiyu Yang ,&nbsp;Weijie Ding ,&nbsp;Yongfei Hu ,&nbsp;Wenzhuo Yang ,&nbsp;Jingning Wang ,&nbsp;Zhiyun Zhang ,&nbsp;Kangli Fan ,&nbsp;Zhihui Sun ,&nbsp;Yue Liang ,&nbsp;Xiaoyue Lin ,&nbsp;Jun Chen ,&nbsp;Ying Zhang","doi":"10.1016/j.pnpbp.2025.111317","DOIUrl":"10.1016/j.pnpbp.2025.111317","url":null,"abstract":"<div><h3>Background</h3><div>Previous studies have reported Parkinson's disease (PD) patients usually have changes in brain image-derived phenotypes (IDPs). However, the role of genetic factors in their association and biological mechanism remains unclear. We aimed to unveil genetic and biological links between brain IDPs and PD.</div></div><div><h3>Methods</h3><div>Using genome-wide association study (GWAS) summary statistics and single-cell RNA sequencing (scRNA-seq) data, we performed a comprehensive analysis between 624 brain IDPs and PD. The genetic correlations and causality were examined by linkage disequilibrium score regression (LDSC), two-sample bidirectional Mendelian randomization (MR) and meta-analysis. Potential shared genes were identified using MAGMA and PLACO. Finally, pathway enrichment using FUMA and Metascape, and scRNA-seq analysis were performed to determine biological mechanisms and gene expression atlas across various cell types in brain tissue.</div></div><div><h3>Results</h3><div>LDSC revealed that 50 brain IDPs were genetically correlated with PD (<em>P</em> &lt; 0.05), in which 5 IDPs, exhibited putative causality on PD through MR (<em>P</em> &lt; 0.05). For instance, we identified that the increased volume of the right thalamus (IVW: OR = 2.08, 95 % CI: 1.33 to 3.25, <em>PFDR</em> = 0.03) was positively correlated with the risk of PD, which was also supported by replicated MR (IVW: OR = 1.63, 95 % CI: 1.17–2.26, <em>PFDR</em> = 0.02) in FinnGen and meta-analysis (OR = 1.78, 95 % CI: 1.36–2.31, <em>PFDR</em> = 5.00 × 10⁻⁴). Additionally, we identified 56 unique pleiotropic genes, such as FAM13A, with notable enrichment in neuronal cells. Biological mechanism analysis revealed these genes were enriched in brain tissues and a variety of pathways such as negative regulation of neuron apoptotic processes.</div></div><div><h3>Conclusion</h3><div>We indicated the shared genetic architecture and biological mechanisms between brain IDPs and PD. These findings might provide insights on the therapeutic intervention and early prediction of PD at the brain imaging level.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111317"},"PeriodicalIF":5.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurovascular coupling alterations related to cognitive impairment in cerebral small vessel disease: A multiscale brain network perspective","authors":"Ying Hu ,&nbsp;Yage Qiu ,&nbsp;Yuewei Chen ,&nbsp;Yuanzheng Wang ,&nbsp;Yongming Dai ,&nbsp;Qun Xu ,&nbsp;Yan Zhou","doi":"10.1016/j.pnpbp.2025.111311","DOIUrl":"10.1016/j.pnpbp.2025.111311","url":null,"abstract":"<div><div>Evidence suggests that neurovascular coupling (NVC) dysfunction in cerebral small vessel disease (CSVD) may precede typical clinical and imaging manifestations. Here, we explored the underlying brain alterations of multiscale networks in CSVD patients related to cognitive impairment based on the method of NVC. We investigated 124 CSVD patients, including 70 patients with mild cognitive impairment (MCI) and 54 patients with no cognitive impairment (NCI). Functional MRI and arterial spin labeling were employed to estimate the coupling of spontaneous neuronal activity and cerebral blood perfusion based on the regional homogeneity and cerebral blood flow at the whole-brain, modular, and regional levels. We showed that the NVC of the dorsal attention network (DOR), ventral attention network (VEN) and default mode network (DMN) in the MCI were significantly lower than those in the NCI. The NVC of the DOR, VEN, and DMN in the NCI group exhibited correlations with the executive function. Furthermore, mediation effect of CSVD lesion load was observed for the association between NVC alterations and cognitive function. The abnormal NVC features achieved effective classification performance for MCI and NCI. These findings underscore the significance of specific modular and regional NVC dysfunction in the cognitive outcomes of CSVD. This study revealed the potential of NVC as a focal point for future research on cognitive impairment in CSVD, particularly from the perspective of multiscale brain network analysis.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111311"},"PeriodicalIF":5.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588252","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":"Exploring the combined effects of serum tumor necrosis factor-alpha and serotonin on antidepressant efficacy in depression: A 12-week prospective analysis","authors":"Jae-Min Kim ,&nbsp;Hee-Ju Kang ,&nbsp;Ju-Wan Kim,&nbsp;Ha-Yeon Kim,&nbsp;Min Jhon,&nbsp;Ju-Yeon Lee,&nbsp;Sung-Wan Kim,&nbsp;Il-Seon Shin","doi":"10.1016/j.pnpbp.2025.111328","DOIUrl":"10.1016/j.pnpbp.2025.111328","url":null,"abstract":"<div><h3>Background</h3><div>This study investigated the interplay between serum tumor necrosis factor-alpha (sTNF-α) and serotonin (s5-HT) levels in predicting 12-week antidepressant treatment outcomes among patients with depressive disorders.</div></div><div><h3>Methods</h3><div>We analyzed baseline sTNF-α and s5-HT levels in 1086 patients enrolled in a naturalistic study of stepwise antidepressant treatment. Remission was defined as achieving a Hamilton Depression Rating Scale score of 7 or less at 12 weeks. Logistic regression analyses adjusted for sociodemographic and clinical covariates were utilized to explore the relationships between biomarker levels and treatment outcomes.</div></div><div><h3>Results</h3><div>Elevated sTNF-α levels were significantly associated with non-remission at 12 weeks in patients with lower s5-HT levels. Conversely, in patients with higher s5-HT levels, sTNF-α levels did not show a significant association with remission outcomes. The interaction between sTNF-α and s5-HT levels significantly predicted remission status even after adjusting for potential confounders.</div></div><div><h3>Conclusions</h3><div>The findings suggest that the combined assessment of immune and serotonergic biomarkers can enhance the prediction of antidepressant treatment outcomes. This underscores the potential of integrating biomarker profiles to tailor antidepressant strategies, thereby advancing personalized treatment approaches in depression. Future studies should explore the underlying mechanisms of these interactions to better understand their role in treatment responsiveness.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111328"},"PeriodicalIF":5.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598150","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":"Integrative bioinformatics analysis reveals mitochondrial-Immune crosstalk in depression and stroke: a multi-omics mechanistic exploration","authors":"Xijuan Xia ,&nbsp;Yue Yu ,&nbsp;Yun Liu ,&nbsp;Kehan Yan ,&nbsp;Hu Xu ,&nbsp;Yang Ji ,&nbsp;Xiaolan Zhu ,&nbsp;Yuefeng Li","doi":"10.1016/j.pnpbp.2025.111308","DOIUrl":"10.1016/j.pnpbp.2025.111308","url":null,"abstract":"<div><div>Stroke, a leading cause of disability and mortality globally, often cooccurs with depression or poststroke depression (PSD). The intricate interplay between mitochondrial metabolism and immune-related inflammation in depression and stroke remains a pivotal yet unresolved area. This study harnessed bioinformatics to elucidate the distinct contributions of mitochondrial metabolism and the immune microenvironment, as well as their complex interactions, to the pathogenesis of depression and stroke. By analyzing gene expression profiles from depression and stroke datasets alongside mitochondrial gene data, differentially expressed genes (DEGs) were meticulously identified, with a particular focus on mitochondria-related DEGs (MitoDEGs). Comprehensive functional investigations of common DEGs were conducted through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A robust protein–protein interaction (PPI) network was constructed, pinpointing ten hub-MitoDEGs intricately linked to depression and stroke. Furthermore, leveraging single-cell RNA sequencing analysis has shed light on gene expression across a myriad of cell types. Notably, these findings demonstrated immune cell dysregulation, revealing significant alterations in neutrophil and CD8+ T-cell infiltration within both the depression and stroke contexts. Correlation analyses revealed profound associations of the hub-MitoDEGs with mitochondrial metabolism, immune-related genes, and immunocytes. Importantly, this study also delineated ten potential drugs that target key genes implicated in depression and stroke, identifying promising avenues for innovative therapeutic interventions in these debilitating disorders.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111308"},"PeriodicalIF":5.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588280","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":"Persistent behavioural consequences of chronic adolescent cannabidiol (CBD) in a mouse model with increased susceptibility to Δ9-tetrahydrocannabinol and schizophrenia","authors":"Gabriela Visini,&nbsp;Rose Chesworth ,&nbsp;Tim Karl","doi":"10.1016/j.pnpbp.2025.111306","DOIUrl":"10.1016/j.pnpbp.2025.111306","url":null,"abstract":"<div><div>Increasingly, the <em>cannabis sativa</em> plant compound cannabidiol (CBD) is used to treat various psychiatric and neurological health conditions which occur in early life or adolescence, including schizophrenia and autism spectrum disorder. However, behavioural effects CBD during adolescence have received limited attention, and the long-lasting behavioural consequences of adolescent CBD treatment are unknown. Thus, this study investigated the effects of chronic CBD in adolescence on behaviours in adulthood, in a mouse model of susceptibility to cannabinoid drugs and schizophrenia, i.e. <em>Neuregulin 1 transmembrane domain</em> heterozygous (<em>Nrg1 TM</em> HET) and wildtype-like (WT) controls. We also assessed if adolescent CBD may affect behavioural responses to acute low dose Δ⁹-tetrahydrocannabinol (THC) in adulthood. Male <em>Nrg1 TM</em> HET mice and WT controls were administered 30 mg/kg CBD daily intraperitoneally for 3 weeks in adolescence, and then at 5–6 months of age were tested for locomotion, social behaviour, sensorimotor gating and cognition, as well as sensitivity to acute THC-induced behaviours. Adolescent CBD supressed locomotion, exploration, and social behaviours, and reduced anxiety-like behaviours in adult mice. An acute THC challenge in adulthood suppressed social behaviours and acoustic startle in all mice, and adolescent CBD exacerbated THC-induced suppression of acoustic startle in <em>Nrg1</em> mutant mice. CBD did not alter schizophrenia-relevant behaviours in <em>Nrg1 TM</em> HET mice. To conclude, adolescent CBD exposure had persistent effects on behavioural domains in adulthood including anxiety, locomotion and social behaviours. Furthermore, CBD exposure early in life affected behavioural responses to acute THC in the presence of a risk gene which enhances cannabinoid sensitivity.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111306"},"PeriodicalIF":5.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588274","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":"Fear conditioning: Insights into learning, memory and extinction and its relevance to clinical disorders","authors":"Simon Trent ,&nbsp;Muhammad Hazim Abdullah ,&nbsp;Krishma Parwana ,&nbsp;Maria Alcocer Valdivieso ,&nbsp;Zurina Hassan ,&nbsp;Christian P. Müller","doi":"10.1016/j.pnpbp.2025.111310","DOIUrl":"10.1016/j.pnpbp.2025.111310","url":null,"abstract":"<div><div>Fear, whether innate or learned, is an essential emotion required for survival. The learning, and subsequent memory, of fearful events enhances our ability to recognise and respond to threats, aiding adaptation to new, ever-changing environments. Considerable research has leveraged associative learning protocols such as contextual or auditory forms of fear conditioning in rodents, to understand fear learning, memory consolidation and extinction phases of memory. Such assays have led to detailed characterisation of the underlying neurocircuitry and neurobiology supporting fear learning processes. Given fear processing is conserved across rodents and humans, fear conditioning experiments provide translational insights into fundamental memory processes and fear-related pathologies. This review examines associative learning protocols used to measure fear learning, memory and extinction, before providing an overview on the underlying complex neurocircuitry including the amygdala, hippocampus and medial prefrontal cortex. This is followed by an in-depth commentary on the neurobiology, particularly synaptic plasticity mechanisms, which regulate fear learning, memory and extinction. Next, we consider how fear conditioning assays in rodents can inform our understanding of disrupted fear memory in human disorders such as post-traumatic stress disorder (PTSD), anxiety and psychiatric disorders including schizophrenia. Lastly, we critically evaluate fear conditioning protocols, highlighting some of the experimental and theoretical limitations and the considerations required when conducting such assays, alongside recent methodological advancements in the field. Overall, rodent-based fear conditioning assays remain central to making progress in uncovering fundamental memory phenomena and understanding the aetiological mechanisms that underpin fear associated disorders, alongside the development of effective therapeutic strategies.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111310"},"PeriodicalIF":5.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}