Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"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}

{"title":"Pharmacogenetics of obsessive-compulsive disorder: Investigations of intragenic and regulatory region genetic variations","authors":"Gwyneth Zai ,&nbsp;Clement C. Zai ,&nbsp;Vanessa F. Gonçalves ,&nbsp;Karen Wigg ,&nbsp;Christine Lochner ,&nbsp;Dan J. Stein ,&nbsp;Carol A. Mathews ,&nbsp;James L. Kennedy ,&nbsp;Margaret A. Richter","doi":"10.1016/j.pnpbp.2025.111315","DOIUrl":"10.1016/j.pnpbp.2025.111315","url":null,"abstract":"<div><div>Few pharmacogenetic studies on the use of genetic variations to predict antidepressant response in obsessive-compulsive disorder (OCD) have been published. This study expanded on the limited literature on single nucleotide polymorphisms (SNPs) across previously identified putative susceptibility genes for OCD, by incorporating known functional regulatory elements for all genes of interest. We investigated 17 SNPs in 12 genes implicated in OCD risk in 206 European ancestry OCD patients with selective serotonin reuptake inhibitor (SSRI) antidepressant response data, examining functional polymorphisms in remote regulatory regions. No association was observed between any regulatory region markers tested and drug response. We observed nominally significant associations between SNPs within the serotonin 1B receptor (<em>5HT1B</em>; SNP rs1778258), SLIT and NTRK-like family member 5 (<em>SLITRK5</em>; SNP rs10450811), and fas apoptotic inhibitory molecule 2 (<em>FAIM2</em>; SNP rs706795), with response to any SSRI, which did not survive multiple comparisons. This study supports a potential role for a number of OCD-associated risk genes in response to antidepressant treatment, warranting further investigation.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111315"},"PeriodicalIF":5.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588277","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":"Snapshot of disease continuum centered on Alzheimer's disease: Exploring modifiable risk factors","authors":"Ming Zheng MD, PhD","doi":"10.1016/j.pnpbp.2025.111316","DOIUrl":"10.1016/j.pnpbp.2025.111316","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a leading neurodegenerative disorder, characterized by progressive cognitive decline and memory impairment, with a complex etiology involving genetic, environmental, and lifestyle factors. Traditionally, AD has been studied in isolation, but emerging evidence highlights its interconnectedness with various comorbidities across multiple organ systems. This study introduces a Disease-Wide Association Study (DWAS) approach to explore the disease continuum centered around AD. Using the FinnGen cohort, which includes over 392,000 participants, this study systematically analyzed the comorbidities associated with AD, spanning cardiovascular, metabolic, musculoskeletal, digestive, and oncological conditions. These findings reveal that AD is part of a much broader, systemic disease continuum, with shared pathophysiological mechanisms, including chronic inflammation, metabolic dysregulation, and vascular health, which may influence AD onset and progression. Temporal analysis of pre- and post-AD comorbidities identifies modifiable risk factors such as hypertension, atherosclerosis, and type 2 diabetes that may not only precede AD but also exacerbate its progression. The study emphasizes the importance of an integrated care approach for AD patients, addressing both neurological and systemic health to improve outcomes. Furthermore, by identifying modifiable risk factors, this research opens new avenues for early interventions aimed at delaying or preventing AD. These findings challenge the traditional view of AD as an isolated disease and provide insights into the shared etiology of AD and its comorbidities, offering potential targets for personalized therapeutic strategies and public health policies.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111316"},"PeriodicalIF":5.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580268","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":"Noradrenergic modulation of stress induced catecholamine release: Opposing influence of FG7142 and yohimbine","authors":"Vladimir Visocky,&nbsp;Carleigh J. Turner,&nbsp;Matthew H. Lowrie,&nbsp;Anthony Alibro,&nbsp;Fany Messanvi,&nbsp;Yogita Chudasama","doi":"10.1016/j.pnpbp.2025.111314","DOIUrl":"10.1016/j.pnpbp.2025.111314","url":null,"abstract":"<div><div>Life stress modulates decision making, particularly in the face of risk, in some cases prompting vulnerable populations to make suboptimal, life-altering choices. In the brain, stress is known to alter the extracellular release of catecholamines in structures such as basolateral amygdala (BLA) and nucleus accumbens (NAc), but the relationship between catecholamines and decision-making behavior under stress has not been systemically explored. We developed an operant touchscreen decision-making task for rats comprising elements of loss aversion and risk seeking behavior. Rats were first injected systemically with an adrenergic α_2A-receptor agonist (guanfacine) and antagonist (yohimbine), as well as a partial inverse GABA_A agonist, FG 7142, known to induce anxiety and stress related physiological responses in a variety of species, including humans. We then used fiber photometry to monitor NE in the basolateral amygdala (BLA), and DA activity in the nucleus accumbens (NAc) while animals engaged in decision-making and following systemic injections of FG 7142 and yohimbine. We found that neither yohimbine nor guanfacine had any impact on decision making strategy but altered motivational state with yohimbine making the animal almost insensitive to the reward outcome. The pharmacological induction of stress with FG 7142 biased the rats' decisions towards safety, but this bias shifted towards risk when co-treated with yohimbine. In the BLA and NAc, FG 7142 altered catecholamine release with systemic yohimbine producing opposing effects on NE and DA release. These findings highlight the catecholamine basis of loss aversion and neuromodulation of critical brain structures during stress through α2_A adrenoreceptors.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111314"},"PeriodicalIF":5.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588255","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}