Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献_第2页

Integrative bioinformatics analysis reveals mitochondrial-Immune crosstalk in depression and stroke: a multi-omics mechanistic exploration

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-03-08 DOI: 10.1016/j.pnpbp.2025.111308

Xijuan Xia , Yue Yu , Yun Liu , Kehan Yan , Hu Xu , Yang Ji , Xiaolan Zhu , Yuefeng Li

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.

{"title":"Integrative bioinformatics analysis reveals mitochondrial-Immune crosstalk in depression and stroke: a multi-omics mechanistic exploration","authors":"Xijuan Xia , Yue Yu , Yun Liu , Kehan Yan , Hu Xu , Yang Ji , Xiaolan Zhu , 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}

引用次数: 0

Persistent behavioural consequences of chronic adolescent cannabidiol (CBD) in a mouse model with increased susceptibility to Δ9-tetrahydrocannabinol and schizophrenia

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-03-07 DOI: 10.1016/j.pnpbp.2025.111306

Gabriela Visini, Rose Chesworth , Tim Karl

Increasingly, the cannabis sativa 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. Neuregulin 1 transmembrane domain heterozygous (Nrg1 TM 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 Nrg1 TM 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 Nrg1 mutant mice. CBD did not alter schizophrenia-relevant behaviours in Nrg1 TM 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.

{"title":"Persistent behavioural consequences of chronic adolescent cannabidiol (CBD) in a mouse model with increased susceptibility to Δ9-tetrahydrocannabinol and schizophrenia","authors":"Gabriela Visini, Rose Chesworth , 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 Δ<sup>9</sup>-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}

引用次数: 0

Fear conditioning: Insights into learning, memory and extinction and its relevance to clinical disorders

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-03-06 DOI: 10.1016/j.pnpbp.2025.111310

Simon Trent , Muhammad Hazim Abdullah , Krishma Parwana , Maria Alcocer Valdivieso , Zurina Hassan , Christian P. Müller

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.

{"title":"Fear conditioning: Insights into learning, memory and extinction and its relevance to clinical disorders","authors":"Simon Trent , Muhammad Hazim Abdullah , Krishma Parwana , Maria Alcocer Valdivieso , Zurina Hassan , 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}

引用次数: 0

Pharmacogenetics of obsessive-compulsive disorder: Investigations of intragenic and regulatory region genetic variations

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-03-05 DOI: 10.1016/j.pnpbp.2025.111315

Gwyneth Zai , Clement C. Zai , Vanessa F. Gonçalves , Karen Wigg , Christine Lochner , Dan J. Stein , Carol A. Mathews , James L. Kennedy , Margaret A. Richter

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 (5HT1B; SNP rs1778258), SLIT and NTRK-like family member 5 (SLITRK5; SNP rs10450811), and fas apoptotic inhibitory molecule 2 (FAIM2; 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.

{"title":"Pharmacogenetics of obsessive-compulsive disorder: Investigations of intragenic and regulatory region genetic variations","authors":"Gwyneth Zai , Clement C. Zai , Vanessa F. Gonçalves , Karen Wigg , Christine Lochner , Dan J. Stein , Carol A. Mathews , James L. Kennedy , 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}

引用次数: 0

Snapshot of disease continuum centered on Alzheimer's disease: Exploring modifiable risk factors

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-03-05 DOI: 10.1016/j.pnpbp.2025.111316

Ming Zheng MD, PhD

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.

{"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}

引用次数: 0

Noradrenergic modulation of stress induced catecholamine release: Opposing influence of FG7142 and yohimbine

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-03-05 DOI: 10.1016/j.pnpbp.2025.111314

Vladimir Visocky, Carleigh J. Turner, Matthew H. Lowrie, Anthony Alibro, Fany Messanvi, Yogita Chudasama

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.

{"title":"Noradrenergic modulation of stress induced catecholamine release: Opposing influence of FG7142 and yohimbine","authors":"Vladimir Visocky, Carleigh J. Turner, Matthew H. Lowrie, Anthony Alibro, Fany Messanvi, 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<sub>2A</sub>-receptor agonist (guanfacine) and antagonist (yohimbine), as well as a partial inverse GABA<sub>A</sub> 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<sub>A</sub> 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}

引用次数: 0

Improved recognition memory and reduced inflammation following β-caryophyllene treatment in the Wistar-Kyoto rodent model of treatment-resistant depression

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-03-04 DOI: 10.1016/j.pnpbp.2025.111312

Helen Clunas , Samara Walpole , Ilijana Babic , Mayank Nair , Naomi May , Xu-Feng Huang , Nadia Solowij , Kelly A. Newell , Katrina Weston-Green

Persistent low mood, anxiety and cognitive deficits are common symptoms of depression and highly efficacious treatments that address symptoms including cognitive dysfunction are still required. β-caryophyllene (BCP) is a terpene with anti-inflammatory and pro-cognitive properties; however, its efficacy on cognition in depression remains unclear. This study aimed to investigate acute and chronic BCP treatment effects on cognitive, depressive- and anxiety-like behaviours, and inflammation in male and female Wistar-Kyoto (WKY) rats, a rodent model of treatment-resistant depression. Rats were administered either BCP (50 mg/kg) or vehicle (control). Open field (OFT), social interaction, sucrose preference, novel object recognition (NOR) and elevated plus maze (EPM) tests were conducted after acute (1 h) and chronic (2 weeks) treatment. Peripheral plasma inflammatory cytokine levels were examined. BCP acutely increased locomotor activity in the OFT but did not improve social interaction, whereas chronic BCP prevented increased latency to first interaction in females (not males). BCP did not improve sucrose preference or prevent anxiety-like behaviours in the EPM. BCP significantly increased novel object discrimination in the NOR test in male and female WKY rats and reduced cytokine levels after chronic treatment. This study shows for the first time that chronic BCP treatment improved recognition memory and exerted anti-inflammatory properties in a rodent model of depressive-like behaviours. BCP did not significantly improve anxiety-like behaviours, social interaction or anhedonia in WKY rats of either sex. These findings demonstrate the pro-cognitive effects of BCP in a rodent model of treatment-resistant depression worthy of further investigation.

{"title":"Improved recognition memory and reduced inflammation following β-caryophyllene treatment in the Wistar-Kyoto rodent model of treatment-resistant depression","authors":"Helen Clunas , Samara Walpole , Ilijana Babic , Mayank Nair , Naomi May , Xu-Feng Huang , Nadia Solowij , Kelly A. Newell , Katrina Weston-Green","doi":"10.1016/j.pnpbp.2025.111312","DOIUrl":"10.1016/j.pnpbp.2025.111312","url":null,"abstract":"<div><div>Persistent low mood, anxiety and cognitive deficits are common symptoms of depression and highly efficacious treatments that address symptoms including cognitive dysfunction are still required. β-caryophyllene (BCP) is a terpene with anti-inflammatory and pro-cognitive properties; however, its efficacy on cognition in depression remains unclear. This study aimed to investigate acute and chronic BCP treatment effects on cognitive, depressive- and anxiety-like behaviours, and inflammation in male and female Wistar-Kyoto (WKY) rats, a rodent model of treatment-resistant depression. Rats were administered either BCP (50 mg/kg) or vehicle (control). Open field (OFT), social interaction, sucrose preference, novel object recognition (NOR) and elevated plus maze (EPM) tests were conducted after acute (1 h) and chronic (2 weeks) treatment. Peripheral plasma inflammatory cytokine levels were examined. BCP acutely increased locomotor activity in the OFT but did not improve social interaction, whereas chronic BCP prevented increased latency to first interaction in females (not males). BCP did not improve sucrose preference or prevent anxiety-like behaviours in the EPM. BCP significantly increased novel object discrimination in the NOR test in male and female WKY rats and reduced cytokine levels after chronic treatment. This study shows for the first time that chronic BCP treatment improved recognition memory and exerted anti-inflammatory properties in a rodent model of depressive-like behaviours. BCP did not significantly improve anxiety-like behaviours, social interaction or anhedonia in WKY rats of either sex. These findings demonstrate the pro-cognitive effects of BCP in a rodent model of treatment-resistant depression worthy of further investigation.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111312"},"PeriodicalIF":5.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574466","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}

引用次数: 0

Sex differences in behavioral and neural responses induced by witnessing social defeat stress during adolescence or adulthood in mice

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-03-04 DOI: 10.1016/j.pnpbp.2025.111313

Lucas Canto-de-Souza , Daniela Baptista-de-Souza , Mariana Thiele , Vitor Gonçalves Garcia , Katellyn Costa Silva , Fernanda Victorino de Souza , Carlos C. Crestani , Ricardo Luiz Nunes-de-Souza

Psychosocial stress can lead to emotional disorders and memory-related cognitive impairments. Evidence suggests that stress effects vary with age and sex, involving brain structures such as the medial prefrontal cortex (mPFC), amygdala, and hippocampus. This study hypothesized that witnessing social defeat stress (WSDS) during adolescence or adulthood would produce anxiety- and depression-like behaviors and cognitive deficits in adulthood, with outcomes affected by sex. We examined WSDS effects on male and female mice exposed during adolescence or adulthood, assessing: (i) social avoidance in the social interaction test, (ii) anxiety in the elevated plus-maze (EPM) and open field tests, (iii) cognition in the object recognition test, (iv) depression-like behaviors in the sucrose splash test, and (v) ΔFosB expression in neurons within the mPFC, basolateral amygdala (BLA) and dorsal hippocampus (DH). WSDS during adolescence resulted in reduced EPM open-arm exploration in both sexes and impaired novel object discrimination in males. In adulthood, WSDS reduced open-arm entries only in females and impaired novel object discrimination in both sexes. Female mice showed higher mPFC ΔFosB labeling than males, while control males exhibited higher labeling in the BLA and DH, which was not observed in WSDS mice. In conclusion, this study shows that WSDS during adolescence or adulthood induces anxiety-like behavior in both sexes, cognitive impairments in males, and sex-specific patterns of neuronal activation.

{"title":"Sex differences in behavioral and neural responses induced by witnessing social defeat stress during adolescence or adulthood in mice","authors":"Lucas Canto-de-Souza , Daniela Baptista-de-Souza , Mariana Thiele , Vitor Gonçalves Garcia , Katellyn Costa Silva , Fernanda Victorino de Souza , Carlos C. Crestani , Ricardo Luiz Nunes-de-Souza","doi":"10.1016/j.pnpbp.2025.111313","DOIUrl":"10.1016/j.pnpbp.2025.111313","url":null,"abstract":"<div><div>Psychosocial stress can lead to emotional disorders and memory-related cognitive impairments. Evidence suggests that stress effects vary with age and sex, involving brain structures such as the medial prefrontal cortex (mPFC), amygdala, and hippocampus. This study hypothesized that witnessing social defeat stress (WSDS) during adolescence or adulthood would produce anxiety- and depression-like behaviors and cognitive deficits in adulthood, with outcomes affected by sex. We examined WSDS effects on male and female mice exposed during adolescence or adulthood, assessing: (i) social avoidance in the social interaction test, (ii) anxiety in the elevated plus-maze (EPM) and open field tests, (iii) cognition in the object recognition test, (iv) depression-like behaviors in the sucrose splash test, and (v) ΔFosB expression in neurons within the mPFC, basolateral amygdala (BLA) and dorsal hippocampus (DH). WSDS during adolescence resulted in reduced EPM open-arm exploration in both sexes and impaired novel object discrimination in males. In adulthood, WSDS reduced open-arm entries only in females and impaired novel object discrimination in both sexes. Female mice showed higher mPFC ΔFosB labeling than males, while control males exhibited higher labeling in the BLA and DH, which was not observed in WSDS mice. In conclusion, this study shows that WSDS during adolescence or adulthood induces anxiety-like behavior in both sexes, cognitive impairments in males, and sex-specific patterns of neuronal activation.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111313"},"PeriodicalIF":5.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574468","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}

引用次数: 0

Genetic causal effects of multi-site chronic pain on post-traumatic stress disorder: Evidence from a two-sample, two-step Mendelian randomization study

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-03-03 DOI: 10.1016/j.pnpbp.2025.111307

Zuxing Wang , Qiao Lu , Shuyu Hou , Hongru Zhu

Background

Existing evidence supports a correlation between multi-site chronic pain and post-traumatic stress disorder (PTSD), but it is yet to be determined if this correlation is causal and in what direction the causation works.

Methods

Applying two-sample Mendelian randomization (MR) analysis to data from available genome-wide association studies in populations of European ancestry, we estimated the causal association between multi-site chronic pain and no pain versus PTSD. Moreover, we used multivariable and mediation MR analysis to assess the mediating effects of 13 lifestyle factors or diseases on the causal relationship between multi-site chronic pain and PTSD. The MR analyses were mainly conducted with the inverse variance weighted (IVW) method, followed by various sensitivity and validation analyses.

Results

Multi-site chronic pain dramatically increases the risk of developing PTSD (odds ratio [OR]_IVW = 2.39, 95 % confidence interval [CI] = 1.72–3.31, p = 2.10 × 10⁻⁷), and no pain significantly reduces the risk of developing PTSD (OR_IVW = 0.12, 95 % CI = 0.05–0.30, p = 3.14 × 10⁻⁶). Multivariable MR found that 13 potential confounding factors do not influence the causal effect of multi-site chronic pain on PTSD. Moreover, body mass index (BMI) (6.98 %), educational attainment (8.79 %), major depressive disorder (MDD) (36.98 %) and insomnia (27.25 %) mediate the causal connection between multi-site chronic pain and PTSD.

Conclusion

Overall, individuals with multi-site chronic pain may be at a higher risk of developing PTSD, and this risk is partially influenced by the pathways involving BMI, educational attainment, MDD, and insomnia. These factors offer potential targets for therapeutic interventions.

{"title":"Genetic causal effects of multi-site chronic pain on post-traumatic stress disorder: Evidence from a two-sample, two-step Mendelian randomization study","authors":"Zuxing Wang , Qiao Lu , Shuyu Hou , Hongru Zhu","doi":"10.1016/j.pnpbp.2025.111307","DOIUrl":"10.1016/j.pnpbp.2025.111307","url":null,"abstract":"<div><h3>Background</h3><div>Existing evidence supports a correlation between multi-site chronic pain and post-traumatic stress disorder (PTSD), but it is yet to be determined if this correlation is causal and in what direction the causation works.</div></div><div><h3>Methods</h3><div>Applying two-sample Mendelian randomization (MR) analysis to data from available genome-wide association studies in populations of European ancestry, we estimated the causal association between multi-site chronic pain and no pain versus PTSD. Moreover, we used multivariable and mediation MR analysis to assess the mediating effects of 13 lifestyle factors or diseases on the causal relationship between multi-site chronic pain and PTSD. The MR analyses were mainly conducted with the inverse variance weighted (IVW) method, followed by various sensitivity and validation analyses.</div></div><div><h3>Results</h3><div>Multi-site chronic pain dramatically increases the risk of developing PTSD (odds ratio [OR]<sub>IVW</sub> = 2.39, 95 % confidence interval [CI] = 1.72–3.31, <em>p</em> = 2.10 × 10<sup>−7</sup>), and no pain significantly reduces the risk of developing PTSD (OR<sub>IVW</sub> = 0.12, 95 % CI = 0.05–0.30, <em>p</em> = 3.14 × 10<sup>−6</sup>). Multivariable MR found that 13 potential confounding factors do not influence the causal effect of multi-site chronic pain on PTSD. Moreover, body mass index (BMI) (6.98 %), educational attainment (8.79 %), major depressive disorder (MDD) (36.98 %) and insomnia (27.25 %) mediate the causal connection between multi-site chronic pain and PTSD.</div></div><div><h3>Conclusion</h3><div>Overall, individuals with multi-site chronic pain may be at a higher risk of developing PTSD, and this risk is partially influenced by the pathways involving BMI, educational attainment, MDD, and insomnia. These factors offer potential targets for therapeutic interventions.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111307"},"PeriodicalIF":5.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552886","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}

引用次数: 0

Evaluating the causal effects of circulating metabolic biomarkers on Alzheimer's disease 评估循环代谢生物标志物对阿尔茨海默病的因果效应。

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-03-02 DOI: 10.1016/j.pnpbp.2025.111309

Jianbin Du , Ancha Baranova , Hongbao Cao , Fuquan Zhang

Background

The diagnosis and treatment of Alzheimer's disease (AD) is challenging due to the complexity of its pathogenesis. Although research suggests a link between circulating metabolites and AD, their causal relationship is not fully understood.

Methods

Based on publicly available genome-wide association study data, we investigated the causative relationship between AD (7759 cases and 334,740 controls) and 233 traits describing circulating metabolites (136,016 participants) using a two-sample Mendelian randomization (MR) method. We adopted the inverse variance weighted approach as the priority and performed sensitivity analyses with MR-Egger intercept method and Cochran's Q test.

Results

The overall causal effect of circulating metabolic traits on AD was significantly higher than the inverse effect (beta: 0.15 ± 0.42 vs. 0.04 ± 0.07; p < 0.05). A total of 72 circulating metabolic traits (odd ratio (OR): 1.16–2.48) had a significant positive causal effect on AD, while a total of 16 circulating metabolic traits with significant negative causal effects on AD were detected (OR: 0.38–0.88). AD had a significant positive causal effect (OR: 1.02–1.17) on 142 circulating metabolic traits and a negative causal effect (OR: 0.87–0.99) on 43 circulating metabolic traits. Circulating metabolites that have a bi-directional causative relationship with AD mainly include apolipoprotein B levels, total cholesterol levels, total triglycerides levels, and omega-6 fatty acids levels.

Conclusion

The causative relationship between AD and the circulating metabolic traits is complex and bidirectional. Analyzing metabolites causally involved in the development of AD may provide clues for identifying preventive and therapeutic targets for this disorder.

{"title":"Evaluating the causal effects of circulating metabolic biomarkers on Alzheimer's disease","authors":"Jianbin Du , Ancha Baranova , Hongbao Cao , Fuquan Zhang","doi":"10.1016/j.pnpbp.2025.111309","DOIUrl":"10.1016/j.pnpbp.2025.111309","url":null,"abstract":"<div><h3>Background</h3><div>The diagnosis and treatment of Alzheimer's disease (AD) is challenging due to the complexity of its pathogenesis. Although research suggests a link between circulating metabolites and AD, their causal relationship is not fully understood.</div></div><div><h3>Methods</h3><div>Based on publicly available genome-wide association study data, we investigated the causative relationship between AD (7759 cases and 334,740 controls) and 233 traits describing circulating metabolites (136,016 participants) using a two-sample Mendelian randomization (MR) method. We adopted the inverse variance weighted approach as the priority and performed sensitivity analyses with MR-Egger intercept method and Cochran's Q test.</div></div><div><h3>Results</h3><div>The overall causal effect of circulating metabolic traits on AD was significantly higher than the inverse effect (beta: 0.15 ± 0.42 <em>vs.</em> 0.04 ± 0.07; <em>p</em> < 0.05). A total of 72 circulating metabolic traits (odd ratio (OR): 1.16–2.48) had a significant positive causal effect on AD, while a total of 16 circulating metabolic traits with significant negative causal effects on AD were detected (OR: 0.38–0.88). AD had a significant positive causal effect (OR: 1.02–1.17) on 142 circulating metabolic traits and a negative causal effect (OR: 0.87–0.99) on 43 circulating metabolic traits. Circulating metabolites that have a bi-directional causative relationship with AD mainly include apolipoprotein B levels, total cholesterol levels, total triglycerides levels, and omega-6 fatty acids levels.</div></div><div><h3>Conclusion</h3><div>The causative relationship between AD and the circulating metabolic traits is complex and bidirectional. Analyzing metabolites causally involved in the development of AD may provide clues for identifying preventive and therapeutic targets for this disorder.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111309"},"PeriodicalIF":5.3,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558876","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}

引用次数: 0