Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Psychedelic-related deaths in England, Wales and Northern Ireland (1997–2022)","authors":"Emma I. Kopra ,&nbsp;Jenni Penttinen ,&nbsp;James J. Rucker ,&nbsp;Caroline S. Copeland","doi":"10.1016/j.pnpbp.2024.111177","DOIUrl":"10.1016/j.pnpbp.2024.111177","url":null,"abstract":"<div><h3>Background</h3><div>Psychedelic drugs are increasingly visible in society once more, but their risks and adverse effects have received less attention than perhaps they should. While fatalities associated with psychedelics appear rare, a systematic approach to characterising their aetiology is required to inform harm minimisation efforts.</div></div><div><h3>Aims</h3><div>This study aimed to analyse prevalence and characteristics of psychedelic-related deaths in England, Wales, and Northern Ireland, between 1997 and 2022.</div></div><div><h3>Methods</h3><div>We analysed coroner reports submitted to the National Programme on Substance Use Mortality where psychedelic serotonergic agonist drugs were involved in the death, and conducted a thematic framework analysis to explore potential factors associated with their occurrence.</div></div><div><h3>Results</h3><div>We identified 28 cases where psychedelics were implicated (75 %, <em>N</em> = 21) or potentially implicated (25 %, <em>N</em> = 7) in the death; 19 of these involving psychedelic tryptamines (LSD 39 %, <em>N</em> = 11; Psilocybin 21 %, <em>N</em> = 6; DMT 7 %, <em>N</em> = 2), and 9 psychedelic phenethylamines (incl. NBOMes 18 %, <em>N</em> = 5). Most deaths were deemed accidental by the coroner (86 %, <em>N</em> = 24), including both traumatic injuries and drug toxicities; most cases involved multiple implicated drugs (68 %, <em>N</em> = 19); and most of the deceased were under 30 years of age (82 %, <em>N</em> = 23). Thematic framework analysis identified nine themes in the deaths across three categories. ‘Polysubstance use’ was the most common theme (82 % of cases, <em>N</em> = 23/28), followed by a suboptimal ‘physical environment’ (70 % of cases where this information was available, <em>N</em> = 14/20).</div></div><div><h3>Conclusions</h3><div>The profound and often unpredictable effects of psychedelics pose a unique profile of risks and adverse reactions. Nevertheless, psychedelic-related deaths remain very rare in comparison to other recreational drugs, and frequently involve polydrug use. Implications for harm reduction and policy are discussed.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111177"},"PeriodicalIF":5.3,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513102","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":"Cannabidiol exerts antipyretic effects by downmodulating inflammatory mediators in LPS-induced fever","authors":"Emilly S.S. Andres ,&nbsp;Patrícia Passaglia ,&nbsp;Wanderson S. Santos ,&nbsp;Isis P. Trajano ,&nbsp;Renato Nery Soriano ,&nbsp;Lucas Miranda Marques ,&nbsp;Glauce C. Nascimento ,&nbsp;Elaine Del-Bel ,&nbsp;Luiz G.S. Branco","doi":"10.1016/j.pnpbp.2024.111178","DOIUrl":"10.1016/j.pnpbp.2024.111178","url":null,"abstract":"<div><div>Contrasting to tetrahydrocannabinol (THC), cannabidiol (CBD) has virtually no psychoactive effects and thus presents a minor risk for abuse. Furthermore, emerging preclinical and clinical evidence indicates that CBD exerts several beneficial pharmacological effects, including anti-inflammatory and antioxidant properties. Even though fever is one of the responses associated with systemic inflammation, no previous study assessed the putative impact of CBD on lipopolysaccharide (LPS)-induced fever. The present study aimed to evaluate whether CBD exerts effects on febrile responses, by modulating the hypothalamic-pituitary-adrenal (HPA) axis, and the inflammatory reflex, in this response. CBD caused no change in euthermic mice, indicating that it does not alter euthermia. Conversely, CBD blunted all the assessed systemic inflammation parameters including fever (a hallmark of infection), plasma pro-inflammatory cytokines and prostaglandin E₂ (PGE₂) surges, and hypothalamic PGE₂ (the proximal mediator of fever) synthesis. Moreover, CBD also reduced LPS-induced increase in plasma corticosterone levels and spleen TNF-α. These data are consistent with the notion that CBD has antipyretic effects, reducing peripheral febrigenic signaling (plasma pro-inflammatory cytokines levels), and eventually down-modulating hypothalamic PGE₂ production, possibly in a corticosterone- and inflammatory reflex-dependent manner.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111178"},"PeriodicalIF":5.3,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513100","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":"NRN1 genetic variability and methylation changes as biomarkers for cognitive remediation therapy response in schizophrenia","authors":"Carmen Almodóvar-Payá ,&nbsp;Irene París-Gómez ,&nbsp;Mariona Latorre-Guardia ,&nbsp;Maria Guardiola-Ripoll ,&nbsp;Rosa Catalán ,&nbsp;Bárbara Arias ,&nbsp;Rafael Penadés ,&nbsp;Mar Fatjó-Vilas","doi":"10.1016/j.pnpbp.2024.111175","DOIUrl":"10.1016/j.pnpbp.2024.111175","url":null,"abstract":"<div><div>Cognitive remediation therapy (CRT) demonstrates potential in enhancing cognitive function in schizophrenia (SZ), though the identification of molecular biomarkers remains challenging. The Neuritin-1 gene (<em>NRN1</em>) emerges as a promising candidate gene due to its association with SZ, cognitive performance and response to neurotherapeutic treatments. We aimed to investigate whether <em>NRN1</em> genetic variability and methylation changes following CRT are related to cognitive improvements.</div><div>Twenty-five SZ patients were randomly assigned to CRT or treatment-as-usual (TAU) groups, with cognitive function and <em>NRN1</em> methylation assessed pre- and post-intervention using the MATRICS Consensus Cognitive Battery and EpiTYPER. Besides, eleven <em>NRN1</em> polymorphisms were genotyped. Methylation changes (Δm = post - pre) were analyzed via sparse Partial Least Square Discriminant Analysis (sPLS-DA) to identify latent components (LCs) distinguishing CRT from TAU. To further explore methylation patterns of these LCs, CpG units were grouped into two subsets, yielding Δm means for those with increased and decreased methylation. Cognitive changes (Δcog = post - pre) were used to identify CRT improvers (CRT-I, Δcog ≥ 1), and the association between methylation changes and cognitive improvements post-therapy was also tested.</div><div>We identified two LCs that differentiated CRT from TAU with a classification error rate of 0.28. The main component, LC1, included 25 CpG units. The subsets of CpG units with increased and decreased post-therapy methylation differed significantly between the two treatment arms, suggesting that differences were not merely data-driven but reflected meaningful biological variation. Additionally, CpG units linked to therapy were also associated with cognitive improvement, with LC1 and the subset of CpG units showing increased methylation post-therapy distinguishing CRT-I from the rest of the patients across multiple cognitive domains. Furthermore, the effect of LC1 on speed processing improvement after CRT was enhanced by considering the <em>NRN1</em>-rs9405890 polymorphism. Notably, these CpG units, particularly those with increased methylation after CRT, overlapped with key gene regulatory elements.</div><div>Our model, integrating genetics and epigenetics, boosts the understanding of CRT response variability and highlights this multi-level approach as a promising strategy for identifying potential <em>NRN1</em>-related biomarkers of CRT effects, though further studies with larger samples are needed.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111175"},"PeriodicalIF":5.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481079","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 genetic landscape of the brain-heart axis: A comprehensive analysis of pleiotropic effects between heart disease and psychiatric disorders","authors":"Qifeng Song ,&nbsp;Cheng Zhang ,&nbsp;Wei Wang ,&nbsp;Cihan Wang ,&nbsp;Chenlong Yi","doi":"10.1016/j.pnpbp.2024.111172","DOIUrl":"10.1016/j.pnpbp.2024.111172","url":null,"abstract":"<div><h3>Background</h3><div>The genetic links between heart disease and psychiatric disorders are complex and not well understood. This study uses genome-wide association studies (GWAS) and advanced multilevel analyses to explore these connections.</div></div><div><h3>Methods</h3><div>We analyzed GWAS data from seven psychiatric disorders and five types of heart disease. Genetic correlations and overlaps were examined using linkage disequilibrium score regression (LDSC), high-definition likelihood (HDL), and Genetic analysis incorporating Pleiotropy and Annotation (GPA). Pleiotropic single-nucleotide variations (SNVs) were identified with pleiotropic analysis under the composite null hypothesis (PLACO) and annotated via Functional mapping and annotation of genetic associations (FUMA). Potential pleiotropic genes were identified using Multi-marker Analysis of GenoMic Annotation (MAGMA) and Summary data-based Mendelian Randomization (SMR).</div></div><div><h3>Results</h3><div>Among 35 trait pairs, 32 showed significant genetic correlations or overlaps. PLACO identified 15,077 SNVs, with 287 recognized as pleiotropic loci and 20 colocalization sites. MAGMA and SMR revealed 75 potential pleiotropic genes involved in diverse pathways, including cancer, neurodevelopment, and cellular organization. Mouse Genome Informatics (MGI) queries provided evidence linking multiple genes to heart or psychiatric disorders.</div></div><div><h3>Conclusions</h3><div>This analysis reveals loci and genes with pleiotropic effects between heart disease and psychiatric disorders, highlighting shared biological pathways. These findings illuminate the genetic mechanisms underlying the brain-heart axis and suggest shared biological foundations for these conditions, offering potential targets for future prevention and treatment strategies.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111172"},"PeriodicalIF":5.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481078","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":"Levodopa therapy affects brain functional network dynamics in Parkinson's disease","authors":"Xiaojin Liu ,&nbsp;Yuze Zhang ,&nbsp;Yihe Weng ,&nbsp;Miao Zhong ,&nbsp;Lijuan Wang ,&nbsp;Zhenni Gao ,&nbsp;Huiqing Hu ,&nbsp;Yuhu Zhang ,&nbsp;Biao Huang ,&nbsp;Ruiwang Huang","doi":"10.1016/j.pnpbp.2024.111169","DOIUrl":"10.1016/j.pnpbp.2024.111169","url":null,"abstract":"<div><div>Levodopa (L-dopa) therapy is the most effective pharmacological treatment for motor symptoms of Parkinson's disease (PD). However, its effect on brain functional network dynamics is still unclear. Here, we recruited 26 PD patients and 24 healthy controls, and acquired their resting-state functional MRI data before (PD-OFF) and after (PD-ON) receiving 400 mg L-dopa. Using the independent component analysis and the sliding-window approach, we estimated the dynamic functional connectivity (dFC) and examined the effect of L-dopa on the temporal properties of dFC states, the variability of dFC and functional network topological organization. We found that PD-ON showed decreased mean dwell time in sparsely connected State 2 than PD-OFF, the transformation of the dFC state is more frequent and the variability of dFC was decreased within the auditory network and sensorimotor network in PD-ON. Our findings provide new insights to understand the dynamic neural activity induced by L-dopa therapy in PD patients.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111169"},"PeriodicalIF":5.3,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481080","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":"Disentangling negative reinforcement, working memory, and deductive reasoning deficits in elevated BMI","authors":"Gibson Weydmann ,&nbsp;Igor Palmieri ,&nbsp;Reinaldo A.G. Simões ,&nbsp;Samara Buchmann ,&nbsp;Eduardo Schmidt ,&nbsp;Paulina Alves ,&nbsp;Lisiane Bizarro","doi":"10.1016/j.pnpbp.2024.111173","DOIUrl":"10.1016/j.pnpbp.2024.111173","url":null,"abstract":"<div><div>Neuropsychological data suggest that being overweight or obese is associated with a tendency to perseverate behavior despite negative feedback. This deficit might be observed due to other cognitive factors, such as working memory (WM) deficits or decreased ability to deduce model-based strategies when learning by trial-and-error. In the present study, a group of subjects with overweight or obesity (Ow/Ob, <em>n</em> = 30) was compared to normal-weight individuals (<em>n</em> = 42) in a modified Reinforcement Learning (RL) task. The task was designed to control WM effects on learning by manipulating cognitive load and to foster model-based learning via deductive reasoning. Computational modelling and analysis were conducted to isolate parameters related to RL mechanisms, WM use, and model-based learning (deduction parameter). Results showed that subjects with Ow/Ob had a higher number of perseverative errors and used a weaker deduction mechanism in their performance than control individuals, indicating impairments in negative reinforcement and model-based learning, whereas WM impairments were not responsible for deficits in RL. The present data suggests that obesity is associated with impairments in negative reinforcement and model-based learning.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111173"},"PeriodicalIF":5.3,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441719","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":"Understanding sex and populational differences in spatio-temporal exploration patterns and homebase dynamics of zebrafish following repeated ethanol exposure","authors":"Cássio M. Resmim ,&nbsp;João V. Borba ,&nbsp;Falco L. Gonçalves ,&nbsp;Laura W. Santos ,&nbsp;Julia Canzian ,&nbsp;Barbara D. Fontana ,&nbsp;Maribel A. Rubin ,&nbsp;Denis B. Rosemberg","doi":"10.1016/j.pnpbp.2024.111171","DOIUrl":"10.1016/j.pnpbp.2024.111171","url":null,"abstract":"<div><div>Ethanol (EtOH) is one of the most widely consumed substance, affecting neurobehavioral functions depending on multiple environmental and biological factors. Although EtOH modulates zebrafish (<em>Danio rerio</em>) anxiety-like behaviors in novelty-based paradigms, the potential role of biological sex and populational variability in the exploratory dynamics in the open field test (OFT) is unknown. Here, we explored whether a repeated EtOH exposure protocol modulates the spatio-temporal exploration and homebase-related parameters in a population- and sex-dependent manner. Male and female fish from the short-fin (SF) and leopard (LEO) phenotypes were exposed to EtOH for 7 days (1 % <em>v</em>/v, 20 min per day). On the 8th day, the OFT was performed to assess locomotor and exploratory behaviors. We verified significant populational differences in the baseline spatio-temporal exploration patterns, supporting a pronounced anxiety in LEO with a higher homebase index compared to SF. We also found sex-dependent differences in EtOH sensitivity, where SF was more sensitive to EtOH, especially in females, which showed marked alterations in thigmotaxis and homebase occupancy. Conversely, only LEO female subjects showed increased center occupancy following EtOH. Principal component analysis (PCA) showed the main components that explained data variability, which were sex- and population-dependent. Overall, our novel findings support the utility of zebrafish-based models to assess how EtOH influences the exploratory profile in the OFT, as well as to elucidate potential differences of sex and population in the neurobehavioral responses of alcohol exposure in a translational perspective.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111171"},"PeriodicalIF":5.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445843","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":"Associations between intestinal fatty-acid binding protein and clinical and metabolic characteristics of depression","authors":"Oliwia Gawlik-Kotelnicka ,&nbsp;Karolina Czarnecka-Chrebelska ,&nbsp;Aleksandra Margulska ,&nbsp;Ewa Pikus ,&nbsp;Jakub Wasiak ,&nbsp;Anna Skowrońska ,&nbsp;Ewa Brzeziańska-Lasota ,&nbsp;Dominik Strzelecki","doi":"10.1016/j.pnpbp.2024.111170","DOIUrl":"10.1016/j.pnpbp.2024.111170","url":null,"abstract":"<div><div>Introduction: The topic of increased intestinal permeability is associated with disruption of the intestinal barrier, leading to the “leaky gut” syndrome. Depressive disorders often coexist with abdominal obesity, metabolic syndrome, or its components and complications. Intestinal permeability has been proven to relate to all of the above. Methods: In this cross-sectional study, we aimed to assess the “leaky gut” blood biomarker - intestinal fatty acid-binding protein (I-FABP) - in 114 adult patients diagnosed with depressive disorders depending on abdominal obesity comorbidity, depression, anxiety, and stress level, or antidepressant use. The corrected <em>p</em>-value was set at 0.02. We analyzed patients' mental state, diet, anthropometric parameters, metabolic laboratory markers and I-FABP. Results: There was no difference in circulating I-FABP levels between obese and non-obese patients with depressive disorders (<em>p</em> = 0.648). Similarly, I-FABP levels were not different in patients with different emotional symptoms severity (<em>p</em> = 0.829 for self-assessed depression, <em>p</em> = 0.164 for anxiety, and <em>p</em> = 0.543 for stress). But, I-FABP levels differed significantly between patients treated and not treated with antidepressants (<em>p</em> = 0.011). In general linear model analysis treatment with antidepressants, anxiety severity level, their interaction, along with smoking status, drinks intake, and using dietary supplements were shown to significantly explain I-FABP variance (<em>p</em> &lt; 0.001, R²_adj = 0.261). Conclusions: Comorbid obesity did not increase intestinal permeability circulating marker, I-FABP, in the population of patients with depressive disorders. Treatment with antidepressants may be connected to higher I-FABP levels. Using dietary supplements, drinks intake, smoking status, or anxiety level may serve as explanatory factors.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111170"},"PeriodicalIF":5.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407180","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":"Genetic association and drug target exploration of inflammation-related proteins with risk of major depressive disorder","authors":"Wenxi Sun ,&nbsp;Hongbao Cao ,&nbsp;Dongming Liu ,&nbsp;Ancha Baranova ,&nbsp;Fuquan Zhang ,&nbsp;Xiaobin Zhang","doi":"10.1016/j.pnpbp.2024.111165","DOIUrl":"10.1016/j.pnpbp.2024.111165","url":null,"abstract":"<div><h3>Background</h3><div>In numerous observational studies, circulating inflammation-related proteins have been linked with major depressive disorder (MDD), yet the precise causal direction of this relationship remains unclear. This study aims to investigate the potential causal link between inflammation-related proteins and the risk of developing MDD.</div></div><div><h3>Methods</h3><div>We utilized summary data from a genome-wide association study (GWAS) of 91 circulating inflammation-associated proteins in 14,824 individuals of European descent. Additionally, we incorporated findings from a substantial GWAS on MDD, which included 294,322 cases and 741,438 controls. Our analysis employed a two-sample bidirectional Mendelian randomization (MR) approach, with inverse variance weighting (IVW) as the primary method. We augmented this with two supplementary techniques (MR-Egger and weighted median approaches) to detect and address potential pleiotropy. Furthermore, to identify and evaluate possible drug targets, we conducted a thorough search within the Drug-Gene Interaction Database (DGIdb).</div></div><div><h3>Results</h3><div>Analysis using MR unveiled significant and causative associations between genetically determined CASP-8 (odds ratio (OR): 0.97), CD40 (OR: 0.96), IL-18 (OR: 0.98), SLAMF1 (OR: 0.97), and uPA (OR: 0.98) with MDD. Conversely, reverse MR analysis indicated causal associations between MDD and CCL19 (OR: 1.15), HGF (OR: 1.15), IL-8 (OR: 1.10), IL-18 (OR: 1.11), IL20RA (OR: 1.12), TGFA (OR: 1.12) and TNFSF14 (OR: 1.16). Notably, a significant bidirectional causal link was observed between IL-18 and MDD. Gene-drug analysis identified CD40, HGF, IL-8, IL-18, SLAMF1, and TGFA as potential therapeutic targets.</div></div><div><h3>Conclusions</h3><div>We've pinpointed causal links between inflammation-related proteins and MDD, offering compelling and innovative evidence to enhance our understanding of the inflammatory mechanisms involved in MDD and to investigate potential targets for anti-MDD medications.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111165"},"PeriodicalIF":5.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395291","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":"Melanin-concentrating hormone promotes feeding through the lateral septum","authors":"Mikayla A. Payant,&nbsp;Anjali Shankhatheertha,&nbsp;Melissa J. Chee","doi":"10.1016/j.pnpbp.2024.111163","DOIUrl":"10.1016/j.pnpbp.2024.111163","url":null,"abstract":"<div><div>Feeding is necessary for survival but can be hindered by anxiety or fear, thus neural systems that can regulate anxiety states are key to elucidating the expression of food-related behaviors. Melanin-concentrating hormone (MCH) is a neuropeptide produced in the lateral hypothalamus and zona incerta that promotes feeding and anxiogenesis. The orexigenic actions of MCH that prolong ongoing homeostatic or hedonic feeding are context-dependent and more prominent in male than female rodents, but it is not clear where MCH acts to initiate feeding. The lateral septum (LS) promotes feeding and suppresses anxiogenesis when inhibited, and it comprises the densest projections from MCH neurons. However, it is not known whether the LS is a major contributor to MCH-mediated feeding. As MCH inhibits LS cells by MCH receptor (MCHR1) activation, MCH may promote feeding via the LS. We bilaterally infused MCH into the LS and found that MCH elicited a rapid and long-lasting increase in the consumption of standard chow and a palatable, high sugar diet in male and female mice; these MCH effects were blocked by the co-administration of a MCHR1 antagonist TC- MCH 7c. Interestingly, the orexigenic effect of MCH was abolished in a novel, anxiogenic environment even when presented with a food reward, but MCH did not induce anxiety-like behaviors. These findings indicated the LS as a novel region underlying orexigenic MCH actions, which stimulated and enhanced feeding in both sexes in a context -dependent manner that was most prominent in the homecage.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111163"},"PeriodicalIF":5.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402002","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}